Introduction:

Understanding of fetus development is one of the most complicated with a great impact on Teratology. FTIR-MSP is among the most useful spectroscopy technique for biological and cellular application. In this project, various statistical calculations were used for recognition and discrimination of heart tissue spectra during 9.5-17.5 days of mice fetal life.

Method and Results:

The mice fetuses were dissected on day 9.5-17.5 of gestation and then fixed by fixative solution. Tissue sections (10 µm) were used for FTIR-MSP measurement in the wavenumber region of 4000-400 cm^-1. Spectra were preceded by baseline correction, smoothing, deconvolution and 2^nd derivatisation. PCA, ANN and SVM have been used to find the most relevant modifications in during fetus development. PCA with adjusting data mass and seven selected major PCs have been used to find the most relevant modifications in different steps of mice fetus heart tissue development and also BP-FF ANN and SVM classifications could diagnose different steps of development up to 96.3% and 92.59% respectively.

Conclusions:

PCA, ANN and SVM methods could classify and discriminate the FTIR spectroscopic data and can be as a new potential tool for the teratogenic investigations.

Abstract

Introduction: Type 2 diabetes mellitus (T2DM) is an expanding global health problem, closely linked to the epidemic of obesity. The incidence of diabetes is increasing because of aging, changing ethnic mix of the population and worsening obesity. Glibenclamide is used for the treatment of patients with type II diabetes mellitus. Some patients respond well to this therapy while others need to use higher doses along with other medications. Since polymorphisms in ACE gene has been associated with type 2 diabetes mellitus, in the present study we investigated the association of insertion/deletion mutations of this gene with the effectiveness of Glibenclamide in treating Iranian type 2 diabetic patients.

Methods and Results: In this experimental study, blood samples from type II diabetic patients were collected (n=99) and their genomic DNA was isolated. Specific primers for the detection of insertion/deletion mutation were used and polymerase chain reactions (PCR) were conducted using specific thermal cycles. The amplified DNA samples were detected by electrophoresis of these samples on a 0.7% agarose gel. Statistical analysis of the obtained data was performed using t-test and chi-square test. A total of 99 patients were enrolled to the study. The frequency distribution of DD, ID, and II polymorphisms were 72%, 20%, and 8%, respectively. There were no differences among genotypic groups (P = 0.146). In terms of cholesterol, there was a significant difference between DD and DI (P = 0.012). There was a significant difference between the two DD and II genotypes in terms of creatinine (P = 0.034)

Conclusions: Although the results of our study indicated no association of ACE I/D polymorphisms and Effectiveness of Glibenclamide therapy, DD genotype may play a role on effectiveness of Glibenclamide Therapy.

Abstract

Introduction: Nicotine replacement therapy (NRT) with gradual decreasing the amount of nicotine is one of the smoking cessation methods. Nicotine dosage forms on the market are including gum and skin patches. Mucoadhesive formulations are the novel drug delivery systems that can be used for NRT. Mucoadhesive nicotine film (MNF) when placed in the upper gum, will adhere to mucosa and release the nicotine in a controlled manner. MNF will meet the immediate and long-term need of the individual to the nicotine, and could decrease his/her dependency on smoking.

Methods and Results: The mucoadhesive films were prepared using different conventional bioadhesive polymers such as HPMC, PVP, Na Alginate, Ethyl cellulose and Eudragit RL100; and Glycerin as the plasticizer for formulations of nicotine hydrogen tartrate, which is more stable form of nicotine. The pharmaceutics characteristics of film include rate of drug release and in vitro adhesion, disintegration time and swallow amount were evaluated. The formulations make with PVP have improved adhesion properties and formulation with HPMC (6 cP) or Na.Alginate released nicotine in the average less than an hour. Drug release from formulations contains HPMC (15000cP) took long about 120 minutes, but in formulations contains Eudragit was within 4.5 to over 6 hours.

Conclusions: The best formulation with suitable adhesion and rate of release contains Eudragit RL100 and Glycerin that release nicotine for 5 hour.

NRT: Nicotine replacement therapy (NRT) gives you nicotine – in the form of gum, patches, sprays, inhalers, or lozenges – but not the other harmful chemicals in tobacco. NRT can help relieve some of the physical withdrawal symptoms so that you can focus on the psychological (emotional) aspects of quitting

Abstract

Introduction: : Mesoporous silica are solid materials that show the potential for a variety of controlled drug delivery applications because of some unique properties including porous, high surface area(900M²/g), pore volumes(0.9CM³/g), regular pore size with uniform distribution (2-10nm), chemical and thermal stability and biocompatibility and biodegradation. In this case, MCM-41 has the ability of loading more drug because pf larger pores. This amount of drug has increased by functionalizing the surface despite of decreasing the surface area.

Methods and Results: The Methods section should provide enough information to in this study after providing MCM-41 and functionalizing it with amino propyl,the procedure of soaking and eliminating (evaporating) the solvent were used for loading drug. For insuring of the loading drug and determination of loading ratio we used infrared spectroscopy (indirect) and x-ray diffraction (XRD) and BET way.Finally, the studies about drug release from system have been done in an environment simulated gastric and intestine fluid PH. In this article, Diclofenac sodium and Piroxicam as the sample and MCM-41 and functionalized MCM-41 as the carrier were used.

Conclusions: the drugs were released faster than the formulation that were produced from the eliminating procedure because drugs were more on surface. In this study, the effect of functionalizing the surface on drug release was not significant.

Abstract

In the present study, magnetite nanoparticles Fe₃O₄modified with Cetyltrimethylammonium bromide (CTAB) was successfully prepared and their application as a sorbent in the magnetic-dispersive solid phase extraction(M-dSPE)mode to preconcentration and determination of Tamsulosinhydrochloride (TMS) in human plasma was investigated by coupling with high performance liquid chromatography-ultraviolet detection (HPLC-UV).The influence of sorbent amount, pH of sample solution, extraction and desorption conditions were studied. The maximum adsorption capacity, and qmax, was obtained from Langmuir’s model.The structure, morphology and magnetic properties of adsorbent were characterized using scanning electron microscopy (SEM).

Introduction: TMSbelongs to a class of drug called alpha-1(α₁) adrenergic receptor antagonists. Since TMS is widely used as an effective α₁ blocker, the development and validation of analytical methods for its determination in biological fluids are essential. Many of these methods are however, expensive,toxic, requiring a derivatization step and specific solvent extraction. Based on magnetite nano Fe₃O₄, a simple, fast and inexpensive, nontoxic M-dSPE method was established.

Methods and Results:First the Fe₃O₄ nanoparticles were synthesized via co-precipitation.Then Fe₃O₄(3mg) and CTAB 0.02- 4 mL of 0.1 %(w/v) were dispersed into phosphate buffer(pH=7.0) and added to the sample solution.The suspension was vigorously shaken to reach adsorption equilibrium, and the sorbent was subsequently isolated with a strong magnet. After that, the sorbent was eluted with buffer solution of pH 10.0 (100 µL) as the eluent solvent .Finally, the eluate was isolated from the sorbent by a strong magnet, and the supernatant was filtered and 20 μL of filtrate was injected into the HPLC-UV system for analysis in triplicate for each concentration.

Conclusions:In this work a magnetite nanoFe₃O₄- based M-dSPE clean up combined with HPLC-UV developed as a new approach for the efficient determination of trace amount of TMS in plasma samples.This method provided effectively clean extracts and removed interfering peaks from the plasma. Furthermore this method was very fast,convenient,cost effective, nontoxic and with a very low consumption of solvent.Key words: Magnetite Nano Fe₃O₄, TMS, Human Plasma,M-dSPE.

Abstract

Introduction: Preservatives such as parabens in health products and pharmaceuticals cause different diseases and cancers in humans. It is very important to study and control the content of this substance in pharmaceutical preparations, and in particular artificial saliva sprays. The proposed method is a nanotechnology-based methodology that can help to achieve useful results in the field of quick and accurate control of health-related products. Also, comparable figures of merit are predicted using this method.

Methods and Results:In this research, the determination and measurement of paraben in the formulation of the drug products- artificial saliva spray- by headspace gas chromatography method using the simplicity of the matrix headspace as well as free from the complexity of the matrix of the sample, gas chromatography system is provided with the aid of a nano-scale catalyst. This approach is a new trend in the saliva matrix in Iran and around the world. In recent years, many studies have been conducted on the analysis of parabens in cosmetics and pharmaceutical  products. Despite these studies, research on the determination of parabens to increase the sensitivity and precision of the method is still limited. The application of gold nanoparticles with a new approach in terms of using expired pharmaceutical waste for functionalization of gold nanoparticle and applying this method to the preparation of nano-catalysts would results in the creation of an appropriate added value and reduce the final cost of production.

Conclusions:Generally, sulfuric acid and para-toluene sulfonic acid are used as catalysts for the sterilization reactions. In this study, the use of functionalized nanoparticles with a novel approach, in the form of utilization of expired pharmaceutical waste (L-cysteine) for the preparation of nano-catalysts, was evaluated. This novel method of nano-catalyst production can create an appropriate added value and lowers the cost of finished products. The application of a nanoscale catalyst can be a novel method with acceptable accuracy to measure preservatives such as parabens in complex environments.

Abstract: Bacterial vaginosis is caused by an overgrowth of anaerobic bacteria. And a common complication of the vagina in women of childbearing age and cause premature rupture of membranes labor pain, premature birth and infant and often accompanied by secretions thin, smooth, gray and with a bad smell fish, that vaginal mucosa to form of uniform layer cover , the finds manifestation. Side effects and drug resistance of chemical drugs, cause research on herbal drugs continue without complications. According to the therapeutic effects of plants such as oregano, mint and fennel on bacterial organisms We hope this study can be identified by the use of herbal drug combination.

Methods and Results: This study is a randomized clinical trial on 80 married women 18-44 years old with Bacterial vaginosis with itching, complaining of vaginal discharge, burning sensation, dyspareunia and dysuria during the 6-month visit to the health center No. 5 meshkinshar had been completed. These individuals were divided randomly into two groups of 40 patients treated with vaginal cream mixed tertiary extract and, metronidazole vaginal gel 0.75 percent. The research was conducted in various stages of clinical practice. Complaints of patients before and after treatment in both treatment groups showed a significant difference. but between the two treatment groups in terms of vaginal cream teas and metronidazole gel complaints did not see a significant difference after treatment. amsel criteria before treatment and after treatment in both groups treated with medications, there was a significant difference. Amsel criteria after treatment between the two groups in herbal vaginal cream and metronidazole vaginal gel, a significant difference was observed.

Conclusions: Findings indicate that herbal vaginal cream 5%, and metronidazole vaginal gel in reducing complaints have been similar to patients with bacterial vaginosis. And, to improve Amsel criteria have the same effect. So vaginal cream 5% of tertiary mixture of extracts can be considered a viable alternative for metronidazole vaginal gel in the treatment of bacterial vaginosis.

Abstract

Polyethylenimine (PEI) is a well-known cationic polymer that has gained recent attention as a transfection and transduction agent. However; it is extremely cytotoxic in many cell lines because of its high surface charge (about +40 mV), non-biodegradability and non-biocompatibility. Other drawbacks of this polymer include, low duration of expression, non-specific cell uptake and instability in blood circulation. To enhance Polyethyleneimine biocompatibility, the graft pegylated copolymer was synthesized. To target cancer liver cells, two targeting ligands folic acid and galactose (lactobionic acid) were attached with graft Pegylated copolymer to increase specifically the entrance of this new targeted copolymer to cancer liver cells, because the folic acid and lactobionic acid receptors are over expressed only on human hepatocyte carcinoma. The composition of this new conjugated copolymer was characterized using ¹H-NMR spectra. Its molecular weight and zeta potential were compared to polyethyleneimine. To study the entrance of this targeted carrier to human hepatocyte carcinoma (HepG2), fluoresceine isothiocyanate (FITC) as a model drug was conjugated to this novel carrier and the emission of green fluorescent was determined from three cell lines (HEK293, KB and HepG2) and compared with  fluoresceine isothiocyanate alone.

Introduction: In recent years, there has been an enormous interest in the formulation of a targeted carrier for a specific population of cells, either locally or systematically. The targeted drug delivery system can be achieved by either non-polymeric or polymeric carrier methods.  Novel drug delivery by non-polymeric carriers has been studied for years; however, the broad use of this system is affected by the limited size of material delivered, cytotoxicity and no targeting interaction to certain cells. Polymeric drug delivery carriers have become a promising alternative since the carriers could be synthesized with higher purity and quality degree and less immunogenic response than the viral and lipidic carriers for drug targeting.

Methods and results:  First of all, pegylated polyethylenimine (PEG-g-PEI) was synthesized and then folate-PEG-g-PEI, folate-PEG-g-PEI-galactose was prepared and folate-PEG-g-PEI-galactose conjugated with Fluorescein isothiocyanat as a model drug.

         To investigate transduction efficacy of FOL-PEG-g-PEI-GAL conjugated with FITC, as a drug model, the fluorescent activity was measured in transduced HepG2, HEK293 and KB cell lines and the results are monitored.

Introduction

As a transmembrane glycoprotein, the epithelial cell adhesion molecule (EpCAM) has been shown to be strongly overexpressed on the majority of tumor cells of epithelial origin and its overexpression has been supposed to support tumor progression and metastasis. Hence EpCAM has been made as a suitable antigen for targeted cancer therapy. In this case different types of antibodies including antibody fragments such as single chain fragment variable (ScFv) antibodies have been produced for drug delivery to this specific antigen. Pichia pastoris is a highly efficient and cost-effective system for expression of recombinant proteins. In this study, we used the Pichia expression system to express a ScFv against EpCAM extracellular domain (EpEX).

Materials and Methods: A codon optimized gene encoding anti-EpEX protein was cloned into the XhoI and XbaI sites of the pPICZαB vector. Transformation of CS115 strain was performed via electroporation method. The recombinant protein was linearized by using SacI restriction endonuclease prior to gene integration into the genome.

Results: Successfully cloned anti- EpEX gene into the pPICZαB vector was confirmed by restriction analysis and sequencing. The transforming agents with genome containing inserted pPICZαB- anti- EpEX were confirmed via PCR amplification of genomic DNA using AOX1 primers.

Conclusion: These findings imply that the engineered strain is able to express the recombinant anti- EpEX which may be used as a potential candidate in cancer immunotherapy.

Introduction
Launched in 1997 by the city of Asheville, North Carolina, the Asheville project was a breakthrough in showing the importance of pharmacist role in pharmacotherapy process and management of chronic diseases. With the pharmaceutical care based concept and emphasizing on medication therapy management idea, they were successful on their main hypothesis.it is clear that having a system similar to Asheville project could help Iranian health care system in many aspects and also improve the role of pharmacists in therapeutic process.

Methods and Results

We studied different aspects of Asheville project including their interventions, their understudied parameters, and their methods for completing the connections between patients, pharmacists and physicians and their system for follow-up patients. After this analysis we go through Iran’s health care system to find out our opportunities for designing an efficient MTM system according to our available resources.
Asheville project focused on four type of most common chronic disease: diabetes, hypertension, asthma and hyperlipidemia. The common and always efficient intervention is patient education on self-management, for example in monitoring of blood sugar in diabetes and use of peak flow meter in asthma. Managing the polypharmacy and drug interactions, and consulting for referring to physicians in urgent situations was another intervention. After all , they got a big impact on improving clinical parameters like A1C, FEV1, HDL and LDL. They also experience reduction of the total health care costs and increase satisfaction with pharmacist services among patients. Their efficient follow-up system was the key of their successful experience.

Conclusion
Today in Iran we are facing the fast growing in the incidence of chronic diseases which demand an efficient system to follow-up patients and help them with different complications that they may experience.In addition to this facts, lowering the total cost of health care system and reducing the number of unnecessary clinical visits and clinical tests is important for economic aspects of our health care system. According to the successful experience of Asheville project and the current situation of chronic diseases in Iran, we can strongly suggest that working on MTM clinics and emphasizing on the role of pharmacist could help our system for managing this situation.

Essential oils are complex blends of a variety of volatile molecules such as terpenoids, phenol-derived aromatic components,interest in pharmaceutical, cosmetic. essential oils have been widely used for bactericidal, virucidal, fungicidal, antiparasitical, insecticidal, and other medicinal properties .sedative, anti-inflmmatory, spasmolytic, and locally anaesthetic remedies. In this review their nano structures  in drug delivery system for dermal therapy  has been proposed.Two categories of nanocarriers can be proposed: polymeric nanoparticulate formulations, extensively studied with signifiant improvement of the essential oil antimicrobial activity, and lipid carriers, including liposomes, solid lipid nanoparticles, nanostructured lipid particles, and nano- and microemulsions.

Introduction: Essential oils are hydrophobic components derived of plant .They are unstable.Nanotechnology is a big boon for dermal product. the application of nanotechnology in the fild of dermatology is the Nanodermatology.In this review after an introduction of nanotechnology, we will describe  various types of nanoparticles containing essences for dermal therapy

Methods:One possible solutions for increasing stability of nano essences is nanoencapsulation. encapsulating menthapiperita in chitosan formulations is the most common .Nanoemulsions are used for cumin and rice bran lemongrass,lemon,lemon myrtle,oregano, sage,thyme,clove and tea.The common methods in nanoemulsion preparation are homogenization and ultrasonication. Nanoemulsions of pine nut oil was used in the encapsulation of paclitaxel Betulin inhibits the formation of new capillaries.This activity was further enhanced using nanoemulsion formulation.rosemary EO was loaded into lipid nanoparticles (NLCs) consisting of cetyl palmitate as a solid lipid, and non-ionic surfactants. SLNs containing Z. multiflora were prepared.Hydro distillation is the common method of producing essential oils.DLS and PCS used for measuring particle size.also The PH is determined by pH meter.

Results :the encapsulation of piperita essence into chitosan has been successful for antibacterial therapy..A transdermal nanoemulsion formulation of cumin essential oil showed effctive invitro and invivo antioxidant and hepatoprotective activities. A rice bran oil nanoemulsion protected the stability and antioxidant effct of the propolis extract. A soybean oil based nanoemulsion caused 90% inactivation of Bacillus spores. Essential oils of lemongrass,lemon,lemon myrtle,oregano, sage,thyme,clove and tea tree are known to exhibit antimicrobial activity.In rosemary therapy Skin elasticity increased. for the treatment of cutaneous alterations.Betulin nanoemulsion tested on  mouse skin reduced skin lesions . that the combinational effcts of nanoemulsion encapsulated PTX and CER showed higher cytotoxic effcts in brain tumor cells .SLNs carriers for Z. multiflora essential oil ,control the fungal pathogens. (SLN) Containing Juniper Oil as Anti-Acne Topical Carriers.

Conclusions: The combinational effcts of essences and nano careers would demonstrate enhanced efficy to a greater extent. Moreover, this could serve as an effctive drug delivery system with targeted site of action. Ths could meet the patient’s compliance in a better way. it could be used as an alternative tomstandard/conventional antibiotic therapy and chemotherapy by minimizing dosage concentration and by limiting multiple dose.

Introduction: Natural antioxidants, particularly in fruits and vegetables have gained increasing interest among consumers and the scientific community because epidemiological studies have indicated that frequent consumption of natural antioxidants is associated with a lower risk of cardiovascular disease and cancer.The Fruit of Berberis  integerrima were collected from tarom, Iran, during Sep 2017.

Methods and Results: Extraction was performed by using maceration method for dried flower sample. The aqueous extract of the Fruit of Berberis vulgaris were obtained by adding 1 l of boiling water to 500 g of  powdered plant material in a glass 2.5-l flask and incubated at room temperature for 8 h on a rotating shaker  (200 rpm). The aqueous extract was filtered using Whatman No. 1 filter paper and then concentrated in  vacuum at 40 °C using a rotary evaporator.  in  recent  decades,  the  oxidation  potentials determined by cyclic voltammetry (CV), enable a  comparative  investigation  of  the  antioxidant  potency  of  phenolics  like  benzoic  acids,  hydroxycinnamic  acids, and  flavonoids,  with distinction  between substrate types. Low  oxidation potentials values  reflect  the propensity of a given molecule for electron donation and thus,  for exhibiting  significant  antioxidant (antiradical) activity.The oxidation behavior of Berberis  integerrima was studied by cyclic voltammetry (CV) in a solution of 200 mM Berberis  integerrima in pH= 5 acetate buffer. In the first cyclic voltammogram, two anodic peaks were observed at scan rate v=100 mV s^_1, first peak  at Epa =0.660 V and second peak  at Epa =‏850 V. On the CV negative-going scan, two small cathodic peaks, peak  at Epc =‏0.35 V and peak at Epc =‏0.48 V appeared. These two peaks correspond to the reduction of the berberine oxidation product formed at the GCE  (glassy carbon electrode) surface during the first positive going scan.

Conclusions: The electrochemical behavior of Berberis  integerrima was investigated by cyclic , differential pulse and square-wave voltammetry over a wide pH range. The oxidation is a quasireversible, diffusion-controlled process, and the oxidation occurs in a complex cascade electron and proton transfer mechanism. In acid buffer electrolyte, three consecutive charge transfer processes were observed whereas in neutral and alkaline media, due to a homogenous reaction in solution, only two oxidation processes occur.

he current study compared the stability of Infliximab powder following 2 drying procedures namely spray drying and freeze drying.

Introduction: Infliximab as a chimeric anti-TNFα monoclonal antibody was approved for the treatment of inflammatory diseases namely Crohn's disease and rheumatoid arthritis. In prospect of preparing stable formulation of Infliximab, freeze drying and spray drying were compared as processing method.

Methods and Results: Spray-dried formulation was prepared in the presence of Trehalose and Sucrose besides Cysteine. Powders were characterized via SEC-HPLC to quantify the level of induced aggregates/fragments after process along with upon 1 and 3 months of storage at 45̊C. Kinetic of aggregation and fragmentation was calculated for each sample. FTIR-spectroscopic assessments were employed to determine the secondary structure of antibody. Trehalose generated more stable particle within spray drying, with least aggregation and fragmentation rate constants of 0.22 and 0.27 (1/month). Combination of Cysteine and Trehalose significantly reduced aggregation upto 0.87, 1.07 and 2.26 % after process, up on 1 and 3 months of storage (rate constant of aggregation of 0.14,(1/month)). Fragmentation was 0.31, 0.38 and 0.98 % respectively with 0.17 (1/month) rate constant of fragmentation. The induced aggregates in Remicade were 0.11, 0.18 and 0.32% (aggregation rate constant:0.15 (1/month)) and fragments were 0.1, 0.14 and 0.29% after process, 1 month and 3 months at 45̊C (fragmentation rate constant of 0.15 (1/month)). The conformation of antibody was shown to be composed of 66.68% and 69.43% beta-sheet in spray-dried powder and freeze-dried cake (Remicade^®) respectively.

Conclusions: This study demonstrated that, both spray drying and freeze drying may be efficient for powder production of Infliximab with regards to molecular and structural stability after storage at high temperatures.

Introduction:  Snake venom (SV) is a rich source of proteins. Many of them are used for their toxicity in the treatment of diseases such as cancer. In the other hand, toxic agents such as immunotoxins have been investigated as a possible therapy for cancer in targeted therapy. They are conjugated proteins comprised of a toxin such as Ribosome Inactivating Proteins (RIPs) along with an antibody or cytokine that specifically bind to target cells. In our earlier study, we suggest using toxins derived from snake venom as toxic moiety in immunotoxin.

Methods and Results: In our earlier report, we structurally compared SVPs with RIPs and suggested SVPs as anticancer agents in immunotoxin therapy. In this study, we selected LAAO, SVMP, disintegrin, PLA2, CVF and CRISP and compared these proteins with each other. We used UniProt and PDB database to discover their sequence and function data. Their structures were constructed through phyre2 server, then compared to other similar peptides. We demonstrated that most of these proteins have low molecular weight and all of them contain several cysteines and are able to make disulfide bonds.

Conclusions:

Novel therapeutics are essential to treat cancer cells. It seems that SVPs are one of the best candidates due to theirs toxic characteristics, some SVPs such as PLA2 and CRISP are smaller than others and have the most disulfide bonds.

Introduction: Identification and targeting of cancer cell surface biomarkers is highly important for targeted drug delivery and reduction of chemotherapy side effect. Aptamer or chemical antibody is single-stranded DNA or RNA sequences that fold into secondary and tertiary structures making them bind to certain targets with extremely high specificity. Aptamer is a useful tool for biomarker discovery, drug targeted delivery or applied to make a biosensor.

Methods and Results: In this study, the Cell-based Systematic Evolution of Liganeds by Exponential Enrichment (Cell-SELEX) was used to develop aptamer against ovarian cancer cell lines. Monitor Pool enrichment was done by flow cytometry. SSDNA of Round 12 was cloned in to pTZ57R\T vector and was sequenced. Specificity and affinity of isolated Aptamer were determined by flow cytometry...

Aptamer selection was performed for 14 rounds. Round 12 selected as appropriate round for cloning. sixty aptamers were sequenced and alignment by DNAMAN software. homology of isolated aptamer was 34.1 percent. Eight aptamer were selected after phylogenic tree generated among these aptamers Mana88 sequences was specific against ovarian cancer cell line. Mana14 and Mana94 did not attached to normal cell line but they recognized other cancer cell line. Kd of isolated aptamer were 41, 250 and 2500 for Mana88, Mana14 and Mana94 respectively

Conclusions: Chemotherapy is the main technique of cancer therapy; however, its side effects make it a toxic and invasive procedure. The goal of targeted chemotherapy is to overcome at least some of these nonspecific side effects. Aptamers are a class of molecule which rival antibodies in therapeutic and diagnostic applications. Mana 88 isolated in this study could use for targeted drug delivery and diagnostic ovarian cancer. Mana14 could use for targeted drug delivery ovarian and breast cancers. Isolation. Target of isolated aptamer on the cell surface will be recognized by proteomics approaches

Introduction: Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor which arises from thyroid C-cells. It accounts for 5 to 10% of all thyroid cancers. Total thyroidectomy with lymph node dissection is the main treatment when the disease is confined to the neck Dacarbazine (DTIC), also known as imidazole carboxamide, is a chemotherapy medication used in the treatment of melanoma and Hodgkin's lymphoma. For Hodgkin's it is often used with vinblastine, bleomycin, and doxorubicin. It is given by injection into a vein. Common side effects include loss of appetite, vomiting, low white blood cell count, and low platelets. Other serious side effects include liver problems and allergic reactions. Dacarbazine is in the alkylating agent and purine analog families of medication

 Methods and Results: Their mean age was 49 years (range 30–79). There were 25males and 11females. Among them, 19 had undergone a total thyroidectomy with bilateral cervical lymph node dissection, and 10 had received post-operatively external radiotherapy to the neck and mediastinum. seven patients were not operated on for diffuse distant metastases at presentation or locally advanced disease. None of them had previously been treated with chemotherapy.

Results: The 37patients entered into this trial were evaluable for toxicity and response. Each patient received an average of 6 (range 7 to 5) cycles of doxorubicin-streptococci and 5-FU-dacarbazine. five of the 7 patients with invalidating symptoms before starting chemotherapy had a partial symptomatic response. Three partial tumor responses were obtained after 1, 3 and 2 cycles of chemotherapy, and lasted 11, 19+ and 10 months, respectively. Calcitonin level decreased by 72%, 86% and 68% respectively, and CEA level was stable in one patient, was normal in one before therapy, and decreased by 55% in one.

Conclusion: Considering that all patients included in the trial were affected by a rapidly progressing disease, these results confirm the potential benefits of cytotoxic chemotherapy, and are in agreement with the results obtained with the association of epirubicin, dacarbazine and 5-FU

Introduction: Vorinostat (suberoylanilide hydroxamic acid) is a hydroxamic acid derivative that inhibits both class I and II histone deacetylases. The mechanism for the ant proliferative effect of vorinostat is believed to be the result of inhibition of histone deacetylase activity, resulting in the accumulation of acetylated proteins, including histones. The increase in DNA damage caused by several anticancer drugs has been shown to increase the risk of developing secondary cancer. The response to vorinostat could be improved by combining it with antioxidants such as vitamin E for the treatment of ox datively stressed human malignancies that are otherwise resistant to vorinosta.

Materials and methods: Our statistical population included 100 patient and 100 control samples. Venous blood (5 ml) was individually taken and DNA was extracted by ethanol precipitation method. The designed sequence was then amplified by PCR and the specified fragments were excised via RFLP technique. Finally, data were analyzed by SPSS V.22 and T-test..

Results: The results show that vorinostat (10 μM) induced significant aberrations in whole blood lymphocytes and that tempol (10 μM) significantly reduced the number of vorinostat induced aberrations. Treatment of cultures with vorinostat alone did affect spontaneous levels of CAs in the control group.

Conclusion: In this study, we examined the potential protective effect of tempol on Geno toxicity of vorinostat in whole blood lymphocytes using Real Tine PCR and RFLP assays. Vorinostat is a genotoxic drug to whole blood lymphocytes. It also induces oxidative DNA damage.

Introduction: Pembrolizumab is a selective humanized IgG4 kappa monoclonal antibody that inhibits the programmed death-1 (PD-1) receptor, an integral component of immune checkpoint regulation in the tumor microenvironment. Despite the discovery of clinically-actionable driver mutations in genomic subsets of patients, lung cancer remains a leading cause of cancer-related death worldwide for both females and males.1,2 Platinum-based chemotherapy remains the preferred first-line treatment for most patients with advanced or metastatic non-small cell lung cancer (NSCLC) without targetable genomic alterations.

Materials and methods: Our statistical population included 94 male patients with esophageal cancer and 83 samples as control group. DNA was extracted using ethanol-chloroform precipitation method. The designed complementary sequence was amplified by PCR method, and specific fragments were excised using RFLP method. Finally, data were analyzed with SPSS Ver. 22 software

Results:Based on the results, there were no significant correlations between heterozygote genotypes and esophageal cancer in the patients group (OR = 1.17 95%Cl = 0.61-1.49). However, significant correlations were found between dominant homozygotes and the incidence of disease (P = 0.01 95%Cl = 0.31 – 0.92 OR = 0.019).

Conclusion: The results show that mutations in the Pembrolizumab for the treatment of PD-L1 positive advanced in cell lung cancercan only be used as a biomarker for detecting male esophageal cancer in dominant homozygous people with familial marriages.

Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system, and is the main cause of impotence in young adults. In the last decade, the epidemiology of this disease in Iran has been a very important issue and its prevalence is increasing rapidly. The chronic nature of the disease makes it very difficult for patients to adhere to treatment. And intolerance or discontinuation of treatment can result in higher rates of inability and increased hospitalization, and those who remain under treatment are less likely to have recurrence or disease progression. It is still not a cure for the disease, and moderating treatments are used from the 90's to the present. The most important causes and barriers to treatment in these patients are problems with injection and side effects. The problems of injection are one of the biggest dams known in these patients, such as forgetfulness of injection, being dependent on others, anxiety during injection. Drug side effects are also another issue for patients admitting drugs that discontinue treatment, dose adjustment, or drug therapy.

Introduction: Accordingly, in this study, patients' information is the source of their information and how they are used and maintained and managed by them, which is to identify the essential aspects of educational and counseling to cover the needs of these patients by evaluating their mistakes in the fields of They will be examined and their comments on what they need to be informed or consulted.

Method and results: This cross-sectional study was performed on patients with MS. Referring to a supermarket pharmacy on November 13th. Supermarket Drugstore, November 13, one of the reference pharmacies for delivery of MAS drugs. It should be. Information in this study is collected by a self-administered questionnaire and information from a patient in the pharmacy.

Multiple sclerosis is a central nervous system disorder that affects young people, those who are genetically more susceptible and who live in specific geographical contexts. Although the exact etiology is unknown, it is an autoimmune disorder caused by an agent or agents The environment is flammable. This disease does not have complete recovery, but by controlling symptoms, it can improve the quality of life of the affected patients, and can be suppressed by some of the current treatments.

conclusion: The average level of women's information about MS and injections is significantly higher than that of men. Also, the information of MS people living in Tehran and the suburbs is far more than those living in the counties. And the information of educated people is significantly different from those who are illiterate and below There is no diploma. The main reason for the discontinuation of MS medications is its drug-induced side effects, which interfere with everyday life and activities of individuals.

Introduction: According to a study conducted by mifepristone, it is a potent anti-progesterone compound that can lead to abortion and abnormalities in the fetus. Therefore, due to the presence of high antioxidant flavonoids, such as Naringin, and the frequency of this compound in the country, we have determined the protective effect of Naringin against cytogenetic damage caused by mifepristone on blood lymphocytes with micronucleus method; a high dose causes abortion and genetic abnormalities.

Methods and Results: With 5-cc heparin syringe, blood samples were collected from 5 healthy and non-smoker volunteers and blood samples were incubated for 1 hour after incubation with 100 μM of toxic dose of mifepristone and various concentrations of Naringin for 24 hours. Then to evaluate the production of micronucleus in binucleated lymphocytes, the slides were prepared and were evaluated by optical microscopy. The mean values were compared using the Spss software and the Anova test (posttest: Tukey). That p <0.05 has been made as meaningful. Incubation of blood samples with mifepristone induces genotoxicity in lymphocytes and the adjacency of cells with Naringin significantly reduces the number of micronucleus (p<0.05). The results of this study have shown a significant role of Naringin as the protective factor against the genotoxicity of mifepristone.

Conclusion: In this study, Naringin was found to be a protective agent against the DNA damage caused by mifepristone, and since Naringin alone has no genetic disorder; it can be used as a protective agent against the toxic effects of mifepristone.

Background : baclofen is gamma-amino butyric acid (GABA) agonist is an inhibitory neurotransmitter in the mammalian nervous system and is also found in peripheral tissue including lung. It is also used in muscle spacity and cerebral spacity . in this study the efficacy of baclofen cream 5 % in reducing postoperative pain during defecation after hemorrhoidectomy was investigated.

Introduction: A total of 66 patient with third and fourth degree hemorrhoids open hemorrhoidectomy were included  in this prospective double blind randomized controlled trial. The patients were randomly assigned to either baclofen cream or placebo immediately after surgery and then every 12 h for 14days. The primary outcomes were intensity of pain during defecation, measured with a visual analog scale.

Methods and Results: there was no significant difference in the average postoperative pain score in the first 48 h ( P₂₄= 0.3 , P₄₈= 0.5 ) after the surgery between the two groups, but at week 1 the pain score during defecation were considerably lower in the baclofen group than in placebo group ( P=0.01) , which also was the same at the week 2 (P=0.02) . there was no significant difference in the average acetaminophen administration at 24 , 48 h between 2 group after surgery, but  Acetaminophen requirement after week1  and week 2 in baclofen group significant lower than placebo ( P_week1= .025      P_week2 = .024 )  

Conclusions:

. compared with baclofen cream and placebo reduced postoperative pain and painkiller requirment during defecation .

Introduction:

Evening primrose oil is a rich source of linoleic acid and gamma-linolenic acids and can be quite beneficial for reducing the inflammation caused by acne. Besides, by restoreing  hormonal balance, evening primrose oil can prevent acne flare ups in women. Among different strategies of delivering oils, nanoemulsions possess improved transdermal and dermal delivery properties in vitro and in vivo. Nanoemulsions, transparent dispersions of oil and water stabilized by an interfacial film of surfactant having the droplet size less than 200 nm, are thermodynamically stable. The aim of the present study is to develop and optimize an evening primrose oil-based nanoemulsion and investigate its physicochemical properties intended for topical applications.

Methods and Results:

The nanoemulsions were prepared by stepwise addition of water to the mixture of Tween 80 and evening primerose oil (as surfactant and oil phase) followed by homogenization and sonication.  The mean droplet size, polydispersity index, zeta potential and short and long term stability properties of the optimized preparation were evaluated.

The optimized nanoemulsion was composed of 20% tween 80, 5% evening primerose oil and 75% water. The results showed that the mean particle size of optimized nanoemulsion was 164 nm with a uniform size distribution (PDI< 0.3) and It had a zeta potential of -0.28. The aformentioned nanoemulsion showed the ideal physicochemical stability in a 90 days period

Conclusions:

According to the results of size, zeta potential and stability tests, incorporation of evening primerose oil into a nanoemulsion formulation can be a promising tool for topical administration of this anti-acne medicine. nanoemulsion appears to be a good choice for the treatment of acne and other skin disorders including eczema and psoriasis and may also be used as a vehicle to carry other lipophilic drugs for more effective treatment against acne.

Introduction:

Pigmentation disorders are common skin diseases caused by a wide range of etiologic factors such as pregnancy, sunshine and some drugs, for example minocycline etc. Vesicle-entrapped anti-hyperpigmentation agents can protect the therapeutic compounds from environmental destructive causes (light, oxygen and …) and they also provide a sustained release condition in the skin application of these medications. Hereby, we present the initial report, on the basis of our knowledge, on a niosomal preparation with two active pharmaceutical agents.

.

Methods and Results:

Kojic acid (KA) and hydroquinone (HQ) were chosen as typical depigmentation agents. Many niosomal formulations were prepared by film hydration method in which co-encapsulation or separate entrapment of these compounds were evaluated. Span (20, 40, 60 or 80), Tween (20, 40, 60 or 80) and cholesterol were the main bilayer formation compounds and deionized water, normal saline and phosphate buffer were utilized as hydration media. A few formulations resulted in formation of stable multilamellar vesicles (MLVs) with high encapsulation efficiency of active agents. Therefore, we used direct mixing method for niosome formation which showed appropriate formulation properties with average volume diameter less than 10 µm, high encapsulation efficiency and high protection ability for HQ against oxidation depicted as no color change was detected during the long term storage in open door jars. Release studies on prepared formulations showed a sustained drug delivery profiles for all vesicular formulations.

Conclusions:

Obtained results promised a new and appropriate drug delivery system for KA and HQ. Clinical trials with permitted ethical requirements should be done for application of these niosomes in topical niosomal gel, cream or lotion formulations.

Introduction: Interleukin 18 is a proinflammatory cytokine from IL-1 cytokine family and plays a central role in inflammation. In fact, it is an IFN-gamma-inducing factor (IGIF). Interleukin 18 increases the response of Th1 cells, cells that are dominant in atherogenesis and cause growth of atherosclerosis plaques. The concentration of circulating IL-18 predicts the probable mortality from cardiovascular problems in CAD patients and plays a key role in atherosclerosis, which is one of the reasons for CHF.

Methods and Results: The proinflammatory cytokines of IL-1β, TNF-α, IL-6 and LPS induce IL-18 gene expression and IL-18 causes an increase in the proinflammatory cytokines of IL-1β, IL-6, TNF-α, GM-CSF growth factor, and nitric oxide and cyclooxygenase (cox-2) and thus interleukin 18 causes inflammatory diseases. The Heterodimeric IL-18 receptor is expressed in a variety of cells, including macrophages, T lymphocytes, and NK cells. These cells have a key role in atherosclerotic plaque rupture. The IL-18 binding protein, a natural endogenous inhibitor that is present in high concentration in the extracellular environment and is highly associated with IL-18, interferes with its receptor interaction, thus inhibits IL-18 activity. The level of IL-18 in coronary patients significantly increases and its serum level in CAD patients who die from cardiovascular problems is more than CAD patients who are still alive. In animal models, IL-18 administration has been shown to increase the size and number of clots associated with T lymphocytes and this effect has been eliminated in animals with interferon-gamma deficiency. Angiotensin II increases the expression of IL-18 in arterial smooth muscle cells by AT1 receptors. Losartan will slow down this process. We also know that losartan increases EF and decreases TNF-α and improves left ventricular function in HF patients. It has been shown in a study that stimulation of β-adrenergic receptors by isoproterenol during a series of events increases the transcription and expression of the IL-18 gene, and these events can occur similarly in HF.

Conclusions: There is a strong association between serum IL-18 level and future cardiovascular problems so Inhibition of IL-18 signaling by IL-18 binding protein will be a new therapeutic strategy.

Introduction: The treatment of skin burning is one of the most important problems in medical sciences. Burns are divided into 3 degrees and each degree has different damage and effects on skin and other related tissues. Many efforts have been applied by clinicians to manage wound healing through the use of genes, cytokines, chemokines and surgery. Some involved mechanisms in the process are local tissue hypo perfusion, edema, prolonged inflammation, hypercoagulability, free radical damage and accumulation of cytotoxic cytokines.

Methods and Results: Twenty-six female laboratory Wistar rats weighing 200-250 grams obtained, and all the rats were kept in controlled temperature of 23-25 ºC and light period of 12-hours lightening and 12-hours darkness. Due to make burns after rats’ general anesthesia Ketamine (40 mg/kg) and Xylazine (5 mg/kg) by Intraperitoneal (IP) method was performed, after shaving of rats, a brass metal piece 1.4 cm × 3 mm thickness with 100 ºC was kept on back of rats for 15 seconds and it was made similar deep second-degree burns. No significant difference was found among four groups regarding the primary wound surface area. The rats randomly were separated into 4 groups each one consisting of 6 rats. In the control group the burn injury only was covered with sterile gauze, Artaderm ointment group, cod liver oil group, Eucerin group. The injury area was covered with sterile gauze bandage and this process continued for 21 days. On the 0, 7th, 14th and 21st day of the experiment, tissue samples were taken under anesthesia from predetermined areas from all subjects in all groups. Wounds were daily examined for any changes in appearance of wounds, the color, and smell of any discharge and time of scar separation.

Conclusions: Statistical comparison of the burn area of study groups on days 7-14 and 21 post-burn, showed a significant difference (p< 0.05) between the control group and other groups. The best results obtained from the group treated by Artaderm. According to studies, pathology quickly restored with Artaderm. Cell repair in the treated group by Artaderm herbal ointment was significant compared to other groups after staining with H&E. Finally, Artaderm successfully demonstrated its therapeutic effect in terms of healing the wounds.

Introduction: : Recently, considerable attention has been devoted to biopolymers because of their unique properties and high usage in different fields such as pharmaceutical industry, health promotion and cosmetic applications .Pectin is a high-molecular weight and anionic natural heteropolysaccharide extracted from cell walls of higher plants which is non-toxic and biocompatible.(1)

A cross-link is a bond that links one polymer chain to another. Strontium (Sr+2) establish covalent bonds (chemical method) and physical interaction (physical method) between anionic pectin chains that makes polymer stronger.

Methods and Results: : Firstly, specific amounts of pectin were dissolved in distilled water. Then, a fixed amount of triethyl citrate (1:6 ratio related to total polymer content) was added to solution as a plasticizer. After 24 hour, free film was cross-linked with 1% strontium carbonate solution for 1 minute .For swelling experiment, a piece of dried cross-linked and non cross-linked pectin based free film was weighted and immersed in flasks of dissolution test containing 250 ml of acidic media(PH=1.2) and phosphate buffer media(PH=6.8) at 37 ℃. sampling time was started from 2 minutes to 60 minutes. To quantify the swelling process, the swelling index, Is (%),was calculated(2).

Thickness of both cross-linked and non cross linked pectin based free film was 0.16

The present study was designed to investigate the possible hepatoprotective effect of berberine (BBR) nano micelles on liver cirrhosis induced by bile duct ligation model (BDL) in male rats.

Introduction: The anti-fibrotic effect of chronic berberine (BBR) had previously demonstrated in a rat model of bile duct ligation (BDL) - induced liver fibrosis. As a result, the aim of present study was to investigate the possible hepatoprotective effect of BBR nanomicelles on liver cirrhosis induced by Bile duct ligation model (BDL) in male rats.

Methods and Results: Male Wistar rats were divided into 7 groups (n= 6) including sham-operated, BDL + saline, BDL + nanoBBR (50 mg/kg, p.o.), BDL + nanomicelles, BDL + BBR (50 and 100 mg/kg, p.o.), BDL + silymarin (100 mg/kg, p.o.). After 21 days of drugs' treatments following bile duct ligateation, the serum and tissue levels of some hepatic markers were measured and pathologic evaluations performed.BDL could markedly increase aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBIL) serum levels and tissue tumor necrosis factor-alpha (TNF-α), level along with reductions in tissue levels of glutathione (GSH), superoxide dismutase (SOD) and total protein levels. On the other hand, BBR nanomicelles (50 mg/kg, p.o.) and silymarin (100 mg/kg, p.o.) markedly decreased the serum levels of AST and ALT while enhanced GSH level. In addition, BBR nanomicelles (50 mg/kg, p.o.), silymarin (100 mg/kg, p.o.) and BBR (100 mg/kg, p.o.) groups showed a considerable increase in SOD levels. BBR nanomicelles (50 mg/kg, p.o.) significantly lowered TNF-α level. In addition, nanoBBR group prevented liver cirrhosis in histopathologic analysis.

 Conclusions:Therefore, formulation of BBR nanomicelles may represent a good approach to enhance the effect of BBR in liver injuries.

Introduction: The statistics show that the numbers of cancer reports is increasing and need for development of new anticancer drugs is a principal aim in current medicinal chemistry. Due to very limitations of current antineoplastic therapeutics such as high incidence of adverse effects and intuitive resistance of tumor, discovery of new anticancer agents feel to be crucial.

Methods and Results: Synthesis and cytotoxicity assessment of 1,3,4-thiadiazole derivatives led to the discovery of new compounds with potential anticancer activity. MTT assay was done against three cancerous cell lines containing PC3 (prostate carcinoma), HT-29 (human colon adenocarcinoma) and SKNMC(neuroblastoma) in comparison with doxorubicin as reference drug. All synthesized compounds were identified using spectroscopic techniques like ¹HNMR, IR and MS. The synthesized derivatives were afforded with high yields. All target compounds were tested against MCF-7 (breast cancer), H1299 (non-small cell lung carcinoma), A2780 (ovarian carcinoma). Tested derivatives exhibited favorable anticancer activity in vitro compared to doxorubicin in MTT assay. Various derivatives such as Cl, Br, CH₃ and F substituents were the best moieties for para positions of the phenyl ring (less than 1 µM). Some of tested compounds with these moieties showed superior activity than doxorubicin. Caspases activation was also explored for tested derivatives.

Conclusions: The 1,3,4-thiadiazole derivatives that prepared in the current project displayed significant anticancer activity and apoptosis induction. These agents could be proposed as novel anticancer lead compounds.

Origanum majorana (Lamiaceae) is well-known for high Phenolic contents. These compounds prone to have antibacterial activity. UTI with high prevalence and increasing resistance to conventional antibiotics is a matter of concern for health services. E.coli is the most detected pathogen in UTI cases(1). So the aim of present study was to investigate the effects on O.majorana essential oil on and E.coli and it’s chemical constituents.

 Materials and Methods:

Aerial Parts of O.majorana were collected from population growing in Golestan province. A voucher specimen was deposited to the plant species in herbarium of Department of Pharmacognosy, School of Pharmacy, Hamadan University of Medical Sciences. The air dried plant material was subjected to hydrodistillation to prepare essential oil. The essential oil kept in refrigerator until use. The essential oil was injected to GC/MS for identification of constituents. The zone of inhibition against E.coli were determined using Agar well diffusion method.

Results:

Forty-four Compounds were identified in the essential oil. The major compounds were Thymol (18.58%), P-cymen (14.34%), 4-terpineol (13.25%), γ-terpineol (10.88%), α-terpineol (5.63%), linaleol (4.98%) and E.caryophyllene (3.53%), respectively.

The zone of O.majorana essential oil against E.coli was.

Discussion:

The findings of present study shows profound antibacterial effects of O.majorana essential oil on E.coli.

the main component of the plant is thymol as detected by GC/MS. Thymol has a phenolic structure. The profound effect of plant on E.coli may be related to Thymol(1).

Conclusion:

O.majorana essential oil may be a candidate for treatment of UTI.

surface properties in tissue engineering can be considered as novel approach. In this research diverse substrate with different physical parameters are designed according to specific cellular functions.

Introduction: In the context of tissue engineering, surface features can be considered as important design parameters. In this regard, chemical and physical cues in synthesized substrate modulate biological reactions. Therefore to obtain desirable cellular functions, optimized features of surface substrate were necessary. Roughness and stiffness are physical characteristics which affect cellular fate.

Methods and Results: SYLGARD 184 (silicone elastomer kit) was purchased from Dow Corning, Tokyo, Japan. To achieve diverse stiffness in PDMS (poly- dimethyl sulfoxide) three compositions of precursor and curing agent were mixed and samples of S1, S2, and S3 with the proportion of 1.6, 5 and 16 bases to curing agent were prepared, respectively. In the procedure of PDMS fabrication, after through mechanical stirring, each sample was degassed under vacuum for 20 minutes and the mixture was poured into the mold and cured at 75 °C for 24 hours. To gain assorted roughness in PDMS substrates, SDBD plasma (Iran) was applied. The proportion of base to curing agent for plasma treatment was set 10:1 and the plasma power and electrode distances were 30 W and 2 mm, respectively. Different roughness in PDMS surface was accomplished by different processing durations of 30, 90 and 180 seconds (R2, R3, and R4) with a template without any plasma exposure as the control (R1). Atomic force microscopy (AFM) and bulk elasticity were measured by tensile test. AFM images of various surface substrates in which exposure plasma times were altered, quantitative root mean square roughness of R2, R3 and R4 were assigned as 174.92, 189.22 and 326.7 nm, respectively. Hence, surface topography has changed with changes in plasma radiation times on the surface.

Conclusions: This study showed that by changing in plasma time exposure and proportion of base to curing agent in PDMS, roughness and stiffness can be optimized base on specific cellular reactions. So, synthesized substrates with distinctive physical properties can be appropriated for particular cellular function. 

Introduction: Sorafenib is an antineoplastic and tyrosine kinase inhibitor. Sorafenib used as a treatment for renal cell carcinoma (RCC), unresectable hepatocellular carcinomas (HCC) and thyroid cancer. In this study, niosomes containing sorafenib were formulated by thin film hydration method for improve the therapeutic performance of sorafenib. 

Methods and Results : Different niosomal formulations comprised of non-ionic surfactants including sorbitan esters (Span 20, 40, 60, 80) and polysurbates (Tween 20, 40, 60, 80), cholesterol were prepared using thin film hydration method to investigate the physicochemical characteristics of niosomes including particle size, microscopic stability, sorafenib release into deionized water/ethanol (40:60) from the niosomes using Franz cell,  sorafenib entrapment measurement. The sorafenib concentration was determined by spectrophotometer in 265 nm. Span/Tween 80 did not form niosome, but the other formulation formed niosomal suspensions. Most of the niosomes were multilamellar vesicles (MLV). The release data was best fitted by Baker-Lonsdale’s release model.

Conclusions: A normal logarithmic particle size distribution was observed in some of the formulations. Niosomes had high physical stability during 6 months storage at refrigerator temperature. For clinical applications more studies on in vivo will be required in future studies.

Labor pain relief is one of the challenges in health care systems in the most countries and is the main goal in midwifery cares.

Introduction: This study aimed to investigate the chamomile breath on this pain intensity in the first stage of labor on prim parous women in Abhar Emdadi hospital in 2013.

Methods and Results: This study was a randomized clinical trial carried out on 130 eligible prim parous women (65 in intervention and 65 in control group) at Emdadi Hospital of Abhar. The pain severity was measured at the moment of enrolling in the study. In the aroma therapy group gauze was soaked in 2 drops of Matrica camomilla water and in the control group gauze were soaked in 2 drops of distilled water and attached to the woman collars. The intervention was repeated every half an hour. Pain severity was measured in first and after intervention in 3-4, 5-7, and 8-10 centimeter dilatations. The samples were followed up until delivery. The materials used in this study were the demographic and obstetrics questionnaire, observation and exam checklist and the numeral scale of pain measurement. Independent T-test, the Mann-Whitney and Chi-squared test was implemented to analyze the data using SPSS v22 while the significance level was (0.05).

The two groups were homogenized regarding age, profession, education, wanted pregnancy and number and severity of uterus contraction. The bishop score was calculated as well. Before intervention, the mean pain severity score after the intervention in intervention group in 3-4 cm (5.75±1.99), 5-7cm (7±1.52) and 8-10cm (7.01±1.22) decreased significantly compared with control group in dilatation 3-4 cm (8.93±1.96), 5-7 cm (9.41±0.63) and 8-10 cm (9.8±0.40) (p<0.005).

Conclusions: The findings of the study revealed that aromatherapy of M. chamomilla water alleviates the labor pain. Therefore this method is recommended due to reducing the labor pain.

Introduction: Insomnia is a common problem among the people all over the world. This problem affects both sleep’s quantity and quality. Among sedative-hypnotic drugs, barbiturates are more toxic than benzodiazepines. Besides, current benzodiazepines have many side effects like dependence, muscle relaxation, and withdrawal syndrome. Attention to synthesize novel benzodiazepine like derivatives, which have fewer side effects, has been improved. Thiazolidinone derivatives are novel benzodiazepine-like compounds that have all pharmacophores like lipophilic group and aromatic ring for binding to the benzodiazepine receptor (GABA).

Methods and Results: In this research hypnotic effect of two novel thiazolidinone derivatives were evaluated, using pentobarbital-induced loss of righting reflex test. Open field test, was used to evaluate the locomotor activity of the mice in all groups. Male mice in the range of 18-25 g of weight were used in all tests. Moreover, diazepam and flumazenil were used as an agonist and antagonist of GABA-A receptor respectively to indicate that the novel compounds show their effects through interacting with benzodiazepine receptors. Compound SM4 at the dose of 20, 30, and 40 mg/kg (i.p.) and compound SM6 at the dose of 30 and 40 mg/kg (i.p.) increased the sleeping time dose-dependently and showed significant hypnotic effects compared to the control group in the righting reflex test. Also, the sleeping time was decreased by the injection of flumazenil as an antagonist of GABA-A receptor after the injection of each compound. In the open field test, both compounds at the dose of 20, 30, and 40 mg/kg (i.p.) decreased the total distance moved which indicates sedative effect of the novel compounds.

Conclusions:The results indicate that both compounds (SM4 and SM6) have sedative-hypnotic effects, which may be due to an interaction between novel benzodiazepine-like compounds and GABA-A receptor. We recommend further studies to determine the exact mechanism of action and toxicity of the novel compounds.

Introduction: Poor water-solubility is a common characteristic of drug candidates in pharmaceutical development pipelines today. Various  processes  have  been  developed  to  increase  the  solubility,  dissolution  rate  and bioavailability  of  these  active  ingredients  belonging  to  BCS  II  and  IV  classifications. Therefore, enhancement in the solubility of such drugs would be important to the pharmaceutical industry. There is a number of formulation approaches to resolve the problems of low solubility and low bioavailability of drugs. These techniques for solubility enhancement have some limitations and hence have limited utility in solubility enhancement. Nanotechnology can be used to resolve  the  problems  associated  with  these  conventional approaches  for  solubility  and  bioavailability  enhancement

Methods and Results: There are many techniques which are used to enhance the aqueous solubility. The ability to increase aqueous solubility can thus be a valuable aid to increase efficiency and/or reducing side effects of drugs. This is true for parenterally, topically and orally administered solutions. Hence various techniques are used for the improvement of the solubility of poorly water soluble drugs including hydrotrophy, use of salt form, use of precipitation inhibitors, alteration of pH of the drug micro-environment, solvent deposition, precipitation pH adjustment, co-solvency, micellar solubilization, super critical fluid techniques, solid dispersions, complexation, micro-emulsions, solid solutions, eutectic mixtures, selective adsorption on insoluble carriers, evaporative precipitation into aqueous solutions, use of surfactants, use of amorphous, anhydrates, solvates and nanonisation.

Conclusions:

Solubility is a major challenge for formulation scientist. Any drug to be absorbed must be present in the form of solution at the site of absorption. Various techniques used for the enhancement of the solubility of poorly soluble drugs like physical and chemical modification of have specific advantages and draw backs. Selection of solubility improving method depends on drug property, site of absorption, and required dosage form characteristics.

Introduction: Cyclophosphamide is used to treat cancers and autoimmune diseases. It is used to quickly control the disease. Because of its toxicity, it is replaced as soon as possible by less toxic drugs. Regular and frequent laboratory evaluations are required to monitor kidney function, avoid drug-induced bladder complications and screening for bone marrow toxicity.

Methods and Results: The statistical population consisted of 75 blocked and paraffinized prostate cancer samples and 60 healthy tissue samples obtained from the Iranian Tissue Bank. RNA was extracted using TRIzol™ precipitation method. Specific sequences were then amplified for both groups by RT-PCR. Afterward, specific regions were cut by RFLP technique.

Results: Based on the results, 65% of the patient samples showed significant relationships with CD82 gene expression (P = 0.01, OR = 0.94, Cl = 0.61-2.23). The gene expression also increased with age to a certain degree in the patient group (P = 0.1, OR = 0.82, Cl = 0.60 – 1.98).

Conclusion: The expression Cyclophosphamide for the treatment of Prostate Cancer Skeletal Metastasis compared to  the control group. This result could indicate that the gene can be used as a biomarker for the identification of people at the risk of prostate cancer.

Introduction: Microencapsulation technology is a valuable technique for protection and delivery of materials which cannot be administered alone due to their low solubility, volatility and etc. A biopolymer alginate has been used most commonly as microcapsule forming material. In order to increase the mechanical stability and safety of alginate microcapsules, multilayered microcapsules are prepared. Alginate-poly l-lysine alginate, is the oldest multilayered microcapsule. Introducing another polycationic polymer which has similar properties to poly l-lysine (PLL) and also is  much more cost effective , so it might be a valuable suggestion. The aim of this study was to compare linear (LPEI) and branched (BPEI) form of polyethylene imine, with the oldest and rather expensive one, PLL, and also, we have compared sodium cellulose sulfate (NCS) as an anionic layer with sodium alginate in outer layer of multilayered microcapsules to investigate the effect of different covering layers in microcapsule’s cytotoxicity.

Methods and Results: In this study by using electrostatic bead generator different types of microcapsules, APA, ALA and ABA were produced. Shape, size, surface morphology, mechanical stability and cytotoxicity of microcapsules were evaluated using optical microscope, SEM, explosion test and MTT assay respectively. According to shape and size evaluation, multilayered microcapsules with different cationic layer concentrations (0.01, 0.03 and 0.06 W/V %) were spherical, with a diameter range of 500- 900 μm. SEM images showed uniform and smooth surfaces. Explosion test revealed that applying cationic solutions with 0.03% and 0.01% concentration resulted in higher mechanical stability for ALA and APA in comparison to ABA (P<0.05), while mechanical strength induced by cationic solutions with 0.06% concentration were not statistically different in all three groups of microcapsules (P>0.05). MTT assay on HepG2 cell line was performed using microcapsules ALA, ALN, APA and APN and showed no statistically significant difference in cell viability for the all types.

Conclusions: According to our results, LPEI as a covering layer for alginate microcapsules showed the same properties as PLL. Therefore it could be introduced as a cost effective alternative to PLL in fabrication of multilayered microcapsules.

Introduction: Skin is the most important barrier to protect our body, therefore supporting this fundamental organ against to sun rays is very important. Herbal formulations may  have less harmful effects. Considering the previous studies carried out on Punica granatum var.pleniflora (Golnar-e-Farsi), an approximately unknown Iranian plant, have shown the sunscreen effects, the phototoxicity and cytotoxicity of this plant was evaluated in this research.

Methods and Results: In this study, five different concentrations of methanolic extracts of plant (50, 75,100,125,150µg/L) were provided. The prepared extracts were determinded for SPF and PIF values. Evaluation of cytotoxicity and phototoxicity effects  were used by B16  and 3T3 cells with a number of 5000 cells for each skin in a 96-well plate. Positive controls were taxol and chlorpromazine respectively .The results were indicated as Mean ±SEM and were compared using ANOVA with TukeyPost Hoc. To calculate IC50, Probit analysis was used. At the applied concentration,10μg/ml, all of the extracts, showed a little cytotoxicity, however calculated PIF did not show any phototoxicity for the extracts. Transmittance values for concentrations 50, 75,100,125,150µg/L. The wavelength range 292.5-337.5 nm was measured at intervals of 5 nm. For this plant calculated PIF did not show any phototoxicity for the extracts SPF is calculated 9.35 for metanolic extract.The extracts did not have cytotoxic effects and also at the above-mentioned concentration they did not show phototoxicity. Thus, the extracts can be considered as appropriate agent  for herbaceous sunscreen products.

Conclusions: The extracts of Punuca Granatum did not have cytotoxic effects and also at the above-mentioned concentration they did not show phototoxicity. Thus, the extracts can be considered as appropriate candidate for herbaceous sunscreen products, after doing more tests.

A new series of anti-cancer agents based on cyclopeptide scaffold containing methyl sulfonyl group at the para position of the C-4 phenyl ring were synthesized and their cytotoxic activities were determined against several human cancer cell lines. compounds, c Glu-Ser-Pro-Lys-PhSO₂Me (1v), c Gly-Pro-Ala-Lys-PhSO₂Me (2v) c Ser-Glu-Gly-Pro-Lys-PhSO₂Me (3v) c Lys-Gly-Pro-Asp-PhSO₂Me (4v)   c Asp-Gly-Pro-Lys-PhSO₂Me (5v) were synthesized and characterized by lc-mass spectroscopy and NMR .based on the results  the most potent cytotoxic cyclicpeptide against A549 cell line was (1v) with IC50 values 3.18 µM  and the most potent cytotoxic cyclicpeptide against MCF-7 cell line was (5v) with IC50 values 2.46 µM   respectively, while most of the compounds had sufficient activity against MCF-7, HEPG-2 , HT-29 and A-549 cell lines are with mean IC50 values ranging from 2.46 to 31.44 µM.

Introduction: The logical design of this study was based on the use of pharmacophoric moiety of COX-2 inhibitors with aromatic or cyclic amino acids and acidic amino acids to simulate the structure of COX-2 inhibitors. As a result, it would be appealing to COX-2 inhibitors with peptide structure which show antitumor and anti-inflammatory effects.

Methods and Results: The results clearly indicated that modified cyclopeptides (1v - 5v), showed significant cytotoxic activity against all chosen cell lines. Compound (5v) showed a great anti-cancer activity against MCF-7 cell line and Compound (3v) showed a great anti-cancer activity against A549 cell line.

Conclusions:

In this study we synthesized 5 modified cyclopeptides by solid phase peptide synthesis approach and examined the cytotoxicity of them on 4 different cell lines. This study indicates that all synthesized compounds showed significant cytotoxicity against different cell lines specially against MCF-7 and A549 cell lines. In addition, modifications on the sequence of modified cyclopeptides had a significant influence on the cell cytotoxicity.

Introduction: Apoptosis is a process of programmed cell death that plays several critical roles in normal biological events happening in multi cellular organisms. Tissue homeostasis, defense against pathogens and involvement in development by controlling the number of cells are some of these critical roles. The two best-described activation mechanisms are the intrinsic (also called the mitochondrial pathway) and the extrinsic pathways. The formation of a supramolecular complex called apoptosome in mammals is tightly linked to ignition of the intrinsic pathway. This complex mainly consists of Apaf-1 molecules (apoptotic factor protease activating 1). The assembled Apaf-1 in apoptosome leads to the formation of functional caspase-9 that it further triggers the caspase cascade, a fundamental cascade that subsequently causes cell death. So detecting the formation of the apoptosome complex will help to screen the drugs and substances inducing intrinsic pathways also it helps in cell death related researches.

Methods and Results: we utilized previously developed split luciferase biosensor to investigate apoptosome activity of cells that were treated with Tunicamycin. Tunicamycin is an inhibitor of glycosylation that disturbs protein folding machinery in eukaryotic cells. Tunicamycin causes accumulation of unfolded proteins in cell endoplasmic reticulum (ER) and induces ER stress. ER stress is an essential mechanism for cellular homeostasis which has a role in cell death via reprogramming of protein processing, regulation of autophagy and apoptosis. Therefore, it can trigger apoptosis by induction of protein release such as cytochrome c that stimulates apoptosome formation. The biosensor consists of two separate constructs, N-terminal luciferase-Apaf-1 and C-terminal luciferase-Apaf-1. These constructs are cotransfected into mouse embryonic fibroblasts cells by polyethyleneimine (PEI). When apoptosome complex forms the assembling of Apaf-1 proteins brings the Nlucs and Clubs in spatial proximity that enables the enzyme to catalyst its substrate luciferin and bioluminescence. Split luciferase activity measured in several times after induction by Tunicamycin

Conclusions: apoptosome activity has fluctuation mode and we can control this complex activity by pharmacokinetic features of related drugs.

Introduction: Acrylamide (ACR) is used in an extensive industrial applications and scientific studies. ACR can be produced through food processing at high temperatures via the Maillard reaction. ACR as a chemical and its metabolite glycidamide causes cell toxicity and damage to DNA and proteins in the body. This study was designed to investigate the ACR-induced apoptotic effects on NIH/3T3 fibroblasts in cell culture.

Methods and Results: The NIH/3T3 cells were treated with ACR in different concentrations (1, 2, 5, 10 mM). After 24 hours incubation, early and late apoptosis, necrosis, and viable cells were counted. Type of cell death (apoptosis, necrosis) induced by ACR is characterized by Annexin V-FITC and Propidium Iodide (PI). Moreover, caspase 9 and 3 were measured via colorimetric assay. Flow cytometric result showed, the percentage of live cells in 10 mM of ACR were significantly reduced compared to the control group that was accompanied by an increase in necrotic cell death. ACR compound caused an increased in Caspase 9 activity in a dose-dependent manner, the activities of caspase 3 also showed a significant increase compared to the control group only at concentration of 10 mM.

Conclusions:

Our findings showed that exposure to ACR could induce apoptosis at high concentrations in embryonic fibroblast cell. Moreover, it was shown that acrylamide induces necrotic cell death at the high concentration of 10 mM ACR.

Introduction: Sepsis, a common and costly cause of inpatient mortality in both sexes and all age groups (particularly in intensive care units), ensues an inflammatory process involving a variety of pathogen-expressed conserved structures called pathogen associated molecular pattern (PAMP) which are considered the main cause of oxidative stress and increase in inflammatory markers.

Methods and Results: In this murine model study, male Wistar rats were assigned into three groups: CLP with gauge 18, CLP with gauge 21, and a sham group (a group without CLP). Subsequently, 24 hours following the surgery, all animals were sacrificed and inflammatory markers such as myeloperoxidase (MPO), reactive oxygen species (ROS) and lipid peroxidation (LPO) were measured in their cardiac tissues. In CLP group with gauge 18, LPO, ROS, and MPO were significantly increased in comparison with the other two groups. Moreover, although lower in comparison with the gauge 18 CLP group, LPO, ROS, and MPO were significantly higher in gauge 21 CLP group compared to the sham group.

Conclusions: In murine models of sepsis, the gauge size can be influential in study outcomes and inflammatory changes observed in gauge 18 CLP mice can be considered as the most reliable and clinically-relevant indicators of sepsis-induced inflammation in humans. 

Introduction: Aging is a process characterized by an irreversible growth arrest in somatic cells which caused reactive oxygen species (ROS) products, lipid peroxidation, and DNA and proteins damage. The specific objective of this study was to assess a well-known natural antioxidant compound, Gallic acid (GA) for its anti-aging potential, and evaluate the mechanisms involved in attenuating H₂O₂ induced cellular senescence in rat embryonic fibroblast (REF) cells.

Methods and Results: To begin this process, REF cells were pre-incubated with GA for 24 hours, subsequently were exposed to hydrogen peroxide (H₂O₂) for 2 hours. After the incubation time, cell viability, ROS level as well as senescence-associated (beta)-galactosidase (SA-β-GAL) activity, mitochondrial complex I, II and IV enzyme activities, and cell cycle distribution via flow cytometry were investigated. GA declined the cytotoxic effects of H₂O₂ in REF cells. Analysis of cell cycle showed in REF cells treated by GA the percentage of G0/G1 arrest was diminished compared to the H₂O₂ group. Additionally, GA potently decreased the levels of ROS as well as mitochondrial complex activities. Furthermore, qualitative and quantitative investigation of SA-β-GAL activity demonstrated GA can also decrease cellular senescence.

Conclusions: The findings of this study offer some important insights into the protective effect of GA on controlling cellular senescence and aging process. The results presented support to these hypotheses that GA diminish the oxidative stress of REF cells in cellular senescence. Moreover, incorporation of GA as a protective antioxidant agent works by attenuating the ROS, subsiding mitochondrial complex activities, and affecting cell division.

Introduction: Farnesyl transferase inhibitors (FTIs) are a new class of drugs which are under clinical trial examinations for cancer treatment. Saffron extracted components have been reported to be of pharmaceutical properties when are applied in vivo/ in vitro against variety of diseases including cancer. Crocin is one the main chemicals in saffron which is suggested to be of cytotoxic effects against cancer cell lines. However, the exact mechanism of function of crocin against cancer cell lines is still remained to be illustrated by more research. In the present study the effect of crocin in inhibition of lamin B farnesylation was examined.

Methods and Results: Crocin was extracted from saffron and purified by column chromatography as described by bathaie et.al. MCF-7 was cultured on DMEM media containing 10% FBS. Using 96-well-plates, cells treated with an increasing concentration range of 10-5000 ug/ml of crocin. After 24h, MTT assay was carried out to determine the IC₅₀. Cells were treated with crocin (IC₅₀) for 24h to induce cell death, and expression of Lamin B, as well as pernylated/ unprenylated Lamin B was assessed by western blotting, using primary antibody against lamin B (Santacruz, USA) and secondary HRP-tagged anti-rabbit (Sigma, Germany).

Our results indicated that 3500ug/ml of crocin induced cell death in half of cell population upon 24h. We also observed that treatment of MCF-7 cells with 3500ug/ml for 24h results in an obviously significant decrease in lamin B protein expression. Data from gel shift assay analysis also showed that crocin induces prenyl-transferase- inhibitory mechanism in cells which is seen as a two separated bands of lamin B (including prenylated and unprenylated forms) compared to single band pattern in control.

Conclusions: In conclusion, our results proposed that crocin induces prenyl transferase inhibition in MCF-7 cell line of breast cancer and therefore, it could be suggested as a potent phyto-compound for research and developing FTIs.

Introduction: Iron, through the reaction of Fenton, generates free radicals such as active oxygen radicals and activates the oxidative stress pathway. The oxidative stress due to the increased iron level in the brain regions plays  an important role in creation of neurodegenerative diseases.

Methods and Results:In this study, the mitochondria of the brain tissue of Wild Wistar Rat isolated from various centrifuge rounds and with the concentrations of Fe (so4).7H2o were incubated at 30 and 60 minutes. To determine IC50 Fe (so4).7H2o, the mitochondrial survival ratio was measured by MTT test. Mitochondrial suspension with the concentration of 0.5 mg protein/ml at various concentrations of Fe (so4).7H2o was placed in a shaker incubator at 37° C for 30 and 60 minutes. Then the activity of mitochondrial complex 2 and the formation ratio of reactive oxygen species was investigated. The results showed that IC50 ratio for Fe (so4).7H2o was 20 and 5 μg/ml at 30 and 60 minutes, respectively, and mitochondria incubation isolated from the brain tissue of the rat with Fe (so4).7H2o can disrupt be the electron transfer chain and significantly increases the formation of reactive oxygen species compared to the control group (P <0.001).

Conclusions:The findings of this study indicate that Fe (so4).7H2o disrupts electron transfer chain in the mitochondria and causes increasing ROS production. This excessive increase of ROS can activate the oxidative stress pathway and ultimately activate the cell toxicity pathways.

Introduction: Leishmania is a major public health problem worldwide. The aim of the present study was to investigate medicinal plants with anti-Leishmania activity which used in the world.

Methods and Results: Data were systematically gathered from five English databases including Ebsco, Science Direct, PubMed, Google Scholar and Scopus, and four Persian databases including Magiran, Irandoc, Iran medex, and the Scientific Information Database (SID) from 2000 to April 2017. Obtained information included plant family, extraction method, extract concentration, animal models and parasite species. A total of 27 papers, including 44 experiments (26 in-vitro and 18 in-vivo), were eligible between 2000 and 2017 for systemic review and meta-analysis. Various species of Allium spp. were studied in Leishmania species. The study showed that there is not much diversity among studies. Result showed the highest proportion of Allium species used in the world as anti-leishmaniasis was Allium sativum.

Conclusions: The present systemic review provides valuable information about natural products with anti-Leishmania activity, which would be examined in future experimental,  clinical trials, and herbal combination therapy.

Introduction: Pain is a kind of problem that almost all humans have experienced. Although it does not require treatment in mild cases, pharmacotherapy is essential in severe ones. Various drugs are currently being used for this purpose. One of the problems with all these drugs is high rate of side effects. Therefore, there is always a desire for discovering and use of compounds that, despite high efficacy, have fewer side effects. Some natural substances have such criteria. Many pharmacological activities have been reported for Allium paradoxum. The aim of present study was to investigate analgesic activities of its aerial parts extract for the first time.

Methods and Results: Total phenolic and flavonoids were measured by colorimetric method using Folin-Ciocalteu and Aluminum chloride reagents, respectively. Analgesic activity of methanolic extract was evaluated by Hot plate and acetic acid induced Writhing test on male Balb/C mice. Extracts showed significant Analgesic activity in both models. In writhing test extract showed significant analgesic activity in all doses tested compered to control group and reduced writhing behaviors (p<0.001). In Hot plate test Extract caused increase in pain threshold compared to control specifically in 30^th minute of the test (p<0.001).

Conclusions: Our studies indicate that Allium paradoxum showed significant analgesic activity. It produced dose dependent effect on both models. These results introduced this plant as easily accessible source of natural analgesics.

Introduction: Prostate cancer is the second deadly cancer in men. One way to deal with tumor resistance is using natural sources like snake venoms that contain a wide spectrum of anti-cancer components. The aim of this study was to review the anti-neoplastic property of snake venom against prostate cancer.

Methods and Results: In this systematic review, based on PRISMA guidelines, two persons independently searched MeSH and other relevant terms like “snake venom”, “prostatic neoplasms” and 3 others in databases including PubMed, Medline, Scopus, Sciverse( Elsevier, ScienceDirect), Cochrane library, Sid, Magiran, and iranmedex up to October 2017, and all articles with considered inclusion criteria were added to the study. 82 articles were obtained by primary searching and after removing irrelevant and duplicate articles 14 articles with all inclusion criteria were added to this study. Many snake venoms’ components are effective on prostate cancer; some of them changed gene expression of tumor cells while others like enzymes have a direct effect on cancer cells. Although there are many compounds with anti-cancer property in snake venoms there are some with carcinogenic effect. For example Prokineticins and Hyaluronidase in some venoms induced angiogenesis and growth of the tumor. Walterinnesia aegyptia venom alone and its combination with silica nanoparticles, Rhodostomin, a proteinase from Vipera lebetina, Vipera lebetina turanica venom, cysteine-rich secretory proteins, Disintegrins, lectin and many other components had wide range of anti-cancer properties like inhibiting cancer cells’ invasion, migration, growth, and their adhesion to the extracellular matrix, inducing apoptosis by down-regulated antiapoptotic proteins like Bcl-2 and increasing the expression of proapoptotic proteins like Bcl-2-binding component 3, Bax, caspase-3, caspase-9 and other mechanisms.

Conclusions: Snake venoms are good sources for treating prostate cancer but application of nanoparticles in combination with venoms could make the results more efficient. However, their side effects must be considered.

Introduction: One of the most dangerous brain tumors is Glioblastoma multiforme (GBM).The MMPs are very important biomarker in pathologic conditions and be known as metastatic factor. Temozolomide is an oral alkylating agent, and has a good effect on GBM. Gefitinib is a low–molecular weight tyrosine kinase inhibitor that is used in tratmeant of tumor.

Methods and Results: The human GBM cell line, U87 mg was obtained from Pasteur Institute of Iran. Cells grown in RPMI 1640 supplemented with 10% fetal bovine serum in a humidified incubator at 37^0C with 5% CO2. Cell viability after treatment, was measured by MTT test. MMP-2, MMP-9, Quantikine^® ELISA kits (R&D systems, Minneapolis, USA) were used to measure supernatants MMPs. Effect of the drugs on the enzyme  activity of MMP-2 and MMP-9 was assessed by gelatin zymography. Synergism of Temozolomide and Imatinib can reduce the IC50 of temozolomide. Our results show that combination of Imatinib and Temozolomide decreased the level and activity of MMP-2 and MMP-9 in supernatant of culture medium versus to control cells when only Temozolomide or Imatinib was added to their culture medium.

Conclusion: Combination of Imatinib as a tyrosine kinase inhibitor and Temozolomide as an alkylating agent is more potent than Temozolomide and it can reduce IC50 and decrease level and activitity of MMP-2 and MMP-9.The current strategies for treatment of glioblastoma are not beneficial enough. Combination therapy probably can reduce the dose of drug, cost of treatment, adverse effects and increase the survival rate of life.

Introduction:Echinophoracinerea is a plant from Apiaceae family and it is used as vegetable, yogurt and cheese seasoning and is used for gasteric ailments in ChaharMahalBakhtiari province. It is a rich source of antioxidant constituents, hence it canpotentially  have protective effects. So, its phytochemical investigation seems to be crucial.

Methods and Results:Plant material was extracted. The latter extract was fractionated with VLC and further purified using reversed phase HPLC. The structures of pure compounds were elucidated using spectroscopic methods such as ¹HNMR and mass. Cytotoxic effects of cisplatin alone and with other fractions were tested. The effects of isolated compounds against apoptosis induced by CIS were investigated through the measurement of mitochondrial membrane potential, Bax and Bcl2 and caspase-3 activation. We also assessed the oxidative stress by measuring reactive oxygen species. Six compounds (quercetin-3-O-β-D-glucopyranoside, Kaempferol glycoside, osthol, verbenone, isoimperatorin and echinophorin B) were purified and identified. Treatment of cells with QUE and OST before exposure to the CIS increased cell viability. These compounds protected the cells against CIS–induced cytotoxicity. In addition, pretreatment with QUE and OST decreased CIS- induced apoptosis through up-regulation of Bcl2, inhibition of caspase-3 activity and increasing of mitochondrial membrane potential. As well, OST decreased ROS generation.

Conclusion:Given that flavonoids are the most important groups of phenolic compounds found in nature, and due to their antioxidant and antiapoptotic effect these could be considered as neuroprotective agent.

Introduction: Mercury has hematotoxic, hepatotoxic, neurotoxic, nephrotoxic and genotoxic effects. Tissue damage induced by mercuric chloride (HgCl₂) is associated with the promotion of oxidative stress. In this study, Gallic acid (GA), as potent antioxidant compound, was examined against mercuric chloride (HgCl₂)-induced kidney injury in Wistar rats.

Methods and Results: In this experimental study, animals were divided into five groups (n=7). Groups 1 and 2 respectively received normal saline (2 ml/kg, orally.) and HgCl₂ (0.4 mg/kg, orally) for 28 consecutive days. Group 3 only received GA (200 mg/kg, orally) for 28 consecutive days. Groups 4 and 5 received orally GA at doses of 50 and 200 mg/kg, respectively, one hour after administration of HgCl₂ for 28 consecutive days. Then On the 29^th day, the rats were sacrificed, and blood samples were collected to determine biochemical parameters such as serum creatinine (Cr) and blood urea nitrogen (BUN) levels. For oxidative stress evaluation, malondialdehyde (MDA) and reduced glutathione (GSH) levels and also catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity were evaluated in left kidney tissue. The right kidney was used for histological examination. The results obtained from our study showed a significant increase in the levels of MDA, Cr and BUN, and decrease of GSH, CAT and SOD after ingestion of HgCl₂ (p<0.05). Pre-treatment with GA showed diminished in the levels of MDA, Cr and BUN and enhanced of GSH, CAT, GPx and SOD activity (p<0.05). Additionally the nephroprotective effect of the GA was established by the histological evaluation of the kidneys.

Conclusions: Our results indicate that GA has protective effect against HgCl₂-induced renal damage probably by scavenging free radicals, reducing the oxidative stress, and increasing the antioxidant defense mechanism.

Introduction: Intrathecal infusion of some enkephalin derivatives has been shown to restore analgesia in morphine tolerant patients with less adverse effects such as respiratory depression and constipation compared to morphine. Therefore developing new enkephalin derivatives is of central interest in pain management. In this study, antinociceptive effects of intrathecal administration of two novel acetyl met-enkephalin analogues were evaluated compared to met-enkephalin.

Methods and Results: To permit the intrathecal administration of drugs into the lumbar subarachnoid space in adult Wistar rats, polyethylene (PE10) catheters were implanted in the L2 and L3 spinal segments in anesthetized animals. After a recovery time of 4-5 days, to protect the drugs from biodegradation, all rats were pretreated with peptidase inhibitors (APC) including Amastatin (A), Phosphoramidon (P) and captopril (C). Animals were dosed with intrathecal infusion of the analogues followed by tail flick latency test for an hour. Acetyl-Met-enk-CHO and Acetyl-Met-enk did not show significant antinociceptive effects in 10 nM (10^-8 M) concentration. However Acetyl-Met-enk-CHO described discernible effects in 100 nm (10^-7 M) in comparison with enkephalin. To estimate resistance against peptidase, molecular modeling was performed and showed compound Acetyl-Met-enk-CHO has low affinity to active site of aminopeptidase, dipeptidylcarboxypeptidase-I and neutral endopeptidase; the degrading endogenous enkephalin opioid peptides.

Conclusions: According to our results, Acethyl-Met-enk-CHO may provide comparable analgesic effects with, although with 10 folds less potency. With likely resistance against endogenous peptidase, this molecule could be a valuable lead compound for further studies.

Introduction: Bee pollen is a natural honeybee product promoted as a valuable source of nourishing substances and energy. Bee pollen contains several nutrients and bioactive compounds: proteins, which are among the main components of Bee pollen, include enzymes and both essential and nonessential amino acids. In fact, Bee pollen is referred to as the “only perfectly complete food”, as it contains all the essential amino acids needed for the human organism. A large number of carbohydrates, lipids, sugars, fibers, vitamins and mineral salts are also found in this substance. The health-enhancing value of bee pollen is expected due to the wide range of secondary plant metabolites such as tocopherol, thiamine, biotin, polyphenols, carotenoid pigments, phytosterols. It has many beneficial effects such as antioxidant, anti-inflammatory, anti-carcinogenic, antibacterial, antifungal, hepatoprotective, anti-atherosclerotic and immune enhancing. So there are many therapeutic goals for Bee pollen.

Methods and Results: This article is based on different original articles on PubMed‚ and ScienceDirect data bases.  Almost 50 articles have been studied that 20 of them were really useful in writing this abstract. Bee pollen has many beneficial effects like antioxidant, anti-inflammatory, anti-carcinogenic, antibacterial, antifungal, hepatoprotective, anti-atherosclerotic, anti-estrogenic and immune enhancing activity. It also can be used as a promising agent in the burn Wounds treatment.

Conclusions: Bee pollen as a natural honeybee product؛ has a lot of biological and therapeutic effects. It is useful for treatment of many diseases. In principle, we can unequivocally recommend bee pollen as a valuable dietary supplement. Also, the bee-pollen components have potential bioactive and therapeutic properties. Extensive research is required before bee pollen can be used in therapy.

Introduction: Several chemical compounds and drugs have been known to directly or indirectly modulate cardiac mitochondrial function, which can account for their cardiotoxic and arrhythmic properties. Non-steroidal anti-inflammatory drugs (NSAIDs) are most prescribed drugs in human and veterinary medicine that provide anti-inflammatory, antipyretic, analgesic, antispasmodic and anticoagulant effects.

Methods and Results: Rat heart mitochondria were obtained by differential ultracentrifugation and incubated with different concentrations of highly prescribed NSAIDs (diclofenac, naproxen, celecoxib). Our results showed that NSAIDs (diclofenac, naproxen, celecoxib) induced a rise in cardiac mitochondrial reactive oxygen species (ROS) formation, lipid peroxidation, and mitochondrial membrane potential (MMP) collapse before mitochondrial swelling ensued on isolated rat heart mitochondria. Disturbance in oxidative phosphorylation was also confirmed by the decrease in ATP concentration in the NSAIDs (diclofenac, naproxen, celecoxib)-treated heart mitochondria. In addition, the collapse of MMP and mitochondrial swelling produced the release of cytochrome c via outer membrane rupture or mitochondrial permeability transition (MPT) pore opening.

Conclusions: Our results suggested that NSAIDs (diclofenac, naproxen, celecoxib)-induced toxicity in heart tissue is the result of disruptive effect on mitochondrial respiratory chain that leads to ROS formation, lipid peroxidation, MMP decline, and cytochrome c expulsion which results in apoptosis signaling and cell loss in heart myocardial tissue.

Introduction: Thymus vulgaris (thyme) is commonly used in folk medicine for several therapeutic purposes. The aim of this study was to evaluate the effects of peritoneal injection of essential oil of thymus vulgaris on the liver as an organ involved in metabolism. It also examines toxic effects following a high dose of the drug.

Methods and Results: Twenty-four mice were divided randomly into three groups. Group 1 was the control group without treatment, group 2 has received a dose of thyme essential oil, 0.4 mg/kg intraperitonealy for 10 days and group 3 has received a dose of thyme essential oil, 0.6 mg/kg intraperitonealy for 10 days. A score of liver damage severity was semi-quantitatively assessed using the modified Histological Activity Index ‘(modified HAI). Statistical analysis was performed by using computer program SPSS (19). The results showed the statistically significant increase (P≤ 0.05) in the histopathological scoring in Group2 when compared with Group1.

Conclusions: The histopathological examination of control group reveals normal hepatic tissue, no portal or periportal inflammation, necrosis, congestion, Infiltration of WBC and fibrosis. While there was a significant loss in hepatic architecture in Group 2 which showed portal inflammation with periportal interface hepatitis (piecemeal necrosis) centrilobular necrosis, congestion, infiltration of WBC and bridging necrosis. The results were revealed statistically significant increase (P≤ 0.05) in the histopathological scoring in Group3 when compared with Group2. The histopathological examination of thyme treated group (Gp3) showed significant toxic effects with moderate acute inflammation of mononuclear cells. It has been determined that Thymus vulgaris (thyme) leads to histological damage including portal inflammation with centrilobular necrosis. The histological alterations may occur through oxidative properties.

Industrial waste water is of global concern due to its severe effects on the environment. Recent studies have suggested that these compounds can cause toxicity via mitochondria-involved mechanisms. According to the fact, that these compounds are freely dispersed in the environment, it is crucial to determine the exact mechanism of toxicity.

Introduction: Compared with municipal waste water, industrial waste water generally contains high concentration of toxic or non-biodegradable pollutants. Recently, it was shown that scallop could filter waste water, but heavy metal such as Ag and TiO₂ could induce Reactive Oxygen Species (ROS) in mitochondria isolated from scallop. Recent studies have suggested that mitochondria have a key role in toxicity via mitochondrial membrane potential collapse and generation of ROS. Therefore, it was decided to determine the mechanistic toxicity of waste water contained heavy metals towards isolated scallop muscle mitochondria using new and reliable methods.

Methods and Results: Isolated scallop mitochondria were obtained by differential ultracentrifugation at before and after exposure to waste water. Our results showed that two heavy metals induced mitochondrial dysfunction via an increase in mitochondrial ROS production and membrane potential collapse, which correlated to cytochrome C release.

Conclusions:

Our results suggest that waste water contained heavy metals-induced toxicity in scallop is result of a disruptive effect on the mitochondrial respiratory chain and increasing the chance of cell death signaling in scallop muscle cells.

Introduction: Intrathecal infusion of some enkephalin derivatives has been shown to restore analgesia in morphine tolerant patients with less adverse effects such as respiratory depression and constipation compared to morphine. Therefore developing new enkephalin derivatives is of central interest in pain management. In this study, antinociceptive effects of intrathecal administration of two novel acetyl met-enkephalin analogues were evaluated compared to met-enkephalin.

Methods and Results: To permit the intrathecal administration of drugs into the lumbar subarachnoid space in adult wistar rats, polyethylene (PE10) catheters were implanted in the L2 and L3 spinal segments in anesthetized animals. After a recovery time of 4-5 days, to protect the drugs from biodegradation, all rats were pretreated with peptidase inhibitors (APC) including Amastatin, Phosphoramidon and captopril. Animals were dosed with intrathecal infusion of the analogues followed by tail flick latency test for an hour. Acetyl-Leu-enk-CHO and Acetyl-Leu-enk did not show any significant antinociceptive effects in 10 nM (10^-8 M) concentration. However Acetyl-Leu-enk demonstrated considerable effects in 100 nm (10^-7 M) compared to Leu-enkephalin. Surprisingly, Acetyl-Met-Leu-enk-CHO antinociception did not improve but decreased with increasing intrathecal dosage to 100 nm, probably working as a partial agonist on opioid receptors.

Conclusions: According to our results, Acetyl-Leu-enk may provide better analgesic effects, compared to Acetyl-Leu-enk-CHO. With likely reverse dose-response effects on tail flick test, Acetyl-Leu-enk-CHO might be considered as a particular ligand for opioid receptors without full agonistic effect for further studies.

Introduction: The present research is a resource-based retrospective study with reference to conducted studies and the results of the cinnamon study by referring to various foods and attaries (groceries) factories such as Golha, Bartar, Yekoyek, and Hati Kara companies in Iran has been answered to the questions related to probable toxicity of cinnamon.

Methods and results: In this study, which is both a research and library study for this research topic, referring to sites, articles, journals, and various search engines including Science Direct and Google Scholar and SCOPUS, provide necessary information in regard to cinnamon types, cinnamon history, Cinnamon advantages and disadvantages, types of cinnamon ingredients, were found to be the cause of the toxicity of the probable types of cinnamon, and the results obtained that were related to the subject. According to the obtained data, it was found that cinnamomum zeylanicum bloom (Cinnamomum verum J. Presl) is less common (0-486 mg/kg) and (190 mg/kg)  also it is known as a good cinnamon for cinnamon cassia (Chinese) (Cinnamomum aromaticum Nees or Cinnamomum cassia (L) J. Presl) (coumarin is between 40 and 12180 mg / kg in the sample) and 700 mg/kg, and in Iran, abundance, import and use of cinnamon zeylanicum (Ceylon) is more than the other.

Conclusions: According to obtain results, it was not proved camarin hepatic toxicity among the whole population and highest sensitivity was observed among people with previous hepatic disease, its daily use (permissible use on a daily basis is 1.5 mg/kg). With regard to this fact that in Iran, cinnamon as is used a flavoring of food and medicine, and the frequency of more Indian cinnamon (Ceylon , zeylanicum) than other cats in market due to higher quality. It can be concluded that with the max daily usage is (for a person body weight 60 kg) 1.5 mg of comarin per day, humans may be exposed to its complications, and that in Iran cinnamon species, which is most commonly used for cinnamomum zeylanicum cinnamon food, medicine (diabetes, etc.) and in various industries, and that it is not possible to enter this amount of comarin per day through the use of cinnamon to the body, it can be said that Iran is not exposed to the (probable) toxicside effects.

Introduction: Diabetes mellitus is known as the most common metabolic disease. Urtica dioica is a plant in Iranian traditional medicine which is used as an antidiabetic and blood sugar lowering medication. This study aims to evaluate the effect of aqueous extract of Urtica dioica on blood glucose level, insulin level, body weight and pancreatic tissue of the Balb/C mice.

Methods and Results: After grouping 80 female Balb/C mice into 6 groups, Streptozotocin (STZ) at the dose of 130 mg/kg was injected to mice, and their blood sugar were recorded by a glucometer. Then mice were treated by the aqueous extract of U. dioica at different doses (1, 2, and 4 gr/kg) for 14 consecutive days. At the end, blood samples of mice were collected under anesthesia to obtain serum and plasma. Finally, blood glucose and insulin level were measured. Data was analyzed using SPSS 23 software and Duncan post test. 

Result: Aqueous extract of U. dioica had an effect on pancreas tissue (number and size of pancreatic islets) and led to increase blood insulin level and body weight of mice. Beside, U. dioica decreased blood glucose level in mice. Injection of low dose of U. dioica in group 1 was effective on mentioned factors, but the impact was very low and not significant. Injection of high dose of aqueous extract of U. dioica in group1 was very affective on mentioned factors, and it was significant.

Conclusions: According to our findings, aqueous extract of U. dioica at high dose was very effective, and can be used as a new medicine in the treatment of diabetes mellitus in order to decrease blood sugar (glucose), and to increase blood insulin level.

Introduction: In most cases, drugs used for chemotherapy are ineffective and have unpleasant side-effects. This has made scientists to find more effective drugs with less toxicity. Lagenaria siceraria is an important medicinal plant in the world and anti-tumoral activity of Lagenaria species has been reported in some studies.In this study, the preventive effects of hydraualcoholic lagenaria siceraria on the toxicity resulting from doxorubicin in the cells of normal and cancer cells were investigated.

Methods and Results: Hydroalcoholic extract of Lagenaria siceraria was prepared by percolation method. Then, the effects of solutions containing the sample with different concentrations (1, 50, 100, 250, 500, 1000 µg/ml) of each extract were provided and then were studied  by the evaluation method MTT on the renal fibroblast cell line (NIH3T3) and breast cancer cell line (MCF7). Doxorubicin was considered as positive control. The results were analyzed through ANOVA and T-test. P<0.05 is considered as the level of significance. The findings indicated that the IC₅₀ dose of Doxorubicin on the normal fibroblast cell line (NIH3T3) and breast cancer cell line (MCF7) is 402± and 101± µg/ml, respectively. On the other hand, lagenaria siceraria has no significant cytotoxic effects.

Conclusions: This extract lagenaria siceraria caused a significant decrease in proliferation of breast cancer cells. Therefore, it is recommended to diagnose the active materials in this extract and determine the mechanism of their effect.

Introduction: Depression is one of the most common diseases. Studying the anti-depressant effect of herbs and comparing them with anti-depressant drugs, this result showed that not only some herbs such as saffron have anti-depressant effects comparing to anti-depressant drugs due to anti-oxidant properties; but also the side effects of these herbs are less than chemical anti-depressant drugs. According to previous studies, E. platyloba has anti- oxidant properties. The aim of this study was to evaluate the phytochemical properties and the antioxidant effect of E. platyloba essence and its effect on the improvement of depression symptoms.

Methods and Results: In this experimental study, 60 mice were divided into 6 groups including 10 subjects. Control group received only 1ml/kg of normal saline. Group two received 0.5 cc of reserpine. Groups (3-5) received 50, 75 and 100 mg/kg of Echinophoraplatyloba essence in addition to receiving 5 mg/kg of reserpine respectively and group six received fluoxetine in 10 mg/kg after receiving 0.5 mg/kg of reserpine. Then the rats were evaluated by forced swimming and tail suspension. Finally, biochemical tests such as measuring the antioxidant capacity of the serum and brain were done by FRAP method and measuring the level of malondialdehyde in plasma and brain. All information was analyzed by SPSS16 statistical software and the significance level was considered as p<0.05.The main components of the essence were Myristicin (76.6%), α-Phellandren (5.9%) and Neocnidilide (4.4%). An increase in antioxidant capacity of serum and brain, a decrease in malondialdehyde level of serum and brain and a decrease in the duration of immobilization in the forced swimming test and hanging tail test were observed in the groups receiving essence which indicates the anti- depressant effect of this essence.

Conclusion: The results of this study indicate the anti-depressant effects of E.platyloba, which is justified by the main components of the essential oil composition of the herb. The essence of this herb, in addition to having anti-oxidant compounds that have anti-depressant properties, contains substances with similar function of neurotransmitters in the prevention and treatment of depression.

Infliximab is a human mouse human chimeric IgG1 antibody that includes human stable regions and variable mouse regions that have inhibitory effects on TNFα, and has recently been used to treat Crohn's disease, urticaria colitis, rheumatoid arthritis, and psoriatic arthritis. This study was conducted to determine the effect of TNFα inhibition on infectious stress and serum lactate levels in infants after isoproterenol induced myocardial infarction in rats.

Methods and Results: For induction of myocardial infarction (MI), isoproterenol (100 mg/kg) was injected subcutaneously in a 24-hour saline solution in normal saline for 24 days. Animals after 24, 48, 72 and 96 hours after the second dose of isoproterenol was surgically treated. After infusion of inflections, 24, 48, 72 and 96 hours of surgery were performed. Anesthesia for animal surgery with ketamine and xylazine (3 to 2. Blood samples were collected from the hepatic vein and serum was used after the isolation to measure biochemical factors. At the end of the test, the heart was quickly separated and washed with normal cold saline and water was taken and weighed. Induced infarction with isoproterenol 100 mg/kg changes the pattern and parameters of electrocardiography and hemodynamics, and also causes hypertrophy, necrosis, edema and severe cardiac inflammation. Injection of infliximab at a dose of 7 mg/kg in the mentioned intervals did not have an effect on induced hypertrophy due isoproterenol. Isoproterenol increases lipid peroxidation, lactate dehydrogenase, total serum antioxidant and heart tissue, and serum lactate, which seems to be a significant reduction in the levels of MDA, TAC, LDH, and LDH, especially in the early hours of myocardial infarction. Lactate reduces serum levels. But in some cases, with the passage of time does not apply photo effects.

Conclusion: The results of this study showed that infliximab, at 24-48 hours after MI, has a protective effect on cardiac myocardial infarction, and in the long term may exacerbate oxidative activity.

Introduction: Beef burgers made in Iran contain various compounds such as meat, cereals flour, as well as some spices which can be contaminated with Bacillus cereus, causing gastroenteritis in the consumer. This study is focused on occurrence of B.cereus in beef burgers marketed in Tehran, capital of Iran.

Methods and Results: In this cross-sectional study, a total of 80 samples of different types of beef burgers marketed in Tehran, Iran were randomly collected based on their percentage of meat content, including 30% (n=25), 60% (n=40) as well as 90% (n=15). The samples were analyzed microbiologically by routine culture assay and biochemical tests to find B.cereus. Data were analyzed statistically by Microsoft Office Excel 2010.  Twenty-five out of 80 (31.25%) beef burger samples were contaminated by B. cereus. Based on the percentage of meat content in the samples, the beef burger with 90% meat were significantly (p<0.05) more contaminated than the others. Also, the contamination rate was significantly (p<0.05) higher in summer compared to winter.

Conclusion: This survey showed that the beef burgers supplied in Iran markets is main source of B.cereus that can cause disease in Iranian consumers. More attempts must be focused on cold-chain maintenance in production, distribution, and storage of the meat products.

Introduction: Eupatorium cannabinum belonging to Asteraceae family is commonly known as hemp agrimony. E. cannabinum is used to treat headache, hepatitis, diarrhea, diabetes mellitus and hypertension. Considerable researches have been indicated various biological activities of E. cannabinum such as cytotoxic, antioxidant, antimicrobial, anti-inflammatory, immunological and hepatoprotective activities. Since the cytotoxic activity of E. cannabinum on human breast adenocarcinoma cell line (MCF-7) have not been reported, the current study was conducted to evaluate the cytotoxicity of the total extract of E. cannabinum on MCF-7 cells.

Methods and Results: MCF-7 cell line was treated with different concentrations (3.125 to 100 μg/mL) of the E. cannabinum total (methanolic) extract. After 48 hrs, the cytotoxic activity was assessed through MTT (3-[4, 5-Dimethylthiazol-2-Yl]-2, 5-diphenyltetrazolium bromide) assay. The methanolic extract demonstrated cytotoxicity against MCF-7 cell line with IC₅₀ (the concentrationthat inhibited cell growth by 50%) value of 69.5 μg/mL.

Conclusions: The methanolic extract of E. cannabinum showed considerable cytotoxic activity. Evaluating the apoptosis induction ability of E. cannabinum could be suggested for further studies.

Introduction: The ocean, which is called the “mother of origin of life,” is also the source of structurally unique natural products that are mainly accumulated in living organisms. The cyanobacteria (blue-green algae) are photosynthetic prokaryotes having applications in human health.  Bioactive compounds of marine cyanobacteria have biological activity in deadly diseases like cancer.

Methods and Results: Peer-reviewed publications were identified through searches in pubmed, scopus, science direct and google scholar by using the search terms "anti-cancer," "bioactive compounds," "pharmaceutical agents," " cyanobacteria,". In this search, 127 articles were found that studied 21 of them. Based on this search, anti-cancer  compounds  such as  apratoxin A, tolyporphin, curacin A, dolastatin 10  in cyanobacteria act through mechanisms  such as induction of G-1 phase cell cycle arrest, inhibition of microtubule dynamics,  inhibition of actin filaments, inhibition of histone deacetylase, inhibition of proteasome activity, induction of apoptosis in cancer cells and inhibition epidermal growth factor receptor (EGFR).

 Conclusions: The fact that cyanobacteria are one of the richest sources of known and novel bioactive compounds including toxins with wide pharmaceutical applications is unquestionable. Many compounds from cyanobacteria are useful for welfare of mankind. Advantage of cyanobacteria as an anti-cancer source for drug discovery lies in the economy of their cultivation compared with other microorganisms, as they require only simple inorganic nutrients for growth. Thus, it seems that the cyanobacteria have the potential for expanded utilization in drug discovery.

Introduction: Cancer is known as the second cause of death worldwide which results in serious problems in human life. It is developed by uncontrolled growth of a cell or a group of cells. Caryophyllaceae is a large family which has been reported to possess cytotoxic species and in the present study, the cytotoxic activity of two plants from this family has been evaluated.

Methods and Results: Dried powder of Gypsophila bicolor (Freyn & Sint.) Grossh and Gypsophila ruscifolia Boiss. aerial parts were extracted with methanol 80% by maceration method (10 g). For fractionation, 30 g of the dried powder of both species was macerated with petroleum ether at room temperature. After 24 hours, the mixture was filtered and the plant residues were extracted with chloroform and methanol successively through the same process. Then they were concentrated using a rotary evaporator apparatus. The cytotoxic activity was evaluated against MCF-7 (human breast adenocarcinoma), A-549 (non-small cell lung carcinoma) and AGO-1522 (human fibroblast) cell lines using MTT assay. The chloroform fractions of both Gypsophila species showed cytotoxic effects against MCF-7 cells with IC₅₀ value <100 μg/mL. None of the extracts or fractions demonstrated cytotoxicity to A-549 or AGO-1522 cells up to the tested concentrations.

Conclusions: The selective toxicity of the chloroform fractions of the species only to the MCF-7 cell line suggested that Gypsophila bicolor and G. ruscifolia could be proper candidates for further studies in the field of cancer researches.

Introduction: Selegiline, a selective monoamine oxidase type B inhibitor, has been shown to have neurotrophic and anti-apoptotic properties and to protect neurons in experimental models of cerebral ischemia. The aim of this study was to investigate whether selegiline could enhance cognitive and functional recovery in stroke disease. Selegiline is a drug that has demonstrated antioxidant and neuroprotective effects, as documented in the permanent middle cerebral artery occlusion model in rats. Widely used in the treatment of Parkinson's disease and in recent studies showed anti-inflammatory and anti-apoptotic properties. It has been shown to reduce total brain damage after transient hypoxia– Ischemia.

Methods and Results: The male rats were randomized into four groups: Control groups, Control + Selegiline (2 mg/kg), stroke induction groups and stroke+ Selegiline (2 mg/kg). Selegiline was gavaged after 4 days from beginning of the investigation. In this regard, we tested whether 1) Administration of selegiline is able to inhibit abnormality behaviors related to global ischemia in Male Rats 2) Behavioral changes are associated with mitochondrial dysfunction in the hippocampus and 3) Administration of selegiline is able to alter immune-inflammatory factors in the hippocampus. Therefore, using valid and qualified behavioral tests for the assessment of stroke like behaviors such as novel object recognition test (NOR) were used for confirmation of stroke induction in rats. Then, animals were sacrificed and hippocampi were dissected out and stored at -80 °C. The samples were divided into two different groups; first set of samples were used for preparation of tissue homogenate, on which measurement of oxidative stress parameters and nitrite levels were performed. The second set of samples were fixed in 10% formalin, sectioned, and stained with hematoxylin and eosin (H&E) for pathological evaluations. The statistical analysis showed a significant improvement in most neuropsychological tests after two weeks in the study group.

Conclusions: Data on experimental models of cerebral ischemia have suggested a marked activation of the nigrostriatal dopaminergic system by selegiline that might contribute to the protection against ischemia-induced neurodegeneration.

Introduction: In this research synthesis of hybridized benzylthio-thiadiazol-isatin derivatives has been reported and then the effects of the synthesized compounds were  investigated on cancer cell lines and molecular docking was also studied on proposed receptor.

Methods and Results: This project was done in 2 steps that includes the synthesis of new hybrids of thiadiazole-isatin derivatives and characterized by various spectroscopy methods such as "Mass spectroscopy, Infrared spectroscopy, and ¹H NMR". To study cytotoxic effects of the compounds, different concentrations of synthesized derivatives were  prepared and tested on the three rank 7 cellular MCF-7 "breast cancer", PC3 "Prostate carcinoma", and SKNMC "Norobelastoma". The method used was MTT that after various stages of the solution and added MTT, the color was measured by the producted formazan during measurements suitable wave. The color ratio was  as equal as  the number of living cells. For comparing the  cytotoxicity we  used doxorubicin as control drug.

Conclusions: The most potent of the compounds were 3b, 4c, and 4d against MCF7 cell line, 3b, 4h against PC3 cell line, and 3b,4f, and 4h against SKNMC cell line which seems to be the best ones relative to the control drug. Also we found that treatment with 3b led to  decrease in IC₅₀ and significantly increased cytotoxicity effects of the compound in PC3, SKNMC and MCF7 cells lines.

Introduction: Quinoxalines belong to the N-containing heterocyclic compounds that stand out as having promising biological activity due to their privileged scaffold. Quinoxaline derivatives constitute the basis of many insecticides, fungicides, herbicides, as well as being important in human health and as receptor antagonists. On the other, the compounds containing thiazolidine-2,4-dione have demonstrated wide range of pharmacological activities, which include antimicrobial, antiviral, antidiabetic and anticancer activity. In this research, we have synthesised a new quinoxaline derivatives containing N-substituted thiazolidine-2,4-dione derivatives and evaluated for antitumor activity against a 3-cell line panel, consisting of MCF7 (breast), NCI-H460 (lung), and SF-268 (CNS).

Methods and Results: In a 250 ml three necked flask equipped with teflon coated mechanical stir bar, chloroacetic acid and thiourea have been dissolved in distilled water and the contents of the flask were heated in the presence of hydrochloric acid. The precipitate was filtered and washed with water and dried before recrystalization. Consequently, the new synthesized thiazolidinedione derivatives were condensed in situ by quinoxaline aldehydes and substituted benzyl halides in N,N-Dimethylformamide. The resulted products were washed with water and then recrystallized in appropriate solvent. Structures of all the synthesized compounds were confirmed by IR, ¹H NMR, ¹³CNMR, and Mass spectral data. The MTT assay of synthesized hybrids showed promising and effective anti-cancer activity against 3-cell cell lines. The current results indicate that these quinoxaline derivatives are novel and promising agents for further development towards a treatment for cancer.

conclusion: In the present study, series of new N-thiazolidine-2,4-dione incorporated quinoxaline ring were synthesized. All compounds were screened against two different cancer cell lines using MTT assay method.

Introduction: Among heterocyclic anticancer compounds, quinoxalines and imidazolidine-2,4-dione are the most prominent since they constitute important classes of natural products and synthetic pharmaceuticals. In general, they are used as valuable intermediates and building blocks in pharmaceutical synthesis. Therefore, much attention has been paid to the synthesis of quinoxaline derivatives bearing imidazolidine-2,4-dione either by classic methods or by multicomponent reactions.

 Methods and Results: The title compound was prepared through a three- step procedure. In the first step, equimolar amounts of D-glucose and o-phenylenediamine were reacted with phenyl hydrazine in the presence of acetic acid, to form the pyrazolo[4,5-b]quinoxaline  derivative.

The second step involved oxidation of the resulted compound by use of sodium metaperioddate.

Finally, the related aldehyde was condensed by imidazolidine-2,4-dione to yield the corresponding 3-alkylidene pyrazolo[4,5-b]quinoxaline .

Conclusions:

The procedure applied in this study established a convenient method for the preparation of the title compounds. The process was straight forward and it used abundant and readily available staring materials. Due to its chemical structure, and in particular the presence of the quinioxaline ring, which is a commonly encountered motif in compounds of medicinal interest, the prepared product is expected to show anticancer activity.

Introduction: Propranolol (PROP) as a nonselective β-adrenergic receptor blocker mainly used for the treatment of various cardiovascular disorders, such as hypertension, angina pectoris, cardiac arrhythmias, and myocardial infarction. PROP is rapidly metabolized after oral administration, and even traces of the drug may be difficult to detect in biological fluids sometime after administration. Hence its detection is of tremendous importance. A novel and sensitive modified carbon paste electrode (MCPE) employing ZnFe₂O₄ nanoparticles (ZnFe₂O₄/NPs) and 1-butyl-3-methylimidazolium tetrafluoroborate (BMITFB) ionic liquid was used for trace level analysis of propranolol (PROP) in aqueous solutions.

Methods and Results: Carbon paste electrode (CPE) was modified with ZnFe2O4/NPs and BMITFB as a binder. A portion of the paste was filled firmly into one glass tube to prepare BMITFB/ZnFe₂O₄/NPs/MCPE. The electrochemical investigations were carried out using square wave voltammetry (SWV) and cyclic voltammetry (CV) techniques. Scanning electron microscope (SEM) and X-ray powder diffraction (XRD) studies were applied to characterize the synthesized ZnFe₂O₄/NPs. The obtained result shows that, the electro-oxidation signals were increased at the surface of MCPE compared to bare CPE. At pH 7.0 phosphate buffer (0.1 M), the catalytic oxidation signal exhibited a wide linear range with a low detection limit.

Conclusions: It can be concluded that, the developed BMITFB/ZnFe₂O₄/NPs/MCPE in the current work was a promising approach for successful detection of PROP in biological and pharmaceutical samples.

Introduction: Resorcinol (RC) used extensively for the treatment of chronic skin diseases such as psoriasis, hidradenitis suppurative, and eczema of a sub-acute character. RC as a phenolic compound with high toxicity causes giddiness, deafness, salivation, sweating, and convulsions. It is noteworthy to mention that, RC can be easily absorbed through the gastric tract and human skin and caused dermatitis, catarrh, cyanopathy, and even death. The current work deals with fabrication of a high sensitive modified carbon paste electrode employing ZnFe₂O₄ nanoparticles and 1-butyl-3-methylimidazoliumtetrafluoroborate (B3M) for determination of trace amount of RC using cyclic voltammetry and square wave voltammetry techniques.

Methods and Results: The modified carbon paste electrode (B3M/ZnFe₂O₄/NPs/MCPE) was prepared by hand mixing of 0.80 g of graphite powder, 0.20 g ZnFe₂O₄/NPs plus 0.90 g paraffin and 0.10 g B3M as an ionic liquid for 120 min until a uniformly wetted paste was obtained. The proposed sensor revealed good electrocatalytic activity towards RC in aqueous solution. The obtained results revealed that the electro-oxidation peak current was proportional to the RC concentration in the range of 3-500 μM with the detection limit of 1.46 μM.

Conclusions: The excellent properties of the B3M/ZnFe₂O₄/NPs/MCPE make it a promising tool for application to the real sample analysis. The proposed modified carbon paste electrode (B3M/ZnFe₂O₄/NPs/MCPE) was applied successfully for analysis of trace amount of RC in some pharmaceutical and biological samples.

An efficient method for the synthesis of pyrazolophthalazine derivatives was developed by using tetrabutylammonium bromide (TBAB) as ionic liquid catalyst in excellent yields (88-95%).

Introduction: Most of the significant advances against disease have been made by designing and testing new structures, which are often heteroaromatic derivatives. In addition, over 80% of the top small molecule drugs by U.S. retail sales in 2010 contain at least one heterocyclic fragment in their structure. Therefore, researchers are on a continuous pursuit to design and produce better pharmaceuticals, pesticides, insecticides, rodenticides, and weed killers by following natural models. A significant part of such biologically active compounds is composed of heterocycles [1]. Moreover, phthalazine derivatives possess a versatile pharmacological properties including anticonvulsant, vasorelaxant, and cardiotonic activities.

Methods and Results: We report here an efficient method for the synthesis of pyrazolophthalazine derivatives by a four-component reaction of equimolar amounts of phthalic anhydride, hydrazine hydrate, arylaldehydes and malononitrile in the presence of 20 mol tetrabutylammonium bromide (TBAB) ionic liquid as catalyst, in excellent yields.

Conclusions:

The protocol described here produced the desired pyrazolophthalazines in excellent yields (88-95%) and lower reaction times. The catalyst was reused at least 5 times without appreciable reduction in catalytic activities.

An effective one-pot synthesis of indole derivatives using functionalized SBA-15 as Brønsted acid. It efficiently catalyzed synthesis of indole derivatives through the Fischer Indole reaction. One pot synthesis procedure, mild reaction conditions, and simple workup are attractive features of this method.

Introduction:

Due to indole structure ubiquity in nature and its broad application in chemistry, indole derivatives are valuable heterocycles. Numerous methods have been developed for the synthesis of indole derivatives and more efficient straightforward synthetic strategies still continue to be pursued. Fischer Indole method is one of the most powerful routes of indole synthesis. In view of the versatility of indoles and its derivatives in material sciences, There is an increasing sensitivity for environmental protection and using green methodologies for effecting the Fischer indole synthesis. We were interested in developing a new, easy workup procedure with high yielding synthetic protocol for indole derivatives using modified SBA-15 with HO₃S- functional group as a recyclable and environmentally benign catalyst.

Methods and Results: To develop Indole scaffold we considered a reaction of phenylhydrazine or its nitro derivatives, a ketone (typically, cyclohexanone), and SBA-15-Pr-SO₃H as Brønsted acid. The present methodology also offers the advantages of excellent yields, short reaction time, and milder reaction conditions.  All the synthesized compounds were characterized by ¹H NMR, IR spectral data.

Conclusions:

The target compounds were obtained from phenylhydrazines and ketones with good to excellent yields.

Introduction: Alzheimer’s disease (AD) is a progressive neurodegenerative condition of the central nervous system among old people. AD is characterized by two neuropathological hallmarks: Extracellular senile plaque deposits, composed of amyloid beta (Aβ), and Intracellular neurofibrillary tangles (NFTs), made of truncated and hyperphosphorylated tau. Previous studies suggest that Asparagine Endopeptidase (AEP), a lysosomal cysteine proteinase, is activated during aging process. It proteolytically degrades tau and abolishes its microtubule assembly function, induces tau aggregation and triggers neurodegeneration.
Methods and Results: Therefore, AEP is an attractive target of drug discovery against AD. In this study, we investigated the important pharmacophore feature required for inhibitors of AEP by generating a structure-based pharmacophore model followed by virtual screening and subsequent validation by molecular docking. The computational findings discussed in our study provide initial information of inhibitory effects of ligand, (ZINC3979524), over AEP.

Conclusions: VS of the ZINC database against AEP led to select some good inhibitors for the treatment of Alzheimer’s disease. Therefore, this study can be a good starting point for in vitro and in vivo experimental studies and can establish as a novel therapeutic agent against AD

Introduction: The overexpression of P-gp in cancer tumor cells results in increased efflux of chemotherapeutic compounds. This phenomenon leads to the wide-spectrum resistance of cancer cells to variant drugs or multi drug resistance (MDR). Regarding the important biological role of P-gp with regard to cancer therapy, in silico analysis of binding affinity/mode of diverse anticancer drugs toward P-gp may be an active area of research since it provides more insight into the binding interactions and key amino acid residues that were involved.

Methods and Results: Ligand-flexible docking studies were performed using the molecular docking software, AutoDock 4.2. To elucidate the interactions of selected anticancer drugs, all the related structures were docked into the active site of validated P-gp target (4XWK). Quantum mechanical calculations were applied to intermolecular binding energy analysis in terms of drug-residue binding interactions via functional B3LYP in association with split valence basis set using polarization functions (Def2-SVP).

Mitomycin was found to be the weakest binder with -7.29 kcal/mol energy. Bisantrene was the top-ranked binder (-10.59 kcal/mol) with H-bond and lipophilic interaction patterns. To explain more, Asn838 participated in bidentate H-bonding with nitrogen atom of imidazole ring. Another H-bond interaction was detected in the case of Ser725 within the same ring but different nitrogen atom of the drug molecule. Besides hydrogen bonding, it was revealed that 12 hydrophobic residues interacted with Bisantrene. Within the evaluated drugs, unlike Epothilone E and F, no H-bonds could be detected for Epothilone A, B, C & D. Such observation was pertained to the presence of hydroxymethyl moiety on the thiazole ring of Epothilone E and F which provided well-oriented H-bonds with Ala307. Despite observed interactive residues, lower binding affinity of Epothilone F persuaded us to run QM job in terms of drug-residue binding interactions. It was interestingly concluded that a few residues made repulsive forces with the drug, a result that might explain lower affinity of this molecule toward P-gp.

Conclusions: Collective in silico exploration of a few anticancer drugs provided some insights into the binding mode toward P-gp as an interfering target in chemotherapeutic strategies. On the basis of obtained results, structure binding relationship pattern for studied anticancer drugs were developed.

P-glycoprotein (P-gp) is a membrane ATP-binding transporter that detoxifies cells from different xenobiotics. Multiple drug resistant (MDR) cells can be sensitized toward anticancer agents when treated with P-gp inhibitors/modulators (chemo-sensitizers). Regarding the requirement of high serum concentrations of P-gp inhibitors leading to potential toxicity, dietary phytochemicals are very important and they may interact with co-administered pharmaceuticals as P-gp substrates, leading to altered pharmacokinetics. In silico models for predicting probable binding mode of dietary phytochemicals to P-gp are useful in the early phase of drug discovery projects since they describe structural features in binding to P-gp and hence designing novel anti-MDR scaffolds.

Introduction: As a part of our ongoing studies on virtual analysis of bioactive phytochemicals and to explore new substances that do not exhibit significant toxicity at doses required for P-gp inhibition, we aimed to get more insight into the interactions of P-gp and a few dietary natural constituents as tumor chemosensitizing agents.

Methods and Results: Radiographic 3D holo structure of P-gp was retrieved from protein data bank (4XWK; www.rcsb.org). Lamarckian genetic algorithm of AutoDock 4.2 was used to simulate the binding of dietary compounds. All ab initio studies were done with functional B3LYP associated with split valence basis set using polarization functions (Def2-SVP) by ORCA quantum chemistry package. Our study proposed the dominant role of R-site in binding to Curcuminoids (Curcumin II;  -8.17 kcal/mol). In the case of black pepper, hydrophobic contacts seemed to be important in Piperine/P-gp complex. It was also proposed that Piperine carbonyl might be a good mimic of Curcumin II enone group due to the formation of H-bonds (Gln986). Among the catechins of green tea, Epicatechin gallate might not be identified as modulator/substrate since relatively similar ΔG_bs were recorded within M, H and R sites. Quercetin was not preferentially docked within H-site (-4.77 kcal/mol) in accordance to the previous reports. Within the H-site, Epigallocatechin (green tea) was the weakest binder (-4.31 kcal/mol) and amino acid decomposition analysis dedicated -2.66 and -8.76 kcal/mol attractive forces for interaction with Glu180 and Lys185, respectively.

Conclusions: Combined molecular docking/quantum mechanical studies revealed that among assessed phytochemicals, Bergapten (grape fruit) might be identified as P-gp modulator. Other constituents exhibited more affinity toward R-site with Curcumionoids being the top-ranked ones. Results indicated Lys185, Glu871 and Glu986 as important interacted residues with Curcuminoids due to strong hydrogen bondings.

A novel series of carbohydrazide indole-isoxazole hybrid derivatives have been synthesized. All the title compounds were characterized by ¹H NMR, ¹³C NMR, MS and IR spectral data. The in vitro anti-cholinesterase activity of all the compounds were evaluated.

Introduction: Alzheimer disease (AD) has emerged as the most prevalent age-related neurodegenerative diseases and the main cause of dementia, which is very common in elder population with high morbidity in such a manner that the daily activity of patients is completely affected by the resulting cognitive impairments. In recent years, most of therapeutic treatments for AD has focused on the inhibition of acetylcholinesterase (AChE) to increase the level of ACh in cholinergic synaptic cleft. Indole and its derivatives are very important heterocyclic compounds in drug-discovery studies that exhibit diverse range of biological activities like antimicrobial, anticancer, anti-Alzheimer and anti-platelet aggregation activity.

Herein, in this study on the synthesis of bioactive compounds, we describe design, synthesis and anti-cholinesterase activity of N-benzylidene-5-(1-methyl-1H-indol-3-yl)isoxazole-3-carbohydrazide.

Methods and Results: The title compounds were prepared via the 5-(1-methyl-1H-indol-3-yl)isoxazole-3-carbohydrazide which is key intermediate for the production of the desired compounds. Condensation with carbaldehydes in water and acetic acid afforded the title compounds. All the synthesized compounds were characterized by ¹H NMR, ¹³C NMR, MS and IR spectral data. The in vitro anti-cholinesterase activity of all the compounds were evaluated.

Conclusions: The target compounds were obtained from proper aldehydes and N-benzylidene-5-(1-methyl-1H-indol-3-yl)isoxazole-3-carbohydrazide condensation with good to excellent yields. The AChE and BuChE inhibition activity of the synthesized compounds were evaluated.

Novel 1,2,3-triazole indolinone derivatives have been synthesized. All the titled compounds were characterized by ¹H NMR, ¹³C NMR, MS and IR spectral data. The in vitro AChE and BChE inhibitory activity of all the compounds were evaluated.

 Introduction:

Alzheimer disease is the most frequent cause of dementia, which is very common in elder population with high morbidity. Treatment of this disease is one of the most promising targets in medicinal chemistry researches. Design and synthesis of novel 1,2,3 diazole indolinone derivatives as cholinesterase inhibitor (ChEI), are investigated in this study. Indolinone derivatives with 1,2,3-triazole moiety have been recently reported as potential AChE and BuChE inhibitors. There is also, a growing interest in evaluating the biological activity of these compounds and their derivatives to investigate their role in the prevention of neurodegenerative diseases.

Methods and Results:

The target compounds were prepared via the 1-methyl-3-((prop-2-yn-1-yloxy)imino)indolin-2-one as an intermediate in click reaction with substituted benzyl halides in water and DMF as solvent in room temperature. All the synthesized compounds were characterized by ¹H NMR, ¹³C NMR, MS and IR spectral data. The in vitro AChE and BuChE inhibitory activity of all the compounds were evaluated.

Conclusions:

In conclusion, various novel 1,2,3-triazole indolinone derivatives were designed, synthesized, and evaluated against AChE and BChE. All these results clearly confirmed the efficacy of the corresponding compounds for further drug discovery developments.

Cancer is a disease in which a group of cells show an uncontrolled growth (Cell division beyond the normal range), invasion (Penetration into and destruction of adjacent tissues), and in some cases, metastasis (Spreading to other parts of the body via lymph or blood systems). These three destructive nature of cancerous tumors distinguish them from benign tumors. Undoubtedly, early detection of cancer is associated with an increased survival of these patients.

Introduction             

SPECT/CT (Single Photon Emission Computed Tomography) give us a signal for cancer diagnosis. The use of radiopharmaceuticals such as technetium improves images. Technetium is one of the famous contrast agent used in this technique, which is toxic and should be used as a complex with a ligand.

In this study (Technetium-99m)-(DOTA-NHS-ester)-Methionine radio drug was synthesized. Technetium-99m is an isomer of isotope-^99mTC, which is attempted by isomeric transition. Methionine is an essential amino acid which has important roles in cancerous cells. DOTA was used to conjugate with Methionine and then labeled with ^99mTc to improve tumor selectivity. This synthesized radio drug would be able to nominate as a SPECT-CT imaging candidate.

Methods and results

In this current study, a novel structure of DOTA-NHS ester conjugated to essential amino acid methionine was synthesized, and then labeled by a radionuclide technetium. The final radiopharmaceutical characterized and then studied as a contrast agent in SPECT/CT   imaging.

Conclusion

(Technetium-99m)-(DOTA-NHS-ester)-Methionine synthesized radio drug showed significant (P<0.05) Cellular uptake in cancerous cells in comparison with other normal cells and Cellular toxicity was observed in those cancerous cell lines.

According to the final data, the synthesized radiopharmaceutical, was detected in the tumor with high and significant appearance in SPECT/CT technique.

Targeted Nano-based imaging methods have been used to precisely diagnose different diseases lately. In this research, chitosan was synthesized and confirmed using Zeta Sizer and AFM. AGRO 100 Aptamer was conjugated on the surface of chitosan nanoparticles and then conjugate labeled with BODIPY-FL. Then, in vitro assays such as XTT and uptake assessment were preformed. Data showed successful synthesis of nanoparticle and conjugate. Cellular uptake in cancer cells was increased and no significant (p value<0.05) cytotoxicity has been found on normal cells. Taking everything into account, the mentioned fluorescent labeled bioconjugate seems to be an appropriate fluorescent diagnostic agent for the future in vivo studies.

Introduction: Recently, many aptamers such as MUC1, A30, AGRO 100,and etc. have been found which work as therapeutic/diagnostic agents through shape complementary with their specific cancerous cell membrane overexpressed receptors. AGRO 100 is now in the second phase of clinical trials of two cancers as a therapeutic agent and it specifically targets nucleolin which is overexpressed on the cancer cells’ surface and constrains tumor growth. Nowadays, aptamer based drug delivery/ imaging is being used as a novel pharmaceutical approach in vitro/ in vivo. These aptamers based on their ability to detect cell surface disease specific biomarkers and treat diseases are termed as smart devices in Nano-Theranostics applications.

Methods and Results: In the current project, chitosan was synthesized and confirmed using Zeta Sizer (size, charge and molecular weight) and AFM. Aptamer AGRO 100 (APT AS1411 ) was conjugated successfully on the surface of chitosan nanoparticles using a covalent bond (carboxyl active groups to amine active groups) using NHS and EDC, then conjugate labeled with BODIPY-FL.

Conclusion: Using AGRO 100 aptamer, chitosan nanoparticles and BODIPY-FL the desired targeted fluorescent diagnostic agent was constructed. Based on the in vitro results, no significant cytotoxicity on HEK-293 has been found. Moreover, bioconjugate had a good cellular uptake on T47D cells. Taking everything into account, the mentioned fluorescent labeled bioconjugate seems to be an appropriate fluorescent diagnostic agent for the future in vivo studies.

Introduction: Platinum-based drugs have become a mainstay of cancer therapy, approximately half of all patients undergoing chemotherapeutic treatment receive a platinum drug. Despite the pervasiveness of platinum drugs in cancer treatment regimens, a number of attendant disadvantages such as resistance to some cancer types and side effects exist. Gold complexes are also emerging as a new class of metal complexes with outstanding cytotoxic properties and are presently being evaluated as potential antitumor agents.

Methods and Results: Here, some novel heterobimetallic platinum(II)–gold(I) complexes were synthesized and their cytotoxic activities against different human cancer cell lines such as A549 (human lung cancer),

SKOV3 (human ovarian cancer) and MDA-MB-231 (human breast cancer) were evaluated. Electrophoresis mobility shift assay and molecular modeling investigations have been performed to determine the specific binding mode or the binding orientation of these compounds to DNA. Molecular docking studies of them on DNA were performed by means of AutoDock 4.2. Fluorescence emission properties of them were assessed using fluorescent microscopy imaging.

In comparison to cis-platin, these compounds displayed significantly higher in vitro cytotoxicity on the studied cell lines. They enter SKOV3 cells rapidly, retaining their phosphorescence and localise simultaneously in cytoplasm, especially in perinuclear regions. So they are suitable candidates for time resolved emission imaging microscopy (TREM). Electrophoresis mobility shift assay showed a little shift and little interaction with plasmid DNA, though this shift is not as much as cis-platin. They may exert their cytotoxic effect through a different mechanism.

Conclusions: According to the results, careful drug design would result in producing potential antitumor agents with high efficacy. These Pt(II)-Au(I) complexes can be used in biological labelling and cellular imaging studies, due to desirable absorption and emission of them in solution under ambient conditions. Hence, they had a potential value for drug development as anticancer agents.

Introduction: A cyclic compound is common motif in natural product structures. Cyclic peptides, a vast subset of natural products, display a wide variety of biological activities. Owing to their size, cyclic peptides are particularly attractive scaffolds for interrogating challenging biomolecular interactions, such as those at protein–protein interfaces.

Methods and Results:

This review takes an overview of the literature for the synthesis of peptide and non-peptide macrocycles, concentrating on advances in the last five years up to the end of 2017. These methods are clustered by strategies for preparation and further derivatization of preformed macrocycle-containing building blocks. Examples of the use of macrocycles in medicinal chemistry are reported, including a collation of macrocycle derivatives appearing in recent patents for medicinal chemistry applications.

Conclusions:

This review aims to provide an overview of the extensive recent studies involving macrocycles in synthesis and medicinal chemistry and to highlight the continuing challenges.

Perovskone (1) was isolated as an antiplasmodial lead from Salvia hydrangea, semisynthetic derivatization of (1) let to find more potent antiplasmodial compound (2)(IC₅₀=0.08 μM, SI=83.8).The perovskone content in leaves and flowers was 0.053% and 0.04% of dried weight of plant material, respectively.

Introduction: Malaria, caused by five different Plasmodium species, is the most virulent tropical parasitic disease. According to latest WHO estimates, 212 million cases of malaria and 429 deaths have been reported in 2015. Artemisinin-resistant P. falciparum strains have been detected in some countries recently, which is really problematic and illustrates the urgent need for new drugs or lead structures. 

Natural products have served as a major source of drugs for centuries, and about half of the pharmaceuticals in use today are derived from natural products.

As a part of an ongoing screening for new antiplasmodial natural products, an n-hexane extract of S. hydrangea showed promising activity with the IC₅₀value of 3.2 μg/mL.

S. hydrangea distributed widely in Iran. Preparations from flowers serve as an anthelmintic and antileishmanial in the Pars province.  Large scale isolation of the n-hexane extract led to (1). Herein we report on the isolation, derivatization and quantification of (1) together with in vitro antiplasmodial activity.

Methods and Results:Fractionation of the n-hexane extract by open column chromatography on silica gel afforded (1) as a major constituent. It has shown potent in vitro antiplasmodial activity with IC₅₀ value of 0.19 μM and selectivity index (SI) of 169.5. The semisynthetic derivatization of (1) resulted compound(2). As for (2) antiplasmodial activity was improved in comparison with (1). The perovskone content of different parts of plant (leaves and flowers) was analyzed by HPLC using UV detection. Its level in leaves and flowers was 0.053% and 0.04% of dried weight of plant material, respectively.

Conclusions:Perovskone, a major constituent from S. hydrangea, can be considered as a potential antiplasmodial lead compound. In order to find more potent antiplasmodial semisynthetic derivatives and mechanism of action as well as in vivo examinations, further studies are suggested.

Introduction: Sea cucumbers, sometimes referred to as marine ginseng, produce an assortment of bioactive compounds with diverse functions, and are potential sources of active ingredients for nutraceutical, pharmaceutical and cosmeceutical products. This project aimed to identify and characterize novel bioactive compounds from the sea cucumber Actinopyga spinea Cherbonnier, 1980, with an emphasis on the triterpene glycosides, saponins.

Methods and Results: The sea cucumbers were extracted with 70% ethanol and this extract was purified by a liquid-liquid partition process and column chromatography using Amberlite XAD-4 resin, followed by iso-butanol extraction. The iso-butanol saponins-enriched mixture was further purified by high performance centrifugal partition chromatography (HPCPC). The resultant purified polar samples were analyzed using high performance liquid chromatography (HPLC) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF/ MS) and ESI-MS, and MS/MS to identify saponins and characterize their molecular structures. Further, the antifungal activity of saponins was examined against a few prevalent dermatophytes.

As a result, at least 45 saponins were tentatively identified in the sea cucumber A. spinea with a high structural diversity, including 20 new sulfated and non-sulfated triterpene glycosides, containing different aglycone and sugar moieties. The TLC profiles of the purified saponins mixture and MALDI analyses revealed that this species possesses a unique pattern of saponins. Further, the purified saponins showed the potent antifungal activity against the examined dermatophytes.

Conclusions:

The high structural diversity and novelty of saponins from A. spinea with potential functional activities presents a great opportunity to exploit their applications for industrial, agricultural and pharmaceutical use.

Introduction: AIDS therapeutic targets principally consists of three enzymes: reverse transcriptase (RT), protease (PR) and integrase (IN). Integrase strand transfer inhibitors among the HIV inhibitors has the advantage of suitable safety profile and high potency. The chelating motif and coplanar hydrophobic aryl group are the common pharmacophores of an integrase strand transfer inhibitor (INSTI). According to the cyclic chelating group of dolutegravir, we incorporated the chelating group into a cyclic motif and novel 2-mercaptooxazoloxocumarin tricyclic scaffold was designed. Hydrophobic part of the ligand was attached through s-arylation to occupy the same position as the halobenzyl pharmacophoric group of INSTIs.

Methods and Results: 4-Hydroxy-3-nitro coumarin was prepared in a nitration procedure of 4-hydroxy coumarin with the aid of concentrated nitric acid and sulfuric acid. Reduction of the 4-hydroxy-3-nitro coumarin in the presence of sodium dithionite and sodium acetate in water gave the 3-amino-4-hydroxy coumarin. 2-Mercaptooxazolocoumarin was prepared by the reaction of carbon disulfide with 3-amino-4-hydroxy coumarin in methanolic potassium hydroxide. Then, this intermediate was treated with substituted benzyl halides in the presence of potassium carbonate and acetone. Final derivatives were recrystallized from ethanol and confirmed by IR, LC-MS (ESI), ¹HNMR & ¹³CNMR. According to the docking results, the tricyclic scaffold could п-stack the 3’-end reactive adenosine in the IN active site just same as the co-crystallized ligand dolutegravir and the ligand heteroatoms complexes the magnesium cofactors in the IN.

Conclusions: Here, we introduced a novel scaffold for anti-HIV activity. The superimposed structure with co-crystallized ligand dolutegravir confirmed the potential for integrase inhibitory activity just same as the second generation integrase inhibitor dolutegravir.

Introduction: Nowadays, due to many years of taking antibacterial, antifungal and antiprotozoal drugs, human has faced drug resistance. It is predicted that death caused by drug resistance will surpass the death from cancer in future.  Therefore, studies done by world’s pharmacy researchers have been extended to synthesis of new compounds which potentially influence micro-organisms and protozoa. One of the acceptable methods of medicinal chemistry researches is propagation of new molecules according to known previous structures. One of these structures is 5-nitro-2-methyl imidazole that is a component of some drugs such as Metronidazole, Tinidazole and Secnidazole. In the present study we propagated this molecule further and synthesized some of the new derivatives of this family. Subsequently, according to the previous reports for similar compounds and their ability to link to FabH enzyme, new structures were surveyed using molecular docking approaches.

Methods and Results: First, the compounds 5a-e were synthesized. The structures of synthesized compounds were determined by IR, ¹HNMR and ¹³CNMRspectra. Then, the components were drawn in ChemDraw software. The structures were energetically optimized by Open Babel software and they were saved in AutoDock software as ligand with PDB format. Then the receptor structure (FabH) was obtained from Protein Data Bank (www.rcsb.org) and refined for docking simulation. AutoDock 4.2 software was applied for molecular docking approach.

Results: IR, ¹HNMR and ¹³CNMR spectra indicated that all the derivatives were successfully synthesized in laboratory and they had an appropriate intermolecular binding energy upon docking modeling.

Conclusion: According to the docking results, all the synthesized derivatives were accommodated properly in the active site of FabH enzyme and they made hydrogen and hydrophobic bondings with the amino acids. Amongst the synthesized compounds, compound 5b showed the best inhibition activity against enzyme FabH due to its lowest ΔG and highest lipophilicity.

Introduction:Cardiovascular and thromboembolic diseases are one of the most common causes of death in the world. Platelets play an important role in the pathogenesis of cardiovascular diseases. The use of antiplatelet drugs is one of the most important ways of prevention and treatment cardiovascular disorders. Looking at the various complications of the anti platelet drugs of the old generation, researchers are always looking for new drugs in the field of anti platelet therapy. There are some reports indicating that α-phenyl cinnamonitrile can be useful for treatment of cardiovascular diseases.  Therefore this study is designed to explore the anti platelet activity of a selected group of α-phenyl cinnamonitriles.

Methods and Results:Benzyl cyanide and various benzaldehyde derivatives were reacted in 90% ethanol to obtain the title compounds. A solution of sodium methoxide in methanol was added to this mixture dropwise, with stirring.. The product, thus obtained, was filtered off and crystallized from proper solvent. In the next step using hydrolysis of the synthesized derivatives in the presence of TFA, acetic acid and98% sulfuric acid, amide derivatives of the nitrile compounds were synthesized.

The structure of the synthesized compounds was confirmed by using NMR, IR, and MS spectrometry methods.

Invitro anti platelet activity of α-phenyl cinnamonitriles  and  their amide congeners were evaluated by using arachidonic acid (AA) and adenosine diphosphate (ADP) as inducer according to born method on human platelet rich plasma (PRP).

For all compounds IC50s were calculated and compared. The result showed that α-phenyl cinnamonitrile, 4- methoxy-α-phenyl cinnamonitrile, were the most potent anti platelet aggregation agents with IC50 values of 17.79 and 38.2 µM respectively.

R=2-Cl; 2-Br; 2-OH; 3-F;3-Cl;3-Br;3-OH; 4-H; 4-OMe;4-F; 4-Cl; 4-CN; 4-Br; 3,4-diOMe ;3, 4, 5-triOMe.

Conclusions:A group of α-β unsaturated nitrile derivative is introduced as new anti platelet aggregation agents proving the eligibility of this scaffold for anti platelet activity.

Introduction: Reteplase is a fibrin-specific thrombolytic drug and non-glycosylated modified recombinant form of human tissue plasminogen activator (t-PA). It is containing kringle-2 and serine protease domains but the epidermal growth factor and fibronectin finger domains are absent. The lack of finger domain in reteplase cause decrease fibrin specificity. Since the enhancing fibrin specificity is one of the aim for development new thrombolytic drug, due to decreasing side effect such as hemorrhage, also reteplase is non-glycosylated and can be produced in bacterial system at low cost, in this study a new generation of reteplase designed with more fibrin specificity. 

Methods and Results: According to the sequence of protein drugswith more fibrin specificity, mutations in reteplase sequence consist of substitution mutation in Kringle 2 domains and adding sequence of mutated finger domain to reteplase sequence. 3D structure of this new reteplase was created by Modeller9.17 software and then simulated by Gromacs 5 software for 20 ns. Docking simulation was performed between new and wild reteplase with fibrin by HADDOCK server separately. The results showed that new reteplase has better interaction with fibrin compared with wild type (table1).

Parameter

Wild reteplase

New  reteplase

HADDOCK score^*

-35.8 +/- 8.3

-43.2 +/- 21.3

            *More negative score is better score

 Conclusions: In this study a new generation of reteplase with more fibrin specificity was designed in silico. Since the production of reteplase has low cost compared with tPA, improvement its structure to desirable features such as increasing fibrin specificity, can be a way to achieve a favorable thrombolytic drug.

Introduction: Soluble epoxide hydrolase (sEH) inhibitors have been shown to effectively increase the levels of epoxyeicosatrienoic acids and reduce the levels of dihydroxyeicosatrienoic acids, which may be translated to therapeutic potentials for hypertension, diabetes, stroke, dyslipidemia, pain, immunological disorders, eye diseases, neurological diseases and other indications. Since most sEH inhibitors have poor pharmacokinetic properties, development of novel inhibitors is a great deal of attention.

Methods and Results: Based on the structure activity relationship of soluble epoxide hydrolase inhibitors and docking studies, some novel compounds with amide moiety and triazole ring as a first and second pharmacophore respectively were designed. These structures were synthesized through 4 step reaction with proper yields. Initially, 4-nitrobenzoyl chloride was reacted with hydrazine hydrate and then in the presence of benzonitrile and catalytic amounts of copper iodide, 1,2,4-triazole was closed. Final products were obtained by reduction of nitro group and reaction with various benzoyl chlorides. Docking studies on the designed sEH inhibitors confirm that the amide groups of the analogues fit properly in the active site of sEH and have a suitable distance from the amino acids of Tyr466 and Asp335 for effective hydrogen bonding. These novel compounds were synthesized in appropriate yield and their structure was approved by instrumental methods including IR, Mass, HNMR and ^CNMR spectroscopies.

Conclusions: In conclusion, some novel amide-based soluble epoxide hydrolase enzyme inhibitors with a 1,2,4-tri azole as a novel secondary pharmacophore were designed, synthesized and structurally approved by IR, NMR and Mass spectra.

Response surface methodology (RSM) was applied to develop an RP-HPLC method in which paracetamol was analyzed and determined on a C18 column with UV detection. To explain more, RSM was used to statistically model the impact of flow rate (ml.min^-1) (A), column temperature (°C) (B) and mobile phase composition (H₂O: MeOH) (C)on the retention time (RT) of Paracetamol within tablets.

Introduction: The major goal of this investigation was to optimize an RP-HPLC method which is simple, linear, accurate, sensitive and selective in determination of Paracetamol in solid dosage forms.

Methods and Results:Three distinctive levels were dedicated to each evaluated factor.Box-Behnken experimental design including seventeen independent runs within a range of 25-50% MeOH ratio (mobile phase), 25-45 ºC and 0.7-1.3 mL. min^-1 flow rate were carried out to explore the effectivefactors onRT of Paracetamol using RP-HPLC method. ANOVA results revealed that quadratic model was significant (Model F-value of 225.65) and could best describe the relationship between dependent variable (RT) and independent ones:

RT= 3.30 - 1.2A - 0.38B - 0.80C + 0.30AC + 0.43BC + 0.53A²

As can be understood from the model terms, the most significant term was the solvent ratio and all the factor levels were indirectly proportional to the Rt. Moreover, the interaction of column temperature and solvent ration seemed to be more important. It was also predicted that optimum assay condition included 1:2 ratio of methanol to water, column temperature of 35ºC and mobile phase flow rate of 1.3 mL.min⁻¹. Using this optimum condition, baseline separation of the drug was achieved with a good resolution and a run time of 2.1 min. The optimized method was validated in terms of linearity, accuracy, limit of detection and limit of quantification of paracetamol within a few commercially available Paracetamol tablets.

Conclusions:The optimized RP-HPLC technique provided a convenient and efficient method toward qualitative/quantitative analysis of Paracetamol in its tablets. The improved method is also rapid and sensitive enough to be used for single tablet analysis.

Introduction: Hawthorn (Crataegus L.) is a well-known widely used medicinal plant with more than 280 species that are spread in all over the world [1]. There are seven species of Crataegus growing in the Kazakhstan flora, from which only Crataegus almaatensis Pojark (C. almaatensis) is an endemic one. It is a dense, spiny tree up to 3-4 m tall producing dense white colored flowers.  It is spread in the foothills of Ile-Alataumountains inAlmaty [2,3]. Crataegus is used as an alternative medicine for ailments of the cardiovascular, digestive and endocrine systems[4]. These plants are rich in biologic active compounds, such as flavonoids, hydrocinnamic acids, sugars, organic or phenolic acids, terpenes and essential oils [5]. There are a few scientific studies on the biochemistry of cultivated C. almaatensis fruits, focused on the determination of carotene, bioflavonoids, sugar and organic acids contents [6,7]. There is no full-scale study of the C. almaatensis to date. The authors of this work, from Kazakhstan and from two other European Universities are carrying out joint scientific full-scale studies with this endemic plant. .

The aim of this study is to present preliminary results on isolationand quantification of the main constituents of C. almaatensis flowers, leaves and fruits by means of high speed counter current chromatography (HSCCC) and HPLC respectively.

Methods and Results:The HSCCC was performed using an instrument IntroPrep^TM (Quattro). The solvent system HEMWat was chosen according to the partitioning of the constituents of the plant material on a TLC analysis. Identification of the isolated compounds was carried out by means of different NMR spectra. Reverse phase HPLC system (Waters) was used for the quantification of the isolated compounds using the following mobile phase: (A) 40mM potassium dihydrogen phosphate (pH 2.3 with 85% Orthophosphoric acid); (B) Methanol, 0-52.5 min 95%A-5%B; 52.5-57 min 58%A-42%B; 57-60 min 95%A-5%B, with a flow of 1ml/min.

Two main flavonoids hyperoside and quercetin-3-O-rhamnoside were isolated and identified. The quantity of hyperoside was determined to be 19.79±0.36 mg/g, 14.70±0.37 mg/g and 0.27±0.01 mg/g for flowers, leaves and fruits respectively.

The concentration of quercetin-3-O-rhamnoside in the extract was found to decrease from leaves (51.00±0.92mg/g) to flowers (1.23±0.05 mg/g)to fruits (almost undetectable).                            

Thymus Vulgaris  (Lamiaceae) with common name “Thyme” is a well- known plant with different medicinal uses. Dental Caries and Periodontal disease are one of the common bacterial infections in human beings. Streptococcus mutans is the most etiologic agent. Finding natural sources with capability to inhibit the growth of S.mutans is the focus center of most researches. Investigations on the effects of T.vulgaris essential oil on S.mutans and identification of the constituents of the oil were the aims of present study.

 Materials and Methods:

The plant was collected from the populations growing in Hamadan province and was authenticated in Department of Pharmacognosy, School of pharmacy, Hamadan university of Medical sciences. The aerial parts of the plant were dried in shade and powdered. The essential oil was obtained by Clevenger type apparatus. Oil was subjected for GC/MS. Zone Of Inhibition of the essential oil against S.mutans were determined by Agar well diffusion test.

 Results:

Forty- one compounds were identified and 4- Terpineol(16.55%) was the main component. ZOI, for thyme essence were 80mm. Thyme essential oil presents considerable anti streptococcus activity.

 Discussion:

Considering the constituents of essence, 4- Terpineol is an Oxygenated monoterpene with reported antibacterial effects in previous studies. The results of present study may be attributed to presence of 4- Terpineol and it’s synergistic effects with another constituents present in the oil.

 Conclusion:

T.vulgare essential oil with profound antibacterial activity may be used in oral hygiene products.

Introduction: Malva sylvestris is one of medicinal plants from Malvaceae family. According to some important Iranian traditional medicine’s references (ITMR) all parts of this plant can be used for treatment of “Zahir” that this disease has similar signs and symptoms to Ulcerative Colitis (UC). UC is one of the common types of Inflammatory Bowel Disease (IBD) which mostly affects distal colon and rectum in many new cases each year. Because of low efficacy and high adverse effect of today’s drugs, many refers of ITMRs, high frequency in Iran and our team’s previous study of several extraction from this plant on UC induction in mice, we decided to use aqueous extraction to prepare an oral colon specific formulation.

Methods and Results: The fresh plant was collected from North of Fars province. Hydro extraction was done with maceration route in the refrigerator and out of light and then the concentrated extraction was lyophilized. Polysaccharides extraction was done with absolute acetone and poly phenolic compounds were extracted with n-hexane and ethyl acetate. For all of total sugar evaluated with Phenol-Sulfuric acid method. Also Gallic acid and Folin-Ciocalteu reagents were used for determination of total phenolic compounds. Twelve formulations prepared and in vitro evaluations were done based on US Pharmacopoeia. Disintegration time test, dissolution time test, hardness, weight variation, content uniformity and release test were performed on tablets. Yield of total extraction and polysaccharides extraction were 10.83% and 9.6% W/W. Be calculated 0.18 mg poly phenolic compounds in each 1 g of lyophilized extraction. Other Pharmacognosy’s tests (Linearity, intra and inter day accuracy and precision) and pharmaceutical tests (Hardness, weight variation and content uniformity of tablets) were in the acceptable range. Tablets coated with Eudragit S100 (E) 2% solution exhibited 7.3% release after 2 hours, 42.33% after 6 hours and 96.21% after 10 hours.

Conclusions:Tablets that used Malva sylvestris as active pharmaceutical ingredient and prepared by direct compression method and coated with E 2% solution, showed the most suitable results for clinical trials in UC cases.

Introduction: The order Sinularia is a large, diverse and ecologically important group of marine invertebrates. In this work, we present an overview of the most promising marine bioactive compounds isolated from Sinularia species in the first decade of the 21st century, which may have applications in the therapy of human diseases. The present study also discusses future perspectives for the bio-prospecting of new marine natural product that produced by this species group of marine invertebrates.

Methods and Results: This study was systematic review and reviewed publications were identified through searches in Scopus, science direct, PubMed, Proquest, Ovid and also Wiley by using the search terms “sinularia”, “metabolite” and “pharmacology”. The search was completed through December 2017, and was limited to articles published in English. Relevant articles were identified based on the expertise and clinical experience of the authors. This review covered about several effects of sinularia secondary metabolites and we categorized our result in different pharmacological effects including:  cytotoxic, antitumor and anticancer activity against antibiotic-resistant and antibacterial activity, anti-inflammatory, antiviral, antialgeal, and antifouling effects. Also inhibitory effect on HIV-1 reverse transcriptase and p56lck tyrosine kinase, HIF-2α Induced Gene Expression, the release of elastase by human neutrophils, the generation of the superoxide anion.

Conclusions:

Finally, the review speculates sinularia secondary metabolite was a potent bioactive compound that had a potential to introduce as a lead compound in many diseases especially in cancer and anti-inflammatory diseases.

introduction: Ferula assafoetida is a source of sesquiterpenes [1]. According to an investigation, phenolic compounds at physiological concentration can inhibit inflammatory enzymes [2]. These enzymes digest the extracellular matrix and provide the conditions for activation and migration and proliferation of endothelial cells. Reported studies on medicinal plants for their inhibitory effect on MMP are very limited.

Methods and Results:

Acetone extract of plant was prepared and Sesquiterpenes were purified using HPLC preparative analyses and their structures were elucidated. After culturing the cell at confluence, cells were isolated and the supernatant was removed. The pure substances were applied on cell lines U87MG and Wehi activities. Besides the structure has been docked in the active site of metalloproteinase, and significant interactions were determined.Subsequently, ligand-protein complexes were subjected to molecular dynamics simulation in water and thermodynamic properties were calculated. In the phytochemistry field galbanic acid, mogoltadone, kellerin, polyanthin and polyanthininwere produced from F. assafoetida. The results of celluar toxicity study shows that IC50 of Galbanic acid, Mogoltadone and Polyanthin in Wehi cell line were 925.2703, 721.86, and 680.3 µg/ml in U87MG cell line were 952.193, 752.352, 678.742. Galbanic acid, mogoltadone, kellerin, polyanthin and polyanthininwere solated from F. assafoetida. The results of celluar toxicity study show that IC50 of Galbanic acid, Mogoltadone and Polyanthin in Wehi cell line were 925.2703, 721.86, and 680.3 µg/ml in U87MG cell line were 952.193, 752.352, 678.742

Conclusion: Investigation revealed that the coumarins have inhibitory effects on the content and activity of MMP 2.9 and showed anti-angiogenetic effect. So, they can be potentially effective in the treatment of cancer. Interactive and competitive binding between MMP-9 and Galbanic acid were studied with FT-IR, UV-Vis and fluorescence methods and MMP-9 structure was changed in these interactions.

Ferulago macrocarpa contains prantschimgin and grandivitin from phenolic class. Studies have shown that phenolic compounds at physiological concentrations could inhibit two groups of gelatinase matrix metalloproteinases (MMP2, MMP9). Due to the high diversity of coumarin in the plant, the possibility ability of the compounds to inhibit plant enzymes seem to be mentioned.

introduction: Ferulago macrocarpa of Apiaceae, native to the highlands of the West of Iran (Zagros Mountains) includes Prantschimgin and Grandivitin from phenolic class. researches have shown that phenolic compounds at physiological concentrations could prevent two groups of gelatinase matrix metalloproteinases (MMP2, MMP9). Because of the high variety of coumarin in the plant, the potency of the compounds to inhibit plant enzymes seem to be refered.

Methods and Results: Acetone extract of the plant was provided and then winterized. Thereafter, Prantschimgin and Grandivitin were purified using normal phase column chromatography and preparative HPLC, and their structures were verified. After culturing the cells, at confluence step, Supernatants were collected at24 and 48h soup (broth supernatant containing medium containing 2% albumin, and glutamine and antibiotics and enzymes secreted by the different concentrations of active ingredients) and non-proliferation medium containing 2% albumin was amplified. The pure substances were applied on cell lines U87MG and Wehi for evaluation of VEGF, MMP-2 and 9 activities. In the computational processing, the structures have been docked in the active site of metalloproteinases9, and important interactions were detennined. then, ligand-protein complexes were subjected to molecular dynamics simulation in water, and thermodynamic attributes were calculated. (MMP9 code= 1L6J, MMP2 code= 1CK7).

prantschimgin and grandivitin were purified fromF.macrocarpafruits. Regarding cytotoxicity results IC50 of Prantschimgin and Grandivitin in Wehi cell line were 521.63,232.66, and in U87MG cell line were575.58,322.0 lpg/ml, respectively. Biological experiment indicated significant changes in the amount and activity of matrix metalloproteinase and vascular endothelial growth factor.

Conclusion: Two coumarins, prantschimgin and grandivitin with the potential inhibitory effects on the activity of MMP2,9 and anti-angiogenesis were purified from F. macrocarpa fruits. The application can be expected to have therapeutic efficacy in cancer cell lines U87MG and Wehi

Introduction: Multi-particulate dosage form of pellet is formed by agglomeration of fine powdered drugs and excipients, leading to free flowing spherical particles. The multi-step process of extrusion & spheronization are mostly applied for preparation of uniformly-sized pellets. Golqand, a product of Traditional Persian Pharmacy containing Rosa damascena Mill petals is a heart and brain tonic, refresher, astringent, and a stomachic. It helps to improve appetite and relieves digestive diseases. Also, Golqand calms down nervous system. Based on traditional texts, it has been produced as a Jam-like preparation, imposing some difficulties in taking and dosing. In this study, we have prepared Golqand in pellet form, a novel solid dosage form and optimized this natural formulation.

Methods and Results: In this study, a 20 runs D-optimal method was applied as an experimental design to establish the optimum conditions for Golqand pellet preparation by extruder spheronizer equipment. The preparation process of pellets was optimized by a systematic multi-objective-optimization approach in terms of D- values for the particle size distribution (i.e. D10, D50 & D90) which are the intercepts for 10%, 50% and 90% of the cumulative mass obtained via sieving method.

The Model F-value of 6.58 implied the models were significant.  There is only a 0.34% chance that a "Model F-Value" this large could occur due to noise. The R², adjusted R², predicted R², and adequate precision for D50 model were calculated 82%, 72%, 46%, and 10.06, respectively which means that there is a good correlation between parameters and model.

Conclusions: In conclusion, presented models conducted us to prepare Golqand pellets with unimodal particle size distribution and pre-defined particle size. Applying pelletization method for Golqand preparation could resolve some critical challenges of natural formulations like taking similar doses.

Abstract: Extraction was performed by using maceration method for dried flower sample. Then, the antimicrobial effect of aqueous and ethanolic extracts on eight bacterial sp. and two fungi were tested using disc diffusion method. The antioxidant effect was also determined through ferric reducing potency and phosphor molybdenum followed by total phenol determination.

 Introduction: The Astragals. is high in certain antioxidants. The fruit is noted for its high level of vitamin C, and is used to make syrup, tea, and marmalade. It has been grown or encouraged in the wild for the production of vitamin C from its fruit (often as rose-hip syrup), especially during conditions of scarcity or during wartime. The species has also been introduced to other temperate latitudes. During World War II in the United States, Rosa canina was planted in victory gardens, and can still be found growing throughout the country, including roadsides and in wet, sandy areas along the coastlines.

Methods and Results: Extraction was performed by using maceration method for dried flower sample. Then, the antimicrobial effect of aqueous and ethanolic extracts on eight bacterial sp. and two fungi were tested using disc diffusion method. The antioxidant effect was also determined through ferric reducing potency and phosphomolybdenum followed by total phenol determination. Finally, partial detection of bioactive compounds was conducted using chemical and calorimetric methods. The results showed that ethanolic extract had the most antimicrobial effect; while aqueous extract weakly affected bacterial and fungal strains. Antioxidant experiments also revealed that ethanol extract had more antioxidant effects than aqueous extract. The most content of total phenolic compounds was found in ethanol extract. The results of the plant chemical determination showed the presence of flavonoids, alkaloids, anthraquinones, tannins, glycosides, and reducing sugars.

Conclusions: Considering that few reports about the therapeutic effect of Astragals. has been published, this study could be considered as a valuable report about the important role of this plant on preventing infections and neutralizing oxidant agents.

Introduction: Multiple sclerosis (MS) is an inflammatory chronic neurological disease, which affects young and middle aged adults, leading to demyelination, neuronal and axonal damage and finally atrophy of the brain, the spinal cord, and the retina in most patients. MS can cause sensory, motor and visual defects, lack of coordination and cognitive disabilities resulting in quality of life reduction. The aim of the present article was to review the clinical evidence related to medicinal plants in the treatment of symptoms associated with MS patients.

Methods and Results: Electronic databases, including the Pubmed, Scopus and Cochrane Library were searched for clinical studies that evaluated the positive effects of medicinal plants in MS. The searched keywords were ‘multiple sclerosis’ in the title/abstract, and ‘plant’, ‘herb’, and ‘phytochemical’ in the whole text. To ensure a better comparison between trials, the Jadad score was used to assess the methodological quality of trials. Findings of the study revealed significant effects of different medicinal plants on MS. This plants are including Andrographis paniculata (King of bitters), Boswellia papyrifera (Bitter frankincense), Cannabis sativa (Hemp), Ginkgo biloba (Ginkgo), Aloysia citrodora (Lemon verbena), Ruta graveolens (Rue) and Panax ginseng (Korean ginseng). C. sativa had the highest level of clinical evidence, supporting its efficacy in MS symptoms. The main complications of MS in which natural drugs were effective include spasticity, fatigue, scotoma, incontinence, urinary urgency, nocturia, memory performance, functional performance, and tremor.

Conclusions: Further well-designed human studies with a large sample size and longer follow-up period are recommended to confirm the role of medicinal plants and their metabolites in the management of MS.

Introduction: Plants, which are source of a large proportion of bioactive components, have been used for the treatment of several human ailments for thousands of years. Many herbal remedies are traditionally used as contraceptives, abortifacients, emmenagogue or oxytocic agents. The term "abortion" actually refers to any premature expulsion of a human fetus, whether naturally spontaneous or artificially induced. An abortifacient is a substance that induces abortion. In case of medical abortion techniques and usage of medicines, it has more disadvantages and side effects, but according to the studies medicinal plants have better compatibility with the human body that can cause abortion with different mechanisms. The purpose of this study is to review the medicinal plants and natural products used to induce abortions.

Methods and Results: Searching keywords such as medicinal plant, natural compound, abortion and abortifacient resulted in many published articles.

Many medicinal plants have been reported in literatures with antifertility effect and some of them reported as abortifacient which belonged to different plant families like Fabaceae (Dolichos trilobus), Apiaceae (Apium graveolens), Amaryllidaceae (Allium sativum), Rutaceae (Ruta graveolens), Apocynaceae (Holarrhena pubescens) and etc. Based on the researches, medicinal plants can cause abortion with  different mechanisms including estrogenic activity, increases menstrual flow and induces abortion, Uterine stimulant, increase the risk of bleeding, Uterine Contraction, Uterotrophic activity and stimulant action on uterine muscles. Some articles were referred for citing the proved abortifacient effects of plants or isolated constituents in laboratory animals. Some of these phytoconstituents include Yuanhuacine from Daphne genkwa, Methyl aristolate from Aristolochia indica, Momorcochin from Momordica cochinchinensis, Plumbagin from Plumbago zeylanica.

Conclusions: Abortion can be caused by abortifacient medicines or medicinal plants. Although using abortifacient pills or new techniques are faster, but since the medicines have disadvantages and side effects, it is beneficial to use plants. Some medicinal plants have abortifacient potential and there is a need to more clinical studies and newer techniques from these plants and their natural components.

Introduction: Men above fifty-five years old are at high risk for malignant prostate cancer. Currently surgery is the only treatment and the patients must use medicines post-operation. This process may exert extreme side effects and reduce their quality of life. On the other hand, in some cases, cancer cells start to multiply again. There is a simple solution for prevention of prostate cancer that we want introduce.

 Methods and Results: The prostate cancer cells need Glutamine amino acid for their proliferation. Two substances; Ursolic acid and Resveratrol can inactivate some enzymes which prevent reabsorption of Glutamine. Therefore, they can stop cancer cell proliferation. On the other hand, Curcumin can cause apoptosis of cancer cells and destroy them. Ursolic acid, Curcumin and Resveratrol exist in skin of red apple, turmeric and black grapes respectively which are readily available and their consumption together as potion can be useful. Simultaneouse use of Resveratrol and Ursolic acid could extremely reduce danger of prostate cancer by decreasing Glutamine reabsorption in cancer cells. In addition, Curcumin consumption causes apoptosis in cancer cells and destroys them. Therefor we can use it for prevention of prostate cancer.

Conclusions: Since the above substances (Resveratrol, Curcumin, Ursolic acid) exist in available compounds like skin of red apple, turmeric and black grapes, men above forty years old can reduce risk of prostate cancer by combining a big apple with some turmeric and black grapes (as a potion) So the prostate would be protected from cancer, After prostate surgery that PSA may raise again. Consumption of this potion in these cases can replace current medications with several side effects. We could combine these materials and determine the amount of dose, same as a drug. In the next step, this combination was tested on animals and humans. Based on human gene plan (HGP) a lack of Allosteric enzymes which by two material Ursolic Acid and Resveratrol will be inactivate and therefore non-proliferation prostate cancer cells.  

Introduction:

Saponins are plant glycosides and possess great diversity in their  structure. They are common in a variety of higher plants. Saponins display various biological activities. Recently intensive research has been focused on developing saponins for tumor therapies. But they have high toxicity effect in clinical uses. Herein, saponin-phospholipid complex have been synthesized in order to reduce the cytotoxicity, increase the efficiency and selectivity of saponin-enriched extract on melanoma cell line.

 Methods and Results:

In this work, saponins were extracted from Zizyphus spina-christi using ethanol 70% as solvent. The ethanol extract was fractionated by liquid-liquid extraction process using chloroform, ethyl acetate and finally with water-saturated n-butanol. The presence of saponins was confirmed with FT-IR and UV spectroscopy. Then the nanocomplex was prepared using emulsion /solvent evaporation method and with various ratios from soybean lecithin:cholesterol:saponin extract. The generation saponin/phospholipid complex was demonstrated by FT-IR. Scanning electron microscopy (SEM) of the nanocomplex showed spherical shape and their size were lesser than 40 nm. Zeta potential of synthesised nanocomplex was -32 mV. The calculated entrapment efficiency was 81/82%. The synthesized nanocomplexes and saponins were analyzed by MTT for their toxicity on B16F10 cell line. The results showed high cytotoxicity of saponin-enriched extract of Zizyphus spina-christi and a decrease in cytotoxicity of nanocomplexes compared to saponin in cell culture.

 Conclusions:

The results of this study demonstrated that saponin-enrich extract derived from Zizyphus spina-christi has a strong potential in controlling the cancer cell growth. Also synthesis of nanocomplexes of saponin/phospholipid can improve saponin effects and decrease its cytotoxicity.

Introduction: The genus Eremurus is native to Eastern Europe and temperate Asia. Particularly, Eremurus persicus (Joub. & Spach) Boiss. is highly valued in traditional foods and medicine. Scientific knowledge about E. persicus chemical composition and bioactivity is required.

 Methods and Results: The present study is aimed to determine the volatile composition of E. persicus essential oil (EO) by means of gas chromatography coupled to flame ionization/mass spectrometry detector. Moreover, the antioxidant, antimicrobial, anticancer, and acetylcholinesterase inhibitory activities of the EO were tested. Interestingly, the anti-dermatophyte potency was close to that of the drug griseofulvin, with minimum fungicidal concentration ranging between 0.7 and 4.5% depending on the fungi strain. The EO was also effective against hepatocellular carcinoma (Hep-G2) and breast adenocarcinoma (MCF-7) human cancer cell lines in a concentration (200-1500 ng/mL)-dependent manner, with a decrease of the cell viability up to 65% and 52%, respectively. The E. persicus EO was rich in terpenes and oxygenated terpene derivatives. Individually, limonene (16.25%), geranylgeraniol (15.23%), n-nonanal (9.48%), geranyl acetone (9.12%), benzene acetaldehyde (8.51%), linalool (7.93%), α-pinene (6.89%), and 1,8-cineol (5.22%) were the most abundant volatile compounds and could be chosen as analytical markers of this essential oil.

Conclusions:

In conclusion, our results suggested that this EO possesses a wide range of bioactive properties that could be useful in nutraceutical, functional foods and cosmeceutical formulations.

Introduction: In recent years, with increased prevalence of viral infections and having no specific treatment  and also the continuous appearance of resistant viral strains, finding of novel antiviral agents is necessary.

 Methods and Results: In this study, monoterpenes of thymol, carvacrol and p-cymene were screened for their inhibitory effect against herpes simplex virus type 1 (HSV-1) in vitro on Vero cell line CCL-81-ATCC using a plaque reduction assay. The antiviral activity of three monoterpenes (thymol, carvacrol and p-cymene) were evaluated by cytotoxicity assay, direct plaque test. In addition, the modes of antiviral action of these compounds were investigated during the viral infection cycle. Results showed that the inhibitory concentrations (IC₅₀) were determined at 0.002%, 0.037% and >0.1%, for thymol, carvacrol, p-cymene, respectively. A manifestly dose-dependent virucidal activity against HSV-1 could be exhibited for compounds tested. In order to determine the mode of the inhibitory effect, compounds were added at different stages during the viral infection cycle. At maximum non-cytotoxic concentrations of the compounds, plaque formation was significantly reduced by more than 80% when HSV-1 was pre incubated with p-cymene. However, no inhibitory effect could be observed when the compounds were added to the cells prior to infection with HSV-1 or after the adsorption period.

Conclusions:

These results indicate that compounds affected HSV-1 mostly before adsorption and might interact with the viral envelope. Thymol exhibited a high selectivity index and seems to be a promising candidate for topical therapeutic application as antiviral agent for treatment of herpetic infections.

Introduction: Harmine is one of the Harmal-deived alkaloids with anti-proliferatory effect on cell lines. Nicotine is a major toxic component of cigarette smoke and it is a major risk factor in the development of functional disorder of several organ systems. Nicotine from tobacco products is absorbed into the blood across the lungs,  nasal and buccal mucosa. The current study aimed to investigate the effect of Harmine and Nicotine on the weight of kidney and number of glumeruli and glomerular diameter, kidney tissue and serum levels of nitric oxide, BUN, Creatinine and TAC in mice.

Methods and Results: In this study, 48 male Mice were divided in to 8 groups: control, nicotine–treated group (2.5 mg/kg/day); harmine-treated groups (5,10, 15 mg/kg./day); and nicotine and harmine treated group intraperitoneal administration for successive 14 days. These mice were randomly assigned to 8 groups(n=6). After 24 hours animal were killed , the kidney was sampled: tissue sections were prepared and examined by light microscope. weight of kidney  and number of glumeruli and glomerular diameter and serum levels of nitric oxide, BUN, Creatinine and TAC (Total antioxidant capacity) were analyzed (one-way ANOVA). Then data were P<0.05 was considered significant. The results indicate that nicotine administration significantly increased BUN, creatinine and nitric oxide levels compared to saline group (P<0/05). Harmine   (10, 15 mg/kg./day) significantly decreased BUN, creatinine and nitric oxide levels  compared to control group and nicotine group (p<0.05). Nicotine treatment significantly increased glomerular diameter compared to control group (p<0.05). as well as, nicotine administration significantly decreased TAC levels compared to saline group (P<0/05). Histopathology of the kidney confirmed the changes induced by nicotine and the renal protection effect of harmine.

Conclusions: It seems that harmine administration could improve kidney changes and prevented nicotine-induced adverse effects on serum levels of nitric oxide, BUN and Creatinine and Total antioxidant capacity.

Introduction: Arsenic (As³⁺⁾ is a toxic metalloid and a potent environmental toxicant that has been reported to cause severe liver injury. Long-term exposure to arsenic through food and contaminated water can result in a chronic As³⁺ poisoning. One of the main hypotheses about the mechanism of As³⁺ toxicity is oxidative stress so that As³⁺  toxicity which may be due to direct reaction of reactive oxygen species with cell biomolecules, causing damages to lipids, proteins, and DNA, hence leading to cell death. In the present study, the protective role of hydro alcoholic and aqueous extract of Achillea wilhelmssi (A. Wilhelmsii) against liver injury induced by As³⁺ toxicity.

Methods and Results: Hepatocytes were obtained by collagenase perfusion of the liver and their viability was assessed by the trypan blue (0.2% w/v) exclusion test. Cytotoxicity was associated with reactive oxygen species (ROS) formation, lipid peroxidation and loss of mitochondrial membrane potential which were prevented by antioxidants and ROS scavengers (DMSO, mannitol), mitochondrial permeability transition (MPT) pore sealing agent (carnitine) and the ATP generator (L-glutamine),  Lysosomal protective agent and glutathione discharge. We used aqueous and hydroalcoholic extracts of Achillea wilhelmssi with concentrations 25μg/ml, 50μg/ml and 100μg/ml for 3h to evaluate the protective effect of these extracts on the As³ –induced oxidative stress in isolated rat hepatocytes. Also the protective and antioxidant effects of Quercetin and Gallic acid polyphenols in the A. Wilhelmsii have been investigated as control. According to the results, the concentration of As³⁺, which can cause death of 50% of cells, is equivalent to 50 μM, that could significantly increase cell death, ROS production, lipid peroxidation induction and mitochondrial membrane slump compared to the control group (p <0.05). Achillea wilhelmssi extract could significantly decrease produce ROS, lipid peroxide and loss of mitochondrial membrane decline.

Conclusions:

In the present study, result showed the hepatoprotective role of hydroalcoholic and aqueous extract of Achillea wilhelmssi against liver injury induced by arsenic in rats had been studied by determining their effects on decrease produce ROS, lipid peroxide and loss of mitochondrial membrane decline. Because of existence large amounts of flavonoids and polyphenols, including quetitintin and Gallic acid in A. Wilhelmsii can hepatoprotective effects be attributed to these compounds.

Introduction: Acne is an infectious chronic inflammatory disorder occurring in skin's outer tissue and characterized by seborrhea, pimples, papules, comedowns and nodules based on severity. It can be caused by increased sebum production, abnormalities in epithelium, inflammation and microbiological reasons. Several natural active herbal compounds have been reported  with anti-acne effects.

 Methods and Results: Various literatures containing the keywords including Anti-acne medicinal plants, Anti-acne herbal remedies, Anti-acne herbs have been extracted from different databases including PubMed, Science Direct and Scopus. Among medicinal plants, Pinaceae, Berberidaceae, Asteraceae, Zingiberacea and Piperaceae families had shown anti-acne effects. Among the aforementioned families for example, Abies koreana essential oil has shown anti-microbial and anti-inflammatory effects. Moreover, ethanol extract of Ammannia baccifera and Berberis aristata had anti-bacterial effects on acne-induced microrganisms. Berberis vulgaris was also evaluated and its anti-bacterial, anti-inflammatory and anti-lipogenic effects were confirmed. Also, Curcuma longa showed anti-oxidant effects that can be applied in acne therapy. Various herbal compounds from these medicinal herbs have been reported as anti-acne agents, due to their anti-bacterial, anti-inflammatory, anti-sebum and anti-androgen effects. Chemical identity of these agents was confirmed as phenol derivatives, flavonoid and tannin compounds, e.g. Rhodomyrtone, Pulsaquinone, Hydropulsaquinone, Honokiol, Magnolol, Xanthohumor and lupulones. In this study, we classified and summarized these reports to identify the best effective herbal medicines for acne therapy.

Conclusions: Nowadays herbal medicine and natural compounds provide valuable, effective and safe agents for the treatment of acne. According to the studies, there are numerous herbs and herbal compounds with anti-acne effects and they can be used as an alternative treatment against this inflammatory disorder.

Introduction: Lower Urinary Tract symptoms (LUTS)? impacts the quality of life of about 23.8% of the male population in Iran, diagnosed with Benign Prostatic Hyperplasia, annually . The current pharmacological treatment protocol for LUTS are α-blockers and 5-alpha reductase inhibitors (such as Dutasteride). This study was designed to estimate the cost-utility of dutasteride plus tamsulosin therapy for LUTS from the perspective of the Iran Health System.

Methods and Results: A Markov model was developed to estimate healthcare costs and patient outcomes, measured by quality-adjusted life years (QALYs), for patients with moderate to severe LUTS. The model, compared four mutually exclusive health states in two alternative treatment options: tamsulosin (0.4 mg/day) and dutasteride plus tamsulosin (0.5mg+0.4 mg/day). time horizon was 35 years, with the duration of one year per cycle. The discount rates for utilities and costs were 3% and 5% respectively. A meta-analysis was conducted to estimate advese drug reactions (ADRs) and After Surgery Events (ASEs) probabilities. Total Cost consists of the direct costs of medications, as well as inpatient and outpatient services (general practice and urology specialist examinations, hospitalizations, laboratory services, diagnostic procedures, TURP surgical procedures, treatment of AUR, and treatment in emergency care services). One-way sensitivity testing and Probabilistic Sensitivity Analyses (PSA) were performed for virtual cohort of 1,000 patients with LUTS.

Utility weights for each health states were obtained from a meta-analysis of published studies with EQ5D method. These weights are calculated 0.86, 0.79, 0.72 and 0 in mild, moderate, severe and death states, respectively. The probability of ASEs (CI 95%) were calculated as: TUR syndrome (0-0.0109), Blood transfusion (0.0296-0.0676), Urinary incontinence (0.0198-0.1894), urethral stricture (0.0392-0.0769) and UTI (0.0169-0.0787). After 35 years, the incremental cost-effectiveness ratio for combination therapy was $5159, well within the threshold range typically applied in Iran. PSA showed that the probability of being cost-effective in combination therapy is 89% to 94%, also the model showed the most sensitivity to dutasteride unit price and surgery incidence with monotherapy.

Conclusions: Combination therapy has a high probability of being cost-effective in comparison to tamsulosin monotherapy in Iran.

Introduction: With the emergence of new challenges in the field of pharmacy, the identity of this field and its vital role in the health system of the country, dealing with these challenges and making appropriate and strategic decisions is necessary. Hence, designing student based centers, focusing on research with strategic and national approach, and the purpose of educating students to help decision-makings in the pharmaceutical community can be beneficial.

Methods and Results: The Pharmaceutical Strategic Studies Office established with the aim of knowing and studying on the drug and pharmaceutical issues nationally and strategically, using data collected from the Ministry of Health, Food and Drug organization, Medical Sciences universities, research centers and pharmaceutical companies. This office, in the format of professional workgroups, collects required information through research projects, workshops, holding seminars and scientific visits and present them along with suggesting solutions for improving the health status of the community and the position of the pharmacist in new formats such as professional meetings with the competent and decision maker authorities.

The mentioned idea has led to the attraction of about 100 students in the format of 12 workgroups of career opportunities, education, Pharmaceutical Organizations in the World and Iran, economy and industry, laws, service centers, human resources estimation, ethics, socio-cultural, media, medicinal plants and future studies.

The information of workgroup were gathered through 30 specialized workshops and seminar meetings, 3 special workshops for students and teachers of Education and Training General Office, scientific visits from policy-making institutions, scientific and industrial institutions of Tehran, Isfahan, Mashhad and Shiraz cities;  And their results were presented through holding two specialized congresses on the challenges of pharmaceutical and bioethics with the presence of professors and national authorities.

Conclusions: It is a necessity to design the student base centers such as the Pharmaceutical Strategic Studies Office focusing on national providential researches and strategic thinking, in order to learn decision-making and help the executing authorities of the country by modern methods and eliminate the absence of thinking in the universities, it will be possible to achieve the main objective of the advancement in medicine and pharmacy.

Introduction: pharmacists' job opportunities in Iran are limited to the presence in the industry, pharmacy, hospital, research-centers and faculty of universities. The need of our community to the pharmacist is quantitatively 32 pharmacists per 100,000 people. Every year, 1000 pharmacists graduate in Iran; but there are not enough adequate employment opportunities for them. Given the huge costs of establishing and purchasing a pharmacy and a factory. Job opportunity for pharmacists should be created based on entrepreneurship principles. These opportunities can be defined in the format of designing knowledge-based models that are managed by the pharmacist. There are remarkable amounts of natural products required by healthcare providers on a small scale every day. Manufacturing these products is not cost-effective for a large industrial complex. Small-median enterprises model is one of the reasons for the success of the BRICK countries based on the small-scale chain production ultimately make a huge economic network structure­­ with high profitability.
Methods and Results: Regulations of Health Ministry, the GMP principles for herbal productions, regulations of nutrition supplements registration, the process of issuing the production license, the process of issuing the establishment permit, the minimum requirements for establishing the units of medicinal plants packaging and production of plant extracts, the regulation for getting packaging and production license for plant products,supportive-policy package, industry relations with the university in the area of food and drug, regulations and guidelines for registration and establishment of knowledge-based companies, all were investigated.According to the existing criteria, the following proposed models can be presented:1) Small production with maximum 10 employees; including solids, semisolid and liquids production departments.2)Production workshop model outside the city with maximum 50 employees. 3) Providing consultation and training services in the field of medicine.

Conclusions: As the pharmaceutical community need to the job that by applying a not-so-great capital to have a proper efficiency, and the pharmacist to use his knowledge, a set of products as a network can besides providing these needed items, provide the country with natural products. Therefore, the facilities to create new pharmaceutical job opportunity as well as holding empowerment courses for pharmaceutical students in this field are required.

Introduction: Regarding the needs of pharmacy field to targeted planning, ­­strategic and field visits with objective preconditioning approach is one of the effective methods for preparing students for strategic planning.

Methods and Results: In this study, first, the papers were reviewed since1993to2016.Then opportunities and challenges such as the importance of strategic visits to education and research, the pharmacist's future job, the content of the visit, the achievements, and the place and time of the visit were assessed by Likert questionnaire contains 20questions and through google form for 2categories of students. The first group included students who had experiences of visiting during the travel conducted by the Strategic Studies Center; and second group included the students who did not have experience of Strategic Visits.

Conclusions: In the first group with 20 people as statistical population, 90% agreed to the role of the visits in increasing the ability and creating educational and research attitudes, 70.4% opposed with the feeling of disappointment and confusion by visiting, 85% agreed to motivate and acquaint with job opportunities. In addition, 95% agreed to visit the policy-making centers, 100% agreed to visit the industry and university, and 30% agreed to visit cultural centers. 60% agreed to pass 2related syllabuses before visiting the relevant center, 45% agreed with the requirement of mentioned cases, and 65% agreed to make the visit in the elementary courses of education. These obtained results for the second group with 130 people as statistical population were 87.1%, 67.8%, 96.8%, 93.5%, 48.4%, 93.5%, 19.4%, 67.8%, 58.1% and 58.4%, respectively.

Introduction: In different countries, various organizations and associations are active in the field of pharmacy. These activities mainly consist of policy-making, implementation, training and supervision. In Iran, different tasks are concentrated in one or two institutions; and the active presence of the private sector is not tangible. On the other hand, in developed countries, tasks are divided between public and private institutions. In this article, by investigating and comparing these institutions in different countries and drawing conclusions, systems for dividing tasks with greater efficiency will be achieved.

Methods and Results: The workgroup on "Investigating Pharmaceutical Institutions" of Pharmaceutical-Strategic-Studies-Office conducted a study on the responsibilities of each of these institutions, their target population, efficiency rate on the defined objectives in policy, implementation, monitoring and education areas in Iran, neighboring countries and developed countries, as well as their different and similar duties with each other. In this review article, several searches have been done in databases such as PubMed, Google Scholar, Scopus, specialized books as well as websites related to each of these institutions.

The results show that in developed countries an average of six pharmaceutical associations exist, all of which are active in the field of education. In the United States, an organization that approves the competency of pharmacists and issues pharmacy establishment permits has been separated from overseeing organizations. In Japan, other than the Health Ministry as a policy-maker and a special council for legislative purposes, a formal overseeing institution, an Office of Health Assessment and two associations with a scientific-trade and research approach are active. In Australia, one third of the associations are active in the area of law enforcement; and the organization which is active in the field of policy-making and supervision does not have any executive activities. In the European Union, one institution has a role in the field of macro policy-making and two associations are involved in micro policy-making. In India and Pakistan, practically all affairs are carried out in the governmental format; NGOs operate in the field of education, research and government consultation. Overall, China is the most similar to Iran.

Introduction: In spite of undebated benefits of the use of aspirin for the prevention of cardiovascular disease (CVD), due to the side effects of aspirin, which are  mainly gastrointestinal bleeding and hemorrhagic stroke, its use in primary prevention is still contentious. Stroke is one of the important CVD events which is responsible for a major cause of death among Iranian women. For the first time, the cost-effectiveness and cost-utility of the use of aspirin for the primary prevention of stroke among women in Iran with an average risk of CVD was evaluated in this study.

Methods and Results: The incremental cost-effectiveness ratios (ICERs) were estimated using a semi-Markov model in which the cost-effectiveness of the use of 80mg aspirin  was compared to control group The adopted time horizon was life-long and the analysis was performed from the payer's perspective. The target population was a hypothetical cohort of 55-year women with a 10-year CVD risk of 15% and no history of previous CVD. A loss of 0.4 QALYs (Quality-Adjusted-Life-Years) and 0.58 LYG (Life-Years-Gained) with an extra cost of 6,150,946 Rials per patient were estimated in this study,. The implemented one-way and probabilistic sensitivity analyses represented the robustness of the model.

Conclusion: The use of aspirin for the primary prevention of stroke among women with an average CVD risk, seems not to be a cost-effective intervention in Iran. However the cost-effectiveness of the use of aspirin for other CVD including myocardial infarction (MI) needs to be taken into account in decision making.

Introduction: Effective and efficient treatment for patients with metastatic colorectal cancer that can increase survival rate with limited side effects, is important. The purpose of this study was health technology assessment of Bevacizumab compare with combination of Bevacizumab with Erlotinib for treatment of patients with metastatic colorectal cancer.

Methods and Results:In the present investigation first a systematic review on finding the studies was conducted. To reach this goal a comprehensive search in PubMed, Cochrane Library, Scopus, CRD, American Society of Clinical Oncology and European Society for Medical Oncology databases using the PICO based keywords was performed. Then, a retrieved study by means of two independent and expert reviewer during several steps (based on title, abstract and full-text, excluding of duplicated or unrelated cases) was chosen and non-qualified studies was exiled from the study. After that, 20 chosen randomized trial studies were evaluated by two experienced evaluators by Cochrane tool in terms of types of Bias. Eventually obtained data from the investigation was meta-analyzed by Revman5.3 software and safety, effectiveness and economical evaluation of the device were studied based on this data. To calculate the expenses of Bevacizumab and Erlotinib, Cost-effectiveness Analysis with the perspective of the service provider in the public sector was performed. In total, three randomized controlled trials with 682 patients met the inclusion criteria.  The combination of Bevacizumab with Erlotinib for maintenance therapy of patients with metastatic colorectal cancer improved progression free survival by 0.19 and overall survival by 0.22. Degree three and four side effects of developed during treatment were limited and manageable. The combination of the two drugs was cost effective from the perspective of the service provider.

Conclusions:Based on current evidence, prescribing the combination of Bevacizumab and Erlotinib in the maintenance treatment of metastatic colorectal cancer patients is cost effective from the perspective of service provider in the public sector, and the use of this combination in the health system is economically viable.

Background:

 Previous studies of health policies in Iran have not focused exclusively on the drug reimbursement process.

Objective:

The aim of this study was to describe the entire drug reimbursement process and the stakeholders, and discuss issues faced by policymakers.

Methods:

Review of documents describing the administrative rules and directives of stakeholders, supplemented by published statistics and interviews with experts and policymakers.

Results:

Iran has a systematic process for the assessment, appraisal, and judgment of drug reimbursements. The two most important organizations in this process are the Food and Drug Organization, which considers clinical effectiveness, safety, and economic issues, and the Supreme Council of Health Insurance, which considers various criteria, including budget impact and cost-effectiveness. Ultimately, the Iranian Cabinet approves a drug and recommends its use to all health insurance organizations. Reimbursed drugs account for about 53.5% of all available drugs and 77.3% of drug expenditures. Despite its strengths, the system faces various issues, including conflicting stakeholder aims, lengthy decision-making duration, limited access to decision-making details, and rigidity in the assessment process.

Conclusions:

The Iranian drug reimbursement system uses decision-making criteria and a structured approach similar to those in other countries. Important shortcomings in the system include out-of-pocket contributions due to lengthy decision making, lack of transparency, and conflicting interests among stakeholders. Iranian policymakers should consider a number of ways to remedy these problems, such as case studies of individual drugs and closer examination of experiences in other countries.

Introduction

Pharmacotherapy is an indicator of severity of hyperglycemia in pregnancy that may reflect β-cell dysfunction in women with gestational diabetes mellitus.

Methods and Results

 Life after gestational diabetes Ahvaz Study (LAGAs) is a population-based prospective cohort study to investigate potential short and long-term metabolic outcomes of gestational diabetes in mothers and their offsprings. Pregnant women attending 25 urban public and private centers seeking prenatal care were recruited from March 2015. 19.3% (34/176) of women with gestational diabetes required pharmacotherapy in pregnancy (12.5% insulin and 6.8% metformin). The mean age of women who needed pharmacotherapy was 31.0 (SD, 4.6) years vs 29.3 (SD, 5.3) years in diet-treated women. Cesarean delivery, higher FPG at first visit of pregnancy and premature delivery were significantly associatiated  with need to pharmacotherapy in pregnancy (p<0.05). 

Conclusions

Although the use of oral anti-diabetic drugs in pregnancy is not recommended by the American diabetes Association (ADA), consumption of them in women exposed to gestational diabetes is considerable. Use of insulin or metformin for management of hyperglycemia in pregnancy strongly prognoses metabolic disturbance later in life.  Therefore postpartum prevention and screening program for cardiovascular risk factors is important for women with GDM who required pharmacotherapy for management of hyperglycemia in pregnancy.

Probiotics are defined as nonpathogenic bacterial depravities (Lactobacillus GG Enterococcus faecium,Lactobacilus acidophilus & Bifidobacterium bifidum) that provides better ,and normal intestinal floral and  function ,which balances Intestinal micro-organism and supports the immune system. One of the most common form of diarrhea is Antibiotic induced diarrhea, in which probiotics are used as preservative therapy. A significant number of patients with diarrhea are children (infant –toddler), who have underdeveloped immune system and diarrhea may cause life-threatening event. GE reflux is a common disease in infants. probiotics are now taking a part in the treatment of these children but it is not approved by FDA, although some surveys have shown its benefits.

Introduction: The aim of this study is to see the role of probiotics in prevention and treatment of diarrhea and control of GE reflux, versus its high cost.

Methods and Results: Four groups were studied in this analysis. The first group had diarrhea without probiotic treatment, the second group were patients with GE Reflux without probiotic treatment. The third group had diarrhea treated with probiotics, and the fourth group had GE reflux and were treated with probiotics. We used patients precise age, weight. variables were sex(female/male)age, (months), weight duration of disease with and without probiotics. In this study mean age was 24 months ,the minimum was 6 months and maximum was 78 months.58%of them were male and 42% were female. The mean treatment duration in group1 was 10 days. In third group was 7days which was reduced by 3 days. The mean treatment duration in group 2 was nearby 26 days. In third group was  near 25 days.

Conclusions:

Probiotics have significantly reduced the duration of diarrhea but there has not been a prominent improvement in duration of disease in GE Reflux.

Introduction

Up to now, limited and contradictory results have been published on the role of prognostic values of lipid profile molecules including: HDL (High Density Lipoprotein), LDL (Low Density Lipoprotein), TG (Triglyceride), Total Cholesterol and PCSK9 (Proprotein Convertase SubtilisinKexin type 9) molecule in occurrence and development of Parkinson’s disease (PD). The aim of this study was to investigate the role of lipid profile and PCSK9 in patients with PD and to compar it with healthy individuals.

Methods and Results

In the present case-evidence study, 32 individuals diagnosed with PD were compared with 32 healthy individuals. After receiving the  participant's consent forms, 5 ml blood was taken from

vein and the level of HDL(High -Density Lipoprotein), LDL (Low-Density Lipoprotein), TG (Triglyceride),Total Cholesterol and PCSK9 in the blood samples were measured. The Elisa method was used for measuring PCSK9 level in blood serum. Data were analyzed using SPSS17 software. The P values smaller than 0.05 were considered significant.

The mean age of participants in the PD and control group was 56.9±8.8 and 53.7±10.1 years respectively (P>0.05). Twenty seven individuals (87.1%) and 13 individuals (41.9%) in the PD group and control group were men, respectively. The remaining participants were women (P=0.000). LDL level (84.2±24.9 ml/dl vs. 105.5±16.8, P=0.000), HDL (45.5±8.7 ml/dl vs. 51.1±9.5 ml/dl, P=0.000), total cholesterol (155.3±31.2 ml/dl vs. 192.8±32.5 ml/dl P=0.000) were lower and TG level was higher in the PD group (133.3±79.3 ml/dl vs. 131.2±58.6 ml/dl, P=0.9) compared with the control group. PCSK9 level was higher in the PDgroup, but no significant difference was found (141.6±70 vs. 129.7±51 ng/ml, P=0.5).

Conclusions
Our findings showed that individuals with PD have lower level of HDL, LDL and total cholesterol compared with the control group, but PCSK9 levels were same in both groups.

Introduction:

N-acetylcysteine (NAC) is an amino acid that contains a cysteine group and is currently used widely in various fields of medical research especially in cardiology. In this review, potential benefits of NAC in the aggregation of platelet and reperfusion injury are evaluated.

Methods and Results:

The available evidence was collected by searching Scopus, Pub-Med, Medline, Cochrane central register of controlled trials, and Cochrane database systematic reviews. Our searching was performed without time limitation and only English language articles were included in this review. Key words used as search terms included “N-acetylcysteine”, “platelet aggregation”, “reperfusion injury”. Over the past decade, several investigations were carried out to ascertain reperfusion injury and antiplatelet properties of NAC, and in this article the results of investigations in both models (human and animal) were addressed in details. The results revealed that NAC has an important antiplatelet property in animal models while this effect is not very significant in human models and needs more investigations. However, its reperfusion injury in both models is worth noticing.

Conclusions:

Due to the limited data about effectiveness of NAC in both human and animal as antiplatelet agent, more investigation is needed to evaluate NAC efficacy in platelet aggregation and reperfusion injury especially in human studies in the future.

Introduction

Neutropenia is an abnormality in neutrophil count which lessens to lower than 1500 / microL (<1.5×109/L). Early recognition and treatment are needed in neutropenia cases. Matricaria chamomilla (chamomile) belongs to Asteracea family which often is referred as "star among medicinal species". Recently, valuable effects of chamomile in multitherapy, cosmetics and nutrition has been published in several papers. The phytochemical analysis exhibited flavonoids, essential oils, cumarins and sesquiterpene lactones derivatives like matricin and chamazulene in the plant. The aim of this research wasevaluation of chamomile essential oil on granulocyte count in patients with neutropenia.

Methods and Results

Essential oil of chamomile was collected consecutively via Clevenger method.  85 people were participated in the clinical trial and divided into three groups. 15 healthy people as control group received chamomile drop, 35 neutropenia patients induced by chemotherapy received chamomile drop as treatment group and 35 neutropenia patients induced by chemotherapy did not receive the drop as non-treated group. Blood sampling was done at the time of the admission and every other day for 10 consecutive days after chamomile drop consumption. Granulocytes, polymorphonuclear cells (PMNs) and white blood cells (WBC) were counted after every sampling. The average of WBC, PMNs and granulocytes numbers were significantly raised in control and treatment group with P<0.05 90±11/ 3520±611, 1.14±0.83/ 17.37±22.8 and 150±0.07/ 1537±305, respectively. In non-treated group the WBC, PMNs and granulocyte were 40±72, 7.91±22.96 and 190±48, respectively.       

Conclusion
Consumption of chamomile drop significantly increased the level of WBC, PMNs and granulocyte in control and treatment groups in comparison to non-treated group. As the result, chamomile essential oil could be considered as an adjuvant in neutropenia or other immune system deficiencies.

Introduction

The Mitral Stenosis is a common disease, which increased heart rate can be a sign of deterioration. Patient heart rate regulation, especially during exercise, is very important. The aim of this study was to evaluate the efficacy of Ivabradine in comparison with Atenolol and Metoprolol beta-blockers by examining Maximum exercise heart rate in patients with Mitral Valve Stenosis.

Methods and Results

In order to evaluate the efficacy of Ivabradine in comparison with beta-blockers, the systematic search was conducted using PICO keywords in the most important electronic databases, Cochrane Library, PubMed, Web of Science, CRD, Scopus, and Google Scholar. The articles were selected separately by reviewing the titles, abstract and full text of the articles, and extracting unrelated and repetitive articles by two individuals. Extracting the article information based on the measured outcome of Maximum exercise heart rate was done by two individuals independently.  In cases where there was disagreement, the decision was made by a third person. To evaluate the quality of the articles, the Cochrane tool and the Revman software version 5.3 were used. The I² index was used to investigate the heterogeneity of the products. The publication bias between studies was evaluated using a Funnel Plot and Egger's Regression Test. The results of the fixed effects model were used to combine the results and the mean difference with 95% confidence interval for the consequences was calculated. This meta-analysis was performed using the Meta Package R software. Finally, four studies entered meta-analysis. The total number of patients treated with Ivabradine and beta-blockers was 128 and 132, respectively. Homogeneity between studies was not significant (I² = 36%; P-value = 0.20). The results of meta-analysis showed that the difference in mean Max Exercise HR of patients was 3.73, which was statistically significant (Mean Difference = 3.73; 95% CI: 1.52; 5.94; P-value = 0.001).

Conclusions

The administration of Ivabradine, in contrast to Atenolol and Metoprolol, greatly increases the ability of a person to test exercise, administration of this drug in patients with mitral valve stenosis can lead to a decrease in heart rate, which in turn causes reducing the risk of heart attacks in these patients.

Introduction: Targeting the therapeutic agents to the anterior and posterior segments of the eye has attracted extensive attention from the scientific community. Significant key factor in the success of ocular therapy is the development of safe, effective, economic and non-invasive novel drug delivery systems.  Microspheres of poly carbolactone(PCL) and poly ethylene glycol containing gentamycine were prepared by a solvent diffusion-evaporation method as non-invasive ocular drug delivery systems.
Methods: The oil-in-water emulsion prepared in an aqueous solution of 0.05% poly(vinyl alcohol) medium with PCL and PEG , a water-soluble and less toxic solvent, was used as the dispersing solvent. The yield of the microspheres was up to 80%.
Result: Scanning electron microscopy (SEM) confirmed the microspheres had smooth surfaces, with sizes in the range of 489–550 μm. The drug loaded in microspheres was in an amorphous state, as confirmed by differential scanning microscopy (DSC). The release of the drugs was controlled for 2-7 days. The release kinetics followed different transport mechanisms depending on the drug to polymer ratio. Based on microbial assay of antibiotic test the microspheres showed excellent antibacterial activity against Staphylococcus aureus.

Conclusion: Therefore, a floating dosage form that is able to sustain release hydrophilic drugs within its extended retention time has been developed. We will be able to manufacture biodegradable biomimetic microsphere for long-term drug delivery of gentamycine  in ocular.

Introduction: Nanotubes are formed through the self-assembly of many types of organic molecule. Peptide nanotubes (PNTs) are important due to their wide range of bio functionalities which leads to many potential uses in nanotechnology and biomedicine. Self-assembled cyclic peptide nanotubes (CPNs) show a potential use in drug delivery. Ghadiri et al. pioneered the design of PNTs based on the stacking of cyclic peptides containing even numbers of alternating D- and L- amino acids. Recently, self-assemblies of PNTs have appeared as one of the most interesting nanostructures to be explored in the field of nanotechnology. These smart assemblies can have diverse applications, such as in the design of sensors, electronics, and stimulus-responsive materials. In this study, a CPN with transferability was tested for the transport of glucose.

Methods and Results: To explore the transportation mechanism of CPNs, computational studies have been performed on the CPN models stacked by 7 subunits, including quantum calculations, conventional molecular dynamics (CMD) simulations, and steered molecular dynamics (SMD) simulations in the environment of hydrated dimyristoylphosphatidylcholine (DMPC) lipid bilayer, separately.

Conclusions:

The calculated interaction energy glucose with the cyclic peptide is -7.4 kcal/mol. The CMD simulation along the 30 ns demonstrated that CPN tilted with respect to the normal of the bilayer. The hydrogen bond network formed by the carbonyl and amide group of the backbone in CPN contributed to the stability and tilt of the tube. Some water molecules were found in the tube that preferred to reside in the middle zone of neighboring cyclic peptide subunits. The SMD simulation demonstrated that the glucose molecule was transported by hopping via different potential energy minimum distributed along subunits.

Introduction:

 Androgenetic alopecia (AGA) is a common disease in both male and female genders which affect millions of people worldwide.

Minoxidil and Aminexil can improve the blood supply of hair follicles by different mechanisms. Here, we report for the first time, the preparation and physicochemical evaluation of aminexil niosomes.

Methods and Results:

 We developed new noisome encapsulated aminexil formulation composed of sorbitan esters (Span™), their ethoxylated derivatives (Tween™) with cholesterol by lipid film hydration method. Four molar ratio were used. The suspension was centrifuged and the absorbance of the supernatant analyzed by UV spectrophotometer at the λ max. The morphological studies of niosomes of aminexil have been done by using transmission electronic microscope (TEM). Size distribution were evaluated by Malvern size analyzer. Release rate of niosomal aminexil was evaluated by Franz diffusion cell through abdominal skin of rat.

Results showed that the prepared niosomes has good physical stability depicted as unchanged size distribution curves during six month storage formulation composed of the highest encapsulation. The formulation prepared was stable at room temperature. Slow and biphasic release profile of aminexil was also shown which could be contributed to slow diffusion of aminexil through lipid bilayer.

Conclusions:

It can be concluded that niosomes can be used as stable carriers for topical delivery of aminexil.

Introduction: Recently, magnetic nanoparticles (MNPs) drew a great attention for application in drug delivery systems. Due to their biocompatibility and non-toxic properties, they have potential to create versatile drug delivery systems. Brimonidine (a relatively selective alpha-2 adrenergic receptor agonist) has a significant effect on lowering intraocular pressure in glaucoma. In this study MNPs were coated with alginate and chitosan and loaded by brimonidine to prepare a drug delivery system applicable in glaucoma treatment.

Methods and Results: Brimonidine, sodium alginate and MNPs have been prepared as a dispersion. Chitosan solution was added dropwise to the previous dispersion. The dispersion was centrifuged and the absorbance of the supernatant analyzed by UV spectrophotometer at the λmax of 246 nm. The final dispersion was freeze-dried. The morphological studies of chitosan alginate MNPs(C-A-MNPs) have been done by using transmission electronic microscope (TEM). The release rate of brimonidine tartrate was evaluated by Franz diffusion cell through cellophane membrane.

Results showed that more than 93% of the brimonidine tartrate was loaded on the C-A-MNPs. The formulation prepared was stable at room temperature protected from light. Release study showed that less than 40% of the brimonidine was released after 2 hours compared to simple formulation of brimonidine solution which showed more than 80% release after 2 hours. This finding showed sustained release in C-A-MNPs formulation. Kinetic of drug release from C-A-MNPs was slower than blank and followed zero order. The stability of formulation was more than 2 years.

Conclusions:

It can be concluded that loading of brimonidine on C-S-MNPs may decrease the frequency of administration and increase the efficacy of the product.

Introduction:

Despite all progress in vaccine research against toxoplasmosis, subunit vaccines still deal with poor immunogenicity, which could be overcome by using efficient delivery vehicles like PLGA. The proteinaceous nature of antigens makes the loading of protein more challenging than chemical medicines. Here, we prepared rSAG1-PLGA by adsorption and encapsulation methods and compared their characterizations.

Methods and Results:

Blank PLGA and rSAG1-encapsulated PLGA nanospheres were prepared using double emulsion solvent evaporation technique at room temperature. rSAG1-adsorbed PLGA nanospheres were prepared by incubating a suspension of freeze-dried blank PLGA with rSAG1 in PBS (pH 7.4) and it was mixed at 4°C overnight. Size, PDI, zeta potential, preparation yield, and adsorption/encapsulation efficiency of all prepared PLGA nanospheres were characterized and summarized in table below:

Formulation

Size

(nm)

PDI*

Zeta potential (mV)

A/E efficiency

(%)

Yield

(%)

Blank PLGA

438 ± 11

0.12 ± 0.01

-5.56 ± 0.68

-

86.8 ± 3.56

rSAG1-adsorbed  PLGA

486 ± 9.9

0.14 ± 0.02

-1.00 ± 0.33

69.73 ± 3.05

87.4 ± 2.7

rSAG1-encapsulated PLGA

471 ± 8.5

0.20 ± 0.04

-4.66 ± 0.6

46.93 ± 2.51

86.8 ± 2.86

*Poly Dispersity Index, A; adsorption, E; encapsulation

Moreover, in vitro release profile of both PLGA nanospheres during 4 weeks demonstrated more or less similar release pattern (zero-order release patterns). However, rSAG1 release in rSAG1-encapsulated PLGA happened slower than release in rSAG1-adsorbed one.

Conclusions:

 Based on obtained size, both rSAG1-adsorbed and rSAG1-encapsulated particles could be efficiently taken up by presenting cells. Higher efficiency of adsorption than encapsulation makes adsorption method more economic in large scale. Protein during encapsulation process faces some stability problems due to exposure to harsh mechanical thermal and chemical stresses affecting protein integrity and immunogenicity. Therefore, protein adsorption would be applied as a suitable method for protein loading. We are going to evaluate the efficiency of both particles in eliciting immune responses in BALB/c.

Introduction: Human papilloma virus (HPV) causes common warts, laryngeal papilloma and genital condylomata and might lead to development of cervical cancer. Lactoferrin (LF), a member of the transferrin family, is a bi-globular protein and has antiviral activity against HPV-16.  LF is an important player in the defense against pathogenic microorganisms and has also shown to have activity against several viruses including herpesvirus, adenovirus, rotavirus and poliovirus.  Bovine LF has been reported to be a more potent inhibitor of HPV entry than human LF. The goal of the present study was to formulate, evaluate and optimize transfersomal vesicles as a transdermal drug delivery system for the lactoferrin which assumed to be a suitable non-invasive transdermal delivery system for treatment of genital warts.

Methods and Results: Transfersomes have been prepared by two methods of reverse phase evaporation and thin film hydration with different ratios of cholesterol: lecithin: DOTAP in the presence of SDS or Tween 80. The transferosomes were then evaluated regarding size, polydispersity and LF loading.  In vitro release studies in pH 5.3, stability evaluation in 4°^c and 24°^c and TEM imaging has been performed on optimized transferosomal lactoferrin. The optimized transferosomes were found to have 100 nm sizes with good PDI and encapsulation efficiency of 91% for lactoferrin as well as sustained release of lactoferrin during 24 hours. It was shown that unlike lactoferinn which should be stored in cold temperature, transferosomal lactoferrin would be stable in cool conditions.

Conclusions:

The elastic vesicular systems like transferosomes are one of the most controversial methods for transdermal delivery of active substances specially macromolecules and proteins. It was found that transferosomes would be ideal nano carriers with high loading efficiency and size uniformity as well as improving stability of lactoferrin. Further study is needed to investigate its efficacy in treatment of HPV caused genital warts and its viral inhibitory function.

Introduction: Povidone-Iodine was introduced to the pharmaceutical market as an antiseptic agent in the 1950’s. In this study, we presented a measurement method for “Free” Iodine in Povidone-Iodine solutions and its effect on disinfection of these solutions was investigated.

Methods and Results: In this study, Povidone-Iodine solutions were prepared with different concentration of free iodine but with the same available iodine, then free iodine in these solutions was measured by heptane extraction method. pH, available Iodine and Iodide was measured according to BP2017 pharmacopeia. The antibacterial activity of these specimens was investigated after 15, 30, 60, 120 seconds on two microorganisms including pseudomonas aeruginosa and staphylococcus aureus.

All specimens were acceptable according to pharmacopeia acceptance criteria and because the amount of molecular iodine (so-called free iodine) determines the level of antibacterial activity in Povidone-Iodine, the reduction in free iodine until a specified concentration in this study, did not decrease on acceptable antibacterial activity.

Conclusions: Because high free iodine is the main factor for skin irritations, reducing free iodine in Povidone-Iodine disinfectants until a specific concentration, in addition to preserve antibacterial properties, reduces skin irritation considerably.

The aim of controlled drug delivery is to manage the time and site of drug release according to the patients’ need.In this paper, Micro Electro-Mechanical Systems (MEMS) technology is described.This technology employs microelectronics and microprocessor circuits in order to reach individualized, targeted and controlled drug release and would construct the future drug delivery systems.

Introduction: Controlled drug delivery systems are the state of the art in drug delivery technology with the goal of controlling the drug release at right time and site to satisfy the patient’s pathophysiological requirements. In spite of great improvements in this field, it still remains an open research area.MEMS employs sophisticated systems in a small scale. In last few decades, this technology has increasingly attracted the researchers’ attention due to its successful miniaturization of complicated drug delivery systems to address unmet dosing requirements more precisely.MEMS drug delivery systems are fabricated using the microelectronics and microprocessor circuits of highly-advanced technology. This provides the opportunity to implement several drug reservoirs and billions of electronic devices in few millimeters.

Methods and Results:In this study, MEMS technology is introduced along with describing the fabrication process. Two main categories of MEMS devices including internal and transdermal devices and their applications in drug delivery systems are presented. Various actuators applied in these devices are described, including electrical, electrochemical, electromechanical, and electrothermal types. Finally, emerging technologies and prospects are briefly reviewed.

Conclusions: MEMS techniques can be easily combined with microprocessors and sensors to implement an intelligent system which can determine the proper drug dosage and release time according to the signals received by biosensors. When placed inside the body, biocompatibility and biofouling issues should be well-considered, since the device will remain in the patient’s body for a long time. Therefore, MEMS technology seems to be the future aspect of targeted drug delivery systems.

Introduction: oral dosage forms are the safest, the most convenient and the most economical method of drug delivery system in the pharmaceutical industry but, in geriatric and pediatric patients who have swallowing difficulty and in the emergency situations, we need the fastest therapeutic effects on conventional oral drug delivery because  of time issue. To troubleshoot? such problems a new dosage form known as orally disintegrating tablets (ODT) can be useful and more effective. Lorazepam is  a benzodiazepine drug that stimulates GABA receptor and is used in the prevention of panic attack, management of anxiety disorders, treatment of status epilepticus andetc. Based on these details, ODT form of Lorazepam can be helpful for geriatric and pediatric patients and also handling emergency situations.

Methods and Results: In this study, various formulations were designed and prepared by using direct compression method. All of our formulations contained 2 mg of Lorazepam as API. We used 3 differences bulking agents (mannitol, lactose, avicel) and the percentages of disintegrating agent (5%, 10%, 15% of crosscarmelose).then, for examining our formulations and choosing the best formulation we carried out or conducted physicochemical tests like flowability of powder, tablet appearance, thickness, uniformity of weight, hardness, friability and disintegration time. Finally, one of these formulations (lactose as bulking agent and 10% crosscarmelose as disintegrating agent) which showed optimum physicochemical properties was selected for further studies.

Conclusions:  regarding our study and literatures, we attempted to evaluate a novel formulation of Lorazepam ODT. physicochemical test results showed this formulation  ideal for developing new dosage forms of Lorazepam for resolving some of the patient's problems.

 Introduction: Acne vulgaris is one of the most common skin disorders, which various factors are involved in its pathogenesis. Recent investigations on intracellular signaling pathway show that the over expression of mTORC1 complex (mammalian target of rapamycin), leads to increased sebum production and altered keratinization, therefore it has an important role in acne pathogenesis. Another studies also showed that the expression of mTORC1 is significantly increased in the skin cells of the patients, which confirm the linkage between acne pathogenesis and mTORC1 over expression. The aim of this study is to represent a way to confront the impaired endocrine signaling, in order to relieve the acne symptoms.

Methods and Results: The linkage between acne pathogenesis and endocrine signaling pathway was demonstrated through the collected signaling data from popular scientific databases such as www.Kegg.Jp. Insulin resistance is one of the major factors that leads to mTORC1 over expression. Metformin, a biguaniide that increases the cell's sensitivity to insulin, is the drug of choice for this condition, as it is able to suppress mTORC1 over expression through AMPK (5' adenosine monophosphate-activated protein kinase) activation. So, applying a topical form of the drug on acne spots, may lead to relieve the symptoms. Topical semi solid formulation of metformin was prepared with the use of suitable thickening polymers and formulation was optimized through the point of viscosity and rheological behaviors of the aqueous gel, so the optimum ratio of the thickening polymers was determined.

Conclusions: Signaling pathways show that acne pathogenesis is mediated through mTORC1 over activation, so we were aimed to design a formulation which is able to suppress this over expression in order to relieve acne symptoms. Metformin, formulated in a topical form, is the drug of choice, as it is a safe drug which can suppress the mTORC1 over expression through AMPK activation in the skin of acne patients.

Introduction: Cancer is defined as the abnormal cell growth. It has always been a great health problem all over the world despite growing advances in its prevention and treatment strategies, which can cause life-threatening malignancies with high financial costs for patients as well as the health care system. Mounting evidence suggested that curcumin is potentially able to act as chemo-preventive and chemotherapeutic agent in different types of cancer. Nanotechnology has shown promising effects in the treatment of cancer. Nanoformulation provides improvements in bioavailability, biodistribution, specificity, and pharmacokinetics of drugs delivered to the site of tumor. The aim of current study is to comprehensively review the pharmacological effects and molecular mechanisms of nanoformulated curcumin and its derivatives as adjunctive therapy in preventing and treating malignancies.

Methods and Results: Electronic databases including “Scopus”, “PubMed”, and “ScienceDirect” were searched with the keywords “cancer” in title/abstract, along with “curcumin” and “nanoformulation” in the whole text. Data were collected from the inception date until June 2017. Articles that had assessed nanoformulations of curcumin derivatives in an in vitro or in vivo model of cancer were selected for this study, and conventional formulations without using a nano­nization technique were excluded. Various curumin nanoformulations have been prepared as anticancer agents including PLGA nanoparticles, cyclodextrin/cellulose nanocrystals, folate-modified PLA-PEG micelles, dendrosomal nanoparticles and lipid–polymer hybrid nanoparticles. Curcumin nanoformulations perform their anticancer activity via several cellular mechanisms, including induction of cell cycle arrest at different phases of cancer cell cycle, acti­vation of caspase enzymes, reduction of tumor vasculariza­tion, reducing tumor cell invasion and metastasis, induction of mitochondrial damage, as well as apoptosis in the neoplasm.

Conclusions: Nanoformulations of curcumin, result in better bioefficacy for the prevention and treatment of cancer. The most important improvement in nanoformulated curcuminoids, in comparison to their free molecules, is their better antineoplastic function and improved bioavailability that can result in production of natural anticancer agents with passive targeting of cancerous cells. However, a long path lies ahead of commercializing these agents, including assessment of their safety and efficacy in healthy as well as cancerous subjects in clinical settings.

Introduction: Alginates are non-toxic, hydrophilic, biocompatible, biodegradable and low cost polymers which make them suitable for many biomedical applications. Due to their good tissue compatibility, they have been widely used in enhancing the healing process. However, they have limitations in mechanical characteristics and drug release. Adding metal ions could add some features to these films in order to improve their properties.

The purpose of this study is to compare alginate blend films cross-linked with different concentrations of strontium in order to submit one as the best in topical applications.

Methods and Results:Sodium alginate (2 g/100 g) was first dissolved in 50 mL de-ionized water. Di butyl phthalate (16%w/w) was added as plasticizer. After dissolution, the solution was poured into Petri dishes and dried at 40°C for 24 h. Alginate films were chemically cross-linked by immersing in different concentrations of strontium carbonate (0.1-1-10% w/v) for 1 minute. The films were then dried at oven at 40 °C for 24 h. The swelling test was performed in acidic(HCl 0.1N) and phosphate buffer media (pH=6.8) for 90 minutes.

Thickness of alginate film before and after the strontium crosslinking procedure was0.178mm and 0.26 mm, respectively. Swelling index (IS) in acid and buffer media was 280.70% and 263.64%, respectively.

Conclusions:The swelling test of cross-linked films has demonstrated satisfying results by increasing in swelling properties, hence promising outcome for wound healing conditions. Also, the results showed pH-responsive swelling behaviors with surprisingly more swelling in acidic media compared to buffer.

Introduction:

 Melasma is a common hypermelanotic disorder affecting the face that is associated with considerable psychological impacts that one of the treatment options is hydroquinone. The phenolic and hydroquinone derivatives and derivatives thereof, including the sesquiterpenoid hydroquinone and quinone, are widely used to inhibit bacteria, fungi and viruses, on the other Polymeric drug delivery system are able to improve therapeutic efficacy, reduce toxicity, and prolong drug release by adjusting the degradation rate of the polymer. So in this study we product and investigate of antifungal activity of Hydroquinone nanofibers.

Methods and Results:

 Films containing hydroquinone were produced from electrospining method. The physicochemical properties of prepared films were investigated by electronic microscopy and FTIR. Physical stability and degradation rate of nanofibers as well as the rate of hydroquinone release were also studied. In this study, the antifungal effects of hydroquinone were studied in laboratory conditions. The release test revealed that the release rate of hydroquinone nanofibers increased with increase in temperature. Hydroquinone prevents the growth of the fungal species of Candida albicans

Conclusions:

 Hydroquinone is widely used in the treatment of melasma, but no report has yet been made of the use of hydroquinone in the treatment of fungal diseases. Antifungal effects of hydroquinone on the Candida albicans species have been tested in laboratory conditions and its positive effect has been determined.

Introduction: Sunlight has some benefits and also harms like as skin aging, photosensitivity, irregular hyper-pigmentation and skin cancer. So the use of sunscreen creams is proposed for protection and minimizes harmful adverse effects of sunlight. Solid lipid nanoparticles (SLN) and microemulsions (ME) are new drug delivery systems that are suitable for sunscreen delivery.

Methods and Results: Different concentrations of lipid (Witepsol H35 and H15) and surfactants (Tween^® 60 and Span^® 60) were used as an ingredient for SLN formulations. Parsol^® 1789, 5000 and MCX are used as active agents. SLN and ME were prepared by using High-shear Homogenization and ultrasound method. The particle size analysis, drug release، encapsulation studies and SPF evaluation of different SLN samples were examined. Stability of microemulsions was performed using a centrifuge. Also we used different concentrations of isopropyl myristate as a lipid, Tween^® 80 and propylene glycol as a surfactant for preparing ME formulations. After adding sunscreen ingredients, particle size analysis and physical stability tests were studied. According to particle size analysis the best formulations for H35consists of 5% lipid, 15% surfactant with HLB=12 and for H15 consists of 5% lipid, 5% surfactant with HLB=11. Particle size of all of the formulations were less than 1µm, encapsulation efficacy was more than 70%. The maximum SPF was 38.75 and belongs to SLN formulation with lipid H35 and MCX (5%). According to turbidity and particle size the best formulation for ME was chosen. All of the ME formulations containing sunscreen agents have less than 500 nm particle size.

Conclusions: Our result shows that SLN formulation is good carriers for sunscreen delivery. SLN particles act as a barrier for sunlight. So loading a UV absorbent like as MCX can improve sun screen ability of the formulation. Our result shows a SPF equal to 38.75. Also in SLN formulations the release of UV absorbent may be slower and has more duration in time. So the adverse effect may be lower and duration of action may be better. Finally we conclude that formulation of sunscreen in SLN base can improve sunscreen properties of products.

Key words: .

Introduction: Arbutin (ABU) inhibits tyrosinase and thus prevents the formation of melanin, therefore, it used as a skin-lightening agent. Ascorbic acid (AA) used in therapeutical fields such as improving immunity, skin disorders, amelioration of injuries and burns. Hydroquinone (HQ) as one of the important skin-bleaching agents used to lighten areas of darkened skin such as freckles, melasma, age spots, and acne scars. Moreover, owing to ability of Kojic acid (KA) in preventing melanin formation, it used in whitening products because of this ability to limit melanin production. Due to the importance of quantitative determination of the four above mention drugs loading efficiency in niosomal formulations, a great attempt was made in the current work to provide a promising sensor using voltammetric techniques.

Methods and Results: BMITB/NiO/NPs/MCPE was prepared by mixing 0.2 g of 1-butyl-3-methylimidazoliumtetrafluoroborate (BMITB) as a binder, 0.8 g of paraffin, 0.1 g of NiO nanoparticles and 0.9 g of graphite powder. The electro-oxidation signals of ABU, KA, AA, and HQ were increased at the surface of modified sensor compared to the bare electrode. The obtained result shows that, at pH 7.0 phosphate buffer (0.1 M), the catalytic oxidation signals exhibited a wide linear range with a satisfactory low detection limit.

Conclusions: The proposed sensor revealed good electrocatalytic activity towards ABU, KA, AA, and HQ. The proposed modified carbon paste electrode (BMITB/NiO/NPs/MCPE) was applied successfully for simultaneous analysis of trace amount of four above mention drugs in niosome carrier real samples.

Introduction:

 Gliclazide is a second-generation sulfonylurea used in the treatment of non-insulin dependent diabetes mellitus. Gliclazide is practically insoluble in water, therefore, researchers try to find techniques to improve its physicochemical properties. On the other hand, researches has shown that nanoparticles are effective in improving the physicochemical characteristics of poorly water-soluble drugs. There are many methods to prepare nanoparticles, among all, electrospraying as a one-step and cost-benefit technique can  be easily applied in industrial scale.

Methods and Results:

 Gliclazide and polymer (Eudragit RS100 or PEG6000) were co-dissolved in acetone with drug: polymer ratios of 1:5 and 1:10, so that the polymer solution concentrations were 10, 15 and 20% (w/v). Then these solutions were electosprayed. The particle size and morphology were evaluated using scanning electron microscopy (SEM). The physicochemical characteristics of nanofibers and nanoparticles were evaluated by DSC thermograms, FTIR spectroscopy and X-Ray crystallography. Drug release profiles were studied as well. The size of prepared nanofibers and nanobeads, ranged from 100 nm-500 nm. Based on the physicochemical characteristics, there was a transition from crystalline to amorphous state of Gliclazide. No interaction between drug and polymers were observed in the prepared nanoparticles. In vitro drug release studies revealed that the drug-release patterns were improved in the prepared nanoparticles.

Conclusions:

 Electrospraying is a simple and low-cost method that can be used to produce Gliclazide nanoparticles in industrial scale and improve physicochemical properties of the drug.

Introduction: Methamphetamine is a highly potent, addictive drug that is widely abused in many countries around the world. Methamphetamine produces a general state of well-being along with increased wakefulness, talkativeness, and physical activity and decreased appetite. Behavioral treatment programs have had some success in the treatment of methamphetamine addiction, yet many patients continue to relapse after repeatedly seeking treatment. Thus, pharmacotherapies treatments for methamphetamine addiction are being evaluated.

Bupropion is an atypical antidepressant with stimulant properties. This drug has been used off-label to treat methamphetamine addicts, thus prompting the need for systematic investigations of its efficacy.

Methods and Results:Male wistar rats, weighing 200–250 g (8 weeks old) at the start of the experiment. In the self-administration study, rats were surgically prepared with indwelling jugular catheters. After the surgery rats were trained to press a lever of methamphetamine reinforcement (0.05 mg/kg/injection) in operant boxes under baseline conditions. When responding stabilized, rats entered the acute testing phase. Each rat was tested with a unique order of vehicle, 10, 30, and 60 mg/kg bupropion. Each solution was administered IP 5 min before placement in the chamber for a regular self-administration session and each test was separated by at least 2 maintenance days of methamphetamine self-administration without drug pretreatment. Bupropion pretreatment appeared to decrease active lever responding. Consistent with the active lever data, rats treated with 60 mg/kg bupropion took significantly fewer total methamphetamine infusions in comparison to the other 2 groups. When Control rats (n=6) (i.e., those pretreated with saline in the previous phase) were given an acute injection of 30 mg/kg bupropion, lever pressing decreased.

Conclusions: Several questions remain about bupropion’s impact during withdrawal, abstinence, and relapse in a preclinical setting. Research investigating these aspects of addiction will help provide a clearer picture on the effects of bupropion on methamphetamine self-administration in laboratory animals and methamphetamine abuse in humans.

Introduction: The aim of this study was to improve the dissolution profile of risperidone and increase the compliance of psychotic patients through the design of an oral disintegration tablet­ (ODT) of microparticles containing nanoparticles.

Methods and Results: In order to prepare nanoparticles, the effect of six surfactants on the size and stability of nanoparticles was evaluated. The nanoaggregate fabricated via the spray freeze drying ­(SFD) process using mannitol, lactose and maltodextrin as a matrix agent. Nine formulations were prepared and evaluated on the particle size, dissolution rate , and other physicochemical properties.Finally, the formulations of ODT were designed and evaluated.

The results show that using of cremophore EL and hydroxypropyl methyl cellulose E15 with the synergic effect can develop the risperidone nanosuspension with nano range particle size (~188 nm). Also, it is showed that fabrication of risperidone microparticles containig nanoparticles enhanced the drug dissolution up to 2 min for  lactose-based microparticles (as a superior formulation) that is very faster time than coarse risperidone powder with dissolution time of 60 min. the formulations of  ODT containing  10%  Sodium Starch Glycolate and 88% Microcrystalline Cellulose as Super disintegrants were selected with a disintegration time of fewer than 30 seconds and dissolution time of 10 min in superior formulation.

Conclusions: It is indicated that the simultaneous use of non-ionic surfactants can prepare risperidone nanoparticles by creating a steric barrier around the drug particles. In addition, the dissolution rate of risperidone has increased significantly due to the small particle size of nanoparticles according to Noyes-Whitney equation. The use of sugars maintains the size of the nanoparticles and prevents the formation of irreversible coalescence of nanoparticles. Thus, this investigation shows that the preparation of microparticles containing nanoparticles using SFD is an easy and usable method for improving the dissolution profile of many low solubility drugs.

Introduction: The purpose of this article was to design a bilayer floating- drug delivery system using mucoadhesive microparticles of olanzapine as a model drug.

Methods and Results: Mucoadhesive Microparticles were fabricated with coacervation method by using of mucoadhesive polymers such as sodium bicarbonate, chitosan and ethyl cellulose. The floating layer containing sodium bicarbonate, HPMC, carbapol, PVP and olanzapine mucoadhesive microparticles was compressed and an immediate release layer was added and then both layers were compressed. Floating properties of the tablets, the in vitro drug release, buoyancy lag-time and swelling index were evaluated. The results showed that incorporation of olanzapine mucoadhesive microparticles in floating tablet improved the release kinetic to biphasic so the drug was immediately release in 30 min after floating and lasted more than 8 hours. Also the release of olnzapine was  based on zero order kinetic. This suggested the synergic effect of micro particulate system as well as floating property in long time drug release in gastric fluid.

Conclusions: This kind of tablet is suitable for long term delivery of olanzapine in upper gastric parts or segments.

Introduction: The delicate area around the eye is the first place to show signs of aging due to the fact that the skin around the eye is thinner than the skin on the face. Also, facial movements and emotional expression affect this area as well. There are many carriers to apply to the skin. Among them, the pad is a carrier that uses a certain amount of nutrients. Conventional pads are fabrics that are prewetted with nutrients. The problem with them is that the solution phase increases the rate of degradation of unstable elements. Nanofiber pad has high surface-to-volume ratio and its size is within the range of skin pore size, which increases the contact surface between pad and face and improves the nutrients absorption. In this research, we are trying to develop a polymeric nanofiber eye pad which has nutrients within its structure.

Methods and Results: The nanofiber eye pad was prepared from gelatin solution containing Q10 powder, Aloe Vera, and ascorbic acid by electrospinning machine at 20 kv on the spunlace media.

The results of SEM images show continuous nanofibers without any beeds with an average diameter of 80-300 nm. Microbial analysis was performed on the polymeric solution. The colon size of aerobic bacteria (P.aeruginosa, E.coli and S.aureus) were measured in one-gram solution. The results showed no colonization of these bacteria. A Patch test was performed by inserting a pad on the skin of the volunteer’s arm and recording the results after specific time. The results showed that this pad did not create any redness and swelling on the skin and did not cause any irritation.

Conclusions: The nanofiber eye pad containing nutrients does not provide any irritation for the skin, and is a good candidate for replacing an ordinary pad.

Introduction: Celecoxib is a weakly acidic drug and has low aqueous solubility (3–7 μg/ml). Low solubility of drugs in water results in poor bioavailability because the solubility of a drug is an important factor in determining its absorption rate. According to the Noyes–Whitney equation, the saturation solubility and dissolution rate of poorly water soluble drugs can be enhanced by reducing the particle size, which increases the total surface area. Nanocrystals possess outstanding features enabling to overcome the solubility problems of poorly soluble drugs. The objective of this study was to investigate the dissolution behavior improving effects of differently sized nanocrystals of a poorly soluble model drug, Celecoxib.

Methods and Results: Nanocrystals were prepared by antisolvent precipitation followed by high pressure homogenization (HPH) technique in the presence of varying percentage of SLS as a stabilizer (0.2 or 0.4%) and rate of homogenization (26500 or 12500 rpm). The obtained nanoparticles were analyzed in terms of particle size distribution, polydispersity index, saturation solubility, thermal behavior (DSC) and dissolution behavior. The particle size of nanosuspensions was between 140 and 532 nm with poly dispersibility index less than 0.5. That minimum of particle size relate to formulation which contained 0.4% stabilizer with rate of 26500 rpm. This formulation also revealed the highest saturation solubility (18.1 µg/ml) and dissolution efficiency compared to pure Celecoxib. The DSC results indicated the absence of any interactions between drug and stabilizer. These studies showed a decrease in crystalinity of Celecoxib.

Conclusions: All microcrystals significantly (P<0.05) increased Celecoxib aqueous solubility and dissolution rate compared to plain drug. This result seemed to be due the significant particle size reduction and decreased drug crystallinity. Significant influence of increasing in rate of homogenizer on size reduction was observed.  As well as, high stabilizer concentration and rate of homogenizer had Significant influence on saturated solubility of Celecoxib compared to pure drug (P<0.05). DSC study showed that there is no change in the crystal structure of Celecoxib during the process and showed that nanocrystals exhibited decreased crystallinity.           

Introduction: Despite the success of current vaccines, there is a clear need for the development of vaccines with novel approaches against resistant pathogens such as HIV, HCV and TB (tuberculosis). Vaccine improvements may include the addition of new adjuvants, which are able to induce higher immune responses. SWCNTs display characteristics that are potentially useful in their development as scaffolds for vaccine compositions. These features include stability in vivo, multivalency and lack of intrinsic immunogenicity. In addition, the particulate nature of carbon nanotubes and their rapid entry into antigen-presenting cells, such as dendritic cells, make them especially useful carriers of antigens. Recent studies have demonstrated that carbon nanotube-based vaccines are promising in both infectious disease settings and cancer. In this study, we have developed optimized DSPE-PEG-SWCNTs for optimized HbS antigen loading and immune responses. 

Methods and Results: Firstly, noncovalent functionalization of SWCNTs with DSPE-PEG5000-COOH and DSPE-PEG2000-COOH were performed to improve aqueous dispersibility, biocompatibility, immune stimulatory and antigen loading. HbS antigen loading was then optimized through D-optimal design. DSPE-PEG-SWNT type was a categorical factor and HbS antigen concentration, incubation time, temperature and stirring speed were numerical independent factors. Optimized solutions with LE% of 53% were achieved at 300 µg/ml of HbS antigen concentration with DSPE-PEG-2000-COOH.

Conclusions: Numerous approaches are in process in vaccine development including the use of nanocarriers with special features such as multivalency, stability, and a likelihood of internalization into antigen presenting cells. The use of carbon nanotubes is just beginning and a better understanding of the specifications that control this process, are required to optimize their future use in this field.

Introduction: Modafinil is a wake-promoting agent approved by FDA for the treatment of narcolepsy and shift work sleep disorder. Due to its insolubility in water, the drug exhibits low oral bioavailability. Studies have shown that formulating poorly-soluble drugs as nanoparticles can improve the drugs physicochemical properties. Electrospraying is an uncomplicated and cost-benefit method for preparing nanoparticles that can easily be scaled up.

Methods and Results: Modafinil and Eudragit RS100 were co-dissolved in methanol and acetone (1:1) with the drug: polymer ratios of 1:5 and 1:10 at various total solution concentrations (10%, 15% and 20%). The solutions were injected through a capillary tube on a Teflon screen at a rate of 2 ml/h. A voltage of 20-25 kV was applied between the injection needle and the Teflon screen. The particle size and morphology of resultant nanoparticles and nanofibers were evaluated via scanning electron microspore (SEM). Thermal behavior and crystallinity of the samples were studied by differential scanning calorimeter (DSC) and Powder X-ray diffraction (PXRD). Fourier transform infrared spectroscopy (FTIR) was used to determine any possible interaction between the drug and the polymer. In vitro drug release profile was studied at a pH of 6.8 via USP apparatus II.

SEM results suggested that solutions with lower concentration created nanoparticles (100-300 nm) while increasing the concentration resulted in formation of nanofibers (50-100 nm). DSC and PXRD analysis revealed that electrosprayed Modafinil was transferred from crystalline to amorphous state. FTIR results indicated that hydrogen bonds might have formed between the drug and polymer. Drug release profile revealed that electrospraying process modified drug release pattern. Some of the formulations managed to increase the release rate whereas other formulations resulted in slower release.

Conclusions: Electrospraying is a suitable method for fabricating nanofibers and nanoparticles of Modafinil. The resultant nanoformulations show properties such as reduced size, decreased crystallinity and modified release rate, thus help Modafinil to have higher oral bioavailability.

Abstract

In this study, the lipophilic drug is solubilized using PF127-Chol micelles and then the solubilized drug was incorporated in to chitosan/HPMC gel in order to use as a wound dressing.

Introduction: Simvastatin (Sim) is a HMG-COA reductase inhibitor, and is used conventionally for cholesterol reduction but recent studies demonstrated the potential of this agent for diverse pathologic conditions such as wound healing due to its antioxidant, anti-inflammatory, and antibacterial properties. However, the systemic bioavailability of Sim is very low (approximately 5%). Moreover, the systemic administration of Sim can cause several adverse effects such as myopathy and liver problems. Therefore, topical application of Sim can increase the accessibility of drug in wound area at lower systemic level and decrease the possible incidence of side effects.

Methods and Results: Polymeric micelles containing Sim were prepared by the thin film hydration method and optimized using irregular full factorial design. The mean diameter, PDI, and zeta potential of the prepared drug loaded micelles were determined by dynamic laser scattering method using Malvern nanosizer. The gels were prepared using chitosan or/and HPMC at 3% (W/W). Bioadhesion was determined using a tensile strength machine. The in vitro release of Sim from different gel formulations was studied using dialysis method. Statistical analysis showed that solvent type had the most impact on the amount of drug loading and zeta potential. The optimized formulation suggested by desirability of 93.5% was prepared using 1 mg of Sim, 10 mg of copolymer, dichloromethane as the organic solvent, hydration time of 45 min, and hydration temperature of 25 ^oC. The release of the drug from nanomicelles was found to be biphasic and showed a rapid release in the first stage followed by a sustained release for 96 hrs. The gel-contained nanomicelles exhibited pseudo-plastic flow and more sustained drug release profile compared to nanomicelles.

Conclusions: The results indicate the obtained composite gel has great potential for topical applications at the site of wounds.

Introduction:

About 15-25% of diabetic patients suffer from foot ulcers. Diabetic foot ulcers often require specialized treatment and multidisciplinary approach. the choice  of appropriate drug delivery system for antibiotics and pain refiner is an important remedy. Venlafaxine is an antidepressant drug of the serotonin-norepinephrine reuptake inhibitor (SNRI) class which is a safe and well-tolerated analgesic drug for neuropathic pain in diabetic’s foot ulcers.  On the other hand Doxycycline inhibits metalloproteinases activity through the chelation of calcium and zinc ions which inhibits extra cellular matrix destruction mediated by metalloproteinases. Films of cellulose nanofibers are biocompatible with excellent physical properties and can be appropriate choice for wound dressing in diabetic foot ulcers.

In the present study, films of cellulose nanofibers were loaded by Venlafaxine and Doxycycline for simultaneous delivery to diabetic foot ulcers.

Methods and Results:

Doxycycline and Venlafaxine were dissolved in 10 cc water and then Films were putted on them and stirred for 24 hours to reach or until drugs are loaded drugs loading. Drug loading efficiency and release profiles were investigated by UV spectroscopy in 275 and 225 nm, respectively. The influence of the pH from 3 to 9 and the ratio of the drugs to carrier (1:1, 1:2 and 1:3) were assessed on the drug loading and release profiles. Efficiency of drugs loading was decreased by increase in  pH possibly due to the negative charge of cellulose and positive charge of Venlafaxine and Doxycycline in lower pH. On the other hand, the ratio of 1:2 of drugs to carrier was the most efficient ratio for drug loading that was 20% and 69% and also, 60% and 35% release for Venlafaxine and Doxycycline respectively.

Conclusions:

Films of cellulose nanofibers proved to be an appropriate carrier for co-delivery of Venlafaxine and Doxycycline as wound dressing. Further clinical studies are needed to evaluate their effectiveness in alleviating the inflammation and neuropathic pain of the diabetic foot ulcers.

Glioma is the most common primary tumor of the brain and CNS tumors and 80% of the malignant brain tumors. The average life time of patients with glioblastoma is 14.6 months due to various therapeutic options, including surgery, radiotherapy and chemotherapy. In recent years, biodegradable polymer nanoparticles have attracted attention as pharmaceutical carriers. Polymeric nanoparticles can be formed by polymerization of monomers or polymers. On the other hand apoptosis or a planned cell death is a regulated normalized cell suicide process that enables the living being to maintain the number of cells and eliminate unwanted cells that threaten existing survival. So, in this study, the effect of cytotoxicity and induction of apoptosis nano-cysplatinum was studied. To date, various carriers have been used to deliver cisplatin. We plan to load cisplatin on polybutyl cyanacrylate nanoparticles and compare its effect with the standard drug in the carcinoma cell of the brain C6 and examine its properties in the laboratory environment.

Introduction: Cancer is an important issue in modern medicine and is the most common cause of death after cardiovascular disease. Meanwhile, brain cancer is one of the most common causes of cancer deaths among women and men, with the third highest incidence among other cancers. Therefore, chemotherapy drugs aimed at preventing abnormal cell proliferation in certain tissues of the body and, on the other hand, inducing apoptosis in tumor cells are considered important candidates for cancer treatment. Due to the role of apoptosis induction, cisplatin can be used as anticancer therapeutic agent.

Methods and Results: The cytotoxic effect and induction of apoptosis cisplatin on brain cancer were investigated. The cytotoxicity of cisplatin by MTT was evaluated on brain cancer cell line (C6).Finally, to evaluate the effect of nanosilver platinum on the apoptosis process, a staining method with a Hawkish color 33258 was used by fluorescent microscope. The results of this study showed that nano-cysplatinum had more cellular cytotoxic activity than free drug and the effect of induction of apoptosis with nano-drug was investigated.

Conclusions: Our results showed that synthesized nanorods can be used as a new nano-medicine to replace chemotherapy, and the effect of inducing apoptosis by nano-nutrition has been shown to provide favorable results.

Introduction: Nowadays, obesity has become a major global health challenge and it is closely linked with many metabolic disorders like diabetes and hypertension. Although various types of drugs have been developed, the prevalence of obesity is increasing worldwide. One of the effective way to treat obesity and prevent metabolic disorders coming after, is using nanoparticles as new therapeutic methods.  This study reviewed nanoparticles effects on monitoring and treating obesity.

Methods and Results: In this systematic review, based on PRISMA guidelines, two persons independently searched MeSH terms “nanoparticles”, “drugs” and “obesity” and some other relevant terms in databases including PubMed, Medline, Scopus, and Cochrane library up to July 2017, and all the articles with considered inclusion criteria were added to the study.

145 articles were obtained by primary searching. After removing 12 irrelevant and 57 duplicate articles, 76 with inclusion criteria were added to this study. Nanoparticles could be used on both monitoring and treating obesity. These nanoceria when conjugated with antibodies are used for monitoring proteins involve in inflammation and insulin signaling without cell lysis. For example, due to TNF- α inflammatory cytokine that has an important role in insulin resistance in obesity, these nanoceria can be applied on monitoring some proteins like multiple kinases that ameliorate insulin resistance in obesity. Drug delivery via nanoparticles made it more possible to have better effects on regulating lipase cycle in adipose cells and tissues. Furthermore, application of nanoparticles conjugated with some agents can affect intracellular signaling or mechanisms in order to treat obesity. For example, silica nanoparticle has anti-brown adipogenic effect via regulation of p38 phosphorylation which involves in obesity.

Conclusions: Application of nanoparticles increases the accessibility of adipose targeting cells. these nanoceria might be used to detect and treat many metabolic disorders like obesity. Producing more efficient and complicated nanoparticles in sizes depended manner, provides more opportunities to access better on targeted cells for treatment, however,  their side effects on normal cells should be considered.

Introduction: The gene delivery vectors are generally classified into two types: viral and non-viral. The chemical vectors have several advantages such as convenient synthesis or chemical modification, unlimited DNA carrying capacity, and low immunogenicity. Recently, Ionic Liquids (ILs) have attracted more and more interest for gene delivery. Magnetic nanoparticles (MNPs) act as effective carriers for DNA, the surface of the particles is better to be modified to enable attachment of the target molecules. Here, we design a particular carrier including the MNPs and ILs to transfer GFP gene to cells.

Methods: First, imidazolium-type ILs-modified magnetite nanoparticle was synthesized. By this mean, Magnetic nanoparticles were modified with acryloyl amide according to reported procedure. Then, vinyl imidazole was copolymerized by free radical polymerization. Poly(vinylimidazole)-grafted silica-MNP was treated with methyl iodide to form a quaternary salt of poly(vinylimidazole). The chemical structure characterization was carried out by FT-IR and the organic content was determined by CHN analysis. The topography was studied by SEM, TEM, AFM. On the next step, The Green Florescent Protein (GFP) gene was attached to synthesized polymer by electrostatic interactions. The complex of polymer-DNA was added to cell line (HepG2) and the expression of GFP was evaluated.

Results and Discussion: The result of chemical structure characterization was in line with our expectations. Imidazolium-type ILs-modified magnetite nanoparticle was characterized. This novel functionalized nanoparticle was a potential vehicle for gene delivery.

Conclusion: In summary, we have reported the synthesis of poly-(vinylimidazolium)-modified iron oxide nanoparticles and estimated their potential gene delivery application. The Polyvinylimidazolium provided an efficient cationic group to increase binding capacity for biomolecules such as DNA.

Exosomes are extracellular vesicles with nano size range. The use of exosomes as drug delivery vehicle has useful advantages compared to other vesicular systems. Exosomes are nonimmunogenic, nontoxic, and stable with good composition and potency for crossing blood brain barrier. They can be used as theranostic agents and vaccine therapy. The exosomes are a new choice for nonimmunogenic targeted drug delivery vehicle.

Introduction: Exosomes are nano size vesicles secreted by different cell types. The main role of exosomes in the body is a cell to cell communication. They are not immunogenic due to similar structure as body cells. They can cross blood brain barrier, stable in the blood circulation, biocompatible, with low toxicity, suitable size, and structure. These endogenous vesicles can be used for drug delivery, immunevaccines and as diagnostic agents.

Methods: The following databases were reviewed for bibliography of using exosomes as delivery agents: Web of science, Scopus, Medline, and Embase.

Results: Exosomes can deliver different kinds of cargos (RNA, proteins and small molecules) to the target cells. Exosome as a biomarker of diseases (cancer, cardiovascular disease, MS, etc) personalized therapy with the exosomes that generated from induced pluripotent stem cell (iPSC) derived that used for patient specific and disease specific cell therapy. They have specific role in tissue repair and regeneration, vaccines for immunotherapy (phase II of clinical trial). The strategies to introduce drugs into exosomes are active and passive loading. Artificial exosome mimetics can be isolated from exosome secreting cell lines but these exosomes in comparison with autologous are immunogenic. Isolation techniques of exosomes are ultracentrifugation, electron microscopy, and SDS page. Exosomes were mainly taken up by macrophages in the liver after IV administration. Exosomes characterization methods are biophysical, molecular and microfluidics.

Conclusion: Exosomes are good carriers for delivery of drugs and genes to the target without immunogenic reaction. They can be used as immunovacines for the cancer treatment by activating immune system against tumor cells. Exosomes can substitution the liposomes because of their size, structure, non-immunogenicity and their natural composition.

Introduction: Antibiotic resistance in one of the biggest threats to global health, food security and development today and it has emerged as a medical catastrophe. Antibiotic resistance is also rising to dangerously high levels in all parts of the world. Nanotechnology provides a chance to overcome antibiotic resistance by multiple antibiotic mechanisms. The aim of this study was to examine antibacterial effects of the colloidal gold nanoparticles (GNP) against Staphylococcus aureus, Staphylococcus saprophyticus, Staphylococcus epidermidis, Enterococcus faecalis, and Enterococcus faecium and also the GNP synergistic effects with three antibiotics including Bacitracin, Polymixin B, Gentamicin, Erythromycin and Clindamycin.

Methods and Results: Standard agar diffusion method was used to determine the zone of inhibition of each antimicrobial compound and GNP. Standard broth microdilution method was also used to determine the minimum inhibitory concentration (MIC). The different ratios of each antibiotic and GNPs were then prepared and the antibacterial activities of antibiotic/GNP mixture was assessed one by one. Finally, the results of triplicate examinations were analyzed statistically. the results showed that the combination of gold nanoparticles with the most of the antibiotics with the ratio of 25%-75% had the increased antibacterial effect against the majority of strains with considerable MIC compared with all other antibiotic/GNPs ratio. Therefore, the gold nanoparticles in combination with antibiotics in specific concentrations cab increase the antibacterial effects of the antibiotics.

Conclusions: bacterial resistance to available antibiotics is an increasing problem and improved methods to identify and treat pathogenic bacterial strains quickly would be of enormous benefit to public health. Our findings indicated that a combination of antibiotics and gold nanoparticles has considerable efficiency against some gram positive bacteria. The alteration of normal mode of metabolite pathway and the release mechanism could involve in antimicrobial process.

Introduction: Zataria multiflora Boiss, a member of Labiatea family, grows in countries such as Pakistan, Afghanistan and Iran. The previous studies have been reported that Zataria multiflora Essenital Oil (ZEO) showed medical applications. In this study we have investigated the antimicrobial activity of ZEO nanoemulsion (ZEN) formulations on Escherichia coli and Estaphylococcus aureus. ZEN has been investigated as a potential strategy for improving their utilization stability and efficacy. To the best of our knowledge there is no previous study about antimicrobial effect of ZEO as a nanoemulsion in the literature.

Methods and Results: ZEN was prepared by high energy emulsification method. Distilled water was added dropwise into ZEO, surfactant and Oleic acid as oil phase while stirring. The prepared emulsion was sonicated by probe sonicator to obtain the appropriate size. Nanoemulsion size was evaluated by Malvern nano sizer. Thermodynamic stability tests were performed to select stable nanoemulsion formulations. ZEN were subjected to centrifugation. Then the stable formulations on centrifugation were subjected to heating-cooling and freeze-thaw cycles. Antimicrobial activities were evaluated by well-plate and microtiter methods.

The selected ZEN formulation droplet size and PDI were found 73.58 ± 10.59 and 0.350 ± 0.077 nm respectively. Stability tests showed appropriate thermodynamic stability. Antibacterial activity showed that nanoemulsion of ZEO exhibited high antibacterial activity against Escherichia coli and Estaphylococcus aureus.

Conclusions: The enhanced stability and efficacy of ZEN described in the current investigation may have different industrial or medical applications. For instance they can be used as antibacterial medicines for vaginitis. They could also be used in food preservation as a biodegradable coating films.

Introduction: Intelligent systems which release insulin in response to glucose level have been investigated thoroughly and many researches work in this area. In this work we present preparation and characterization of a novel Nano system composed of chitosan and PLGA nanoparticles, incorporating insulin, glucose oxidase and catalase.

Methods and Results: Chitosan nanoparticles were prepared through ionic gelation method. First chitosan solution (2 mg/ml) in acetic acid 1% (v/v) was prepared. 2 mg insulin was dissolved in 5 ml of this solution. TPP solution was added dropwise. Stirring the solution was continued for 1 hour. Chitosan nanoparticles were separated by ultracentrifugation. Size of these nanoparticles was found to be 180-200 nm. Preparation of PLGA nanoparticles containing glucose oxidase (GOx) and catalase (CAT) was done by double emulsification technique.  PLGA was dissolved in ethyl acetate then aqueous solution of GOx and CAT were added to this organic phase. Sonication was performed to prepare w₁/o emulsion. Deionized water was added and by second sonication w₁/o/w₂ emulsion was formed_. Theorganic phase was removed by vacuum rotary evaporator and nanoparticles were separated through filtration, in size range of 130-150 nm. Chitosan NPs were added to PLGA NPs and the Nano system was formed through an electrostatic attraction between two oppositely charged particles. In vitro insulin release from this Nano system was investigated through radiolabeling method at two different glucose concentrations of 70 and 400 mg/dl.

Conclusions: At high glucose concentration after glucose entrance into PLGA NPs it was converted to gluconic acid. Lowering of the Nano system microenvironment pH caused protonation and swelling of chitosan NPs and hence insulin release.

Introduction: Alzheimer is a brain dysfunctional disease which could destroy the cognition and learning capabilities of the patient. Rivastigmine is an acetylcholine esterase inhibitor which can improve brain function in both Alzheimer and Parkinson's diseases. Hereby, we prepared niosomal formulations of rivastigmine for better penetration of this drug to brain.

Methods and Results: Sorbitan esters (Span 20, 40, 60 and 80), their water-soluble derivatives (Tween 20, 40, 60 and 80) and cholesterol were used for preparation of niosomes by film hydration method. Deionized water was used as hydration medium. Volume diameter, drug release profile, rivastigmine encapsulation efficiency and vesicular stability were evaluated. All used surfactant combinations formed round and tubular multilamellar vesicles (MLVs). Single mode size distribution, high encapsulation efficiency (more than 70%), good stability of vesicles depicted as unchanged size and finally, diffusion-based release profiles were shown for many of niosomal formulations.

Conclusions: Incorporation of rivastigmine into bilayer assemblies of niosomes compromises a good candidate for new drug delivery system which further studied in animal models will prove or reject its applicability in human.

Introduction: Skin aging is a complicated process which is one of the major issues in the field of dermatology and cosmetic products. Peptides are one of the novel ingredients included in the anti-aging formulations. KTTKS (Lys-Thr-Thr-Lys-Ser) and its derivative, PAL-KTTKS (Palmitic acid-KTTKS), have attracted a lot of attention in arresting or delaying skin aging, but unfortunately, there are almost no preformulation studies available about them.

Methods and Results:Both peptides were synthesized by solid phase peptide synthesis and identified by Mass spectroscopy technique. UV absorption ability, percentage of crystallinity, melting point, decomposition temperature and thermal behavior of both peptides were analyzed by UV spectroscopy, XRD, TGA and DSC techniques respectively. Partition coefficient was also determined by ACD/chemsketch software. In addition stability studies for the aqueous solution of KTTKS were performed at 32 and 37 ℃.

 The results of UV spectroscopy showsthe wavelength of maximum absorbance of both peptides is in the vacuum UV range. Based on the results of melting point and TGA apparatuses, KTTKS and PAL- KTTKS decompose at about 154 ℃ and 112 ℃ respectively and there is no melting point for them before decomposition. The results of DSC thermogramsindicate an endothermic peak at the temperature below 60 ℃ for both peptides which is probably due to intrinsic structural rearrangement or evaporation of volatile solvents. Crystallinity percentage for KTTKS and PAL-KTTKS are 62% and 32% respectively. cLogp of KTTKS is -3.27 and cLogp of PAL-KTTKS is 3.32.

Conclusions:

The results of this investigation can be employed for the formulation of these peptides for TTD.

A multifunctional nanocarrier based on cystamine (Cys) and β-cyclodextrin (β-CD) modified graphene oxide (GO) was designed for targeted delivery of Doxorubicin (DOX). The obtained CD-Cys-GO nanosheet was characterized by thermogravimetric analysis, Fourier transform infrared spectroscopy, Raman  spectroscopy, Atomic force microscopy and Field emission scanning electron microscopy, which confirmed that Cys and CD had been effectively functionalized on the surface of GO. DOX loading and delivery were also examined and the results suggested that multi-functionalized GO is an efficient nanocarrier for targeted delivery and controlled release of anticancer drug for biomedical applications.

Introduction: Graphene oxide (GO) based drug carriers have been introduced as an important topic of research at the interface of nanotechnology and biomedicine due to their high specific surface area, enriched oxygen-containing groups, low cost and scalable production, excellent biocompatibility, and physiological stability. Cyclodextrin (CD) is a cyclic oligomer which its biological nature makes it attractive in pharmaceutical field. Moreover, the hydrophobic cavity of CD can selectively bind various organic, inorganic and biological molecules to form supramolecular complexes without structural changes.

Methods and Results: In this research, GO nanosheet was synthesized according to Hummer’s method and then was functionalized by Cys in order to design a targeted and controlled drug delivery system. In the next step, β-CD was attached to free amine groups of attached Cys moieties on GO surface. DOX was used as a model drug to assess the drug-loading and releasing properties and the effect of pH was examined. The synthesized graphene-based nanomaterials were structurally and morphologically characterized with FT-IR, CHN, Raman, TGA, XRD and FE-SEM techniques. In addition, the CD-Cys-GO exhibited remarkably higher loading capacity for DOX than Cys-GO and GO. The release of drug was pH-sensitive which would control the release in acidic cytoplasm of cancer cells and can be due to the existence of disulfide bonds in the structure of this nanocarrier.

Conclusions:

In summary, a unique CD-Cys-GO system has been developed. The versatile system combines the advantages of graphene, Cys and CD that provides multifunctional and inter-reversible anchor sites. The hybrid is found to possess a high drug-loading capacity and strong targeting effect.

Introduction: Lung cancer is the most malignant cancer today. Doxorubicin, an anthracycline antibiotic, is a widely used antineoplastic agent. Despite the good efficacy of doxorubicin, cardiotoxicity is the serious side effect that follows the treatment. Additionally, anthracyclines are likely to cause alopecia and myelosuppression and oral ulcerations. This toxicity and non-specific distribution of the drug often results in chemotherapeutic failure. The focus should be made on efforts to kill cancer cells by more specific targeting while sparing normal cells. Solid lipid nanoparticle (SLN) delivery strategies of doxorubicin have been developed to minimize the exposure of drug to the normal tissues.

Methods and Results: SLNs were prepared by the modified high shear homogenization (HSH) method. Lipid matrix was melted and doxorubicin was added to obtain a clear melting solution. After, double distilled water was heated. surfactant was added to the water. Next, the aqueous surfactant solution was added to the melted lipid. Then, the hot water-surfactants solution was poured into the hot lipid phase, and the HSH method was employed to produce the nanoemulsion, then cooled under the room temperature to obtain the SLNs.

Doxorubicin loaded SLNs were prepared with a mean size of 210 nm, doxorubicin encapsulation of 71% and yield of 68%. higher release rate of doxorubicin was achieved at lower pH, with the present system. Because of the basic nature of doxorubicin (pKa = 8.3), it has higher solubility at lower pH.

Conclusions:

These SLNs had superior in vitro anti proliferation activity against the A549 cell line. Doxorubicin loaded SLNs in comparison with free drug exhibits better selectivity for target cells and the formulation was less toxic to normal lung cells than against malignant A549 cells. These observations suggest that present system offers an exciting mode of delivery to the lipophilic anticancer drugs.

Introduction: Targeted delivery systems such as smart polymers based on in situ forming gel can form controlled release formulations. These smart polymers based on in situ forming gel are thermosensitive and converse to gel in the site of injection and body temperature. Tramadol is an opiate-like analgesic that has tendency to μ-receptors of opioids. It inhibits the re-uptake of monoamines and serotonin in the central nervous system. In this research our goal is preparation, optimization and characterization of a parenteral in situ forming gel formulation of tramadol to use in chronic pains.

Methods and Results:Optimization of formulation done by a D-optimal method. We found the effect of different factors such as; polymers’ concentrations, type and concentration of gelating agent on gelation time. The prepared in situ forming gel formulation in vitro were fully characterized. Morphologic study such as AFM and drug release in PBS environment with Franz cell were done. The release kinetics study was also performed.

In optimum situation, the resulted concentration of chitosan, glycerophosphate, poloxamer F-127 and TPP are 1%, 14.5%, 20% and 0.5%. Gelation time and temperature were validated and the results show about 1.5 minutes and 37 ℃ respectively. The drug release profile of free drug showed the fastest release rate with about 100% at 8 h whereas the formulations with TPP and without TPP were about 94% and 38% at 28 h respectively.

Conclusions:

A parenteral in situ forming gel formulation was designed and in vitro evaluation showed that our gel formulation has a uniform texture and can release drug through its nanostructured pores, properly. So, it can be useful in chronic pains, according to its features and reduces the frequency of consumption. 

Introduction: Simvastatin is a semisynthesis statin. Statins inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase, a key enzyme of cholesterol synthesis, in AMPK (AMP-activated protein kinase) signaling pathway. Simvastatin is able to cross blood brain barrier more than the other statins, due to its lipophilic nature. There is controversy about the effect of simvastatin on Alzheimer’s disease (AD). For example, simvastatin can induce AD through insulin signaling pathway but can ameliorate AD via MAPK (Mitogen-Activated Protein Kinase) signaling pathway.  In this study, we report the synthesis of a conjugated form of simvastatin with citicoline, to block negative effect of simvastatin on insulin signaling pathway and increase positive effect of simvastatin on MAPK signaling pathway and chitosan as a linker between these two drugs.  

Methods and Results: for simvastatin-n-succinyl chitosan-citicoline synthesis, chitosan reacted with succinic acid to form n-succinyl chitosan. Then simvastatin connected to n-succinyl chitosan via acetylation reaction. After 24 hours citicoline was added to reaction media. H-NMR and FT-IR were done to examine whether the conjugation reaction has been done or not. Characterization and morphology tests have been done on reaction result.

H-NMRresults approved the synthesis of drug-polymer. FT-IR results showed both amide and ester peaks.  Maximum absorptions (λ_max) of all primary chemicals were seen in UV visible spectroscopy results of conjugated form.SEM result showed that the conjugated form has nanoparticulate structure in size range of 100-300 nanometers. X-RD result showed a peak under 25 theta. Another characterization test wasRBC hemolysis with six different concentrations, in which normal saline was negative control and Triton was positive control.

Conclusions: Conjugation of lipophilic simvastatin with hydrophilic citicoline to improve AD can be done with helping of a polymer which is rich in carboxylic acid.

Introduction:
Alzheimer's disease (AD) is a multisystem and multifactor disease with a long no-symptom stage, hence likely not modeled by one or even a few models and very likely not be treated by a single drug. We propose that a more effective approach to use fMRI as a still emerging, repeatable and non- invasive neuroimaging tools that can be very useful for evaluating, diagnosis, treatment and drugs- development.

Methods and Results:

Factors of Alzheimer's disease (AD) is divided into two general types of genetic and non-genetic. We studied 30 articles which published between 2008-2017 that included the effects of different biomarkers and tools for diagnosing AD and assessing, improving and detection of Alzheimer's medications. Attractive alternatives to the animal and human experimental modeling approaches are the “multi-scale”and “multi-level” computational modeling approaches to AD drug discovery and therapy. 6 articles (20%) were about the animal models while we should try accepting the limitations of animal models and focus more on humanize researches so we used it less considering, also as regard to the long waiting queue in AD drug development that we feel crucial factors have been overlooked which could have been important like promising biomarkers including novel imaging methodologies (specially fMRI), metabolomics, proteomics, electroencephalogram and even digital health platform technologies that will reduce the time for validation and encourage data integration across studies. Peer-reviewed publications were identified through search in PubMed, Google scholar and SCI-HUB by using the search terms "fMRI", "Alzheimer", "cognitive side effects", "drug", "pharmacological neuroimaging". The search was limited to articles published in English. Relevant articles were chosen based on clinical experiences and the expertise of the authors.

Conclusion:
FMRI measures hold promise for multiple clinical applications. Generally, models especially pharmacological fMRI showed that drug repositioning is a cost-effective way to develop disease-modifying treatments over shorter timescale and future models should provide a theory of how increasing Ach levels using cholinesterase inhibitors and N-methyl-d-aspartate antagonists (NMDA)   impact neural and behavioral processes in AD. Models should also investigate how memantine (NMDA antagonists) can reduce toxicity of beta-amyloids as reported in experimental studies.

Introduction:

Liquisolid system has been used to increase the dissolution rate of hydrophobic drugs. Since drug solubility play an important role in drug release profile, using appropriate solvent can lead the system to become sustain release. The aim of this study was to investigate the effect of different liquid vehicles and Eudragit RSPO on release characteristics of atorvastatin as a hydrophobic drug.

Methods and Results:

Several Liquisolid compacts with Propylene glycol and tween80 with different drug solvent ratio was prepared. The ratio of the carrier material (Eudragit RSPO: microcrystalline cellulose, (60:40)), for coating material (silica) was 2 in all formulations. To evaluate any interaction between atorvastatin and the other components, the differential scanning calorimeter (DSC) and Fourier transform infrared spectroscopy (FTIR) was used. Atorvastatin Liquisolid compacts containing Propylene glycol and tween80 as liquid vehicle increased dissolution rate of drug from 23.75±0.33 (in conventional matrix formulation) to 38.66±1.77 and 99.95±4.2 respectively, in first 480 minute. By increasing the ratio of tween80 to drug from 1:1 to 4:1 reduced drug retardation was seen, consequently the release percentage increased from 60.50±3.1 to 99.95±4.2. This was contrary to propylene glycol drug formulation. The resultant difference in effect of formulations was probably due to more solubility of atorvastatin in tween80 (26.77 g/100ml) in comparison to Propylene glycol (11.65 g/100ml). It was observed that a slight change on carrier (55.66 increased to 57.54%) and drug percentage (3.15% decreased to 2.59%) in formulation with Tween80:drug ratio (4:1), presented more retardation effect so that release percentage decreased from 99.95±4.2 to 75.92± 2.20. All formulations had hardness and friability between (35.6±0.57 - 43.4±1.14) N and (0.67% - 1.3%), respectively. The DSC, FTIR and X-ray evaluations revealed no interaction between drug and excipients.

 Conclusions:

The liquisolid compacts with the suitable carrier can be promising technique to sustain release drugs, in addition, type of nonvolatile solvent has an important effect on liquisolid release profile.

Introduction

Superoxide dismutase enzyme (SOD) with high antioxidant activity and, by controlling oxidative stress and reducing the activity of free radicals like ROS, reduces injury and accelerates healing. NLCs were used as the main formulation due to their small particle size, better permeability, higher shelf-life and etc. The purpose of this study was to investigate the effect of nanostructured lipid carriers (NLC) on SOD activity in burn wound healing.

Method:

27 rats were divided to 3 groups: target, positive and negative control. Formulations were examined for particle size, enzyme activity and loading. Each formulations were used for 21 days on rats and at the end of each week they were examined by macroscopic and microscopic Methods. Each group was given a score based on the histology characteristics.

Results:

Physicochemical properties showed that the particle size was between 35 and 85 nm, and the percentage of enzyme loading was 78% and the enzyme activity was 39.3% in the formulation of NLC+ENZ. Macroscopic examination showed that the best recovery rate was in the target group (NLC+ENZ) and showed better performance on the second and third weeks (p_val=0.029 in day 14 and p_val=0.000 in day 21). In pathological studies also shown that the angiogenesis and granulation tissue of the target group has a significantly better performance.

In Granulation scores first week NLC+ENZ P_val = 0.003

In Granulation scores second week NLC+ENZ P_val = 0.001

In angiogenesis scores first week NLC+ENZ P_val = 0.000

Conclusion:

This study showed that the formulation of the prepared nanoparticles had an acceptable enzymatic activity and loading percentages. The formulations of NLC+ENZ in comparison to the other two groups shows significantly improvement of pathologic factors, particularly angiogenesis, granulation tissue, and a faster reduction of inflammatory cells.

Introduction: Frequent use of highly concentrated solutions may induce toxic side effects and cellular damage at the ocular surface. To enhance the amount of active substance reaching the target tissue or exerting a local effect in the cul-de-sac, the residence time of the drug in the tear film should be lengthened. The purpose of the study was to formulate biodegradable film loading nanoparticles (NPs) as ophthalmic insert, which could be easily placed into the cul-de-sac, and be capable of delivering therapeutic concentrations of Erythromycin for a prolonged period of time in a much lower dose.

 Methods and Results: A Novel quasi-emulsion solvent diffusion method to prepare the controlled-release nanoparticles of drug model with Eudragit polymers has been developed. FTIR and scanning electron microscopy (SEM), loading analyses of the nanoparticles, mechanical properties, water vapor permeability, thermal stability of the films were analyzed. An agar well diffusion bioassay method for determination of erythromycin in ophthalmic samples, using Micrococcus Luteus ATCC 9341 as the assay organism, was carried out. In vivo studies were performed in New Zealand albino rabbits using a film loading nanoparticles. SEM revealed irregularly shaped particles. Mean particle size of nanoparticles ranged between 118 and 203 nm, while zeta potential ranged between +15 and +22 mV. The inserts were found to be uniform, tough, elastic and bioadhesive. In-vitro release studies were performed and slowed release up to 28 h with non-Fickian diffusion behavior. Drug levels in the ocular tears in rabbit were significantly higher in comparison to treatment with a pomade formulation.

Conclusions: Erythromycin NPs loaded Eudragit were successfully prepared by spontaneous emulsification technique. The insert would degrade during the specified time with no residue to be removed after the medication.

The purpose of this study was to encapsulate curcumin and imatinib in nanostructures and target them with HDL for scavenger receptor type B-1, a high-affinity HDL receptor expressed by lymphoma cells.

Introduction:

Among numerous drug-delivery approaches, high-density lipoprotein (HDL) nanocarriers have proven particularly applicable for delivering highly hydrophobic drugs by their high affinity to SR-B1.

In this study, we have investigated the enhancement of the therapeutic impact of curcumin, a naturally occurring polyphenol substance extracted from the roots of Curcuma Longa that has been extensively studied for its broad-spectrum anticancer effects by co-delivery with imatinib. The potential benefits of curcumin are, however, limited due to its poor water solubility and rapid degradation which results in low bioavailability on administration. The drug of choice in lymphoma is imatinib.

Methods and Results:

Curcumin and imatinib nanostructured lipid carriers (NLCs) were prepared by dissolving 10 mg of lecithin, 2 mg of stearyl amine, 25% of oleic acid and 7.5 mg of curcumin or 2.5 mg of imatinib in 2 ml of ethanol (mixed with 100 µl acetone or 100 µl chloroform) and then added to 20 ml of stirring deionized water including 0.5 % of Tween 80 at room temperature and was left for 3 hours for solvent evaporation. The NLCs were conjugated to HDL by EDC chemistry and then tested by MTT assay for their cytotoxicity on two types of lymphoma cells including; Ramus as B cell lymphoma expressing SR-B1 receptors and Jurkat as T cell lymphoma without SR-B1 receptors. The results showed the best designed nanoparticles had the particle size of 182 nm, zeta potential of -3 mV, curcumin and imatinib loading efficiency of 100 % and 98 %, respectively. They released imatinib and curcumin within 24 and 48 hours, respectively. The NLCs caused more significant cytotoxicity than each separate drug encapsulated in NLCs or free drugs.

Conclusions: Co-delivery of curcumin and imatinib in NLCs targeted by HDL may be more useful than imatinib alone in the treatment of B cell lymphoma.

The rapid and uncontrolled growth of microorganisms can lead to serious problems. With the development of nanotechnology over the last decade, golden opportunities have been created to discover the antibacterial effects of metallic nanoparticles. Metallic nanoparticles have an antibacterial effect, in addition to the inhibition effect of the particle, due to its small size, large surface area and large outer surface area. Scientists believe that nanoparticles can be used as appropriate alternative to used biochemicals.

Introduction: In the past two decades, the field of nanotechnology has grown exponentially since its birth and has made an immense impact on physical, chemical, earth and biological sciences. There has been an immense extension of nanomaterial applications and uses as a result of basic and applied research from scientists all over the world. One such class of nanomaterials are metal oxide (MeO) and metalsulfides (MeS) nanoparticles (NPs), ranging in size from 1 to 100 nm, available in different shapes and sizes.

 Methods and Results: In this research, nanoparticles were first made in 1, 5 and 1.5 mg/l concentrations, then we study antimicrobial properties of nanoparticles by MIC methods and several gram-negative bacteria were examined for several nanostructures. 0.0064 g nanoparticles solved to prepare 100 cc of the medium, weigh the hinton broth 2.1 grams, and in another stock 7.6 g hinton agar in 200 cc water, Then we make microbial leachate from the tested microorganisms and compare with the half McFarland their turbidity, to the extent that they are half McFarland. Then, with a micropipette of 2.5 microns from the lagoon, remove the bacteria on the plates, and finally place the plates in the incubator for 24 hours, and the next day the results are read.

Conclusions: After making nanoparticles and investigating nanostructures on bacterial strains, we found that 32µg/ml of nanoparticles prevents the growth of bacteria in the control.

Introduction: Curcumin is a compound possessing different pharmacological effects which is poorly soluble. Also, bioavailability of curcumin is low. In this study we aimed to improve solubility and bioavailability of curcumin by developing a self-nanoemulsifying drug Delivery system (SNEDDS) for oral delivery of curcumin.

Methods and Results: Box –behnken was used to design optimum run. Several factors such as concentration of solvent, surfactant, and co-solvent were independent while dependent factors include droplet size, PDI (poly dispersity index), and zeta potential. Although, release test and study EE % (Entrapment efficiency) were done and images were taken using a TEM microscope.

Droplet size of optimized formulation SNEDDS was 245.22 nm. PDI and zeta potential were 0 .38 and -1.28 mv, respectively. TEM images showed that the particles were spherical with no sign of aggregation. Also, our results revealed slow release profile.

Conclusions: The obtained results indicated that SNEDDS could be considered as a good candidate for oral delivery of curcumin to improve its solubility and bioavailability as an active ingredient.

Introduction: One of the causes of the skin drying is lack of oil secretion by sebaceous glands in skin. Then this can make skin sensitive to environmental factors and some substances. Ancient Iranians have used rose water for washing the face and increase moister of skin. Nano-emulgel Due to its high stability, biocompatibility and proper solubility in water are considered as good carriers for targeted drug delivery, and have a good potential for drug delivery because they have the properties of nanoparticles of colloids and hydrogels simultaneously. In this research, effects of rose oil nanoemulgel %0.1 are evaluated on the normal and dried skin.

Methods and Results:

Different formulations of rose oil were evaluated using suitable surfactants. Then the best ratio of nano-emulgel Red flowers and sustainability criteria were determined. Rose oil components were identified by GC/MS. Clinical studies were conducted for an eight-week on 60 healthy volunteers in two groups. A nano-emulgel %0.1 rose oils and other non-essential emulgel with the same basic materials were used and the amount of sebum secretion, melanin, skin redness, hydration and elasticity of the skin and also complications were determined. Quantitative data analysis was done by using Chi-square test and P≤0.05 were considered significant. The results have demonstrated the effectiveness of the rose oils in skin hydration. Two groups with other characteristics such as the skin secretion of sebum, elasticity, pigmentation , and redness have shown similar effects. However, both groups did not show any complications.

Conclusions:

In this study, the main ingredient of essential oil is alcohol. The most important terpene alcohols are, 31% Nonadecane, 38% Citronellol, 23% Linalool , and 17% Heneicosane. The good effectiveness of Rose oil on increasing of skin moisture is the appropriate treatment of skin drying.

Introduction: For the treatment of eye infections using anti-infective agents, topical ocular application is the most convenient route of administration. Topical delivery of drug agents is associated with a number of problems and challenges owing to the unique structure of the eye. The efficacy of conventional ocular formulations is limited by poor corneal retention and permeation, resulting in low ocular bioavailability. The objective of the present study was to develop ocular delivery for Chloramphenicol used to treat bacterial infections of the eye, which can prevent frequent drug administration and enhance patient compliance.

Methods and Results: Chitosan/TPP nanoparticles were prepared by an ionic gelation method. CS was dissolved in acetic acid (1% v/v) to obtain the cationic phase. CS-NPs were obtained upon the addition of TPP by drop-wise to chitosan solution under magnetic. The chloramphenicol-loaded nanoparticles were characterized for particle size, morphology, zeta potential, drug encapsulation efficiency, and subsequent release and corneal penetration study.  HPLC Method was prepared for chloramphenicol determination. Stability of NPs has been tested. The obtained nanoparticles had small particle size and positive surface charges, which improved good stability in six months. The NPs thus produced improved high penetration through isolated sheep cornea due to the interaction with negatively charged biological membranes. These coatings achieved pronounced penetration enhancing effect as compared to chloramphenicol solution. This formulation of nanoparticles has a strong potential for a sustained release effect of the drug, when applied to the eye topically.

Conclusions: It is notable that the chitosan coating as biocompatible and biodegradable polymer, has the potential to be used as a non-toxic penetration enhancer in nanoparticle form, especially for ocular drug delivery.

Introduction: Cochleates are  cylindrical lipid structures that are more stable against oxidation and temperature than liposomes.  Our research is formulation of  cochleates for oral delivery of insulin as a model protein drug. Protein drugs are softer from environmental degradation and poor oral absorption; therefore any carrier system for their oral delivery must have protection against enzymes and absorption  enhancing ability.

Methods and Results: In this study, liposomes with different proportion of lipids (DPPC and DMPC) and cholesterol were prepared by film hydration method and converted to cochleates by hydrogel method with CaCl₂ and MgCl₂. Microscopically observation of structures was carried out by phase-contrast microscope and Scanning Electron Microscope (SEM). Physicochemical characteristics of these structures were evaluated by measuring size distribution  using with  laser light scattering technique, entrapment efficiency percentage, investigation of release profile, and stability of selected cochleates. HPLC method  was used for analytical evaluation of entrapped and released insulin.Best formulation of liposomes contains 70% of lipid and 30% of cholesterol. According to microscopic size distribution, cochleates with CaCl₂ bridges were better. The size of vesicles was less than 6 µm. Insulin entrapment efficiency of cochleates with DPPC was more than DMPC type. Between 60-70% of encochleated insulin released after 2-4 hours in a buffer with pH 6.8.

Conclusions:The results shows that cochleates can be suitable oral delivery systems for insulin.

Introduction: Colorectal cancer is one of the most commonly diagnosed cancers in the world. The main and classic treatment of this cancer is 5-fluorouracil (5-Fu) that its cytotoxicity and low systemic absorption restricted its therapeutic efficacy. To overcome these problems, mucoadhesive and colonic microbially degradable formulations based on chitosan and dextran sulphate hydrogels could be effective.

Methods and Results: 5-Fu loaded hydrogel microparticles were formed via polyelectrolyte complexation technique using chitosan and dextran sulphate solutions. It was optimized by a systematic multi-objective optimization approach in terms of the particle size and loading efficiency of the resulting microparticles. Under this condition, the molecular weight of chitosan and 5-Fu concentration are the two factors which significantly influence the particle size and loading efficiency, respectively. Then the optimized microparticles were prepared and were characterized based on particle size, zeta potential, drug loading and drug release behavior. Finally the cytotoxicity of optimized microparticles was assessed by MTT assay (SW742 cell line) compare to free drug solution. Therefore, spherical particles of 51.33±0.95 μm mean diameter and a narrow size distribution were obtained under optimal conditions. The zeta potential, loading efficiency and loading capacity of optimized microparticles were 18.1±0.87mv, 26.96±0.38 and 13.12±0.65%, respectively. The in vitro drug release profile was fitted on Higuchi model and the cytotoxicity MTT results indicated the higher cytotoxicity of studied formulation on cells compare to free drug. The hydrogel microparticles were further lyophilized to prepare the enteric coated tablets and all tests endorsed that the coating process was suited.

Conclusions:

The designed formulations have provided appropriate properties and offer a potential mean for colon specific delivery of 5-Fu via oral administration.

Introduction: Rosuvastatin (ROS) calcium is the latest synthetic drug in the statin group that has an anti-hyperlipidemic activity. It is available as tablets, and its poor aqueous solubility, slow dissolution rate and low-absorption extent result in less than 20% bioavailability and about 80% being excreted unchanged in the feces without absorption. The present study aimed at developing an optimal oral nanoemulsion formulation containing rosuvastatin using different proportions of oil and surfactant system for enhancing its water solubility and bioavailability.

Methods and results: The solubility of ROS in different oils, surfactants and co-surfactants was tested. Based on the solubility study, liquid formulations were prepared using Arachis oil as oil phase and Tween 80 as surfactant and polyethylene 400 as co-surfactant. Pseudo-ternary phase diagrams were developed and various nanoemulsion formulations were prepared and evaluated for globule size, zeta potential, and emulsion properties. The formulations were subjected to different thermodynamic stability studies such as centrifugation, heating-cooling cycle and freeze-thaw cycle, to avoid the selection of metastable formulations. Transmittance study and in-vitro dissolution studies were carried out. An optimal nanoemulsion system was successfully developed with the droplet size of 260 nm and a composition of (Arachis oil; 20%), Tween 80 (40%) and PEG 400 (40%). The cumulative percentage drug release from optimal nanoemulsion formulation was found to be 93.29±1.11% for 50 minutes, which was significantly higher than the drug suspension (43.42±1.30%). Thus, in vitro results reveal that the prepared nanoemulsion formulations showed improved solubility of ROS.

Conclusions: Nanoemulsion formulations of ROS represent a promising novel formula with a higher dissolution rate when compared to the drug in suspension.  

Introduction:

 The poor bioavailability and therapeutic response exhibited by conventional ophthalmic solutions may be overcome by use of in situ gel-forming systems. Alginate has properties that make a sol to gel transition in the presence of multivalent cations. Chitosan has mucoadhesive properties due to its ability to make electrostatic interaction with the negative charges of mucus.

Methods and Results:

 Alginate was used in combination with chitosan. Ketorolac tromethamine, the drug which is applicable as an anti-inflammatory agent was used as model drug to check the efficacy of the formulation. Different compositions were examined and optimized formulation was selected based on clarity, gelling capacity in the face of simulated tear fluid, rheological study, mucoadhesive capacity examined by excised calf corneal membrane, in-vitro drug release through cellophane membrane and eye irritation tests.

A concentration of 0.5% chitosan and 0.5% alginate underwent a rapid gelation upon facing with Ca²⁺ in tear, based on its satisfactory viscosity and gelling capacity. The developed formulation showed sustained release of drug for up to 8 hrs. In rheological studies, formulation presented a pseudoplastic as well as thixotropic behavior, which were suitable for ocular uses. Moreover, acceptable mucoadhesion was found due to the presence of chitosan. No ocular damage or abnormal clinical signs to the cornea, iris or conjunctiva were visible. Alginate-chitosan solution as a base for ion triggered in-situ gel forming eye drop showed appreciable properties via enhanced viscosity and bioadhesion on application in eye.

Conclusions:

 Alginate-chitosan solution as a base for ion triggered in-situ gel forming eye drop showed appreciable properties via enhanced viscosity and bioadhesion on application in eye.

Introduction: Cancer is one of the major causes of death in many industrialized countries and its incidence is continually increasing. The most effective treatment for tumor is chemotherapy that lead to severe side effects due to their effects on normal non-targeted organs. Nanoparticulate carriers perform as vehicle, protecting the therapeutic agent from the biological milieu and improve cellular uptake and accumulation inside tumor sites. Chitosan nanoparticles (NPs) can be considered suitable vehicles for site-specific delivery of gemcitabine. Wheat germ agglutinin (WGA) is one of the least immunogenic lectins and putative nontoxic that has been demonstrated as somewhat more specific to intestinal cell lines of human origin, human colonocytes and prostate cancer cells.

Methods and Results: Nanoparticles were generated by adding tripolyphosphate (TPP) to chitosan in acetic acid containing 1mg drug under magnet stirring and centrifuged at 30,000 rpm, then lyophilized. To conjugate the surface of NPs with WGA, NPs were incubated in tow repeatable cycles with anhydrous acetone containing carbonyldiimidazole (CDI). Then, the activated bead were suspended in borate buffer, pH 9.0 to which 0.1 mg of WGA was added under vortexing. After washing, NPs dispersed in water, freeze-dried and stored at 4̊ C.

Gemcitabine-loaded NPs conjugated by WGA were prepared with a mean size of 160 nm, gemcitabine encapsulation efficiency of 63% and yield of 60%. These NPs had superior in vitro anti proliferation activity against the Caco2 and HT29. Conjugated NPs in comparison with unconjugated NPs and free drug exhibit better selectivity for target cells and tissues.

Conclusions: NPs conjugated WGA by enhanced cytotoxicity could be considered as a good candidate for oral delivery of anticancer drug. However other studies should be performed to evaluate in vitro test of these NPs.

Introduction:

The antibody display technology (ADT) such as phage display (PD) has substantially improved the production of monoclonal antibodies (mAbs) and Ab fragments through bypassing several limitations associated with the traditional approach of hybridoma technology.

In the current study, we capitalized on the PD technology to produce high affinity single chain variable fragment (scFv) against Vascular Endothelial Growth Factor Receptor 2 (VEGFR2). VEGFR and its receptor (VEGFR2) play an important role in angiogenesis associated with tumor growth and metastasis.

Methods and Results:

To pursue production of scFv antibody fragments against human VEGFR2, we performed four rounds of biopanning using stepwise decreased amount of VEGFR2 peptide (1 to 0.1 μg), a semi-synthetic phage antibody library (Tomlinson I + J) and TG1 cells.

Antibody clones were isolated and selected through enzyme-linked immunosorbent assay (ELISA) screening. The selected scFv antibody fragments were further characterized by means of ELISA, PCR and Western blot analyses as well as fluorescence microscopy and Wound healing assay. Based upon binding affinity to VEGFR2, 5 clones were selected out of 30 positive clones enriched from PD in vitro selection. The selected scFvs displayed high specificity and binding affinity with Kd values at nm range to human VEGFR2. The immunofluorescence analysis revealed significant binding of the selected scFv antibody fragments to the HUVEC cell line. The effectiveness of the selected scFv fragments was further validated by Western blot analyses and Wound healing assay.

Conclusions:

Based on these findings, we propose the selected fully human anti- VEGFR2 scFv antibody fragments as potential immunotherapy agents that may be translated into preclinical/clinical applications.

Introduction:

Allogeneic islet transplantation serves as an ideal source for insulin-secreting beta cells, maintenance of normal glucose levels and treatment of diabetes. However, limited availability of islets, high rates of the islet graft failure and the need for life-long nonspecific immunosuppressive therapy have been a major obstacles in the widespread adoption of this therapeutic option. In this study, we attempted to determine whether the inclusion of mesenchymal stem cells (MSCs) with islet transplantation could  improve the survival and function of the islet graft.

 Methods and Results:

Islets were transplanted, either alone or with in vitro-expanded adipose tissue-derived MSCs, into omental pouch in a rat model of streptozotocin (STZ)-induced diabetes. After transplantation, non-fasting blood glucose level was monitored every 5 days using samples obtained from the tail vein. Normoglycemia was defined as two consecutive blood glucose determinations of less than 250 mg/dl. In addition, the grafted animals were monitored every 5 days for the changes in their body weight.

The transplantation of islets into the omentum of STZ-induced diabetic rats decreased blood glucose levels in a time-dependent manner, established normoglycemia after 20 days and sustained euglycemia until the last day of the 75-day study period. Interestingly, co-transplantation of islets with MSCs, with half of the required number of islets for successful islet transplantation alone, resulted in an improvement of islet allograft outcome similar to that of sole islet transplantation.

Conclusions:

Our results indicated that co-transplantation of adipose tissue-derived MSCs with islet graft promoted survival and function of the graft and reduced the islet mass required for reversal of diabetes. This innovative protocol may allow “one donor to one recipient” islet transplantation.

Introduction:

Apoptosis or programmed cell death (PCD) plays an important role not only in physiology but also in pathology. One of the most prominent features of apoptosis is externalization of phosphatidylserine (PS), which in healthy cells are located in the inner leaflet of the plasma membrane. PS-externalization have made a well-explored phenomenon to image cell death for diagnostic and therapeutic purposes. Since many drugs induce a therapeutic effect through the activation of PCD in target cells, imaging of cell death offers a direct way to image therapy response. Moreover, failure of therapy is frequently a result of resistance against apoptosis. Therefore detection and quantification of apoptosis are some of the significant clinical value for diagnosis and assessment for  therapeutic efficacy. In this research we emphasize the expression and purification of recombinant polyhistidine-tagged human annexin V protein that binds to PS with high affinity and has been developed as a molecular imaging agent to measure cell death in vitro and  in vivo in animal models and in patients with cardiovascular diseases and cancer. We also describe conjugation of this protein to the Fluorescein isothiocyanate (FITC) fluorophore for the detection of apoptotic cells by flow cytometry or fluorescence microscopy.

Methods and Results:

In this project we transformed recombinant plasmid including annexin V gene into competent BL21 strain. after an overnight incubation at 37°C in LB medium,1 mL of that was used to inoculate 100 mL of TB culture.

The expression of annexin V was induced with 1 mM IPTG (isopropyl-b-D-thiogalactopyranoside).

The expression level of annexin V was evaluated by SDS-PAGE. Recombinant annexin V was expressed and purified to high yields. FITC as the fluorescent conjugate and a signal detector was used to attach to annexin V. we detected apoptotic cells in culture by annexin V-FITC produced probe in real time, using fluorescence microscopy and flow cytometry.

 Conclusions:

Annexin V staining is a simple and widely used method for detection of apoptosis in a rapid and highly quantitative manner for both early monitoring of therapy capability and assessment of disease development.

Introduction: Peptides and proteins are bio-macromolecules with diverse interesting bioactivities, formed of amino acids joined by peptidic bounds. Their resources include animals, plants, fungi, bacteria and insects. Various biological effects from these agents including antioxidant, antimicrobial, anti-inflammatory, anti-hypertensive and opioid activity have been reported. Antimicrobial peptides have been isolated from roots, seeds, flowers, stems, and leaves of a wide variety of species and have demonstrated activities towards phytopathogens, as well as against human pathogenic organisms such as viruses, bacteria, fungi, protozoa and parasites.

Antifungal proteins have captured the attention of a large number of investigators regarding to their economic implications. Plants are one of the attractive sources of antifungal peptides and proteins.

Methods and Results: Searching keywords of bioactive peptides and proteins, antimicrobial, antifungal and plant in different search engines resulted in numerous published articles. According to the litritures, herbal antifungal proteins and peptides can be classified, based on their structures and/or functions, into groups including chitinases, glucanases, thaumatin-like proteins, thionins, and cyclophilin-like proteins. These proteins may demonstrate different fungal specificities. The mechanisms of antifungal actions of only several antifungal proteins including thaumatin-like proteins and chitinases have been elucidated. Some of the chitinase-like proteins have been reported from plants for instance: Dolichin, an antifungal protein from field beans (Dolichos lablab) with strong antifungal activity against Rhizoctonia solani, a 28 kDa, protein from cowpea (Vigna unguiculata) seeds, pinto bean (Phaseolus vulgaris cv. pinto) seeds, and ricebean (Delandia umbellata) seeds, another protein from Panax notoginseng (sanchi ginseng) roots with potent antifungal activity against F. oxysporum and Pananotin from sanchi ginseng roots.

Conclusions: From this survey it can be concluded that different proteins and peptides of diverse structures are elaborated by a diversity of plants with wide antifungal activities. Some of these antifungal proteins have also exhibited antiviral inhibitory activitis toward the enzymes of human immunodeficiency virus.

Abstract:  Successfully cancer therapies aim to induce apoptosis in cancer cell lines. Recent advances in cancer therapy based on the use of some recombinant proteins such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). TRAIL is a new member of the TNF superfamily. In this paper, we report the expression, purification, and  preparation of a recombinant form of the extracelluar domain of the TRAIL (sTRAIL) in Escherichia coli rosetta gami under the control of T7 promoter; which  may selectively induce apoptosis of tumor cells in vitro. To obtain recombinant sTRAIL protein, the encoding region for sTRAIL was cloned between Xho1 and BamHI in pET28a expression vector. The results showed that the recombinant sTRAIL was efficiently produced in Ecoli rosetta gami strain.

Introduction: Apoptosis is an evolutionarily conserved and essential for maintenance of  tissue homeostasis and removal of unwanted cells. TRAIL belongs to the group of therapeutic agents selectively targeting a wide variety of cancer cells without affecting the normal cells .The therapeutic potential of TRAIL is attributed to its receptor expression in a variety of tissues; which initiates apoptosis in cancer cells through interaction with the death receptors DR4 and DR5. Due to its selective nature, it is considered as a significant therapeutic agent in cancer therapy. The purpose of this study was to produce recombinant human sTRAIL in Rosetta Gami2 E.coli strain and its functions on cancerous cells in vitro.

Methods and results:  we optimized the coding sequence of this protein. The recombinant plasmid was transformed into Rosetta Gami2 E.coli strain for expression. The transformed bacteria which contain recombinant plasmid were cultured in 37ºC with 250 rpm in LB and in 20ºC in TB medium for 18 hours. TRAIL was purified by Ni sepharose column, and the presence of the recombinant protein was confirmed by SDS-PAGE. The concentration of purified protein was measured by Bradford assay. Our finding showed that the recombinant protein (34kD) has been successfully produced for next experiments, the purified protein was desalted and applied toward cancerous cells.

Conclusions: In summary, TRAIL can be considered as a promising therapeutic agent for effective, targeted and less toxic agents for treatment of cancers.

The first 34 amino acids of parathyroid hormone has complete activity of 84 amino acids parathormone and is produced as recombinant form, teriparatide. This recombinant peptide drug increases bone density leads to fracture risk reduction. This drug has been used for treatment of osteoporosis in women and men. A new 115 amino acids teriparatide fusion protein was purified from total protein of host cell with elution buffer in different pHs.

Introduction: Proteins are widely used in pharmacology, medicine, diagnostics and researches. Escherichia coli is one of the most frequently used hosts for recombinant drug production. Consequently, purification of recombinant protein expressed in this host is very important. This study was done to find the best pH of elution buffer for purification of recombinant teriparatide fusion protein expressed in E.coli BL21 (DE3). For this purpose, elution stage was performed in 3 different pHs.

Methods and Results: Teriparatide fusion protein was purified with nickel affinity chromatography in denaturing buffers with different pHs. There are 3specified steps in this type of chromatography includes interacting between the fusion protein and the positive nickel ions of the resin, washing the host proteins, and to finish eluting the fusion protein. Non-specific proteins were eliminated from the column with pH 6.3 washing buffer [100mM NaH₂PO₄, 10mM Tris buffer, 8M Urea, 20mM 2-Mercaptoethanol] and recombinant  fusion teriparatide has the His-tag  was eluted via elution buffers [as same as washing buffer] in 3 states with 3 pHs of 5.8, 4.6 and 4.2.The micro Bradford test was done in all mentioned stages. As a final point, the samples were flow thrown, washed and eluted observed in SDS-PAGE.

Conclusions: Six histidin residues in N-terminal of fusion teriparatide sequence were interacted easily with the positively charged nickel ions of resin. In this way, the recombinant fusion protein, teriparatide, was hold in the resin at pHs higher than His-tag pI (5.1) and disconnected from the resin at pH slower than it. In this work, major amounts of teriparatide were exited from column at pH 4.6.

Introduction: The kinetoplastid protozoan parasites of the genus Leishmania cause diseases for which treatment is difficult and there is still no vaccine for use in humans. Leishmanolysin is the major enzymatic protein component of the promastigote surface. Because of its role as a ligand involved in the interaction of the parasite with defensive systems of the host, including components of the complement system and the macrophage surface is an attractive candidate for designing peptide vaccines.

 Methods and Results: In the current study, PEPOP was used to predict peptides from Leishmanolysin in the form of discontinuous B-cell epitopes. PEPOP identified segments comprised of accessible and sequence continuous amino acids. These segments were clustered according to their spatial distances using method of extensions: Optimized Nearest Neighbor (ONN), Optimized Flanking Nearest Neighbor (OFN), Optimized Patched segments Path (OPP), Traveling Salesman Problem (TSP), and Shortest Path (SHP). Each peptide sequence has been generally comprised of several segments. From 3D structure of Leishmanolysin, PEPOP identified 100 segments gathered in three clusters according to their spatial distances. In this study, we wanted to predict peptides from a specific region of the protein, the residue 264-345 on the active site of Leishmanolysin. It corresponds to the segments S34 to S48. The predicted peptides, which did not relate to this region (264-345) were removed and at last 29 peptides were selected.

Conclusions:

These results using bioinformatics analyses could be conducted in vaccine design against Leishmania infections.

Introduction: The insulin-like growth factor-1 receptor (IGF-1R) plays a key role in proliferation, growth, differentiation, and development of several human malignancies including breast and pancreatic adenocarcinoma. IGF-1R targeted immunotherapeutic approaches are particularly attractive, as they may potentially elicit even stronger antitumor responses than traditional targeted approaches. Cancer peptide vaccines can produce immunologic responses against cancer cells by triggering helper T cell (Th) or cytotoxic T cells (CTL) in association with Major Histocompatibility Complex (MHC) class I or II molecules on the cell surface of antigen presenting cells.

 Methods and Results: In our previous study, we set a technique based on molecular docking in order to find the best MHC class I and II binder peptides using GOLD. In the present work, molecular docking analyses on a library consisting of 30 peptides mimicking discontinuous epitopes from IGF-1R extracellular domain identified peptides 249 and 86, as the best MHC binder peptides to both MHC class I and II molecules. The receptors most often targeted by peptide 249 are HLA-DR4, HLA-DR3 and HLA-DR2 and those most often targeted by peptide 86 are HLA-DR4, HLA-DP2 , and HLA-DR3.

Conclusions:

These findings, based on bioinformatics analyses, can be conducted in further experimental analyses in cancer therapy and vaccine design.

Introduction: Plasmin is a trypsin like serine protease that can catalyze the hydrolytic cleavage of peptide bonds at the COOH sides of arginines and lysines in extracellular matrix (ECM) components including fibrin, laminin and fibronectin. Microplasminogen (µPlg) is the COOH-terminal portion of plasminogen from 531 to 791, and has molecular weight of about 30kDa. µPlg consists of the catalytic domain of plasminogen and can be converted by many plasminogen activators, for example, streptokinase (SK) into microplasmin, which shares the same catalytic properties as human plasmin. µPlg can be used as a therapeutic agent in vitreoretinopathies and thrombotic diseases.

Methods and Results: The purpose of this study was production and activation of recombinant µPlg. After codon optimization and synthesis of the µPlg gene, it was inserted into expression vector pPICZα and this plasmid was transformed into Pichia pastoris X-33 cells by electroporation. The selected positive transforments were transferred into YPM (yeast extract-peptone-methanol) medium and were induced by methanol. The recombinant protein (33kDa) was successfully secreted into the supernatant of the induction medium and was purified by Ni-sepharose column. The presence of the recombinant µPlg was confirmed by SDS-PAGE. The activation of µPlg by streptokinase was performed at a 1:1 molar ratio of streptokinase to µPlg at 37°C for 2hr in Tris-HCl buffer, pH=7.8. Microplasminogen activity was measured by FDP (Fibrinogen Degradation Product) ELISA kit. In a blood sample the clot is broken down by plasmin. Some of These broken fibrin fragments are called d-dimers. In general, D-dimer elevation indicates increased fibrin turnover. In this procedure, 30 μL of active enzyme was added. And the rate of D-dimers was measured at 380 μg/mL. While the natural amount of D-dimers in the blood is less than 40 μg/mL.

Conclusions: The availability of microplasminogen with lower molecular weight can be a valuable pharmaceutical tool for treatment of thrombotic diseases and vitreoretinopathies because the isolation of autologous plasmin is an expensive and time-consuming process. In this study we managed to produce microplasminogen and successfully turn it into active microplasmin. However more effort is needed to increase the yields of Protein Production.

The risk of acquisition of resistance to chemotherapy remains a major hurdle in the management of various types of cancer patients. Several cellular and non-cellular mechanisms are involved in developing both intrinsic and acquired resistance in cancer cells toward chemotherapy. This review covers the various multidrug resistance (MDR) mechanisms observed in cancer cells as well as the various strategies developed to overcome these MDR mechanisms. Extensive studies have been conducted during the last several decades to enhance the efficacy of chemotherapy by suppressing or evading these MDR mechanisms including the use of new anticancer drugs that could escape from the efflux reaction, MDR modulators or chemosensitizers, multifunctional nanocarriers, and RNA interference (RNAi) therapy.

Introduction:

 The risk of tumors acquiring resistance to chemotherapy (multidrug resistance) remains a major hurdle to the successful treatment of various types of cancers including blood, breast, ovarian, lung, and lower gastrointestinal tract cancers. Multidrug resistance (MDR) is a phenomenon in which cancer cells exhibit a cross-resistant phenotype against multiple unrelated drugs that are structurally and/or functionally different and may also have different molecular targets.

Methods and Results:

 Hypoxia in cancer might lead to multidrug resistance via different cellular pathways such as lost sensitivity to p53-mediated apoptosis, and enhanced P-glycoprotein expression. Till now , the most widely studied MDR mechanisms are those associated with drug efflux mechanisms involving ATP-binding cassette (ABC) membrane transporters .

Conclusions:

Targeted nanocarriers present a powerful and versatile platform to overcome this life threatening disease.

Introduction:

Over the years, the use of plastics has complicated the problem of disposal of solid wastes. One strategy to reduce plastic waste is the use of biodegradable plastics. A group of these plastics are polyhydroxyalkanoates (PHAs). To date more than 250 different microorganisms are known to synthesize and accumulate PHA. Most Pseudomonas strains are able to accumulate mcl-PHA. In previous studies, the phaC1 and phaC2 genes were identified in Pseudomonas aeruginosa (P.aeruginosa) PTCC 1310 and were cloned. The aim of this study was to express these genes and optimize the conditions for their expression.

 Methods and Results:

The inserts obtained from vectors pTZPHAC1 and pTZPHAC2 were subcloned into pET15b expression vector. After transformation of competent Escherichia coli (E.coli) BL21 (DE3) cells with recombinant plasmids, expression was induced using IPTG. By changing expression conditions such as IPTG concentration, time and temperature of incubation with IPTG, the expression conditions for these enzymes were optimized, and the obtained results were compared using proper statistical analysis.

Conclusions:

The PHA synthase genes were induced with IPTG and the expressed 62 kDa protein was observed and purified. By changing expression conditions, 1 mM IPTG, 37°C and a 2 hr incubation provided the highest level of protein production in E.coli cells. These results suggest that induction condition of PhaC genes can influence expression of PHA synthase enzymes.

Introduction: Recent advances in genome engineering are starting a revolution in biological research. The clustered regularly interspaced short palindromic repeats (CRISPR) and its associated protein (Cas9) enables diverse manipulations of genome function. It has become a predictable and precise method of choice for genome engineering by specifying a 20-nt targeting sequence within its guide RNA. Regarding its simplicity, broad applicability, and high efficiency, CRISPR-Cas9 tool can be used in understanding of cellular mechanisms, generating animal models, correcting defective gene(s) causing diseases, cancer treatment, removal of bacterial/ viral infections, and in drug discovery. Moreover, the capability of CRISPRi to gene regulation without altering its function can be utilized for exceeding our knowledge of gene expression in prokaryotic and eukaryotic systems.

Results: In this lecture, the history and biology of CRISPR system were described firstly. Also, the applications of CRISPR-Cas9 in various ways, such as efficient generation of a wide variety of biomedical important cellular models as well as animal ones, modifying epigenomes, conducting genome-wide screens, labeling specific genomic loci in living cells, genome editing applications in xenotransplantation and endogenous gene expression regulation by an altered version of this system were reviewed. Moreover, we describe how this technology can be used as an antimicrobial or antiviral tool. However, this technology still needs optimization and will require a better understanding of how this system works on molecular level.

Conclusions: The broad applications of CRISPR-Cas9 technology in biological research will greatly advance our knowledge of basic biology as well as opening a door to treat a wide spectrum of human diseases.

Introduction:

 Mesenchymal stem cells (MSCs) have differentiation capacity to multi lineage cells, such as osteoblasts. As has been reported recently, osteogenic differentiation can be regulated by microRNAs. Although platelet-rich plasma (PRP) is used in the osteogenic differentiation process, the molecular mechanism of the effect of PRP on the induction of osteogenic differentiation by microRNAs is not well understood. We evaluated the effect of PRP on the expression of mir-29a as a key microRNA on the osteogenic differentiation process of hMSCs.

Methods and Results:

Mesenchymal cells were isolated from human adipose tissue and differentiated into osteoblasts. The effects of 10% PRP on bone differentiation evaluate by alkaline phosphatase activity and calcium deposition. We also evaluated gene expression of Runx2 and OPN along with the expression of mir-29a by Real-time PCR. Adipose-derived cells with differentiation potential to adipocyte and osteoblast cell lines, show significant increase in osteoblast differentiation rate, enzyme activity, mineralization upregulation of the mir-29a and gene markers when treated by 10% PRP.

Conclusion:

The present study showed that micro-RNAs such as mir-29a seem to play an active role in the process of bone differentiation during PRP treatment, which in turn affects the signaling pathways of mesenchymal stem cells. Determining the signaling pathways of PRP effect on osteogenic differentiation can optimize the use of this substance in the cell therapy for bone injury and fracture.

In the present study, the novel implantable drug delivery chip was designed by silicon reservoir and Ionic Polymer Metal Composite (IPMC) actuator integration. The whole design was tested to be biocompatible. The reservoir was developed by high technique silicon lithography and the IPMC strip was attached as the gate of the drug reservoir. The IPMC actuation and subsequently the drug release was controlled by a manipulated communication system based on transmitter and receiver circuits, designed for wireless power transmission. Electromagnetic waves with 2 MHz frequency were for power transmission. The wireless transmission is on the order of 5 cm due to the chip potential to get implanted in the patient's body, near the cancerous organ.

Introduction: Drug delivery systems are divided into two main categories: passive systems and active systems, where the drug release is controlled by an external source. The active systems involve remote controlled drug delivery chips based on silicon, a remarkable technology, which releases a certain dose of drug on demand from outside the body. Both systems are designed to facilitate cancer treatment and prevent patients from getting involved with the chemotherapy's side effects.

Methods and Results:IPMC was fabricated by electroless deposition of nafion as a smart polymer with the ability to bend in low applied voltages. The prepared IPMC was attached to an etched silicon as a single drug reservoir chip. The transmitter section included a microcontroller, a driver, an amplifier and a coil. Electromagnetic waves generated in the transmitter section were captured by the receiver section, converted to electrical voltage and transferred toIPMC actuator to unseal the drug reservoir.Figure 1 shows the schematic of the drug delivery chip with wireless communications.

Conclusions:The single reservoir, wirelessly controlled drug delivery chip was designed using IPMC actuator as the gate of the reservoir. The drug was released on demand by generating electromagnetic waves that were converted to electrical voltage and transferred to IPMC actuator in receiver section on the chip.

Introduction:Defective apoptosis (programmed cell death) is a major contributor to the process of cancer progression and metastasis. Over the last decade, new drug compounds were designed to enhance apoptosis in the tumor cells. Hsp70 chaperone is an anti-apoptotic protein and its inhibitors serve as suitable compounds in cancer treatment strategies. A number of different techniques such as x-ray crystallography are available for studying inhibitory effects of apoptosis-inducing compounds on Hsp70 activity. These techniques are expensive and time-consuming because of long sample preparation steps prior to analysis, and the functional analysis of new compounds synthesized cannot be examined in vivo. In order to overcome these problems, for the first time, a rapid, sensitive and inexpensive real-time biosensor system in vivo is introduced using intracellular reporter. In real-time biosensor system, because of the availability of a rapid and sensitive activity assay using biolominometer in vivo without cell lysis, luciferase has been considered as proper candidate.

Methods and Results:Co-transformation of the cells was carried out with two expression vectors containing Hsp70 and firefly luciferase, and the assessment of new drug compounds on Hsp70 activity under the stress conditions was evaluated. Our result showed that Hsp70 plays a crucial role in suppressing inactivation of luciferase in vivo during heat-treatment. On the other hand, the activity of heat-inactivated luciferase was approximately regained in cells expressing Hsp70 after incubation at room temperature for 60 min. According to the results, the reactivation of thermally inactivated luciferase was inhibited in the cells by treating with Ver-155008 and PFT-μ compounds (as apoptosis-inducing compounds) with IC₅₀ of 124 and 384 μM, respectively. Also, the sensitivity of this method for detecting Ver-155008 and PFT-μ compounds was as low as 8 and 23 μM, respectively, and it showed no response to doxorubicin anti-cancer drug which binds to DNA, and used as control.

Conclusions:Real-time biosensor system using luciferase can be a class of in vivo biochemical tests used for simple, rapid and sensitive detection of apoptosis-inducing compounds based on Hsp70 inhibition to facilitate clinical and therapeutic studies in the years to come.

Introduction: Currently, the major concern with biomaterial implantation or tissue grafting is adverse responses of immune system. To remove these barriers, some immunosuppressive drugs are used. But they are associated with adverse effects of systemical delivery. Adhesion of immune cells to foreign body by cell adhesion molecules such as integrins,triggers their activation that leads to immune response. It is demonstrated that this is directed by the ability of dendritic cells (DCs) to drive adaptive immune cells in situ toward adverse reactions and play as a bridge between innate and adaptive immune cells. Thus our focus is on β₂ integrin receptors on DC. This study aims to modulate the immune response by inhibiting  β₂integrins marker on DC.

Methods and Results:to control of DC maturation,αlβ2 and αmβ2 surface markers on DCs should be blocked, hence, the novel aptamer-blocking technique was utilized. For this purpose, immature DCs (iDC) were derived from human peripheral blood monocytes. The antagonist biomolecules (aptamer) that simulated based on inverse of DC markers (αlβ2 and αmβ2) from selex,were embedded into injectable alginate-branched polyethyleneimine by physical entrapment. Then, derived iDCs were treated with synthesized hydrogels in RPMI-1640 media. Interaction of released antagonist aptamers from hydrogels andiDC was analyzed. DC adhesion and subsequently its maturation and potential for adaptive immune cell activation were measured by flowcytometry.When iDCs were treated with hydrogels the levels of DC markers (CD80 and CD86) expression as DC maturation criteria were measured. Expression level ratio for CD80 and CD86 to control sample show significant reduction, about 40 and 50, respectively. Released cytokinesfrom administrated DC by trappedaptamerswithAlg-PEI hydrogel indicate that DC behavior against a chemical foreign body was modulated considering the amount of released cytokines were decreased by10%.

Conclusions:The results of this study demonstrated that this presented drug delivery system based on αlβ2 and αmβ2 aptamers can be used as an immune response modulator in health-related application. αlβ2 and αmβ2 aptamers as a new age of state of the art drug technology could be a good substitute for monoclonal antibody drugs to reduce their side effects and draw backs.

Introduction:

Tumor necrosis factor alpha (TNF-α) expression amplifies to excess amounts in several disorders such as rheumatoid arthritis and psoriasis. Although, Anti-TNF biologics have revolutionized the treatment of these autoimmune diseases, formation of anti-drug antibodies (ADA) has dramatically affected their use. The next generation antibodies (e.g. Fab, scFv) have not only reduced resulted immunogenicity, but also proved several benefits including better tumor penetration and more rapid blood clearance.This study highlights the use of phage display for identification of human single chain fragment antibody against disulfide-bonded TNF-α using phage display technology.

Methods and Results:

Using affinity selection procedures in this study, a scFv antibody clone was isolated from naïve Tomlinson I phage display library that specifically recognizes and binds to TNF-α. The TNF-α recombinant protein was expressed in genetically engineered Escherichia coli SHuffle^® T7 Express, for the first time, which is able to express disulfide-bonded recombinant proteins into their correctly folded states.

Conclusions:

ELISA-based affinity characterization results indicated that the isolated novel 29.2 kDa scFv binds TNF-α with suitable affinity. In silico homology modeling study using ‘ModWeb’ as well as molecular docking study using Hex program confirmed the scFv and TNF-α interactions with a scFv-TNF- α binding energy of around -593 kj/mol which is well in agreement with our ELSIA results. The cloned scFv antibody may potentially be useful for research and therapeutic applications in the future.

Introduction: Proteases are one of the most applicable hydrolyzing enzymes especially in food and beverage industries. Isolation of thermophilic or halophilic proteases was aimed by many investigations. The present study was designed to screen soil samples for halophilic actinomycetes capable to produce protease and evaluation of factors affect on the enzyme production. 

Methods: Twenty soil samples were collected from salty land around Kerman, Iran and aseptically transferred to biotechnology lab and allowed to dry. Ten grams of each soil was extracted using NaCl (0.9%) sterile solution and added to Casein Glycerol Agar (CGA) or nutrient agar medium containing skim milk (1%) and NaCl (10%) and incubated at 30◦C untill the halo zone of protease activity was formed. The ratio of halo zone/colony size of isolated actinomyctes was used as an index to select the most suitable strains. Morphological and biochemical tests as well as molecular identification using 16S rDNA technique were then applied for identification of the strain. Evaluation of chemical factors such as carbon sources, nitrogen sources and inorganic salts as well as physical factors such as temperature and pH on protease production of the selected strain was performed using one factor at a time approach.

Results: Seven protease-producing actinomycetes were isolated in preliminary studies among which one isolate (identified as Nocardiopsis sp.) was the most efficient one able to produce 650 U/mL protease after 5 days incubation in CG medium containing 10% NaCl. Evaluation of factors is now conducting to obtain the maximum protease production.

Conclusion: one halophilic actinomycete able to produce protease was isolated in the present study and evaluation of factors affect on the enzyme production is now performing.

Introduction: An important issue in cancer therapy is the achievement of desired therapeutic response with the least adverse effects. To achieve this goal, targeted drug delivery systems were developed. Aptamers, mainly DNA/RNA aptamers, are the attractive affinity ligands for the cancer cell surface specific antigens. Besides, microRNAs are another type of therapeutic and diagnostic oligonucleotides that have been recently studied in various cancers. miRNAs are small double stranded RNAs with important roles in cell regulatory pathways. Profile changes of miRNAs can result in cancer development. External addition of miRNAs or their elimination using antagomiR can lead to the efficient treatment of related disease. Targeted delivery of therapeutic agents to the site of action with less adverse effects is the most challenging issue in anticancer chemotherapeutic agents as well as miRNA therapy. In addition, miRNAs stability in biological systems can be improved by targeting strategy. In this study, a cancer specific aptamer (anti-nucleolin aptamer) and a functional miRNA in cell growth and proliferation (miRNAlet-7d) were used in the development of targeted nano-molecules as an efficient anti-proliferative agent for cancer cells.

Methods and Results: Sequences of A1411 aptamer and miRNA let-7d were extracted from related databanks and were chemically synthesized with amine and thiol modification in the 3' terminals or with a 17 nucleotides sticky extension at 3' terminal.  The sequences were conjugated covalently using SM(PEG)₂ hetero-bi-functional cross-linker or un-covalently by annealing the sticky ends. Conjugation was confirmed using polyacrylamide gel electrophoresis 15%. The serum stability of these two types of conjugates were evaluated using up to 48 h incubation of conjugates in human serum (AB⁺). Stability of covalent conjugate using SM(PEG)₂ linker was at least two hours more than the un-covalent one.  

Conclusions: Remarkable advantages of this nano-molecule were targeted and relative stable delivery of miRNA as the therapeutic agent with probable synergistic effect of two oligonucleotides of miRNA and aptamer in the proliferation inhibition of cancer cells.