Introduction: Metronidazole (MET) and Miconazole (MIC) are antiprotozoal and imidazole antifungal agents, respectively. The aim of this study was to assess the usefulness of Fourier Transform Infrared micro-spectroscopy (FTIR-MSP) for discriminating and detecting spectral changes of mouse fetus liver tissue after mother’s exposure to concomitant use of MET and MIC.

Methods and Results: The control group received only normal diet and the exposure groups received MET, MIC, and concomitant MET and MIC. The pregnant mice were anesthetized and their fetuses were surgically removed on gestation day 15. Fixative slides without any staining were put on KBr disc with a 1mm thick for IR micro spectroscopy. All information obtained from the spectra were analyzed using routine FTIR software. Based on our results, MET and MIC, alone and in combination together, have created some changes in the mice fetus liver biomolecules.

Conclusions: FTIR biospectroscopy application in teratology is very challenging, but it has been accepted as a reliable technique; however, it is necessary to do more investigations.

Introduction: Hepatocellular carcinoma (HCC) or primary liver cancer is one of the most prevalent and deadliest cancers, which has been increasing greatly worldwide. Diethylnitrosamine (DEN) is a well-known environmental toxin and potent hepatocarcinogenic dialkylnitrosoamine present in air, water, and in a number of foodstuffs. In the present study, we evaluated preventive effect of aqueous extract of quince (Cydonia oblonga Mill.) fruit (ACO) against DEN-induced hepatocellular carcinoma (HCC) in rats.

Methods and Results: The model of hepatocellular carcinoma was induced by a single intraperitoneal injection of DEN (200 mg/kg) as an initiator that after two weeks followed by daily oral administration of 2-acetylaminofluorene (30 mg/kg) as a promoter for two weeks. Quince-treated rats were pretreated with ACO intragastrically at three different doses two weeks prior to DEN injection. The marked reduction of serum biomarkers of liver damage and cancer, including alfa-fetoprotein (AFP), gamma glutamyl transpeptidase (GGT), alanine transaminase (ALT), and aspartate transaminase (AST) were observed in ACO supplemented animals as compared with HCC rats at the end of the experiment. Moreover, the quince extract exhibited in vivo antioxidant activity by elevating glutathione (GSH) contents as well as preventing lipid peroxidation in the liver tissues of DEN-treated rats. The relative weight of liver was also reduced in quince-treaded rats as a prognostic marker in HCC.

Conclusions: Our results clearly demonstrated that quince has a chemopreventive effect against HCC in rats and can be proposed as a promising candidate for the prevention of DEN-induced hepatocarcinogenesis.

Milk is one of the most important foods in the dietary regimen of children which can be contaminated with toxic elements such as lead (Pb) and cadmium (Cd). In this study, the concentrations of Cd and Pb were determined in the milk distributed among school-aged children in Tehran. Differential-pulse anodic stripping voltammetry (DPASV) method using hanging mercury drop electrode (HMDE) was performed.
The obtained limit of detection (LOD) and limit of quantification (LOQ) were 0.31 ppb and 1.03 ppb for Pb and 0.09 ppb and 0.32 ppb for Cd, respectively. The concentration of Pb and Cd in the examined milk was 3.34 ± 0.63, and 0.42 ± 0.47 ppb, with recovery range between 85-109% and 91-112%, respectively.
The results demonstrated that the levels of Pb and Cd were considerably less than the maximum residue limit (MRL), mentioned by the regulatory organizations.

Aim

Carnosine (β-alanyl-L-histidine) is a naturally occurring dipeptide widely and abundantly distributed in the muscle and nervous tissues of animal species. Carnosine contains several beneficial biological properties such as antiglycating and antioxidant activities. It also contains antineoplastic effects in human cell culture as well as in animal experiments, however, the clear molecular basis of this activity has not been known yet. In the present study, in order to further examine structural basis of Carnosine for the anticancer activity, some linear and cyclic Carnosine peptide analogues were synthesized and their cytotoxicity were examined.

Material and Methods

 Linear and cyclic Carnosine peptide analogues were synthesized with appropriate protected amino acids and reagents using solid-phase peptide synthesis strategy, and anti-neoplastic activity of the synthesized compounds were examined on cancer cell lines of HepG2 (Human Liver Cancer Cell Line) and HT-29 (Human Colorectal Adenocarcinoma Cell Line) using MTT assay and flow cytometry analysis. Safety profile of the synthesized Carnosine analogues was also examined using skin fibroblast cells.

Results

 Our results showed that Carnosine analogues were toxic against HepG2 and HT-29 cell lines with a mean IC₅₀ value 12.7 µg/mL. Flow cytometry analysis showed that such toxic activity could be, at least partly, through apoptosis induction.

Conclusion

 According to our experiments, in overall, compound 3b can be a good candidate for the further development of safe anticancer agents. On the other hand, cyclic peptides analogues of Carnosine, 1c and 2c, considering the properties of toxicity activities good enough on cancerous cell lines along with high safety profiles on normal skin cells, could be candidates for further works on finding anticancer agents with peptide structure giving better physicochemical properties for oral administration.  

Melanoma is an aggressive and highly lethal cancer with poor prognosis and resistance to current treatments. Apoptosis signaling is believed to be suppressed in melanoma. Evidence suggests that compounds isolated from marine sponges have anti-cancer properties. This study was designed to evaluate the apoptotic effect of methanolic, diethyl ether, and n-hexane extracts of Irciniamutans (I.mutans) on skin mitochondria isolated from mice animal models of melanoma. Mitochondria were isolated by differential centrifugation. According to our results, methanolic, diethyl ether, and n-hexane extracts of I.mutans raised the reactive oxygen species (ROS) level only in the cancerous skin mitochondria group. Furthermore, methanolic, diethyl ether, and n-hexane extracts induced swelling in the mitochondria, decreased the mitochondrial membrane potential (MMP) and the release of cytochrome c from the mitochondria. Based on these results, the potentially bioactive compounds found in I.mutans render the sea sponge as a strong candidate for further researches in molecular identification and confirmatory in-vivo researches.

Generating of an expression clone that can produce the pharmaceutical proteins in an efficient and soluble form at high levels is considered as an important step in pharmaceutical industry. Recombination-based cloning could be a quick and efficient way for generating expression vectors. Thus, both efficient and robust subcloning is vital for the construction of gene expression vectors. In this study, we used the traditional restriction enzyme-based cloning methods for generation of expression-ready clones by the most well-known commercial cloning technologies, Gateway.

Introduction: Diabetes mellitus is a metabolic disease that has affected approximately 10% of population worldwide. Cydonia oblonga Mill. (C. oblonga), commonly called quince, contains diverse phytochemical constituents with a broad range of pharmacological activities. The current study is aimed to investigate the antihyperglycemic effect of aqueous extract of Cydonia oblonga Mill. fruit (ACO) in streptozotocin-induced diabetic rats and to identify the active fraction.

Methods and Results: Diabetes was induced in rats by a single intraperitoneal (i.p.) injection of 60 mg/kg streptozotocin. The antihyperglycemic activity of different concentrations of ACO (80, 160 and 240 mg/kg body weight daily for a period of 28 days) was evaluated in the diabetic rats by measuring their fasting blood glucose (FBG). Furthermore, the antihyperglycemic effects of two major fractions of ACO were evaluated for the identification of active fraction. Finally, the chemical composition of the active fraction, methanolic fraction (MF), was examined by gas chromatography-mass spectrometry (GC-MS) assay. The oral administration of ACO on diabetic rats resulted in a significant collapse in FBG in a dose-dependent manner. In addition, the MF was the active fraction and exhibited antihyperglycemic activity in diabetic rats during the experiment. The main component of MF was identified as 5-hydroxymethylfurfural or 5-HMF (a well-known natural compound) that may be responsible, at least partly, for the antidiabetic and antihyperglycemic effects of quince.

Conclusion: Our results have demonstrated for the first time that quince possesses antihyperglycemic effect in diabetic rats and the MF of the aqueous extract is active fraction.

Introduction: Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and the third most common cause of cancer-related death worldwide. Melissa officinalis L. (M. officinalis L.), known as lemon balm is a medicinal plant, which has a wide range of pharmacological properties. This study was aimed to assess the chemopreventive effect of aqueous extract of M. officinalis (AMO) against diethyl nitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in rats.

Methods and Results: The model of hepatocellular carcinoma was induced by a single intraperitoneal injection of DEN (200 mg/kg) as an initiator and after two weeks was followed by daily oral administration of 2-acetylaminofluorene (30 mg/kg) as a promoter for two weeks. Lemon balm-treated rats were pretreated with AMO intragastrically at three different doses two weeks prior to DEN injection. At the end of the experiment, the marked reduction of serum biomarkers of liver damage and cancer, including alfa-fetoprotein (AFP), gamma glutamyl transpeptidase (GGT), alanine transaminase (ALT), and aspartate transaminase (AST) were observed in AMO complemented rats compared to DEN-treated animals. Furthermore, the extract exhibited in vivo antioxidant activity by elevating GSH concentration and preventing lipid peroxidation in the liver tissues of HCC rats. The relative weight of liver was also reduced in lemon balm-treated rats as a prognostic marker in HCC.

Conclusion: Our findings demonstrated that M. officinalis has a chemopreventive effect against HCC in rats and can be suggested as a potential agent for the prevention of primary liver cancer.

Introduction: Chitosan (poly-β-(1-4)-D-glucosamine) is a linear polysaccharide polymer known as a potential bioactive material that is useful in pharmaceutical applications. This is due to its bioadhesive, antimicrobial, permeability enhancing and biodegradable properties. However, since it is poorly soluble under physiological conditions, this drawback makes chitosan difficult to formulate and utilize in biological applications.

Methods and Results: In this study, we optimized the hemicellulase enzymatic hydrolysis of medium molecular weight chitosan (MWCS) by varying the reaction time: 2 hours, 4 hours and 6 hours. The resulting chitosan was characterized for the change in its physical characteristics using Fourier transform infra-red (FTIR), x-ray diffraction (XRD), contact angle analyses and scanning electron microscopy (SEM). FTIR results showed no significant changes in the functional groups present in the chitosan after enzymatic degradation. XRD diffract grams depict changes of chitosan internal crystal structure from amorphous to crystalline, which improves its stability. SEM images showed an increase in smoothness on the chitosan’s surface morphologies. The surface contact angle analysis showed reduced contact angle as the reaction time increased and this results in the improvement of wetting properties of medium molecular weight chitosan, hence improved water solubility.

Conclusions: In conclusion, as the duration of enzymatic hydrolysis increased, the water solubility properties, as well as other physical and chemical properties of low molecular weight chitosan was also improved.

Since the commercialization of the first therapeutic monoclonal antibody (mAb) product in 1986, this class of biopharmaceutical products have grown significantly. Due to the enhanced antigen binding and reduced cellular toxicity, they result in more efficacy in treatment of variety of diseases. The global sales of mAbs which was 95.1 b$ in 2017 have grown annually due to the dramatic increase in cancer and severe diseases rates and are estimated to reach 131.33 b$ by 2023, this represents a clear accelerating trend with more than 5.53% growth. In this review, we discuss some of these mAbs which have been approved by the FDA as well as others that are experiencing or being evaluated in clinical phases. Global sales of some monoclonal antibodies in 2016 are also considered, suggesting a significant increase in sales of mAbs over the years ahead.

• Introduction: Sorafenib is a multi-kinase inhibitor and decreases tumor cell proliferation. This study aimed to systematically review the existing evidence related to its cost-effectiveness. 
• Methods and Results: EMBASE, MEDLINE, PUBMED, Google Scholar, and the Scopus database were searched and articles were selected on the basis of their correlation with the economic evaluations of Sorafenib. The quality of the selected studies was assessed using the Quality of Health Economic Studies instrument. This review revealed costs per quality-adjusted life years in the range of US $89,160 to $118,825, depending on whether the setting was first-line or second-line and which comparator is utilized. The results indicated that Sorafenib had not been considered as an appropriate treatment option for patients with metastasis Renal Cell Carcinoma (mRCC). Sorafenib was dominated (i.e. higher cost and lower efficacy) in comparison with Sunitinib in all cases. However, Sorafenib would be more cost-effective in comparison with bevacizumab plus interferon alfa in the treatment of mRCC. 
• Conclusion: Sorafenib was more effective with higher cost than Best Supportive Care but Sorafenib was not cost-effective in view of current willingness to pay threshold.