Research/Original Articles


Niosomal Formulation for Co-Administration of Hydrophobic Anticancer Drugs into MCF-7 Cancer Cells

Iman Akbarzadeh, Mahdi Fatemizadeh, Fatemeh Heidari, Neda Mousavi Niri

Archives of Advances in Biosciences, Vol. 11 No. 2 (2020), 16 May 2020
https://doi.org/10.22037/aab.v11i2.28906

Introduction: Designing and developing drug delivery systems has received tremendous attention during the last decade. The treatment of cancer cells is a complicated process due to the existence of different biological pathways. Therefore, the co-delivery of different drugs could have a synergic effect on the treatment process.

Materials and Methods: In this study, different types of span (20, 60, 80) and cholesterol were utilized to formulate tamoxifen/curcumin co-loaded niosomes as a drug carrier system for breast cancer chemotherapy. Niosome characterization was performed through a set of instrument analysis techniques including scanning electron microscopy (SEM) and dynamic light scattering. Release behavior was studied by dialysis method at (pH = 5, 7.4). The stability was monitored during two months storage at two temperatures (4 and 25 °C). Cytotoxicity activity of the best niosomal formulation were assessed on MCF-7 cells, using MTT assay.

Results: The optimal niosomal formulation with span 80 and lipid-to-drug molar ratio of 20 was selected, with maximum encapsulation of both drugs and minimum size. Drug release behavior at physiological pH (7.4) (with significant drug release under acidic conditions (pH = 5) and storage stability of up to 2 weeks with little change in drug efficacy and measurement makes it a proper candidate for breast cancer treatment.

Conclusion: Finally, the results of this study showed the importance of creating highly biocompatible formulations, allowing the simultaneous transfer of two drugs with controlled release to cancer cells which could improve the chemotherapy process with the synergistic effect of the two drugs.

Background: Inflammation is basically caused with conversion of Arachidonic acid into Prostaglandin H2 by CycloOxygenase. In this study a new algorithmic procedure is applied in order to screen molecules not only with high affinity to COX-2, but also different from their ancestor compounds.

Methods: NSAIDs, COX-1 and COX-2 molecules were downloaded from Drug Bank and Protein Data Bank. Drugs were docked with both proteins by FlexX software. Top 10 molecules with lowest COX-2 interaction energies and highest differences between COX-2 and COX-1 IEs were selected for structural similarity searches in PUBCHEM and ENCANCED NCI databases. Second generation molecules were docked with proteins once again. Compounds with lower IEs than parents, were collected. Bioactivities and bioavailabilities of compounds were analyzed by PASS software and Lipinski rules. A best multi linear regression model was developed based on some physicochemical descriptors for further studies.

Results: 50 NSAIDs were selected and 2000 similar molecules gathered. Screening the molecules based on Lipinski rules, bioactivities and drug likenesses, a trustable BMLR model was developed with more than 80% accuracy including following descriptors: Log P, Log D, Molar Refractivity, Polarity Number, and Aromaticity Ratio. Finally, 6 compounds were selected as best structurally new compounds for further in vitro analysis.

Conclusions: Final molecules having high druglikeness and affinity and structurally different from their ancestors, can be used in order to develop new lead compounds with higher selectivity.

Cultivation and Neural Differentiation of Embryonic Cerebrospinal Fluid Treated Adipose Stem Cells on the Scaffold of Amniotic Membrane

Raziyeh Keshavarzi, Mohammad Nabiuni, Hanieh Jalali

Archives of Advances in Biosciences, Vol. 11 No. 2 (2020), 16 May 2020 , Page 20-28
https://doi.org/10.22037/aab.v11i2.30373

Introduction: Adipose stem cells (ASCs) are ideal candidates for cell therapy of neurological disorders. In vitro methods require the use of a variety of growth factors and multi-step protocols to induce neuronal differentiation. This study was aimed to assess the neural differentiation of adipose stem cells in a co-culture system.


Material and Methods: ASCs were obtained from male Wistar rats and were characterized, using flow cytometry. Harvested ASCs were cultured on a scaffold prepared from amniotic membrane (AM). Cerebrospinal fluid (CSF) was collected from rat embryos and was added to culture medium for 7 days. Structure of scaffold and cell attachment was assessed through scanning electron microscopy (SEM). Neural differentiation of ASCs in the co-culture system was confirmed with immunofluorescence (IF) staining for β-tubulin III and MAP-2 markers.


Results: SEM results confirmed the decellularization of AM and attachment of ASCs on the AM derived scaffold. MTT assay revealed that ASCs proliferated on AM significantly during the 7 days of culture. IF data confirmed that the CSF treated cells were expressed by β-tubulin III and MAP-2 but untreated cells were negative for the expression of neural markers.


Conclusion: Cultivation of ASCs on the scaffold and their treatment with CSF induced them into the neural lineage fate in the absence of any chemical inducing factor. This method of co-culture may represent a new method to improve in vitro neural differentiation of ASCs.

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Introduction: Acquired immunodeficiency syndrome (AIDS) is one of the most common infectious diseases in the world. It is transmitted via the Human Immunodeficiency Virus (HIV-1). So, a HIV-1 vaccine should be effective in the prevention of virus infection and induces immune responses. The main aim of this study was to evaluate the humoral immune induction through measuring the expression of interleukin4 (IL-4) in response to levamisole, as an adjuvant, with the HIV-1 Nef-p24 fusion protein as an immunogenic sequence.


Materials and Methods: In this study, 56 BalB/c female mice, aged 6 to 8 weeks were divided into 4 groups. There were 14 mice in each group. Prime and Booster injections were arranged in these groups receiving PBS, levamisole, Nef-p24, and Nef-p24 along with levamisole (Nef-p24/levamisole). All injections were performed peritoneally.


Results: Real-time PCR results showed that IL-4 transcripts level increased significantly (P <0.05) in boostered groups, receiving levamisole, Nef-p24, and Nef-p24/levamisole compared to primed groups. However, the results of ELISA revealed the enhancement in IL-4 expression in levamisole primed groups in comparison to Nef-p24/levamisole boostered group.


Conclusion: The results of the present study showed that the HIV-1 Nef-p24 fusion protein and levamisole could be considered as effective candidates as to increase the expression of IL-4 which may stimulate the humoral immune response.

The Effects of Conditioned Medium from Bone Marrow-derived Mesenchymal Stem Cells on EMT Markers

Sepideh Mirzaei, Kaveh Baghaei, Kazem Parivar, Mehrdad Hashemi, Hamid Asadzadeh Aghdaei

Archives of Advances in Biosciences, Vol. 11 No. 2 (2020), 16 May 2020 , Page 38-46
https://doi.org/10.22037/aab.v11i2.31055

Abstract

Introduction: Epithelial-Mesenchymal Transition in colorectal cancer cell is a critical process in which cells lose their epithelial properties and obtain mesenchymal characteristics, resulting in tumor cells and metastasis. This study attempted to work on the effects of conditioned medium from bone marrow-derived mesenchymal stem cells on EMT markers.


Materials and Methods: In this study, HT29 was used  which is the colorectal cancer cell line. Cells were treated for 72 hours with BMSC-CM in order to induce EMT in HT29. The Real-Time PCR was used for evaluating EMT markers such as E-cadherin- β-catenin -vimentin-and transcription factors.


Results: Inducing EMT in colorectal cancer cells caused morphological changes. It was manifested that E-cadherin is downregulated after induction of EMT with treated BMSC-CM. On the other hand, there were a significant increase in β-catenin, Vimentin, Snail and ZEB1 expression.


Conclusion: Understanding the molecular basis of tumor metastasis is critical for colorectal cancer treatment. Findings demonstrated morphological alterations in consequence MSCs-CM activates induction of EMT. This process affects EMT markers of E-cadherina, Vimentin, β-Catenin and transcription factors of Snail and ZEB1. This model helps knowing cancer and metastasis pathway and also could be used in drug screening procedures.

Evaluating the Effect of Socio-Economic Status on DMFT Index in Children Aged 12 in Iran through Zero-Inflated Poisson Regression

Erfan Ghasemi, Farid Zayeri, Alireza Akbarzadeh Baghban

Archives of Advances in Biosciences, Vol. 11 No. 2 (2020), 16 May 2020 , Page 47-53

Introduction: The most common index in dental studies is the decayed, missing, or filled teeth (dmft)/DMFT. Risk factor evaluation in order to investigate the significant factors that affect this DMFT in children has an important role in dental epidemiological studies. The aim of this study was to investigate the association between socioeconomic factors and dental caries.


Materials and Methods:  This cross-sectional study was a part of a national survey for assessing the oral health status of Iranian citizens in 2012. The target population was children aged. The data and oral examination results were collected by the clinical examination form and trained calibrated dental group (dentists and hygienists). A zero-inflated Poisson regression model (ZIP) with a random effect was utilized for evaluating the effect of socioeconomic status on DMFT.


Results:  In general, 1564 subjects were studied. From the entire subject in this study, the frequency of zero was 4176 (67%). The result of the ZIP model with random effect in zero part showed that socioeconomic status (OR = 1.97; P-value <0.001) had a significant effect on zero DMFT occurrences. The variance component of the random intercept in zero part was significant too (σ2 =17.11, P < 0.001).


Conclusion: The zero-inflated Poisson model with random effect in zero part was fitted to this data. Children from lower socioeconomic classes experienced more DMFT.


 

The Effect of Happiness on Social and Economic Decision-Making Utility

AmirHossein Sadeghi Roshan, Ahmad Sarlak, Mohammad Nasehi, solmaz khalifeh

Archives of Advances in Biosciences, Vol. 11 No. 2 (2020), 16 May 2020 , Page 54-59
https://doi.org/10.22037/aab.v11i2.30942

Introduction:


Neuroeconomics is a field of study that brings together economics, psychology and neuroscience. Human economic and rational decision making is affected by mood and feelings like happiness, sadness, etc.  In the current study, effects of happiness in economic decision making was examined, using the Prisoner’s Dilemma game.


Materials and Methods: Male participants were chosen for each group based on self-rating about their feeling of happiness in life, followed by Oxford Happiness Questionnaire. Two groups were considered: group one who felt happy and group two who did not feel happy.  The ability of making rational decision was examined in Prisoner’s Dilemma game. Two players simultaneously decide their strategy: betray the other by testifying that the other committed the crime, or cooperate with the other by remaining silent. 


Results: The influence of feeling happy on social and economic decision-making was detected in two different groups; the percentage of cooperation in the group which did not feel happy (group two) was 1.5 fold (***P<0.001) which was more than other group. This data manifests non-rational decision making in group two (unhappy) compared to group one.


Conclusion: The main finding of the present study is the significant relationship between happiness and economic decision making. Game theory paradigms suggested that cooperation is not considered as a rational decision. Current data shows that cooperative choices were significantly more in the group which was not happy, showing the effect of happiness in rational decision making.

Review Article


Challenging Approaches in Combating Streptococcus Pneumonia Infection

Amin Talebi Bezmin Abadi

Archives of Advances in Biosciences, Vol. 11 No. 2 (2020), 16 May 2020 , Page 60-66
https://doi.org/10.22037/aab.v11i2.25010

Context: Streptococcus pneumoniae [pneumococcus] induces a large variety of the diseases burden such as bacteremia, meningitis, otitis media and pneumonia in human. Among these, the meningitis can be disclosed with long-lost diseases sequelae. Over the last decades, various recommendations and consensus were released to better manage this major respiratory disease.
 Evidence Acquisition: However, there is a controversy among the clinicians about the best strategy in dealing with this chronic infection. In brief, using proper antibiotics or conjugate vaccine to battle this bacterium is a critical question for the clinical setting.

Results: Taken together, it seems that the best possible adopted strategy is to apply the pneumococcal conjugate vaccines in management due to the following two reasons: 1) reducing the bacterial antibiotic resistance rates and 2) decreasing the prevalence of pneumoniae mortality and morbidity at global scale


Conclusion: Conclusively, continuous surveillance surveys determining antibiotic resistance seem inevitable to track pneumococcal genetical variable populations for both successful antibiotic therapy and proper vaccination.