Modares Journal of Biotechnology

Abstract Gastric cancer is one of the most common cancers in the world. Its treatments are costly and can cause severe side effects. As a result, treatments with natural compounds, well-established therapeutics, or combinations of both groups may be effective alternatives. p-Coumaric acid (pCA) and metformin (Met) are among such anticancer treatments. Epithelial-mesenchymal transition (EMT) is a multi-purpose process that plays a critical role in gastric cancer. This process involves a complex network of biological markers participating in gastric cancer initiation and metastasis. Subsequently, the agents downregulating the expression of EMT markers may be potential anti-gastric cancer therapeutics. Because the effects of pCA, Met, and their combination on the expression of EMT markers ZEB1, Snail2, Vimentin, and VEGFA have not been inspected, the present study aimed at assessing these effects. MTT assay determined the cytotoxicity of pCA and Met on the AGS cells for 48 hours. Real-time PCR was used to evaluate the changes in the expression levels of these EMT genes after 48 hours. A combination of pCA and Met downregulated the expression of ZEB1 and Vimentin genes at low, non-cytotoxic concentrations. Therefore, they may be potential candidates for further investigations in fighting against gastric cancer.

Abstract SH-SY5Y is a neuroblastoma cell line which used as a cancer and neurodegenerative disorders model and its neuro-experimental studies. The different diseases cause by a defect in apoptosis pathway. Disruption of apoptotic proteins has an effect on the treatment process and response to drugs. In nerve cells, due to the high expression of apoptosis inhibitory proteins, the efficacy of drugs is low. Combination therapy is one of the developing treatment methods. The aim of this research is to evaluate the effectiveness of doxorubicin drug on apoptosis in SH-SY5Y cells under the conditions of high expression of caspase9. Caspase9 is a key enzyme in intrinsic apoptosis. First, cell viability was obtained through MTT assay under the different drug concentrations. Then, caspase9 gene was transfected in cells and affected by the concentration lower than IC50 of drug, and cell energy level and cell death were checked by different methods. ATP assay showed that the expression of caspase9 with drug lead to ATP decreases. Caspase3/7 activity indicated an increase in cell death by drug and caspase. Propidium staining to hoechst showed that the expression of caspase9 in combination with doxorubicin induce more death. To ensure the expression levels of protein that induces cell death, the amount of caspase3 protein was checked by western blotting, which showed a significant increase in combination of caspase9 and drug. Our findings showed that the induction of caspase9 expression intensifies the effect of drug and the combined treatment may be effective on the responsiveness of neuronal diseases.

Abstract Investigation of the biomechanical properties of cancer cells is essential for progress in treatment and a better understanding of cancer’s invasion mechanisms. Most of the research carried out in recent years has been done on two-dimensional cultured cells, while the study of cultured cells in three-dimensional mode is more difficult due to the growth of cells in all dimensions and the presence of cell-cell and cell-extracellular matrix connections. It is preferable to a two-dimensional culture. Three-dimensional cell culture, compared to two-dimensional culture, is physiologically closer to in-vivo environmental conditions, but it is currently not considered a common approach for cell culture and preclinical experiments. The lack of a suitable substrate and the limitations of common techniques in characterizing various parameters of cells in three-dimensional mode are considered limitations of this type of culture.
In this research, initially, the substrate was made using PDMS to generate a platform for spheroids, and then the formed spheroids were exposed to Taxol as an anti-cytoskeletal drug. Consequently, by imaging them for a certain period of time, their survival rate was checked, and finally, in order to obtain mechanical parameters, the spheroids’ outer surface was scanned by an atomic force microscope.
The results show that the drug Taxol could reduce the survival rate of tumors, and also affect the biomechanical characteristics of cells in a three-dimensional state. In this case, Young's modulus has decreased from an average of 4.84 kPa to 3.67 kPa under the treatment with Taxol.

Abstract Microorganisms play an important role in formation of mines. In this research, the bacteria inhabiting in Aq-Darreh Takab gold mine were isolated and compared with agricultural soils. The isolates were characterized using 16S rDNA sequencing and the homology searches were performed using BlastN, EzTaxon, and RDP Classifier web tools. Resistance of the isolates was also investigated against arsenic and silver in the presence and absence of 3.5 ppm gold. Although the control soil showed a wide variety of bacterial diversity (43 isolates belonging to 13 genera), only 17 isolates belonging to 11 genera were isolated from mine soils including Acinetobacter, Agrobacterium, Comamonas, Deinococcus, Listeria, Microbacterium, Micrococcus, Pseudomonas, Rhizobium, Roseomonas and Staphylococcus. Among the isolates, A. radiobacter, D. ficus, M. antarcticus, M. luteus, R. radiobacter and R. selenitidurans were able to tolerate different amounts of arsenic and silver in the presence of gold, among which A. radiobacter and D. ficus showed the highest resistance in such a way that they grew in the presence of 50 ppm arsenic, 50 ppm silver, and 3.5 ppm gold. Our results showed that bacterial diversity in soils containing gold, silver and arsenic metals is less than agricultural soils. It was also found that the bacterial diversity in gold mines depends on the amount of gold and the amount and type of associated elements. Due to high resistance of two endogenous bacterial species to arsenic and silver, A. radiobacter and D. ficus, have also the potential for industrial purposes in environments contaminated with these metals.

Abstract Aim: Follistatin-like protein 1 (FSTL1) is a secreted glycoprotein that plays an important role in regulating cell survival, proliferation, differentiation, migration, inflammation, and modulating the immune system. The FK domain in FSTL1 has 10 conserved cysteine residues that form 5 disulfide bonds. Despite extensive studies on the function of FSTL1, limited structural information is available about this biologically important molecule.
Materials and Methods:Using the SWISS-MODEL server and using the crystal structure of the FK domain of the mouse FSTL1 protein with the code (PDB: 6jzw) as a template, structural models of the FK domain of the human FSTL1 protein were prepared. In the next step, the resulting structures were checked using Swiss-PDB Viewer 4.10, Chimera 1.12 software, Ramachandaran diagram and PDBSUM server, in terms of the distance between two cysteine residues, the modeling error range, and the formation of disulfide bonds. Molecular dynamics simulations were performed using the AMBER software package with the ff14SB force field.
Results: The results showed that the FK domain without disulfide bond has root mean square deviations (RMSD) and root mean square fluctuations (RMSF), higher than the native FK domain. In addition, the radius of gyration in domain without disulfide bonds is significantly lower than that of native FK domain. The results show that the disulfide bonds of the FK domain play a role in the stability of the structural folding of the FK domain and the removal of these bonds increases the structural flexibility of this domain.

Abstract Nanotechnology mainly shows its inhibitory effect on the tumor microenvironment by modulating the immune suppression mechanism. Success in this field largely depends on the physicochemical characterization of nanoparticle vaccines. The goal of this study was to produce anti PD-L1 monoclonal antibody decorated nanoparticles containing linrodostat mesylate with desirable properties and to investigate their physicochemical characterization .
Nanoparticles were prepared using double emulsion-solvent_evaporation method. Size and morphology of the particles were investigated using the FESEM microscope method and polydispersity index and zeta potential of the particles using the DLS method, as well as release rate and encapsulation efficiency.
The research results showed that nanoparticles had a suitable uniform dispersion. In the group of nanoparticles containing linrodostat mesylate, the polydispersity index of particles was 0.06 and after the binding of anti-PDL1 monoclonal antibody was 0.24. All particles were spherical with a smooth surface. The ideal particle size for nanoparticles containing linrodostat mesylate was estimated to be 210.14 nm, and it was estimated to be about 270.35 nm after binding anti-PDL1 monoclonal antibody to nanoparticles. Binding of anti-PDL1 monoclonal antibody decreased the amount of encapsulated linrodostat mesylate. The release of linrodostat mesylate was biphasic, it has an initial phase with a steep slope and the next phase is a slow and controlled release.
The results showed that the vaccine based on nanoparticles produced by the double emulsion-solvent-evaporation method containing linrodostat mesylate and decorated with anti-PDL-1 monoclonal antibody has very suitable physicochemical characterization to be used as an immunotherapy vaccine.

Abstract Aims
Alzheimer's disease (AD) is a neurodegenerative disease characterized by the progressive loss of neurons leading to cognitive and memory decay. Accumulation of phosphorylated cis-tau inside neurons is considered a factor in AD's pathological features. This study investigated the effects of extremely low-frequency (EMF) and radiofrequency (RF) electromagnetic fields on the proliferation and expression of phosphorylated tau in SH-SY5Y neuroblastoma cells.
Materials and Methods
SH-SY5Y cells treated were exposed to 50 Hz, 20 mT EMF, and 900 MHz for 24, 48, 72, and 96 hours, and the number of the viable cell were determined by MTT assay. Tau protein phosphorylation level was examined after exposure to EMF and RF at different time intervals.
Results
Exposure to the EMF and RF alone had no significant effect on the viability of SH-SY5Y cells compared to sham-exposed cells. However, the expression of phosphorylated cis-tau was significantly increased after exposure.
Conclusion
This study suggests that exposure of human neuroblastoma cells to a 50 Hz electromagnetic field and 900 MHz radiofrequency might induce phosphorylated cis-tau and thus enhance the potency of AD.

Abstract With the wide spread of electromagnetic waves in living environment, concerns about the harmful effects of these waves on human health have increased. However, many studies have been conducted on the biological effects of non-ionizing radiation, but there is no certainty about the effects of these radiation, especially on the nervous system. The achieved results from studies have many differences and even conflicting results have been reported. According to the previous studies, it is not yet concluded whether non-ionizing electromagnetic radiation damaging to the nervous system. The purpose of this study is to analyze published articles about the effects of non-ionizing electromagnetic radiation on the nervous system in order to extract quantitative data on the effects of these waves. The purpose of this study is to analyze published articles about the effects of non-ionizing electromagnetic radiation on the nervous system in order to extract quantitative data on the effects of these waves. At first, the articles published in the ORSAA database were reviewed and divided into two categories: cellular and molecular parameters and neurological and cognitive parameters. The results obtained from the reviews and quantitative analyzes of the articles in the ORSAA database showed that in the category of cellular and molecular parameters, non-ionizing electromagnetic waves have the greatest effect on the change of enzyme activity and damage to proteins with 418 cases. Also, in the category of neurological and cognitive parameters, non-ionizing waves have the greatest effect on behavior and cognitive effects with 171 reported cases.