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Backgrounds & objectives: Colorectal cancer (CRC) is the third leading cause of cancer death worldwide. Micro RNAs are a group of non-coding small RNAs that inhibit the translation of target mRNA. MiR-146a-5p, as a tumor suppressor, has abnormal expression in many cancers. In this basic research, our goal was to restore the expression level of miR-146a-5p to normal level and to investigate its effect on the expression of the MMP9 gene in HT-29 cells.
Methods: this study evaluates the effect of transfection of miR-146a-5p in HT-29 cell line. At first, the HT-29 cell line from colorectal cancer was cultured in RPMI-1640 culture media and then  were transfected with miR-146a-5p using Jet-PEI reagent. qRT-PCR technique was employed to evaluate the expression level of miR-146a-5p and MMP9 genes. The statistical analysis was performed using GraphPad Prism 6 software.
Results: According to the obtained data, the onset of the invasion and metastasis, in particular, at the final stage of colorectal cancer may be related to a reduction in the expression of miR-146a-5p. The results of the qrRT-PCR test showed that by increasing the expression level of miR-146a-5p in HT-29 cells, the expression level of MMP9 gene decreased in the miR-146a-5p transfected group compared to the control group.
Conclusions: According to this study, activation of metastatic pathways was due to the down regulation of miR146a-5p. Accordingly, miR-146a-5p can inhibits migration of these cells through down-regulating the expression of metastasis-related genes. Hence, miR-146a-5p can be a new diagnostic biomarker and new therapeutic target for CRC.
 

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Background & objectives: MEFV gene has a major role in Familial Mediterranean Fever (FMF) as an auto-inflammatory disorder. FMF is most often seen in the people of the Mediterranean area. Considering the significant role of the MEFV gene in many rheumatologic diseases and even non-rheumatologic disorders, it is necessary to identify different variations of these mutations in the healthy and normal population of this area.
Methods: 224 healthy people entered into this study. The blood samples were screened for the 12 most common MEFV gene variants according to manufacturer’s instructions. (FMF Strip Assay, Vienna lab, Vienna, Austria)
They filled a questionnaire containing the required information. All patients were initially evaluated for the FMF symptoms and signs in themselves and their first-degree relatives based on clinical criteria. Chi-squared test and t-test were employed for statistical analysis using SPSS ver.24.  
Results: Among 224 cases, 113 cases (50.4%) were male, and 111 cases (49.6%) were female. MEFV mutations were detected in 57 patients (25%) of them, 28 cases were male (49.1%) and 29 cases were female (50.9%). The most frequent mutations were E148Q (18.3%, 41cases), followed by P369S (3.1%, 7 cases), V726A (2.2%, 5cases), A744S (1.3%, 3cases), F479L, M694V and R761H (0.8%, each 2 cases), and eventually K695R (0.4%) respectively. Some mutations such as M694I, M680I (G/C), M680I (G/A), I692del were not seen in these samples. There were compound heterozygous mutations of E148Q/P369S, E148Q/V726A, E148Q/P369S, and P369S / F479L in normal population without any findings in favor of FMF.
Conclusion: Twenty-five percent of the normal population of the northwest of Iran carrying a heterozygous variant of the MEFV gene, E148Q (18.3%) as a most common mutation, which can be considered as a normal variant in the healthy population. The presence of M694I, M680I (G/C), M680I (G/A) and I692del mutations in the normal population can be interpreted with cautiously, while particular compound heterozygous mutations can be considered as normal variants.
 

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Background & objectives: Breast cancer is one of the most important causes of cancer deaths especially in developing countries. However, some synthetic compounds such as thiosemicarbazone and its metal derivatives can play a very significant role in reducing the death rate from cancer. The aim of this study was to investigate alterations in the expression of BRCA1, p53 and Bcl-2 genes in breast cancer cell line.
Methods: In this study, the effect of pyrazole derivative of thiosemicarbazone (T) as well as T-bound iron oxide magnetite nanoparticles (T/ Fe₃o₄ np) were investigated on expression changes of Bcl-2, BRCA1 and p53 in MCF-7 cells. For this purpose, the toxicity of the compounds was first measured using the MTT reaction for 24 hr. Then, the mRNA expression levels were evaluated using real-time PCR reaction.
Results: The results showed a high toxicity for the nano-pyrazole derivative of thiosemicarbazone magnetite so that; the fatality rate for treated thiosemicarbazone magnetite derivative cells was much higher than the compound without any nanoparticle. Also, real-time polymerase chain reaction analysis of gene expression indicated a high effect of the derivative on increasing the expression levels of BRCA1 and p53 genes and also decreasing the Bcl-2 gene expression of Bcl-2.
Conclusion: The use of anticancer compounds like thiosemicarbazone which bound to iron oxide nanoparticles would increase the toxicity of the anticancer compounds along with enhancment of delivery of them with high solubility to target tissue.
 

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Background & objectives: Urinary tract infection (UTI) is one of the most common types of hu­man infections and Escherichia coli and Klebsiella pneumonia are the main causes of urinary tract infection among the gram negative bacteria. The prevalence of extended-spectrum β-lactamases (ESBLs) among these bacteria and hence resistant strains to β-lactam antibiotics have increased in recent decades. Several types of extended-spectrum β-lactamases, such as TEM, SHV and CTX-M have been identified, which are prominently present in the strains of E. coli and K. pneumoniae. The objective of this study was to determine the prevalence of TEM and SHV genes in E. coli and K. pneumoniae isolates of urinary tract infections by using phenotypic and molecular (PCR) tech­niques in microbiology laboratory at medical school of Tabriz Islamic Azad University.
Methods: In this cross-sectional descriptive study, 50 isolates of E. coli and 50 isolates of K. pneumoniae collected from uri­nary tract infections from out-patients in Tabriz. Antibiotic sensitivity patterns of isolates were stu­died against 14 antibiotics by disk diffusion test (Kirby Bauer) and also confirmatory tests were performed using combined antibiotic tests. Finally TEM and SHV genes were investigated using molecular methods (PCR).
Results: Twenty five isolates (25%) out of 100 bacterial isolates were identified as ESBL-producing isolates of which 13 isolates (26%) were E. coli and 12 isolates (24%) were K. pneumoniae. The TEM and SHV genes were detected in 2% and 4% of E.coli and 0% and 2% of K. pneumoniae isolates, respectively.
Conclusion: The presence of these genes among our isolates confirmed ESBL genes in these medically important bacteria leading to resistance against β-lac­tam antibiotics which are routinely used in their treatments. The low frequency of the studied genes could be because of the source of our isolates from out-patients which are not generally exposed to antibiotics

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Background & objectives: Colon cancer is a common disease in the world that causes high mortality in affected people. The lack of appropriate diagnostic and prognostic markers has led to the failure in early diagnosis of colorectal malignancies. MicroRNAs play an important role in controlling the expression of target genes involved in the development and progression of colon cancer. The aim of the present study was the bioinformatics identification of microRNAs with distinct expression in cancerous and non-cancerous colon samples.
Methods: This type of study was theoretical bioinformatics and microarray data of 1513 colon cancer samples with the accession number of GSE115513 were obtained from the GEO site and marker genes were selected by using R program. Target genes of the identified microRNAs were provided by TARGETSCAN software and finally, the graphical network was plotted in Cytoscape software.
Results: Analysis of microarray data showed that has-miR-663b, has-miR-650, has-miR-17-5p, has-miR-4539 and has-miR-501-3p have biomarker potential in cancer samples. Statistical analysis and investigation of the target genes indicated that miR-663b (ROC^AUC=0.8965, p=0.001) and has-miR-650 (ROC^AUC=0.9104, p=0.001) had significant distinct expression between cancerous and non-tumor margins with biomarker potential.
Conclusion: The has-miR-663b and has-miR-650 genes can be used as diagnostic markers to distinguish colon cancer from non-cancerous samples

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Background & objectives: Mucopolysaccharidosis IVA (Morquio syndrome type A) is a lysosomal storage disorder caused by a mutation in the GALNS gene located on chromosome 16q24.3 and is inherited in an autosomal recessive manner. To date, more than 300 different mutations associated with MPS IVA, have been reported. Mutational heterogeneity can lead to difficulties in interpretation of molecular testing results, as novel mutations/variants of unknown significance may be detected relatively frequently. The purpose of this study is to analyze the GALNS mutations in Iranian MPS IVA patients.
Methods: Mutation screening of the GALNS gene was performed using direct sequence analysis on DNA samples from 8 unrelated Iranian MPS IVA patients.
Results: We have identified three novels and four previously reported mutations in 8 Iranian patients. We identified three novel missense mutations including: c.680T>C (p.F227S) in exon 7, c.G949C (p.G317R) and c.956G>C (p.R319T) in exon 9 in three different Iranian MPS IVA patients.  Bioinformatics analysis predicted the novel mutations as being disease-causing.
Conclusion: Our findings indicate the molecular heterogeneity of GALNS gene in Iranian patients. We also managed to find three new mutations of MPS IVA in Iranian patients, which are helpful in diagnosis, genetic counseling and prenatal diagnosis in affected families

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Background & Objectives: Gastric cancer is the fourth most common cancer in the world and Ardabil province is in the top ranks in the world. MicroRNAs are non-coding RNA molecules with a length of 18 to 21 nucleotides and due to their regulatory role in post- transcriptional gene expression; single nucleotide polymorphisms (SNPs) could affect their function on target genes regulation.
Methods: Genomic DNA was extracted from peripheral blood of 150 healthy volunteers, which were born and living in Ardabil province, 30 SNPs in microRNA genes have been detected by the Whole Exome Sequencing assay. Then, the obtained results were evaluated using Sanger-based PCR-Sequencing method. The Pearson correlation test was used for finding significant relationships.
Results: After confirming the WES results, the population frequency of the selected variants was compared with the general populations of Iran, Europe and the world. Based on the age-standardized rate (ASR), six variants with significant differences, including rs10061133, rs12220909, rs12983273, rs2292832, rs2505901 and rs6505162 were observed.
Conclusion: According to the previous case-control studies which indicate the association between the variants rs10061133, rs12220909, rs12983273, rs2505901, and rs6505162 and gastric carcinogenesis in various populations, the observed significant differences in our population could imply on the presence of the cancer susceptibility in Ardabil province.

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Background & objectives: Sex impacts the manner in which a person responds to such disease as susceptibility and progression. The aim of this study was to investigate the sex differences in the genotype distribution and allele frequency of some of the adiponectin gene polymorphisms and the comparison of the interaction of the studied polymorphisms and type 2 diabetes-related environment risk factors between males and females.
Methods: This study included 103 males and 79 females with type 2 diabetes and 94 healthy males and 61 healthy females for control. Genotyping was performed using amplification refractory mutation system-PCR (T-ARMS-PCR). Statistical analysis was done using SPSS-26.0. The interaction between SNP-SNP and SNPs-environmental factors was analyzed using MDR (version 3.0.2) software.
Results: Sex-genotype interaction effect was significantly associated only for triglycerides with SNP-11391G/A (p= 0.027). For SNP+45T/G, the difference genotypes were distinctly associated with hemoglobin A1c (p=0.024), body mass index (p=0.033) and body fat percentage (p=0.018). For +276G/T fasting insulin level detected a potential difference in genotypes (p=0.016). Regarding to the results of MDR analysis, the combination of fasting blood glucose, rs17300539 and sex was the best three-factor model. In this model, the distribution of patients according to sex is demonstrated that most men with GA and AA genotypes of -11391G/A had Hemoglobin A1C more than 8.5 while in women there was no relation to genotype found.
Conclusion: Sexual difference impact the interaction between adiponectin gene polymorphisms and environmental risk factors. According to the findings of this study, the effect of environmental risk factors on the progression of type 2 diabetes related to Adiponectin gene polymorphisms are demonstrated within the males more than females.

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Background & objectives: Low immunogenicity and targeted migration of mesenchymal stem cells to inflammatory sites have introduced these cells as the best vehicle for the delivery of gene or therapeutic products. Lentiviral vectors can be used as an efficient vehicle for inserting ectopic genes into stem cells. Therefore, the evaluation of the effect of lentiviral vectors on the identity, behavior and functional characteristics of the stem cells can show that vectors are safe tools in cell manipulation and gene therapy.
Methods: At first, three vectors of lentivirus were added to HEK-293T cells using calcium phosphate method. After confirming the expression of GFP protein in more than 80% of HEK-293T cells, viral supernatant was collected and concentrated. Human adipose-derived mesenchymal stem cells (hASCs) were transduced with condensed viruses. After the elimination of the non-transduced cells by puromycin, transduced hASCs were evaluated for immunophenotyping and differentiation to adipocyte and osteocyte. Behavioral characteristics such as viability, migration and invasion were analyzed using MTT and transwell methods, respectively.
Results: In the current study, there was no significant difference in the expression of CD29, CD34, CD73 and differentiation to adipocyte and osteocyte in the test group when compared to the control group. Moreover, there was no significant difference between two study groups in the behavioral characteristics such as proliferation, invasion and migration.
Discussion: The findings of this study declare that lentiviral vectors do not have adverse effects on the identity and functional characteristics of stem cells. Therefore, they can be used in gene manipulation of the target cell.
 

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Background & objectives: Tissue engineering is a growing field to repair and replace the defective function of damaged tissue or organ, and today it is proposed as a new treatment to replace conventional transplant methods. For this purpose, polymeric biomaterials (scaffolds) and living cells are used. The purpose of this study is to fabricate polycaprolactan (PCL) nanoscaffold and load silymarin on the nanoscaffold to check the biocompatibility and proliferation ability of pc12 cells on it.
Methods: In order to prepare polycaprolactan nanoscaffold and load silymarin on it, 7% polycaprolactan solution (dissolved in acetic acid) was mixed with silymarin solution with a concentration of 0.9% (weight percent), and then the scaffold was prepared using electrospinning device. The morphology of the scaffold was evaluated by scanning electron microscope (SEM) and the chemical structure of the scaffold was evaluated by ATR-FTIR spectroscopy. Toxicity of the scaffold and cell survival of PC12 cells were investigated by MTT test and SEM microscope respectively.
Results: Examining the morphology of the scaffold and its chemical structure showed the appropriate porosity of the scaffold and the successful loading of silymarin on the PCL scaffold. The toxicity of the scaffold was investigated 24, 48 and 72 hours after the cultivation of PC12 cells, and the results showed an increase in cell viability and proper attachment of cells on the scaffold.
Conclusion: The results of this research showed that the loading of silymarin on polycaprolactan scaffold increases the proliferation and survival of PC12 cells. Therefore, this scaffold can be a suitable candidate for nerve tissue engineering.
 

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Background & objectives: One of the functions of RNA editing is to change the RNA sequence without changing the genomic DNA sequence and changing the fate of cellular RNA. Therefore, studying the clinical application of RNA editing for targeted therapies is necessary.
Methods: All articles related to the subject of the study were searched in the Scopus,
PubMed/Medline, ISI Web of Knowledge, and Google Scholar database.
Results: The changes that occur within the RNA editing are A to I base replacement by adenosine deaminase (ADAR) on RNA and C to U replacement by the apolipoprotein B mRNA-editing enzyme, catalytic polypeptide1 (APOBEC1). Recently, the role of RNA editing in human diseases has been reported.
Conclusion: RNA editing can be used as a new strategy to identify new disease biomarkers and more personalized treatments for various diseases.
 

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Background & objective: The causes of Alzheimer's disease are currently unknown. Genetic and environmental factors can be effective in creating of this disease. In recent studies, one of the genes and its polymorphisms that was known to affect Alzheimer is SHARPIN. This study aimed to investigate the presence of rs34674752 polymorphism in the SHARPIN gene and its relation with Alzheimer's disease in the population of Iranian patients.
Methods: This study was performed on 50 people with Alzheimer's disease and 50 healthy controls. After blood sampling and DNA extraction, genotyping was done by Tetra ARMS PCR. The data was statistically analyzed.
Results: Results showed that the frequency of GG, GT and TT genotypes of rs34674752 polymorphism in control and patient groups was 100%, 0% and 0%, respectively. Both control and patient groups were in Hardy Weinberg equilibrium. There was no significant correlation between people's genotype and the possibility of Alzheimer's disease, and among the demographic factors, only the relationship between age group and the disease was significant (p=0.029).
Conclusion: According to the results of this study, there was no statistically significant association between the rs34674752 polymorphism in the SHARPIN gene and Alzheimer's disease in the studied Iranian population. To confirm the present study results, the investigation of populations with different societies and a larger quantity of samples are recommended.

 

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