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Background & objectives: Nuclear Factor kappa B (NF-κB), a master switch transcription factor, plays a critical role in the progression and development of hyperglycemia-induced microangiopathy. Hyperglycemia activates NF-κB, and subsequently increases pro-inflammatory cytokines such as TNF-α, IL-6 and IL-1β leading to development of inflammation. Some new studies have revealed the involvement of microRNA-146a (miR-146a) in the pathogenesis of diabetic complications through an NF-κB-dependent negative feedback loop manner. Despite numerous reports indicating changes of plasma miR-146a during hyperglycemia, the origin of this change remains unclear. This study was designed to evaluate the role of NF-κB on the miR-146a gene expression level in human umbilical vein endothelial cells (HUVECs) during a hyperglycemic condition.
Methods: HUVECs were cultured in normal glucose (5 mmol/L), and hyperglycemic (25 mmol/L) endothelial cell growth medium in the six well plates for 24 h. JSH-23 (30 μmol/L), as an inhibitor of NF-κB translocation to the nucleus, was added to the culture medium, 30 min before induction of hyperglycemia. Quantitative Real Time PCR was performed to measure the expression levels of miR-146a and mRNA NF-κB. NF-κB activity was measured by Elisa.
Results: Hyperglycemia markedly increased the NF-κB activity and mRNA level in HUVECs. The expression of miR-146a significantly increased in hyperglycemic group compared to the normoglycemic group. On the other hand, JSH-23 prevented from miR-146a increment in hyperglycemic group and also it increased the mRNA expression level of NF-κB in this group.
Conclusion: This result shows that NF-κB increases the gene expression of miRNA-146a in the early phase of hyperglycemia in HUVECs.
 

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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: 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: Evidence suggests that microRNAs (miRNAs) are essential for immune cell differentiation and function. In addition, miRNAs play an essential role in regulating the expression of pro-inflammatory genes in neurons. Therefore, we investigated the relationship between miRNA expression and inflammatory markers in the CSF of patients with multiple sclerosis.
Methods: RT-PCR analysis was performed on CSF samples from patients with multiple sclerosis (MS) and a control group to measure the expression level of miRNA-21, miRNA-155, miRNA-182, and miRNA-437. In addition, the levels of the inflammatory cytokines including IL-1β, IL-6, and TNF-α in CSF were measured using ELISA. A quantitative turbidimetric method was also used to measure high-sensitivity C-reactive protein (hs-CRP).
Results: A significant difference was found in the expression level of miRNAs and inflammatory factors in the CSF of patients with MS compared with the control group (p<0.05). The results of receiver operating characteristic (ROC) analysis showed the area under the curve for miRNA-21 (AUC=0.97, p<0.0001), miRNA-182 (AUC=0.97, p<0.0001), and miRNA-155 (AUC=0.96, p<0.0001). The miRNA-155 level in CSF played a very important role in the accurate diagnosis of MS. Significant correlations were found between inflammatory cytokines and miRNA-21, miRNA-155, and miRNA-182, as well as an indirect and moderate correlation between miRNA-437 and hs-CRP.
Conclusion: In MS patients, CSF levels of IL-1, IL-6, TNF-α, hs-CRP, and selected miRNAs can be used as biomarkers of CNS inflammation and neurodegenerative processes.