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Aim: Impaired apoptosis and proliferation resulted in autoreactive lymphocyte development and inflammation in Rheumatoid arthritis (RA). TP53, BAX, FOXO1, and RB1 are related genes in cell survival, proliferation, and inflammation which could be important in RA development and disease severity. Here we investigated their expression in peripheral blood mononuclear cells (PBMCs) from RA patients in comparison to healthy controls. Methods: Fifty healthy controls and 50 RA patients were selected. The quantitative real‐time polymerase chain reaction was used to assess the gene expression level in PBMCs. Results: The mRNA expression of TP53 (FC = 0.65, p =.000), BAX (FC = 0.76, p =.008), FOXO1 (FC = 0.59, p =.000) and RB1 (FC = 0.50, p =.000) were significantly reduced in RA PBMCs. TP53 expression was negatively correlated with miR‐16‐5p (p =.032) and FOXO1 expression was negatively correlated with miR‐335‐5p (p =.005) and miR‐34a‐5p (p =.014). A positive correlation was seen between TP53 expression and its downstream gene, BAX (p =.001). FOXO1 expression was also negatively correlated with disease activity, DAS28 (p =.021). Conclusion: All selected genes have downregulated expression in RA PBMCs which could be correlated with RA pathogenesis by regulating apoptosis, cell survival, inflammatory mediator production, and proliferation. Due to the correlation of miR‐16‐5p, miR‐34a‐5p, and miR‐335‐5p with TP53 and FOXO1 expression in RA PBMCs, they could be used as future therapeutic targets. [ABSTRACT FROM AUTHOR]

Fibroblast-like synoviocytes (FLSs) have been introduced in recent years as a key player in the pathogenesis of rheumatoid arthritis (RA), but the exact mechanisms of their transformation and intracellular pathways have not yet been determined. This study aimed to investigate the role of fibroblast activation protein-alpha (FAP-α) in the regulation of genes involved in the transformation and pathogenic activity of RA FLSs. Synovial FLSs were isolated from RA patients and non-arthritic individuals (n=10 in both groups) and characterized; using immunocytochemistry and flow cytometry analysis. FLSs were divided into un-treated and Talabostat-treated groups to evaluate the FAP-α effect on the selected genes involved in cell cycle regulation (p21, p53, CCND1), apoptosis (Bcl-2, PUMA), and inflammatory and destructive behavior of FLSs (IL-6, TGF-β1, MMP-2, MMP-9, P2RX7). Gene expression analysis was performed by quantitative real-time polymerase chain reaction (qRT-PCR), and immunoblotting was carried out to evaluate FAP-α protein levels. The basal level of FAP-α protein in RA patients was significantly higher than non-arthritic control individuals. However, no differences were observed between RA and non-arthritic FLSs, at the baseline mRNA levels of all the genes. Talabostat treatment significantly reduced FAP-α protein levels in both RA and non-arthritic FLSs, however, had no effect on mRNA expressions except an upregulated TGF-β1 expression in non-arthritic FLSs. A significantly higher protein level of FAP-α in FLSs of RA patients compared with that of healthy individuals may point to the pathogenic role of this protein in RA FLSs. However, more investigations are necessary to address the mechanisms mediating the FAP-α pathogenic role in RA FLSs. [ABSTRACT FROM AUTHOR]

Background: Ankylosing spondylitis (AS) is considered as a subtype of spondyloarthritis (SpA) that mainly leads to fatigue, stiffness, spinal ankylosis, and impaired physical functions with reduced quality of life. Interleukin (IL)-17A provokes additional inflammatory mediators and recruits immune cells to the inflamed site. IL17 expression increased in various inflammatory disorders including psoriasis, rheumatoid arthritis, multiple sclerosis, crohn's disease, and ankylosing spondylitis. The current study aimed to evaluate the association of IL17RA copy number changes with the susceptibility to AS and their correlation to IL17RA expression in Iranian population. Methods: IL17RA copy number genotyping assessments were carried out in 455 AS patients and 450 healthy controls, using custom TaqMan CNV assays. TaqMan primers and probe were located in Chr.22:17109553 based on pre-designed IL17RA Copy Number Assay ID, Hs02339506_cn. mRNA expression of IL17RA was also measured by SYBR Green real-time polymerase chain reaction (PCR). Results: A IL17RA copy number loss (< 2) was associated with AS compared to 2 copies as reference (OR:2.18, 95% CI: (1.38–3.44), P-value < 0.001) and increased the risk of AS. IL17RA mRNA expression showed a significant increase in peripheral blood mononuclear cells (PBMCs) of all AS individuals than controls. The mRNA expression level of 2 copies was significantly higher in AS patients. Conclusions: Our findings revealed that a low copy number of IL17RA might confer a susceptibility risk to AS. However, it is probably not directly involved in the regulation of IL17RA mRNA expression. Epigenetic mechanisms like DNA methylation, post-transcriptional, and -translational modifications that regulate the expression of the genes may contribute in upregulation of IL17RA mRNA expression in the loss of gene copy number condition. [ABSTRACT FROM AUTHOR]

This study has been conducted to evaluate the allele, genotype and haplotype frequencies of the polymorphic gene coding TGF-β in recurrent aphthous stomatitis (RAS). TGF-β gene typing was done by polymerase chain reaction with sequence-specific primers (PCR-SSP) assay. Allele frequencies were estimated by direct gene counting. C allele at codon 25 was significantly increased, while G allele at this position was significantly decreased in patients compared to the controls. A significantly higher frequency of CG genotype at codon 25 was found in control group. CC genotype and TT genotype at codon 10 of the gene was significantly decreased, while CT genotype at the same position was significantly increased in patients, indicating that CT heterozygosity at codon 10 TGF-β is associated with greater risk of RAS. CG and TG haplotypes were significantly decreased while CC and TC haplotypes were significantly increased in patients compared with controls. This study indicates the TGF-β single nucleotide polymorphisms could play a role in RAS pathogenesis. Thereby certain SNPs of TGF-β gene have an association with RAS pathogenesis. © 2017 Tehran University of Medical Sciences. All rights reserved. [ABSTRACT FROM AUTHOR]

Background: In recent years, the confidential unit exclusion (CUE) option has been used to increase blood safety at blood transfusion centers in several countries. The epidemiologic characteristics of diseases and demographic characteristics of patients vary in different countries; therefore, we investigated whether the CUE option is useful in Iran. In this study, we determined the prevalences of hepatitis B virus (HBV) and hepatitis C virus (HCV) in CUE-positive and CUE-negative units, as well as the efficacy of the CUE option. Objectives: The aim of this study was to evaluate the efficacy of the CUE option in reducing the prevalences of HBV and HCV in blood units. Patients and Methods: All donors were tested for the HCV antibody (anti-HCV) and hepatitis B surface antigen (HBsAg). Supplemental tests were performed to confirm the presence of viruses in the units that tested positive. In total, 2000 units (1000 CUE-positive units and 1000 CUE-negative units) were tested using the nucleic acid testing (NAT) method. The prevalence of infectious markers was estimated in all demographic subgroups. Results: The prevalences of HBV and HCV markers were higher in donors who opted for CUE than in those who did not. The CUE option had low sensitivity (21.5%) and positive predictive value (PPV; 20.9%) for the markers. Most of the donors who opted for CUE for the first time were men with low levels of education. Conclusions: The CUE option has low sensitivity and PPV, and its effectiveness in reducing the transmission of infectious diseases through window-period units is minimal. The CUE process can be continued in Iran because Iran is geographically located in a region where HBV is endemic; however, higher levels of education are necessary to make this process effective. [ABSTRACT FROM AUTHOR]

Background: Inflammatory cytokines have been known to be associated with Chronic Heart Failure (CHF). Given the importance of cytokines in the context of the failing heart, the prevalence of Interleukin-2 (IL-2) and Interferon-gamma (IFN-γ) polymorphisms was studied in patients with CHF due to ischemic heart disease in a case-control study. Methods: Fifty-six Iranian patients with CHF were enrolled in this study as the case group and compared with 139 healthy subjects, using polymerase chain reaction with sequence-specific primers method, so as to determine the frequency of alleles, genotypes and haplotypes of IFN-γ (+874 A/T) and IL-2 (-330 G/T, +166 G/T) SNPs. Results: The GG genotype at IL-2 -330 in patients with CHF was significantly over-represented in comparison with the control group (p=0.013). Such a positive genotypic association was also observed for IL-2 +166/TT (p=0.022). Meanwhile, the GT genotype frequency at IL-2 -330/GT in the patient group was significantly lower than the one in healthy controls (p=0.049). No significant association was detected between the IFN-γ gene polymorphisms and individuals' susceptibility to CHF. Conclusion: Certain genotypes in IL-2 gene were overrepresented in patients with CHF, which could render individuals more vulnerable to this disease. [ABSTRACT FROM AUTHOR]

Background: Proinflammatory cytokines have been known to be elevated in patients with Chronic Heart Failure (CHF). Given the importance of proinflammatory cytokines in the context of the failing heart, the prevalence of Tumor Necrosis Factor-α (TNF-α), Interleukin (IL)-6 polymorphisms in patients with CHF was studied due to ischemic heart disease. Methods: Forty three patients with ischemic heart failure were enrolled in this study and compared with 140 healthy individuals. The allele and genotype frequency of four Single Nucleotide Polymorphisms (SNPs) within the IL-6 (-174, nt565) and TNF-α (-308, -238) genes were determined, using Polymerase Chain Reaction with Sequence-Specific Primers (PCR-SSP) assay. Results: The frequency of the TNF-α (-238) A/A genotype was significantly higher in patients comparing to controls (p=0.043), while TNF-α G/A genotype at the same position decreased significantly, in comparison with controls (p=0.018). The most frequent haplotype for TNF-α was A/A in the patient group in comparison with controls (p=0.003). There was no significant difference in allele and genotype frequencies of IL-6 at positions -174 and nt565, and TNF-α at position -308. Conclusion: Certain alleles, genotypes, and haplotypes in TNF-α, but not IL-6, gene were overrepresented in patients with ischemic heart failure, which may, in turn, predispose individuals to this disease. [ABSTRACT FROM AUTHOR]