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Multiple sclerosis (MS) is one of the most prevalent autoimmune diseases, which involves the central nervous system. In this illness, Treg/Th17 cell imbalance causes the defect. Several studies revealed that T helper 17 (Th17) cells play a crucial role in pathogenesis, inflammation, and autoimmunity of several autoimmune diseases such as MS. In the present study, we assessed transcript levels of miR-27a and miR-214, in purified CD4 T cells of MS patients, during relapsing and remitting phases in inducing differentiation of T naïve cells to Th17 cells. Forty RR-MS patient samples including those in relapsing ( n = 20) and remitting ( n = 20) phases were participated in this study. In addition, transcript levels of IL-17A, RORγt, IL-23R, Foxp3, and TGF-β in purified CD4 T cells of patients in relapsing and remitting phases of RRMS patients were compared to healthy controls. Expression levels of miR-27a and miR-214 were measured by RT-qPCR and compared to healthy control group ( n = 10). Data indicated upregulation of miR27a in relapsing phase of multiple sclerosis compared to remitting phase and healthy volunteers while miR-214 downregulated in relapsing phase of MS compared to remitting phase and healthy volunteers. In silico studies demonstrated pathways which miR-27a and miR-214 could effect on CD4 T cell lineage fate including TGF-β and mTOR signaling, respectively. Our data suggest that miR-27a may probably inhibit negative regulators of Th17 cell differentiation, thus promoting its differentiation while miR-214 has an adverse effect. [ABSTRACT FROM AUTHOR]

Background: Heat shock protein A2 (HSPA2) is correlated with sperm maturity and function. Therefore, dysfunctional expression of this gene results in abnormal spermatogenesis. On the other hand, DNA damage in spermatozoa is considered to be an important cause of male infertility, and the presence of sperm with DNA fragmentation and chromatin abnormalities in human ejaculates is well documented, in particular in men with poor semen quality. Therefore, the aim of this study is to evaluate HSPA2 expression and its relation with DNA fragmentation, protamine deficiency involved in DNA packaging and semen parameters in varicocele patients in comparison to fertile men before and after varicocelectomy. Materials and Methods: This study included 52 fertile individuals as the control group and 70 infertile individuals with varicocele as the experimental group. Sperm DNA fragmentation, protamine deficiency and relative HSPA2 expression were evaluated by the sperm chromatin dispersion test, chromomycin A3 staining and RT-PCR, respectively. Results: The mean values of abnormal morphology, protamine deficiency and DNA fragmentation were significantly lower in varicocele individuals following varicocelectomy when compared to fertile individuals. The correlation between these parameters were studied and discussed in the text. Conclusion: There is a decrease in relative HSPA2 expression which is possibly due to chronic induced hyperthermia in varicocele individuals. Removal of this stress increases HSPA2 expression and results in the proper folding of proteins involved in spermatogenesis; therefore resulting in improved DNA packaging, as well as better sperm morphology and motility which may indirectly reduce sperm DNA fragmentation. [ABSTRACT FROM AUTHOR]

Objective: MicroRNAs (miRNA) are a class of non-coding RNAs which play key roles in post-transcriptional gene regulation. Previous studies indicate that miRNAs are dysregulated in patients with multiple sclerosis (MS). Th17 and regulatory T (Treg) cells are two subsets of CD4+ T-cells which have critical functions in the onset and progression of MS. The current study seeks to distinguish fluctuations in expression of CD4+ T-cell derived miR-223 during the relapsing-remitting (RR) phase of MS (RR-MS), as well as the expressions of Th17 and Treg cell markers. Materials and Methods: This experimental study used real-time quantitative polymerase chain reaction (qRT-PCR) to evaluate CD4+ T cell derived miR-223 expression patterns in patients that experienced either of the RR-MS phases (n=40) compared to healthy controls (n=12), along with RNA markers for Th17 and Treg cells. We conducted flow cytometry analyses of forkhead box P3 (FOXP3) and RAR-related orphan receptor γt (RORγt) in CD4+ T-cells. Putative and validated targets of miR-223 were investigated in the miRWalk and miRTarBase databases, respectively. Results: miR-223 significantly upregulated in CD4+ T-cells during the relapsing phase of RR-MS compared to the remitting phase (P=0.000) and healthy individuals (P=0.036). Expression of RORγt, a master transcription factor of Th17, upregulated in the relapsing phase, whereas FOXP3 upregulated in the remitting phase. Additionally, potential targets of miR-223, STAT1, FORKHEAD BOX O (FOXO1) and FOXO3 were predicted by in silico studies. Conclusion: miR-223 may have a potential role in MS progression. Therefore, suppression of miR-223 can be proposed as an appropriate approach to control progression of the relapsing phase of MS. [ABSTRACT FROM AUTHOR]