Background DNA repair pathways, cell cycle arrest checkpoints, and cell death induction are present in cells to process DNA damage and prevent genomic instability caused by various extrinsic and intrinsic ionizing factors. Mutations in the genes involved in these pathways enhances the ionizing radiation sensitivity, reduces the individual’s capacity to repair DNA damages, and subsequently increases susceptibility to tumorigenesis. Body BRCA1 and BRCA2 are two highly penetrant genes involved in the inherited breast cancer and contribute to different DNA damage pathways and cell cycle and apoptosis cascades. Mutations in these genes have been associated with hypersensitivity and genetic instability as well as manifesting severe radiotherapy complications in breast cancer patients. The genomic instability and DNA repair capacity of breast cancer patients with BRCA1/2 mutations have been analyzed in different studies using a variety of assays, including micronucleus assay, comet assay, chromosomal assay, colony-forming assay, γ -H2AX and 53BP1 biomarkers, and fluorescence in situ hybridization. The majority of studies confirmed the enhanced spontaneous & radiation-induced radiosensitivity of breast cancer patients compared to healthy controls. Using G2 micronucleus assay and G2 chromosomal assay, most studies have reported the lymphocyte of healthy carriers with BRCA1 mutation are hypersensitive to invitro ionizing radiation compared to non-carriers without a history of breast cancer. However, it seems this approach is not likely to be useful to distinguish the BRCA carriers from non-carrier with familial history of breast cancer. Conclusion In overall, breast cancer patients are more radiosensitive compared to healthy control; however, inconsistent results exist about the ability of current radiosensitive techniques in screening BRCA1/2 carriers or those susceptible to radiotherapy complications. Therefore, developing further radiosensitivity assay is still warranted to evaluate the DNA repair capacity of individuals with BRCA1/2 mutations and serve as a predictive factor for increased risk of cancer mainly in the relatives of breast cancer patients. Moreover, it can provide more evidence about who is susceptible to manifest severe complication after radiotherapy.

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 (qRTPCR), 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 FAPα 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.

Systemic sclerosis (SSc, scleroderma) is a multisystemic chronic autoimmune connective tissue disorder characterized by extensive fibrosis, vascular abnormalities, and immune dysfunction [1]. The exact etiopathogenesis of SSc remains unknown, although in genetically susceptible individuals, environamental triggers and dysregulated epigenetic changes contribute to the development of SSc [2]. Systemic sclerosis is more prevalent in black people; however, it is found in all racial groups and all geographic regions [3]. A serological hallmark of systemic sclerosis is the presence of serum autoantibodies against various intracellular antigens. Autoantibodies have been observed at first diagnosis in more than 95% of patients affected with systemic sclerosis [4]. Each of the autoantibodies is beneficial in the diagnosis of affected patients. Different autoantibodies have been associated with different disease subtypes and with differences in disease severity, including the extent of skin involvement, internal organ manifestations, as well as determining the prognosis [5]. All of these antibodies are directed against structures within the nucleus of the cell and, thus, are ANAs. Some ANAs, including ACA, ATA/anti-Scl-70 antibody, antifibrillarin/anti-U3-ribonucleoprotein (AFA), anti-PM/Scl antibody, anti-Th/To antibody, and anti-RNAP III are found in the sera of systemic sclerosis patients [4]. Original Article Open Access Systemic sclerosis is an autoimmune disease clinically characterized by vascular and immune dysfunction, leading to fibrosis that can damage multiple organs. The presence of non-overlapping SSc-associated autoantibodies best presents the autoimmune nature of systemic sclerosis. The primary purpose of this study was to investigate the autoantibody profile in Iranian patients with systemic sclerosis. Sera from 481 patients with systemic sclerosis were collected from 2013 to 2016. Levels of anti-nuclear antibodies (ANA) were quantitatively detected using the indirect immunofluorescence (IIF) method, and levels of specific autoantibodies including anti-topoisomerase I antibody (ATA), anti-centromere antibody (ACA) and anti RNA polymerase III antibody (anti-RNAP III) were determined qualitatively using the enzyme-linked immunosorbent assay (ELISA) technique. Among all patients evaluated, a predominance of females (86.7%) was found, and 434 (90.2%) patients showed positive ANA results by IIF. ANA was detected in 87.3% and 92.0% of limited cutaneous systemic sclerosis (lcSSc) and diffuse cutaneous systemic sclerosis (dcSSc) patients, respectively, which was not significantly different. The frequency of anti-RNAP III, ACA, and ATA was 5.19%, 6.09%, and 72.3%, respectively. Furthermore, anti-RNAP III, ATA, and ANA levels were correlated with dcSSc, whereas ACA levels were correlated with lcSSc. It was confirmed that ATA expression is significantly higher in dcSSc patients. This study had a lower frequency of ACA (6.09%) than most previous cohorts. The results demonstrated that the clinical subtype of systemic s...

Background: Mesenchymal stem cells (MSCs) with immunoregulatory properties affect immune systems.Many studies showed that antioxidants such as vitamin E (Vit E) and selenium (Se) could improve stem cells survival. This study aims to investigate the effects of MSC conditioned media (CM) treated with Vit E and Se on immune cells. Methods: MSCs were isolated and cultured with Vit E and Se. Immature dendritic cells (DCs) and peripheral blood mononuclear cells (PBMCs) were cultured with MSC CM treated with Vit E and Se. The expression of HLA-DR, CD86, CD40, and CD83 on mature DC were evaluated. DC supernatant and PBMCs supernatant was collected for the study of TGF-β, IL-10, and IL-12. PBMCs evaluated for the expression of T-bet, GATA3, RORγt, and FOXP3. Results: MSC CM increased CD40 on myeloid DC (mDC). CD40 has been decreased in DC treated with MSC (Vit E) and MSC (Se) CM. HLA-DR expression on DCs and IL-12 level were significantly reduced in MSC (Vit E) CM. IL-10 concentration increased in DCs treated with MSC (Vit E) and MSC (Se) CM. Treatment of PBMCs with MSC CM decreased IL-10 level, FOXP3, and RORγt expression. On the other hand, the MSC (Vit E) CM and MSC (Se) CM decreased the IL-10 level and increased IL-12, T-bet, and RORγt.Conclusions: According to the results, the treatment of MSC with Vit E and Se enhanced the ability of MSCs to inhibit DCs and improved immunomodulatory effects. Concerning the effect of MSC on PBMC, it seems that it increased RORγt expression through monocytes.