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), CCP-positive RA (P=0.01) and RF-positive RA (P=0.01). Consistently, stratification analysis found that significant associations of RA with ATG16L1 rs2241880, rs6758317 polymorphisms were only detected among individuals carrying C/T genotype of the ATG16L2 rs11235604 polymorphism.

Our results indicated that ATG16L1 rs2241880 polymorphism was associated with RA in Chinese population, and provided evidence for genetic interaction between ATG16L1 and ATG16L2 in determing the development of RA, highlighting the involvement of autophagy in the pathogenesis of RA.

Our results indicated that ATG16L1 rs2241880 polymorphism was associated with RA in Chinese population, and provided evidence for genetic interaction between ATG16L1 and ATG16L2 in determing the development of RA, highlighting the involvement of autophagy in the pathogenesis of RA.

B cells play a key role in the pathogenesis of immune thrombocytopenia (ITP) by producing platelet autoantibodies. Accumulating evidence suggest that microRNA (miRNA) is a critical regulator in B cells. The contribution of miRNA to B cell dysfunction in ITP has not been described. The aim of this study was to examine the expression of miRNA let-7b-5p in B cells of ITP patients and investigate its possible association with B cell function in ITP.

The CD19

cells were isolated from peripheral mononuclear cells of ITP patients and healthy controls using immunomagnetic microbeads. B cell survival in vitro was evaluated by cell counting. The level of let-7b-5p was quantified by quantitative PCR. The surface expression of B cell activating factor receptor (BAFF-R) was detected by flow cytometry. The role of let-7b-5p was examined in isolated B cells by transfecting miRNA mimics or inhibitors.

The results showed that let-7b-5p in B cells was elevated, and B cell survival was enhanced in ITP patients compared with healthy controls. BAFF and B cell receptor stimulation can induce the expression of let-7b-5p in vitro. Overexpression of let-7b-5p in B cells enhanced the expression of surface BAFF-R and promoted B cell survival. Moreover, let-7b-5p enhanced the phosphorylation of NF-κB2 p100 and upregulated the expression of survival factor Bcl-xL after BAFF induction.

Let-7b-5p is a pro-survival miRNA in B cells and increased let-7b-5p is associated with enhanced surface BAFF-R in ITP.

Let-7b-5p is a pro-survival miRNA in B cells and increased let-7b-5p is associated with enhanced surface BAFF-R in ITP.Endothelial dysfunction is a typical characteristic of sepsis. Endothelial nitric oxide synthase (eNOS) is important for maintaining endothelial function. Our previous study reported that the NLRP3 inflammasome promoted endothelial dysfunction by enhancing inflammation. However, the effects of NLRP3 on eNOS require further investigation. Therefore, the present study aimed to investigate the role of NLRP3 on eNOS expression levels in cecal ligation and puncture-induced impaired endothelium-dependent vascular relaxation and to determine the protective effects of melatonin. eNOS expression levels were discovered to be downregulated in the mesenteric arteries of sepsis model mice. Inhibiting NLRP3 with 10 mg/ kg MCC950 or inhibiting IL-1β with 100 mg diacerein rescued the eNOS expression and improved endothelium-dependent vascular relaxation. In vitro, IL-1β stimulation downregulated eNOS expression levels in human aortic endothelial cells (HAECs) in a concentration- and time-dependent manner, while pretreatment with 1 µM of the proteasome inhibitor MG132 reversed this effect. In addition, treatment with 10 mg/kg MG132 also prevented the proteolysis of eNOS and improved endothelium-dependent vascular relaxation in vivo. Notably, treatment with 30 mg/kg melatonin downregulated NLRP3 expression levels and decreased IL-1β secretion, subsequently increasing the expression of eNOS and improving endothelium-dependent vascular relaxation. In conclusion, the findings of the present study indicated that the NLRP3/IL-1β axis may impair vasodilation by promoting the proteolysis of eNOS and melatonin may protect against sepsis-induced endothelial relaxation dysfunction by inhibiting the NLRP3/IL-1β axis, suggesting its pharmacological potential in sepsis.

The reduced osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is the typical characteristics of pediatric aplastic anemia (AA) pathogenesis. Subasumstat concentration Long non-coding RNA MEG3 is reported to promote osteogenic differentiation of BMSCs via inducing BMP4 expression.

This study aims to investigate the mechanism of DNMT1/MEG3/BMP4 pathway in osteogenic differentiation of BMSCs in pediatric AA.

BMSCs were isolated and purified from bone marrows of pediatric AA patients (n=5) and non-AA patients (n=5). The expression of DNMT1, MEG3, and BMP4 in isolated BMSCs was detected using quantitative real-time PCR and western blot analysis. Osteogenic differentiation was determined using Alizarin red staining. The methylation of MEG3 promoter and the interaction between DNMT1 and MEG3 promoter were detected using methylation-specific PCR and chromatin immunoprecipitation assay, respectively.

Lowly expressed MEG3 and BMP4 and highly expressed DNMT1 were observed in BMSCs of pediatric AA patients. The overexpression of MEG3 promoted osteogenic differentiation of BMSCs. Luciferase reporter assay showed that MEG3 overexpression increased transcriptional activity of BMP4. The inhibitor of methylation, 5-azacytidine, suppressed DNMT1 expression and reduced methylation of MEG3 promoter. Overexpression of DNMT1 increased the binding between DNMT1 and MEG3 promoter. The simultaneous overexpression of DNMT1 and MEG3 restored the inhibition of osteogenic differentiation caused by DNMT1 overexpression alone.

Our findings indicated that DNMT1 mediated the hypermethylation of MEG3 promoter in BMSCs, and DNMT1/MEG3/BMP4 pathway modulated osteogenic differentiation of BMSCs in pediatric AA.

Our findings indicated that DNMT1 mediated the hypermethylation of MEG3 promoter in BMSCs, and DNMT1/MEG3/BMP4 pathway modulated osteogenic differentiation of BMSCs in pediatric AA.