No abstract

Resveratrol (RSV) has beneficial effects on renal diseases, but its underlying mechanisms are still unclear. In the present study, we investigate the renoprotective effects of RSV on obesity-related renal diseases and clarify the potential mechanisms. Male C57BL/6J mice were fed with high-fat diet (HFD) with or without 400 mg/kg RSV treatment for 12 weeks. Feeding HFD induced renal injuries, but treating them with RSV significantly decreased glomerular volume (p < 0.05), glycogen (p < 0.01) and collagen (p < 0.05) in renal tissues. Although slightly changed body weight and fasting blood glucose, RSV attenuated renal dysfunction, including decreased levels of blood urea nitrogen (p < 0.05), urea protein (p < 0.01), and microalbuminuria (p < 0.01). Furthermore, RSV treatment markedly reduced gene expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and inducible nitric oxide synthase (iNOS) (all p < 0.05), 4-Hydroxynonenal expression (p < 0.01), and lipid accumulation. Mechanistically, RSV enhanced the expression of lipolytic genes, peroxisome proliferator-activated receptor (PPAR)-α (p < 0.001), carnitine palmitoyltransferase (CPT)-1 (p < 0.05), and medium-chain acyl-coenzyme A dehydrogenase (MCAD) (p < 0.01), but had no effect on lipogenic genes, PPAR-γ and sterol regulatory element-binding protein (SREBP)-1c. RSV also obviously increased renal PPAR-α protein expression (p < 0.001) and the phosphorylation of AMPK level. Collectively, these results support the therapeutic effects of RSV on high-fat diet-induced renal damages at least partially through targeting on PPAR-α signaling pathway.

Primary Sjögren’s syndrome (pSS) is a chronic systemic autoimmune disease characterized by exocrine gland damage and extraglandular involvements. To identify potential biomarkers for the early detection of pSS and to further investigate the potential roles of the biomarkers in the progression of pSS, our previous RNA sequencing data and four microarray data of salivary glands (SGs) were combined for integrative transcriptome analysis between pSS and non-pSS. Differential gene expression analysis, gene co-expression network analysis, and pathway analysis were conducted to detect hub genes, which were subsequently investigated in peripheral blood mononuclear cell (PBMC) and plasma. Correlation analysis, single-gene Gene Set Enrichment Analysis, and receiver operating characteristic (ROC) curve were applied to investigate the potential function of the hub genes and their classification capacity for pSS. A total of 51 common up-regulated genes were identified among different pSS cohorts. A key module was found to be the most closely linked to pSS, which was significantly associated with inflammation-related pathways. Seven overlapped hub genes (ICOS, SELL, CR2, BANK1, MS4A1, ZC3H12D, and CCR7) were identified, among which ICOS was demonstrated to be involved in most crucial immune pathways. ICOS was up-regulated not only in SGs but also in PBMC and plasma in pSS, and the expression of ICOS was closely associated with lymphocytic infiltration in SGs and disease activity of pSS patients. It showed a strong classification capacity with classic clinical index in SGs (ROC curve 0.9821) and significant distinct discrimination in PBMC (ROC curve 0.9107). These findings are expected to gain a further insight into the pathogenesis of pSS and provide a promising candidate for the early detection of pSS.

Background: Growing data have indicated that broblast-like synoviocytes (FLS) and miRNAs are implicated in the pathogenesis of rheumatoid arthritis (RA). This study was aimed to evaluate the function of miR-6089 in the regulation of RA-FLSs. Methods: The expression of miR-6089 was measured by quantitative real time PCR (qRT-PCR). The RA-FLSs were transfected with si-CCR4 plasmids or miR-6089 mimic, and subjected to CCK-8 and ow cytometry to analyze proliferation and apoptosis. The concentrations of MMP-1, TNF-α and IL-6 in RA-FLSs supernatant were detected using ELISA. The protein expression of caspase-3,-8 and-9 was detected using western blot. Results: The levels of miR-6089 were detected to be signi cantly lower in the synovial tissues and FLSs of RA than in the synovial tissues and FLSs of healthy controls. The miR-6089 up-regulation in RA-FLSs signi cantly inhibited the proliferation and promoted cell apoptosis accompany with an increase protein expression of caspase-3,-8 and-9. Furthermore, CCR4 was determined to directly target miR-6089, and its expression was signi cantly increased in the synovial tissues of RA than in the synovial tissues of healthy controls. Moreover, CCR4 overexpression effectively reversed the effect on proliferation and apoptosis induced by miR-6089 in RA-FLSs. Conclusion: Our results revealed that miR-6089 may be a potential target for RA prevention and therapy of RA.

Rheumatoid arthritis (RA) is an autoimmune disease, associated with chronic inflammation and the imbalance of Th17/Treg. Stanniocalcin‐1 (STC‐1), a glycoprotein, was found to have anti‐inflammatory, anti‐oxidative stress and anti‐apoptosis properties. The present study aimed to investigate the immunomodulatory effect of STC‐1 and its potential value in the treatment of RA. Here, a mouse model of collagen‐induced arthritis (CIA) was established. Then body weight, joint erythema and swelling were measured in CIA mice with or without STC‐1 treatment. Haematoxylin and eosin (H and E) staining was performed to determine histopathological change. Moreover, the percentage of Th17 and Treg cells in the spleen and inguinal lymph nodes (ILNs) and the culture supernatant in polarizing conditions were examined by flow cytometry. Cytokines in serum were detected by ELISA. As a result, the arthritis score, histologic inflammation and cartilage destruction were decreased in CIA mice treated with STC‐1. STC‐1 increased the level of transforming growth factor‐β and inhibited the expression of interleukin‐17. In CIA mice, the percentage of CD4+IL‐17A+ cells in the spleen and ILNs were decreased after STC‐1 treatment, while the level of CD4+Foxp3+ cells did not change significantly. In vitro, STC‐1 inhibited Th17 cell differentiation and STAT3 phosphorylation in CD4+ T cells under Th17 cell‐polarizing conditions. Collectively, the results demonstrated that STC‐1 alleviated RA by inhibiting Th17 cell differentiation through regulating STAT3 phosphorylation. STC‐1 may be a potential drug for the treatment of RA.