Background Osteoarthritis (OA) is the most common chronic degenerative joint disease and is mainly characterized by cartilage degeneration, subcartilage bone hyperplasia, osteophyte formation and joint space stenosis. Recent studies showed that synovitis might also be an important pathological change of OA. However, the molecular mechanisms of synovitis in OA are still not well understood. Objective This study was designed to identify key biomarkers and immune infiltration in the synovial tissue of osteoarthritis by bioinformatics analysis. Materials and Methods The gene expression profiles of GSE12021, GSE55235 and GSE55457 were downloaded from the GEO database. The differentially expressed genes (DEGs) were identified by the LIMMA package in Bioconductor, and functional enrichment analyses were performed. A protein-protein interaction network (PPI) was constructed, and module analysis was performed using STRING and Cytoscape. The CIBERSORT algorithm was used to analyze the immune infiltration of synovial tissue between OA and normal controls. Results A total of 106 differentially expressed genes, including 68 downregulated genes and 38 upregulated genes, were detected. The PPI network was assessed, and the most significant module containing 14 hub genes was identified. Gene Ontology analysis revealed that the hub genes were significantly enriched in immune cell chemotaxis and cytokine activity. KEGG pathway analysis showed that the hub genes were significantly enriched in the rheumatoid arthritis signaling pathway, IL-17 signaling pathway and cytokine-cytokine receptor interaction signaling pathway. The immune infiltration profiles varied significantly between osteoarthritis and normal controls. Compared with normal tissue, OA synovial tissue contained a higher proportion of memory B cells, naive CD4+ T cells, regulatory T cells, resting dendritic cells and resting mast cells, while naive CD4+ T cells, activated NK cells, activated mast cells and eosinophils contributed to a relatively lower portion (P > 0.05). Finally, the expression levels of 11 hub genes were confirmed by RT-PCR. Conclusion The hub genes and the difference in immune infiltration in synovial tissue between osteoarthritis and normal controls might provide new insight for understanding OA development.

Panax notoginseng saponins (PNS) are active extracts obtained from the P. notoginseng plant. PNS exhibit various anti-inflammatory, anti-oxidant and anti-aging pharmacological properties in some cells. However, the effects of PNS on senescence and apoptosis in chondrocytes have not been studied to date. In the present study, whether PNS could limit tumor necrosis factor (TNF)-α-induced senescence and apoptosis in chondrocytes and whether they could slow down cartilage degeneration in a surgery-induced rat osteoarthritis (OA) model by regulating the phosphatidyl inositol 3 kinase (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) signaling pathway was examined. A potential mechanism underlying these effects was further elucidated. The present in vitro experiments showed that PNS significantly inhibited senescence and apoptosis in OA chondrocytes and prevented a decrease in the mitochondrial membrane potential and excessive mitochondrial permeability. In addition, the expression levels of autophagy-related proteins and the anti-apoptotic protein Bcl-2 were significantly increased in PNS-treated OA chondrocytes, but the expression levels of Bax and caspase-3 were decreased; these effects were concentration-dependent. TNF-α significantly increased the expression of p-PI3K/p-AKT/p-mTOR in OA chondrocytes, whereas PNS reduced PI3K, AKT and mTOR phosphorylation. The results of the in vivo experiments demonstrated that PNS significantly inhibited the PI3K-AKT-mTOR signaling pathway and collagen II degradation, as well as reduced matrix metalloproteinase (MMP)-3 and MMP-13 expression in chondrocytes in a rat OA model, thus attenuating cartilage destruction in OA. The results obtained in the rat model were consistent with the in vitro experimental results. Furthermore, histological analyses and ultrastructural observations confirmed these results. Taken together, the results of the present study demonstrated that PNS may protect osteoarthritic chondrocytes from senescence and apoptosis by inhibiting the PI3K-AKT pathway, thus delaying the degradation of articular cartilage.

Many studies have investigated the association between the allergic conditions and the risk of glioma. However, the evidence is inadequate to draw robust conclusions because most studies were generally small and conducted in heterogeneous populations. To shed light on these inconclusive findings, we conducted a meta-analysis of studies relating the allergic conditions to the risk of glioma. We identified the relevant studies by searching ISI Web of Science, PubMed, EMBASE, Chinese National Knowledge Infrastructure (CNKI) databases, and Wanfang database by October 2013. We included studies that reported odds ratio (OR) or hazard ratio (HR) with its 95% confidence interval (CI) for the association between the allergic condition and the risk of glioma. Eighteen independent publications, with 9,986 glioma cases and 118,950 controls, were included. Our results showed that allergic condition was reversely associated with the risk of glioma (OR = 0.78, 95% CI 0.73-0.83, P < 0.001). The results of our meta-analysis indicated that allergic conditions significantly reduce the risk of glioma.

Retinoic acid could disturb the notochord and tail bud development in the process of primary and secondary neurulation in rat embryos, which cause lumbosacral NTDs including myeloschisis and hamartoma. The morphology is very similar to that happens in humans.

Hypoxia/reoxygenation (H/r) may play an important role via senescence in the mechanism of osteoarthritis (oa) development. The synovial membrane is highly sensitive to H/r due to its oxygen consumption feature. excessive mechanical loads and oxidative stress caused by H/r induce a senescence-associated secretory phenotype (SaSP), which is related to the development of oa. The aim of the present study was to investigate the differences of SaSP manifestation in synovial tissue masses between tissues from healthy controls and patients with oa. The present study used tumor necrosis factor-α (TnF-α) to pre-treat synovial tissue and fibroblast-like synoviocytes (FLS) to observe the effect of inflammatory cytokines on the synovial membrane before H/R. It was determined that H/R increased interleukin (IL)-1β and il-6 expression levels in TnF-α-induced cell culture supernatants, increased the proportion of Sa-β-gal staining, and increased the expression levels of high mobility group box 1, caspase-8, p16, p21, matrix metalloproteinase (MMP)-3 and MMP-13 in the synovium. Furthermore, H/R opened the mitochondrial permeability transition pore, caused the loss of mitochondrial membrane potential (ΔΨm) and increased the release of reactive oxygen species (roS). Moreover, H/r caused the expansion of the mitochondrial matrix and rupture of the mitochondrial extracorporeal membrane, with a decrease in the number of cristae. in addition, H/r induced activation of the JnK signaling pathway in FlS to induce cell senescence. Thus, the present results indicated that H/r may cause inflammation and escalate synovial inflammation induced by TnF-α, which may lead to the pathogenesis of oa by increasing changes in synovial SaSP and activating the JnK signaling pathway. Therefore, further studies expanding on the understanding of the pathogenesis of H/r etiology in oa are required.