LINC00926 is involved in hypoxia-induced vascular endothelial cell dysfunction via miR-3194-5p regulating JAK1/STAT3 signaling pathway.

Vascular endothelial cell (VEC) dysfunction is associated with the development of coronary heart disease (CHD). Long intergenic non-protein coding RNA 926 (LINC00926), a kind of long noncoding RNA (lncRNA), has been found to be abnormally expressed in CHD patients. However, the biological role of LINC00926 has not been reported. In our research, we intended to explore the regulatory mechanism of LINC00926 in hypoxia-exposed HUVEC cells (HUVECs). In our in vitro study, HUVECs were exposed under hypoxic conditions (5% O2) for 24 h. RT-qPCR and Western blotting assay were used to detect the mRNA and protein levels. CCK-8 assay, flow cytometry, transwell assay and in vitro angiogenesis assay were performed to measure cell proliferation, apoptosis, migration and tube formation, respectively. Bioinformatics analysis was applied to predict the target of LINC00926 and miR-3194-5p, which was verified by dual-luciferase reporter assays. The results showed that LINC00926 was highly expressed in CHD patients and hypoxia-exposed HUVECs. LINC00926 overexpression suppressed cell proliferation, migration and tube formation and increased cell apoptosis. MiR-3194-5p was a target of LINC00926 and can target binding to JAK1 3'UTR. LINC00926 could up-regulate JAK1 and p-STAT3 levels via miR-3194-5p. In addition, overexpressed LINC00926 suppressed cell proliferation, migration and tube formation and increased cell apoptosis via miR-3194-5p/JAK1/STAT3 axis. In summary, LINC00926 aggravated endothelial cell dysfunction via miR-3194-5p regulating JAK1/STAT3 signaling pathway in hypoxia-exposed HUVECs.

MicroRNA-27a alleviates IL-1ß-induced inflammatory response and articular cartilage degradation via TLR4/NF-κB signaling pathway in articular chondrocytes.

Osteoarthritis (OA) is a common disease of the articular cartilage, and inflammatory response and articular cartilage degradation have been implicated in the pathogenesis of OA. In recent years, microRNAs (miRNAs) have been potentially involved in the pathogenesis of OA. However, little is known about the role of miRNAs in the inflammatory response and articular cartilage degradation in OA and the underlying molecular mechanism. In the present study, we analyze miRNA profiles in the articular tissues from OA patients using microarray. miR-27a has attracted considerable interest for its suppressive effects on inflammation. Subsequently, the expression levels of miR-27a were validated in the articular tissues of OA patients and IL-1ß-stimulated chondrocytes. Using this IL-1ß-induced chondrocyte injury model, we found that upregulation of miR-27a suppressed articular cartilage degradation, the reactive oxygen species (ROS) production and inflammatory response as reflected by reductions in pro-inflammatory cytokines, including interleukin (IL)-6 and IL-8 and tumor necrosis factor (TNF)-α. Moreover, toll-like receptor 4 (TLR4), one upstream molecule of NF-κB signaling pathway, was identified as a direct target of miR-27a in chondrocytes. Furthermore, it was demonstrated that overexpression of TLR4 by pcDNA-TLR4 markedly abrogated the inhibitory effects of miR-27a on the inflammatory response and the degeneration of articular cartilage induced by IL-1ß. Our findings suggest that miR-27a may be considered as a potential therapeutic target in the treatment of OA.

The comparative risk of developing postoperative complications in patients with distal radius fractures following different treatment modalities.

In this study, we performed a network meta-analysis to compare the outcomes of seven most common surgical procedures to fix DRF, including bridging external fixation, non-bridging external fixation, K-wire fixation, plaster fixation, dorsal plating, volar plating, and dorsal and volar plating. Published studies were retrieved through PubMed, Embase and Cochrane Library databases. The database search terms used were the following keywords and MeSH terms: DRF, bridging external fixation, non-bridging external fixation, K-wire fixation, plaster fixation, dorsal plating, volar plating, and dorsal and volar plating. The network meta-analysis was performed to rank the probabilities of postoperative complication risks for the seven surgical modalities in DRF patients. This network meta-analysis included data obtained from a total of 19 RCTs. Our results revealed that compared to DRF patients treated with bridging external fixation, marked differences in pin-track infection (PTI) rate were found in patients treated with plaster fixation, volar plating, and dorsal and volar plating. Cluster analysis showed that plaster fixation is associated with the lowest probability of postoperative complication in DRF patients. Plaster fixation is associated with the lowest risk for postoperative complications in DRF patients, when compared to six other common DRF surgical methods examined.

Involvement of Notch1/Hes signaling pathway in ankylosing spondylitis.

We aimed to investigate the role of Notch1/Hes signaling pathway in the pathogenesis of abnormal ossification of hip ligament in patients with ankylosing spondylitis (AS). 22 AS patients scheduled for artificial hip arthroplasty were randomly chosen as AS group. As controls, we used 4 patients diagnosed with transcervical fracture who underwent hip replacement surgery. Notch1 and Hes mRNA expressions were detected by real-time fluorescent quantitative polymerase chain reaction (RFQ-PCR). Immunohistochemistry (IHC) was used to detect Notch1 and Hes protein expression. Correlation analyses of Notch-l and Hes with AS-related clinical factors were conducted with spearman's correlation analysis and partial correlation analysis. RFQ-PCR results showed significant differences in Notch1 and Hes mRNA expressions between AS group and the control group (all P<0.05). IHC analysis further indicated positive nuclear signals of Notch1 and Hes protein, indicating functional activation of the Notch1 and Hes pathways. Semi-quantitative IHC showed a higher Notch1 and Hes expression levels in AS group compared to the control group (all P<0.05). Correlation analysis suggested that Hes protein expression was positively associated with the clinical course of the disease in AS patients. In conclusion, Notch1 and Hes overexpression was clearly detected in hip joint ligaments of AS patients, Hes protein expression was associated with the clinical course of AS. Taken together, we suggest that signaling pathways mediated by Notch1-Hes may contribute to ligament ossification of hip joints in AS patients.

Role of growth differentiation factor-5 and bone morphogenetic protein type II receptor in the development of lumbar intervertebral disc degeneration.

The present study was designed to evaluate the role of growth differentiation factor-5 (GDF-5) and bone morphogenetic protein type II receptor (BMPR-II) in the development of lumbar intervertebral disc degeneration (IDD). A total of 24 patients with lumbar IDD (experiment group) and 6 patients with lumbar vertebral fracture (control group) were enrolled in the study. Tissue samples of IVD from the experiment group and control group were obtained during lumbar fusion operation, respectively. Fixation and decalcification of IVD tissue were performed, and then HE staining was carried out to observe the morphological changes of the lumbar IVD tissues. The expression of GDF-5 and BMPRII in human lumbar IVD was detected by immunohistochemical staining. HE staining results showed that non- and minimal degeneration was found in 11 cases (score range, 0-3), moderate degeneration in 12 cases (score range, 4-8), and severe degeneration in 7 cases (score range, 9-12). According to the immunohistochemical results, the positive expression rates of GDF-5 and BMPRII in NP were higher than those in AF of the non- and minimal degeneration group, moderate degeneration group and severe degeneration group (all P < 0.05). However, no significant difference in GDF-5 or BMPRII positive expression was observed among the normal, non- and minimal, moderate and severe degeneration groups in neither NP area nor AF area (all P > 0.05). In conclusion, our results showed that GDF-5 and BMPRII expressed both in normal and degenerated IVD tissues, and GDF-5 might have an inhibition effect on degenerated lumbar IVD, suggesting that gene therapy may be a useful approach in producing physiological effects during early- and late-phase of lumbar IDD.