Investigation on the molecular mechanism of SPA interference with osteogenic differentiation of bone marrow mesenchymal stem cells.

Binding of Staphylococcus aureus protein A (SPA) to osteoblasts induces apoptosis and inhibits bone formation. Bone marrow-derived mesenchymal stem cells (BMSCs) have the ability to differentiate into bone, fat and cartilage. Therefore, it was important to analyze the molecular mechanism of SPA on osteogenic differentiation. We introduced transcript sequence data to screen out differentially expressed genes (DEGs) related to SPA-interfered BMSC. Protein-protein interaction (PPI) network of DEGs was established to screen biomarkers associated with SPA-interfered BMSC. Receiver operating characteristic (ROC) curve was plotted to evaluate the ability of biomarkers to discriminate between two groups of samples. Finally, we performed GSEA and regulatory analysis based on biomarkers. We identified 321 DEGs. Subsequently, 6 biomarkers (Cenpf, Kntc1, Nek2, Asf1b, Troap and Kif14) were identified by hubba algorithm in PPI. ROC analysis showed that six biomarkers could clearly discriminate between normal differentiated and SPA-interfered BMSC. Moreover, we found that these biomarkers were mainly enriched in the pyrimidine metabolism pathway. We also constructed '71 circRNAs-14 miRNAs-5 mRNAs' and '10 lncRNAs-5 miRNAs-2 mRNAs' networks. Kntc1 and Asf1b genes were associated with rno-miR-3571. Nek2 and Asf1b genes were associated with rno-miR-497-5p. Finally, we found significantly lower expression of six biomarkers in the SPA-interfered group compared to the normal group by RT-qPCR. Overall, we obtained 6 biomarkers (Cenpf, Kntc1, Nek2, Asf1b, Troap, and Kif14) related to SPA-interfered BMSC, which provided a theoretical basis to explore the key factors of SPA affecting osteogenic differentiation.

Augmented Microfracture Technique Versus Microfracture in Talar Cartilage Restoration: A Systematic Review and Meta-Analysis.

The aim of this meta-analysis was to compare the efficacy and safety between the microfracture (MFx) and augmented microfracture (MFx+) techniques for articular cartilage defects of the talus (OLTs). PubMed and EMBASE were searched from January 1950 to October 2020. Only randomized controlled trials, quasi-randomized controlled trials, and observational studies (retrospective and prospective) applying MFx and MFx+ techniques to treat talar cartilage defects were selected. Ten trials with 492 patients were included. There was significant difference in final American Orthopaedic Foot & Ankle Society score (AOFAS) (mean difference [MD] = 7.07; 95% confidence interval [CI], 3.70-10.44; p < .01), AOFAS change (MD = 7.97; 95% CI, 4.27-11.66; p < .01), visual analog scale (VAS) change score (MD = 0.44; 95% CI, 0.29-0.59; p < .01), Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score (MD = 12.51; 95% CI, 7.16-17.86; p < .01), complication (RR = 0.33; 95% CI, 0.16-0.69; p < .01), and revision (Relative risk = 0.34; 95% CI, 0.15-0.77; p < .05), between the MFx and MFx+ groups. No significant difference was observed for final VAS pain score (MD = -0.53; 95% CI, -1.2 to 1.05; p = .13) and Tegner scale (MD = 0.31; 95% CI, -1.05 to 1.66; p = .66) in either group. Our results suggest that augmented microfracture is superior to microfracture alone in the treatment of talar OLTs based on the AOFAS, MOCART, VAS score, complication rate, and revision ratio. Therefore, microfracture with augmentation should be considered as a treatment for OLTs of talus. However, more randomized trials are still required to determine the long-term superiority of MFx+.

Functional polymorphism rs3783553 in the 3'-untranslated region of IL-1A increased the risk of ischemic stroke: A case-control study.

Accumulating evidence indicates interleukin-1 (IL-1) is a critical mediator of inflammatory responses in ischemic stroke (IS). The aim of this study was to investigate whether rs3783553 in the 3'-untranslated region of IL-1A was associated with the risk of IS. In this hospital-based case-control study, we genotyped the rs3783553 using polymerase chain reaction in 316 patients with IS and 332 age, sex, and ethnicity-matched controls. Plasma level of IL-1α was measured by enzyme-linked immunosorbent assay. The relative luciferase activities were measured by the Dual Luciferase assay system. The presence of ins/ins genotype was associated with higher odds ratios (ORs) of IS compared with del/del genotype (ins/ins vs del/del: adjusted OR 1.77, 95% confidence interval [CI] 1.06-2.98; recessive model: adjusted OR 1.69, 95% CI 1.06-2.70). The higher risk of IS was also observed in allele comparison (adjusted OR 1.29, 95% CI 1.00-1.65). Multivariate logistic regression analysis showed that age, hypertension, total cholesterol, triglyceride, low-density lipoprotein, and rs3783553ins/ins genotypes were independent risk factors for IS. Plasma level of IL-1α was higher among IS patients compared with controls (P = .03). Notably, IS patients with the TTCA/TTCA genotype had a higher level of IL-1α compared with those with the del/del genotype (P = .01). Luciferase reporter assay showed that the vector containing the TTCA del allele exhibited a reduced transcriptional activity in the presence of miR-122 and miR-378. These findings indicate that IL-1A rs3783553 ins/ins genotype may increase the susceptibility to IS, possibly by interrupting the binding site of miR-122 and miR-378.