Mecobalamin, a form of vitamin B12 containing a central metal element (cobalt), is one of the most important mediators of nervous system function. In the clinic, it is often used to accelerate recovery of peripheral nerves, but its molecular mechanism remains unclear. In the present study, we performed sciatic nerve crush injury in mice, followed by daily intraperitoneal administration of mecobalamin (65 μg/kg or 130 μg/kg) or saline (negative control). Walking track analysis, histomorphological examination, and quantitative real-time PCR showed that mecobalamin significantly improved functional recovery of the sciatic nerve, thickened the myelin sheath in myelinated nerve fibers, and increased the cross-sectional area of target muscle cells. Furthermore, mecobalamin upregulated mRNA expression of growth associated protein 43 in nerve tissue ipsilateral to the injury, and of neurotrophic factors (nerve growth factor, brain-derived nerve growth factor and ciliary neurotrophic factor) in the L4–6 dorsal root ganglia. Our findings indicate that the molecular mechanism underlying the therapeutic effect of mecobalamin after sciatic nerve injury involves the upregulation of multiple neurotrophic factor genes.

Background Osteosarcoma (OS) is the most common primary bone malignancy. It has an aggressive nature and produces drug resistance in diseased patients, which in turn causes obstacles in treating cancer with chemotherapy. The objective of our investigation was to analyze the function and hsa_circ_0010220 mechanism in doxorubicin (DOX) resistance to OS. Methods The hsa_circ_0010220, IL-6, and miR-574-3p levels in OS diseased tissues and cell resistance towards DOX drug were elucidated by qRT-PCR and Elisa assay. The DOX half-inhibitory concentration (IC50) was quantified by Cell Counting Kit-8. For this study, we used RNA pull-down, RNA immunoprecipitation, and a dual-luciferase reporter experiment to identify the proteins that interacted with has_circ_0010220, IL-6, and miR-574-3p in OS cells that have developed resistance towards DOX. Results The results indicated upregulated Hsa_circ_0010220 and IL-6 expression, However, DOX-resistant OS tissues and cells showed a downregulation of miR-574-3p. Reducing DOX resistance in vitro was achieved by silencing Has_circ_0010220. Further, by sponging miR-574-3p, increasing has_circ_0010220 boosted DOX resistance. However, miR-574-3p bound to IL-6 and inhibited DOX resistance. Additionally, it was discovered that hsa_circ_0010220 sponged miR-574-3p for upregulating IL-6 expression. Conclusions Hsa_circ_0010220 encouraged OS resistance to DOX by miR-574-3p/IL-6 axis regulation, suggesting its potency as a promising biomarker for treating OS.

Background: The most common joint illness is osteoarthritis (OA). The goal of this work was to find changes in gene signatures between normal knee joints and OA tissue samples and look for prospective gene targets for OA. Methods: The gene expression profiles of GSE12021, GSE51588, and GSE55457 were downloaded from Gene Expression Omnibus (GEO). Total 64 samples (40 OA and 24 standard control samples) were used. The limma program was used to find differentially expressed genes (DEGs) in OA versus NC. Functional annotation and protein-protein interaction (PPI) network construction of OA-specific DEGs were performed. Finally, the candidate drugs and herbs as potential drugs to treat OA were predicted in the DGIdb and TCMIO databases. Results: 19 upregulated and 27 downregulated DEGs between OA and NC samples. DEGs such as PTN, COMP, NELL1 and MN1 have shown a significant correlation with OA and are expected to become new biomarkers. Cellular senescence,Positive regulation of ossification and Vascular endothelial growth factor (VEGF) were significantly enriched for OA‐specific DEGs.In cell composition analysis, DEGs were also found to be highly enriched in the cytosol.We have identified a total of 68 types of drugs or molecular compounds that are promising to reverse OA-related DEGs.Honeycomb and cinnamon oil have the possibility of treating OA. Conclusion: Our findings suggest new biomarkers that can be used to diagnose OA. Furthermore, we tried to find drugs and traditional Chinese medicine that may improve the progress of OA. This research may improve the identification and treatment of these uncontrollable chronic diseases.