Background Peripheral nerve injury (PNI) causes motor and sensory defects, has strong impact on life quality and still has no effective therapy. Miconazole is one of the most widely used antifungal drugs; the aims of the study were to investigate the effects of miconazole during sciatic nerve regeneration in a mouse model of sciatic nerve crush injury. Methods We established peripheral nerve crush model and investigated the effects of miconazole by multiple aspects. We further studied the potential mechanism of action of miconazole by Western blotting, fluorescence immunohistochemistry, and PCR analysis. Results Miconazole improves the symptoms of crushed nerve by improving inflammatory cell infiltration and demyelinating myelin of sciatic nerve. Affected by miconazole, the proportion of inflammatory M1 macrophages in the distal part of the sciatic nerve was reduced, and the proportion of anti‐inflammatory M2 macrophages was increased. Finally, the neuroprotective properties of miconazole may be regulated by the nuclear factor (NF)‐κB pathway. Conclusions Our data suggest that miconazole can effectively alleviate PNI, and the mechanism involves mediating a phenotype change of M1/ M2 macrophages. Thus, miconazole may represent a potential therapeutic intervention for nerve crush injury.

The aim of this study was to investigate the potential mechanisms of long noncoding (lnc) RNA Just proximal to X-inactive specific transcript (JPX) in interleukin (IL)-1β-stimulated chondrocytes. Human C28/I2 chondrocytes were treated with IL-1β to simulate osteoarthritic (OA) injury. The expression levels of JPX, microRNA (miRNA/miR)-25-3p, and peptidylprolyl isomerase D (PPID) were measured using reverse transcription-quantitative PCR or western blotting. The IL-1β-stimulated injury was assessed using a Cell Counting Kit-8 assay, flow cytometry, and western blot analysis. The targeted relationship between miR-25-3p, JPX, and PPID was verified using a dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. The results showed that JPX expression was upregulated in OA patients and IL-1β-stimulated chondrocytes. JPX knockdown enhanced cell viability and suppressed apoptosis of IL-1β-stimulated chondrocytes. miR-25-3p inhibition rescued the inhibitory effect of JPX knockdown on IL-1β-stimulated injury. PPID overexpression eliminated the effects of JPX knockdown on IL-1β-stimulated chondrocytes. In conclusion, JPX knockdown increased cell viability and reduced apoptosis in IL-1β-stimulated chondrocytes, and this involved modulation of a miR-25-3p/PPID axis.

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