A Bioinformatics Study of Immune Infiltration-Associated Genes in Sciatica.

Sciatica has been widely studied, but the association of sciatica with immune infiltration has not been studied. We aimed to screen key genes and to further investigate the impact of immune infiltration in patients with sciatica. The bioinformatics analyzes were performed based on the GSE150408 dataset. Subsequently, we used CIBERSORT to study the immune infiltration in the disease group. Results showed that 13 genes were with differentially expressions in the sciatica group compared to healthy participants, including 8 up-regulated and 5 down-regulated genes. Through the LASSO model and SVM-RFE analysis, a total of 6 genes have intersections, namely SLED1, CHRNB3, BEGAIN, SPTBN2, HRASLS2, and OSR2. The ROC curve area also confirmed the reliability of this method. CIBERPORT analysis showed that T cell gamma delta infiltration decreased and neutrophil infiltration increased in the disease group. Then the association of these six key genes with immune infiltration was further verified. We found six overlapping genes and found that they were closely associated with the total immune infiltration in the sciatic nerve disease group. These findings may provide new ideas for the diagnosis and therapeutics of patients with sciatica.

Piezo1 mediates neuron oxygen-glucose deprivation/reoxygenation injury via Ca2+/calpain signaling.

OBJECTIVE: We investigated whether Piezo1 could regulate oxygen-glucose deprivation/reoxygenation injury of neurons through Ca2+/calpain signaling. METHODS: Piezo1 expression in rat brain cortex and PC12 cells were confirmed by immunohistochemistry, immunofluorescence and Western blotting. The effects of Yoda1 and GsMTx4 on OGD/R-induced decrease in cell viability, increase in cell apoptosis and activation of downstreaming Ca2+/calpain signaling were investigated. Furthermore, calpain signaling was inhibited by PD151746 to see whether Ca2+/calpain signaling participated in the neurotoxic effects of Piezo1 activation. RESULTS: Piezo1 expression was increased in rat cerebral cortex after ischemia/reperfusion and in PC12 cells after OGD/R. Activation of Piezo1 by Yoda1 enhanced OGD/R-induced cell viability inhibition, apoptosis, increase intracellular calcium levels and enhanced calpain activity while GsMTx4 showed the opposite effects. The effects of Piezo1 activation on cell viability and apoptosis were reversed by PD151746. CONCLUSION: Piezo1 could regulate neuron oxygen-glucose deprivation/reoxygenation injury via activation of Ca2+/calpain signaling.