Propose:To investigate the molecular mechanisms underlying the protective effects of ischemic pre-conditioning(IPC)in patients undergoing total knee arthroplasty.Methods:GSE21164 was extracted from an online database,...Propose:To investigate the molecular mechanisms underlying the protective effects of ischemic pre-conditioning(IPC)in patients undergoing total knee arthroplasty.Methods:GSE21164 was extracted from an online database,followed by an investigation of differentiallyexpressed genes(DEGs)between IPC treatment samples at 2 time points(T0T and T1T).Function andpathway enrichment analyses were performed on the DEGs.A protein-protein interaction network wasconstructed to identify hub genes according to 5 different algorithms,followed by enrichment analysis.In addition,long noncoding RNAs(lncRNAs)were identified between the T0T and T1T samples.Furthermore,a competing endogenous RNA network was predicted based on the identified lncRNA-messenger RNA(mRNA),lncRNA-microRNA(miRNA),and mRNA-miRNA relationships revealed in thisstudy.Finally,a drug-gene network was investigated.Statistical analyses were performed usingGraphPad Prism 8.0.Differences between groups were determined using an unpaired t-test.p<0.05 wasconsidered significant.Results:A total of 343 DEGs at T0 and 10 DEGs at T1 were identified and compared with their respectivecontrol groups,followed by 100 DEGs between T0T and T1T.Based on these 100 DEGs,protein-proteininteraction network analysis revealed 9 hub genes,mainly with mitochondria-related functions andthe carbon metabolism pathway.Six differentially expressed lncRNAs were investigated between T0T andT1T.A competing endogenous RNA network was constructed using 259 lncRNAemiRNAemRNA in-teractions,including alpha-2-macroglobulin antisense RNA 1-miR-7161-5p-iron-sulfur cluster scaffold.Finally,13 chemical drugs associated with the hub genes were explored.Conclusion:Iron-sulfur cluster scaffold may promote IPC-induced ischemic tolerance mediated by alpha-2-macroglobulin antisense RNA 1-miR-7161-5p axis.Moreover,IPC may induce a protective responseafter total knee arthroplasty via mitochondria-related functions and the carbon metabolism pathway,which should be further validated in the near future.展开更多
文摘Propose:To investigate the molecular mechanisms underlying the protective effects of ischemic pre-conditioning(IPC)in patients undergoing total knee arthroplasty.Methods:GSE21164 was extracted from an online database,followed by an investigation of differentiallyexpressed genes(DEGs)between IPC treatment samples at 2 time points(T0T and T1T).Function andpathway enrichment analyses were performed on the DEGs.A protein-protein interaction network wasconstructed to identify hub genes according to 5 different algorithms,followed by enrichment analysis.In addition,long noncoding RNAs(lncRNAs)were identified between the T0T and T1T samples.Furthermore,a competing endogenous RNA network was predicted based on the identified lncRNA-messenger RNA(mRNA),lncRNA-microRNA(miRNA),and mRNA-miRNA relationships revealed in thisstudy.Finally,a drug-gene network was investigated.Statistical analyses were performed usingGraphPad Prism 8.0.Differences between groups were determined using an unpaired t-test.p<0.05 wasconsidered significant.Results:A total of 343 DEGs at T0 and 10 DEGs at T1 were identified and compared with their respectivecontrol groups,followed by 100 DEGs between T0T and T1T.Based on these 100 DEGs,protein-proteininteraction network analysis revealed 9 hub genes,mainly with mitochondria-related functions andthe carbon metabolism pathway.Six differentially expressed lncRNAs were investigated between T0T andT1T.A competing endogenous RNA network was constructed using 259 lncRNAemiRNAemRNA in-teractions,including alpha-2-macroglobulin antisense RNA 1-miR-7161-5p-iron-sulfur cluster scaffold.Finally,13 chemical drugs associated with the hub genes were explored.Conclusion:Iron-sulfur cluster scaffold may promote IPC-induced ischemic tolerance mediated by alpha-2-macroglobulin antisense RNA 1-miR-7161-5p axis.Moreover,IPC may induce a protective responseafter total knee arthroplasty via mitochondria-related functions and the carbon metabolism pathway,which should be further validated in the near future.