Novel insights into immune-related genes associated with type 2 diabetes mellitus-related cognitive impairment

BACKGROUND The cognitive impairment in type 2 diabetes mellitus(T2DM)is a multifaceted and advancing state that requires further exploration to fully comprehend.Neu-roinflammation is considered to be one of the main mechanisms and the immune system has played a vital role in the progression of the disease.AIM To identify and validate the immune-related genes in the hippocampus associated with T2DM-related cognitive impairment.METHODS To identify differentially expressed genes(DEGs)between T2DM and controls,we used data from the Gene Expression Omnibus database GSE125387.To identify T2DM module genes,we used Weighted Gene Co-Expression Network Analysis.All the genes were subject to Gene Set Enrichment Analysis.Protein-protein interaction network construction and machine learning were utilized to identify three hub genes.Immune cell infiltration analysis was performed.The three hub genes were validated in GSE152539 via receiver operating characteristic curve analysis.Validation experiments including reverse transcription quantitative real-time PCR,Western blotting and immunohistochemistry were conducted both in vivo and in vitro.To identify potential drugs associated with hub genes,we used the Comparative Toxicogenomics Database(CTD).RESULTS A total of 576 DEGs were identified using GSE125387.By taking the intersection of DEGs,T2DM module genes,and immune-related genes,a total of 59 genes associated with the immune system were identified.Afterward,machine learning was utilized to identify three hub genes(H2-T24,Rac3,and Tfrc).The hub genes were associated with a variety of immune cells.The three hub genes were validated in GSE152539.Validation experiments were conducted at the mRNA and protein levels both in vivo and in vitro,consistent with the bioinformatics analysis.Additionally,11 potential drugs associated with RAC3 and TFRC were identified based on the CTD.CONCLUSION Immune-related genes that differ in expression in the hippocampus are closely linked to microglia.We validated the expression of three hub genes both in vivo and in vitro,consistent with our bioinformatics results.We discovered 11 compounds associated with RAC3 and TFRC.These findings suggest that they are co-regulatory molecules of immunometabolism in diabetic cognitive impairment.

Correlation of Wnt/β-catenin pathway changes with cytokines and apoptosis genes in diabetic foot wound

Objective:To study the correlation of Wnt/β-catenin pathway changes with cytokines and apoptosis genes in diabetic foot wound.Methods:diabetic foot patients admitted to our hospital between February 2015 and October 2017 were selected as the diabetic foot group,and non-diabetic patients admitted to our hospital during the same period were selected as the control group.Wound tissues of the diabetic foot group and normal skin tissues of the control group were collected to determine the mRNA expression levels of Wnt/β-catenin pathway molecules and apoptosis genes as well as the contents of cytokines.Results:The mRNA expression levels of Wnt1,β-catenin and B-cell lymphoma-2(Bcl-2)as well as the contents of vascular endothelial growth factor(VEGF),insulin-like growth factor-1(IGF-1)and basic fibroblast growth factor(bFGF)in the wounds of the diabetic foot group were significantly lower than those of the control group whereas the mRNA expression levels of glycogen synthase kinase-3(GSK-3β),Bcl-2-associated X protein(Bax)and cysteinyl aspartate specific proteinase-3(Caspase-3)as well as the contents of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)were significantly higher than those of the control group;Wnt1 andβ-catenin were positively correlated with VEGF,IGF-1,bFGF and Bcl-2,and negatively correlated with TNF-α,IL-6,Bax and Caspase-3;GSK-3βwas negatively correlated with VEGF,IGF-1,bFGF,and Bcl-2,and positively correlated with TNF-α,IL-6,Bax and Caspase-3.Conclusion:Wnt/β-catenin pathway is inhibited in diabetic foot wound and it is related to the changes in cytokine secretion and apoptosis gene expression.