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This study aims to investigate the role of anoikis-related genes in diabetic foot (DF) by utilizing bioinformatics analysis to identify key genes associated with anoikis in DF. We selected the GEO datasets GSE7014, GSE80178 and GSE68183 for the extraction and analysis of differentially expressed anoikis-related genes (DE-ARGs). GO analysis and KEGG analysis indicated that DE-ARGs in DF were primarily enriched in apoptosis, positive regulation of MAPK cascade, anoikis, focal adhesion and the PI3K-Akt signalling pathway. Based on the LASSO and SVM-RFE algorithms, we identified six characteristic genes. ROC curve analysis revealed that these six characteristic genes had an area under the curve (AUC) greater than 0.7, indicating good diagnostic efficacy. Expression analysis in the validation set revealed downregulation of CALR in DF, consistent with the training set results. GSEA results demonstrated that CALR was mainly enriched in blood vessel morphogenesis, endothelial cell migration, ECM-receptor interaction and focal adhesion. The HPA database revealed that CALR was moderately enriched in endothelial cells, and CALR was found to interact with 63 protein-coding genes. Functional analysis with DAVID suggested that CALR and associated genes were enriched in the phagosome component. CALR shows promise as a potential marker for the development and treatment of DF.
by Chao Li, Zhong Liu, Justin Anderson, Zhongyu Liu, Liping Tang, Yao Li, Ning Peng, Jianguo Chen, Xueming Liu, Lianwu Fu, Tim M. Townes, Steven M. Rowe, David M. Bedwell, Jennifer Guimbellot, Rui Zhao
A major unmet need in the cystic fibrosis (CF) therapeutic landscape is the lack of effective treatments for nonsense CFTR mutations, which affect approximately 10% of CF patients. Correction of nonsense CFTR mutations via genomic editing represents a promising therapeutic approach. In this study, we tested whether prime editing, a novel CRISPR-based genomic editing method, can be a potential therapeutic modality to correct nonsense CFTR mutations. We generated iPSCs from a CF patient homozygous for the CFTR W1282X mutation. We demonstrated that prime editing corrected one mutant allele in iPSCs, which effectively restored CFTR function in iPSC-derived airway epithelial cells and organoids. We further demonstrated that prime editing may directly repair mutations in iPSC-derived airway epithelial cells when the prime editing machinery is efficiently delivered by helper-dependent adenovirus (HDAd). Together, our data demonstrated that prime editing may potentially be applied to correct CFTR mutations such as W1282X.To find potential biomarkers based on miRNA and their potential targets in splenic monocytes in burn-injured mice. Male Balb/c mice were subjected to sham or scalding injury of 15% total body surface area. Spenic CD11b+ monocytes were purified with magnetic beads. The monocytes were cultured in the presence of lipopolysaccharide. The proliferation of monocytes was detected by MTT assay, and the cytokines in the supernatant were examined by enzyme linked immunosorbent assay. The purified monocytes were also under total RNA extraction. The differential monocytic miRNAs expression between the sham and burn-injured mice was analysed by miRNA microarray. The activity of monocytes was comparable between the two groups (p > 0.05). However, monocytes from burn-injured mice secreted higher levels of tumour necrosis factor (TNF)-α and transforming growth factor-β, but lower level of monocyte chemoattratctant protein-1. A total of 54 miRNAs were differentially expressed in monocytes from burn relative to sham-injured mice (fold >3). Further quantitative reverse transcription polymerase chain reaction confirmed that the expression of miR-146a was significantly down-regulated, while miR-3091-6p was up-regulated after burn injury. Using the combination of Miranda and TargetScan softwares, we found that mir-146a may regulate 180 potential target genes including TNF receptor related factor 6 (TRAF6), interleukin-1 receptor related kinase 1 (IRAK1) and CD28. Mir-3091-6p may regulate 39 potential targets, including SOCS7 (cytokine signal transduction inhibitor 7) and ARRB2 (arrestin, β 2). The miRNAs expressed by monocytes after burn injury may be involved in the regulation of innate immune response in burn injury.
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