Identification of hub genes associated with oxidative stress in heart failure and their correlation with immune infiltration using bioinformatics analysis.

Both oxidative stress and the immune response are associated with heart failure (HF). In this study, our aim was to identify the hub genes associated with oxidative stress andimmune infiltration of HF by bioinformatics analysis and experimental verification. The expression profile of GSE36074 was obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were screened by GEO2R. The genes related to oxidative stress were extracted from GeneCards websites. Then, the functional enrichment analysis of oxidative stress-related DEGs (OSRDEGs) was performed using DAVID. In addition, we constructed a protein-protein interaction (PPI) network using the STRING database and screened for hub genes with Cytoscape software. We also used CIBERSORTx to analyze immune infiltration in mice heart tissues between the TAC and Sham groups and explored the correlation between immune cells and hub genes. Finally, the hub genes were carried out using reverse transcription quantitative PCR (RT-qPCR), immunohistochemistry (IHC) and western blot. A total of 136 OSRDEGs were found in GSE36074. Enrichment analysis revealed that these OSRDEGs were enriched in the mitochondrion, HIF-1, FoxO, MAPK and TNF signaling pathway. The five hub genes (Mapk14, Hif1a, Myc, Hsp90ab1, and Hsp90aa1) were screened by the cytoHubba plugin. The correlation analysis between immune cells and hub genes showed that Mapk14 was positively correlated with Th2 Cells, while Hif1a and Hsp90ab1exhibited a negative correlation with Th2 Cells; Myc exhibited a negative correlation with Monocytes; whereas, Hsp90aa1 was negatively correlated with NK Resting. Finally, five hub genes were validated by RT-qPCR, IHC and western blot. Mapk14, Hif1a, Myc, Hsp90ab1, and Hsp90aa1 are hub genes of HF and may play a critical role in the oxidative stress of HF. This study may provide new targets for the treatment of HF, and the potential immunotherapies are worthy of further study.

Gu J ，Zhang LN ，Gu X ，Zhu Y ... -  《PeerJ》

Identification of Ferroptosis-Related Genes in Heart Failure Induced by Transverse Aortic Constriction.

Gu JJ ，Du TJ ，Zhang LN ，Zhou J ，Gu X ，Zhu Y ... -  《Journal of Inflammation Research》

Identification of hub glycolysis-related genes in acute myocardial infarction and their correlation with immune infiltration using bioinformatics analysis.

Glycolysis and immune metabolism play important roles in acute myocardial infarction (AMI). Therefore, this study aimed to identify and experimentally validate the glycolysis-related hub genes in AMI as diagnostic biomarkers, and further explore the association between hub genes and immune infiltration. Differentially expressed genes (DEGs) from AMI peripheral blood mononuclear cells (PBMCs) were analyzed using R software. Glycolysis-related DEGs (GRDEGs) were identified and analyzed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) for functional enrichment. A protein-protein interaction network was constructed using the STRING database and visualized using Cytoscape software. Immune infiltration analysis between patients with AMI and stable coronary artery disease (SCAD) controls was performed using CIBERSORT, and correlation analysis between GRDEGs and immune cell infiltration was performed. We also plotted nomograms and receiver operating characteristic (ROC) curves to assess the predictive accuracy of GRDEGs for AMI occurrence. Finally, key genes were experimentally validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting using PBMCs. A total of 132 GRDEGs and 56 GRDEGs were identified on the first day and 4-6 days after AMI, respectively. Enrichment analysis indicated that these GRDEGs were mainly clustered in the glycolysis/gluconeogenesis and metabolic pathways. Five hub genes (HK2, PFKL, PKM, G6PD, and ALDOA) were selected using the cytoHubba plugin. The link between immune cells and hub genes indicated that HK2, PFKL, PKM, and ALDOA were significantly positively correlated with monocytes and neutrophils, whereas G6PD was significantly positively correlated with neutrophils. The calibration curve, decision curve analysis, and ROC curves indicated that the five hub GRDEGs exhibited high predictive value for AMI. Furthermore, the five hub GRDEGs were validated by RT-qPCR and western blotting. We concluded that HK2, PFKL, PKM, G6PD, and ALDOA are hub GRDEGs in AMI and play important roles in AMI progression. This study provides a novel potential immunotherapeutic method for the treatment of AMI.

Zhang X ，Zhang L ，Gao Y ，Liu Z ，Gong K ... -  《BMC Cardiovascular Disorders》

Identification of Ferroptosis-Related Hub Genes and Their Association with Immune Infiltration in Chronic Obstructive Pulmonary Disease by Bioinformatics Analysis.

Ferroptosis and immune infiltration are involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). We aim to identify ferroptosis-related hub genes and analyze their association with immune infiltration in COPD through bioinformatics methods. The mRNA microarray data of GSE38974 were downloaded from Gene Expression Omnibus to obtain differentially expressed genes (DEGs). The DEGs were intersected with ferroptosis-related genes (FRGs) from FerrDb to obtain differentially expressed FRGs. GO and KEGG enrichment and protein-protein interaction (PPI) analyses of differentially expressed FRGs were conducted in R software and STRING database. The key module and hub genes were screened by Cytoscape software. MiRNAs, transcription factors and signal molecules were predicted in miRNet and NetworkAnalyst. The disease correlation in the Comparative Toxicomics Database (CTD) and the receiver operating characteristic (ROC) curves of hub genes were analyzed. Immune infiltration was evaluated by CIBERSORT algorithm. Spearman correlation analyses were conducted between hub genes and differentially infiltrated immune cells. Fifteen differentially expressed FRGs were identified, which were enriched in some terms involving airway inflammatory responses and structural remodeling. Five hub genes were selected including HIF1A, IL6, PTGS2, CDKN1A and ATM. Inference scores in CTD indicated their association with COPD. Two miRNAs, five transcription factors and one signal molecule were predicted. The combination of hub genes could be a fine diagnostic indicator of COPD (AUC: 0.981, CI: 0.940-1.000). Immune infiltration evaluation showed that monocytes and M0 macrophages were upregulated in COPD lung tissues, while CD8 T cells, activated NK cells, M2 macrophages, resting dendritic cells and resting mast cells were downregulated. The hub genes were significantly associated with differentially infiltrated immune cells. We identified five ferroptosis-related hub genes (HIF1A, IL6, PTGS2, CDKN1A and ATM) in COPD, and found that they may influence the pathogenesis of COPD by regulating ferroptosis and thus affecting infiltrating immune cells.

Yang YC ，Zhang MY ，Liu JY ，Jiang YY ，Ji XL ，Qu YQ ... -  《International Journal of Chronic Obstructive Pulmonary Disease》

Identification of biomarkers, pathways, and potential therapeutic targets for heart failure using next-generation sequencing data and bioinformatics analysis.

Ganekal P ，Vastrad B ，Vastrad C ，Kotrashetti S ... -  《-》