Decoding HiPSC-CM's Response to SARS-CoV-2: mapping the molecular landscape of cardiac injury.

BACKGROUND: Acute cardiac injury caused by coronavirus disease 2019 (COVID-19) increases mortality. Acute cardiac injury caused by COVID-19 requires understanding how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly infects cardiomyocytes. This study provides a solid foundation for related studies by using a model of SARS-CoV-2 infection in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) at the transcriptome level, highlighting the relevance of this study to related studies. SARS-CoV-2 infection in hiPSC-CMs has previously been studied by bioinformatics without presenting the full molecular biological process. We present a unique bioinformatics view of the complete molecular biological process of SARS-CoV-2 infection in hiPSC-CMs. METHODS: To validate the RNA-seq datasets, we used GSE184715 and GSE150392 for the analytical studies, GSE193722 for validation at the cellular level, and GSE169241 for validation in heart tissue samples. GeneCards and MsigDB databases were used to find genes associated with the phenotype. In addition to differential expression analysis and principal component analysis (PCA), we also performed protein-protein interaction (PPI) analysis, functional enrichment analysis, hub gene analysis, upstream transcription factor prediction, and drug prediction. RESULTS: Differentially expressed genes (DEGs) were classified into four categories: cardiomyocyte cytoskeletal protein inhibition, proto-oncogene activation and inflammation, mitochondrial dysfunction, and intracellular cytoplasmic physiological function. Each of the hub genes showed good diagnostic prediction, which was well validated in other datasets. Inhibited biological functions included cardiomyocyte cytoskeletal proteins, adenosine triphosphate (ATP) synthesis and electron transport chain (ETC), glucose metabolism, amino acid metabolism, fatty acid metabolism, pyruvate metabolism, citric acid cycle, nucleic acid metabolism, replication, transcription, translation, ubiquitination, autophagy, and cellular transport. Proto-oncogenes, inflammation, nuclear factor-kappaB (NF-κB) pathways, and interferon signaling were activated, as well as inflammatory factors. Viral infection activates multiple pathways, including the interferon pathway, proto-oncogenes and mitochondrial oxidative stress, while inhibiting cardiomyocyte backbone proteins and energy metabolism. Infection limits intracellular synthesis and metabolism, as well as the raw materials for mitochondrial energy synthesis. Mitochondrial dysfunction and energy abnormalities are ultimately caused by proto-oncogene activation and SARS-CoV-2 infection. Activation of the interferon pathway, proto-oncogene up-regulation, and mitochondrial oxidative stress cause the inflammatory response and lead to diminished cardiomyocyte contraction. Replication, transcription, translation, ubiquitination, autophagy, and cellular transport are among the functions that decline physiologically. CONCLUSION: SARS-CoV-2 infection in hiPSC-CMs is fundamentally mediated via mitochondrial dysfunction. Therapeutic interventions targeting mitochondrial dysfunction may alleviate the cardiovascular complications associated with SARS-CoV-2 infection.

Effects of Nurse-Led Interventions on Comprehensive Rehabilitation of Atrial Fibrillation: A Systematic Review And Meta-Analysis.

Objective: This meta-analysis aimed to assess and evaluate the effect of nurse-led health management on the quality of life of patients with atrial fibrillation. Methods: We compared the outcomes of patients who received nurse-led intervention during hospitalization with those who did not, using a systematic retrospective and randomized controlled trial (RCT) analysis. We searched the studies in Cochrane Central Register, including PubMed, EmBase, Web of Science, Cochrane Library, WAN Data, CBM, CNKI, etc. Bias risks included in the study were evaluated by Cochrane Bias risk tool , and combined risk estimates were calculated. The main endpoints are the SF-36 and HADS scores and endpoints after surgery. We used a random effects model to combine the data. For continuous variables (such as SF-36 and HADS scores), we used standard mean difference for analysis, and for binary variables (such as the presence or absence of mental health problems), we used hazard ratio for analysis. The data are based on fixed or stochastic effects models, with standard mean differences and risk ratios for continuous and heterotaxic variables. Results: 3064 patients from 7 clinical studies were included in this meta-analysis. Postoperative SF-36 scores at 6 months in the nurse-led group were significantly higher than those in the routine nursing group in Role-Physical and Mental health. Postoperative SF-36 scores at 12 months in the nurse-led group were not significantly higher than those in the routine nursing group. The nurse-led group had a significantly lower HADS depression score than the conventional care group, but there was no significant difference in HADS anxiety score between the two groups. Conclusion: The main findings of this meta-analysis are that the nurse-led comprehensive management of atrial fibrillation can significantly improve the role-physical and mental health status of SF-36, reduce the HADS depression score, the incidence of cardiovascular hospitalization and atrial fibrillation at 6 months atrial fibrillation surgery. Additional high-quality RCTs should be conducted in the future. nurse-led interventions have the potential to significantly impact the care of patients with atrial fibrillation. By providing comprehensive management, education, and support, nurses can improve patient outcomes, enhance quality of life, and reduce healthcare burdens for both patients and providers. While this meta-analysis provides valuable insights, there are limitations that should be considered. Standardizing interventions and outcome measures, conducting larger studies with longer follow-up periods, including diverse populations and settings, and assessing the economic impact of nurse-led interventions are potential directions for future research in this field. Addressing these limitations would provide a more comprehensive understanding of the role of nurse-led interventions in the care of patients with atrial fibrillation.

Microarray analysis reveals the potential molecular mechanism of Lp299v in stable coronary atherosclerotic disease.

A growing body of evidence has confirmed that inflammatory mechanisms are involved in the formation and treatment of coronary atherosclerotic disease (CAD). An increase in circulatory levels of inflammatory cytokines has been found in patients with CAD, while the molecular mechanisms of inflammation still remain elusive. This study was designed to identify differentially expressed genes (DEGs), and to explore the molecular mechanism and hub genes that are involved in the effects of Lactobacillus plantarum 299v (Lp299v) supplementation. Microarray dataset (GSE156357) was downloaded from the Gene Expression Omnibus (GEO) database. The DEGs were identified by the R software. Then, the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses and construction of protein-protein interaction (PPI) network were performed by DAVID, STRING, and Cytoscape software. In daily alcohol user (DAU) group, 7,541 DEGs were identified, including 206 up-regulated and 7,335 down-regulated DEGs. In non-daily alcohol user (non-DAU) group, 2,799 DEGs were identified (2,491 up-regulated and 308 down-regulated DEGs). The GO enrichment analysis revealed that miosis was up-regulated and immune response was down-regulated. The KEGG enrichment analysis showed that Lp299v supplementation reduced the levels of chemotactic cytokines, and weakened immune response. Proteins of G protein-coupled receptor, inflammatory response, regulation of cell proliferation and apoptosis-related proteins were found in the PPI network. The hub genes were associated with G protein-coupled receptor, inflammatory response, and cell proliferation and apoptosis. The weighted gene co-expression network analysis (WGCNA) enriched the DEGs in 4 modules. This study indicated the expressions of chemokine receptors and regulation of immune response in the Lp299v supplementation. Meanwhile, it was supposed that chemokine receptors may have a cellular effect.