Kidney-tonifying blood-activating decoction delays ventricular remodeling in rats with chronic heart failure by regulating gut microbiota and metabolites and p38 mitogen-activated protein kinase/p65 nuclear factor kappa-B/aquaporin-4 signaling pathway

Hypertrophic cardiomyopathy (HCM) is a global health problem characterized by left ventricle become thick and stiff with effect of indication including chest pain, fluttering, fainting and shortness of breath. In this investigation, we aimed to identify diagnostic markers and analyzed the therapeutic potential of essential genes. Next generation sequencing (NGS) dataset GSE180313 was obtained from the Gene Expression Omnibus (GEO) database and used to identify differentially expressed genes (DEGs) in HCM. DEGs were screened using the DESeq2 Rbioconductor tool. Then, Gene Ontology (GO) and REACTOME pathway enrichment analyses were performed. Moreover, a protein-protein interaction (PPI) network of the DEGs was constructed, and module analysis was performed. Next, miRNA-hub gene regulatory network and TF-hub gene regulatory network were constructed and analyzed. Finally, diagnostic values of hub genes were assessed by by receiver operating characteristic (ROC) curve analysis. By performing DEGs analysis, total 958 DEGs ( 479 up regulated genes and 479 down regulated genes) were successfully identified from GSE180313, respectively. GO and REACTOME pathway enrichment analyses revealed that GO functions and signaling pathways were significantly enriched including response to stimulus, multicellular organismal process, metabolism and extracellular matrix organization. The hub genes of FN1, SOX2, TUBA4A, RPS2, TUBA1C, ESR1, SNCA, LCK, PAK1 and APLNR might be associated with HCM. The hub gens of FN1 and TPM3, together with corresponding predicted miRNAs (e.g., hsa-mir-374a-5p and hsa-miR-8052), and SH3KBP1 and ESR1 together with corresponding predicted TFs (e.g PRRX2 and STAT3) were found to be significantly correlated with HCM. This investigation could serve as a basis for further understanding the molecular pathogenesis and potential therapeutic targets of HCM.

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New insights into the intestinal barrier through “gut-organ” axes and a glimpse of the microgravity’s effects on intestinal barrier

Nie,

Ge,

Huang

et al. 2024

Front. Physiol.

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Gut serves as the largest interface between humans and the environment, playing a crucial role in nutrient absorption and protection against harmful substances. The intestinal barrier acts as the initial defense mechanism against non-specific infections, with its integrity directly impacting the homeostasis and health of the human body. The primary factor attributed to the impairment of the intestinal barrier in previous studies has always centered on the gastrointestinal tract itself. In recent years, the concept of the “gut-organ” axis has gained significant popularity, revealing a profound interconnection between the gut and other organs. It speculates that disruption of these axes plays a crucial role in the pathogenesis and progression of intestinal barrier damage. The evaluation of intestinal barrier function and detection of enterogenic endotoxins can serve as “detecting agents” for identifying early functional alterations in the heart, kidney, and liver, thereby facilitating timely intervention in the disorders. Simultaneously, consolidating intestinal barrier integrity may also present a potential therapeutic approach to attenuate damage in other organs. Studies have demonstrated that diverse signaling pathways and their corresponding key molecules are extensively involved in the pathophysiological regulation of the intestinal barrier. Aberrant activation of these signaling pathways and dysregulated expression of key molecules play a pivotal role in the process of intestinal barrier impairment. Microgravity, being the predominant characteristic of space, can potentially exert a significant influence on diverse intestinal barriers. We will discuss the interaction between the “gut-organ” axes and intestinal barrier damage, further elucidate the signaling pathways underlying intestinal barrier damage, and summarize alterations in various components of the intestinal barrier under microgravity. This review aims to offer a novel perspective for comprehending the etiology and molecular mechanisms of intestinal barrier injury as well as the prevention and management of intestinal barrier injury under microgravity environment.

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Kidney-tonifying blood-activating decoction delays ventricular remodeling in rats with chronic heart failure by regulating gut microbiota and metabolites and p38 mitogen-activated protein kinase/p65 nuclear factor kappa-B/aquaporin-4 signaling pathway

Cited by 3 publications

References 168 publications

The role of serine/threonine protein kinases in cardiovascular disease and potential therapeutic methods

The role of serine/threonine protein kinases in cardiovascular disease and potential therapeutic methods

Identification of novel key genes and signaling pathways in hypertrophic cardiomyopathy: evidence from bioinformatics and next generation sequencing data analysis

New insights into the intestinal barrier through “gut-organ” axes and a glimpse of the microgravity’s effects on intestinal barrier

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