Myocardial remodeling and the limited regenerative capacity of mammalian cardiomyocytes constitute major barriers to heart failure therapy. Current therapies cannot reliably restore lost cardiomyocytes, and advanced heart failure may ultimately require mechanical circulatory support or transplatation. This review synthesizes recent advances in endogenous cardiac regeneration mechanisms, focusing on three key regulatory pathways: intracellular signaling, extracellular matrix (ECM) interactions, and exogenous cell-based therapies. We examine strategies to enhance the reprogramming of non-cardiomyocytes into functional cardiomyocytes, leveraging insights from regeneration-competent animal models including zebrafish and neonatal mice. Additionally, we explore the emerging role of hypoxia as a pro-regenerative signal, particularly in the context of cyanotic congenital heart disease (CCHD) such as tetralogy of Fallot (TOF) and pulmonary atresia (PA) with intact ventricular septum or ventricular septal defects. While stem cell technologies and intrinsic cardiomyocyte proliferative mechanisms have shown preclinical promise, clinical translation remains fraught with challenges. This review aims to provide a comprehensive, integrated perspective on endogenous regeneration pathways and their therapeutic potential to transform heart failure management. We further emphasize the unique therapeutic value of these regenerative mechanisms in CCHD: chronic hypoxia triggers hypoxia-inducible factor 1α (HIF-1α)-mediated metabolic reprogramming and cell-cycle regulation, which paradoxically activates pro-regenerative signaling and establishes a transient myocardial regenerative window. This window can be harnessed via early neonatal surgical intervention to facilitate myocardial repair.
To characterize trends, disparities, and forecast trajectories in mortality with systemic lupus erythematosus (SLE) as the underlying cause among U.S. adults aged ≥ 25 years from 1999 to 2023 while describing differences by sex, age, race/ethnicity, region, and state. We analyzed CDC WONDER Underlying Cause of Death data for ICD-10 codes M32.0, M32.1, M32.8, and M32.9. Crude, age-specific, and age-adjusted mortality rates (AAMRs) per 100,000 were calculated. Archived joinpoint estimates were supplemented by weighted log-linear sensitivity analyses, and seven log-scale forecasting models were compared by rolling-origin validation. The selected model was refitted through 2023 for primary forecasts and through 2019 and 2021 for sensitivity scenarios. Among 28,323 deaths, the AAMR decreased from 0.68 to 0.33 per 100,000 (AAPC, –3.24
To investigate the potential mechanism of cinobufotalin against colorectal cancer (CRC) through network pharmacology and experimental approaches. Overlapping targets between cinobufotalin and CRC were identified, yielding 165 potential therapeutic targets. A protein–protein interaction (PPI) network was constructed using Cytoscape software, and key genes were subjected to Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. In vitro experiments were performed to evaluate the effects of cinobufotalin on CRC cell proliferation, apoptosis, and autophagy-related markers. Pharmacological inhibition of autophagy was also applied to examine its modulation of the antiproliferative effect of cinobufotalin. Enrichment analysis indicated that the overlapping targets were significantly associated with apoptosis signaling and autophagy pathways. In vitro experiments confirmed that cinobufotalin inhibited CRC cell proliferation and induced apoptosis, accompanied by changes in autophagy-related markers. Pharmacological inhibition of autophagy enhanced the antiproliferative effect of cinobufotalin, suggesting a regulatory role of autophagy in cellular response. Cinobufotalin exerts antitumor effects against CRC by promoting apoptosis and targeting autophagy pathways, and modulation of autophagy can further enhance its therapeutic efficacy.
The gut–lung axis (GLA) is increasingly recognized as a biological communication pathway relevant to lung cancer. However, the potential molecular associations between gut microbial metabolites and lung adenocarcinoma (LUAD) remain incompletely understood. By integrating public databases, including gutMGene, GeneCards, and TCGA, with computational tools such as WGCNA, STRING, and CIBERSORT, candidate genes and gut microbiota-derived metabolites potentially associated with LUAD were identified. A microbiota–metabolite–targets–pathway (MMTP) interaction network was constructed, followed by functional enrichment, immune infiltration analysis, miRNA–target prediction, and drug-likeness analyses. Among the 12 key targets identified, JUN, IL6, and CXCL8 were prioritized as core genes. These targets mainly involved miRNA-related processes and immune pathways like IL-17 signaling, Toll-like receptor, and Th17 differentiation. Immune infiltration showed that core gene expression correlated with specific immune cell patterns, indicating inflammatory and immunosuppressive features of the tumor microenvironment (TME). The MMTP network further suggested that several gut microbial metabolites, including butyrate, propionate, acetate, succinate, 3-indolepropionic acid, and trimethylamine N-oxide, may be associated with core gene-related pathways. In silico drug-likeness and toxicity predictions indicated that these metabolites generally met basic Lipinski-based criteria; however, several predicted toxicity signals, particularly human hepatotoxicity, warrant cautious interpretation. Key gut microbial metabolites may be linked to LUAD progression via inflammatory and immune pathways involving JUN, IL6, and CXCL8, along with miRNA regulatory processes. These findings offer a bioinformatics framework for understanding GLA-related molecular links in LUAD and may help find biomarkers or metabolites for further study.
Adenoid hypertrophy (AH) is among the most common otolaryngologic disorders in childhood, and its development cannot be adequately explained by a single inflammatory process. Increasing evidence suggests that the adenoid functions not only as an important component of upper airway mucosal immunity but also as a critical site for persistent microbial colonization and local immune remodeling. This review examines AH from structural, immunologic, and microecological perspectives, offering an integrated analytical framework to better understand coordinated imbalance within the adenoidal microenvironment. Furthermore, we investigate the relationships between distinct microenvironmental patterns and clinical phenotypes and discuss both current therapeutic strategies and emerging precision intervention approaches. Collectively, existing evidence indicates that AH is a multifaceted disorder closely associated with microenvironmental reprogramming, and its clinical heterogeneity appears to be attributed to diverse underlying biological processes.
