Front Cell Infect Microbiol. 2026 Mar 16;16:1793213. doi: 10.3389/fcimb.2026.1793213. eCollection 2026.

ABSTRACT

The progression from cirrhosis to hepatocellular carcinoma (HCC) is a key outcome in the management of chronic liver disease. This process has a long incubation period and significant individual differences, making early warning still difficult. Clinical follow-up mainly relies on imaging examinations and alpha fetoprotein, but the ability to identify high risk precancerous states is limited. The imbalance of gut microbiota and its metabolites may occur earlier than the visible stage of tumors. They can affect barrier integrity, chronic inflammation, immune surveillance, and metabolic homeostasis through the gut liver axis, and participate in the formation of a pro tumor microenvironment. Therefore, such changes may provide more upstream risk stratification clues for the population with cirrhosis. This article summarizes previous research evidence and summarizes the common microbiome and metabolite characteristics of cirrhosis and high-risk populations, including a decrease in short chain fatty acid (SCFA) related symbiotic bacteria, an increase in inflammation related bacteria, bile acid spectrum shift, and other intestinal derived metabolite abnormalities. This article also outlines the key mechanisms that these features may correspond to, such as barrier damage and microbial translocation, immune suppression, etc. There are still significant uncertainties at present. The effect of SCFA is context dependent. Different etiologies, diets, medications, and complications can lead to significant confounding and affect cross cohort consistency. Subsequent research requires longitudinal cohort validation and the promotion of multi omics integration and the construction of interpretable predictive models to support clinical translation.

PMID:41918873 | PMC:PMC13033666 | DOI:10.3389/fcimb.2026.1793213

Int J Mol Sci. 2026 Feb 25;27(5):2170. doi: 10.3390/ijms27052170.

ABSTRACT

Carbosulfan is a widely used carbamate insecticide, yet its mechanisms of respiratory toxicity remain poorly understood. This study integrated network toxicology, untargeted metabolomics, and molecular docking to systematically investigate the potential mechanisms of carbosulfan-induced respiratory toxicity in male Sprague Dawley rats. Rats were administered a single oral dose of carbosulfan (125 or 250 mg/kg) and assessed after 12 h. Exposure resulted in significant pathological lung damage, characterized by disrupted alveolar architecture, inflammatory cell infiltration, and increased serum levels of the pro-inflammatory cytokines IL-6, IL-1β, and TNF-α. Network toxicology analysis identified 51 potential targets associated with respiratory toxicity, with core targets including SRC, EGFR, PTGS2, CXCL8, CYP3A4, and NR3C1. Enriched pathways were primarily related to neuroactive ligand-receptor interaction, VEGF signaling, and arachidonic acid metabolism. Untargeted metabolomics revealed significant metabolic perturbations in pathways central to antioxidant defense and energy homeostasis, including glutathione metabolism, the tricarboxylic acid cycle, and arginine biosynthesis. Molecular docking confirmed stable in silico binding affinities between carbosulfan and the predicted core targets. Integrative analysis suggests that carbosulfan exposure is associated with respiratory damage, potentially through interconnected mechanisms involving oxidative stress, inflammation, and disruption of cell signaling and metabolic enzyme systems. However, given the acute high-dose nature of the model and the interpretative integration of multi-omics data, these findings should be considered hypothesis-generating. This study provides a novel system-level perspective on carbosulfan-induced respiratory toxicity and highlights key pathways and targets for future validation in chronic exposure models.

PMID:41828400 | PMC:PMC12984169 | DOI:10.3390/ijms27052170

Int J Mol Sci. 2026 Feb 25;27(5):2170. doi: 10.3390/ijms27052170.

ABSTRACT

Carbosulfan is a widely used carbamate insecticide, yet its mechanisms of respiratory toxicity remain poorly understood. This study integrated network toxicology, untargeted metabolomics, and molecular docking to systematically investigate the potential mechanisms of carbosulfan-induced respiratory toxicity in male Sprague Dawley rats. Rats were administered a single oral dose of carbosulfan (125 or 250 mg/kg) and assessed after 12 h. Exposure resulted in significant pathological lung damage, characterized by disrupted alveolar architecture, inflammatory cell infiltration, and increased serum levels of the pro-inflammatory cytokines IL-6, IL-1β, and TNF-α. Network toxicology analysis identified 51 potential targets associated with respiratory toxicity, with core targets including SRC, EGFR, PTGS2, CXCL8, CYP3A4, and NR3C1. Enriched pathways were primarily related to neuroactive ligand-receptor interaction, VEGF signaling, and arachidonic acid metabolism. Untargeted metabolomics revealed significant metabolic perturbations in pathways central to antioxidant defense and energy homeostasis, including glutathione metabolism, the tricarboxylic acid cycle, and arginine biosynthesis. Molecular docking confirmed stable in silico binding affinities between carbosulfan and the predicted core targets. Integrative analysis suggests that carbosulfan exposure is associated with respiratory damage, potentially through interconnected mechanisms involving oxidative stress, inflammation, and disruption of cell signaling and metabolic enzyme systems. However, given the acute high-dose nature of the model and the interpretative integration of multi-omics data, these findings should be considered hypothesis-generating. This study provides a novel system-level perspective on carbosulfan-induced respiratory toxicity and highlights key pathways and targets for future validation in chronic exposure models.

PMID:41828400 | PMC:PMC12984169 | DOI:10.3390/ijms27052170