Regulation of Hippo-YAP1/TAZ pathway in metabolic dysfunction-associated steatotic liver disease

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 23, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most prevalent chronic worldwide, but effective treatments are still lacking. disorders such as iron overload, glycolysis, insulin resistance, lipid dysregulation, and glutaminolysis found to induce senescence ferroptosis, which hot topics in research of MASLD. Recent studies have shown that Hippo–YAP1/TAZ pathway is involved regulations metabolism disorders, senescence, inflammation, fibrosis MASLD, their complex connections contrast roles also reported. In addition, therapeutics based on hold promising for MASLD treatment. this review, we highlight regulation molecular mechanism summarize potential therapeutic strategies by regulating pathway.

Language: Английский

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Protective role of ginsenoside Rg1 in the dynamic progression of liver injury to fibrosis: a preclinical meta-analysis

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 28, 2025

Background The pathological progression from liver injury to fibrosis is a hallmark of disease, with no effective strategies halt this transition. Ginsenoside Rg1 has demonstrated range hepatoprotective properties; however, systematic preclinical evidence supporting its therapeutic potential for and remains limited. Purpose. This study evaluated the efficacy underlying mechanisms ginsenoside in animal models fibrosis, providing basis future clinical investigation. Methods A review was conducted on studies published PubMed, Web Science, Embase databases up 1 August 2024, adhereing rigorous quality standards. methodological assessed using SYRCLE’s risk bias tool. Meta-analysis subgroup analysis were performed Revman 5.4 software, while publication through funnel plots Egger’s test STATA 15.0 software. Additionally, time-dose interval curve utilized assess dose-response relationship identify dose treating fibrosis. Results Twenty-four trials involving 423 animals included. findings indicated that significantly improved function markers (ALT AST), reduced indicators associated lowered fibrosis-related (α-SMA, HYP, PCIII). Furthermore, it exhibited beneficial effects mechanistic inflammation, oxidative stress, apoptosis, compared control group ( P < 0.05). Time-dose revealed between 4 800 mg/kg/d. Conclusion at 4–800 mg/kg/d mitigates via anti-inflammatory, antioxidative, anti-apoptotic pathways. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD 42024557878.

Language: Английский

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Kanglexin, a New Anthraquinone Compound, Inhibits Hepatic Fibrosis by Regulating Glutathione Metabolism with Pck1-Mediated Gluconeogenesis

Published: Jan. 1, 2025

Language: Английский

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Uncovering mechanism of hepatotoxicity diseases caused by tetrahydrocannabinol based on novel network toxicology and experimental verification

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 21, 2025

This study systematically investigated the molecular mechanisms underlying tetrahydrocannabinol (THC)-induced hepatotoxicity in humans through an integrated approach combining network toxicology, docking, and experimental validation. Our analysis identified 22 core targets associated with THC-mediated hepatotoxicity. Protein-protein interaction (PPI) revealed significant functional associations among these potential target proteins. KEGG pathway GO term analyses demonstrated that THC potentially exerts hepatotoxic effects multiple biological processes, including endocrine resistance, bile secretion, negative regulation of apoptosis, cellular oxidant detoxification. Disease enrichment further several pathological conditions closely THC-induced hepatic damage. Molecular docking simulations strong binding affinities between domains 17 proteins participated aforementioned enriched pathways. An vitro model hepatocyte injury was successfully established subsequently validated RT-qPCR experiment. exposure significantly altered expression patterns 10 critical genes: ERBB2, GPX1, MAPK14, NR1H4, SOD1, CXCR2, PPARG, EGFR, TYMS KDR. The appear to arise from synergistic interplay pathways coordinated dysfunction various gene products. These findings elucidate key therapeutic hepatotoxicity, providing a theoretical foundation for developing clinical interventions hepatoprotective strategies against cannabis-related liver

Language: Английский

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Colostrum-derived extracellular vesicles: potential multifunctional nanomedicine for alleviating mastitis

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Oct. 16, 2024

Bovine mastitis is an infectious disease that causes substantial economic losses to the dairy industry worldwide. Current antibiotic therapy faces issues of misuse and antimicrobial resistance, which has aroused concerns for both veterinary human medicine. Thus, this study explored potential Colo EVs (bovine colostrum-derived extracellular vesicles) address mastitis. Using LPS-induced murine mammary epithelial cells (HC11), mouse monocyte macrophages (RAW 264.7), a model with BALB/C mice, we evaluated safety efficacy EVs, in vivo vitro. had favorable biosafety profiles, promoting cell proliferation migration without inducing pathological changes after injection into glands. In mastitis, significantly reduced inflammation, improved inflammatory scores, preserved tight junction proteins while protecting milk production. Additionally, vitro experiments demonstrated downregulated cytokine expression, markers, attenuated NF-κB pathway activation. summary, inferred have promise as therapeutic approach treatment, owing their anti-inflammatory properties, potentially mediated through signaling modulation.

Language: Английский

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