From MASH to HCC: the role of Gas6/TAM receptors

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Jan. 17, 2024

Metabolic dysfunction-associated steatohepatitis (MASH) is the replacement term for what used to be called nonalcoholic (NASH). It characterized by inflammation and injury of liver in presence cardiometabolic risk factors may eventually result development hepatocellular carcinoma (HCC), most common form primary cancer. Several pathogenic mechanisms are involved transition from MASH HCC, encompassing metabolic injury, inflammation, immune dysregulation fibrosis. In this context, Gas6 (Growth Arrest-Specific 6) TAM (Tyro3, Axl, MerTK) receptors play important roles. The Gas6/TAM family modulation lipid metabolism, fibrosis, tumor progression metastasis, processes which an role pathophysiology acute chronic diseases. review, we discuss MASH-associated HCC potential involvement system disease progression. addition, since therapeutic strategies limited, also speculate regarding possible future treatments involving targeting or receptors.

Language: Английский

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Transforming Screening, Risk Stratification, and Treatment Optimization in Chronic Liver Disease Through Data Science and translational Innovation

The Indonesian Journal of Gastroenterology Hepatology and Digestive Endoscopy, Journal Year: 2024, Volume and Issue: 25(1), P. 53 - 62

Published: May 16, 2024

Background: Chronic liver diseases continue to face challenges in prognosis, treatment selection, disease mechanisms, screening, and therapeutic optimization. Promising innovations could address these gaps through data integration novel analytic approaches.Main Body: MAPS-CRAFITY integrating clinical variables, AFP, CT/MRI findings, transformer modeling of RFA improve HCC outcome prediction guide management. Analyses revealing IL21R as a PBC susceptibility gene implicating dysfunctional VWF processing portal hypertension deliver mechanistic insights. Quantifying childhood MAFLD informs screening needs, while supporting use G6PD deficient donors enables transplantation access expansion risk stratification. Updating Baveno criteria enhances an prognostic score identifies optimal candidates maximize efficacy.Conclusion: Recent research leverages diverse types, genetics, imaging, machine learning develop integrated predictive systems that allow more personalized therapy selection. Elucidating molecular pathways provides targets biomarkers. Evidence-based models facilitate delivering tailored interventions. Optimization current modalities validation patient selection improves real-world effectiveness. Multifaceted modern approaches promise unmet needs transform hepatology care.

Language: Английский

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Sodium Butyrate Alleviates Free Fatty Acid-Induced Steatosis in Primary Chicken Hepatocytes via Regulating the ROS/GPX4/Ferroptosis Pathway

Antioxidants, Journal Year: 2024, Volume and Issue: 13(2), P. 140 - 140

Published: Jan. 23, 2024

Fatty liver hemorrhagic syndrome (FLHS) in laying hens is a nutritional metabolic disease commonly observed high-yielding hens. Sodium butyrate (NaB) and ferroptosis were reported to contribute the pathogenesis of fatty liver-related diseases. However, underlying mechanism NaB FLHS whether it mediates remains unclear. A chicken primary hepatocyte induced by free acids (FFAs, keeping ratio sodium oleate palmitate concentrations at 2:1) was established, which received treatments with NaB, inducer RAS-selective lethal 3 (RSL3), inhibitor ferrostatin-1 (Fer-1). As result, increased biochemical lipid metabolism indices, antioxidant level, while inhibiting intracellular ROS accumulation activation signaling pathway, as evidenced reduction iron concentration, upregulated GPX4 xCT expression, inhibited NCOA4 ACSL4 expression. Furthermore, treatment Fer-1 reinforced protective effects RSL3 reversed blocking ROS/GPX4/ferroptosis leading droplets oxidative stress. Collectively, our findings demonstrated that protects hepatocytes regulating ROS/GPX4-mediated providing new strategy target for FLHS.

Language: Английский

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Multi-approach analysis reveals the mechanism by which Shugan Xiaozhi decoction protects against metabolic dysfunction-associated steatohepatitis

Phytomedicine, Journal Year: 2025, Volume and Issue: 141, P. 156712 - 156712

Published: April 2, 2025

Metabolic dysfunction-associated steatohepatitis (MASH) is a human health-threatening hepatic disease with limited treatment strategies. As clinical Traditional Chinese Medicine compound for MASH, Shugan Xiaozhi (SGXZ) decoction has definite effect, but its mechanism in treating MASH still not very clear. Exploring the potential of SGXZ through multiomics and animal experimental validation. UPLC-ESI-MS method was used to identify main components decoction. Periodic acid-schiff (PAS), picrosirius red (PSR), oil o staining were assess effect on MCD-induced mouse model. The analyzed using techniques. TUNEL staining, western blot (WB), immunohistochemistry (IHC), kits, transmission electron microscopy (TEM), immunofluorescence (IF) validate MASH. Finally, molecular docking dynamics simulation verify targeting between key important targets intervention. Through analysis, 30 active ingredients obtained from improved as evidenced by improvement histopathology, function indexes, lipid fibrosis indicators. Both proteomic transcriptomic results suggested an role ferroptosis intervention ferroptosis-related pathways significant these analyses. In addition, reduced cell death, inflammation, oxidative stress levels restored impaired mitochondrial morphology mice. Furthermore, Mechanism experiments proved that iron metabolism peroxidation imbalance activated Xc- system does have therapeutic may be related regulation p53/ SLC7A11/GPX4 pathway reduce ferroptosis.

Language: Английский

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Metabolic dysfunction-associated steatotic liver disease: A pathophysiology and clinical framework to face the present and the future

Nutrition Metabolism and Cardiovascular Diseases, Journal Year: 2024, Volume and Issue: 35(2), P. 103702 - 103702

Published: Aug. 5, 2024

Language: Английский

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Management of hepatocellular carcinoma, an important cause of death in Japanese autoimmune hepatitis patients

BMC Gastroenterology, Journal Year: 2024, Volume and Issue: 24(1)

Published: April 1, 2024

Abstract Background Hepatocellular carcinoma (HCC) in autoimmune hepatitis (AIH) was considered rare but is increasing with prolonged prognosis. Its impact on the overall prognosis of AIH unknown, and treatment has not been established. Aim To investigate risk factors HCC patients identify appropriate management strategies. Methods We studied including background liver disease, sex, age, complications, treatment, response to fibrosis, prognosis, treatment. Results In 131 patients, deaths due failure were more common early after onset AIH; however, increased gradually. observed 12 (median 70 years; male/female, 4/8; cirrhosis at onset, 11; median time carcinogenesis, 7 years). Cirrhosis diagnosis identified as a factor for carcinogenesis multivariate analysis (odds ratio, 41.36; p < 0.0001) cumulative cancer rates high. Multidisciplinary therapy other than immune checkpoint inhibitors administered HCC. Two three who used molecular-targeted drugs discontinued because adverse events. Conclusion an important cause death AIH. Currently available drug therapies are limited detection desirable. Trial registration This trial retrospectively registered Ethics Committee Kagawa University School Medicine under identifier 2019 − 238, 4 Feb 2020.

Language: Английский

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Prognostic Impact of Metabolic Syndrome and Steatotic Liver Disease in Hepatocellular Carcinoma Using Machine Learning Techniques

Metabolites, Journal Year: 2024, Volume and Issue: 14(6), P. 305 - 305

Published: May 27, 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD) currently represents the predominant cause of chronic and is closely linked to a significant increase in risk hepatocellular carcinoma (HCC), even absence cirrhosis. In this retrospective multicenter study, machine learning (ML) methods were employed investigate relationship between metabolic profile prognosis at diagnosis total 219 HCC patients. The eXtreme Gradient Boosting (XGB) method demonstrated superiority identifying mortality predictors our Etiology was most determining prognostic factor followed by Barcelona Clinic Liver Cancer (BCLC) Eastern Cooperative Oncology Group (ECOG) classifications. Variables related development hepatic steatosis syndrome, such as elevated levels alkaline phosphatase (ALP), uric acid, obesity, alcohol consumption, high blood pressure (HBP), had impact on prediction. This study underscores importance syndrome progression secondary MASLD. use ML techniques provides an effective tool improve stratification individualized therapeutic management these

Language: Английский

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Exploring the Mechanism of Action of Sericin in Ameliorating non-Alcoholic Fatty Liver Disease in Mice Based on the Nrf2- GPX4/ NF-κB p65 Pathway

Natural Product Communications, Journal Year: 2024, Volume and Issue: 19(10)

Published: Oct. 1, 2024

Objective: To explore the ameliorative effect and mechanism of action sericin on liver injury in Non-Alcoholic Fatty Liver Disease (NAFLD) model mice. Methods: Mice were fed a high-fat diet for 8 weeks to establish NAFLD The mice then randomly divided into 6 groups given 0, 250, 500, 1000 mg/kg body weight sericin, + ML385 (a protein inhibitor Nrf2), Zhibitai Capsules positive drug), by gavage, respectively. levels TC, TG, low-density lipoprotein cholesterol (LDL-C), high-density (HDL-C), alanine aminotransferase (ALT), aspartate (AST) mouse serum MDA, GSH, SOD, TNF-α, IL-6 tissues measured. Pathological changes evaluated using hematoxylin-eosin (HE) Oil Red O staining. Protein expression Nrf2, Keap1, HO-1, GPX4, NF-κB p65 was detected Western blotting, level GPX4 examined immunohistochemistry. Results: Sericin improved hepatic steatosis lipid accumulation LDL-C, down-regulated, HDL-C SOD up-regulated. There no significant difference AST ALT all groups. In addition, upregulated keap1, proteins inhibited lipids indices between group dose Conclusion: has an alleviating oxidative stress inflammatory responses injury. It remains be explored whether this is regulated through Nrf2- GPX4/ signaling pathway.

Language: Английский

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A Practical Format to Organize Cancer Constellations Using Innate Immune System Biomarkers: Implications for Early Diagnosis and Prognostication

International Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 4(4), P. 726 - 739

Published: Dec. 6, 2024

Cancer discovery is directed at the identification of a specific cancer type which allows for therapeutic interventions. Recently, similar immune checkpoint therapeutics have been applied with success across several types, opening field other disruptive interventions that practical applications. We discovered an innate system (InImS) biomarker characterization allied subtypes and outliers might aid diagnosis, treatment, prognostication. These InImS biomarkers are related to PD-L1 treatment outcomes can be potentially manipulated by dietary means. The FERAD (ferritin-fecal p87) absolute neutrophil/lymphocyte (aNLR) ratios two such we show herein, they allow diagnosis prognostication patterns, as demonstrated this study.

Language: Английский

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