Pathogenic Mechanisms of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)-Associated Hepatocellular Carcinoma

Cells, Journal Year: 2025, Volume and Issue: 14(6), P. 428 - 428

Published: March 13, 2025

Hepatocellular carcinoma (HCC) is the sixth most common cancer and third leading cause of deaths worldwide. The etiology HCC has now dramatically changed from viral hepatitis to metabolic dysfunction-associated steatotic liver disease (MASLD). main pathogenesis MASLD-related hepatic lipid accumulation hepatocytes, which causes chronic inflammation subsequent progression fibrosis. Chronic generates oxidative stress DNA damage in contribute genomic instability, resulting development HCC. Several molecular pathways are also linked MASLD. In particular, MAPK PI3K-Akt-mTOR upregulated MASLD, promoting survival proliferation cells. addition, MASLD been reported enhance patients with infection. Although there no approved medication for besides resmetirom USA, some preventive strategies onset Sodium-glucose cotransporter-2 (SGLT2) inhibitor, a class medications, exert anti-tumor effects on by regulating reprogramming. Moreover, CD34-positive cell transplantation improves fibrosis intrahepatic angiogenesis supplying various growth factors. Furthermore, exercise through an increase energy consumption as well changes chemokines myokines. this review, we summarize recent progress made pathogenic mechanisms MASLD-associated introduced new therapeutic preventing based

Language: Английский

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Association of dietary inflammatory index on all-cause and cardiovascular mortality in U.S. adults with metabolic dysfunction associated steatotic liver disease

Frontiers in Nutrition, Journal Year: 2025, Volume and Issue: 12

Published: April 1, 2025

An inflammatory diet is pivotal in metabolic dysfunction-associated steatotic liver disease (MASLD) development. However, it remains unclear whether Dietary Inflammatory Index (DII), which serves as a reliable indicator to assess pro-inflammatory diet, have associative effects on mortality outcomes of MASLD. Participants the National Health and Nutrition Examination Survey (NHANES) database from 1999 2018 years were included. Kaplan-Meier (KM) curves used estimate survival probabilities, while Cox regression analysis restricted cubic splines (RCS) employed association between DII outcomes. The concordance index (C-index) evaluated accuracy multivariate-adjusted for among MASLD participants. cohort consisted 4,510 men 4,323 women with median age 52 years. Multivariate-adjusted revealed that high levels significantly associated all-cause participants (multivariable-adjusted hazard ratio (aHR) = 1.28, 95% confidence interval (CI) 1.10-1.49, p 0.002, aHR cardiovascular CI 1.07-1.53, 0.006). C-index multivariate model, integrating other clinical variables, was 0.837 0.860 mortality. RCS showed positive linear relationship rate (p nonlinearity 0.057), no significant 0.953). Subgroup analyses indicated stronger associations <65 years, married, college education, non-smokers, non-drinkers, those without hypertension. Elevated are linked higher adults MASLD, underscoring index's utility predicting risks. These findings shows dietary interventions targeted inflammation may be helpful this population.

Language: Английский

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Sex-Dependent T Cell Dysregulation in Mice with Diet-Induced Obesity

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8234 - 8234

Published: July 28, 2024

Obesity is an emerging public health problem. Chronic low-grade inflammation considered a major promotor of obesity-induced secondary diseases such as cardiovascular and fatty liver disease, type 2 diabetes mellitus, several cancer entities. Most preliminary studies on immune responses have been conducted in male rodents. Sex-specific differences between men women dysregulation not yet fully outlined but are highly relevant to optimizing prevention strategies for overweight-associated complications. In this study, we fed C57BL/6 female vs. mice with either standard chow or obesity-inducing diet (OD). Blood spleen cells were isolated analyzed by flow cytometry. Lean control showed no sex bias systemic splenic cell composition, whereas the obesity significantly distinct mice. While alterations OD characterized significant reduction T increase myeloid-derived suppressor (MDSC), displayed preserved numbers. The sex-dependent associated varying susceptibility body weight gain disease: Male more hepatic histopathological stigmata comparison Our findings indicate that impacts dysregulation, which might explain different incidences development obesity-associated diseases. These results provide novel insights into understanding chronic from sex-specific perspective. Given most nutrition, exercise, therapeutic recommendations comorbidities do differentiate women, data study clinically should be taken consideration future trials treatment strategies.

Language: Английский

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Carnitine palmitoyltransferase-II inactivity promotes malignant progression of metabolic dysfunction-associated fatty liver disease via liver cancer stem cell activation

World Journal of Gastroenterology, Journal Year: 2024, Volume and Issue: 30(47), P. 5055 - 5069

Published: Nov. 25, 2024

Metabolic dysfunction-associated fatty liver disease (MAFLD) is one of the main chronic diseases. However, roles mitochondrial carnitine palmitoyl transferase-II (CPT-II) downregulation and cancer stem cell (LCSC) activation remain to be identified.

Language: Английский

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