Hepatology International最新文献

Background: With annual global plastic production exceeding 400 million tons, nanoscale polystyrene particles (nPS) have become a major health concern due to their bioaccumulation capacity and ability to cross biological barriers. Surface-charged nPS variants (cationic, anionic, and neutral) show distinct biodistribution patterns, yet the mechanisms underlying their systemic damage remain incompletely understood. This study aimed to investigate the systemic injury mechanisms of nPS with different surface charges.

Methods: Mice were exposed to fluorescently labeled cationic (amino-modified), anionic (carboxyl-modified), and neutral nPS via drinking water (25 mg/mL) for 3 weeks. Tissue distribution was analyzed using fluorescence microscopy; pathological changes were assessed via hematoxylin-eosin (HE) staining; metabolic perturbations were detected by metabolomic profiling. Mechanistic investigations were performed using metabolomics, flow cytometry, and molecular assays in AML12 hepatocytes and vascular endothelial cells.

Results: Fluorescence microscopy showed neutral nPS accumulated in the vascular endothelium of the stomach, intestine, and lung via passive diffusion, while cationic/anionic nPS penetrated hepatic sinusoids through charge-mediated interactions. HE staining revealed severe liver injury, with no significant abnormalities in other tissues. Metabolomic profiling indicated disrupted hepatic amino acid and lipid metabolism, depleted antioxidants (e.g., vitamin E and glutathione), and induced oxidative stress (evidenced by elevated hydroxy fatty acids). In hepatocytes, nPS-induced endoplasmic reticulum (ER) stress triggered excessive reactive oxygen species (ROS) production, inhibiting SLC7A11-mediated cystine uptake and glutathione synthesis, leading to disulfide stress (β-actin disulfide mispairing) and ferroptosis (GPX4 inactivation and iron accumulation). In contrast, neutral nPS induced endothelial cell senescence via phagolysosome dysfunction, causing lysosomal membrane permeabilization and β-galactosidase release.

Conclusions: This study identifies a "charge-specific injury" paradigm: charged nPS induce hepatocyte ferroptosis via an ER stress-disulfide stress cascade, while neutral nPS trigger endothelial senescence through phagocytic dysfunction. These findings provide critical insights for the biosafety assessment of nanoplastics and identify potential targets for preventing plastic pollution-related liver diseases.

Background: The disease burden of alcoholic liver cancer (ALC) has been changing due to socioeconomic development. An up-to-date evaluation of this change can increase public awareness and facilitate health policy development.

Methods: The data were extracted from the Global Burden of Diseases Study (GBD) 2021. Epidemiological changes of morbidity and mortality in different regions, as well as the differences in gender and age were analyzed. Temporal trends were determined using Joinpoint regression analysis and age-period-cohort analysis was employed to evaluate the effects of age, period, and cohort.

Results: Globally, there were 99,543.67 new cases (95% UI 80957.40-120401.87) and 92,227.78 deaths (95% UI 75053.11-112,160.27) in 2021, increased by 158.92% and 141.61%, respectively, compared to 1990. Decomposition analysis revealed that population growth was the primary driver of the increased morbidity (41.13%) and mortality (54.87%). The global estimated annual percentage change (EAPC) of morbidity and mortality exhibited an ascending trend, while differences existed across different regions. The morbidity and mortality rates were higher in males than in females across all age groups. Joinpoint regression analysis showed an increased morbidity and mortality rate. The age effect indicated that the highest risk was observed at 75-79 years for morbidity and 80-84 years for mortality. The period effect showed an increasing risk, while improving cohort risks for mortality were identified.

Conclusion: Alcoholic liver cancer has posed an increasing health burden since 1990, particularly affecting male and the elderly population. Effective prevention policies on specific age groups should be formulated to improve this situation.