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Chronic hepatic injury and inflammation from various causes can lead to fibrosis and cirrhosis, potentially predisposing to hepatocellular carcinoma. The molecular mechanisms underlying fibrosis and its progression remain incompletely understood. Using a proteo-transcriptomics approach, we analyze liver and plasma samples from 330 individuals, including 40 healthy individuals and 290 patients with histologically characterized fibrosis due to chronic viral infection, alcohol consumption, or metabolic dysfunction-associated steatotic liver disease. Our findings reveal dysregulated pathways related to extracellular matrix, immune response, inflammation, and metabolism in advanced fibrosis. We also identify 132 circulating proteins associated with advanced fibrosis, with neurofascin and growth differentiation factor 15 demonstrating superior predictive performance for advanced fibrosis(area under the receiver operating characteristic curve [AUROC] 0.89 [95% confidence interval (CI) 0.81-0.97]) compared to the fibrosis-4 model (AUROC 0.85 [95% CI 0.78-0.93]). These findings provide insights into fibrosis pathogenesis and highlight the potential for more accurate non-invasive diagnosis.
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http://dx.doi.org/10.1016/j.xcrm.2025.101935 | DOI Listing |
Nano Lett
September 2025
State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
An optimal administration approach is critical for effective mRNA delivery and treatment. Nebulizer inhalation offers a mild, convenient, and noninvasive strategy with high translational potential but primarily focused on lung delivery. In this study, we found that surface charges influence tissue targeting of mRNA lipid nanoparticle (mRNA-LNP) postnebulization.
View Article and Find Full Text PDFGut Liver
September 2025
Department of Liver Diseases, The Research Center for Hepatitis and Immunology, National Institute of Global Health and Medicine, Japan Institute for Health Security, Ichikawa, Japan.
Hepatitis C virus (HCV) clearance markedly reduces the risk of hepatocellular carcinoma (HCC); however, HCC continues to develop in a subset of patients, particularly in those with advanced fibrosis or cirrhosis. Leading hepatology societies, including Asian Pacific Association for the Study of the Liver, European Association for the Study of the Liver, American Association for the Study of Liver Diseases, Korean Association for the Study of the Liver, Taiwan Association for the Study of the Liver, and Japan Society of Hepatology, have issued divergent guidelines for HCC surveillance after sustained virologic response, which reflects variations in regional patient populations, healthcare infrastructure, and policy priorities. While traditional risk stratification primarily centers on histological staging of fibrosis, an array of additional host-related factors, including age, sex, alcohol use, metabolic comorbidities, and genetic and epigenetic profiles, further influence individual HCC risks.
View Article and Find Full Text PDFPediatr Transplant
November 2025
D'Or Institute for Research and Education (IDOR), Rio de Janeiro, RJ, Brazil.
Background: Fontan-associated liver disease can progress to advanced fibrosis, raising the potential need for combined heart-liver transplantation (CHLT) in selected patients. However, the benefits of CHLT over isolated orthotopic heart transplantation (HT), particularly in terms of mortality, remain uncertain. In this systematic review, we compared mortality outcomes following CHLT versus HT in patients with Fontan circulation, with the aim of supporting clinical decision-making.
View Article and Find Full Text PDFKorean J Physiol Pharmacol
September 2025
Department of Physiology & Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Korea.
Diabetes mellitus is a major global health concern associated with micro-and macrovascular complications. Among the diverse mechanisms that contribute to vascular dysfunction in diabetes, endothelial to mesenchymal transition (EndMT) has emerged as a key pathological process. EndMT involves the loss of endothelial cell characteristics and the acquisition of mesenchymal features, resulting in impaired endothelial function, increased fibrosis, and inflammation.
View Article and Find Full Text PDFKorean J Physiol Pharmacol
September 2025
Department of Endocrinology, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China.
The progression of renal fibrosis is difficult to reverse, and Poria cocos, one of the main components of Wenyang Zhenshuai Granules, has been shown to be crucial to the development of the epithelial-mesenchymal transition (EMT). This study aimed to examine the molecular mechanism by which Poricoic Acid A (PAA) inhibited the advancement of EMT in renal tubular epithelial (RTE) cells. The protein levels of sprouty RTK signaling antagonist 2 (SPRY2) extracellular regulated protein kinases (ERK), and p-ERK were measured.
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