Autoimmune hepatitis (AIH) is often diagnosed late in the disease course and usually requires lifelong immunosuppressive therapy. Unfortunately, the etiology of the disease and the mechanisms leading to the autoimmune destruction of the liver parenchyma are only poorly understood. For a long time, one reason for this lack of apprehension was the absence of reliable animal models with a chronic immune response against liver tissues. Initial attempts to break tolerance against hepatocytes usually just resulted in mild, transient hepatitis flares. Recently, however, some approaches have been made to establish models of chronic AIH that reflect the immunopathogenic mechanisms seen in humans. In this article, we reflect on recent models, focusing on their feasibility and chances for success in providing a platform for studying the mechanisms of autoimmune liver destruction and the development of possible therapeutic interventions.
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http://dx.doi.org/10.1055/s-0029-1233536 | DOI Listing |
Mol Med
January 2025
Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
Background: Lysinuric protein intolerance is a rare autosomal disorder caused by mutations in the Slc7a7 gene that lead to impaired transport of neutral and basic amino acids. The gold standard treatment for lysinuric protein intolerance involves a low-protein diet and citrulline supplementation. While this approach partially improves cationic amino acid plasma levels and alleviates some symptoms, long-term treatment is suggested to be detrimental and may lead to life-threatening complications characterized by a wide range of hematological and immunological abnormalities.
View Article and Find Full Text PDFBMC Nephrol
January 2025
Department of Nephrology, Japan Community Healthcare Organization Sendai Hospital, 981-3281, Sendai, Miyagi, Japan.
Background: Oliguric acute kidney injury (AKI) is one of the critical conditions which needs emergent treatment due to the lack of the capacity of excreting toxins and fluids, and plasma membrane bleb formation is considered as one of the characteristic morphologic alterations in ischemic AKI in both animal models and human. We present here an autopsy case with clear electron microscopy images capturing a definitive instance of blebbing in ischemic AKI.
Case Presentation: A 66-year-old man was admitted for oliguric AKI with nephrotic syndrome (NS).
Mol Med
January 2025
The First People's Hospital of Lin'an District, No. 360, Yikang Street, Jinnan Subdistrict, Lin'an District, Hangzhou, Zhejiang, 311300, China.
Background: Myocardial infarction (MI) remains a leading cause of mortality globally, often resulting in irreversible damage to cardiomyocytes. Ferroptosis, a recently identified form of regulated cell death driven by iron-dependent lipid peroxidation, has emerged as a significant contributor to post-MI cardiac injury. The endoplasmic reticulum (ER) stress response has been implicated in exacerbating ferroptosis.
View Article and Find Full Text PDFNat Chem Biol
January 2025
Department of Medical Cell Biology, Uppsala University, Biomedical Centre, Uppsala, Sweden.
Diabetes is characterized by variable loss of insulin-producing beta cells, and new regenerative approaches to increasing the functional beta cell mass of patients hold promise for reversing disease progression. In this Review, we summarize recent chemical biology breakthroughs advancing our knowledge of beta cell regeneration. We present current chemical-based tools, sensors and mechanistic insights into pathways that can be targeted to enhance beta cell regeneration in model organisms.
View Article and Find Full Text PDFSci Rep
January 2025
School of Sports and Health, Nanjing Sport Institute, Nanjing, China.
A high-calorie diet and lack of exercise are the most important risk factors contributing to metabolic dysfunction-associated steatotic liver disease (MASLD) initiation and progression. The precise molecular mechanisms of mitochondrial function alteration during MASLD development remain to be fully elucidated. In this study, a total of 60 male C57BL/6J mice were maintained on a normal or amylin liver NASH (AMLN) diet for 6 or 10 weeks.
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