Microcystin-LR (MCLR) is a potent inhibitor of protein phosphatases 1 and 2A and causes alterations in cytoskeletal filaments and morphological changes that underlie apoptosis in rat hepatocytes. It has also been reported that it caused several cases of human deaths and illness. As no study on the effect of microcystins on human hepatocytes was done, yet, the aim of the study is to evaluate the toxicity of MCLR on primary human hepatocytes. The hepatocytes were incubated in 12.5-50 nM MCLR for 3, 6 and 9 h, fixed and stained with fluorescent probes for actin filaments and nuclei. Spectral laser-scanning confocal microscopy revealed that in the MCLR-treated primary human hepatocytes the actin mesh collapsed into the center of the cell, similarly as it has been described for rat hepatocytes. Cells were blebbing, fragmenting, and separated from each other. The nuclei in the affected cells condensed. In conclusion, this study confirms that MCLR is toxic to primary human hepatocytes, and it may be responsible for the liver failure cases observed after acute cyanobacterial poisoning.
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http://dx.doi.org/10.1016/s0166-445x(03)00108-5 | DOI Listing |
PLoS One
January 2025
Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America.
Aflatoxin B1 (AFB1) is a class 1 carcinogen and mycotoxin known to contribute to the development of hepatocellular carcinoma (HCC), growth impairment, altered immune system modulation, and malnutrition. AFB1 is synthesized by Aspergillus flavus and is known to widely contaminate foodstuffs, particularly maize, wheat, and groundnuts. The mechanism in which AFB1 causes genetic mutations has been well studied, however its metabolomic effects remained largely unknown.
View Article and Find Full Text PDFRadiographics
February 2025
From the Department of Radiology, Division of Abdominal Imaging, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905 (K.C.H., M.L.W., C.L.W., J.F., S.K.V.); Department of Medical Imaging, University of Ottawa, Ottawa, Ontario, Canada (K.C.H.); Department of Medical Imaging, Beaujon University Hospital, Clichy, France (M.R.); HT Medica, Madrid, Spain (A.L.); Department of Radiology, University of Vienna, Vienna, Austria (A.B.S.); Department of Radiology, Sun Yat Sen University, Guangzhou, China (J.W.); and Department of Radiology, Division of Abdominal Imaging, Mayo Clinic, Scottsdale, Ariz (A.C.S.).
Hepatobiliary (HB) contrast agents are increasingly valuable diagnostic tools in MRI, offering a wider range of applications as their clinical use expands. Normal hepatocytes take up HB contrast agents, which are subsequently excreted in bile. This property creates a distinct HB phase providing valuable insights into liver function and biliary anatomy.
View Article and Find Full Text PDFNat Biotechnol
January 2025
Department of Surgery, University of California, San Francisco, San Francisco, CA, USA.
Therapeutic efficacy and safety of adeno-associated virus (AAV) liver gene therapy depend on capsid choice. To predict AAV capsid performance under near-clinical conditions, we established side-by-side comparison at single-cell resolution in human livers maintained by normothermic machine perfusion. AAV-LK03 transduced hepatocytes much more efficiently and specifically than AAV5, AAV8 and AAV6, which are most commonly used clinically, and AAV-NP59, which is better at transducing human hepatocytes engrafted in immune-deficient mice.
View Article and Find Full Text PDFHepatol Commun
February 2025
Department of Anesthesiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Background: Cell therapy demonstrates promising potential as a substitute therapeutic approach for liver cirrhosis. We have developed a strategy to effectively expand murine and human hepatocyte-derived liver progenitor-like cells (HepLPCs) in vitro. The primary objective of the present study was to apply HepLPCs to the treatment of liver cirrhosis and to elucidate the underlying mechanisms responsible for their therapeutic efficacy.
View Article and Find Full Text PDFDis Model Mech
January 2025
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LE, UK.
The excessive accumulation of intrahepatic triglyceride (IHTG) in the liver is a risk factor for metabolic diseases, including type 2 diabetes and cardiovascular disease. IHTG can excessively accumulate owing to imbalances in the delivery, synthesis, storage and disposal of fat to, in and from the liver. Although obesity is strongly associated with IHTG accumulation, emerging evidence suggests that the composition of dietary fat, in addition to its quantity, plays a role in mediating IHTG accumulation.
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