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• W2916578758 abstract "Nonalcoholic fatty liver disease is a major liver disease that leads to cirrhosis and/or hepatocellular carcinoma in a subset of patients. The mechanism underlying disease progression is largely unknown. p53-binding protein 1 (53BP1) is a DNA damage response protein that rapidly localizes at the site of DNA double-strand breaks. In this study, we investigated nuclear 53BP1-positive foci formation as an indicator of DNA double-strand breaks in human nonalcoholic fatty liver disease liver tissues by immunofluorescence microscopy. A total of 52 liver tissue samples, including 43 nonalcoholic fatty liver disease samples and 9 controls, were studied. Our results show that the number of abnormal 53BP1-positive foci in hepatocytes (defined as three or more discrete nuclear foci and/or large foci greater than 1 μM) was significantly increased in nonalcoholic fatty liver disease patients compared to that in controls, both in nonalcoholic fatty liver (p < 0.01) and nonalcoholic steatohepatitis patients (p < 0.01). The number of large foci was significantly increased in the nonalcoholic steatohepatitis cases compared to that in the nonalcoholic fatty liver cases (p < 0.05) and correlated with increased stage of fibrosis. The number of large-foci-expressing hepatocytes was positively correlated with increased age (p < 0.01) and negatively correlated with serum platelet count (p < 0.05). In addition, we performed an in vitro assay using rat hepatocytes treated with the saturated free fatty acid palmitate. Treatment appeared to augment the number of abnormal foci, indicating an induction of double-strand breaks in the hepatocytes through free fatty acid treatment in a caspase-dependent manner. This study demonstrates that 53BP1-positive nuclear foci formation is associated with disease progression in nonalcoholic fatty liver disease patients. Analysis of 53BP1 expression might be a feasible technique to estimate genomic instability in nonalcoholic fatty liver disease." @default.
• W2916578758 created "2019-03-02" @default.
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• W2916578758 date "2019-07-01" @default.
• W2916578758 modified "2023-10-01" @default.
• W2916578758 title "Detection of DNA damage response in nonalcoholic fatty liver disease via p53-binding protein 1 nuclear expression" @default.
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• W2916578758 doi "https://doi.org/10.1038/s41379-019-0218-8" @default.
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