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Background/Aims: Alcoholic liver disease (ALD) is one of the leading causes of cirrhosis and yet efficient therapeutic strategies are lacking. Polyenephosphatidylcholine (PPC), a major component of essential phospholipids, prevented alcoholic liver fibrosis in baboons, but its precise mechanism remains uncertain. We aimed to explore the effects of PPC on ALD using ethanol-fed peroxisome proliferator-activated receptor α (Ppara)-null mice, showing several similarities to human ALD. Methods: Male wild-type and Ppara-null mice were pair-fed a Lieber-DeCarli control or 4% ethanol-containing diet with or without PPC (30 mg/kg/day) for 6 months. Results: PPC significantly ameliorated ethanol-induced hepatocyte damage and hepatitis in Ppara-null mice. These effects were likely a consequence of decreased oxidative stress through down-regulation of reactive oxygen species (ROS)-generating enzymes, including cytochrome P450 2E1, acyl-CoA oxidase, and NADPH oxidases, in addition to restoration of increases in Toll-like receptor 4 and CD14. PPC also decreased Bax and truncated Bid, thus inhibiting apoptosis. Furthermore, PPC suppressed increases in transforming growth factor-β1 expression and hepatic stellate cell activation, which retarded hepatic fibrogenesis. Conclusions: PPC exhibited anti-inflammatory, anti-apoptotic, and anti-fibrotic effects on ALD as a result of inhibition of the overexpression of ROS-generating enzymes. Our results demonstrate detailed molecular mechanisms of the anti-oxidant action of PPC., Article, Journal of Hepatology 50(6): 1236-1246(2009)

Author Posting. © The Authors 2008 This is the author's version of the work. It is posted here for personal use, not for redistribution. The definitive version was published in Liver International, 28(8):1104-1111. https://doi.org/10.1111/j.1478-3231.2008.01737.x, Article, LIVER INTERNATIONAL. 28(8):1104-1111(2008)

Article, JOURNAL OF CLINICAL INVESTIGATION. 118(2):683-694(2008)

This is a preprint of an article published in INTERNATIONAL JOURNAL OF CANCER. Copyright (c) 2008 Wiley-Liss, Inc., A Wiley Company, Article, INTERNATIONAL JOURNAL OF CANCER. 122(1): 124-131

Article, CLINICAL IMMUNOLOGY. 122(3): 338-342 (2007)

Article, LIVER INTERNATIONAL. 26(1): 32-38 (2006)

Article, LIVER INTERNATIONAL. 26(1): 90-96 (2006)

Copyright © 2006 American Association for the Study of Liver Diseases, Article, HEPATOLOGY. 43(1): 91-99 (2006)

Copyright © 2005 Wiley-Liss, Inc., A Wiley Company, Article, JOURNAL OF MEDICAL VIROLOGY. 76(2): 170-175 (2005)

SEN virus ( SENV) has been tentatively linked to transfusion- associated non - A - E hepatitis. We investigated SENV’s role in unexplained hepatitis in other settings. Polymerase chain reaction amplification was used to detect 2 SENV variants ( SENV- D and SENV- H) in 1706 patients and control subjects. SENV was detected in 54 ( 22%) of 248 patients with acute or chronic non - A - E hepatitis, 9 ( 35%) of 26 patients with hepatitis-associated aplastic anemia, and 0 of 17 patients with cryptogenic acute liver failure, compared with 150 ( 24%) of 621 control subjects with liver disease and 76 ( 10%) of 794 healthy control subjects. When controlling for geographic region, the prevalence of SENV among case and control subjects was not significantly different. The severity of acute or chronic hepatitis A, B, or C was not influenced by coexisting SENV infection. No etiological role for SENV in the cause of cryptogenic hepatitis could be demonstrated.

Article, JOURNAL OF HEPATOLOGY. 52(Supplement 1):S286-S286 (2010)

Patients with hepatocellular carcinoma (HCC), gastrointestinal, lung, and ovarian cancers were shown to have autoantibodies to nuclear and nucleolar antigens as detected by immunofluorescence on cell substrates. The frequency of antinuclear antibodies (ANAs) was significantly higher (P less than 0.001) in patients with HCC (57/184 = 31%) than in patients with chronic hepatitis or liver cirrhosis (25/187 = 13%). Although a range of fluorescence patterns was observed, a higher percentage of nucleolar fluorescence was detected in HCC, and three of these nucleolar antigens were identified. They were NOR-90, nucleolus organizer region doublet polypeptides of 93 and 89 kDa involved in RNA polymerase I transcription; fibrillarin, a 34 kDa protein of the nucleolar U3 ribonucleoprotein particle which is engaged in preribosomal RNA processing; and nucleophosmin/protein B23, a 37 kDa polypeptide which is associated with ribosome maturation and cellular proliferation. All these antigens are nucleolar components that are engaged in some aspect of ribosome biosynthesis. Since autoantibodies to these nucleolar antigens have also been found in systemic autoimmune diseases, they do not represent autoimmune reactions unique to cancer but might reflect reaction pathways related to immune responses that are antigen-driven. The ANA response in HCC appears to be dynamic reactions to this antigen-drive since some patients with chronic liver disease showed seroconversion to ANA positivity, marked increase in titer and/or change in antibody specificity preceding or coincident with clinical detection of HCC. These changes in ANA showed a close temporal relationship with transformation from long-established chronic liver disease to HCC.