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| 1 | Hyperhomocysteinemia, endoplasmic reticulum stress, and alcoholic liver injury显示文摘Deficiencies in vitamins or other factors (B6, B12, folic acid, betaine) and genetic disorders for the metabolism of the non-protein amino acid-homocysteine (Hcy) lead to hyperhomocysteinemia (HHcy). HHcy is an integral component of several disorders including cardiovascular disease, neurodegeneration, diabetes and alcoholic liver disease. HHcy unleashes mediators of inflammation such as NFkB, IL-1β, IL-6, and IL-8, increases production of intracellular superoxide anion causing oxidative stress and reducing intracellular level of nitric oxide (NO), and induces endoplasmic reticulum (ER) stress which can explain many processes of Hcy-promoted cell injury such as apoptosis, fat accumulation, and inflammation. Animal models have played an important role in determining the biological effects of HHcy. ER stress may also be involved in other liver diseases such as a1-antitrypsin (a1-AT) deficiency and hepatitis C and/or B virus infection. Future research should evaluate the possible potentiative effects of alcohol and hepatic virus infection on ER stress-induced liver injury, study potentially beneficial effects of lowering Hcy and preventing ER stress in alcoholic humans, and examine polymorphism of Hcy metabolizing enzymes as potential risk-factors for the development of HHcy and liver disease. | Neil Kaplowitz | 2004 | World Journal of Gastroenterology2004，10，12： | 63 |
| 2 | The gut microbial metabolite, 3,4-dihydroxyphenylpropionic acid, alleviates hepatic ischemia/reperfusion injury via mitigation of macrophage pro-inflammatory activity in mice显示文摘Hepatic ischemia/reperfusion injury(HIRI) is a serious complication that occurs following shock and/or liver surgery. Gut microbiota and their metabolites are key upstream modulators of development of liver injury. Herein, we investigated the potential contribution of gut microbes to HIRI.Ischemia/reperfusion surgery was performed to establish a murine model of HIRI. 16 S r RNA gene sequencing and metabolomics were used for microbial analysis. Transcriptomics and proteomics analysis were employed to study the host cell responses. Our results establish HIRI was significantly increased when surgery occurred in the evening(ZT12, 20:00) when compared with the morning(ZT0, 08:00);however, antibiotic pretreatment reduced this diurnal variation. The abundance of a microbial metabolite3,4-dihydroxyphenylpropionic acid was significantly higher in ZT0 when compared with ZT12 in the gut and this compound significantly protected mice against HIRI. Furthermore, 3,4-dihydroxyphenylpropionic acid suppressed the macrophage pro-inflammatory response in vivo and in vitro. This metabolite inhibits histone deacetylase activity by reducing its phosphorylation. Histone deacetylase inhibition suppressed macrophage pro-inflammatory activation and diminished the diurnal variation of HIRI. Our findings revealed a novel protective microbial metabolite against HIRI in mice. The potential underlying mechanism was at least in part, via 3,4-dihydroxyphenylpropionic acid-dependent immune regulation and histone deacetylase(HDAC) inhibition in macrophages. | Rui Li Li Xie Lei Li Xiaojiao Chen Tong Yao Yuanxin Tian Qingping Li Kai Wang Chenyang Huang Cui Li Yifan Li Hongwei Zhou Neil Kaplowitz Yong Jiang Peng Chen | 2022 | Acta Pharmaceutica Sinica B2022，12，1： | 8 |
| 3 | Herb-Induced Liver Injury: A Global Concern显示文摘Chinese medicine and herb medicine though used to treat liver diseases are an important cause of liver injury. Many phytochemicals have the potential to injure the liver, some in a dose-related fashion and more often in an idiosyncratic fashion, meaning occurrence is uncommon to rare in the population using these treatments. As is the case with pharmaceuticals, the phytochemicals are usually tolerated despite either no or mild transient subclinical injury but rarely in some susceptible patients cause moderate to severe liver injury which is likely mediated by the adaptive immune system. | Neil Kaplowitz | 2018 | Chinese Journal of Integrative Medicine2018，24，9： | 5 |
| 4 | Impact of Hepatopulmonary Syndrome on Quality of Life and Survival in Liver Transplant Candidates显示文摘 | Michael B. Fallon Michael J. Krowka Robert S. Brown James F. Trotter Steven Zacks Kari E. Roberts Vijay H. Shah Neil Kaplowitz Lisa Forman Keith Wille Steven M. Kawut | 2008 | Gastroenterology2008，，4： | 4 |
| 5 | How Do Delirium and Dementia Increase Length of Stay of Elderly General Medical Inpatients?显示文摘 | Stephen M. Saravay Michael Kaplowitz John Kurek David Zeman Simcha Pollack Sonia Novik Scott Knowlton Michael Brendel Lillian Hoffman | 2011 | Psychosomatics2011，，3： | 3 |
| 6 | Betaine decreases hyperhomocysteinemia, endoplasmic reticulum stress, and liver injury in alcohol-fed mice显示文摘 | Cheng Ji Neil Kaplowitz | 2003 | Gastroenterology2003，，5： | 3 |
| 7 | Current concepts and controversies in the treatment of alcoholic hepatitis显示文摘The treatment of alcoholic hepatitis remains one of the most debated topics in medicine and a field of continued research. In this review, we discuss the evolution of scoring systems, including the recent development of the Glasgow alcoholic hepatitis score, role of liver biopsy and current treatment interventions. Studies of treatment interventions with glucocorticoids, pentoxifylline, infliximab, s-adenosyl-methionine, and colchicine are reviewed with discussion on quality. Glucocorticoids currently remain the mainstay of treatment for severe alcoholic hepatitis. | Catherine Rongey Neil Kaplowitz | 2006 | World Journal of Gastroenterology2006，12，43： | 2 |
| 8 | Regulation of drug-induced liver injury by signal transduction pathways: critical role of mitochondria显示文摘 | Derick Han Lily Dara Sanda Win Tin Aung Than Liyun Yuan Sadeea Q. Abbasi Zhang-Xu Liu Neil Kaplowitz | 2013 | Trends in Pharmacological Sciences2013，，4： | 2 |
| 9 | How do delirium and dementia increase length of stay cff elderly general medical inpatients显示文摘 | Saravay SM Kaplowitz M Kurek J | 2004 | Psychosomafics2004，45，3： | 1 |
| 10 | Drug hepatotoxicity显示文摘 | Nathwani RA Kaplowitz N | 2006 | Clin Liver Dis2006，10，： | 1 |
| 11 | Innate immune system plays a critical role in determining the progression and severity of acetaminophen hepatotoxicity显示文摘 | Liu ZX Govindarajan S Kaplowitz N | 2004 | Gastroenterology2004，，127： | 1 |
| 12 | Drug-induced liver injury显示文摘 | Abboud G Kaplowitz N | 2007 | Drug Saf2007，30，4： | 1 |
| 13 | Liver-specific loss of glucose-regulated protein 78 perturbs the unfolded protein response and exacerbates a spectrum of liver diseases in mice显示文摘 | Ji C Kaplowitz N Lau MY | 2011 | Hepatology2011，54，1： | 1 |
| 14 | Liver biology and pathobiology显示文摘 | Kaplowitz N | 2006 | Hepatology2006，43，21： | 1 |
| 15 | Drug hepatotoxicity 显示文摘 | Nathwani RA Kaplowitz N | 2006 | Clin Liver Dis2006，10，2： | 1 |
| 16 | Unfolding new mechanisms of alcoholic liver disease in the endoplasmic reticulum 显示文摘 | KAPLOWITZ N JI C | 2006 | J Gastroenterol Hepatol2006，21，3： | 1 |
| 17 | Phenotypic characterization of idiosyncratic drug-induced liver injury: the influence of age and sex显示文摘 | Lucena MI Andrade R J Kaplowitz N | 2009 | Hepatology2009，49，： | 1 |
| 18 | Biochemical and cellular mechanisms of toxic liver injury显示文摘 | | 2002 | Semin Liver Dis2002，22，2： | 1 |
| 19 | Drug induced liver injury 显示文摘 | Kaplowitz N | 2004 | Clin Infect Dis2004，38，2： | 1 |
| 20 | Drug hepatotoxicity 显示文摘 | Nathwani RA Kaplowitz N | 2006 | Clin Liver Dis2006，10，2： | 1 |
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