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| 1 | Alcohol metabolites and lipopolysaccharide: Roles in the development and/or progression of alcoholic liver disease显示文摘The onset of alcoholic liver disease (ALD) is initiated by different cell types in the liver and a number of different factors including: products derived from ethanol-induced inflammation, ethanol metabolites, and the indirect reactions from those metabolites. Ethanol oxidation results in the production of metabolites that have been shown to bind and form protein adducts, and to increase inflammatory, fibrotic and cirrhotic responses. Lipopolysaccharide (LPS) has many deleterious effects and plays a significant role in a number of disease processes by increasing inflammatory cytokine release. In ALD, LPS is thought to be derived from a breakdown in the intestinal wall enabling LPS from resident gut bacterial cell walls to leak into the blood stream. The ability of adducts and LPS to independently stimulate the various cells of the liver provides for a two-hit mechanism by which various biological responses are induced and result in liver injury. Therefore, the purpose of this article is to evaluate the effects of a two-hit combination of ethanol metabolites and LPS on the cells of the liver to increase inflamma-tion and fi brosis, and play a role in the development and/or progression of ALD. | Courtney S Schaffert Michael J Duryee Carlos D Hunter Bartlett C Hamilton 3rd Amy L DeVeney Mary M Huerter Lynell W Klassen Geoffrey M Thiele | 2009 | World Journal of Gastroenterology2009，15，10： | 20 |
| 2 | Osteopontin is an important mediator of alcoholic liver disease via hepatic stellate cell activation显示文摘AIM: To investigate over-expression of Osteopontin(OPN) pathway expression and mechanisms of action in human alcoholic liver disease(ALD), in vivo and in vitro acute alcohol models. METHODS: OPN pathway was evaluated in livers from patients with progressive stages of human ALD and serum from drinkers with and without liver cirrhosis. In vitro stellate LX2 cells exposed to acute alcohol and in vivo in acute alcoholic steatosis mouse models were also investigated for OPN pathway expression and function. WT and OPN-/- mice were administered an acute dose of alcohol and extent of liver injury was examined by histopathology and liver biochemistry after 16-24 h. The causative role of OPN was studied in OPN knockout animals and in vitro in stellate LX2 cells, utilizing siRNA, aptamer and neutralizing antibodies to block OPN and OPN pathway. OPN pathway expression and downstream functional consequences were measured for signaling by Western blotting, plasmin activation by spectrophotometric assays and cell migration by confocal imaging and quantitation. RESULTS: OPN expression positively correlated with disease severity in patients with progressive stages of ALD. In vivo, associated with alcoholic steatosis, a single dose of acute alcohol significantly increased hepatic OPN mRNA and protein, and a cleaved OPN form in a dose dependent manner. OPN mRNA and secreted OPN also increased in parallel with activation of LX2 stellate cells within 4 h of a single dose of alcohol. Expression of OPN receptors, αvβ3-integrin and CD44, increased in human ALD, and in vivo and in vitro with alcohol administration. This was accompanied by downstream phosphorylation of Akt and Erk, increased mRNA expression of several fibrogenesis, fibrinolysis and extracellular matrix pathway genes, plasmin activation and hepatic stellate cell(HSC) migration. Inhibition of OPN and OPN-receptor mediated signaling partially inhibited alcohol-induced HSC activation, plasmin activity and cell migration. CONCLUSION: OPN is a key mediator of the alcoholinduced effects on hepatic stellate cell functions and liver fibrogenesis. | Devanshi Seth Alastair Duly Paul C Kuo Geoffrey W McCaughan Paul S Haber | 2014 | World Journal of Gastroenterology2014，20，36： | 5 |
| 3 | Rate Coefficients for the Thermal Decomposition of BrONO2 and the Heat of Formation of BrONO2 显示文摘 | John J O Geoffrey S T | 1996 | J Phys Chem1996，100，19： | 2 |
| 4 | Whey and whey proteins: From 'gutterto-gold'显示文摘 | GEOFFREY W SMITHER S | 2008 | International Dairy Journal2008，18，： | 1 |
| 5 | Coral decline threatens fish biodiversity in marine reserves显示文摘 | GEOFFREY P J MARK I M MAYA S | 2004 | Proceedings of the National Academy of Sciences of the USA2004，101，： | 1 |
| 6 | An interna for the determination of puri fled microcystin-LR and microcystins in cyanobacterial field material显示文摘 | JUTTA F GEOFFREY A C tional intercomparison exercise JAMES S | 2002 | Anal Bioanal Chem2002，374，： | 1 |
| 7 | Effect of organic-matter type and thermal maturity on methane adsorption in shale-gas systems显示文摘 | Zhang T Geoffrey S E Stephen C R etal | 2012 | Organic Geo- chemistry2012，47，： | 1 |
| 8 | Redefining antifouling coating显示文摘 | Geoffrey S | 1999 | Journal of Protec- tive Coatings& Linings1999，16，9： | 1 |
| 9 | Association of fibrinogen with cardlo-vasocular risk factors and cardiovascular disease in the framingham off- spring population显示文摘 | James JS Halit S Geoffrey HT et el | 2000 | Circulation2000，102，： | 1 |
| 10 | Bacterial leaching of nickel laterites using chemolithotrophic microor- ganisms: proxess optimization using response surface meth- odology and central composite rotatable design 显示文摘 | GEOFFREY S S SEHLISELO N MARIEKIE G | 2009 | Hydro- metallurgy2009，98，34： | 1 |
| 11 | Rhinoplasty for cleft and hemangioma-related nasal deformities显示文摘 | Thomas S Geoffrey Lee Schwartz M | 2010 | Head and Neck Surgery2010，18，： | 1 |
| 12 | Selenium:an essential element for immune function显示文摘 | Roderick C M Teresa S R Geoffrey J B | 1998 | Immunology today1998，19，8： | 1 |
| 13 | Simulation of gas-solid flows in riser using energy minimization multiscale model:effect of cluster diameter correlation显示文摘 | Milinkumar T S Ranjeet P U Moses O T Vishnu K P Geoffrey M E | | 0，，： | 1 |
| 14 | Association of fibrinogen with cardio-vascular risk factors and cardiovascular disease in the framingham off- spring populatlon显示文摘 | James JS Halit S Geoffrey HT | 2000 | Circulation2000，102，： | 1 |
| 15 | von Willebrand factor and urinary albumin excretion are possible indicators of endothelial dysfunction in cardiopulmonary bypass显示文摘 | Allen S Pagano D | 1998 | Fur J Cardiothorac Surg1998，，4： | 1 |
| 16 | A sound type system for secure flow analysis显示文摘 | Volpano D Geoffrey S Irvine Cynthia | 1996 | Journal of Computer Security1996，4，3： | 1 |
| 17 | The Grain Refining of Aluminum and Phase Relationships the Al-Ti-B System显示文摘 | Geoffrey K S | 1984 | Metal Trans A1984，15，2： | 1 |
| 18 | Lipid profiling identifies a triacylglycerol signature of insulin resistance and improves diabetes prediction in humans显示文摘 | Rhee Eugene P Cheng Susan Larson Martin G Walford Geoffrey A Lewis Gregory D McCabe Elizabeth Yang Elaine Farrell Laurie Fox Caroline S O’Donnell Christopher J Carr Steven A Vasan Ramachandran S Florez Jose C Clish Clary B Wang Thomas J Ger | 2011 | Journal of Clinical Investigation2011，，4： | 1 |
| 19 | Characteristics of cellulase preparations affecting the simultaneous saccharification and fermentation of cellulose to ethanol显示文摘 | GEOFFREY J D GRANT A S | 2000 | Biotechnology Letten2000，，22： | 1 |
| 20 | Serine 15 phospho rylation of p53 directs its interaction with B56 and the tumor suppressor activity of B56- Specific protein phosphatase 2A显示文摘 | Geoffrey P S Xin Cai Xuan Liu | 2008 | Mol Cell Biol2008，28，： | 1 |
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