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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 | Immunological response in alcoholic liver disease显示文摘The development of alcoholic liver disease (ALD) can be attributed to many factors that cause damage to the liver and alter its functions. Data collected over the last 30 years strongly suggests that an immune component may be involved in the onset of this disease. This is best evidenced by the detection of circulating autoantibodies, infiltration of immune cells in the liver, and the detection of hepatic aldehyde modified proteins in patients with ALD. Experimentally, there are numerous immune responses that occur when proteins are modified with the metabolites of ethanol. These products are formed in response to the high oxidative state of the liver during ethanol metabolism, causing the release of many inflammatory processes and potential of necrosis or apoptosis of liver cells. Should cellular proteins become modified with these reactive alcohol metabolites and be recognized by the immune system, then immune responses may be initiated. Therefore, it was the purpose of this article to shed some insight into how the immune system is involved in the development and/or progression of ALD. | Michael J Duryee Lynell W Klassen Geoffrey M Thiele | 2007 | World Journal of Gastroenterology2007，13，37： | 9 |
| 3 | 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 |
| 4 | FK506对实验性卒中疗效的系统评价和Meta分析显示文摘FK506是治疗急性卒中的一种候选用药。决定一种药物是否可以用于临床试验,应当以全面的、无偏倚的动物实验数据的评估为依据,同时还应考虑到这些数据的局限性。这种评估不但应包括药物疗效,而且也应包括药效在体内的特征和局限性。本研究应用系统评价和Meta分析的方法对FK506在卒中动物模型中保护作用的证据进行评价。总共纳入了29个描述了实验步骤的研究,包括1759只动物。结果显示,FK506疗效的点估计值(结局指标的改善)是31.3%[95%CI(0.272-0.354)]。在采用氯胺酮麻醉和短暂性脑缺血的动物实验中,FK506的疗效更高,在使用大鼠,合并其他疾病的动物及仅以梗死面积为疗效指标的实验中,FK506疗效较低。已发表的实验研究质量均接近临床试验标准,但在高质量的研究中,FK506的疗效较低。FK506在实验性脑卒中的研究中,虽然显示出有明显的疗效,但是应注意由于研究质量和可能的发表偏倚等冈素的影响,FK506的疗效可能被过高估计。 | Malcolm R Macleod Tori O’Collins Laura L Horky David W Howells Geoffrey A Donnan 段建钢 | 2006 | 中国循证医学杂志2006，6，6： | 3 |
| 5 | Insulin resistance is associated with chronic hepatitis C and virus infection fibrosis progression显示文摘 | Jason M Hui Archana Sud Geoffrey C Farrell Priyanka Bandara Karen Byth James G Kench Geoffrey W McCaughan Jacob George | 2003 | Gastroenterology2003，，6： | 2 |
| 6 | Accumulation of colbalt zinc and mang nese by the estuarine green microalgae chlorella salina immobilize in alginatemicrobeads显示文摘 | Rehm H J | 1992 | Environ Sci Technol1992，26，1： | 1 |
| 7 | Whey and whey proteins: From 'gutterto-gold'显示文摘 | GEOFFREY W SMITHER S | 2008 | International Dairy Journal2008，18，： | 1 |
| 8 | Parameters affecting the growth and hydrogen production of the green alga Chlamydomonas reinhardtil显示文摘 | Bojan T Fessehaye W Z Geoffrey C M | 2011 | Intemafional Journal of Hydrogen Energy2011，36，13： | 1 |
| 9 | Estimation of common long-memory components in cointegrated systems 显示文摘 | Raymond W Geoffrey G | 1995 | Journal of Business and Economic Statistics1995，13，1： | 1 |
| 10 | Tourism Attractions: Points, Lines, and Areas显示文摘 | Geoffrey W | 1997 | Annals of Tourism Research1997，24，1： | 1 |
| 11 | Ecotourism: Towards Congruence between Theory and Praetiee显示文摘 | Sheryl R Geoffrey W | 1999 | Tourism Managemertt1999，，20： | 1 |
| 12 | New method of presulfiding catalyst which can reduce releasing thermal of hydrocracking equipment显示文摘 | Stephen B Geoffrey B David W | 1998 | Oil and Gas Journal1998，1，5： | 1 |
| 13 | Privately funded infrastructure in the UK: Participants' risk in the skye bridge project 显示文摘 | Peter M Geoffrey W | 1995 | Transport Policy1995，2，2： | 1 |
| 14 | Hepatitis C virus treatment in the real world: optimising treatment and access to therapies显示文摘 | Zoulim Fabien Liang T Jake Gerbes Alexander L Aghemo Alessio Deuffic-Burban Sylvie Dusheiko Geoffrey Fried Michael W Pol Stanislas Rockstroh Ju?rgen Kurt Terrault Norah A Wiktor Stefan | 2015 | Gut2015，，11： | 1 |
| 15 | Ligand control of coregulator recruitment to nuclear receptors 显示文摘 | KENDALL W N GEOFFREY L G | 2005 | Annual Review of Physiology2005，67，： | 1 |
| 16 | Genetic polynmr- phisms of MDM2, cumulative cigarette smoking and nonsmall cell lung cancer risk显示文摘 | Geoffrey L Wheatley-Price P Zhou W | 2008 | Int J Cancer2008，122，4： | 1 |
| 17 | Bacteriophages: an appraisal of their role in the treatment of bacterial infections显示文摘 | GEOFFREY W H | 2007 | International Journal of Antimicrobial Agents2007，30，： | 1 |
| 18 | Monetary Policy and Financial Liberalization:The Case of United Kingdom Consumption 显示文摘 | Maria C G Geoffrey W | 2001 | Journal of Macroeconomics2001，23，： | 1 |
| 19 | Automated surface subdivision and tool path generation for 3 - axis CNC machining of sculptured parts显示文摘 | Zezhong Chen Zuomin Dong Geoffrey W Vickers | 2003 | Computers in Industry2003，50，： | 1 |
| 20 | Strategies for Two-sided markets显示文摘 | Geoffrey Parker Marshall W | 2006 | Harvard Business Review2006，，12： | 1 |
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