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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 | 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 |
| 4 | 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 |
| 5 | 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 |
| 6 | Tranexamic acid for intracerebral haemorrhage within 2 hours of onset: protocol of a phase Ⅱ randomised placebo-controlled double-blind multicentre trial显示文摘Rationale Haematoma growth is common early after intracerebral haemorrhage(ICH),and is a key determinant of outcome.Tranexamic acid,a widely available antifibrinolytic agent with an excellent safety profile,may reduce haematoma growth.Methods and design Stopping intracerebral haemorrhage with tranexamic acid for hyperacute onset presentation including mobile stroke units(STOP-MSU)is a phase Ⅱ double-blind,randomised,placebo-controlled,multicentre,international investigator-led clinical trial,conducted within the estimand statistical framework.Hypothesis In patients with spontaneous ICH,treatment with tranexamic acid within 2 hours of onset will reduce haematoma expansion compared with placebo.Sample size estimates A sample size of 180 patients(90 in each arm)would be required to detect an absolute difference in the primary outcome of 20%(placebo 39%vs treatment 19%)under a two-tailed significance level of 0.05.An adaptive sample size re-estimation based on the outcomes of 144 patients will allow a possible increase to a prespecified maximum of 326 patients.Intervention Participants will receive 1 g intravenous tranexamic acid over 10 min,followed by 1 g intravenous tranexamic acid over 8 hours;or matching placebo.Primary efficacy measure The primary efficacy measure is the proportion of patients with haematoma growth by 24±6 hours,defined as either≥33%relative increase or≥6 mL absolute increase in haematoma volume between baseline and follow-up CT scan.Discussion We describe the rationale and protocol of STOP-MSU,a phase Ⅱ trial of tranexamic acid in patients with ICH within 2 hours from onset,based in participating mobile stroke units and emergency departments. | Nawaf Yassi Henry Zhao Leonid Churilov Bruce C V Campbell Teddy Wu Henry Ma Andrew Cheung Timothy Kleinig Helen Brown Philip Choi Jiann-Shing Jeng Annemarei Ranta Hao-Kuang Wang Geoffrey C Cloud Rohan Grimley Darshan Shah Neil Spratt Der-Yang Cho Karim Mahawish Lauren Sanders John Worthington Ben Clissold Atte Meretoja Vignan Yogendrakumar Mai Duy Ton Duc Phuc Dang Nguyen Thai My Phuong Huy-Thang Nguyen Chung Y Hsu Gagan Sharma Peter J Mitchell Bernard Yan Mark W Parsons Christopher Levi Geoffrey A Donnan Stephen M Davis | 2022 | Stroke & Vascular Neurology2022，7，2： | 1 |
| 7 | Bioactivity of β-Lactoglobulin and α-alctalbumin-Technological Implications for Processing显示文摘 | DERECK E W C GEOFFREY S PETER R | 2006 | Intemational Dairy Journal2006，，： | 1 |
| 8 | Prevalence of and Risk Factors for Hepatic Steatosis and Nonalcoholic Fatty Liver Disease in People With Type 2 Diabetes: the Edinburgh Type 2 Diabetes Study显示文摘 | Williamson Rachel M Price Jackie F Glancy Stephen Perry Elisa Nee Lisa D Hayes Peter C Frier Brian M Van Look Liesbeth A F Johnston Geoffrey I Reynolds Rebecca M Strachan Mark W J | 2011 | Diabetes Care2011，，5： | 1 |
| 9 | The role of perceived risk in the quality-value relationship:study in a retail envinronment显示文摘 | Sweeney Jillian C Soutar Geoffrey N Johnson Lester W | 1999 | Journal of Retailing1999，75，1： | 1 |
| 10 | Volume h olographic data storage at an areal density of 250 gigapixels/inch2显示文摘 | C Michael Jefferson Hans Coufal | | Op tics Letters0，6，7： | 1 |
| 11 | Air transportation demand forecasts in emerging market economies显示文摘 | Richard C Cline Terry A Ruhl Geoffrey D Gosling David W Gillen | 1998 | Journal of Air Transport Management1998，4，： | 1 |
| 12 | Production of viable homozygous, doubled haploid channel catfish (Ictalurus punctatus) 显示文摘 | Geoffrey C W Brian G B Sylvie M A Q | 2009 | Marine Biotechnology2009，12，： | 1 |
| 13 | Effects of pentoxifylline of cytokine profiles and left ventricular performance in patients with decompensated congestive heart failure secondary to idiopathic dilated cardiomyopathy显示文摘 | KAREN S ANGELA W GEOFFREY C | 2002 | Am J Cardiol2002，90，： | 1 |
| 14 | Accumulation of cobalt,zinc and manganese by the estuarine green microalgae Chlorella salina immobilized in alginate microbeads显示文摘 | Geoffrey W G Geoffrey A C Geoffrey M G | 1992 | Environ Sci Technol1992，26，5： | 1 |
| 15 | Volume holographic data storage at an areal density of 250 gigapixels/in, ^2显示文摘 | Geoffrey W Burr C Michael Jefferson Hans Coufal | 2001 | Opt Lett2001，26，7： | 1 |
| 16 | Phenyl-Perfluorophenyl Stacking Interactions:Topochemical Photodimerization and Photopolymerization of Olefinic Compounds显示文摘 | Geoffrey W C Alex R D Lawrence M | 1998 | J Am Chem Soc1998，110，： | 1 |
| 17 | Monetary policy and financial liberalization:the case of United Kingdom consumption显示文摘 | Maria C G Geoffrey W | | Journal of Macroeco-nomics0，123，： | 1 |
| 18 | The role of perceived risk in the quality-value relationship: A study in a retail environment 显示文摘 | Sweeney J C Geoffrey S N Lester J W | 1999 | Journal of Retailing1999，75，1： | 1 |
| 19 | 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： | 1 |
| 20 | The Role of Perceived Risk in the Quality - Value Relationship: A Study in a Retail Environment显示文摘 | Jillian C Sweeney Geoffrey N Soutar Lester W Johnson | 1999 | Journal of Retailing1999，75，1： | 1 |
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