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| 1 | Dietary advanced glycation end-products aggravate non-alcoholic fatty liver disease显示文摘AIM To determine if manipulation of dietary advanced glycation end product(AGE), intake affects nonalcoholic fatty liver disease(NAFLD) progression and whether these effects are mediated via RAGE. METHODS Male C57Bl6 mice were fed a high fat, high fructose, high cholesterol(HFHC) diet for 33 wk and compared with animals on normal chow. A third group were given a HFHC diet that was high in AGEs. Another group was given a HFHC diet that was marinated in vinegar to prevent the formation of AGEs. In a second experiment, RAGE KO animals were fed a HFHC diet or a high AGE HFHC diet and compared with wildtype controls. Hepatic biochemistry, histology, picrosirius red morphometry and hepatic mR NA were determined. RESULTS Long-term consumption of the HFHC diet generated significant steatohepatitis and fibrosis after 33 wk. In this model, hepatic 4-hydroxynonenal content(a marker of chronic oxidative stress), hepatocyte ballooning, picrosirius red staining, α-smooth muscle actin and collagen type 1A gene expression were all significantly increased. Increasing the AGE content of the HFHC diet by baking further increased these markers of liver damage, but this was abrogated by pre-marination in acetic acid. In response to the HFHC diet, RAGE-/-animals developed NASH of similar severity to RAGE+/+ animals but were protected from the additional harmful effects of the high AGE containing diet. Studies in isolated Kupffer cells showed that AGEs increase cell proliferation and oxidative stress, providing a likely mechanism through which these compounds contribute to liver injury. CONCLUSION In the HFHC model of NAFLD, manipulation of dietary AGEs modulates liver injury, inflammation, and liver fibrosis via a RAGE dependent pathway. This suggests that pharmacological and dietary strategies targeting the AGE/RAGE pathway could slow the progression of NAFLD. | Christopher Leung Chandana B Herath Zhiyuan Jia Sof Andrikopoulos Bronwyn E Brown Michael J Davies Leni R Rivera John B Furness Josephine M Forbes Peter W Angus | 2016 | World Journal of Gastroenterology2016，22，35： | 7 |
| 2 | Mercury Levels in Eggs, Tissues, and Feathers of Herring Gulls Larus argentatus From the German Wadden Sea Coast 显示文摘 | LEWIS S A BECKER P H FURNESS R W | 1993 | Environmental Pollution1993，80，3： | 1 |
| 3 | Historical Changes in Mercury Concentration in the Marine Ecosystem of the North and Northeast Atlantic Ocean as Indicated by Seabird Feathers 显示文摘 | THOMPSON D R FURNESS R W WALSH P M | 1992 | Journal of Applied Ecology1992，29，1： | 1 |
| 4 | nanoporous carbons with a 3D nanonetwork-interconnected 2D ordered mesoporous structure for rapid mass transport 显示文摘 | LIANG Y R LI Z H FUR W | 2013 | J Mater Chem:A2013，1，11： | 1 |
| 5 | Sea- sonal variation in heavy metal levels in tissues of common guillemots, Uria aalge from northwest Scot- land显示文摘 | Stewart F M Thompson D R Furness R W | 1994 | Archives of Environmental Contamination and Toxicology1994，27，2： | 1 |
| 6 | The demands of incubation and avian clutch size 显示文摘 | THOMSON D L MONAGHAN P FURNESS R W | 1998 | Biological Reviews1998，73，3： | 1 |
| 7 | Biomimetic growth of apatite on hydrogen-implanted silicon 显示文摘 | LIU X Y FUR K Y POON R W Y | 2004 | Biomaterials2004，25，6： | 1 |
| 8 | HIV Testing Frequency Among Men Who Have Sex With Men Attending Sexually Transmitted Disease Clinics: Implications for HIV Prevention and Surveillance显示文摘 | Donna J Helms Hillard S Weinstock Kristen C Mahle Kyle T Bernstein Bruce W Furness Charlotte K Kent Cornelis A Rietmeijer Akbar M Shahkolahi James P Hughes Matthew R Golden | 2009 | JAIDS Journal of Acquired Immune Deficiency Syndromes2009，，3： | 1 |
| 9 | Mercury levels in eggs,tissues, and feathers of herring gulls Larus argentatus from the German Wadden Sea coast显示文摘 | LEWIS S A BECKER P H FURNESS R W | 1993 | Enviromental Pollution1993，80，： | 1 |
| 10 | Historical changes in mercury concentration in the marine ecosystem of the north and north-east Atlantic ocean as indicated by seabird feathers显示文摘 | THOMPSON D R FURNESS R W WALSH P M | 1992 | Journal of Applied Ecology1992，29，： | 1 |
| 11 | Mercury level in the Plumage of Red-billed Gulls Larus novaehollandiae scopulinus of known sex and age显示文摘 | FURNESS R W LEWIS S A MILLS J A | 1990 | Enviromental Pollution1990，63，： | 1 |
| 12 | Mercury in feathers of little egret Egretta gazettaand night heron Nycticorax nycticorax chicks and in their prey in the Axios Delta,Greece 显示文摘 | Goutner V Furness R W | 1997 | Archives of Environmental Contamination and Toxicology1997，32，： | 1 |
| 13 | QT dispersion and components of the interval in ischemia and infarction 显示文摘 | Higham P O Furness S S Campbell R W F | 1995 | Br Heart J1995，73，： | 1 |
| 14 | Toxicity of heavy solved in sea water and influences of sex metals dis- and size on metal accumulation and tissue distribution in the nor- way lobster Nephrops norvegicus 显示文摘 | Canli M Furness R W | 1993 | Mar Environ Res1993，36，4： | 1 |
| 15 | Toxicity of heavy metals dissolved in sea water and influences of sex and size on metal accumulation and tissue distribution in the norway lobster Nephrops norvegicus 显示文摘 | CANLI M FURNESS R W | 1993 | Marine Environmental Research1993，36，4： | 1 |
| 16 | Mercury and cadmium uptake from seawater and from food by the Norway lobster Nephrops norvegicus显示文摘 | Canli M Furness R W | 1995 | Environmental Toxicology&Chemistry1995，14，5： | 1 |
| 17 | Seasonal variation in heavy metal levels in tissues of common guillemots, Uria alga from Northwest Scotland显示文摘 | STEWART F M THOMPSON D R FURNESS R W | 1994 | Arch Environ Contam Toxicol1994，27，2： | 1 |
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