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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 | Species sensitivity distributions: data and model choice 显示文摘 | WHEELER J R GRIST E P M LEUNG K M Y | 2002 | Mar Pollut Bull2002，45，： | 1 |
| 3 | Species sensitivity distributions:data and model choice 显示文摘 | WHEELER J R GRIST E P M LEUNG K M ~ | 2002 | Mar PoUut Bull2002，45，123456789101112： | 1 |
| 4 | Screening of anabolic steroids in horse urine by liquid chromatography-tandem mass spectrometry显示文摘 | Yu N H Ho E N M Leung D K K | 2005 | J Pharm Biomed Anal2005，37，： | 1 |
| 5 | Recombi- nation is associated with an outbreak of novel highly pathogenic porcine reproductive and respiratorysyn- drome viruses in China显示文摘 | Shi M Holmes E C Brar M S Leung F C | 2013 | J Virol2013，87，10： | 1 |
| 6 | Studies on thallium toxicity,its tissue distribution and histopathologucal effects in rats显示文摘 | Leung K M Ooi V E C | 2000 | Chemosphere2000，41，： | 1 |
| 7 | Photonic Band Structure: The Face-Centered-Cubic Case Employing Nonspherical Atoms显示文摘 | Yablonovitch E Gmitter T J Leung K M | 1991 | Physical Review Letters1991，672，295： | 1 |
| 8 | Species sensitivity distributions:Data and model choice显示文摘 | Wheeler J R Crista E P M Leung K M Y | 2002 | Marine Pollution Bulletin2002，45，19： | 1 |
| 9 | The Gaussian wire-tap channel显示文摘 | Leung S K Hellman M E | 1978 | IEEE Transaction on Information Theory1978，24，4： | 1 |
| 10 | The development and validation of a dynamic fracture propagation model for gas transmission pipelines显示文摘 | O'Donoghue P E Kanninen M F Leung C P | 1997 | Int J Pres Ves Pip1997，70，1： | 1 |
| 11 | Spe- cies sensitivity distributions:data and model choice显示文摘 | WHEELER J R GRIST E P M LEUNG K M Y | 2002 | Marine Pollution Bulletin2002，45，123456789101112： | 1 |
| 12 | Photonic band structure: the face-centered-cubic case employing nonspherical atoms显示文摘 | Yablonovitch E Gmitter T J Leung K M | 1991 | Physical Review Letters1991，67，17： | 1 |
| 13 | Toll‐like receptors 2 and 4 and the cryopyrin inflammasome in normal pregnancy and pre‐eclampsia显示文摘 | F Xie Y Hu SE Turvey LA Magee RM Brunham K‐C Choi M Krajden PCK Leung DM Money DM Patrick E Thomas P von Dadelszen | 2009 | BJOG: An International Journal of Obstetrics & Gy2009，，： | 1 |
| 14 | The impact of different land-supplying channels on the supply of housing显示文摘 | Hui E C M Leung B Y P Yu K H | 2014 | Land Use Policy2014，39，7： | 1 |
| 15 | Pulmonary cryptococcosis : CT and pathologic findings 显示文摘 | ZINCK S E LEUNG A N FROST M | 2002 | J Comput Assist Toumogr2002，26，3： | 1 |
| 16 | Mouse B7-H3 induces antitumor immunity显示文摘 | Sun X Vale M Leung E | 2003 | Gene Ther2003，10，20： | 1 |
| 17 | Photonic Band Structure:The face-centered-cubicease employing nonspherieal atoms 显示文摘 | Yablonovitch E Gmiter T J Leung K M | 1991 | Phys Rev Lett1991，67，17： | 1 |
| 18 | Photonic band structure:the face-centered-cubic case employing nonspherical atoms显示文摘 | Yablonovitch E Gmitterly T J Leung K M | 1991 | Phys Rev Lett1991，67，： | 1 |
| 19 | Bowel obstruction following appendectomy:what is the true incidence?显示文摘 | LEUNG TT DIXON E GILL M | 2009 | Ann Surg2009，250，1： | 1 |
| 20 | A 16-kDa protein functions as a newregulatory protein for Hsc70molecular chaperone and is identified as a member of the Nm23/uncleoside diphosphatekinase family显示文摘 | Leung S M Hightower L E | 1997 | J Biol Chem1997，272，5： | 1 |
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