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| 1 | Obese diet-induced mouse models of nonalcoholic steatohepatitis-tracking disease by liver biopsy显示文摘AIM:To characterize development of diet-induced nonalcoholic steatohepatitis(NASH)by performing live biopsy in wild-type and genetically obese mice.METHODS:Male wild-type C57BL/6J(C57)mice(DIO NASH)and male Lep ob/Lep ob(ob/ob)mice(ob/ob-NASH were maintained on a diet high in trans-fat(40%)fructose(22%)and cholesterol(2%)for 26 and 12 wk respectively.A normal chow diet served as control in C57 mice(lean chow)and ob/ob mice(ob/ob chow)After the diet-induction period,mice were liver biopsied and a blinded histological assessment of steatosis and fibrosis was conducted.Mice were then stratified into groups counterbalanced for steatosis score and fibrosi stage and continued on diet and to receive daily PO dosing of vehicle for 8 wk.Global gene expression in liver tissue was assessed by RNA sequencing and bioin formatics.Metabolic parameters,plasma liver enzyme and lipids(total cholesterol,triglycerides)as well a hepatic lipids and collagen content were measured b biochemical analysis.Non-alcoholic fatty liver disease activity score(NAS)(steatosis/inflammation/ballooningdegeneration)and fibrosis were scored.Steatosis and fibrosis were also quantified using percent fractional area.RESULTS:Diet-induction for 26 and 12 wk in DIONASH and ob/ob-NASH mice,respectively,elicited progressive metabolic perturbations characterized by increased adiposity,total cholesterol and elevated plasma liver enzymes.The diet also induced clear histological features of NASH including hepatosteatosis and fibrosis.Overall,the metabolic NASH phenotype was more pronounced in ob/ob-NASH vs DIO-NASH mice.During the eight week repeated vehicle dosing period,the metabolic phenotype was sustained in DIO-NASH and ob/ob-NASH mice in conjunction with hepatomegaly and increased hepatic lipids and collagen accumulation.Histopathological scoring demonstrated significantly increased NAS of DIO-NASH mice(0 vs4.7±0.4,P<0.001 compared to lean chow)and ob/ob-NASH mice(2.4±0.3 vs 6.3±0.2,P<0.001compared to ob/ob chow),respectively.Furthermore,fibrosis stage was significantly elevated for DIO-NASH mice(0 vs 1.2±0.2,P<0.05 compared to lean chow)and ob/ob NASH(0.1±0.1 vs 3.0±0.2,P<0.001compared to ob/ob chow).Notably,fibrosis stage was significantly(P<0.001)increased in ob/ob-NASH mice,when compared to DIO-NASH mice.CONCLUSION:These data introduce the obese dietinduced DIO-NASH and ob/ob-NASH mouse models with biopsy-confirmed individual disease staging as a preclinical platform for evaluation of novel NASH therapeutics. | Maria Nicoline Baandrup Kristiansen Sanne Skovgard Veidal Kristoffer Tobias Gustav Rigbolt Kirstine Sloth Tolbol Jonathan David Roth Jacob Jelsing Niels Vrang Michael Feigh | 2016 | World Journal of Hepatology2016，8，16： | 10 |
| 2 | SPE HG-AAS method for the determination of inorganic arsenic in rice-Results from method validation studies and a survey on rice products 显示文摘 | RASMUSSEN RR QIAN Y SLOTH J J | 2013 | Analytical and Bioanalytical Chem- istry2013，405，24： | 1 |
| 3 | Nitrification, denitrification and nitrate ammonification in sediments of two coastal lagoons in Southern France显示文摘 | Rysgaard S Risgaard-Petersen N Sloth N | 1996 | Hydrobiologia1996，329，13： | 1 |
| 4 | Nitrification in sediment cores measured with acetylene inhibition 显示文摘 | Sloth N P Nielsen L P Blackburn T H | 1992 | Linmol Oceanogr1992，37，： | 1 |
| 5 | Risk adjustments of option prices un?der time-changed dynamics显示文摘 | Nicolatoa E Sloth D | 2014 | Quantitative Finance2014，14，1： | 1 |
| 6 | Central venous oxygen saturation cannot replace mixed venous saturation in patients undergoing cardiac urgery 显示文摘 | Lorentzen AG Lindskov C Sloth E | 2008 | J Cardiothorac Vasc Anesth2008，22，6： | 1 |
| 7 | Wave overtopping of rubble mound breakwaters 显示文摘 | Hebsgaard M Sloth P Juhl J | 2012 | Coastal Engineering2012，2，： | 1 |
| 8 | Predilution hermditration displays no hemodynamic advantage over low-flux hemodialysis under matched conditions 显示文摘 | Kamnris N Sloth E Jensen JD | 2005 | Kidney Int2005，67，： | 1 |
| 9 | Remote Ischemic Perconditioning Improves Long-Term Clinical Outcome in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction 显示文摘 | Sloth AD Schmidt MR Munk K | 2012 | JACC2012，60，17： | 1 |
| 10 | Intra-aortic balloon pumping increases renal blood flow in patients with low left ventricular ejection fraction 显示文摘 | Sloth E Sprogoe P Lindskov C | 2008 | Perfusion2008，23，4： | 1 |
| 11 | National systems of production,innovation and corn-petence building显示文摘 | Bengt-Ake Lundvall Bjom Johnson Esben Sloth Andersen Bent Dalum | 2002 | Research Policy2002，，31： | 1 |
| 12 | Sediment mineralization, nutrient fluxes, denitrification and dissimila- tory nitrate reduction to ammonium in an estuarine fjord with sea cage trout farms 显示文摘 | Christensen P B Rysgaard S Sloth N P | 2000 | Aquat Microbial Ecology2000，21，1： | 1 |
| 13 | The dynamics of Staphylococcus aureus intramammary infection in nine Danish dairy herds显示文摘 | Larsen H D Sloth K H lsberg C | 2000 | Vet Microbiol2000，71，： | 1 |
| 14 | Sufentanil preserves hemodynamics and left ventricular function in patients with ischemic heart disease 显示文摘 | BHAVSAR R SLOTH E FOLKERSEN L | 2011 | Acta Anaesthesiol Stand2011，55，8： | 1 |
| 15 | Potential for Improving Description of Bovine Udder Health Status by Combined Analysis of Milk Parameters显示文摘 | K.H.M.N. Sloth N.C. Friggens P. L?vendahl P.H. Andersen J. Jensen K.L. Ingvartsen | 2003 | Journal of Dairy Science2003，，4： | 1 |
| 16 | Ultrasound assessment of inferior vena cava collapsibility is not a valid measure of preload changes during triggered positive pressure ventilation:a controlled cross-over study显示文摘 | Juhl-Olsen P Frederiksen CA Sloth E | 2012 | Ultraschall Med2012，33，2： | 1 |
| 17 | Evolutionary learning in signalling games显示文摘 | JACOBSEN H J JENSEN M SLOTH B | 2001 | Games and Economic Behavior2001，34，1： | 1 |
| 18 | Remote is- chemic conditioning: the cardiologist 's perspective 显示文摘 | Schmidt MR Sloth AD Johnsen J | 2012 | J Cardiovase Med (Hagerstown)2012，13，11： | 1 |
| 19 | nitrification and denitrification from mieroprofiles nitrate in model sediment systems 显示文摘 | Jensen K Sloth N P Risgaard-Petersen N | 1994 | Environmental Microbiology1994，60，6： | 1 |
| 20 | Effects of PYY1-36 and PYY3-36 on appetite,energy intake,energy expenditure,glucose and fat metabolism in obese and lean subjects显示文摘 | SLOTH B HOLST JJ FLINT A | | 0，，： | 1 |
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