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| 1 | Three-dimensional perfused human in vitro model of nonalcoholic fatty liver disease显示文摘AIM To develop a human in vitro model of non-alcoholic fatty liver disease(NAFLD), utilising primary hepatocytes cultured in a three-dimensional(3D) perfused platform. METHODS Fat and lean culture media were developed to directly investigate the effects of fat loading on primary hepatocytes cultured in a 3D perfused culture system. Oil Red O staining was used to measure fat loading in the hepatocytes and the consumption of free fatty acids(FFA) from culture medium was monitored. Hepatic functions, gene expression profiles and adipokine release were compared for cells cultured in fat and lean conditions. To determine if fat loading in the system could be modulated hepatocytes were treated with known anti-steatotic compounds. RESULTS Hepatocytes cultured in fat medium were found to accumulate three times more fat than lean cells and fat uptake was continuous over a 14-d culture. Fat loading of hepatocytes did not cause any hepatotoxicity and significantly increased albumin production. Numerous adipokines were expressed by fatty cells and genes associated with NAFLD and liver disease were upregulated including: Insulin-like growth factorbinding protein 1, fatty acid-binding protein 3 and CYP7A1. The metabolic activity of hepatocytes cultured in fatty conditions was found to be impaired and the activities of CYP3A4 and CYP2C9 were significantlyreduced, similar to observations made in NAFLD patients. The utility of the model for drug screening was demonstrated by measuring the effects of known antisteatotic compounds. Hepatocytes, cultured under fatty conditions and treated with metformin, had a reduced cellular fat content compared to untreated controls and consumed less FFA from cell culture medium.CONCLUSION The 3D in vitro NAFLD model recapitulates many features of clinical NAFLD and is an ideal tool for analysing the efficacy of anti-steatotic compounds. | Tomasz Kostrzewski Terri Cornforth Sophie A Snow Larissa Ouro-Gnao Cliff Rowe Emma M Large David J Hughes | 2017 | World Journal of Gastroenterology2017，23，2： | 6 |
| 2 | Suppression of host immune response by the core protein of hepatitis C virus: possible implications for hepatiits C virus persistence显示文摘 | Large M K Kittlesen D J Hahn Y S | 1999 | J Immunol1999，162，2： | 2 |
| 3 | Measuring glycerol turnover,glu-coneogenesis from glycerol,and total gluconeogenesis withglycerol:role of the infusion-sampling mode显示文摘 | Peroni 0 Large V Odeon M | 1996 | Metabolism1996，45，7： | 1 |
| 4 | Prevalence and Risk Factors of Violence by Psychiatric Acute Inpa- tients: A Systematic Review and Meta-Analysis 显示文摘 | IOZZINO L FERRARI C LARGE M | 2015 | PLoS One2015，10，01： | 1 |
| 5 | Modifications of citric acid cycle activity and gluconeogenesis in streptozotoc in 2 induced diabetes and effect of mefformin显示文摘 | LARGE V BEYLOT M | 1999 | Diabetes1999，48，6： | 1 |
| 6 | Chaperones and protein folding in the archaea显示文摘 | Large A T Goldberg M D Lund P A | 2009 | Biochem Soc Trans2009，37，1： | 1 |
| 7 | Reach-scale sediment transfers: An evaluation of two morphological budgeting approaches显示文摘 | Fuller I C Large A R G Charlton M E | 2003 | Earth Surface Processes and Landforms2003，28，8： | 1 |
| 8 | Characteristics of homicide offenders with Schizophrenia from the Russian Federation显示文摘 | Golenkov A Large M Nielssen O | | 0，，1： | 1 |
| 9 | Multilayer Reflectors in Animals Using Green and Gold Beetles as Con- trasting Examples显示文摘 | PARKER A R MCKENZIE D R LARGE M C J | 1998 | J Exp Biol1998，201，： | 1 |
| 10 | The endothelium in clinical cardiac transplantation显示文摘 | Stoica S C Goddard M Large S R | 2002 | Ann Thorac Surg2002，73，3： | 1 |
| 11 | Chaperones and protein folding in the archaea 显示文摘 | Large A T Goldberg M D Lund P A | 2009 | Biochena Soe Trans2009，37，： | 1 |
| 12 | Basin-scale, high-wavenumber sea surface wind fields from a multiresolution analysis of scattermeterdata显示文摘 | CHIN T M MILLIFF R F LARGE W G | 1998 | J Atmos Oceanic Tech1998，15，： | 1 |
| 13 | The danger of dangerousness : why we must remove the dangerousness criterion from our mental health acts 显示文摘 | LARGE M M RYAN C J NEII-SSEN O B HAYES R A | 2008 | Journal of Medical Ethics2008，34，12： | 1 |
| 14 | High dynamic range characterization of the trauma patient plasma proteome显示文摘 | Liu T Qian W J Gritsenko M A Xiao W Moldawer L L Kaushal A Monroe M E Vamum S M Moore R J Purvine S O Maier R V Davis R W Tompkins R G Camp D G 2nd Smith R D and the Inflammation and the Host Response to Injury Large Scale Collaborative Research Programm | | 0，，10： | 1 |
| 15 | Mental health acts that require dangerousness for involuntary admission may delay the initial treatment of schizophrenia 显示文摘 | LARGE M M NEILSSEN O B RYAN C J | 2008 | Soc Psychiatry Psychiatr Epidemiol2008，，43： | 1 |
| 16 | Hidden scabies:diagnosis by polymerase chain reaction显示文摘 | Bezold G Large M Schiener R | 2001 | Br J Dermatol2001，144，： | 1 |
| 17 | The relationship between the duration of untreated psychosis and outcome in low-and-middle income countries:A systematic review and meta analysis显示文摘 | Farooq S Large M Nielssen O | 2009 | Schizophrenia Research2009，109，13： | 1 |
| 18 | The preclinical pharmacology of 'arimidex' (anastrozole; zd 1033)-a potent, selective aromatase inhibitor 显示文摘 | MICHAEL D EDWARDS PN LARGE M | 1996 | J Steroid Biochem Molec Biol1996，58，4： | 1 |
| 19 | A global land-grab显示文摘 | Large M Ravenscroft N | 2009 | The Ecologist2009，39，2： | 1 |
| 20 | Microstructured polymer optical fibre 显示文摘 | Van eijkelenborg M A Large M C J Argyros A | 2001 | Optics Express2001，，9： | 1 |
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