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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 | Anthocyanin, phenolic composition, colour measurement and sensory analysis of BC commercial red wines显示文摘 | CLIFF M A KING M C SCHLOSSER J | 2007 | Food Research International2007，40，1： | 1 |
| 3 | Peptide composition of enzyme-treated Cheddar cheese slurries,determined by reverse phase high performance liquid chromatography显示文摘 | A J Cliffe B A Law | 1990 | Food Chemistry1990，36，1： | 1 |
| 4 | Anthocyanin, phenolic composi- tion, colour measurement and sensory analysis of BC commercial red wines显示文摘 | Cliff M A King M C Schlosser J | 2007 | Food Research International2007，，40： | 1 |
| 5 | High Performance Liquid Chromatography of Coal Liquefaction Process Streams Using Normal-phase Separation with Diode Array Detection显示文摘 | McKinney D E Cliff ord D J Hou L | 1994 | Amer Chem Soc Div Fuel Chem Prepr1994，39，3： | 1 |
| 6 | Challenges in evolving controllers for physical robots显示文摘 | Mataric M J Cliff D | 1996 | Robotics and Autonomous Systems1996，19，1： | 1 |
| 7 | Single-point and multipoint aerodynamic shape optimization of high-speed civil transport显示文摘 | Cliff S E ReutherJ J Saunders D A | 2001 | Journal of Aircraft2001，38，6： | 1 |
| 8 | Selection for qacA carriage in CC22, but not CC30, methicillinresistant Staphylococcus aureus bloodstream infection isolates during a successful institutional infection control programme 显示文摘 | Otter J A Patel A Cliff P R | 2013 | J Antimicrob Chemother2013，68，5： | 1 |
| 9 | Model building and the analysis of spatial pattern in human geography 显示文摘 | Cliff A D Ord J K | 1975 | Journal of the Royal Statistical Society B1975，37，： | 1 |
| 10 | Testing for Spatial Autocorrelation among Rgression Residuals显示文摘 | Cliff A Ord J K | | 0，，4： | 1 |
| 11 | Experimental investigation of cyclic and time- dependent deformation of titanium alloy at elevated temperature 显示文摘 | CLIFF J L DEVARAJ D STEVEN M A | 2007 | Int J Plasticity2007，23，1： | 1 |
| 12 | Central places in southern Germany显示文摘 | CHRISTALLER Translated BASKIN C W ENGLEWOOD CLIFFS N J | 1966 | London: Prentice Hall1966，，： | 1 |
| 13 | Use of multilocus sequence typing for the investigation of colonisation by Candida albicans in intensive care unit patients 显示文摘 | Cliff PR Sandoe JA Heritage J | 2008 | J Hosp Infect2008，69，1： | 1 |
| 14 | Testing for spatial autocorrelation among regression residuals 显示文摘 | CLIFF A ORD J K | 1972 | Geographical Analysis1972，，3： | 1 |
| 15 | Erosional response of South China to arc rifting and monsoonal strengthening: a record from the South China Sea显示文摘 | Cliff P Lee J I Clark M K | 2002 | Marine Geology2002，184，： | 1 |
| 16 | A New Method for the Detection of Microbial Proteolytic Enzymes in Milk显示文摘 | CLIFFE ALLAN J | 1982 | J Dairy Sci1982，49，： | 1 |
| 17 | Instruction Scheduling for Instruction Level Parallel Processors显示文摘 | Paolo F Fisher J A Cliff Y | 2001 | Proceedings of the IEEE2001，89，11： | 1 |
| 18 | The fate of miniplates in facial trauma and orthognathic surgery:a retrospective study显示文摘 | Trotter M Cliffe J | 1989 | Br J Oral Maxillofac Surg1989，27，： | 1 |
| 19 | Anthocyanin, phenolic composition, colour measurement and sensory analysis of BC commercial red wines显示文摘 | Cliff M A King M C Schlosser J | 2007 | Food Research International2007，40，1： | 1 |
| 20 | Coronary C-reactive protein distribution: its relation to development of atherosclerosis 显示文摘 | ZHANG Y X CLIFF W J SCHOEFL G L | 1999 | Atherosclerosis1999，145，： | 1 |
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