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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 | 'Investor sentiment and the nearterm stock market' 显示文摘 | Brown G W Cliff M T | 2004 | Journal of Empirical Finance2004，11，1： | 1 |
| 4 | Transcription of the herpes simplex virus latency-associated transcript promotes the formation of facultative heterochromatin on lytic promoters 显示文摘 | Cliffe A R Garber D A Knipe D M | 2009 | J Virol2009，83，16： | 1 |
| 5 | 'Investor sentiment and asset valuation'显示文摘 | Brown G W Cliff M T | 2005 | Journal of Business2005，78，2： | 1 |
| 6 | Investor sentiment and the near-term stock market 显示文摘 | Brown G W Cliff M T | 2004 | Journal of Empirical Finance2004，11，1： | 1 |
| 7 | Modeling of power diodes with the lumped charge modeling technique显示文摘 | Cliff M Lauritzen P Sigg A | 1997 | IEEE Transactions on Power Electronics1997，12，3： | 1 |
| 8 | Odour-active components of simulated beef flavour analysed by solid phase microextraction and gas chromatography-mass spectrometry and -olfactometry显示文摘 | MOON S Y CLIFF M A LI-CHAN E C Y | 2006 | Food Research International2006，39，3： | 1 |
| 9 | 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 |
| 10 | Investor sentiment and the near-term stock market 显示文摘 | Brown G W Cliff M T | 2004 | Journal of Empirical Finance2004，11，1： | 1 |
| 11 | Challenges in evolving controllers for physical robots显示文摘 | Mataric M J Cliff D | 1996 | Robotics and Autonomous Systems1996，19，1： | 1 |
| 12 | Investor sentiment and asset valuation显示文摘 | Brown G W Cliff M T | 2005 | Journal Business2005，78，2： | 1 |
| 13 | Investor Sentiment and Asset Valuation 显示文摘 | Brown G W and Cliff M T | 2005 | The Journal of Business2005，78，2： | 1 |
| 14 | Odor-active components of simulated beef flavor analysed by solid phase microextraction and gas chromatography-mass spectrometry and -olfactometry显示文摘 | MOON S Y CLIFF M A EICHAN E C Y | 2006 | Food Research International2006，39，3： | 1 |
| 15 | Investor sentiment and the near- term stock market显示文摘 | Brown G Cliff M | 2004 | Journal of Empirical Finance2004，11，1： | 1 |
| 16 | Investor Sentiment and the Near - term Stock Market 显示文摘 | Brown G W and Cliff M T | 2004 | Journal of Empirical Finance2004，，11： | 1 |
| 17 | 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 |
| 18 | Investor sentiment and the near-term stock market显示文摘 | Brown G W Cliff M T | 2004 | Journal Empirical Finance2004，11，： | 1 |
| 19 | Mixed H2/H∞ optimal control for an elastic aircraft 显示文摘 | Fan Y Q CliffE M Lutze F H | 1996 | Journal of Guidance Control and Dynamics1996，19，3： | 1 |
| 20 | Investor sentiment and asset valua- tion显示文摘 | BROWN G CLIFF M | 2005 | Journal of Business2005，78，： | 1 |
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