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| 1 | Macrophage secretory products induce an inflammatory phenotype in hepatocytes显示文摘AIM:To investigate the influence of macrophages on hepatocyte phenotype and function.METHODS:Macrophages were differentiated from THP-1 monocytes via phorbol myristate acetate stimulation and the effects of monocyte or macrophageconditioned medium on HepG2 mRNA and protein expression determined.The in vivo relevance of these findings was confirmed using liver biopsies from 147 patients with hepatitis C virus(HCV)infection.RESULTS:Conditioned media from macrophages,but not monocytes,induced a transient morphological change in hepatocytes associated with upregulation of vimentin(7.8±2.5-fold,P=0.045)and transforming growth factor(TGF)-β1(2.6±0.2-fold,P<0.001)and downregulation of epithelial cadherin(1.7±0.02-fold,P=0.017)mRNA expression.Microarray analysis revealed significant upregulation of lipocalin-2(17-fold,P <0.001)and pathways associated with inflammation,and substantial downregulation of pathways related to hepatocyte function.In patients with chronic HCV,realtime polymerase chain reaction and immunohistochemistry confirmed an increase in lipocalin-2 mRNA(F0 1.0 ±0.3,F1 2.2±0.2,F2 3.0±9.3,F3/4 4.0±0.8,P= 0.003)and protein expression(F1 1.0±0.5,F2 1.3± 0.4,F3/4 3.6±0.4,P=0.014)with increasing liver injury.High performance liquid chromatography-tandem mass spectrometry analysis identified elevated levels of matrix metalloproteinase(MMP)-9 in macrophageconditioned medium,and a chemical inhibitor of MMP-9 attenuated the change in morphology and mRNA expression of TGF-β1(2.9±0.2 vs 1.04±0.1,P<0.001) in macrophage-conditioned media treated HepG2 cells.In patients with chronic HCV infection,hepatic mRNA expression of CD163(F0 1.0±0.2,F1/2 2.8±0.3,F3/4 5.3±1.0,P=0.001)and MMP-9(F0 1.0±0.4,F1/2 2.8±0.3,F3/4 4.1±0.8,P=0.011)was significantly associated with increasing stage of fibrosis.CONCLUSION:Secreted macrophage products alter the phenotype and function of hepatocytes,with increased expression of inflammatory mediators,suggesting that hepatocytes actively participate in liver injury. | Michelle Melino Victoria L Gadd Gene V Walker Richard Skoien Helen D Barrie Dinesh Jothimani Leigh Horsfall Alun Jones Matthew J Sweet Gethin P Thomas Andrew D Clouston Julie R Jonsson Elizabeth E Powell | 2012 | World Journal of Gastroenterology2012，18，15： | 3 |
| 2 | Senescent human hepatocytes express a unique secretory phenotype and promote macrophage migration显示文摘AIM:To develop a model of stress-induced senescence to study the hepatocyte senescence associated secretory phenotype(SASP).METHODS:Hydrogen peroxide treatment was used to induce senescence in the human Hep G2 hepatocyte cell line.Senescence was confirmed by cytochemical staining for a panel of markers including Ki67,p21,heterochromatin protein 1β,and senescence-associated-β-galactosidase activity.Senescent hepatocytes were characterised by gene expression arrays and quantitative polymerase chain reaction(q PCR),and conditioned media was used in proteomic analyses,a human chemokine protein array,and cell migration assays to characterise the composition and function of the hepatocyte SASP.RESULTS:Senescent hepatocytes induced classical markers of senescence(p21,heterochromatin protein1β,and senescence-associated-β-galactosidase activity);and downregulated the proliferation marker,Ki67.Hepatocyte senescence induced a 4.6-fold increase in total secreted protein(P=0.06)without major alterations in the protein profile.Senescence-induced genes were identified by microarray(Benjamini Hochbergcorrected P<0.05);and,consistent with the increase in secreted protein,gene ontology analysis revealed a significant enrichment of secreted proteins among inducible genes.The hepatocyte SASP included characteristic factors such as interleukin(IL)-8 and IL-6,as well as novel components such as SAA4,IL-32and Fibrinogen,which were validated by q PCR and/or chemokine protein array.Senescent hepatocyteconditioned medium elicited migration of inflammatory(granulocyte-macrophage colony stimulating factor,GM-CSF-derived),but not non-inflammatory(CSF-1-derived)human macrophages(P=0.022),which could contribute to a pro-inflammatory microenvironment in vivo,or facilitate the clearance of senescent cells.CONCLUSION:Our novel model of hepatocyte senescence provides insights into mechanisms by which senescent hepatocytes may promote chronic liver disease pathogenesis. | Katharine M Irvine Richard Skoien Nilesh J Bokil Michelle Melino Gethin P Thomas Dorothy Loo Brian Gabrielli Michelle M Hill Matthew J Sweet Andrew D Clouston Elizabeth E Powell | 2014 | World Journal of Gastroenterology2014，20，47： | 2 |
| 3 | Resveratrol Does Not Benefit Patients with Non-alcoholic Fatty Liver Disease显示文摘 | Veronique S. Chachay Graeme A. Macdonald Jennifer H. Martin Jonathan P. Whitehead Trisha M. O’Moore-Sullivan Paul Lee Michael Franklin Kerenaftali Klein Paul J. Taylor Maree Ferguson Jeff S. Coombes Gethin P. Thomas Gary J. Cowin Carl M.J. Kirkpatrick Joh | 2014 | Clinical Gastroenterology and Hepatology2014，，： | 2 |
| 4 | Exploration of die wall friction for powder compaction using a discrete finite element modelling technique显示文摘 | Gethin D T | 2001 | Modelling and Simulation in Materials Science and Engineering2001，9，： | 1 |
| 5 | Powder compaction modelling via the discrete and finite element method显示文摘 | Gethin D T Khoei A R | 2000 | Materials and Design2000，21，： | 1 |
| 6 | Es- timating costs of pressure ulcer care in one Irish hospital 显示文摘 | Gethin G Jordan -0' Brien J Moore Z | 2005 | J Wound Care2005，14，4： | 1 |
| 7 | Numerical comparison of a deformable discrete element model and an equivalent continuum analysis for the compaction of ductile porous material显示文摘 | Ransing R S Lewis R W | 2001 | Computers and Structures2001，79，： | 1 |
| 8 | Wound measurement comparing the use of acetate tracings and Visitrak digital planimetry显示文摘 | Gethin G Cowman S | 2006 | J Clin Nurs2006，15，4： | 1 |
| 9 | Operating temperatures of oil lubricated medium speed gears: Numerical models and experimental results显示文摘 | Long H Lord A A Gethin D T | 2003 | Journal of Aerospace Engineering2003，217，2： | 1 |
| 10 | Operating Temperatures of Oil-lubricated medium-speed Gears:Numerical Models and Experimental Results显示文摘 | Long H Lord A A Gethin D T | 2003 | Journal of Aerospace Engineering2003，21，2： | 1 |
| 11 | Operating temperatures ofoil -lubricated mediumspeed gears: numerical models and experimental results显示文摘 | H Long A A Lord D T Gethin | 2003 | Journal of aerospace engineering2003，217，2： | 1 |
| 12 | Protein folding in the cell显示文摘 | GETHIN M J SAMBROOK J | 1992 | Nature1992，355，： | 1 |
| 13 | A fmite element approach to analyzing hydrodynamic lubrication in journal bearings显示文摘 | Gethin D T | 1988 | Tribology International1988，21，4： | 1 |
| 14 | Computer-aided simulation of metal powder die compaction processes显示文摘 | Lewis R W Jinka A G K Gethin D T | 1993 | Powder Metallurgy1993，25，6： | 1 |
| 15 | An experiment investigation into the thermohydrodynamic behavior of a high speed cylindrical bore journal bearing显示文摘 | Gethin D T Medwell J O | 1985 | ASME Trans J Trib1985，107，： | 1 |
| 16 | Estimating costs of pressure ulcer care in one Irish hospital显示文摘 | Gethin G Jordan-O'Brien J Moore Z | 2005 | J Wound Care2005，14，4： | 1 |
| 17 | 以碳黑油墨柔印实现电子产品中细实线的印制显示文摘摘译随着印刷电子及相关材料基础研究的发展,显示器、背板、存储器、天线、电池以及其他新兴电子产品正在不断涌现。为了满足这些新兴印刷电子产品的加工需求,科研人员已经针对制造电子产品所采用的接触式和非接触式印刷方式开展了大量的研究工作。目前的研究表明,与非接触式印刷工艺相比,接触式印刷工艺的速度更快并且能够实现大幅面印刷。 | YUSOF M S GETHIN D TA 王晓芳(编译) | 2011 | 中国印刷与包装研究2011，3，3： | 1 |
| 18 | Confidence measures from local posterior probability estimates显示文摘 | Gethin Williams Steve Renals | 1999 | Computer Speech and Language1999，13，4： | 1 |
| 19 | Estimating costs of pressure ulcer care in one Irish hospital显示文摘 | Gethin G Jordan-O'Brien J Moore Z | 2005 | J Wound Care2005，14，4： | 1 |
| 20 | Discovery of a high modecular weight complex of calcium,phosphate,fetuin,and matrix-carboxyglutamic acid protei in the serum of etidronatereated rats显示文摘 | Paul A Gethin R Aaron W | 2002 | J Biol Chem2002，277，6： | 1 |
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