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| 1 | Leukemia:研究鉴定出与34种AML白血病亚群相关联的基因突变显示文摘针对成年急性髓细胞白血病(acute myeloid leukemia,AML)患者的一项新的大型研究将80种癌症相关基因突变与5种AML亚型相关联。这5种AML亚型可通过特异性的染色体异常加以确定。在未来,这些发现可能有助指导基因突变测试和治疗决策。 | A-K Eisfeld K Mrózek J Kohlschmidt D Nicolet S Orwick C J Walker K W Kroll J S Blachly A J Carroll J E Kolitz B L Powell E S Wang R M Stone A de la Chapelle J C Byrd C D Bloomfield | 2017 | 现代生物医学进展2017，17，15： | 7 |
| 2 | 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 |
| 3 | 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 |
| 4 | Reduced ciliary neurotrophic factor-like activity in nerve from diabetic or galactose-fed rats显示文摘 | Calcutt N A Muir D Powell H C | 1992 | Brain Res1992，575，： | 2 |
| 5 | Propranolol for the prevention of postoperative arrhythmias in general thoracic surgery显示文摘 | Charles D Bayliff David R Massel Richard I Inculet Richard A Malthaner Susan D Quinton Frank S Powell Renee S Kennedy | 1999 | The Annals of Thoracic Surgery1999，，1： | 2 |
| 6 | Relationship between ratio of pristane to phytane, crude oil composition and geological environment in Australia显示文摘 | POWELL T G MCKIRDY D M | 1973 | Nature1973，243，124： | 1 |
| 7 | Active immunization against malaria 显示文摘 | Robin D Powell | 1964 | Am J Trop Med Hyg1964，13，1： | 1 |
| 8 | An efficient method for finding the niinimum of a function of several variables without calculating derivatives显示文摘 | Powell M J D | 1964 | Comput J1964，7，： | 1 |
| 9 | Introduction of gaseous hydrides into an inductively coupled plasma mass spectrometer显示文摘 | POWELL M J BOOMER D W MCVICARS R J | 1986 | Analytical Chemistry1986，58，13： | 1 |
| 10 | Treflorine,trenudine,and N-methyltrewiasine:novel maytansinoid tumor inhibitors containing two fused macrocyclic rings显示文摘 | Powell RG Weisleder D Smith CR Jr | 1982 | J Am Chem Soc1982，104，18： | 1 |
| 11 | Coupled finite-element codes for armature design显示文摘 | NEWILL J F POWELL J D ZIELINSKI A E | 2003 | IEEE Transac- tions on Magneties2003，39，1： | 1 |
| 12 | A Model of Fishing Vessel Accident Probability显示文摘 | Jin D Powell H.L.K Thunberg E Solow A.R Talley W.K | | 0，，04： | 1 |
| 13 | Relationship between ratio of pristine to phytane, crude oil composition and geological environments inAustralia显示文摘 | Powell T Mckirdy D M | 1973 | Nature1973，243，： | 1 |
| 14 | Evaluation of the- host-specificity and prevalence of enterococci surface pro- tein marker in sewage and its application for sourcing hu- man fecal pollution 显示文摘 | Ahmed W Stewart J Powell D | 2008 | Journal of Environmental Quality2008，37，4： | 1 |
| 15 | Proteinase inhibition of the detection of Listeria monocytogenes in milk using the polymerase chain reaction 显示文摘 | Powell H A Gooding C M Garrett S D | 1994 | Lett Appl Microbiol1994，18，： | 1 |
| 16 | Granulomtous enterocolitis induced in rat by purified bacterial cell wall fragmentals显示文摘 | CROMARTIE W J POWELL D W | 1985 | Gastroenterology1985，89，： | 1 |
| 17 | Reduced drag coefficient for high wind speeds in tropical cyclones显示文摘 | POWELL M D VICKERY P J REINHOLD T A | 2003 | Nature2003，422，： | 1 |
| 18 | A Method for Assessing Hydrologic Alteration within Ecosystems显示文摘 | Richter B D Baumgartner J V Powell J | 1996 | Conservation Biology1996，10，4： | 1 |
| 19 | A fast algorithm for nonlinearly constrained optimization calculations 显示文摘 | Powell M J D | 1978 | Numerical Analysis1978，，630： | 1 |
| 20 | Modern tidal rhythmites deposited in a deep-water estuaty显示文摘 | Cowan E A Cai J Powell R D | 1998 | Geo-marine Letters1998，18，： | 1 |
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