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| 1 | Extracellular histones stimulate collagen expression in vitro and promote liver fibrogenesis in a mouse model via the TLR4-MyD88 signaling pathway显示文摘BACKGROUND Liver fibrosis progressing to liver cirrhosis and hepatic carcinoma is very common and causes more than one million deaths annually.Fibrosis develops from recurrent liver injury but the molecular mechanisms are not fully understood.Recently,the TLR4-MyD88 signaling pathway has been reported to contribute to fibrosis.Extracellular histones are ligands of TLR4 but their roles in liver fibrosis have not been investigated.AIM To investigate the roles and potential mechanisms of extracellular histones in liver fibrosis.METHODS In vitro,LX2 human hepatic stellate cells(HSCs)were treated with histones in the presence or absence of non-anticoagulant heparin(NAHP)for neutralizing histones or TLR4-blocking antibody.The resultant cellular expression of collagen I was detected using western blotting and immunofluorescent staining.In vivo,the CCl4-induced liver fibrosis model was generated in male 6-week-old ICR mice and in TLR4 or MyD88 knockout and parental mice.Circulating histones were detected and the effect of NAHP was evaluated.RESULTS Extracellular histones strongly stimulated LX2 cells to produce collagen I.Histone-enhanced collagen expression was significantly reduced by NAHP and TLR4-blocking antibody.In CCl4-treated wild type mice,circulating histones were dramatically increased and maintained high levels during the duration of fibrosisinduction.Injection of NAHP not only reduced alanine aminotransferase and liver injury scores,but also significantly reduced fibrogenesis.Since the TLR4-blocking antibody reduced histone-enhanced collagen I production in HSC,the CCl4 model with TLR4 and MyD88 knockout mice was used to demonstrate the roles of the TLR4-MyD88 signaling pathway in CCl4-induced liver fibrosis.The levels of liver fibrosis were indeed significantly reduced in knockout mice compared to wild type parental mice.CONCLUSION Extracellular histones potentially enhance fibrogenesis via the TLR4–MyD88 signaling pathway and NAHP has therapeutic potential by detoxifying extracellular histones. | Zhi Wang Zhen-Xing Cheng Simon T Abrams Zi-Qi Lin ED Yates Qian Yu Wei-Ping Yu Ping-Sheng Chen Cheng-Hock Toh Guo-Zheng Wang | 2020 | World Journal of Gastroenterology2020，26，47： | 3 |
| 2 | 成功联用HPLC-ICP-MS用于食品中的汞形态分析显示文摘汞是对生物体毒性最大的元素之一,因此对其进行可靠的定量分析极其重要。汞在环境中的浓度相对较低,但它可通过食物链放大.在某些食品中的最终浓度可能相当高。另外,其毒性与总浓度和化学形态息息相关.因此食品分析中的汞形态分析对于全面评估这一元素对人类的潜在毒性很有必要。Agilent 7700x ICP—MS可用于快速、简便的汞形态分析. | Sébastien Sannac Yu-Hong Chen Raimund Wahlen Ed McCurdy | 2012 | 食品安全导刊2012，，12： | 2 |
| 3 | Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins 显示文摘 | Aiello LP Pierce EA Foley ED Takagi H Chen H Riddle L et oi | 1995 | Proc Natl Acad Sci USA1995，92，10： | 1 |
| 4 | Prevalence,predictors,and outcomes of patients with non-ST segment elevation myocardial infarction and insignificant coronary artery disease:results from the CRUSADE initiative显示文摘 | Patel MR Chen AY Peterson ED | 2006 | Am Heart J2006，152，4： | 1 |
| 5 | High-level expression and single-step purification of leucyl-tRNA synthetase from Escherichia coli显示文摘 | Chen JF Li Y Wang ED | 1999 | Protein Expression and Purification1999，15，： | 1 |
| 6 | Virtual colonoscopy using oral contrast compared with colonoscopy for the detection of patients with colorectal polyps显示文摘 | Pineau BC Paskett ED Chen GJ | 2003 | Gastroenterology2003，125，2： | 1 |
| 7 | Prevalence, predictors and outcomes of patients with non- ST-segment elevation myocardial infarction and insignificant coronary artery desease: results from the Can Rapid risk stratification of Unstable angina patients Suppress Adverse outcomes with early implimentation of the ACC/AHA Guidelines (CRUSADE) initiative显示文摘 | Patel MR Chen AY Peterson ED | 2006 | Am Heart J2006，152，4： | 1 |
| 8 | Optimal timing of intervention in non-ST-segment elevation acute coronary syndromes: insights from the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines) Registry 显示文摘 | Ryan JW Peterson ED Chen AY | 2005 | Circulation2005，112，20： | 1 |
| 9 | Oxidized low-density lipoprotein receptor LOX-1 and apoptosis in human atherosclerotic lesions显示文摘 | Li DY Chen HJ Staples ED | 2002 | J Cardiovasc Pharmacol Ther2002，7，3： | 1 |
| 10 | Abdominal organ motion measured using 4D CT 显示文摘 | Brandner ED Wu A Chen H | 2006 | Int J Radiat Oncol Biol Phys2006，65，2： | 1 |
| 11 | Agrobacterium-mediated transformation of Fusarium oxysporum:An efficient tool for insertional mutagenesis and gene transfer显示文摘 | Mullins ED Chen X Romaine P | 2001 | Techniques2001，91，2： | 1 |
| 12 | Twist1 activity thresholds define multiple functions in limb development显示文摘 | Dayana Krawchuk Shoshana J. Weiner You-Tzung Chen Benson C. Lu Frank Costantini Richard R. Behringer Ed Laufer | 2010 | Developmental Biology2010，，1： | 1 |
| 13 | Fusion of neural stem cells in culture显示文摘 | Chen KA Laywell ED Marshall G | 2006 | Exp Neurol2006，19，8： | 1 |
| 14 | Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins显示文摘 | Aiello LP Pierce EA Foley ED Takagi H Chen H Riddle L | 1995 | Proc Natl Acad Sci USA1995，92，10： | 1 |
| 15 | Dietary L-arginine supplementation improves glomerular filtration rate and renalblood flow after 24 hours of unilateral ureteral obstruction in rats显示文摘 | ITO K CHEN J VAUGHAN JR ED | 2004 | J Urol2004，171，： | 1 |
| 16 | In-hospital major bleeding during ST-elevation and non-ST-elevation myocardial infarction care: Derivation and validation of a model from the ACTION Registry -GWTGTM 显示文摘 | Mathews R Peterson ED Chen AY | 2011 | Am J Cardiot2011，107，8： | 1 |
| 17 | Oxidized low-density lipoiprotein receptor LOX-1 and apoptosis in human atherosclerotic lesions 显示文摘 | Li DY Chen HI Staples ED | 2002 | J Cardiovasc Pharmacol Ther2002，7，3： | 1 |
| 18 | oxidized low - density lipoprotein receptor LOX - 1 and apotosis in human atherosclerotic lesions 显示文摘 | Li DY Chen HJ Staples ED | 2002 | Cardiovasc Res2002，7，3： | 1 |
| 19 | Optimal timing of intervention in non-ST-segment elevation acute coronary syndromes:insights from the CRUSADE(Can Rapid risk stratification of Unstable angina patients Suppress Adverse outcomes with Early implementation of the ACC/AHA guidelines) Registry显示文摘 | Ryan JW Peterson ED Chen AY | 2005 | Circulation2005，112，20： | 1 |
| 20 | Agrobacterium-mediated transformation of Fusarium oxysporum:an efficient tool for insertional mutagenesis and gene transfer显示文摘 | Mullins ED Chen X Romaine P | 2001 | Phytopathology2001，91，2： | 1 |
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