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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 | Inability of interferon and aminogunidine to alter Cryptosporidium parvum infection in mice with severe combined immunodeficiency显示文摘 | Kuhls T L Mosier D A Abrams V L | 1994 | Journal of Parasitology1994，80，3： | 2 |
| 3 | B-cell receptor signaling in chronic lymphocytic leukemia cells is regulated by overexpressed active protein kinase CbetalI 显示文摘 | Abrams ST Lakum T Lin K | 2007 | Blood2007，109，： | 1 |
| 4 | Airway mangement and mechanical ventilation显示文摘 | Abrams K T | 1995 | Mewhoriz1995，3，3： | 1 |
| 5 | Purification and properties of extracellular lipase from Streptomyces rimosus 显示文摘 | Abramic M Lescic I Korica T | 1999 | Enzyme Microbial Teehnol1999，25，6： | 1 |
| 6 | Circulating histones are mediators of traumaassociated lung injury 显示文摘 | Abrams S T Zhang N Manson J | 2013 | Am J Respir Crit Care Med2013，187，2： | 1 |
| 7 | Maternal weight gainand preterm delivery 显示文摘 | ABRAMS B NEWMAN V KEY T | 1989 | Obstet Obstet Gynecol1989，74，4： | 1 |
| 8 | 成人2型糖尿病不同筛查及预防策略成本效益分析显示文摘目的 比较针对2型糖尿病预防及治疗的4种筛查策略及随后予以的干预措施:(a)筛查2型糖尿病患者使其能接受早期检查及治疗,(b)筛查2型糖尿病和糖耐量受损患者,对糖耐量受损的人群予以生活方式干预以延缓或预防糖尿病的发生,(c)同(b)但予以药物干预措施,(d)不筛查。
设计 成本效益决策分析建立在对概率的发展和评估基础上,是从筛查到死亡的综合性经济决策分析模型。
研究对象 一组假设人群,筛查时年龄45岁,高于平均糖尿病风险水平。
数据来源 电子书目数据库收录的已发表的临床试验和流行病学研究;补充数据分别来自英国和威尔士健康统计署、风险筛查(STAR)研究和ADDITION研究的Leicester部分。
方法 建立一种决策树/Markov混合模型,以模拟每一种筛查策略的长期效用,包括临床和成本效益终点。该模型假设水平跨度为50年时间,其成本效益折损率为3.5%。采用敏感度分析以验证模型假设及确定哪种模型数据输入对结果的影响最大。
结果 与不筛查策略比较,筛查2型糖尿病、筛查糖尿病和糖耐量受损并予以生活方式干预、筛查糖尿病和糖耐量受损并予以药物干预治疗3种策略,每获得一个质量调整生命年(QALY)估计所需成本分别为(每年成本效益贴现率为3.5%)14150英镑(17560欧元;27860美元)、6242英镑和7023英镑。在支付意愿阈值为20000英镑时,各主动筛查策略通过干预产生的成本效益概率分别为49%,93%和85%。
结论 对年龄45岁、高于平均风险水平的人群进行2型糖尿病和糖耐量受损的筛查,并对糖耐量受损人群予以适当的干预似乎具有很好的成本效益。单独筛查糖尿病而不对糖耐量受损人群予以干预的策略具有的成本效益仍不确定,需要进一步研究确定早期检测糖尿病的作用。 | Clare L Gillies Paul C Lambert Keith R Abrams Alex J Sutton Nicola J Cooper Ron T Hsu Melanie J Davies Kamlesh Khunti 张晓梅(译) 纪立农(校) | 2008 | 英国医学杂志中文版2008，11，5： | 1 |
| 9 | Dual Templating of Macroporous Silicates with Zeolitic Microporous Frameworks显示文摘 | Holland B T Abrams L Stein A | 1999 | J Am Chem Soc1999，121，17： | 1 |
| 10 | Note: tree ring respon- ses to drought across species and contrasting sites in the ridge and valley of central Pennsylvania 显示文摘 | Abrams M D Ruffner C M Morgan T A | 1998 | Forest Science1998，44，4： | 1 |
| 11 | Metabolism of ( + )-abscisic acidto ( + )-7'-hydroxyabscisic acid by bromegrass cell cultures显示文摘 | HAMPSON C R REANEY M J T ABRAMS G D | 1992 | Phytochemistry1992，31，： | 1 |
| 12 | Ultrasound-guided obturator nerve block:an interfascial injection approach without nerve stimulation显示文摘 | SINHA S K ABRAMS J H HOULE T T | 2009 | Reg Anesth Pain Med2009，34，3： | 1 |
| 13 | Effects of freezing on mechanical properties of rat skin显示文摘 | Foutz T L Stone E A Abrams C F | 1992 | Am J Vet Res1992，53，： | 1 |
| 14 | Oral mTOR inhibitor everolimus in patients with gemcitabine-refractory metastatic pancreatic cancer显示文摘 | Wolpin BM Hezel AF Abrams T | 2009 | J Clin Oncol2009，27，2： | 1 |
| 15 | Superior induction and maintenance of protective cd8 t ceils in mice infected with mouse cytomegalovirus vector expressing RAE-I'/显示文摘 | Trsan T Busche A Abram M | | Proc Natl Acad Sci U S A0，110，16： | 1 |
| 16 | A, Dual Templating of Macroporous Silicates with Zeolitic Micmporous Frameworks 显示文摘 | Holland B T Abrams L Stein | 1999 | J AmChem Soc (Communication)1999，121，17： | 1 |
| 17 | Pancreaticoduodenectomy for pancreatic adenocarcinoma:postoperative adjuvant chemoradiation improves survival:a prospective,single institution experience显示文摘 | Yeo C Abrams R Grochow L Sohn T Ord S Hruban R | | 0，，： | 1 |
| 18 | Sunitinib inhibits KIT and platelet-derived growth fac- tor receptor in preclinical models of human small cell lung cancer 显示文摘 | ABRAMS T J LEE L B MURRAY L J | 2003 | Mol Cancer Ther2003，2，： | 1 |
| 19 | Coronary risk factors and their modification lipids, smoking, hypertension, estrogen, and the elderly显示文摘 | ABRAMS J VELA B S COULTAS D t | 1995 | Curt Probl Cardiol1995，20，8： | 1 |
| 20 | Relationship of calcium ab- sorption with 25 (OH)D and calcium intake in children with riekets显示文摘 | THACHER T D ABRAMS S A | 2010 | Nutr Rev2010，68，11： | 1 |
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