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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 | Global research trends in the microbiome related to irritable bowel syndrome: A bibliometric and visualized study显示文摘BACKGROUND Irritable bowel syndrome(IBS) is a common functional gastrointestinal disorder. Dysregulation of the gut–brain axis plays a central role in the pathophysiology of IBS. It is increasingly clear that the microbiome plays a key role in the development and normal functioning of the gut–brain axis.AIM To facilitate the identification of specific areas of focus that may be of relevance to future research. This study represents a bibliometric analysis of the literature pertaining to the microbiome in IBS to understand the development of this field.METHODS The data used in our bibliometric analysis were retrieved from the Scopus database. The terms related to IBS and microbiome were searched in titles or abstracts within the period of 2000–2019. VOSviewer software was used for data visualization.RESULTS A total of 13055 documents related to IBS were retrieved at the global level. There were 1872 scientific publications focused on the microbiome in IBS. There was a strong positive correlation between publication productivity related to IBS in all fields and productivity related to the microbiome in IBS(r = 0.951, P < 0.001). The United States was the most prolific country with 449(24%) publications, followed by the United Kingdom(n = 176, 9.4%), China(n = 154, 8.2%), and Italy(n = 151, 8.1%). The h-index for all retrieved publications related to the microbiome in IBS was 138. The hot topics were stratified into four clusters:(1) The gut–brain axis related to IBS;(2) Clinical trials related to IBS and the microbiome;(3) Drugmediated manipulation of the gut microbiome;and(4) The role of the altered composition of intestinal microbiota in IBS prevention.CONCLUSION This is the first study to evaluate and quantify global research productivity pertaining to the microbiome in IBS. The number of publications regarding the gut microbiota in IBS has continuously grown since 2013. This finding suggests that the future outlook for interventions targeting the gut microbiota in IBS remains promising. | Sa'ed H Zyoud Simon Smale W Stephen Waring Waleed Sweileh Samah W Al-Jabi | 2021 | World Journal of Gastroenterology2021，27，13： | 2 |
| 3 | Re-evaluating therapeutic neovascularization显示文摘 | de Muinck ED Simons M | | 0，，01： | 1 |
| 4 | Cognitive demand, imagery, and frequency ofmental rehearsal as factors Infl uencing acquisition of motor skills显示文摘 | Ryan ED Simons J | 1981 | Journal of Sport Psychology1981，3，1： | 1 |
| 5 | Laser capture microdessection and micro-array expression analysis of lung adenocarcinoma reveals tobaccosmoking and prog-nosis-related molecular profiles显示文摘 | Miura K Bowman ED Simon R | 2002 | Cancer Res2002，62，11： | 1 |
| 6 | Nicotinic acetylcholine involvement in cognitive function in animals显示文摘 | Levin ED Simon BB | 1998 | Psychopharmacology (Berl)1998，138，34： | 1 |
| 7 | An Introduction to XML显示文摘 | Ed Simon Paul Madsen Carlisle Adams | 2001 | Digital Signatures2001，8，： | 1 |
| 8 | Mood disturbances and regional cerebral metabolic abnormalities in recently abstinent methamphetamine abusers显示文摘 | London ED Simon SL Berman SM | 2004 | Arch Gen Psychiatry2004，61，1： | 1 |
| 9 | Melanin content of cultured human melanocytes and UV-induced cytotoxicity显示文摘 | Sandra M. De Leeuw Nico P.M. Smit Monique Van Veldhoven Ed M. Pennings Stan Pavel Johannes W.I.M. Simons Albert A. Schothorst | 2001 | Journal of Photochemistry & Photobiology B: Biology2001，，3： | 1 |
| 10 | Genome-wide Generation and Systematic Phenotyping of Knockout Mice Reveals New Roles for Many Genes显示文摘 | Jacqueline K. White Anna-Karin Gerdin Natasha A. Karp Ed Ryder Marija Buljan James N. Bussell Jennifer Salisbury Simon Clare Neil J. Ingham Christine Podrini Richard Houghton Jeanne Estabel Joanna R. Bottomley David G. Melvin David Sunter Niels C. Adams L | 2013 | Cell2013，，2： | 1 |
| 11 | Mood disturbances and regional cerebral metabolic abnormalities in recently abstinent methamphetamine abusers显示文摘 | London ED Simon SL Berman SM | 2004 | Arch Gen Psychiatry2004，61，： | 1 |
| 12 | Live 3D echo guidance of catheter-based endomyocardial injection 显示文摘 | Baklanov DV de Muinck ED Simons M | 2005 | Catheter Cardiovasc lnterv2005，65，3： | 1 |
| 13 | Interpreting the estimated glomerular filtration rate in primary care: Benefits and pitfalls 显示文摘 | Simon J Made M Poggio ED | 2011 | Cleverland Clin J of Med2011，78，3： | 1 |
| 14 | Mood disturbances and regional cerebral metabolic abnormalities in recently abstinent methamphetamine abusers显示文摘 | London ED Simon SL Berman SM | 2004 | Arch Gen Psychiatry2004，61，： | 1 |
| 15 | Live 3D echo guidance of catheter-based endomyocardial injection 显示文摘 | Baklanov DV de Muinck ED Simons M | 2005 | Catheter Cardiovasc lnterv2005，65，3： | 1 |
| 16 | Re-evaluating therapeutic neovascularization显示文摘 | De Muinck ED Simons M | 2004 | J Mol Cell Cardiol2004，36，1： | 1 |
| 17 | Nicotinic acetylcholine involvement in cognitive function in animals显示文摘 | Levin ED Simon BB | 1998 | Psychopharmacol1998，138，： | 1 |
| 18 | Mood disturbances and regional cerebral metabolic abnormalities in recently abstinent methamphetamine abusers显示文摘 | London ED Simon SL Berman SM | 2004 | Arch Gen Psychiat2004，61，1： | 1 |
| 19 | Nicotinic acetylcholine involvement in cognitive function in animals显示文摘 | LEVIN ED SIMON BB | 1998 | Psychopharmacology(Berl)1998，138，： | 1 |
| 20 | Mood disturbances and regional cerebralmetabolic abnormalities in recently abstinentmetham-phetamine abusers显示文摘 | London ED Simon SL Berman SM | 2004 | Arch Gen Psychiatry2004，61，： | 1 |
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