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Specific contribution of mannose-binding lectin murine isoforms to brain ischemia/reperfusion injury

Cellular & Molecular Immunology 2020年第3期17卷 218-226页

作者： Laura Neglia Marco Oggioni Domenico Mercurio Maria-Grazia De Simoni stefano fumagalli1 istituto di ricerche farmacologiche mario negri irccs Department of NeuroscienceMilanItaly

Mannose-binding lectin(MBL),an initiator of the lectin pathway(LP)of complement activation,is detrimental in ischemic stroke,as shown in clinical studies and rodent *** humans have one functional MBL protein,rodents have two isoforms,MBL-A and MBL-C,whose functions relative to that of human MBL are *** permit the clinical translation of preclinical data,we aimed to define the specific contributions of MBL-A and MBL-C to brain *** subjected mice with double(MBL^(−/−))or single(MBL-A^(−/−)or MBL-C^(−/−))MBL isoform depletion to transient middle cerebral artery occlusion(tMCAo).MBL^(−/−) mice had fewer neurological deficits and smaller ischemic lesions than WT ***-A^(−/−) mice had smaller lesions than WT mice and exhibited no significant behavioral defects,whereas MBL-C^(−/−) mice did not differ from WT *** induction of Mbl1 and Mbl2(the MBL-A and MBL-C genes)expression 48 h after tMCAo was similar across *** time course of Mbl1 and Mbl2 expression in WT ischemic mice showed that Mbl1 activation occurred earlier(24 h)than Mbl2 activation(48 h).The plasma levels of MBL-A and MBL-C in MBL-C^(−/−) and MBL-A^(−/−) mice,respectively,were similar to those in WT mice both at baseline and at 48 h after *** 48 h,MBL-A^(−/−)ischemic mice showed higher MBL-C levels in the brain than WT *** and MBL-C^(−/−) ischemic mice had higher LP activity in plasma and,accordingly,higher levels of C3 deposition in the brain than MBL-A^(−/−) and MBL^(−/−) *** conclusion,mice with depletion of both MBL isoforms exhibited strong protection from ischemia/reperfusion ***-A was the main contributor to injury,likely owing to its earlier activation after ischemia and more efficient activation of the complement system than MBL-C.

关键词： injury depletion likely

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Anticoagulation in frail older people

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Journal of Geriatric Cardiology 2019年第11期16卷 844-846页

作者： Sarah Damanti Simon Braham Luca Pasina Geriatric Unit IRCCS Ca’Granda Ospedale Maggiore PoliclinicoMilanItaly Nutritional Sciences PhD Univeristy of MilanMilanItaly Angelo Bianchi Bonomi Hemophilia and Thrombosis Center IRCCS CàGranda Maggiore Hospital FoundationMilanItaly Pharmacotherapy and Appropriateness of Drug Prescription Unit Istituto Di Ricerche Farmacologiche Mario Negri IRCCSVia Giuseppe La MasaMilanItaly

Frailty is a multidimensional dynamic condition characterized by decreased physiological reserves. Therefore,frail people are more vulnerable to ***,minor stimuli,like a new drug prescription,can alter their homeostatic equilibrium determining adverse clinical outcomes(i.e.,falls,institutionalization,disability,and death).[1,2]Since the risk of atrial fibrillation[3]and venous thromboembolism[4]increase with ageing,frail people might require long term anticoagulation.

关键词： Anticoagulation Frailty The elderly

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WJSC 6^(th) Anniversary Special Issues(2):Mesenchymal stem cells Mesenchymal stem cells help pancreatic islet transplantation to control type 1 diabetes

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World Journal of Stem Cells 2014年第2期6卷 163-172页

作者： Marina Figliuzzi Barbara Bonandrini Sara Silvani Andrea Remuzzi Department of Biomedical Engineering IRCCS-Istituto di Ricerche Farmacologiche Mario Negri Department of Industrial Engineering University of Bergamo

Islet cell transplantation has therapeutic potential to treat type 1 diabetes,which is characterized by autoimmune destruction of insulin-producing pancreatic isletβ*** represents a minimal invasive approach forβcell replacement,but long-term blood control is still largely *** phenomenon can be attributed to the lack of islet vasculature and hypoxic environment in the immediate post-transplantation period that contributes to the acute loss of islets by ***,graft failures continue to occur because of immunological rejection,despite the use of potent immunosuppressive *** stem cells(MSCs)have the potential to enhance islet transplantation by suppressing inflammatory damage and immune mediated *** this review we discuss the impact of MSCs on islet transplantation and focus on the potential role of MSCs in protecting islet grafts from early graft failure and from autoimmune attack.

关键词： Mesenchymal stem cell Islet transplantation Type 1 diabetes Vascularization Immune modulation

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Heart‘omicsin’AGEing (HOMAGE):design,research objectives and characteristics of the common database

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The Journal of Biomedical Research 2014年第5期28卷 349-359页

作者： Lotte Jacobs Lutgarde Thijs Yu Jin Faiez Zannad Alexandre Mebazaa Philippe Rouet Florence Pinet Christophe Bauters Burkert Pieske Andreas Tomaschitz Mamas Mamas Javier diez Kenneth McDonald John G F Cleland Hans-Peter Brunner-La Rocca Stephane Heymans Roberto Latini Serge Masson Peter Sever Christian Delles Stuart Pocock Timothy Collier Tatiana Kuznetsova Jan A Staessen Studies Coordinating Centre Research Unit Hypertension and Cardiovascular EpidemiologyKU Leuven Department of Cardiovascular Sciences University of Leuven Centre d'Investigation Clinique Pierre Drouin and U 961 Hypertension and Heart Failure UnitInstitut Lourrain du Coeur etdes VaisseauxInsermNancyFrance Department of Anesthesiology and Critical Care Medicine InsermUMR-S942Hopital LariboisiereUniversite Paris Diderot Equipe obesite et insuffisance cardiaque Universite UPSInserm I2MCUMR 1048ToulouseFrance Inserm U744CHRULilleFrance Department of Cardiology Medical University Graz Cardiovascular Institute University of ManchesterManchesterUK division of Cardiovascular Sciences Foundation for Applied Medical ResearchUniversity of Navarra Heart Failure Unit St Vincent's University Hospital University College Dublin Department of Cardiology University of HullUK Department of Cardiology Maastricht University Medical CentreNetherlands Center for Heart Failure Research Department of CardiologyMaastricht UniversityNetherlands Department of Cardiovascular Research IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri" International Center for Circulatory Health Imperial College Institute of Cardiovascular and Medical Sciences BHF Glasgow Cardiovascular Research CenterUniversity of Glasgow London School of Hygiene and Tropical Medicine

Heart failure is common in older people and its prevalence is *** Heart ＇omics＇ in AGEing（HOMAGE） project aims to provide a biomarker approach that will improve the early diagnosis of heart failure.A large clinical database,based on（1） prospective population studies or（2） cross-sectional,prospective studies or randomized controlled trials（RCTs） of patients at risk for or with overt cardiovascular disease will be constructed to determine most promising ＇omics＇-based biomarkers to identify the risk of developing heart failure and/or *** studies,patient cohorts and RCTs are eligible for inclusion in the common database,if they received ethical approval to obtain and share data and have baseline information on cardiovascular risk ***,the HOMAGE database includes 43,065 subjects,from 20 studies in eight European countries,including healthy subjects from three population studies in France,Belgium and Italy（n = 7,124）,patients with heart failure（n = 4,312） from four cohorts in the UK,Spain and Switzerland and patients at high risk for cardiovascular disease（n = 31,629） in 13 *** is anticipated that more partners will join the consortium and enlarge the pooled *** large merged database will be a useful resource with which to identify candidate biomarkers that play a role in the mechanism underlying the onset and progression of heart failure.

关键词： left ventricle heart failure heart failure with reduced ejection fraction heart failure with preserved ejection fraction population science morbidity mortality

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miR147b:白细胞介素-1β介导的人类星形胶质细胞炎症中的新型关键调节因子

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神经损伤与功能重建 2018年第12期13卷 662-662页

作者： van Scheppingen J Mills JD Zimmer TS Broekaart DWM Iori V Bongaarts A Anink JJ Iyer AM Korotkov A Jansen FE van Hecke W Spliet WG van Rijen PC Baayen JC Vezzani A van Vliet EA Aronica E 聂昊 Department of (Neuro)Pathology Academic Medical Center University of Amsterdam Department of Neuroscience IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri" Department of Pediatric Neurology University Medical Center Utrecht Department of Pathology University Medical Center Utrecht Department of Neurosurgery Rudolf Magnus Institute for NeuroscienceUniversity Medical Center Utrecht Department of Neurosurgery VU University Medical Center Stichting Epilepsie Instellingen Nederland (SEIN)

星形胶质细胞是大脑炎症过程的重要介质,可能在包括癫痫在内的几种神经系统疾病中起重要作用。星形胶质细胞中可生产几种miRNA,是炎症通路的关键调节因子,还可能用作治疗靶标。本研究将探索在体外IL-1β介导的炎症条件下,星形胶质细胞... 详细信息

星形胶质细胞是大脑炎症过程的重要介质,可能在包括癫痫在内的几种神经系统疾病中起重要作用。星形胶质细胞中可生产几种miRNA,是炎症通路的关键调节因子,还可能用作治疗靶标。本研究将探索在体外IL-1β介导的炎症条件下,星形胶质细胞内生成的miRNA及其功能,并在人癫痫脑组织中验证。我们通过测序评估IL-1β刺激的人胎儿星形胶质细胞培养物中的miRNA和mRNA表达。使用miRNA模拟物在细胞培养物中过表达miRNA。使用原位杂交技术检测患有结节性硬化症复合体或颞叶癫痫伴海马硬化患者的切除脑组织中miRNA的表达。我们发现了2种差异表达的miRNA:miR146a和miR147b,它们与免疫/炎症反应相关基因的表达增加有关。既往有研究报道,在星形胶质细胞和结节性硬化复合细胞培养物中使用IL-1β刺激后,miR147b的过表达降低了促炎介质IL-6和COX-2的表达。miR146a和miR147b过表达降低了星形胶质细胞的增殖并促进人神经干细胞的神经元分化。miR147b在致癫痫脑中的星形胶质细胞中表达增加。由于其抗炎和恢复异常星形细胞增殖和促进神经元分化的能力,miR146a和miR147b作为与炎症相关的神经疾病(例如癫痫)的潜在治疗靶标值得进一步研究。

关键词：星形胶质细胞炎症白细胞介素1-β 微小RNA 颞叶癫痫结节性硬化症

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神经重症监护患者的液体治疗:ESICM专家共识及临床实践推荐

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国际脑血管病杂志 2019年第2期27卷 84-97页

作者： Mauro Oddo Daniele Poole Raimund Helbok Geert Meyfroidt Nino Stocchetti Pierre Bouzat Maurizio Cecconi Thomas Geeraerts Ignacio-Martin Loeches Herve Quintard Fabio Silvio Taccone Romergryko G. Geocadin Claude Hemphill Carole Ichai David Menon Jean-Francois Payen Anders Perner Martin Smith Jose Suarez Walter Videtta Elisa R. Zanier Giuseppe Citerio 何毅华(译) 常远(译) 王晓蔷(译) 潘速跃(译) Department of Medic al-Surgical Intensive Care Medicine Faculty of Biology and Medicine Centre Hospitalier Universitaire VauDOIs (CHUV) Lhiversity of Lausanne Rue du Bugnon 46 B4 08.623 1011 Lausanne Switzerland Department of Intensive Care Medicine St James's Lhiversity Hospital James's St Ushers P.O. Box 580 Dublin & Ireland Service de Reanimation Medic o-chirurgic ale Hopital Pasteur 2 UniversiteCote d'Azur CHU de Nice 06000 Nice France Unite CNRS 7275 Sophia-Antipolis France Department of Intensive Care Erasme Hospital University Libre de Bruxelles Brussels Belgium Neurosciences Critical Care Departments of Anesthesiology and Critical Care Medicine Neurology and Neurosurgery Johns Hopkins Lhiversity Baltimore MD USA Department of Neurology University of California San Francisco San Francisco CA LKA Service de Reanimation Polyvalente Hopital Pasteur 2 CHU de Nice 30 Voie Romaine CS 51069 06001 Nice Cedex 1 France division of Anaesthesia University of Cambridge Addenbrooke's Ffospital Box 93 Hfills Road Cambridge Cambridgeshire CB2 2QQ UK Department of Intensive Care 4131 Copenhagen University Hospital- Rigshospitalet Copenhagen Denmark Department of Neuroanesthesia and Neurocritic al Care The National Ffospital for Neurosurgery and Neurology Lhiversity College London Hospitals London UK Anesthesia and Intensive Care Operative th it S. Martino Hospital Belluno Italy Hospital Nacional Professor Alejandro Posadas Buenos Aires Argentina Department of Neurosciences IRCCS-Istituto di Ricerche Farmacotogiche Mario Negri Milan Italy School of Medicine and Surgery University of Milan-Bicocca Milan Italy Neurointensive Care San Gerardo Hospital ASST-Monza 20900 Monza Italy 南方医科大学南方医院神经内科广州510515 Neurological Intensive Care Lhit Department of Neurology Medical University of Innsbruck Innsbruck Austria Department of Intensive Care Medicine University Hospitals Leuven Louvain Belgium Neuroscience Intensive Care Unit Department of Anesthesia and C

目的发布欧洲重症医学学会(European Society of Intensive Care Medicine, ESICM)关于神经重症监护患者液体治疗的专家共识和临床实践推荐意见。设计在2016年10月召开的ESICM LIVE 2016会议上召集了一个由22名国际专家组成的共识委员会... 详细信息

目的发布欧洲重症医学学会(European Society of Intensive Care Medicine, ESICM)关于神经重症监护患者液体治疗的专家共识和临床实践推荐意见。设计在2016年10月召开的ESICM LIVE 2016会议上召集了一个由22名国际专家组成的共识委员会,随后委员会成员通过电话会议和在线讨论制定本专家共识。方法回顾人群、干预、对比和结局(population, intervention,comparison, and outcomes, PICO)问题,根据需要进行更新并得到证据概要。本共识关注3个主要议题:(1)神经重症监护患者的液体复苏和维持;(2)高渗液体在颅内压控制中的应用;(3)蛛网膜下腔出血后迟发性脑缺血的液体管理。经过广泛的文献检索,应用推荐分级的评估、制订与评价(Gradingof Recommendations Assessment, Development and Evaluation, GRADE)系统原则评估证据质量(从高到极低),制定治疗推荐(强或弱),并在适用时发布最佳实践声明。基于文献和专家意见提供的综合证据,应用改良德尔菲方法(使用序贯方法以避免偏倚和误解)产生最终共识声明。结果最终共识包含总共32条声明,其中13条为强推荐,17条为弱推荐,另外2条声明未提供推荐意见。结论我们发布了一份关于神经重症监护患者液体治疗的共识声明和临床实践推荐。

关键词：循证医学指南液体治疗创伤性脑损伤蛛网膜下腔出血脑出血卒中甘露醇高渗神经重症监护

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