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| 1 | Anticancer immunotherapy by CTLA-4 blockade: obligatory contribution of IL-2 receptors and negative prognostic impact of soluble CD25显示文摘堵住抗体 ipilimumab 的细胞毒素的 T 淋巴细胞 antigen-4 (CTLA-4 ) 在很少的病人导致变形黑瘤的调停免疫者的长期的控制。尽管 ipilimumab 无疑经由 immunostimulation 施加它的治疗学的效果,这样远的临床上有用的、 immunologically 相关的 biomarkers 预言治疗效率是逃犯的。这里,我们显示出 IL-2 的那中立化或堵住 α并且 βIL-2 受体的子单元(CD25 和 CD122,分别地) 否则在现出症状之前的潜的老鼠模型由 CTLA-4 封锁导致了,废除了 antitumor 效果和 intratumoral T 受动器对规章的房间(Tregs ) 的比率的伴随的改进,它是。CTLA-4 封锁导致了在失去了 FoxP3 表示并且在 regressing 肿瘤积累了的 IL-2-producing 受动器房间与伴随物上升表示 Lag3, ICOS, IL-10 和 Egr2 的一个镇压 CD4 + T 房间子集的减小。当 recombinant IL-2 改进了 CTLA-4 封锁的治疗学的功效时,圈套 IL-2 受体 α(IL-2Rα, sCD25 ) 禁止了 CTLA-4 的 anticancer 效果封锁。在收到 ipilimumab 的 262 个变形黑瘤病人, sCD25 的基线浆液集中代表了全面幸存的独立指示物,与预言到治疗的抵抗的高水平。总的来说,这些结果解开为在 CTLA-4 的 anticancer 活动的 IL-2 和 IL-2 受体的一个角色封锁。重要地,我们的学习提供第一 immunologically 相关的 biomarker,也就是提高的浆液 sCD25,那与黑瘤在病人预言抵抗到 CTLA-4 封锁。 | Dalil Hannani Marie Vetizou David Enot Sylvie Rusakiewicz Nathalie Chaput David Klatzmann Melanie Desbois Nicolas Jacquelot Nadege Vimond Salem Chouaib Christine Mateus James P Allison Antoni Ribas Jedd D Wolchok Jianda Yuan Philip Wong Michael Postow Andrzej Mackiewicz Jacek Mackiewicz Dirk Schadendorff Dirk Jaeger Alan J Korman Keith Bahjat Michele Maio Luana Calabro Michele WL Teng Mark J Smyth Alexander Eggennont Caroline Robert Guido Kroemer Laurence Zitvogel | 2015 | Cell Research2015，25，2： | 14 |
| 2 | Dihydromyricetin and Salvianolic acid B inhibit alpha-synuclein aggregation and enhance chaperone-mediated autophagy显示文摘Background:Progressive accumulation ofα-synuclein is a key step in the pathological development of Parkinson’s disease.Impaired protein degradation and increased levels ofα-synuclein may trigger a pathological aggregation in vitro and in vivo.The chaperone-mediated autophagy(CMA)pathway is involved in the intracellular degradation processes ofα-synuclein.Dysfunction of the CMA pathway impairsα-synuclein degradation and causes cytotoxicity.Results:In the present study,we investigated the effects on the CMA pathway andα-synuclein aggregation using bioactive ingredients(Dihydromyricetin(DHM)and Salvianolic acid B(Sal B))extracted from natural medicinal plants.In both cell-free and cellular models ofα-synuclein aggregation,after administration of DHM and Sal B,we observed significant inhibition ofα-synuclein accumulation and aggregation.Cells were co-transfected with a Cterminal modifiedα-synuclein(SynT)and synphilin-1,and then treated with DHM(10μM)and Sal B(50μM)16 hours after transfection;levels ofα-synuclein aggregation decreased significantly(68%for DHM and 75%for Sal B).Concomitantly,we detected increased levels of LAMP-1(a marker of lysosomal homeostasis)and LAMP-2A(a key marker of CMA).Immunofluorescence analyses showed increased colocalization between LAMP-1 and LAMP-2A withα-synuclein inclusions after treatment with DHM and Sal B.We also found increased levels of LAMP-1 and LAMP-2A both in vitro and in vivo,along with decreased levels ofα-synuclein.Moreover,DHM and Sal B treatments exhibited anti-inflammatory activities,preventing astroglia-and microglia-mediated neuroinflammation in BAC-α-syn-GFP transgenic mice.Conclusions:Our data indicate that DHM and Sal B are effective in modulatingα-synuclein accumulation and aggregate formation and augmenting activation of CMA,holding potential for the treatment of Parkinson’s disease. | Jia-Zhen Wu Mustafa Ardah Caroline Haikal Alexander Svanbergsson Meike Diepenbroek Nishant N.Vaikath Wen Li Zhan-You Wang Tiago F.Outeiro Omar M.El-Agnaf Jia-Yi Li | 2019 | Translational Neurodegeneration2019，8，1： | 11 |
| 3 | Age-Dependent Alpha-Synuclein Accumulation and Phosphorylation in the Enteric Nervous System in a Transgenic Mouse Model of Parkinson's Disease显示文摘The enteric nervous system(ENS) controls the function of the gastrointestinal tract and has been implicated in various diseases, including Parkinson's disease(PD). PD is a neurodegenerative disease with Lewy bodies(LBs) and Lewy neurites(LNs) as the main pathological features. In addition to the typical motor symptoms in PD,attention has been drawn to non-motor symptoms, such as constipation, implying dysfunction of the ENS. In the present study, we characterized the age-dependent morphological alterations and aggregation of a-synuclein(asyn), the primary protein component in LBs and LNs, in the ENS in an a-syn transgenic mouse model. We found that the expression and accumulation of a-syn increased gradually in neurons of Meissner's and Auerbach's plexuses of the gastrointestinal tract with age(from 1 week to 2 years). In addition, a-syn was increasingly phosphorylated at the serine 129 residue, reflecting pathological alterations of the protein over time. Furthermore, asyn was present in different subtypes of neurons expressing vasoactive intestinal polypeptide, neuronal nitric oxide synthase, or calretinin. The results indicated that BAC-aSyn-GFP transgenic mice provide a unique model in which to study the relationship between ENS and PD pathogenesis. | Chong-Bin Zhong Qian-Qian Chen Caroline Haikal Wen Li Alexander Svanbergssona Meike Diepenbroek Jia-Yi Li | 2017 | Neuroscience Bulletin2017，33，5： | 5 |
| 4 | The role of vascularization in nerve regeneration of nerve graft显示文摘Vascularization is an important factor in nerve graft survival and function. The specific molecular regulations and patterns of angiogenesis following peripheral nerve injury are in a broad complex of pathways. This review aims to summarize current knowledge on the role of vascularization in nerve regeneration, including the key regulation molecules, and mechanisms and patterns of revascularization after nerve injury. Angiogenesis, the maturation of pre-existing vessels into new areas, is stimulated through angiogenic factors such as vascular endothelial growth factor and precedes the repair of damaged nerves. Vascular endothelial growth factor administration to nerves has demonstrated to increase revascularization after injury in basic science research. In the clinical setting, vascularized nerve grafts could be used in the reconstruction of large segmental peripheral nerve injuries. Vascularized nerve grafts are postulated to accelerate revascularization and enhance nerve regeneration by providing an optimal nutritional environment, especially in scarred beds, and decrease fibroblast infiltration. This could improve functional recovery after nerve grafting, however, conclusive evidence of the superiority of vascularized nerve grafts is lacking in human studies. A well-designed randomized controlled trial comparing vascularized nerve grafts to non-vascularized nerve grafts involving patients with similar injuries, nerve graft repair and follow-up times is necessary to demonstrate the efficacy of vascularized nerve grafts. Due to technical challenges, composite transfer of a nerve graft along with its adipose tissue has been proposed to provide a healthy tissue bed. Basic science research has shown that a vascularized fascial flap containing adipose tissue and a vascular bundle improves revascularization through excreted angiogenic factors, provided by the stem cells in the adipose tissue as well as by the blood supply and environmental support. While it was previously believed that revascularization occurred from both nerve ends, recent studies propose that revascularization occurs primarily from the proximal nerve coaptation. Fascial flaps or vascularized nerve grafts have limited applicability and future directions could lead towards off-the-shelf alternatives to autografting, such as biodegradable nerve scaffolds which include capillary-like networks to enable vascularization and avoid graft necrosis and ischemia. | Tiam M.Saffari Meiwand Bedar Caroline A.Hundepool Allen T.Bishop Alexander Y.Shin | 2020 | Neural Regeneration Research2020，15，9： | 5 |
| 5 | Human viral pathogens are pervasive in wastewater treatment center aerosols显示文摘Wastewater treatment center(WTC) workers may be vulnerable to diseases caused by viruses, such as the common cold, influenza and gastro-intestinal infections. Although there is a substantial body of literature characterizing the microbial community found in wastewater, only a few studies have characterized the viral component of WTC aerosols,despite the fact that most diseases affecting WTC workers are of viral origin and that some of these viruses are transmitted through the air. In this study, we evaluated in four WTCs the presence of 11 viral pathogens of particular concern in this milieu and used a metagenomic approach to characterize the total viral community in the air of one of those WTCs. The presence of viruses in aerosols in different locations of individual WTCs was evaluated and the results obtained with four commonly used air samplers were compared.We detected four of the eleven viruses tested, including human adenovirus(h Ad V),rotavirus, hepatitis A virus(HAV) and Herpes Simplex virus type 1(HSV1). The results of the metagenomic assay uncovered very few viral RNA sequences in WTC aerosols, however sequences from human DNA viruses were in much greater relative abundance. | Evelyne Brisebois Marc Veillette Vanessa Dion-Dupont Jacques Lavoie Jacques Corbeil AlexANDer Culley Caroline Duchaine | 2018 | Journal of Environmental Sciences2018，30，5： | 5 |
| 6 | Lethal-7 is down-regulated by the hepatitis B virus x protein and targets signal transducer and activator of transcription 3显示文摘 | Yu Wang Yiwei Lu Soo Ting Toh Wing-Kin Sung Patrick Tan Pierce Chow Alexander Y.F. Chung London L.P. Jooi Caroline G.L. Lee | 2010 | Journal of Hepatology2010，，1： | 3 |
| 7 | Linaclotide, through activation of guanylate cyclase C, acts locally in the gastrointestinal tract to elicit enhanced intestinal secretion and transit显示文摘 | Robert W. Busby Alexander P. Bryant Wilmin P. Bartolini Etchell A. Cordero Gerhard Hannig Marco M. Kessler Shalina Mahajan-Miklos Christine M. Pierce Robert M. Solinga Li Jing Sun Jenny V. Tobin Caroline B. Kurtz Mark G. Currie | 2010 | European Journal of Pharmacology2010，，1： | 2 |
| 8 | The effects of Park sham needles: a pilot study显示文摘BACKGROUND: When performing clinical trials involving acupuncture, it can be difficult to choose a placebo control. OBJECTIVE: To validate the Park sham needle for use as a double-blind control intervention.DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: Two different methods were employed. First, a researcher blinded to needle type administered the Park sham or a real needle, chosen at random, on the arms of 16 healthy volunteers. The researcher and the volunteers independently recorded which needle type they thought had been applied at each acupuncture point. Second, 19 patients with shoulder impingement syndrome were randomly assigned to receive acupuncture applied with the real needle or the Park sham needle, once a week for 6 weeks alongside a course of physiotherapy. At the end of the 6 sessions the patients recorded which needle type they thought was being used. The results were analyzed with a Fisher's exact test. This study was carried out in the Outpatient Department of Physiotherapy in Charing Cross Hospital, London, UK, on healthy volunteers and patients with shoulder impingement pain. The age range was 23 to 54 and 22 to 74 years respectively.RESULTS: Of the healthy volunteers, there was no difference(P=0.23) between the number of needles that were correctly(n=43) or incorrectly identified(n=53). All patients thought that they had received the real needles. The researcher correctly identified all needles that were applied. CONCLUSION: The researcher delivering the acupuncture recognized the needle type. However, both healthy and patient volunteers were blind to the needle type. This demonstrates that the Park sham needle is an effective single-blind control. It should be noted that the number of patients recruited was small and the study was underpowered to detect an effect of treatment. | May To Caroline Alexander | 2015 | Journal of Integrative Medicine2015，13，1： | 2 |
| 9 | Vertebroplasty versus conservative treatment in acute osteoporotic vertebral compression fractures (Vertos II): an open-label randomised trial显示文摘 | Caroline AH Klazen Paul NM Lohle Jolanda de Vries Frits H Jansen Alexander V Tielbeek Marion C Blonk Alexander Venmans Willem Jan J van Rooij Marinus C Schoemaker Job R Juttmann Tjoen H Lo Harald JJ Verhaar Yolanda van der Graaf Kaspar J van Everdingen Al | 2010 | 2010 (9746)2010，，9746： | 2 |
| 10 | Phylogenetic analysis of hemagglutinin, neuraminidase, and nucleoprotein genes of H9N2 avian influenza viruses isolated in Israel during the 2000–2005 epizootic显示文摘 | Shimon Perk Natalia Golender Caroline Banet-Noach Ester Shihmanter Shimon Pokamunsky Michael Pirak Yevgenii Tendler Michael Lipkind Alexander Panshin | 2007 | Comparative Immunology Microbiology and Infectious Diseases2007，，3： | 1 |
| 11 | Paternally Induced Transgenerational Environmental Reprogramming of Metabolic Gene Expression in Mammals显示文摘 | Benjamin R. Carone Lucas Fauquier Naomi Habib Jeremy M. Shea Caroline E. Hart Ruowang Li Christoph Bock Chengjian Li Hongcang Gu Phillip D. Zamore Alexander Meissner Zhiping Weng Hans A. Hofmann Nir Friedman Oliver J. Rando | 2010 | Cell2010，，7： | 1 |
| 12 | Hepatitis B virus hepatotropism is mediated by specific receptor recognition in the liver and not restricted to susceptible hosts显示文摘 | Alexa Schieck Andreas Schulze Caroline G?hler Thomas Müller Uwe Haberkorn Alexander Alexandrov Stephan Urban Walter Mier | 2013 | Hepatology2013，，1： | 1 |
| 13 | Vertebroplasty versus conservative treatment in acute osteoporotic vertebral compression fractures (Vertos II): an open-label randomised trial显示文摘 | Caroline AH Klazen Paul NM Lohle Jolanda de Vries Frits H Jansen Alexander V Tielbeek Marion C Blonk Alexander Venmans Willem Jan J van Rooij Marinus C Schoemaker Job R Juttmann Tjoen H Lo Harald JJ Verhaar Yolanda van der Graaf Kaspar J van Everdingen Al | 2010 | The Lancet2010，，9746： | 1 |
| 14 | Linaclotide is a potent and selective guanylate cyclase C agonist that elicits pharmacological effects locally in the gastrointestinal tract显示文摘 | Alexander P. Bryant Robert W. Busby Wilmin P. Bartolini Etchell A. Cordero Gerhard Hannig Marco M. Kessler Christine M. Pierce Robert M. Solinga Jenny V. Tobin Shalina Mahajan-Miklos Mitchell B. Cohen Caroline B. Kurtz Mark G. Currie | 2010 | Life Sciences2010，，19： | 1 |
| 15 | Linaclotide, through activation of guanylate cyclase C, acts locally in the gastrointestinal tract to elicit enhanced intestinal secretion and transit显示文摘 | Robert W. Busby Alexander P. Bryant Wilmin P. Bartolini Etchell A. Cordero Gerhard Hannig Marco M. Kessler Shalina Mahajan-Miklos Christine M. Pierce Robert M. Solinga Li Jing Sun Jenny V. Tobin Caroline B. Kurtz Mark G. Currie | 2010 | European Journal of Pharmacology2010，，1： | 1 |
| 16 | Linaclotide is a potent and selective guanylate cyclase C agonist that elicits pharmacological effects locally in the gastrointestinal tract显示文摘 | Alexander P. Bryant Robert W. Busby Wilmin P. Bartolini Etchell A. Cordero Gerhard Hannig Marco M. Kessler Christine M. Pierce Robert M. Solinga Jenny V. Tobin Shalina Mahajan-Miklos Mitchell B. Cohen Caroline B. Kurtz Mark G. Currie | 2010 | Life Sciences2010，，19： | 1 |
| 17 | Imaging genetics of FOXP2 in dyslexia显示文摘 | Arndt Wilcke Carolin Ligges Jana Burkhardt Michael Alexander Christiane Wolf Eifi Quente Petr Ahnert Per Hoffmann Albert Bcher Bertram Muller-Myhsok Sven Cichon Johannes Boltze and Holger Kirsten | | 0，，： | 1 |
| 18 | The role of osteoblast cells in the pathogenesis of unicameral bone cysts显示文摘 | Alexander Aarvold James Smith Edward Tayton Caroline Edwards Darren Fowler Edward Gent Richard Oreffo | 2012 | Journal of Children’s Orthopaedics2012，，4： | 1 |
| 19 | Short-Term Outcomes of Acute Myocardial Infarction in Patients With Acute Kidney Injury: A Report From the National Cardiovascular Data Registry显示文摘 | Caroline S. Fox Paul Muntner Anita Y. Chen Karen P. Alexander Matthew T. Roe Stephen D. Wiviott | 2012 | Circulation2012，，3： | 1 |
| 20 | Pulmonary Emphysema: Subjective Visual Grading versus Objective Quantification with Macroscopic Morphometry and Thin-section CT Densitometry显示文摘 | Viviane de Maertelaer Caroline Keyzer | 1999 | Radiology1999，211，3： | 1 |
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