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Gut-brain connection: The neuroprotective effects of the anti-diabetic drug liraglutide

World Journal of Diabetes 2015年第6期6卷 807-827页

作者： Emanuel Monteiro Candeias Inês Carolina Sebastio Susana Maria Cardoso Sónia Catarina Correia Cristina Isabel Carvalho Ana Isabel Plácido Maria Sancha Santos Catarina Resende Oliveira Paula Isabel Moreira Ana Isabel Duarte CNC-center for Neuroscience and Cell Biology Rua Larga Faculty of Medicine (1st Floor) University of Coimbra Institute for Interdisciplinary Research (IIIUC) University of Coimbra Casa Costa Alem?o-Pólo II Rua D Francisco de Lemos 3030-789 Coimbra Portugal Faculty of Medicine University of Coimbra Life Sciences Department University of Coimbra Largo Marquês de Pombal 3004-517 Coimbra Portugal Institute of Biochemistry Faculty of Medicine University of Coimbra Institute of Physiology Faculty of Medicine University of Coimbra

Long-acting glucagon-like peptide-1(GLP-1) analogues marketed for type 2 diabetes(T2D) treatment have been showing positive and protective effects in several different tissues, including pancreas, heart or even brain. This gut secreted hormone plays a potent insulinotropic activity and an important role in maintaining glucose homeostasis. Furthermore, growing evidences suggest the occurrence of several commonalities between T2 D and neurodegenerative diseases, insulin resistance being pointed as a main cause for cognitive decline and increased risk to develop dementia. In this regard, it has also been suggested that stimulation of brain insulin signaling may have a protective role against cognitive deficits. As GLP-1 receptors(GLP-1R) are expressed throughout the central nervous system and GLP-1 may cross the blood-brain-barrier, an emerging hypothesis suggests that they may be promising therapeutic targets against brain dysfunctional insulin signaling-related pathologies. Importantly, GLP-1 actions depend not only on the direct effect mediated by its receptor activation, but also on the gut-brain axis involving an exchange of signals between both tissues via the vagal nerve, thereby regulating numerous physiological functions(e.g., energy homeostasis, glucose-dependent insulin secretion, as well as appetite and weight control). Amongst the incretin/GLP-1 mimetics class of anti-T2 D drugs with an increasingly described neuroprotective potential, the already marketed liraglutide emerged as a GLP-1R agonist highly resistant to dipeptidyl peptidase-4 degradation(thereby having an increased half-life) and whose systemic GLP-1R activity is comparable to that of native GLP-1. Importantly, several preclinical studies showed anti-apoptotic, anti-inflammatory, anti-oxidant and neuroprotective effects of liraglutide against T2 D, stroke and Alzheimer disease(AD), whereas several clinical trials, demonstrated some surprising benefits of liraglutide on weight loss, microglia in

关键词： Type 2 diabetes Glucagon-like peptide-1 Gut Brain Insulin Liraglutide Alzheimer disease Neuroprotection

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Paclitaxel liposome for injection (Lipusu) plus cisplatin versus gemcitabine plus cisplatin in the first-line treatment of locally advanced or metastatic lung squamous cell carcinoma: A multicenter, randomized, open-label, parallel controlled clinical study

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Cancer Communications 2022年第1期42卷 3-16页

作者： Jie Zhang Yueyin Pan Qin Shi Guojun Zhang Liyan Jiang Xiaorong Dong Kangsheng Gu Huijuan Wang Xiaochun Zhang Nong Yang Yuping Li Jianping Xiong Tienan Yi Min Peng Yong Song Yun Fan Jiuwei Cui Gongyan Chen Wei Tan Aimin Zang Qisen Guo Guangqiang Zhao Ziping Wang Jianxing He Wenxiu Yao Xiaohong Wu Kai Chen Xiaohua Hu Chunhong Hu Lu Yue Da Jiang Guangfa Wang Junfeng Liu Guohua Yu Junling Li Jianling Bai Wenmin Xie Weihong Zhao Lihong Wu Caicun Zhou Department of Medical Oncology Shanghai Pulmonary Hospital&Thoracic Cancer InstituteTongji University School of MedicineShanghai 200433P.R.China Department of Chemotherapy Anhui Provincial HospitalHefeiAnhui 230001P.R.China Department of Oncology Fuzhou Pulmonary Hospital of FujianFuzhouFujian 350008P.R.China Department of Respiratory Medicine the First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052P.R.China Department of Respiration Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghai 200030P.R.China Cancer center Union Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022P.R.China Department of Medical Oncology the First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230032P.R.China Department of Respiration Henan Cancer HospitalZhengzhouHenan 450008P.R.China Department of Medical Oncology the Affiliated Hospital of Qingdao UniversityQingdaoShandong 266000P.R.China Department of Medical Oncology Hunan Cancer HospitalChangshaHunan 410013P.R.China Department of Pulmonary and Critical Care Medicine the First Affiliated Hospital of Wenzhou Medical CollegeShangcai villageWenzhouZhejiang 325000P.R.China Department of Medical Oncology the First Affiliated Hospital of Nanchang UniversityNanchangJiangxi 330006P.R.China Department of Medical Oncology Xiang Yang Central HospitalXiangyangHubei 441021P.R.China Department of Medical Oncology Renmin Hospital of Wuhan UniversityWuhanHubei 430060P.R.China Department of Respiration General Hospital of Eastern Theater Command of Chinese People’s Liberation ArmyNanjingJiangsu 210002P.R.China Department of Medical Oncology Zhejiang Cancer HospitalHangzhouZhejiang 310022P.R.China Cancer center the First Bethune Hospital of Jilin UniversityChangchunJilin 130021P.R.China Department of Medical Oncology Harbin Medical University Cancer HospitalHarbinHeilongjiang 150081P.R.China Department of Respiratory Medicine Weifang People’s HospitalWeifangShandong

Background:Lipusu is the first commercialized liposomal formulation of pacli-taxel and has demonstrated promising efficacy against locally advanced lung squamous cell carcinoma(LSCC)in a small-scale ***,we conducted a multicenter,randomized,phase 3 study to compare the efficacy and safety of cis-platin plus Lipusu(LP)versus cisplatin plus gemcitabine(GP)as first-line treat-ment in locally advanced or metastatic ***:Patients enrolled were aged between 18 to 75 years,had locally advanced(clinical stage IIIB,ineligible for concurrent chemoradiation or surgery)or metastatic(Stage IV)LSCC,had no previous systemic chemother-apy and at least one measurable lesion as per the Response Evaluation Criteria in Solid Tumors(version 1.1)before administration of the trial *** primary endpoint was progression-free survival(PFS).The secondary endpoints included objective response rate(ORR),disease control rate(DCR),overall survival(OS),and safety *** explore the possible predictive value of plasma cytokines for LP treatment,plasma samples were collected from the LP group at baseline and first efficacy evaluation time and were then subjected to analysis by 45-Plex ProcartaPlex Panel 1 to detect the presence of 45 cytokines using the Luminex xMAP *** correlation between treatment outcomes and dynamic changes in the levels of cytokines were evaluated in preliminary ***:The median duration of follow-up was 15.4 months.237 patients in the LP group and 253 patients in the GP group were included in the per protocol set(PPS).In the PPS,the median PFS was 5.2 months versus 5.5 months in the LP and GP group(hazard rtio[HR]:1.03,P=0.742)*** median OS was 14.6 months versus 12.5 months in the LP and GP group(HR:0.83,P=0.215).The ORR(41.8%versus 45.9%,P=0.412)and DCR(90.3%versus 88.1%,P=0.443)were also similar between the LP and GP group.A significantly lower proportion of patients in the LP group experienced adverse events(AEs)le

关键词： chemotherapy cisplatin clinical trial gemcitabine liposomal paclitaxel(Lipusu) locally advanced lung squamous cell carcinoma metastatic multicenter plasma cytokines

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Hyperhomocysteinemia dysregulates plasma levels of polyunsaturated fatty acids-derived eicosanoids

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Life Research 2022年第2期5卷 32-41页

作者： Mohamed Al-Shabrawey Ahmed Elmarakby Yara Samra Mohamed Moustafa Stephen WLooney Krishna Rao Maddipati Amany Tawfik Department of Foundational Medical Studies and Eye Research center Oakland University William Beaumont School of MedicineRochesterMichiganUSA Eye Research Institute Oakland UniversityRochesterMichiganUSA Department of Oral Biology and Diagnostic Sciences Dental College of GeorgiaAugusta UniversityAugustaGeorgiaUSA Departments of Pharmacology&Toxicology Faculty of PharmacyMansoura UniversityMansouraEgypt Department of Biochemistry Faculty of PharmacyMansoura UniversityEgypt Department of Population Health Sciences Medical College of GeorgiaAugusta UniversityAugustaGeorgiaUSA Bioactive Lipids Research Program Department of PathologyWayne State UniversityMichiganUSA

Hyperhomocysteinemia(HHcy)contributes to the incidence of many cardiovascular diseases(CVD).Our group have previously established crucial roles of eicosanoids and homocysteine in the incidence of vascular injury in diabetic retinopathy and renal *** cystathionine-β-synthase heterozygous mice(cβs^(+/-))as a model of HHcy,the current study was designed to determine the impact of homocysteine on circulating levels of lipid mediators derived from polyunsaturated fatty acids(PUFA).Plasma samples were isolated from wild-type(WT)and cβs^(+/-)mice for the assessment of eicosanoids levels using LC/*** 12/15-lipoxygenase(12/15-LOX)activity significantly decreased in cβs^(+/-)*** control ***-derived metabolites from both omega-3 and omega-6 PUFA were also reduced in cβs^(+/-)mice compared to WT control(Pcontrol ***(COX)metabolites were also significantly decreased in cβs^(+/-)*** control *** data suggest that HHcy impacts eicosanoids metabolism through decreasing LOX and COX metabolic activities while increasing CYP metabolic *** increase in AA metabolism by CYP was also associated with increase in sEH activity and decrease in EETs *** of eicosanoids metabolism could be a contributing factor to the incidence and progression of HHcy-induced CVD.

关键词： homocysteine cystathionine β-synthase eicosanoids cycloxygenase lipoxygenase cytochrome-P450

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Real-world disease activity and sociodemographic,clinical and treatment characteristics of moderate-to-severe inflammatory bowel disease in Brazil

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World Journal of Gastroenterology 2021年第2期27卷 208-223页

作者： Cyrla Zaltman Rogério Serafim Parra Ligia Yukie Sassaki Genoile Oliveira Santana Maria de Lourdes Abreu Ferrari Sender J Miszputen Heda M B S Amarante Roberto Luiz Kaiser Junior Cristina Flores Wilson R Catapani JoséMiguel Luz Parente Mauro Bafutto Odery Ramos Carolina D Gonçalves Isabella Miranda Guimaraes Jose J R da Rocha Marley R Feitosa Omar Feres Rogerio Saad-Hossne Francisco Guilherme Cancela Penna Pedro Ferrari Sales Cunha Tarcia NF Gomes Rodrigo Bremer Nones Mikaell Alexandre Gouvea Faria Mírian Perpétua Palha Dias Parente António S Scotton Rosana Fusaro Caratin Juliana Senra Júlio Maria Chebli Department of Internal Medicine Federal University of Rio de JaneiroRio de Janeiro 21941-913Brazil Department of Surgery and Anatomy Ribeirão Preto Medical SchoolUniversity of São PauloRibeirao Preto 14049-900São PauloBrazil Department of Internal Medicine São Paulo State University(UNESP)Medical SchoolBotucatu 18618-687São PauloBrazil IBD Unit Federal University of BahiaSalvador 41150-000BahiaBrazil Department of Clinical Medicine Medical SchoolUniversidade Federal de Minas GeraisBelo Horizonte 30130-100Minas GeraisBrazil Department of Gastroenterology Escola Paulista de MedicinaSão Paulo 04023-900Brazil Hospital de Clinicas Universidade Federal do ParanaCuritiba 80060-900ParanaBrazil Department of Proctology Beneficencia Portuguesa Hospital/Kaiser Day HospitalSao Jose do Rio Preto 15015110São PauloBrazil Department of Gastroenterology and Hepatology Sciences Hospital de ClínicasUniversidade Federal do Rio Grande do SulPorto Alegre 90560002Rio Grande do SulBrazil Department of Gastroenterology Faculdade de Medicina do ABCSanto Andre 09060-870São PauloBrazil Department of General Medicine Gastroenterology UnitUniversity HospitalFederal University of PiauiTeresina 64049-550PiauíBrazil Department of Gastroenterology Faculdade de MedicinaUniversidade Federal de GoiásGoiania 74535-170GoiasBrazil Department of Surgery Botucatu Medical School at São Paulo State University(UNESP)Botucatu 18618687São PauloBrazil Department of Gastroenterology UNIFESPSão Paulo 04040-002Brazil IBD unit Gastroenterology DepartmentHospital Nossa Senhora das GraçasCuritiba 80810-040ParanaBrazil Department of Proctology Kaiser Hospital DiaSao Jose do Rio Preto 15015-110São PauloBrazil Health Sciences center Epidemiology UnitState University of PiauiTeresina 64001-280PiauíBrazil Department of Gastroenterology CMIP Centro Mineiro de PesquisaJuiz de Fora 36010-570Minas GeraisBrazil Scientific Affairs Takeda Pharmaceuticals BrazilSão Paulo 04709-011Brazil Clinical Research Takeda Pharma

BACKGROUND Understanding the treatment landscape of inflammatory bowel diseases(IBD)is essential for improving disease management and patient *** is the largest Latin American country,and it presents socioeconomic and health care differences across its geographical *** country has the highest increase in IBD incidence and prevalence in Latin America,but information about the clinical and treatment characteristics of IBD is *** To describe the sociodemographic,clinical,and treatment characteristics of IBD outpatients in Brazil overall and in the Southeast,South and Northeast/Midwest *** Multicenter,cross-sectional study with a 3-year retrospective chart review *** with moderate-to-severe Crohn’s disease(CD)or ulcerative colitis(UC)were consecutively enrolled between October 2016 and February *** CD at enrollment was defined as a Harvey Bradshaw Index≥8 or a CD Activity Index≥220 or a calprotectin level>200μg/g or an active result based on colonoscopy suggestive of inadequate control during the previous year;active UC was defined as a partial Mayo score≥*** statistics were used to analyze all *** In a total of 407 included patients,CD was more frequent than UC,both overall(264 CD/143 UC patients)and by region(CD:UC ratios of 2.1 in the Southeast,1.6 in the South and 1.2 in the Northeast/Midwest).The majority of patients were female(54.2%of CD;56.6%of UC),and the mean ages were 45.9±13.8 years(CD)and 42.9±13.0 years(UC).The median disease duration was 10.0(range:0.5-45)years for both IBD *** enrollment,44.7%[95%confidence interval(CI):38.7-50.7]of CD patients and 25.2%(95%CI:18.1-32.3)of UC patients presented with active *** than 95%of IBD patients were receiving treatment at enrollment;CD patients were commonly treated with biologics(71.6%)and immunosuppressors(67.4%),and UC patients were commonly treated with mesalazine[5-Aminosalicylic acid(5-ASA)]derivates(69.9%)and

关键词： Inflammatory bowel disease Crohn's disease Ulcerative colitis Disease activity Epidemiology Treatment

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以气候行动助力健康老龄化

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科学通报 2023年第33期68卷 4472-4479页

作者：蔡闻佳张弛张诗卉白玉琪 Max Callaghan 常楠陈彬陈慧琪程亮亮崔学勤戴瀚程 Bawuerjiang Danna 董文轩范维澄房小怡高仝耿阳关大博胡艺馨华峻翊黄存瑞黄弘黄建斌江林朗蒋俏蕾姜晓朋金虎 Gregor Kiesewetter 梁璐林波荣林华亮刘欢刘起勇刘涛刘小波刘心远刘钊刘竹楼书含鲁晨曦罗震宇孟文君苗卉任超 Marina Romanello Wolfgang Schopp 苏婧汤绪王灿王琼 Laura Warnecke 文三妹 Wilfried Winiwarter 谢杨徐冰颜钰杨秀姚芳虹俞乐袁嘉灿曾仪娉张镜张璐张锐张尚辰张少辉赵梦真赵琦郑大山周浩周景博罗勇宫鹏清华大学地球系统科学系北京100084 北京理工大学管理与经济学院北京100081 Mercator Research Institute on Global Commons and Climate Change Mercator Research Institute on Global Commons and Climate ChangeBerlin 10829Germany 南京医科大学公共卫生学院南京211166 北京师范大学环境学院北京100875 中山大学公共卫生学院广州510080 北京大学环境科学与工程学院北京100871 清华大学新闻与传播学院北京100084 清华大学公共安全研究所北京100084 清华大学工程物理系北京100084 中国气象科学研究院气象影响与风险研究中心北京100086 山东师范大学商学院济南250013 清华大学建筑学院北京100084 东南大学经济管理学院南京211189 中国海洋大学国际事务与公共管理学院青岛266003 清华大学万科公共卫生学院北京100084 中国科学技术大学计算机科学与技术学院合肥230027 世界卫生组织驻华代表处北京100600 复旦大学大气与海洋系/大气科学研究院上海200438 复旦大学极端天气/气候事件与人体健康风险互联和治理国际卓越中心上海200438 Pollution Management Research Group EnergyClimateand Environment ProgramInternational Institute for Applied Systems Analysis(IIASA)Laxenburg 2361Austria Department of Geography and the Environment University of North TexasDenton TX 76203-5017USA 清华大学环境学院北京100084 中国疾病预防控制中心传染病预防控制所传染病溯源预警与智能决策全国重点实验室北京102206 北京经济管理职业学院临空经济管理学院北京100102 Belfer center for Science and International Affairs Harvard UniveristyCambridge 02138USA 北京大学城市与环境学院北京100871 香港大学建筑学院中国香港999077 Institute for Global Health University College LondonLondon WC1H 0ALUK 清华大学人文学院北京100084 北京航空航天大学经济与管理学院北京100083 山东大学齐鲁医学院公共卫生学院流行病学系济南250002 清华大学气候变化与可持续发展研究院北京100084 北京大学体育教研部北京100871 清华大学苏世民学院北京100084 山东大学气候变化与健康研究中心济南250002 清华大学城市治理与可持续发展研究院北京100084 百度研究院北京100091 香港大学地球科学系和地理系中国香港999077

在中国宣布碳中和目标以及频繁遭受极端气候事件的背景下,2021年以来中国社会对气候变化的关注度持续高涨.与此同时,随着中国人口老龄化趋势愈加明显,气候变化所带来的健康风险问题日益突出.采取健康友好型的气候变化应对策略及碳中和... 详细信息

在中国宣布碳中和目标以及频繁遭受极端气候事件的背景下,2021年以来中国社会对气候变化的关注度持续高涨.与此同时,随着中国人口老龄化趋势愈加明显,气候变化所带来的健康风险问题日益突出.采取健康友好型的气候变化应对策略及碳中和实现路径,将可以有效减少人类(尤其是老年人群)的空气污染暴露情况.这方面的行动不仅有助于改善人类健康和福祉,还能够促进经济社会的高质量发展.

关键词：健康老龄化碳中和气候变化应对极端气候事件人口老龄化趋势老年人群健康风险实现路径

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