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Complex diseases demand novel treatment strategies: understanding drug combination

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Drug Combination Therapy 2022年第2期4卷 5-16页

作者： Renata Siqueira de Mello Vanessa Fernandes Arnaud-Sampaio Lucas Ferreira Maciel Vanessa de Sá Talita glaser Henning Ulrich Claudiana Lameu Departamento de Bioquímica Instituto de QuímicaUniversidade de São PauloSPBrazil

For many multigene or multifactorial diseases,the one-drug therapy for inhibiting a defined molecular target is often less effective than combined ***,drug combination therapies are multitargeted,so the mechanisms or even interactions are often *** drug-drug interactions may promote alteration of pharmacokinetic or pharmacodynamic activities of one drug by another *** interactions may change the expected effect of medications through polymorphisms that alter the expression or activity of the drug-mediated enzyme and the cell signaling cascade,such as drug-gene interactions and drug-drug-gene *** number of possible existing interactions requires appropriate methods of *** this review,we summarized combination therapies for cancer,as well as for viral,cardiovascular,and neurological ***,we also highlight known methodologies,such as in vitro methods based on Loewe’s and Bliss’s pioneer models and in silico methods based on online available *** more elaborate methods and reliable results,multitarget therapies through drug combinations may increasingly benefit patients suffering from complex diseases.

关键词： drug combinations multitarget therapy combination therapy drug-drug interaction in vitro in silico methods and models

A Naval Race with China Is Unnecessary and Will Likely Backfire

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A Naval Race with China Is Unnecessary and Will Likely Backf...

America and China: Destined for Conflict or Cooperation? We Asked 14 of the World's Most Renowned Experts

作者： JOHN glaser foreign policy studies at the Cato Institute a leading Washington think-tank

WASHINGTON-Policymakers increasingly perceive China’s growing naval strength in Asia as an acute threat to American interests that must be met with a corresponding surge in *** power in the ***,precisely what tangibl... 详细信息

关键词： A Naval Race with China Is Unnecessary and Will Likely Backfire

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America and China: Destined for Conflict or Cooperation? We ...

A Common Peptidolytic Mechanism for Targeting Peptide Degradation in Mitochondria and Chloroplasts

作者： JOHN glaser the Cato Institute

The future of the Sino-American relationship is deeply *** the United States will remain at the top of the international hierarchy for the foreseeable future, it is undoubtedly experiencing relative decline, while China is indisputably on the rise. The two titans of the 21st century maintain an uneasy rapport, conscious of each other’s power, suspicious of each other’s intentions, and covetous of the stature that accompanies global supremacy.

关键词： America and China We Asked 14 of the World's Most Renowned Experts Destined for Conflict or Cooperation

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Molecular Plant 2018年第2期11卷 342-345页

作者： Beata Kmiec Rui M.M. Branca Monika W. Murcha Janne Lehtio Elzbieta glaser Pedro F. Teixeira Department of Biochemistry and Biophysics Stockholm University Arrhenius Laboratories for Natural Sciences 106 91 Stockholm Sweden Clinical Proteomics Mass Spectrometry Department of Oncology-Pathology Science for Life Laboratory and Karolinska Institutet Stockholm Sweden ARC Centre of Excellence in Plant Energy Biology University of Western Australia Crawley WA Australia School of Molecular Sciences University of Western Australia Crawley WA Australia

Dear Editor Mitochondria are multifunctional organelles of eukaryotic cells. Biogenesis and functionality of mitochondria require the import of more than 90% of its resident proteins after synthesis by cytosolic ribos... 详细信息

关键词： PRESEQUENCES PREP

MR弹性成像生物学标志物检测不伴肝纤维化的非酒精性脂肪性肝病组织学改变的研究

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国际医学放射学杂志 2022年第1期 118-119页

作者： Y.Qu M.S.Middleton R.Loomba K.J.glaser J.Chen 张跃

摘要目的在确诊或疑似的不伴肝纤维化的非酒精性脂肪性肝病（NAFLD）成年病人中，评估多参数MR弹性成像(MRE)测得的肝脏机械学特性与组织学之间的关联。方法

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Purinergic Receptors in Basal Ganglia Diseases:Shared Molecular Mechanisms between Huntington’s and Parkinson’s Disease

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Neuroscience Bulletin 2020年第11期36卷 1299-1314页

作者： Talita glaser Roberta Andrejew Agatha Oliveira-Giacomelli Deidiane Elisa Ribeiro Lucas Bonfim Marques Qing Ye Wen-Jing Ren Alexey Semyanov Peter Illes Yong Tang Henning Ulrich Department of Biochemistry Institute of ChemistryUniversity of Sao PauloAv.Prof.Lineu Prestes 74&Sao PauloSP 05508-000Brazil Key Laboratory of Sichuan Province for Acupuncture and Chronobiology Chengdu 610075China Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of SciencesMoscow 117997Russia Sechenov First Moscow State Medical University Moscow 119992Russia Rudolf-Boehm-Institut ftir Pharmakologie und Toxikologie Universitat LeipzigLeipzig 04107Germany International Collaborative Centre on Big Science Plan for Purine Signaling Chengdu University of Traditional Chinese MedicineChengdu 610075China

Huntington’s(HD)and Parkinson’s diseases(PD)are neurodegenerative disorders caused by the death of GABAergic and dopaminergic neurons in the basal ganglia leading to hyperkinetic and hypokinetic symptoms,*** review here the participation of purinergic receptors through intracellular Ca^2+signaling in these neurodegenerative *** adenosine A2A receptor stimulates striatopallidal GABAergic neurons,resulting in inhibitory actions on GABAergic neurons of the globus pallidus.A2A and dopamine D2 receptors form functional heteromeric complexes inducing allosteric inhibition,and A2A receptor activation results in motor ***,the A2A receptor physically and functionally interacts with glutamate receptors,mainly with the mGlu5 receptor *** interaction facilitates glutamate release,resulting in NMDA glutamate receptor activation and an increase of Ca2+influx.P2X7 receptor activation also promotes glutamate release and neuronal ***,modulation of purinergic receptor activity,such as A2A and P2X7 receptors,and subsequent aberrant Ca^2+signaling,might present interesting therapeutic potential for HD and PD.

关键词： Purinergic receptor Central nervous system Huntington’s disease Parkinson’s disease 6-hydroxydopamine

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Four Minutes That Get You Hired

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语言教育 1995年第3期 29-34页

作者： Connie Brown glaser Barbara Steinberg Smalley 诸葛勤

The 28-year-old had spent six years working at night whileshe attended university during the day.“I always wanted to be ateacher,”she says,“and I worked hard to earn my *** Ifinally graduated.I was very optimistic.... 详细信息

关键词： night university interview nearby wanted spent worked likely someone verbal

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Adoptive transfer of Pfkfb3-disrupted hematopoietic cells to wild-type mice exacerbates diet-induced hepatic steatosis and inflammation

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Liver Research 2020年第3期4卷 136-144页

作者： Xin Guo Bilian Zhu Hang Xu Honggui Li Boxiong Jiang Yina Wang Benrong Zheng Shannon glaser Gianfranco Alpini Chaodong Wu Department of Nutrition Texas A&M UniversityCollege StationTXUSA Department of Nutrition and Food Hygiene School of Public HealthCheeloo College of MedicineShandong UniversityJinanChina Department of VIP Medical Service Center The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina Medical Physiology Texas A&M University College of MedicineBryanTXUSA Hepatology and Gastroenterology MedicineIndiana UniversityIndianapolisINUSA Richard L.Roudebush VA Medical Center IndianapolisINUSA

Background and objectives:Hepatic steatosis and inflammation are key characteristics of non-alcoholic fatty liver disease(NAFLD).However,whether and how hepatic steatosis and liver inflammation are differentially regulated remains to be *** that disruption of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3(Pfkfb3/iPfk2)dissociates fat deposition and inflammation,the present study examined a role for Pfkfb3/iPfk2 in hematopoietic cells in regulating hepatic steatosis and inflammation in ***:Pfkfb3-disrupted(Pfkfb3^(+/-))mice and wild-type(WT)littermates were fed a high-fat diet(HFD)and examined for NAFLD ***,bone marrow cells isolated from Pfkfb3^(+/-)mice andWT mice were differentiated into macrophages for analysis of macrophage activation status and for bone marrow transplantation(BMT)to generate chimeric(WT/BMT-Pfkfb3^(+/-))mice in which Pfkfb3 was disrupted only in hematopoietic cells and control chimeric(WT/BMT-WT)*** latter were also fed an HFD and examined for NAFLD *** vitro,hepatocytes were co-cultured with bone marrowderived macrophages and examined for hepatocyte fat deposition and proinflammatory ***:After the feeding period,HFD-fed Pfkfb3^(+/-)mice displayed increased severity of liver inflammation in the absence of hepatic steatosis compared with HFD-fed WT *** inflammatory activation was analyzed,Pfkfb3^(+/-)macrophages revealed increased proinflammatory activation and decreased anti-proinflammatory *** NAFLD phenotype was analyzed in the chimeric mice,WT/BMT-Pfkfb3^(+/-) mice displayed increases in the severity of HFD-induced hepatic steatosis and inflammation compared with WT/BMT-WT *** the cellular level,hepatocytes co-cultured with Pfkfb3^(+/-) macrophages revealed increased fat deposition and proinflammatory responses compared with hepatocytes co-cultured with WT ***:Pfkfb3 disruption only in hematopoietic cells exacerbates HFD-induce

关键词： 6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase 3(Pfkfb3/iPfk2) Hematopoietic cells Hepatic steatosis Inflammation Macrophages

Bile acid interactions with cholangiocytes

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World Journal of Gastroenterology 2006年第22期12卷 3553-3563页

作者： Xuefeng Xia Heather Francis Shannon glaser Gianfranco Alpini Gene LeSage University of Texas at Houston Medical School Houston TX United States Division of Research and Education Scott & White Hospital and The Texas A&M University System Health Science Center College of Medicine Temple TX United States Department of Medicine Division of Research and Education Scott & White Hospital and The Texas A&M University System Health Science Center College of MedicineTemple TX United States Central Texas Vctcrans Health Care System and Department of Medicine and Systems Biology and Translational Medicine United States

Cholangiocytes 在他们的顶端的膜暴露于胆汁酸的高集中。为胆汁酸的选择 transporter，顶端的钠胆汁酸 Cotransporter (ASBT )( 也叫作 Ibat；基因名字 Slc10a2 ) 在 cholangiocyte 上是局部性的顶端的膜。在 basolateral 膜上，四个... 详细信息

Cholangiocytes 在他们的顶端的膜暴露于胆汁酸的高集中。为胆汁酸的选择 transporter，顶端的钠胆汁酸 Cotransporter (ASBT )( 也叫作 Ibat；基因名字 Slc10a2 ) 在 cholangiocyte 上是局部性的顶端的膜。在 basolateral 膜上，四个运输系统被识别了(t-ASBT，多药抵抗(MDR ) 3，一个未辩别出的阴离子 exchanger 系统和器官的溶质 transporter (Ost ) 异侧 transporter， Ostalpha-Ostbeta。一起，这些单向性地搬运 ers 从管的胆汁的行动胆汁酸到发行量。cholangiocytes 吸收的胆汁酸为重新分泌物经由仙子胆管丛再循环回到 hepatocytes 进胆汁。这再循环在 hepatocytes 和 cholangiocytes 之间的胆汁酸被叫作 cholehepatic 分流小径。最近的研究建议 cholehepatic 分流小径可以由于额外的肝的阻塞在胆汁酸并且到改编的全面肝胆管运输作出贡献到长期的胆汁郁积。ASBT 被腺苷 3' 尖锐地调整， 5'-monophosphate (营地) 依赖者易位到顶端的膜并且由 phosphorylation 依赖的 ubiquitination 和 proteasome 降级。ASBT 被变化长期地响应胆汁的胆汁酸集中和煽动性的 cytokines 在基因表示调整。cholangiocyte ASBT 的另一潜在的功能是允许 cholangiocytes 取样胆汁的胆汁酸以便激活细胞内部的表明小径。在细胞内部的钙，蛋白质激酶 C (PKC ) ， phosphoinositide 3-kinase (PI3K ) ，激活 mitogen 的蛋白质(地图) 激酶和细胞外的调整信号的蛋白质激酶(英皇家空军之阶级最低之兵) 的胆汁酸扳机变化细胞内部的信号。胆汁酸显著地改变 cholangiocyte 分泌物，增长和幸存。不同胆汁酸在 cholangiocyte 上有微分效果细胞内部发信号，并且在一些例子，扳机反对在 cholangiocyte 上完成分泌物，增长和幸存。在这些之上基于概念和观察， cholangiocyte 被建议了是为在肝的胆汁酸的原则目标房间。

关键词：胆汁酸肝疾病病理机制临床