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第八届亚太医学毒理学大会暨全国中毒控制与救治论坛（20...

作者： Nur Afni A Haslina H Adilah MA Rahmat A Razak L Mohamed Izham MI National Poison Centre Penang Malaysia school of pharmaceutical sciences Universiti Sains MalaysiaPenangMalaysia

＜正＞Introduction: This study was undertaken to determine the knowledge and attitude among the general public in Kuala Lumpur,the capital city of Malaysia on poisoning preventive measures

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Specifically targeting human telomeric dimeric G-quadruplexes by polyehter-tethered di-berberine derivatives

Specifically targeting human telomeric dimeric G-quadruplexe...

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中国化学会第四届卟啉与酞菁学术研讨会

作者： Zi-Qi Li Ting-Cong Liao Wen-Hua Chen Chun-Qiong Zhou Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical University

The design and synthesis of binders specifically multiple G-quadruplex units in the 3’-terminal overhang of human telomeric DNA has attracted considerable attention,which will promote to develop some selective anticancer agents with fewer side effects.Herein three polyether-tethered di-berberine compounds（1-3） have been prepared and studied on their binding affinity,selectivity and thermal stabilization towards dimeric quadruplex DNA by UV-Vis titrations,electrophoresis,fluorescence spectroscopy,CD spectroscopy and CD-melting.Compound 1 with the shortest polyether linker has been found to have higher binding affinity,selectivity and thermal stabilization towards mixed-type dimeric quadruplexes over antiparallel dimeric and monomeric quadruplexes than compounds 2-3 with the longer polyether linkers.More intriguingly,four molecules of compound 1 might externally stack on the end G-quartets of the two mixed-type G-quadruplex units on one dimeric quadruplex.In addition,these diberberine derivatives displayed good inhibitory activities toward four tumor cell lines.

关键词： Di-berberine dimeric quadruplex DNA telomere binding selectivity

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相对差异基础上的生物相似性评估标准(英文)

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药物分析杂志 2015年第5期35卷 822-831页

作者： Ying Lu Shein- chung Chow Zhong- zhan Zhang school of sciences Communication University of China Beijing 100024 China school of Medicine Duke University Durham NC 27705 USA College of Applied sciences Beijing University of Technology Beijing 100124 China

为了检测仿制生物制品与其原研生物制品的相似性,目前主要采用基于相对差异指标的统计方法进行评价。常用的统计推断主要基于双序列(two-sequence)、双周期(two-period)的交叉设计,或者在忽略原研药批次间变异情况下的双臂平行设计。本... 详细信息

为了检测仿制生物制品与其原研生物制品的相似性,目前主要采用基于相对差异指标的统计方法进行评价。常用的统计推断主要基于双序列(two-sequence)、双周期(two-period)的交叉设计,或者在忽略原研药批次间变异情况下的双臂平行设计。本文采用三臂平行设计(three-arm parallel design),分别测定仿制生物制品与原研生物制品的绝对差异,原研生物制品不同批次间的绝对差异,并通过该两绝对差异之比来评价仿制生物制品与原研生物制品的生物相似性概率(biosimilar probability)。这种基于生物相似性概率的评价标准,在大样本下具有渐进正态的性质,给出了检验的功效和临床试验中样本量的计算公式。本文通过模拟研究和样本量估算,证明了生物相似性概率的统计检验法具有良好的检验效能。

关键词：三臂式平行设计生物相似性生物相似性概率相对差异绝对差异

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A single amino acid determines the catalytic efficiency of two alkenal double bond reductases produced by the liverwort Plagiochasma appendiculatum

A single amino acid determines the catalytic efficiency of t...

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中国化学会第十届全国天然有机化学学术会议

作者： Yi-Feng Wu Xiao-Juan Han Hong-Xiang Lou Ai-Xia Cheng Key Laboratory of Chemical Biology of Natural Products Ministry of Education School of Pharmaceutical Sciences Shandong University

＜正＞Alkenal double bond reductases（DBRs）catalyze the NADPH-dependent reduction of theα,β-unsaturated double bond of many secondary metabolites.Two alkenal double bond reductase genes Pa DBR1 and Pa DBR2 were isolated from the liverwort species Plagiochasma appendiculatum.Recombinant Pa DBR2 protein had a higher catalytic activity than Pa DBR1 with

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The β-catenin/YAP signaling axis is a key regulator of melanoma-associated fibroblasts

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Signal Transduction and Targeted Therapy 2019年第1期4卷 34-48页

作者： Tianyi Liu Linli Zhou Kun Yang Kentaro Iwasawa Ana Luisa Kadekaro Takanori Takebe Thomas Andl Yuhang Zhang Division of pharmaceutical sciences College of PharmacyUniversity of CincinnatiCincinnatiOH45267USA Division of Gastroenterology Hepatology&NutritionCincinnati Children’s Hospital Medical Center3333 Burnet AvenueCincinnatiOH45229-3039USA Division of Developmental Biology Cincinnati Children’s Hospital Medical Center3333 Burnet AvenueCincinnatiOH45229-3039USA Department of Dermatology College of MedicineUniversity of CincinnatiCincinnatiOH45267USA Center for Stem Cell and Organoid Medicine(CuSTOM) Cincinnati Children’s Hospital Medical Center3333 Burnet AvenueCincinnatiOH45229-3039USA Department of Pediatrics University of Cincinnati College of Medicine3333 Burnet AvenueCincinnatiOH45229-3039USA Institute of Research Tokyo Medical and Dental University 1-5-45 YushimaBunkyo-kuTokyo113-8510Japan Burnett school of Biological sciences University of Central FloridaOrlandoFL32816USA

β-catenin is a multifunctional protein that plays crucial roles in embryonic development,physiological homeostasis,and a wide variety of human cancers.Previously,we showed that in vivo targeted ablation ofβ-catenin in melanoma-associated fibroblasts after melanoma formation significantly suppressed tumor growth.However,when the expression ofβ-catenin was ablated in melanoma-associated fibroblasts before tumor initiation,melanoma development was surprisingly accelerated.How stromalβ-catenin deficiency leads to opposite biological effects in melanoma progression is not completely understood.Here,we report thatβ-catenin is indispensable for the activation of primary human stromal fibroblasts and the mediation of fibroblast-melanoma cell interactions.Using coimmunoprecipitation and proximity ligation assays,we identified Yes-associated protein(YAP)as an importantβ-catenin-interacting partner in stromal fibroblasts.YAP is highly expressed in the nuclei of cancer-associated fibroblasts(CAFs)in both human and murine melanomas.Mechanistic investigation revealed that YAP nuclear translocation is significantly modulated by Wnt/β-catenin activity in fibroblasts.Blocking Wnt/β-catenin signaling in stromal fibroblasts inhibited YAP nuclear translocation.In the absence of YAP,the ability of stromal fibroblasts to remodel the extracellular matrix(ECM)was inhibited,which is consistent with the phenotype observed in cells withβ-catenin deficiency.Further studies showed that the expression of ECM proteins and enzymes required for remodeling the ECM was suppressed in stromal fibroblasts after YAP ablation.Collectively,our data provide a new paradigm in which theβ-catenin-YAP signaling axis regulates the activation and tumor-promoting function of stromal fibroblasts.

关键词： melanoma inhibited homeostasis

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MULTI-WALLED CARBON NANOTUBES-BASED GLUCOSE BIOSENSOR PREPARED BY LAYER-BY-LAYER TECHNIQUE

MULTI-WALLED CARBON NANOTUBES-BASED GLUCOSE BIOSENSOR PREPAR...

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第二届国际传感器科学研讨会

作者： Jun-ichi ANZAI Graduate school of pharmaceutical sciences Tohoku UniversityAramakiAoba-kuSeidai 980-8578Japan

＜正＞ Glucose biosensor is a kind of useful detecting instrument to monitor the content of glucose in blood and urine of human body. Glucose oxidase （GOx） has been widely used in glucose biosensor construction due to its high selectivity to glucose and high activity over a broad range of pH values. The GOx can catalyze the reaction of glucose to form hydrogen peroxide （H2O2）（Eqs.1）, and the biosensor can originate the amperometric response from the oxidation current of H2O2 （Eqs.2）.

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A 2D Cu2+-based metal-organic framework for the dual sensing of Hg2+ and I- via a fluorescence “on” and “off” mechanism

A 2D Cu2+-based metal-organic framework for the dual sensing...

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第十届全国化学生物学学术会议

作者： Pei-Pei Hu Ke-Yang Wu Ling-Yan Zhai Nai-Han Huang Jin-Xiang Chen Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical University

A two-dimensional(2D) metal-organic framework(MOF) {[Cu(Dcbb)(bpe)]·OH·2HO·}n(1) has been synthesized from CuCl and a zwitterionic ligand HDcbbBr in the presence of bpe(HDcbbBr = 1-(3,5-dicarboxybe-nzyl)-4,4’-bipyridinium bromide, bpe = 1,2-bis(4-pyridyl)ethylene). MOF 1 can effectively associate with the thymine-rich(T-rich), carboxyfluorescein(FAM)-labeled probe single-stranded DNA(P-DNA) and quenches the FAM fluorescence with quenching efficiency(QE) of 90.5% to give a non-emissive P-DNA@1 hybrid(off-state). In the presence of Hg, T-rich P-DNA strands can form rigid sandwich duplexes DNA(ds-DNA) due to form T-Hg-T configuration and detach from the surface of MOF 1, leading to the recovery of fluorescence of the FAM(on state) with florescence recovery efficiency of 3.9. Subsequently, upon addition of iodide(I) ions, Hg was released from ds-DNA due to the higher affinity of Hg to the I-, which could induce ds-DNA unwinding to form ss-DNA and resorbed by MOF, thus again resulted in fluorescence quenching(off-state) with QE of 64.7%. The limits of detection for Hg and I-are 3.2 nM and 3.3 nM, respectively.

关键词： metal-organic framework fluorescence sensing Hg2+ sensing I-sensing

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Synthesis and bioactivity of novel coumarin derivatives

Synthesis and bioactivity of novel coumarin derivatives

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中国化学会第十一届全国天然有机化学学术会议

作者： Hui-Hui Sun Dong-Jun Fu Jian-Song Ruo-Han Zhao Sai-Yang Zhang Ying-Chao Liu Feng Li Yan-Bing Zhang Collaborative Innovation Center of New Drug Research and Safety Evaluation School of Pharmaceutical Sciences Zhengzhou University

＜正＞A series of novel coumarin derivatives were synthesized from commercially available chemical agents（Figure 1）.All prepared compounds were evaluated for their in vitro antiproliferative activity against five selected human cancer cell lines（EC109,MGC-803,PC-3,MCF-7,and EC9706）and their in vitro antimicrobial activity against E.coli and M.albicans.4-（3-Bromopropoxy）-2H-chromen-2-one exhibited the highest growth inhibition

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Inflammation, oxidative stress and renin angiotensin system in atherosclerosis

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World Journal of Biological Chemistry 2015年第3期6卷 209-217页

作者： Kazim Husain Wilfredo Hernandez Rais A Ansari Leon Ferder Department of Physiology Pharmacology and Toxicology Ponce School of Medicine Department of Biochemistry Ponce School of Medicine Department of pharmaceutical sciences College of Pharmacy Nova Southeastern University

Atherosclerosis is a chronic inflammatory disease associated with cardiovascular dysfunction including myocardial infarction, unstable angina, sudden cardiac death, stroke and peripheral thromboses. It has been predicted that atherosclerosis will be the primary cause of death in the world by 2020. Atherogenesis is initiated by endothelial injury due to oxidative stress associated with cardiovascular risk factors including diabetes mellitus, hypertension, cigarette smoking, dyslipidemia, obesity, and metabolic syndrome. The impairment of the endothelium associated with cardiovascular risk factors creates an imbalance between vasodilating and vasoconstricting factors, in particular, an increase in angiotensin Ⅱ(Ang Ⅱ) and a decrease in nitric oxide. The renin-angiotensin system(RAS), and its primary mediator Ang Ⅱ, also have a direct influence on the progression of the atherosclerotic process via effects on endothelial function, inflammation, fibrinolytic balance, and plaque stability. Anti-inflammatory agents [statins, secretory phospholipase A2 inhibitor, lipoprotein-associated phospholipase A2 inhibitor, 5-lipoxygenase activating protein, chemokine motif ligand-2, C-C chemokine motif receptor 2 pathway inhibitors, methotrexate, IL-1 pathway inhibitor and RAS inhibitors(angiotensin-converting enzyme inhibitors)], Ang Ⅱ receptor blockers and ranin inhibitors may slow inflammatory processes and disease progression. Several studies in human using anti-inflammatory agents and RAS inhibitors revealed vascular benefits and reduced progression of coronary atherosclerosis in patients with stable angina pectoris; decreased vascular inflammatory markers, improved common carotid intima-media thickness and plaque volume in patients with diagnosed atherosclerosis. Recent preclinical studies have demonstrated therapeutic efficacy of vitamin D analogs paricalcitol in Apo E-deficient atherosclerotic mice.

关键词： Atherosclerosis Renin-angiotensin system Inflammation Oxidants/antioxidants imbalance Antiinflammatory drugs Renin-angiotensin system blockers

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Identification of novel factors for obesity

Identification of novel factors for obesity

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第三届中国生物物理学会代谢生物学分会学术研讨会

作者： Qiao-Ping Wang Armand Valsesia Nele Gheldof Andrew Hicks Herbert Herzog Greg Neely school of pharmaceutical sciences (Shenzhen) Sun Yat-sen University Charles Perkins Centre University of Sydney Nestle Institute of Health sciences

＜正＞Obesity is globally endemic with over 600 million people.Both genetics and environment have played a major role in obesity.Our aim is to identify the novel genes and environmental factors and then dissect the underlying mechanisms to understand the regulation of energy homeostasis.Epidemiological studies showed that artificial sweeteners are potential factors for obesity.We demonstrated that artificially sweetener sucralose caused food intake increase and firstly revealed a

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