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Distinct molecular targets of ProEGCG from EGCG and superior inhibition of angiogenesis signaling pathways for treatment of endometriosis

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Journal of Pharmaceutical Analysis 2024年第1期14卷 100-114页

作者： Sze Wan Hung Massimiliano Gaetani Yiran Li Zhouyurong Tan Xu Zheng Ruizhe Zhang Yang Ding Gene Chi Wai Man Tao Zhang Yi Song Yao Wang Jacqueline Pui Wah Chung tak hang chan Roman A.Zubarev Chi Chiu Wang Department of Obstetrics&Gynaecology The Chinese University of Hong KongHong KongChina Division of Physiological Chemistry I Department of Medical Biochemistry and BiophysicsKarolinska InstitutetStockholmSE 17177Sweden Chemical Proteomics Core Facility Department of Medical Biochemistry and BiophysicsKarolinska InstitutetStockholmSE 17177Sweden Unit of Chemical Proteomics Science for Life Laboratory(SciLifeLab)StockholmSE 17177Sweden Center for Reproductive Medicine Henan Key Laboratory of Reproduction and GeneticsThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou450003China Department of Chemistry McGill UniversityMontrealH3A2K6Canada Department of Pharmacological&Technological Chemistry I.M.Sechenov First Moscow State Medical UniversityMoscow119146Russia Reproduction and Development Li Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong KongChina School of Biomedical Sciences The Chinese University of Hong KongHong KongChina Chinese University of Hong Kong-Sichuan University Joint Laboratory in Reproductive Medicine The Chinese University of Hong KongHong KongChina

Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the *** is a major pathophysiology in *** previous studies have demonstrated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain *** this study,we demonstrated that oral ProEGCG can be effective in preventing and treating ***,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,*** simulation and BioLayer interferometry were used to confirm their binding *** results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)*** vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling ***,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel antiangiogenic therapy for endometriosis.

关键词： Molecular targets ProEGCG EGCG Angiogenesis Treatment Endometriosis

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A Theoretical Study of the Intrinsic Reactivities of Various Allyl-metalstowards Carbonyls and Water

A Theoretical Study of the Intrinsic Reactivities of Various...

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中国化学会第十三届金属有机化学学术讨论会

作者： Lung Wa Chung, tak hang chan, and Yun-Dong Wu, Department of Chemistry, The Hong Kong University of Science & Technology, Clear Water Bay, Kowloon, Hong Kong, Department of Chemistry, McGill University, Montreal, Quebec, Canada H3A 2K6 and State Key Laboratory of Molecular Dynamics and Stable Species, College of Chemistry, Peking University

＜正＞ Quantum mechanics MP2/6-31+G* calculations have been carried out for the reactions of a series of monomeric allyl-metals with water and carbonyl compounds in the gas phase. Allyl complexes of groups ⅠA and ⅡA, and low valent groups ⅢA, and ⅣA metals are in π-complexes or reactive σ-complexes. They show high reactivities towards hydrolysis. Group ⅡB, trivalent group ⅢA, tetravalent group ⅣA, and both tri- and penta-valent group ⅤA metals form σ-complexes with allyl. These allyl-metals are less reactive towards hydrolysis than towards allylation. The calculated intrinsic kinetic preference of allylation over hydrolysis is found to correlate well with the reactivity of hydrolysis, nucleophilicity of the allyl-metals and lateness of hydrolysis transition structures. Both nucleophilicity of the allyl-metal complexes and the thermodynamic driving force are important to the reactivity of hydrolysis. Importantly, there is a large thermodynamic preference for allylation over hydrolysis for all allyl-metals because the hydrolysis has to break a strong O-H bond. So the kinetic preference for allylation is correlated with the degree of H-O bond breaking in the hydrolysis transition structure.

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Curriculum Adaptation in Special Schools for Students with Intellectual Disabilities(SID):A Case Study of Project Learning in One SID School in Hong Kong

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Frontiers of Education in China 2014年第2期9卷 250-273页

作者： Zhang Jia-Wei WONG Lam chan tak-hang CHIU Chi-Shing Hong Kong Institute of Educational Research The Chinese University of Hong KongHong KongChina

Using a qualitative case study approach,the authors analyzed the curriculum adaptation process for one project learning activity in School K,which is a SID school in the context of school-university *** sources of data were collected for triangulation,including interviews,documents and *** adaptation strategies in this study were analyzed from five perspectives:instructional goals,instructional content,instructional strategies,instructional settings,and student behavioral *** was found that curriculum adaptation efforts could help students with ID develop potential at their own level through project learning activates and teachers could also gain professional development during the university-school collaboration *** for future studies,enlarging the sample size,involving teachers’past orientations and motivations in the project learning process,and collecting quantitative data could all be taken into account.

关键词： special education students with intellectual disabilities(SID) curriculum adaptation project learning

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Rapid testing methods for food contaminants and toxicants

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Journal of Integrative Agriculture 2015年第11期14卷 2243-2264页

作者： Jiachi Chiou Arthur Ho Hon Leung hang Wai Lee Wing-tak Wong Department of Applied Biology and Chemical Technology Food Safety and Technology Research CenterThe Hong Kong Polytechnic University Shenzhen Key Laboratory for Food Biological Safety Control Food Safety and Technology Research CentreThe Hong Kong Polytechnic University Shenzhen Research Institute

Food safety is one of the major concerns in every country regardless of the economic and social development. The frequent occurrence of food scandals in the world has led the Chinese government to implement several strategies to fortify the food supply system to a high food safety standard. This relies heavily on laboratory testing services but conventional methods for detection of food contaminants and toxicants are limited by sophisticated sample preparation procedures, long analysis time, large instruments and professional personnel to meet the increasing demands. In this review, we have incorporated most of the current and potential rapid detection methods for many notorious food contaminants and toxicants including microbial agents, toxic ions, pesticides, veterinary drugs and preservatives, as well as detection of genetically modified food genes and adulterated edible oil. Development of rapid, accurate, easy-to-use and affordable testing methods could urge food handlers and the public to actively screen for food contaminants and toxicants instead of passively relying on monitoring by the government examination facility. This review also provides several recommendations including how to encourage the public to engage in the food safety management system and provide optimal education and financial assistance that may improve the current Chinese food safety control system.

关键词： rapid testing food contaminants and toxins microbial agents pesticides veterinary drugs preservatives formaldehyde nitrite nitrate test strips

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The Hong Kong consensus recommendations on the diagnosis and management of pancreatic cystic lesions

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Hepatobiliary Surgery and Nutrition 2023年第5期12卷 715-735,I0019-I0020页

作者： Tan-To Cheung Yuk Tong Lee Raymond Shing-Yan Tang Wong Hoi She Kai Chi Cheng Chin Cheung Cheung Keith Wan hang Chiu Kenneth Siu Ho Chok Wing Sun Chow tak Wing Lai Wai-Kay Seto Thomas Yau Department of Surgery Queen Mary HospitalThe University of Hong KongHong KongChina Gastroenterologist in private practice Hong KongChina Department of Medicine and Therapeutics The Chinese University of Hong KongHong KongChina Department of Surgery Kwong Wah HospitalHong KongChina Department of Surgery Tuen Mun HospitalHong KongChina Department of Radiology&Imaging Queen Elizabeth HospitalHong KongChina Department of Medicine The University of Hong KongHong KongChina Department of Surgery Princess Margaret HospitalHong KongChina Department of Medicine School of Clinical MedicineThe University of Hong KongHong KongChina State Key Laboratory of Liver Research The University of Hong KongHong KongChina

Background:The finding of pancreatic cystic lesions(PCL)on incidental imaging is becoming increasingly *** studies report a prevalence of 2.2-44.7%depending on the population,imaging modality and indication for imaging,and the prevalence increases with *** with PCL are at risk of developing pancreatic cancer,a disease with a poor *** publication summarizes recommendations for the diagnosis and management of PCL and post-operative pancreatic exocrine insufficiency(PEI)from a group of local ***:Clinical evidence was consolidated from narrative reviews and consensus statements formulated during two online meetings in March *** expert panel included gastroenterologists,hepatobiliary surgeons,oncologists,radiologists,and ***:Patients with PCL require careful investigation and follow-up due to the risk of malignant transformation of these *** should undergo clinical investigation and pancreas-specific imaging to classify lesions and understand the risk profile of the *** indicated,patients should undergo pancreatectomy to excise *** pancreatectomy,patients are at risk of PEI,leading to gastrointestinal dysfunction and ***,such patients should be monitored for symptoms of PEI,and promptly treated with pancreatic enzyme replacement therapy(PERT).Patients with poor response to PERT may require increases in dose,addition of a proton pump inhibitor,and/or further investigation,including tests for pancreatic *** are also at risk of new-onset diabetes mellitus after pancreatectomy;they should be screened and treated with insulin if ***:These statements are an accurate summary of our approach to the diagnosis and management of patients with PCL and will be of assistance to clinicians treating these patients in a similar clinical landscape.

关键词： Pancreatic cystic lesions pancreatic endocrine insufficiency pancreatic enzyme replacement therapy

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Synthesis of Permethyl Epigallocatechin gallate and Its Analogues as Nontoxic,Potent,Pgp Specific Multidrug Resistance（MDR） Reversal Agents of Cancer Cells

Synthesis of Permethyl Epigallocatechin gallate and Its Anal...

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2011年全国药物化学学术会议——药物的源头创新

作者： Iris L.K.Wong chan tak hang Larry M.C.Chow Department of Applied Biology and Chemical Technology The Hong Kong Polytechnic University

＜正＞A series of permethyl（-）-epigallocatechin gallate（（-）-EGCG） analogues have been synthesized and tested for their ability to modulate multidrug resistance（MDR） in Pgp overexpressing cell lines （LCC6MDR）,BCRP overexpressing cell lines（HEK293/R2 and MCF7-MX100） and MRPl overexpressing cell lines（2008/MRP1）.The drugs used in the test were paclitaxel(for LCC6MDR

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聚合物支持的三苯基氯硅烷在昆虫性信息素固相合成中的应用

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化学学报 1986年第9期44卷 934-939页

作者：陈德恒黄文强加拿大麦吉尔大学化学系加拿大麦吉尔大学化学系蒙特利尔蒙特利尔天津南开大学高分子化学研究所

1％二乙烯基苯交联的聚苯乙烯树脂在N,N,N′,N′-四甲基乙二胺的存在下用丁基锂进行锂化后与二苯基二氯硅烷反应制得聚苯乙烯支持的三苯基氯硅烷(2).这种聚合物用于一些鳞翅目(Lepidoptera)昆虫的性信息素的固相合成.2与1,9-壬二醇、1,... 详细信息

1％二乙烯基苯交联的聚苯乙烯树脂在N,N,N′,N′-四甲基乙二胺的存在下用丁基锂进行锂化后与二苯基二氯硅烷反应制得聚苯乙烯支持的三苯基氯硅烷(2).这种聚合物用于一些鳞翅目(Lepidoptera)昆虫的性信息素的固相合成.2与1,9-壬二醇、1,10-癸二醇和1,12-十二碳二醇反应分别生成聚合物支持的二醇单硅醚(4a、4b、4c),游离的醇基用Swern试剂(DMSO和草酸酰氯)氧化成聚合物支持的醛(5a、5b、5c),经Wittig缩合反应和用氟离子裂解后分别得到9-十四碳烯醇-1(8a),10-十四碳烯醇-1(8b)和12-十四碳烯醇-1(Sc).化合物8经乙酰化后分别得到9-十四碳烯醇-1乙酸酯(9a),其顺式异构体是秋灰夜蛾(***,Smith)的性信息素;10-十四碳烯醇-1乙酸酯(9b),其顺式异构体是橡卷叶蛾(***,Walker)的性信息素;和12-十四碳烯醇-1乙酸酯(9c).9c与四氯化碲反应,硫化钠还原后转化成E-和Z-异构体比例为54∶46的亚洲玉米螟(Ostrinia furnicalis)的性信息素.

关键词：聚合物十二碳二醇反应大分子化合物昆虫性信息素烯醇乙酸酯羧酸酯固相合成反应合成

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Effects of ginsenosides on vascular reactivity in rat cerebral and renal arteries

Effects of ginsenosides on vascular reactivity in rat cerebr...

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两岸三地药理学与临床药理学术会议

作者： WONG Wing-tak LEUNG Fung-ping YUNG Lai-hang WONG Ricky Ngok Shun Department of Physiology Chinese University of Hong Kong Department of Biology Hong Kong Baptist University

Objective To investigate possible mechanisms underlying the antioxidant property(1)and the in vitro vasodilator effects(2)of the two ginsenosides,Rb1 and Rg1,in isolated rat renal and cerebral arter- *** Arterial rings were mounted in a multi-channel myograph for recording of isometric *** examine the antioxidant activity,some rings were exposed to a free radical-generating reaction(hypoxan- thine and xanthine oxidase)with and without pre-treatment with *** calcium antagonistic ef- fects were tested on rings contracted by membrane depolarization in elevated extracellular potassium ions,a condition that promoted Cainflux in vascular smooth muscle *** Ginsenosides protected en- dothelial function(endothelial nitric oxide-dependent relaxation)against oxidative stress;(2)ginsenoside Rbl reduced the high K+-induced contractions of both renal and cerebral arteries while ginsenoside Rgl re- laxed the rat cerebral artery but not the renal *** Ginsenosides are vaso-protective via(1) the antioxidant activity which protects endothelial cell function and(2)the inhibition of Ca2+influx through voltage-sensitive Cachannels in vascular smooth *** vasodilator effects may suggest the potential preventive or therapeutic values of ginsenosides against stroke and renal hypertension.

关键词： ginsenosides endothelial cells relaxation

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Synthesis of(Z)-3-dodecenolide,the main aggregation pheromone from the flat grain beetle,Crvptolestes Pusillus Sch(?)nerr

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Acta Chimica Sinica English Edition 1989年第5期7卷 407-411页

作者： LI Chao-Jun LI Ji-Sheng Institute of Chemistry,Academia Sinica,Beijingchan tak hang Department of Chemistry,McGill University,Canada Institute of Chemistry Academia Sinica Beijing Department of Chemistry McGill University Canada

The main aggregation pheromone component(1)of stored grain pest,Cryptolestes Pusillus, was synthesized with organosilicon and organolithium reagents in an overall yield of 18% from 1,7- heptanediol.

关键词： Synthesis of nerr dodecenolide,the main aggregation pheromone from the flat grain beetle,Crvptolestes Pusillus Sch

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Switch off “Parallel Circuit”: Insight of New Strategy of Simultaneously Suppressing Canonical and Non-canonical Inflammation Activation in Endotoxemic Mice

Switch off “Parallel Circuit”: Insight of New Strategy of ...

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第十一届全国化学生物学学术会议

作者： Lei Yan Jiaqi Liang Yi Zhou Jian Huang Tianshu Zhang Xiaohui Wang hang Yin Department of Chemistry School of Pharmaceutical SciencesTsinghua University Changchun Institute of Applied Chemistry Chinese Academy of Sciences

Sepsis is a life-threatening inflammatory disease with a high mortality rate and huge implicative cost. Lipopolysaccharide（LPS） from Gram-negative bacteria activates toll-like receptor 4（TLR4） and may trigger septic shock. However, potent TLR4 inhibitors tak-242 and Eritoran were terminated in phase III clinical trials because of inadequate efficacy. Inspired by the recently discovered intracellular, non-canonical LPS receptors, we considered that TLR4-mediated canonical and caspase-mediated non-canonical inflammation could be seen as a "parallel circuit" to induce sepsis and endotoxemia. Logically, we proposed that the dual inhibition of caspase-4/5/11 and TLR4 could be a potential novel strategy to develop new therapeutics for sepsis. To verify the strategy, we have found three potential compounds: C1, C2, and C3 with substantial anti-inflammatory activity in vitro and in vivo. Our results showed that the survival rate of endotoxemic mice treated by these compounds was increased remarkably. LPS-induced organ damage was also prevented. Moreover, these compounds resulted in physical and mental recovery for endotoxemic mice. Notably, C2 exhibited better anti-inflammatory activity than tak-242 at comparable TLR4-inhibitory levels. Our findings indicated that simultaneous inhibition of TLR4 and caspase-4/5/11 could be an anticipative strategy defeating sepsis and endotoxemia, which would be translated into significant medical and economic benefits.

关键词： Non-canonical inflammation Pyroptosis Caspase-4/5/11 TLR4 Sepsis

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