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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 Pt/CeO_(2)Hybrid Nanozyme with Stable Peroxidase Activity for the Detection of Acetylcholine

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chemical Research in Chinese Universities 2024年第2期40卷 268-271页

作者： CUI Xulian MA Baofu PAN Hui XIA Yu LIU Li ZHAO Baofeng LIANG Zhen ZHANG Lihua ZHANG Yukui State Key Laboratory of Medical proteomics Dalian Institute of Chemical PhysicsChinese Academy of ScienceDalian116023P.R.China The Research Center for Medical Genomics Key Laboratory of Medical Cell BiologyMinistry of EducationSchool of Life ScienceChina Medical UniversityShenyang110001P.R.China River Fisheries Research Institute Chinese Academy of Fishery SciencesGuangzhou510000P.R.China

Acetylcholine(ACh)is a common neurotransmitterl)that is secreted by cholinergic neurons[2]and is found mainly in the peripheral and central nervous systems.[3]ACh transmits nerve signals from presynaptic to postsynapt... 详细信息

关键词： Acetylcholine/choline Nanozyme Hydrogen peroxide Alzheimer’s disease

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CYP3A5 unexpectedly regulates glucose metabolism through the AKT-TXNIP-GLUT1 axis in pancreatic cancer

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Genes & Diseases 2024年第4期11卷 381-399页

作者： Ming Shao Qingfei Pan Haiyan Tan Jing Wu Ha Won Lee Andrew D.Huber William C.Wright Ji-Hoon Cho Jiyang Yu Junmin Peng Taosheng Chen Department of chemical Biology and Therapeutics St.Jude Children's Research HospitalMemphisTN 38105USA Department of Computational Biology St.Jude Children's Research HospitalMemphisTN 38105USA Center for proteomics and Metabolomics St.Jude Children's Research HospitalMemphisTN 38105USA Department of Structural Biology St.Jude Children's Research HospitalMemphisTN 38105USA Department of Developmental Neurobiology St.Jude Children's Research HospitalMemphisTN 38105USA

CYP3A5 is a cytochrome P450(CYP)enzyme that metabolizes drugs and contributes to drug resistance in ***,it remains unclear whether CYP3A5 directly influences cancer *** this report,we demonstrate that CYP3A5 regulates glucose metabolism in pancreatic ductal ***-omics analysis showed that CYP3A5 knockdown re-sults in a decrease in various glucose-related metabolites through its effect on glucose trans-port.A mechanistic study revealed that CYP3A5 enriches the glucose transporter GLUT1 at the plasma membrane by restricting the translation of TXNIP,a negative regulator of ***,CYP3A5-generated reactive oxygen species were proved to be responsible for atten-uating the AKT-4EBP1-TXNIP signaling ***3A5 contributes to cell migration by maintaining high glucose uptake in pancreatic *** together,our results,for the first time,reveal a role of CYP3A5 in glucose metabolism in pancreatic ductal adenocarcinoma and identify a novel mechanism that is a potential therapeutic target.

关键词： Cell migration CYP3A5 Glucose metabolism GLUT1 Pancreatic cancer TXNIP

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STRAP binds to and promotes the repair of N1-methyldeoxyadenosine in DNA

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Chinese chemical Letters 2024年第3期35卷 204-207页

作者： Meijuan Zhou Qian Liu Mengting Pan Ying Yang Xiaoxia Dai Changjun You State Key Laboratory of Chemo/Biosensing and Chemometrics Hunan Provincial Key Laboratory of Biomacromolecular Chemical BiologyMolecular Science and Biomedicine LaboratoryCollege of Chemistry and Chemical EngineeringHunan UniversityChangsha 410082China

N1-methyladenosine(m1A)is an important RNA modification that functions in various biological processes by interacting with cellular ***,the binding proteins of N1-methyldeoxyadenosine(1mdA)in DNA remain largely ***,we employed a quantitative proteomics strategy to identify the potential binding proteins of 1mdA in human *** results revealed that serine–threonine kinase receptor-associated protein(STRAP)can bind to 1mdA-carrying *** further demonstrated that STRAP participates in alkylating agent-induced DNA damage response and can promote the repair of 1mdA embedded in ***,we investigated the effects of STRAP on 1mdA-induced perturbation in transcription using a shuttle vector-and next-generation sequencing-based assay,and found that STRAP is involved in the transcriptional bypass of 1mdA in human ***,our study revealed STRAP as a novel 1mdA-binding protein in human cells and provided new insight into the biological implications of STRAP and 1mdA modification in human diseases.

关键词： N1-methyldeoxyadenosine 1mdA-binding protein STRAP DNA repair Transcription

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Proteomic investigations of acute ischemic stroke in animal models:a narrative review

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Journal of Bio-X Research 2023年第1期6卷 15-22页

作者： Fangxu Sun Rong-Fang Gu Ru Wei chemical Biology and proteomics BiogenCambridgeMAUSA

Acute ischemic stroke(AIS),a neurological injury resulting from blood clots,is the second most common cause of death *** therapeutics are urgently *** developments in instrumentation and bioinformatics have resulted in increased use of mass spectrometry-based proteomics as an effective tool for the in-depth study of *** review focuses on proteomics investigations of AIS in animal *** highlight the study findings in system-wide protein abundance changes and molecular mechanisms underlying AIS with or without therapeutic intervention,as well as prestroke prognosis *** review reveals that common molecular pathways related to ischemic injury and spontaneous recovery have been uncovered and part of AIS-changed proteins have been repeatedly identified,indicating the promise of proteomics in generating novel therapeutic targets and biomarker *** also discuss challenges,alleviating strategies,and perspectives of mass spectrometry-based proteomics in AIS research and call for a broad application of systems-level investigations on preclinical AIS molecular mechanism elucidation,target discovery and validation,and therapeutics development.

关键词： acute ischemic stroke ischemic molecular mechanism MCAO model proteomics stroke biomarker

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Role of glycosylation in TGF-β signaling and epithelial-to-mesenchymal transition in cancer

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Protein & Cell 2021年第2期12卷 89-106页

作者： Jing Zhang Peter ten Dijke Manfred Wuhrer Tao Zhang Oncode Institute and Cell chemical Biology Leiden University Medical Center2300 RC LeidenThe Netherlands Center for proteomics and Metabolomics Leiden University Medical CenterLeidenThe Netherlands

Glycosylation is a common posttranslational modification on membrane-associated and secreted proteins that is of pivotal importance for regulating cell *** glycosylation can lead to uncontrolled cell proliferation,cell-matrix interactions,migration and differentiation,and has been shown to be involved in cancer and other *** epithelial-to-mesenchymal transition is a key step in the metastatic process by which cancer cells gain the ability to invade tissues and extravasate into the *** cellular transformation process,which is associated by morphological change,loss of epithelial traits and gain of mesenchymal markers,is triggered by the secreted cytokine transforming growth factor-β(TGF-β).TGF-βbioactivity is carefully regulated,and its effects on cells are mediated by its receptors on the cell *** this review,we first provide a brief overview of major types of glycans,namely,N-glycans,O-glycans,glycosphingolipids and glycosaminoglycans that are involved in cancer ***,we summarize studies on how the glycosylation of TGF-βsignaling components regulates TGF-βsecretion,bioavailability and TGF-βreceptor ***,we review glycosylation changes associated with TGF-β-induced epithelial-to-mesenchymal transition in *** and understanding the mechanisms by which glycosylation affects TGF-βsignaling and downstream biological responses will facilitate the identification of glycans as biomarkers and enable novel therapeutic approaches.

关键词： cancer epithelial-to-mesenchymal transition glycosphingolipids N-glycosylation Oglycosylation transforming growth factor-β

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Cancer stem cells: Involvement in pancreatic cancer pathogenesis and perspectives on cancer therapeutics

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World Journal of Gastroenterology 2014年第31期20卷 10790-10801页

作者： Cristiana Pistol Tanase Ana Iulia Neagu Laura Georgiana Necula Cristina Mambet Ana-Maria Enciu Bogdan Calenic Maria Linda Cruceru Radu Albulescu Department of Biochemistry-proteomics Victor Babes National Institute of Pathology Stefan S Nicolau Institute of Virology Carol Davila University of Medicine and Pharmacy National Institute for chemical Pharmaceutical Research and Development

Pancreatic cancer is one of the most aggressive and lethal malignancies. Despite remarkable progress in understanding pancreatic carcinogenesis at the molecular level, as well as progress in new therapeutic approaches, pancreatic cancer remains a disease with a dismal prognosis. Among the mechanisms responsible for drug resistance, the most relevant are changes in individual genes or signaling pathways and the presence of highly resistant cancer stem cells(CSCs). In pancreatic cancer, CSCs represent 0.2%-0.8% of pancreatic cancer cells and are considered to be responsible for tumor growth, invasion, metastasis and recurrence. CSCs have been extensively studied as of late to identify specific surface markers to ensure reliable sorting and for signaling pathways identified to play a pivotal role in CSC self-renewal. Involvement of CSCs in pancreatic cancer pathogenesis has also highlighted these cells as the preferential targets for therapy. The present review is an update of the results in two main fields of research in pancreatic cancer, pathogenesis and therapy, focused on the narrow perspective of CSCs.

关键词： Cancer stem cells Pancreatic cancer Cancer stem cells signaling pathways Targeted therapy miRNA

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Differential Expression Analysis of Proteins Regulated by Rare Earth Cerium in Soybean Leaves at Seedling Stage

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Journal of Northeast Agricultural University(English Edition) 2024年第1期31卷 42-52页

作者： Ren Hongyu Zhang Tianren Miao Yanli Li Haoyang Zhang Shuying Zhang Xingwen College of Resources and Environment Northeast Agricultural UniversityHarbin 150030China College of Chemistry and chemical Engineering Harbin Institute of TechnologyHarbin 150001China

This study was to explore the functional mechanism of rare earth regulating soybean leaves and the characteristics and functions of differentially expressed proteins under the regulation of rare earth. In this study, Dongnong 42 was used as material, and 30 mg·L^(-1) CeCl_(3) solution was sprayed on soybean leaves at the seedling stage. Tandem mass tag(TMT) quantitative proteomics technique and bioinformatics analysis were used to identify soybean leaf proteins. A total of 8 510 proteins were identified, and 127 differentially expressed proteins(DEPs) in response to rare earth cerium regulation were identified, among which 64 were upregulated and 63 were down-regulated. The gene ontology(GO) annotation indicated that DEPs were mainly involved in metabolic process, cellular process, response to stimulus, biological regulation, and response to a stimulus;DEPs in cell module categories were mainly involved in cells, cell part, organelle, membrane, membrane part, organelle par, and protein-containing complex;DEPs in molecular functional categories were mainly involved in catalytic activity, binding and antioxidant activity. Kyoto encyclopedia of genes and genomes(KEGG) pathway significantly enriched starch and sucrose metabolism, glycolysis/gluconeogenesis, galactose metabolism, pentose phosphate pathway, and MAPK signaling pathway-plant. These DEPs were mainly involved in photosynthesis, glucose metabolism and stress response. Forty-six differential protein interaction networks were identified by protein interaction network analysis. This experiment provided a reference for studies of the mechanism of rare earth cerium regulating soybean leaf function from the proteomic perspective.

关键词： rare earth soybean proteomics tandem mass tag(TMT)

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Renewal and preliminary study of expressed sequence tags database on human fetal liver aged 22 wk of gestation

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Chinese Science Bulletin 2008年第20期53卷 3204-3210页

作者： CHEN TingGui WU SongFeng ZHOU GangQiao ZHU YunPing HE FuChu State Key Laboratory of proteomics Beijing Proteome Research Center Beijing Institute of Radiation Medicine Beijing 102206 China Key Laboratory of chemical Biology and Molecular Engineering of Ministry of Education Shanxi University Taiyuan 030006 China

With the developments of international human transcriptome data and our ESTs of human fetal liver aged 22 weeks (wk) of gestation (HFL22w), the former research must be renewed. In this work, the EST data were firstly clustered by blasting against the ESTs of HFL22w, UniGene, DoTS, MGC and Twinscan-predicted human transcriptome. Then, after EST assembly and gene identification, the known genes were classified by GO (gene ontology), and the unknown genes were predicted by Pfam and ScanProsite to clarify their functions. In the end, the relations of 5 tissues including fetal liver, adult liver, bone marrow, thymus and lymph node that possess hemopoiesis or can indicate fetal liver characteristics were analyzed by hierarchical clustering. The results show that: (i) By comparing the 5 newest human transcriptome databases, we can largely reduce the probability that the ESTs belonging to unconnected parts of one gene were probably divided into different clusters, so it is recommended to blast against the newest databases when clustering EST data; (ii) some previous unknown ESTs had been identified as function-known genes, and 1379 genes were identified as fully new sequences possessed in our lab; (iii) through GO classification, we got a rough understanding of HFL22w, and obtained 6 cell migration genes and 6 hemopoiesis genes; (iv) prediction of gene function had enabled us to obtain 277 profiles, among them, there are 5 categories distributed in more than 10 genes; (v) five tissue relations analyzed by hierarchical clustering are related to their functions; (vi) We have built the world's largest EST database on HFL22w. Renewal and preliminary analysis of EST database on HFL22w will help to understand hemopoiesis and cell migration mechanism, and promote future research on human fetal liver.

关键词：怀孕期胎儿肝脏表达序列基因存在论分级聚类

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Widespread arginine phosphorylation in human cells——a novel protein PTM revealed by mass spectrometry

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Science China Chemistry 2020年第3期63卷 341-346页

作者： Songsen Fu Chuan Fu Quan Zhou Rongcan Lin Han Ouyang Minning Wang Ying Sun Yan Liu Yufen Zhao Department of chemical Biology College of Chemistry and Chemical EngineeringKey Laboratory for Chemical Biology of Fujian ProvinceXiamen UniversityXiamen 361005China School of Life Science University of DundeeDundee DD15EHUK State Key Laboratory of proteomics Beijing Proteome Research CenterBeijing Institute of Radiation MedicineNational Center for Protein Sciences(The PHOENIX Center)Beijing 102206China Key Laboratory of Bioorganic Phosphorus Chemistry and chemical Biology(Ministry of Education) Department of ChemistryTsinghua UniversityBeijing 102206China Institute of Drug Discovery Technology Ningbo UniversityNingbo 315211China

Arginine phosphorylation(p Arg)is recently discovered as a ubiquitous protein N-phosphorylation in ***,its prevalence and roles in mammalian cells remain largely unknown due to the lack of established workflow and the inherent lability of phosphoramidate(P–N)*** evidences suggest that N-phosphorylation may extensively exist in eukaryotes and play crucial *** report a phosphoproteomic workflow,which allows for the first time revealing the widespread occurrence of p Arg in human cells by mass *** virtue of this approach,we identified 152 high-confidence p Arg sites derived from 118 ***,the discovered p Arg phosphorylation motif and gene ontology hint a possible cellular function of arginine phosphorylation which may regulate the favorability of propeptide convertase *** obtained p Arg dataset paves a way for a better understanding of the biological functions of eukaryotic p Arg in the future.

关键词： protein arginine phosphorylation N-phosphorylation proteomics mass spectrometry human cells

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