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GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture

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Nature genetics 2023年第9期55卷 1471-1482页

作者： Remi Stevelink Dorothee Kasteleijn-Nolst Trenite Bobby P. C. Koeleman Dick Lindhout Anja C. M. Sonsma Ciarán Campbell Gianpiero L. Cavalleri Norman Delanty Hany El-Naggar Austin Lacey Peter Widdess-Walsh Colin P. Doherty Siwei Chen Claire Churchhouse Mark J. Daly Yen-Chen A. Feng Daniel P. Howrigan Mitja I. Kurki Benjamin M. Neale Aarno Palotie Wei Zhou Namrata Gupta Henrike O. Heyne Bassel Abou-Khalil Kevin F. Haas R. S. Taneja Oluyomi M. Adesoji Michael Nothnagel Peter Nürnberg Thomas Sander Zaid Afawi Ilan Blatt Amos D. Korczyn Elisabetta Amadori Ganna Balagura Antonella Riva Marcello Scala Paolo Scudieri Pasquale Striano Federico Zara Michele Iacomino Francesca Madia Alison Anderson Patrick Kwan Terence J. O’Brien Slavé Petrovski K. Meng Tan Marian Todaro Joseph Anderson Danielle M. Andrade Quratulain Zulfiqar Ali Grazia Annesi Pauls Auce Andreja Avbersek Simona Balestrini Vera Braatz Claudia B. Catarino Krishna Chinthapalli Jennifer Jamnadas-Khoda Dalia Kasperavičiūte Costin Leu Josemir W. Sander Sanjay M. Sisodiya Sara Zagaglia Melanie Bahlo Karen L. Oliver Mark D. Baker Beata Fonferko-Shadrach William O. Pickrell Carmen Barba Claudia Bianchini Viola Doccini Renzo Guerrini Davide Mei Martino Montomoli Elena Parrini Annalisa Vetro Karen Barboza Fabrice Bartolomei Thomas Bast Bernhard J. Steinhoff Larry Baum Stacey S. Cherny Pak Sham Tobias Baumgartner Christian E. Elger Kerstin Hallmann Wolfram S. Kunz Rainer Surges Randi von Wrede Gábor Zsurka Betül Baykan Nerses Bebek Yeşim Kesim Albert J. Becker Susanne Schoch Felicitas Becker Caitlin A. Bennett Samuel F. Berkovic Stephanie L. Leech Brigid M. Regan Ingrid E. Scheffer Bianca Berghuis Ahmad Beydoun Wassim Nasreddine Francesca Bisulli Lidia Di Vito Lorenzo Ferri Tania Giangregorio Laura Licchetta Raffaella Minardi Barbara Mostacci Carlotta Stipa Paolo Tinuper Lorenzo Muccioli Federica Pondrelli Dheeraj R. Bobbili Emadeldin Hassanin Roland Krause Zied Landoulsi Patrick May Ingo Borggraefe Christian Bosselmann Christian Hengsbach Josua Kegele Stephen Lauxmann Department of Genetics University Medical Center Utrecht Utrecht The Netherlands Stichting Epilepsie Instellingen Nederland (SEIN) Heemstede The Netherlands School of Pharmacy and Biomolecular Sciences The Royal College of Surgeons in Ireland Dublin Ireland The FutureNeuro Research Centre Dublin Ireland Department of Neurology Beaumont Hospital Dublin Ireland Department of Neurology St. James’s Hospital Dublin Ireland Analytic and Translational Genetics Unit Department of Medicine Massachusetts General Hospital and Harvard Medical School Boston MA USA Program in Medical and Population Genetics Broad Institute of MIT and Harvard Cambridge MA USA Stanley Center for Psychiatric Research Broad Institute of Harvard and M.I.T Cambridge MA USA Institute for Molecular Medicine Finland (FIMM) University of Helsinki Helsinki Finland Psychiatric & Neurodevelopmental Genetics Unit Department of Psychiatry Massachusetts General Hospital and Harvard Medical School Boston MA USA Division of Biostatistics Institute of Epidemiology and Preventive Medicine College of Public Health National Taiwan University Taipei Taiwan Hasso Plattner Institute Digital Health Center University of Potsdam Potsdam Germany Hasso Plattner Institute Mount Sinai School of Medicine New York City NY USA Department of Neurology Vanderbilt University Medical Center Nashville TN USA Cologne Center for Genomics (CCG) University of Cologne Faculty of Medicine and University Hospital Cologne Cologne Germany University Hospital Cologne Cologne Germany Department of Neurology Charité Universitaetsmedizin Berlin Campus Virchow-Clinic Berlin Germany Tel-Aviv University Sackler Faculty of Medicine Ramat Aviv Israel Department of Neurology Sheba Medical Center Ramat Gan Israel Department of Neurosciences Rehabilitation Ophthalmology Genetics Maternal and Child Health University of Genova Genova Italy IRCCS Istituto Giannina Gaslini Genova Italy Department of Medicine University of Melbour

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment.

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World Congress Integrative Medicine & health 2017: Part one: Berlin, Germany. 3-5 May 2017

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BMC Complement Altern Med 2017年第SUPPL 1期17卷 322-322页

作者： Benno Brinkhaus Torkel Falkenberg Aviad Haramati Stefan N. Willich Josephine P. Briggs Merlin Willcox Klaus Linde Töres Theorell Lisa M. Wong Jeffrey Dusek Darong Wu David Eisenberg Bettina Berger Kathi Kemper Beate Stock-Schröer Hedda Sützl-Klein Rosaria Ferreri Gary Kaplan Harald Matthes Gabriele Rotter Elad Schiff Zahi Arnon Eckhard Hahn Christina M. Luberto David Martin Silke Schwarz Diethard Tauschel Andrew Flower Harsha Gramminger Hedwig H. Gupta S. N. Gupta Annette Kerckhoff Christian S. Kessler Andreas Michalsen Eun S. Kim Eun H. Jang Rana Kim Sae B. Jan Martin Mittwede Wiebke Mohme Eran Ben-Arye Massimo Bonucci Bashar Saad Thomas Breitkreuz Elio Rossi Rejin Kebudi Michel Daher Samaher Razaq Nahla Gafer Omar Nimri Mohamed Hablas Gunver Sophia Kienle Noah Samuels Michael Silbermann Lena Bandelin Anna-Lena Lang Eva Wartner Christoph Holtermann Maxwell Binstock Robert Riebau Edin Mujkanovic Holger Cramer Romy Lauche Andres Michalsen Lesley Ward Dominik Irnich Wolfram Stör Geoffrey Burnstock Hans-Georg Schaible Thomas Ots Jost Langhorst Tobias Sundberg Catherina Amarell Melanie Anheyer Marion Eckert Mercedes Ogal Annette Schönauer Birgit Reisenberger Bernhard Brand Dennis Anheyer Gustav Dobos Matthias Kroez Aldo Ammendola Jun J. Mao Claudia Witt Yufei Yang Miriam Oritz Markus Horneber Petra Voiß Alexandra von Rosenstiel Catharina Amarell Friedemann Schad Marc Schläppi Matthias Kröz Arndt Büssing Gil Bar-Sela David Avshalomov Samuel Attias Sian Cotton Miek Jong Mats Jong Christian Scheffer Friedrich Edelhäuser Abdullah AlBedah Myeong Soo Lee Mohamed Khalil Keiko Ogawa Yoshiharu Motoo Junsuke Arimitsu Masao Ogawa Genki Shimizu Rainer Stange Karin Kraft Kenny Kuchta Kenji Watanabe D Bonin Harald Gruber Sabine Koch Urs Pohlmann Christine Caldwell Barbara Krantz Ria Kortum Lily Martin Lisa S. Wieland Ben Kligler Susan Gould-Fogerite Yuqing Zhang John J. Riva Michael Lumpkin Emily Ratner Liu Ping Pei Jian Gesa-Meyer Hamme Xiaosong Mao Han Chouping Sven Schröder Josef Hummelsberger Michael Wullinger Marc Brodzky Chr Institute for Social Medicine Epidemiology and Health Economics Charité – Universitätsmedizin Berlin Berlin Germany Department of Neurobiology Care Sciences and Society Division of Nursing Research Group Integrative Care Karolinska Institutet Stockholm Sweden I C – The Integrative Care Science Center Järna Sweden Department of Biochemistry Molecular and Cellular Biology Georgetown University Medical Center Washington DC USA Department of Medicine Georgetown University Medical Center Washington DC USA NCCIH NIH Bethesda MD USA Department of Primary Care and Population Sciences University of Southampton Aldermoor Health Centre Coxford Rd Southampton 2016 5ST UK Institute of General Practice Technical University Munich Munich Germany Department of Neuroscience Karolinska Institute Stockholm Sweden Stress Research Institute Stockholm University Stockholm Sweden Arts and Humanities Initiative Harvard Medical School Boston MA 02115 USA Psychosomatic medicine Neuropsychology Allina Health Minneapolis MN USA nd Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou China Department of Nutrition Harvard University T H Chan School of Public Health Boston MA 02115 USA Department of Health University of Witten/Herdecke Witten/Herdecke Germany OSU Blacklick OH USA Carstens-Foundation and FORUM D-45276 Essen Germany ESIHR (European Society for Integrative Health Care) A-1070 Vienna Austria Hospital Centre of Integrated Medicine Hospital of Pitiglian o ASL SudEst Toscana Grosseto Italy The Kaplan Center for Integrative Medicine Georgetown University McLean VA USA Hospital Havelhöhe Berlin Germany Institute for Social Medicine Epidemiology and Health Economics Charité University Hospital Berlin Germany Internal medicine and Complementary medicine service Bnai Zion Medical Center Haifa Israel Complementary-Integrative Surgery Service Bnai Zion Medical Center Haifa Israel The Emek Yezreel Academic College Yezreel Valley Israel Medicine

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Author Correction: Towards symbiotic approaches between universities, sustainable development, and cities

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Scientific reports 2023年第1期13卷 552页

作者： Walter Leal Filho Liliana Caughman Maria Alzira Pimenta Dinis Fernanda Frankenberger Anabela Marisa Azul Amanda Lange Salvia Department of Natural Sciences Manchester Metropolitan University Chester Street Manchester M115GD UK. Research and Transfer Centre "Sustainable Development and Climate Change Management" Hamburg University of Applied Sciences Ulmenliet 20 21033 Hamburg Germany. Postdoctoral Research Scholar Earth Systems Science for the Anthropocene Arizona State University Tempe USA. UFP Energy Environment and Health Research Unit (FP-ENAS) University Fernando Pessoa (UFP) Praça 9 de Abril 349 4249-004 Porto Portugal. Business School PUCPR Pontifical Catholic University of Paraná Rua Imaculada Conceição Curitiba 1155 Brazil. Brazil Business School Universidade Positivo Rua Pedro Viriato Parigot de Souza Curitiba 5300 Brazil. CNC-Center for Neuroscience and Cell Biology University of Coimbra 3004-504 Coimbra Portugal. CIBB-Center for Innovative Biomedicine and Biotechnology University of Coimbra Coimbra Portugal. IIIUC-Institute for Interdisciplinary Research University of Coimbra 3030-789 Coimbra Portugal. Graduate Program in Civil and Environmental Engineering University of Passo Fundo Campus I - BR285 São José Passo Fundo RS 99052-900 Brazil. amandasalvia@***. European School of Sustainability Science and Research Hamburg University of Applied Sciences Ulmenliet 20 21033 Hamburg Germany. amandasalvia@***.

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Fungal diversity notes 253-366:taxonomic and phylogenetic contributions to fungal taxa

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Fungal Diversity 2016年第3期78卷 1-237页

作者： Guo Jie Li Kevin D.Hyde Rui Lin Zhao Sinang Hongsanan Faten Awad Abdel-Aziz Mohamed A.Abdel-Wahab Pablo Alvarado Genivaldo Alves-Silva Joseph F.Ammirati Hiran A.Ariyawansa Abhishek Baghela Ali Hassan Bahkali Michael Beug D.Jayarama Bhat Dimitar Bojantchev Thitiya Boonpratuang Timur S.Bulgakov Erio Camporesi Marcela CBoro Oldriska Ceska Dyutiparna Chakraborty Jia Jia Chen K.W.Thilini Chethana Putarak Chomnunti Giovanni Consiglio Bao Kai Cui Dong Qin Dai Yu Cheng Dai Dinushani A.Daranagama Kanad Das Monika C.Dayarathne Eske De Crop Rafael J.V.De Oliveira Carlos Alberto Fragoso de Souza JoséIde Souza Bryn T.M.Dentinger Asha J.Dissanayake Mingkwan Doilom E.Ricardo Drechsler-Santos Masoomeh Ghobad-Nejhad Sean P.Gilmore Aristóteles Góes-Neto MichałGorczak Charles H.Haitjema Kalani Kanchana Hapuarachchi Akira Hashimoto Mao Qiang He John K.Henske Kazuyuki Hirayama Maria J.Iribarren Subashini C.Jayasiri Ruvishika S.Jayawardena Sun Jeong Jeon Gustavo H.Jerônimo Ana L.Jesus E.B.Gareth Jones Ji Chuan Kang Samantha C.Karunarathna Paul M.Kirk Sirinapa Konta Eric Kuhnert Ewald Langer Haeng Sub Lee Hyang Burm Lee Wen Jing Li Xing Hong Li Kare Liimatainen Diogo Xavier Lima Chuan Gen Lin Jian Kui Liu Xings Zhong Liu Zuo Yi Liu J.Jennifer Luangsa-ard Robert Lücking H.Thorsten Lumbsch Saisamorn Lumyong Eduardo M.Leaño Agostina V.Marano Misato Matsumura Eric H.C.McKenzie Suchada Mongkolsamrit Peter E.Mortimer Thi Thuong Thuong Nguyen Tuula Niskanen Chada Norphanphoun Michelle A.O’Malley Sittiporn Parnmen Julia Pawłowska Rekhani H.Perera Rungtiwa Phookamsak Chayanard Phukhamsakda Carmen L.A.Pires-Zottarelli Olivier Raspé Mateus A.Reck Sarah C.O.Rocha AndréL.C.M.Ade Santiago Indunil C.Senanayake Ledo Setti Qiu Ju Shang Sanjay K.Singh Esteban B.Sir Kevin V.Solomon Jie Song Prasert Srikitikulchai Marc Stadler Satinee Suetrong Hayato Takahashi Takumasa Takahashi Kazuaki Tanaka Li Ping Tang Kasun M.Thambugala Donnaya Thanakitpipattana Michael K.Theodorou Benjarong Thongbai Tuksaporn Thummarukcharoen Qing Tian Saowaluck Tibpromma Annemieke State Key Laboratory of Mycology Institute of MicrobiologyChinese Academy of SciencesNo 31st West Beichen RoadChaoyang DistrictBeijing 100101People’s Republic of China Centre of Excellence in Fungal Research and School of Science Mae Fah Luang UniversityChiang Rai 57100Thailand Key Laboratory for Plant Diversity and Biogeography of East Asia Kunming Institute of BotanyChinese Academy of ScienceKunming 650201YunnanPeople’s Republic of China Department of Botany and Microbiology College of ScienceKing Saud UniversityP.O.Box:2455Riyadh 1145Saudi Arabia Department of Botany and Microbiology Faculty of ScienceSohag UniversitySohag 82524Egypt ALVALAB C/La Rochela nº47E-39012 SantanderSpain Micolab Programa de Pós-Graduação em Biologia de FungosAlgas e PlantasDepartamento de BotânicaUniversidade Federal de Santa CatarinaCampus Universitário TrindadeCEP:88040-900 FlorianópolisSanta CatarinaBrazil Department of Biology University of WashingtonBox 351800SeattleWA 98195-1800USA Guizhou Key Laboratory of Agricultural Biotechnology Guizhou Academy of Agricultural SciencesGuiyang 550006GuizhouPeople’s Republic of China National Fungal Culture Collection of India(NFCCI) Biodiversity and Palaeobiology GroupMACS’Agharkar Research InstituteG.G.Agarkar RoadPune 411004India PO Box 116 HusumWA 98623-0116USA Formerly Department of BotanyGoa UniversityGoaIndia No.128/1-J Azad Housing SocietyCurcaP.O.Goa Velha 403108India *** 345 Shipwatch LaneHerculesCA 94547USA Microbe Interaction Laboratory(BMIT) BIOTECNational Science and Technology Development Agency(NSTDA)113 Thailand Science ParkThanon PhahonyothinTombon Khlong NuengAmphoeKhlong LuangPathum Thani 12120Thailand Academy of Biology and Biotechnology Southern Federal UniversityRostov-on-Don 344090Rostov regionRussia A.M.B.Gruppo Micologico Forlivese BAntonio“Cicognani” Via Roma Forlì Italy 18 A.M.B.Circolo Micologico“Giovanni Carini”C.P.314BresciaItaly Societàper gli Studi Naturalistici della Romagna C.P.144Bagnacavallo

Notes on 113 fungal taxa are compiled in this paper,including 11 new genera,89 new species,one new subspecies,three new combinations and seven reference *** geographic and taxonomic range of fungal taxa are *** the Ascomycota the new genera Angustospora(Testudinaceae),Camporesia(Xylariaceae),Clematidis,Crassiparies(Pleosporales genera incertae sedis),Farasanispora,Longiostiolum(Pleosporales genera incertae sedis),Multilocularia(Parabambusicolaceae),Neophaeocryptopus(Dothideaceae),Parameliola(Pleosporales genera incertae sedis),and Towyspora(Lentitheciaceae)are *** introduced species are Angustospora nilensis,Aniptodera aquibella,Annulohypoxylon albidiscum,Astrocystis thailandica,Camporesia sambuci,Clematidis italica,Colletotrichum menispermi,***,Comoclathris pimpinellae,Crassiparies quadrisporus,Cytospora salicicola,Diatrype thailandica,Dothiorella rhamni,Durotheca macrostroma,Farasanispora avicenniae,Halorosellinia rhizophorae,Humicola koreana,Hypoxylon lilloi,Kirschsteiniothelia tectonae,Lindgomyces okinawaensis,Longiostiolum tectonae,Lophiostoma pseudoarmatisporum,Moelleriella phukhiaoensis,***,Mucoharknessia anthoxanthi,Multilocularia bambusae,Multiseptospora thysanolaenae,Neophaeocryptopus cytisi,Ocellularia arachchigei,***,Ochronectria thailandica,Ophiocordyceps karstii,Parameliola acaciae,***,Parastagonospora cumpignensis,Pseudodidymosphaeria phlei,Polyplosphaeria thailandica,Pseudolachnella brevifusiformis,Psiloglonium macrosporum,Rhabdodiscus albodenticulatus,Rosellinia chiangmaiensis,Saccothecium rubi,Seimatosporium pseudocornii,***,Sigarispora ononidis and Towyspora *** combinations are provided for Eutiarosporella dactylidis(sexual morph described and illus trated)and Pseudocamarosporium ***,illustrations and/or reference specimens are designated for Aposphaeria corallinolutea,Cryptovalsa ampelina,Dothiorella vidmadera,Ophiocordyceps formosana,P

关键词： Ascomycota Basidiomycota Neocallimastigomycota Oomycota.Zygomycota Phylogeny Taxonomy New genus New species

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Abstracts from the Food Allergy and Anaphylaxis Meeting 2016 Abstracts

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CLINICAL AND TRANSLATIONAL ALLERGY 2017年第SUPPL 1期7卷 10-10页

作者： [Anonymous] Department of Pediatrics Children’s Hospital Roubaix France Division of Pulmonology and Allergology Department of Pediatrics Faculty of Medicine and Children’s Hospital Lille France Allergy Vigilance Network Vandoeuvre les Nancy France Université Lille 2 CHU Lille EA 2694 - Santé Publique: épidémiologie et qualité des soins Lille France Biostatistics Unit Maison Régionale de la Recherche Clinique CHRU Lille Lille France Department of Allergology Emile Durkheim Hospital Epinal France Centre d’Epidémiologie sur les Causes Médicales de Décès INSERM CHU de Bicêtre Le Kremlin-Bicêtre France The Allergy Vigilance Network University Hospital Nancy Nancy France Pediatric Pulmonology and Allergy Department Hôpital Jeanne de Flandre CHU Lille Lille France Charité - Universitätsmedizin Berlin Berlin Germany Institute for Social Medicine Epidemiology and Health Economics Charité - Universitätsmedizin Berlin Berlin Germany Institute of Social Medicine Epidemiology and Health Economics Charité Universitätsmedizin Berlin Berlin Germany Department of Dermatology and Allergology Comprehensive Allergy Center Charité Charité – Universitätsmedizin Berlin Berlin Germany Department of Dermatology and Allergy Allergie-Centrum-Charité Charité-Universiätsmedizin Berlin Berlin Germany Department of Dermatology and Allergology Comprehensive Allergy Center Charité Charité Universitätsmedizin Berlin Berlin Germany University Hospital Basel Basel Switzerland Allergy Unit Department of Dermatology University Hospital Basel Switzerland Universitätsklinikum Salzburg Salzburg Austria Department of Dermatology and Allergy Centre Odense Research Center for Anaphylaxis (ORCA) Odense University Hospital Odense Denmark Odense University Hospital Odense Denmark Serviço de ImunoalergologiaCentro Hospitalar de São João E.P.E. Porto Portugal GRIAC Research Institute University of Groningen University Medical Center Groningen Groningen The Netherlands Serviço de Imunoalergologia Centr

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Abstracts from the 1st JoPPP Conference on Pharmaceutical Policy and Practice Abstracts

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JOURNAL OF PHARMACEUTICAL POLICY AND PRACTICE 2020年第1期13卷 3-3页

作者： [Anonymous] Macter International Limited F-216 S.I.T.E Karachi Pakistan Department of Pharmaceutics Faculty of Pharmacy & Pharmaceutical Sciences University of Karachi Karachi Pakistan Research & Education Centre for Evidence-Based Medicine Cochrane Russia Kazan Federal University Kazan Republic of Tatarstan Russian Federation School of Pharmacy Mongolian National University of Medical Sciences S. Zorig Street Ulaanbaatar 14210 Mongolia Mongolian University of Pharmaceutical Sciences Sonsgolon Road-5 Songinokhairkhan District Ulaanbaatar 18130 Mongolia Drug Research Institute Monos group Sonsgolon Road-5 Songinokhairkhan District Ulaanbaatar 18130 Mongolia Faculty of Health Sciences Curtin University Kent Street Bentley Perth Western Australia 6102 Australia School of Public Health Mongolian National University of Medical Sciences S. Zorig Street Ulaanbaatar 14210 Mongolia Departemen Farmasetika Faculty of Pharmacy Universitas Gadjah Mada Yogyakarta Indonesia School of Pharmacy Taylor’s University Subang Selangor Malaysia Faculty of Pharmacy Universiti Technologi MARA Shah Alam Malaysia Department of Pharmacy Practice School of Pharmacy International Medical University 57000 Kuala Lumpur Malaysia Faculty of Pharmacy Universiti Kebangsaan Malaysia 50300 Kuala Lumpur Malaysia Faculty of Health and Medical Sciences Taylor’s University 47500 Subang Jaya Malaysia Faculty of Pharmacy Cyberjaya University College of Medical Sciences 63000 Cyberjaya Selangor Malaysia Faculty of Pharmacy Level 11 FF1 Building UiTM Puncak Alam Campus . Selangor Malaysia Bandar Pasir Mas Health Clinic Jalan Hospital Pasir Mas Kelantan Malaysia School of Pharmacy Monash University Malaysia Bandar Sunway Selangor Malaysia Asian Centre for Evidence Synthesis in Population Implementation and Clinical Outcomes Health and Well-Being Cluster Global Asia in the 21st Century Platform Monash University Malaysia Bandar Sunway Selangor Malaysia School of Pharmaceutical Sciences Universiti Sains

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Ovatodiolide and antrocin synergistically inhibit the stemness and metastatic potential of hepatocellular carcinoma via impairing ribosome biogenesis and modulating ERK/Akt-mTOR signaling axis

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Phytomedicine : international journal of phytotherapy and phytopharmacology 2023年 108卷 154478页

作者： Ming-Yao Chen Chia-Hung Hsu Syahru Agung Setiawan David T W Tzeng Hon-Ping Ma Jiann Ruey Ong Yi Cheng Chu Ming-Shou Hsieh Alexander T H Wu Yew-Min Tzeng Chi-Tai Yeh Division of Gastroenterology and Hepatology Department of Internal Medicine School of Medicine College of Medicine Taipei Medical University Taipei City 110 Taiwan Division of Gastroenterology and Hepatology Department of Internal Medicine Taipei Medical University-Shuang Ho Hospital New Taipei City 235 Taiwan. Department of Emergency Medicine Taipei Medical University-Shuang Ho Hospital New Taipei City 235 Taiwan Graduate Institute of Injury Prevention and Control College of Public Health Taipei Medical University Taipei City 110 Taiwan Department of Emergency Medicine School of Medicine Taipei Medical University Taipei City 110 Taiwan. International Ph.D. Program in Medicine College of Medicine Taipei Medical University Taipei City 110 Taiwan Department of Medical Research & Education Taipei Medical University - Shuang-Ho Hospital New Taipei City 235 Taiwan. School of Life Sciences The Chinese University of Hong Kong Hong Kong SAR 999077 China Lifebit Mindspace Shoreditch London England EC2A 2AP UK. Department of Medicine St. George's University School of Medicine St. George Grenada. Department of Applied Science National Taitung University Taitung 95092 Taiwan. Electronic address: ymtzeng@nttu.edu.tw. Department of Medical Research & Education Taipei Medical University - Shuang-Ho Hospital New Taipei City 235 Taiwan Continuing Education Program of Food Biotechnology Applications College of Science and Engineering National Taitung University Taitung 95092 Taiwan. Electronic address: ctyeh@s.tmu.edu.tw.

Activation of mitogen-activated protein kinase (MAPK) and PI3K signaling confers resistance against sorafenib, a mainstay treatment for advanced hepatocellular carcinoma (HCC). Antrocin and ovatodiolide constitute as the most potent secondary metabolites isolated from Antrodia camphorata and Anisomeles indica, respectively. Both natural compounds have recently gained a lot of attention due to their putative inhibition of MAPK and PI3K signaling in various solid cancers. However, whether their combination is effective in HCC remains unknown. Here, we investigated their effect, alone or in various combinations, on MAPK and PI3K signaling pathways in HCC cells. An array of in vitro study were used to investigate anticancer and stemness effects to treat HCC, such as cytotoxicity, drug combination index, migration, invasion, colony formation, and tumor sphere formation. Drug effect in vivo was evaluated using mouse xenograft models. In this study, antrocin and ovatodiolide synergistically inhibited the SNU387, Hep3B, Mahlavu, and Huh7 cell lines. Sequential combination treatment of Huh7 and Mahlavu with ovatodiolide followed by antrocin resulted stronger cytotoxic effect than did treatment with antrocin followed by ovatodiolide, their simultaneous administration, antrocin alone, or ovatodiolide alone. In the Huh7 and Mahlavu cell lines, ovatodiolide→antrocin significantly suppressed colony formation and proliferation as well as markedly downregulated ERK1/2, Akt, and mTOR expression. Inhibition of ERK1/2 and Akt/mTOR signaling by ovatodiolide→antrocin suppressed ribosomal biogenesis, autophagy, and cancer stem cell-like phenotypes and promoted apoptosis in Huh7 and Mahlavu cells. The sorafenib-resistant clone of Huh7 was effectively inhibited by synergistic combination of both compound in vitro. Eventually, the ovatodiolide→antrocin combination synergistically suppressed the growth of HCC xenografts. Taken together, our findings suggested that ovatodiolide→antrocin combi

关键词： Advanced HCC Antrocin (ANC) MAPK Ovatodiolide (OVA) PI3K

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The repertoire of mutational signatures in human cancer (vol 578, pg 94, 2020)

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NATURE 2023年第7948期614卷 E41-E41页

作者： Alexandrov, Ludmil B. Kim, Jaegil Haradhvala, Nicholas J. Huang, Mi Ni Ng, Alvin Wei Tian Wu, Yang Boot, Arnoud Covington, Kyle R. Gordenin, Dmitry A. Bergstrom, Erik N. Islam, S. M. Ashiqul Lopez-Bigas, Nuria Klimczak, Leszek J. McPherson, John R. Morganella, Sandro Sabarinathan, Radhakrishnan Wheeler, David A. Mustonen, Ville Getz, Gad Rozen, Steven G. Stratton, Michael R. Department of Cellular and Molecular Medicine Department of Bioengineering Moores Cancer Center University of California San Diego CA USA Wellcome Sanger Institute Wellcome Genome Campus Hinxton UK Department of Cellular and Molecular Medicine and Department of Bioengineering University of California San Diego La Jolla CA USA UC San Diego Moores Cancer Center San Diego CA USA University of California San Diego San Diego CA USA Broad Institute of MIT and Harvard Cambridge MA USA Center for Cancer Research Massachusetts General Hospital Boston MA USA Massachusetts General Hospital Boston MA USA Department of Pathology Massachusetts General Hospital Boston MA USA Harvard Medical School Boston MA USA Laboratory for Medical Science Mathematics RIKEN Center for Integrative Medical Sciences Yokohama Japan Computational Biology Program Ontario Institute for Cancer Research Toronto ON Canada Programme in Cancer & Stem Cell Biology Duke-NUS Medical School Singapore Singapore Centre for Computational Biology Duke-NUS Medical School Singapore Singapore Programme in Cancer and Stem Cell Biology Duke-NUS Medical School Singapore Singapore Programme in Cancer and Stem Cell Biology Centre for Computational Biology Duke-NUS Medical School Singapore Singapore SingHealth Duke-NUS Institute of Precision Medicine National Heart Centre Singapore Singapore Singapore Cancer Science Institute of Singapore National University of Singapore Singapore Singapore Institute of Molecular and Cell Biology Singapore Singapore Laboratory of Cancer Epigenome Division of Medical Science National Cancer Centre Singapore Singapore Singapore Duke-NUS Medical School Singapore Singapore Human Genome Sequencing Center Baylor College of Medicine Houston TX USA Dan L. Duncan Cancer Center Baylor College of Medicine Houston TX USA Department of Molecular and Human Genetics Baylor College of Medicine Houston TX USA Genome Integrity and Structural Biology Laboratory National Ins

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The evolutionary history of 2,658 cancers (vol 578, pg 122, 2020)

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NATURE 2023年第7948期614卷 E42-E42页

作者： Gerstung, Moritz Jolly, Clemency Leshchiner, Ignaty Dentro, Stefan C. Gonzalez, Santiago Rosebrock, Daniel Mitchell, Thomas J. Rubanova, Yulia Anur, Pavana Yu, Kaixian Tarabichi, Maxime Deshwar, Amit Wintersinger, Jeff Kleinheinz, Kortine Vazquez-Garcia, Ignacio Haase, Kerstin Jerman, Lara Sengupta, Subhajit Macintyre, Geoff Malikic, Salem Donmez, Nilgun Livitz, Dimitri G. Cmero, Marek Demeulemeester, Jonas Schumacher, Steven Fan, Yu Yao, Xiaotong Lee, Juhee Schlesner, Matthias Boutros, Paul C. Bowtell, David D. Zhu, Hongtu Getz, Gad Imielinski, Marcin Beroukhim, Rameen Sahinalp, S. Cenk Ji, Yuan Peifer, Martin Markowetz, Florian Mustonen, Ville Yuan, Ke Wang, Wenyi Morris, Quaid D. Spellman, Paul T. Wedge, David C. Van Loo, Peter European Molecular Biology Laboratory European Bioinformatics Institute (EMBL-EBI) Cambridge UK European Molecular Biology Laboratory Genome Biology Unit Heidelberg Germany Wellcome Sanger Institute Cambridge UK Genome Biology Unit European Molecular Biology Laboratory (EMBL) Heidelberg Germany University of Ljubljana Ljubljana Slovenia The Francis Crick Institute London UK Big Data Institute University of Oxford Oxford UK Wellcome Sanger Institute Wellcome Genome Campus Hinxton UK Big Data Institute Li Ka Shing Centre University of Oxford Oxford UK University of Cambridge Cambridge UK Cambridge University Hospitals NHS Foundation Trust Cambridge UK Department of Applied Mathematics and Theoretical Physics Centre for Mathematical Sciences University of Cambridge Cambridge UK Department of Epidemiology and Biostatistics Memorial Sloan Kettering Cancer Center New York NY USA Department of Statistics Columbia University New York NY USA Department of Haematology University of Cambridge Cambridge UK University of Leuven Leuven Belgium Broad Institute of MIT and Harvard Cambridge MA USA Center for Cancer Research Massachusetts General Hospital Charlestown MA USA Department of Pathology Massachusetts General Hospital Boston MA USA Harvard Medical School Boston MA USA Center for Cancer Research Massachusetts General Hospital Boston MA USA Dana-Farber Cancer Institute Boston MA USA Department of Medical Oncology Dana-Farber Cancer Institute Boston MA USA Department of Cancer Biology Dana-Farber Cancer Institute Boston MA USA Oxford NIHR Biomedical Research Centre Oxford UK Oxford NIHR Biomedical Research Centre University of Oxford Oxford UK University of Toronto Toronto Ontario Canada Vector Institute Toronto Ontario Canada Vector Institute Toronto ON Canada Department of Computer Science University of Toronto Toronto ON Canada Ontario Institute for Cancer Research Toronto Ontario Canada University of California Los Angeles

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Genomic basis for RNA alterations in cancer (vol 578, pg 129, 2020)

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NATURE 2023年第7948期614卷 E37-E37页

作者： Calabrese, Claudia Davidson, Natalie R. Demircioglu, Deniz Fonseca, Nuno A. He, Yao Lehmann, Kjong-Van Liu, Fenglin Shiraishi, Yuichi Soulette, Cameron M. Urban, Lara Greger, Liliana Li, Siliang Liu, Dongbing Perry, Marc D. Xiang, Qian Zhang, Fan Zhang, Junjun Bailey, Peter Erkek, Serap Hoadley, Katherine A. Hou, Yong Huska, Matthew R. Kilpinen, Helena Korbel, Jan O. Marin, Maximillian G. Markowski, Julia Nandi, Tannistha Pan-Hammarstrom, Qiang Pedamallu, Chandra Sekhar Siebert, Reiner Stark, Stefan G. Su, Hong Tan, Patrick Waszak, Sebastian M. Yung, Christina Zhu, Shida Awadalla, Philip Creighton, Chad J. Meyerson, Matthew Ouellette, B. F. Francis Wu, Kui Yang, Huanming Brazma, Alvis Brooks, Angela N. Goke, Jonathan Ratsch, Gunnar Schwarz, Roland F. Stegle, Oliver Zhang, Zemin European Molecular Biology Laboratory European Bioinformatics Institute Hinxton UK European Molecular Biology Laboratory European Bioinformatics Institute (EMBL-EBI) Cambridge UK Genome Biology Unit European Molecular Biology Laboratory (EMBL) Heidelberg Germany CIBIO/InBIO - Research Center in Biodiversity and Genetic Resources Universidade do Porto Vairão Portugal Berlin Institute for Medical Systems Biology Max Delbruck Center for Molecular Medicine Berlin Germany German Cancer Consortium (DKTK) partner site Berlin Germany German Cancer Research Center (DKFZ) Heidelberg Germany Berlin Institute for Medical Systems Biology Max Delbrück Center for Molecular Medicine Berlin Germany German Cancer Consortium (DKTK) Partner site Berlin Berlin Germany European Molecular Biology Laboratory Genome Biology Unit Heidelberg Germany Division of Computational Genomics and Systems Genetics German Cancer Research Center (DKFZ) Heidelberg Germany ETH Zurich Zurich Switzerland Memorial Sloan Kettering Cancer Center New York NY USA Weill Cornell Medical College New York NY USA SIB Swiss Institute of Bioinformatics Lausanne Switzerland University Hospital Zurich Zurich Switzerland Computational Biology Center Memorial Sloan Kettering Cancer Center New York NY USA Department of Biology ETH Zurich Zürich Switzerland Department of Computer Science ETH Zurich Zurich Switzerland Korea University Seoul South Korea Computational and Systems Biology Program Memorial Sloan Kettering Cancer Center New York NY USA Department of Physiology and Biophysics Weill Cornell Medicine New York NY USA Institute for Computational Biomedicine Weill Cornell Medicine New York NY USA Controlled Department and Institution New York NY USA Englander Institute for Precision Medicine Weill Cornell Medicine New York NY USA National University of Singapore Singapore Singapore Genome Institute of Singapore Singapore Singapore Computational and Systems Biology Genome Institute of Singap

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