{"id":"https://openalex.org/W3207003382","doi":"https://doi.org/10.21037/atm-21-4764","title":"Metformin alleviates bevacizumab-induced vascular endothelial injury by up-regulating GDF15 and activating the PI3K/AKT/FOXO/ PPAR\u03b3 signaling pathway","display_name":"Metformin alleviates bevacizumab-induced vascular endothelial injury by up-regulating GDF15 and activating the PI3K/AKT/FOXO/ PPAR\u03b3 signaling pathway","publication_year":2021,"publication_date":"2021-10-01","ids":{"openalex":"https://openalex.org/W3207003382","doi":"https://doi.org/10.21037/atm-21-4764","mag":"3207003382","pmid":"https://pubmed.ncbi.nlm.nih.gov/34790753","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/8576656"},"language":"en","primary_location":{"id":"doi:10.21037/atm-21-4764","doi":"https://doi.org/10.21037/atm-21-4764","is_oa":true,"landing_page_url":"https://doi.org/10.21037/atm-21-4764","pdf_url":"https://atm.amegroups.com/article/viewFile/81224/pdf","source":{"id":"https://openalex.org/S2755174949","display_name":"Annals of Translational Medicine","issn_l":"2305-5839","issn":["2305-5839","2305-5847"],"is_oa":true,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","poland-20","vabb-shw"],"host_organization":"https://openalex.org/P4310321814","host_organization_name":"AME Publishing Company","host_organization_lineage":["https://openalex.org/P4310321814"],"host_organization_lineage_names":["AME Publishing Company"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Annals of Translational Medicine","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"diamond","oa_url":"https://atm.amegroups.com/article/viewFile/81224/pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":null,"display_name":"Liqiang Chen","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210106405","display_name":"Fourth Hospital of Hebei Medical University","ror":"https://ror.org/01mdjbm03","country_code":"CN","type":"healthcare","lineage":["https://openalex.org/I4210106405"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Liqiang Chen","raw_affiliation_strings":["Cardiovascular Department, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cardiovascular Department, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China","institution_ids":["https://openalex.org/I4210106405"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5110368029","display_name":"Yajuan Yin","orcid":"https://orcid.org/0000-0002-4629-074X","observed_orcids":["https://orcid.org/0000-0002-4629-074X"]},"institutions":[{"id":"https://openalex.org/I111381250","display_name":"Hebei Medical University","ror":"https://ror.org/04eymdx19","country_code":"CN","type":"education","lineage":["https://openalex.org/I111381250"]},{"id":"https://openalex.org/I4210157729","display_name":"First Affiliated Hospital of Hebei Medical University","ror":"https://ror.org/04z3aby64","country_code":"CN","type":"healthcare","lineage":["https://openalex.org/I4210157729"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Yajuan Yin","raw_affiliation_strings":["Cardiovascular Department, The First Hospital of Hebei Medical University, Shijiazhuang, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cardiovascular Department, The First Hospital of Hebei Medical University, Shijiazhuang, China","institution_ids":["https://openalex.org/I111381250","https://openalex.org/I4210157729"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5019079091","display_name":"Gang Liu","orcid":"https://orcid.org/0000-0002-1430-3016","observed_orcids":["https://orcid.org/0000-0002-1430-3016"]},"institutions":[{"id":"https://openalex.org/I111381250","display_name":"Hebei Medical University","ror":"https://ror.org/04eymdx19","country_code":"CN","type":"education","lineage":["https://openalex.org/I111381250"]},{"id":"https://openalex.org/I4210157729","display_name":"First Affiliated Hospital of Hebei Medical University","ror":"https://ror.org/04z3aby64","country_code":"CN","type":"healthcare","lineage":["https://openalex.org/I4210157729"]}],"countries":["CN"],"is_corresponding":true,"raw_author_name":"Gang Liu","raw_affiliation_strings":["Cardiovascular Department, The First Hospital of Hebei Medical University, Shijiazhuang, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cardiovascular Department, The First Hospital of Hebei Medical University, Shijiazhuang, China","institution_ids":["https://openalex.org/I111381250","https://openalex.org/I4210157729"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":3,"corresponding_author_ids":["https://openalex.org/A5019079091"],"corresponding_institution_ids":["https://openalex.org/I111381250","https://openalex.org/I4210157729"],"apc_list":null,"apc_paid":null,"fwci":0.6279,"has_fulltext":true,"cited_by_count":19,"citation_normalized_percentile":{"value":0.62653891,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":93,"max":99},"biblio":{"volume":"9","issue":"20","first_page":"1547","last_page":"1547"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10422","display_name":"Angiogenesis and VEGF in Cancer","score":0.5449000000953674,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10422","display_name":"Angiogenesis and VEGF in Cancer","score":0.5449000000953674,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11339","display_name":"Metabolism, Diabetes, and Cancer","score":0.23510000109672546,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T13452","display_name":"GDF15 and Related Biomarkers","score":0.009499999694526196,"subfield":{"id":"https://openalex.org/subfields/2745","display_name":"Rheumatology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/metformin","display_name":"metformin","score":1.0},{"id":"https://openalex.org/keywords/bevacizumab","display_name":"bevacizumab","score":0.9980000257492065},{"id":"https://openalex.org/keywords/endothelial-injury","display_name":"endothelial injury","score":0.9539999961853027},{"id":"https://openalex.org/keywords/growth-differentiation-factor-15","display_name":"growth differentiation factor 15","score":0.9580000042915344},{"id":"https://openalex.org/keywords/pi3k-akt-signaling","display_name":"PI3K/Akt signaling","score":0.8619999885559082},{"id":"https://openalex.org/keywords/foxo","display_name":"FOXO","score":0.9580000042915344},{"id":"https://openalex.org/keywords/ppargamma","display_name":"PPAR\u03b3","score":0.9919999837875366},{"id":"https://openalex.org/keywords/endothelial-cell-apoptosis","display_name":"endothelial cell apoptosis","score":0.8029999732971191},{"id":"https://openalex.org/keywords/inflammation","display_name":"inflammation","score":0.7369999885559082},{"id":"https://openalex.org/keywords/human-umbilical-vein-endothelial-cells","display_name":"human umbilical vein endothelial cells","score":0.9390000104904175}],"concepts":[{"id":"https://openalex.org/C2780323712","wikidata":"https://www.wikidata.org/wiki/Q19484","display_name":"Metformin","level":3,"score":0.9060492515563965},{"id":"https://openalex.org/C86554907","wikidata":"https://www.wikidata.org/wiki/Q285613","display_name":"PI3K/AKT/mTOR pathway","level":3,"score":0.7080501317977905},{"id":"https://openalex.org/C2777802072","wikidata":"https://www.wikidata.org/wiki/Q413299","display_name":"Bevacizumab","level":3,"score":0.6685730218887329},{"id":"https://openalex.org/C75217442","wikidata":"https://www.wikidata.org/wiki/Q423650","display_name":"Protein kinase B","level":3,"score":0.5408182144165039},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.5359066128730774},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.4978628158569336},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.47786515951156616},{"id":"https://openalex.org/C2777025900","wikidata":"https://www.wikidata.org/wiki/Q29725","display_name":"Vascular endothelial growth factor","level":3,"score":0.46970173716545105},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.4425343871116638},{"id":"https://openalex.org/C190283241","wikidata":"https://www.wikidata.org/wiki/Q14599311","display_name":"Apoptosis","level":2,"score":0.43972527980804443},{"id":"https://openalex.org/C134018914","wikidata":"https://www.wikidata.org/wiki/Q162606","display_name":"Endocrinology","level":1,"score":0.26016032695770264},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.2568764090538025},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.22426441311836243},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.2136654555797577},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.21013623476028442},{"id":"https://openalex.org/C555293320","wikidata":"https://www.wikidata.org/wiki/Q12206","display_name":"Diabetes mellitus","level":2,"score":0.10438251495361328},{"id":"https://openalex.org/C2776694085","wikidata":"https://www.wikidata.org/wiki/Q974135","display_name":"Chemotherapy","level":2,"score":0.0773308277130127},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.06390118598937988},{"id":"https://openalex.org/C167734588","wikidata":"https://www.wikidata.org/wiki/Q4356503","display_name":"VEGF receptors","level":2,"score":0.0}],"mesh":[],"locations_count":3,"locations":[{"id":"doi:10.21037/atm-21-4764","doi":"https://doi.org/10.21037/atm-21-4764","is_oa":true,"landing_page_url":"https://doi.org/10.21037/atm-21-4764","pdf_url":"https://atm.amegroups.com/article/viewFile/81224/pdf","source":{"id":"https://openalex.org/S2755174949","display_name":"Annals of Translational Medicine","issn_l":"2305-5839","issn":["2305-5839","2305-5847"],"is_oa":true,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","poland-20","vabb-shw"],"host_organization":"https://openalex.org/P4310321814","host_organization_name":"AME Publishing Company","host_organization_lineage":["https://openalex.org/P4310321814"],"host_organization_lineage_names":["AME Publishing Company"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Annals of Translational Medicine","raw_type":"journal-article"},{"id":"pmh:oai:pubmedcentral.nih.gov:8576656","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8576656","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Ann Transl Med","raw_type":"Text"},{"id":"pmid:34790753","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/34790753","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Annals of translational medicine","raw_type":"Journal Article"}],"best_oa_location":{"id":"doi:10.21037/atm-21-4764","doi":"https://doi.org/10.21037/atm-21-4764","is_oa":true,"landing_page_url":"https://doi.org/10.21037/atm-21-4764","pdf_url":"https://atm.amegroups.com/article/viewFile/81224/pdf","source":{"id":"https://openalex.org/S2755174949","display_name":"Annals of Translational Medicine","issn_l":"2305-5839","issn":["2305-5839","2305-5847"],"is_oa":true,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","poland-20","vabb-shw"],"host_organization":"https://openalex.org/P4310321814","host_organization_name":"AME Publishing Company","host_organization_lineage":["https://openalex.org/P4310321814"],"host_organization_lineage_names":["AME Publishing Company"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Annals of Translational Medicine","raw_type":"journal-article"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":1.0}],"sustainable_development_goals_aurora":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.8500000238418579}],"study_designs":[],"awards":[{"id":"https://openalex.org/G373013367","display_name":null,"funder_award_id":"H2019206715","funder_id":"https://openalex.org/F4320322163","funder_display_name":"Natural Science Foundation of Hebei Province"}],"funders":[{"id":"https://openalex.org/F4320308085","display_name":"Massachusetts Department of Agricultural Resources","ror":"https://ror.org/03wjj7779"},{"id":"https://openalex.org/F4320322163","display_name":"Natural Science Foundation of Hebei Province","ror":"https://ror.org/01h0zpd94"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W3207003382.pdf","grobid_xml":"https://content.openalex.org/works/W3207003382.grobid-xml"},"referenced_works_count":42,"referenced_works":["https://openalex.org/W1588051322","https://openalex.org/W1897292152","https://openalex.org/W1974882515","https://openalex.org/W2000475291","https://openalex.org/W2017558215","https://openalex.org/W2116712778","https://openalex.org/W2287378844","https://openalex.org/W2290846307","https://openalex.org/W2342654843","https://openalex.org/W2343577193","https://openalex.org/W2550249228","https://openalex.org/W2605456582","https://openalex.org/W2742133220","https://openalex.org/W2765760802","https://openalex.org/W2768541142","https://openalex.org/W2787621552","https://openalex.org/W2788271038","https://openalex.org/W2795679953","https://openalex.org/W2804416221","https://openalex.org/W2889646458","https://openalex.org/W2898569576","https://openalex.org/W2909264327","https://openalex.org/W2913014410","https://openalex.org/W2921730759","https://openalex.org/W2936977021","https://openalex.org/W2942912685","https://openalex.org/W2943985492","https://openalex.org/W2948412754","https://openalex.org/W2948510422","https://openalex.org/W2953078908","https://openalex.org/W2980318484","https://openalex.org/W2981989842","https://openalex.org/W2988098732","https://openalex.org/W2989244179","https://openalex.org/W2991216697","https://openalex.org/W2992288250","https://openalex.org/W3029108746","https://openalex.org/W3066083631","https://openalex.org/W3087006800","https://openalex.org/W3200039170","https://openalex.org/W3201078406","https://openalex.org/W4234401042"],"related_works":["https://openalex.org/W4394762148","https://openalex.org/W4405780618","https://openalex.org/W2037187996","https://openalex.org/W3037803867","https://openalex.org/W2891617229","https://openalex.org/W6885137694","https://openalex.org/W1486074920","https://openalex.org/W2356144430","https://openalex.org/W2171151314","https://openalex.org/W2153933602"],"abstract_inverted_index":{"BACKGROUND:":[0],"Previous":[1],"studies":[2],"have":[3],"reported":[4],"that":[5],"the":[6,16,33,45,51,111,127,136,163,175,196,201,212,239],"combination":[7],"of":[8,18,35,53,122,138,198,220,236],"metformin":[9,22,36,54,84,152,199],"and":[10,21,62,87,110,126,145,173,238],"bevacizumab":[11],"exhibit":[12],"favorable":[13],"efficacy":[14],"in":[15,29,37,64,149,156,189,209,223],"treatment":[17],"cancer":[19],"patients,":[20],"possesses":[23],"effects":[24,155,197,217],"on":[25,55,200],"relieving":[26],"vascular":[27,40,57,140,165,203,231],"injury":[28,41,59,124,142,167,205,233],"multiple":[30],"diseases.":[31],"Nonetheless,":[32],"effect":[34],"alleviating":[38],"bevacizumab-induced":[39,202,230],"remains":[42],"unknown.":[43],"Therefore,":[44],"present":[46],"study":[47],"aimed":[48],"to":[49,218],"investigate":[50],"impact":[52],"apoptosis,":[56,120,139,164],"endothelial":[58,68,123,141,166,204,232],"marker":[60,143,168],"expressions,":[61,169,172],"inflammation":[63],"human":[65],"umbilical":[66],"vein":[67],"cells":[69],"(HUVECs),":[70],"as":[71,73],"well":[72],"its":[74],"possible":[75],"molecular":[76],"mechanism.":[77],"METHODS:":[78],"HUVECs":[79],"were":[80,131],"treated":[81,89],"with":[82,90],"bevacizumab,":[83],"or":[85],"both,":[86],"subsequently":[88],"growth":[91],"differentiation":[92],"factor":[93],"15":[94],"(GDF15)":[95],"overexpression":[96,161],"plasmid,":[97,101],"negative":[98],"control":[99],"(NC)":[100],"GDF15":[102,160,193,221,237],"small":[103],"interfering":[104],"ribonucleic":[105],"acid":[106],"(siRNA),":[107],"NC":[108],"siRNA,":[109],"phosphoinositide":[112],"3-kinase":[113],"(PI3K)":[114],"inhibitor":[115,214],"LY294002,":[116],"respectively.":[117],"After":[118],"treatment,":[119],"levels":[121,137],"biomarkers":[125],"potential":[128],"downstream":[129],"proteins":[130],"detected.":[132],"RESULTS:":[133],"Bevacizumab":[134],"increased":[135],"expressions":[144,148],"pro-inflammatory":[146,170],"cytokine":[147,171],"HUVECs,":[150],"while":[151],"alleviated":[153],"these":[154],"bevacizumab-treated":[157,190,224],"HUVECs.":[158,191,225],"Furthermore,":[159],"reduced":[162,195],"activated":[174],"PI3K/protein":[176],"kinase":[177],"B":[178],"(AKT)/forkhead":[179],"box":[180],"O":[181],"(FOXO)/peroxisome":[182],"proliferator-activated":[183],"receptor":[184],"\u03b3":[185],"(PPAR\u03b3)":[186],"signaling":[187,241],"pathway":[188],"Subsequently,":[192],"siRNA":[194,222],"(as":[206],"described":[207],"above)":[208],"HUEVCs.":[210],"Lastly,":[211],"PI3K":[213],"exhibited":[215],"similar":[216],"those":[219],"CONCLUSIONS:":[226],"Metformin":[227],"protected":[228],"against":[229],"via":[234],"activation":[235],"PI3K/AKT/FOXO/PPAR\u03b3":[240],"pathway.":[242]},"counts_by_year":[{"year":2026,"cited_by_count":6},{"year":2025,"cited_by_count":5},{"year":2024,"cited_by_count":4},{"year":2023,"cited_by_count":2},{"year":2022,"cited_by_count":2}],"updated_date":"2026-10-28T10:33:24.094632","created_date":"2021-10-25T00:00:00"}