{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:57:25Z","timestamp":1770339445891,"version":"3.49.0"},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T00:00:00Z","timestamp":1692403200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004763","name":"Natural Science Foundation of Inner Mongolia Autonomous Region","doi-asserted-by":"publisher","award":["2022MS08053"],"award-info":[{"award-number":["2022MS08053"]}],"id":[{"id":"10.13039\/501100004763","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004763","name":"Natural Science Foundation of Inner Mongolia Autonomous Region","doi-asserted-by":"publisher","award":["2021MS08152"],"award-info":[{"award-number":["2021MS08152"]}],"id":[{"id":"10.13039\/501100004763","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["IUBMB Life"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Our hospital admitted a patient who had difficulty in coagulation even after blood replacement, and the patient had abused caffeine sodium benzoate (CSB) for more than 20\u2009years. Hence, we aimed to explore whether CSB may cause dysfunction in vascular endothelial cells and its possible mechanism. Low, medium, and high concentrations of serum of long\u2010term CSB intake patients were used to treat HUVECs, with LPS as the positive control. MTT and CCK8 were performed to verify CSB's damaging effect on HUVECs. The expression of ET\u20101, ICAM\u20101, VCAM\u20101, and E\u2010selectin were measured by ELISA. TUNEL assay and Matrigel tube formation assay were carried out to detect apoptosis and angiogenesis of HUVECs. Flow cytometry was applied to analyze cell cycles and expression of CD11b, PDGF, and ICAM\u20101. Expression of PDGF\u2010BB and PCNA were examined by western blot. The activation of MAPK signaling pathway was detected by qRT\u2010PCR and western blot. Intracellular Ca<jats:sup>2+<\/jats:sup> density was detected by fluorescent probes. CCK8 assay showed high concentration of CSB inhibited cell viability. Cell proliferation and angiogenesis were inhibited by CSB. ET\u20101, ICAM\u20101, VCAM\u20101, and E\u2010selectin upregulated in CSB groups. CSB enhanced apoptosis of HUVECs. CD11b, ICAM\u20101 increased and PDGF reduced in CSB groups. The expression level and phosphorylation level of MEK, ERK, JUN, and p38 in MAPK pathway elevated in CSB groups. The expression of PCNA and PDGF\u2010BB was suppressed by CSB. Intracellular Ca<jats:sup>2+<\/jats:sup> intensity was increased by CSB. Abuse of CSB injured HUVECs and caused coagulation disorders.<\/jats:p>","DOI":"10.1002\/iub.2777","type":"journal-article","created":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T21:43:41Z","timestamp":1692654221000},"page":"88-100","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Long\u2010term abuse of caffeine sodium benzoate induces endothelial cells injury and leads to coagulation dysfunction"],"prefix":"10.1002","volume":"76","author":[{"given":"Tianwei","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Transfusion Medicine Peking University Cancer Hospital (Inner Mongolia Campus) &amp; Affiliated Cancer Hospital of Inner Mongolia Medical University  Hohhot Inner Mongolia Autonomous Region People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Peking University Cancer Hospital (Inner Mongolia Campus) &amp; Affiliated Cancer Hospital of Inner Mongolia Medical University  Hohhot Inner Mongolia Autonomous Region People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong","family":"Guo","sequence":"additional","affiliation":[{"name":"Clinical Laboratory Diagnostics Peking University Cancer Hospital (Inner Mongolia Campus) &amp; Affiliated Cancer Hospital of Inner Mongolia Medical University  Hohhot Inner Mongolia Autonomous Region People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianzhong","family":"Liu","sequence":"additional","affiliation":[{"name":"Peking University Cancer Hospital (Inner Mongolia Campus) &amp; Affiliated Cancer Hospital of Inner Mongolia Medical University  Hohhot Inner Mongolia Autonomous Region People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lili","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Peking University Cancer Hospital (Inner Mongolia Campus) &amp; Affiliated Cancer Hospital of Inner Mongolia Medical University  Hohhot Inner Mongolia Autonomous Region People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suri","family":"Guga","sequence":"additional","affiliation":[{"name":"Department of Transfusion Medicine Peking University Cancer Hospital (Inner Mongolia Campus) &amp; Affiliated Cancer Hospital of Inner Mongolia Medical University  Hohhot Inner Mongolia Autonomous Region People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weixin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Transfusion Medicine Peking University Cancer Hospital (Inner Mongolia Campus) &amp; Affiliated Cancer Hospital of Inner Mongolia Medical University  Hohhot Inner Mongolia Autonomous Region People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huiying","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Peking University Cancer Hospital (Inner Mongolia Campus) &amp; Affiliated Cancer Hospital of Inner Mongolia Medical University  Hohhot Inner Mongolia Autonomous Region People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feiya","family":"Suo","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Peking University Cancer Hospital (Inner Mongolia Campus) &amp; Affiliated Cancer Hospital of Inner Mongolia Medical University  Hohhot Inner Mongolia Autonomous Region People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8949-8460","authenticated-orcid":false,"given":"Hao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology (Key Laboratory of Radiation Physics and Biology of Inner Mongolia Medical University) Peking University Cancer Hospital (Inner Mongolia Campus) &amp; Affiliated Cancer Hospital of Inner Mongolia Medical University  Hohhot Inner Mongolia Autonomous Region People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Quanzhi","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Transfusion Medicine Peking University Cancer Hospital (Inner Mongolia Campus) &amp; Affiliated Cancer Hospital of Inner Mongolia Medical University  Hohhot Inner Mongolia Autonomous Region People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,8,19]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1098-7339(99)90057-3"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.5414\/CP203805"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.4103\/0019-5049.144643"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI26987"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000028581.07992.56"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.652859"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-021-03471-2"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199901143400207"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12872-015-0124-z"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.5567"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(83)90303-4"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cr.7290105"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14967"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-411637-5.00001-9"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00408-005-2589-5"},{"key":"e_1_2_13_17_1","first-page":"1997","article-title":"ERK\/MAPK signalling pathway and tumorigenesis","volume":"19","author":"Guo YJ","year":"2020","journal-title":"Exp Ther Med"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a011254"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210394"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00744.x"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20100323"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.1564"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.4251\/wjgo.v12.i2.149"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-30056-6"},{"key":"e_1_2_13_25_1","first-page":"603","article-title":"MAPK signaling mediates low shear stress\u2010induced oxidative damage in human umbilical vein endothelial cells in vitro","volume":"34","author":"Wang Z","year":"2014","journal-title":"Nan Fang Yi Ke Da Xue Xue Bao"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-022-02927-8"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.2741\/3844"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2001.10506720"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-47815-z"},{"key":"e_1_2_13_30_1","first-page":"611","article-title":"Effect of caffeine on anti\u2010clotting activity of warfarin in healthy male albino rabbits","volume":"31","author":"Zafar S","year":"2018","journal-title":"Pak J Pharm Sci"},{"key":"e_1_2_13_31_1","first-page":"1647","article-title":"Anticoagulant effect and inhibitory effect on erythrocyte sedimentation of sodium benzoate","volume":"58","author":"Pulitano E","year":"1951","journal-title":"Policlinico Prat"}],"container-title":["IUBMB Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/iub.2777","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T03:59:43Z","timestamp":1706587183000},"score":1,"resource":{"primary":{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/10.1002\/iub.2777"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,19]]},"references-count":30,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2]]}},"alternative-id":["10.1002\/iub.2777"],"URL":"https:\/\/doi.org\/10.1002\/iub.2777","archive":["Portico"],"relation":{},"ISSN":["1521-6543","1521-6551"],"issn-type":[{"value":"1521-6543","type":"print"},{"value":"1521-6551","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,19]]},"assertion":[{"value":"2023-06-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}