{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T15:11:27Z","timestamp":1787757087553,"version":"build-2784847793"},"reference-count":38,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>About 5%\u201310% of the world's population is affected by gastric ulcers, which can result in gastrointestinal perforation and bleeding. Consequently, we aimed to investigate whether blocking TNF\u2010\u03b1 type 1 receptor (TNFR1) with CAY10500 could diminish experimentally induced gastric ulcer (GU) in rats by modulating vascularization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Rats were administered with a single oral dose of 80\u2009mg\/kg of indomethacin to produce gastric ulcers. Subsequently, some rats were given 1\u2009mg\/kg of CAY10500 orally. Gastric samples were used to assess the genetic expression and protein levels of TNFR1, VEGF, ERK, PI3K, AKT (also known as PKB), and ICAM\u20101. Gastric sections underwent electron microscopic examination and were subjected to hematoxylin and eosin staining and immunostaining using anti\u2010TNFR1, anti\u2010VEGF, and anti\u2010ICAM\u20101 antibodies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CAY10500 demonstrated the ability to inhibit the expression of TNFR1. Examination of micro\u2010images of GU using electron microscopy or H\/E staining revealed extensive necrosis, resulting in the complete loss of regular ultrastructural features of epithelial nuclei and cytoplasmic organelles, as well as the loss of tight junctions and disruption of cell membranes. Significantly, the administration of CAY10500 mitigated these effects. Furthermore, CAY10500 significantly elevated the expressions of VEGF, ERK, PI3K, and AKT, which was associated with a significant reduction in the expression of ICAM\u20101.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>CAY10500 effectively improved experimentally induced GU in rats. It works by inhibiting TNFR1 and activating angiogenesis and cell proliferation pathways, leading to gastric tissue healing. CAY10500 significantly reduced the adhesion molecule pathways.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/iid3.70279","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T19:21:56Z","timestamp":1760556116000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Improvement of Experimentally Induced Gastric Ulcers in Rats by Inhibiting Vascularization Through the Blocking of the TNF\u2010\u03b1 Type 1 Receptor"],"prefix":"10.1002","volume":"13","author":[{"given":"Abdullah","family":"Alattar","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy University of Tabuk Tabuk Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reem","family":"Alshaman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy University of Tabuk Tabuk Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fawaz E.","family":"Alanazi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy University of Tabuk Tabuk Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3584-6674","authenticated-orcid":false,"given":"Omar","family":"Bahattab","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science University of Tabuk Tabuk Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanan M.","family":"Hassan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Biochemistry, Faculty of Pharmacy Delta University for Science and Technology Gamasa City Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4777-3919","authenticated-orcid":false,"given":"Mohammed M. H.","family":"Al\u2010Gayyar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy Mansoura University Mansoura Egypt"},{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy University of Tabuk Tabuk Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,15]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.12998\/wjcc.v7.i9.1006"},{"key":"e_1_2_12_3_1","first-page":"3","article-title":"TGF\u2010Beta Signaling Pathway: Its Role in Gastrointestinal Pathophysiology and Modulation of Ulcer Healing","volume":"56","author":"Tanigawa T.","year":"2005","journal-title":"Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0271284"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2023.117294"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S453425"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/1734752"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2024.117901"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-024-01469-0"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA120.012723"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-025-06122-0"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.32519"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.43317"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/13510002.2023.2218679"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.17305\/bb.2024.10367"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110138"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/13510002.2022.2031515"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2015.10.026"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/13510002.2022.2092378"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12906-022-03680-4"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1684\/ecn.2014.0344"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2013.05.023"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1515\/hsz-2015-0265"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.5946\/ce.2016.129"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/plants12081586"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.01.021"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/3-7643-7311-3_15"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10081964"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.03.021"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fvets.2022.754435"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1155\/2024\/6202123"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986712803414088"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114315"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-0743"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2022.115282"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.2MR0220-549R"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.22038\/IJBMS.2022.66823.14656"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00658-5"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111513"}],"container-title":["Immunity, Inflammation and Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/iid3.70279","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/iid3.70279","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/iid3.70279","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T05:15:31Z","timestamp":1776230131000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/iid3.70279"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":38,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1002\/iid3.70279"],"URL":"https:\/\/doi.org\/10.1002\/iid3.70279","archive":["Portico"],"relation":{},"ISSN":["2050-4527","2050-4527"],"issn-type":[{"value":"2050-4527","type":"print"},{"value":"2050-4527","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"2025-01-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70279"}}