{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:54:23Z","timestamp":1791204863176,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"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":["Veterinary Medicine &amp;amp; Sci"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study aimed to establish an in vitro model of feline endothelial cells (FECs) undergoing apoptosis when cultured under various nutrient deprivation (starvation) conditions to investigate the protective effects of beraprost and its stereoisomers on endothelial cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Various starvation conditions were tested to induce apoptosis in immortalized feline aortic endothelial cells as assessed by measuring caspase\u20103\/7 activity. The anti\u2010apoptotic effects of the racemic mixture of beraprost and the stereoisomers beraprost\u2010314d and beraprost\u2010315d contained in the racemic mixture were determined by measuring caspase\u20103\/7 activity and\n                      <jats:italic>Bax<\/jats:italic>\n                      \/\n                      <jats:italic>Bcl2<\/jats:italic>\n                      gene expression and performing the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Starvation significantly increased caspase\u20103\/7 activity and induced apoptosis in FECs. Beraprost and beraprost\u2010314d efficiently inhibited caspase\u20103\/7 activation in a dose\u2010dependent manner, whereas beraprost\u2010315d exhibited lower potency. Beraprost downregulated\n                      <jats:italic>Bax<\/jats:italic>\n                      expression and reduced the number of TUNEL\u2010positive cells, confirming its anti\u2010apoptotic effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Relevance<\/jats:title>\n                    <jats:p>\n                      Beraprost effectively attenuates starvation\u2010induced apoptosis\u2010associated events in cultured immortalized feline aortic endothelial cells, inhibits caspase\u20103\/7 activity, and modulates\n                      <jats:italic>Bax<\/jats:italic>\n                      expression. These findings suggest a potential hypothesized mechanism that may contribute to the clinical efficacy of beraprost observed in feline CKD, although further validation using renal endothelial cells and in vivo models is required.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/vms3.71127","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T12:44:42Z","timestamp":1786365882000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Beraprost Attenuates Starvation\u2010Induced Apoptosis and Protects Feline Endothelial Cells"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0253-8392","authenticated-orcid":false,"given":"Takumi","family":"Matsuura","sequence":"first","affiliation":[{"name":"Toray Industries Inc.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5767-2881","authenticated-orcid":false,"given":"Cris Ni\u00f1o Bon B.","family":"Marasigan","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Clinical Pathology Department of Veterinary Medical Sciences Graduate School of Agricultural and Life Sciences The University of Tokyo  Tokyo Japan"},{"name":"Department of Veterinary Paraclinical Sciences College of Veterinary Medicine, University of the Philippines Los Ba\u00f1os  Laguna Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3457-9295","authenticated-orcid":false,"given":"Tomohiro","family":"Yonezawa","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Clinical Pathology Department of Veterinary Medical Sciences Graduate School of Agricultural and Life Sciences The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471\u20104159.2002.01015.x"},{"key":"e_1_2_12_3_1","first-page":"3527","article-title":"Endothelial Cells in Physiology and in the Pathophysiology of Vascular Disorders","volume":"91","author":"Cines D. 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