{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T04:23:36Z","timestamp":1789791816574,"version":"4.0.1"},"reference-count":34,"publisher":"Portland Press Ltd.","issue":"5","license":[{"start":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T00:00:00Z","timestamp":1564012800000},"content-version":"vor","delay-in-days":321,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,10,31]]},"abstract":"<jats:p>To explore whether or not inhibition of protein kinase C \u03b2II (PKC \u03b2II) stimulates angiogenesis as well as prevents excessive NETosis in diabetics thus accelerating wound healing. Streptozotocin (STZ, 60 mg\/kg\/day for 5 days, i.p.) was injected to induce type I diabetes in male ICR mice. Mice were treated with ruboxistaurin (30 mg\/kg\/day, orally) for 14 consecutive days. Wound closure was evaluated by wound area and number of CD31-stained capillaries. Peripheral blood flow cytometry was done to evaluate number of circulating endothelial progenitor cells (EPCs). NETosis assay and wound tissue immunofluorescence imaging were done to evaluate the percentage of neutrophils undergoing NETosis. Furthermore, the expression of PKC \u03b2II, protein kinase B (Akt), endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), and histone citrullation (H3Cit) were determined in the wound by Western blot analysis. Ruboxistaurin accelerated wound closure and stimulated angiogenesis in diabetic mice. The number of circulating EPCs was increased significantly in ruboxistaurin-treated diabetic mice. Moreover, ruboxistaurin treatment significantly decreases the percentages of H3Cit+ cells in both peripheral blood and wound areas. This prevented excess activated neutrophils forming an extracellular trap (NETs) formation. The expressions of phospho-Akt (p-Akt), phospho-eNOS (p-eNOS), and VEGF increased significantly in diabetic mice on ruboxistaurin treatment. The expressions of PKC \u03b2II and H3Cit+, on the other hand, decreased with ruboxistaurin treatment. The results of the present study suggest that ruboxistaurin by inhibiting PKC \u03b2II activation, reverses EPCs dysfunction as well as prevents exaggerated NETs formation in a diabetic mouse model; thereby accelerating the wound healing process.<\/jats:p>","DOI":"10.1042\/bsr20171459","type":"journal-article","created":{"date-parts":[[2018,2,13]],"date-time":"2018-02-13T17:09:28Z","timestamp":1518541768000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Specific PKC \u03b2II inhibitor: one stone two birds in the treatment of diabetic foot ulcers"],"prefix":"10.1042","volume":"38","author":[{"given":"Sushant\u00a0Kumar","family":"Das","sequence":"first","affiliation":[{"name":"Department of Interventional and Vascular Surgery, Shanghai Tenth People\u2019s Hospital, Tongji University, 301 Yanchang Road, Shanghai 200072, China"},{"name":"Department of Interventional Radiology, Affiliated Hospital of North Sichuan Medical College, 63 Wenhua Road, Nanchong, Sichuan 637000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u00a0Feng","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Interventional and Vascular Surgery, Shanghai Tenth People\u2019s Hospital, Tongji University, 301 Yanchang Road, Shanghai 200072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mao\u00a0Quan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Interventional and Vascular Surgery, Shanghai Tenth People\u2019s Hospital, Tongji University, 301 Yanchang Road, Shanghai 200072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2018,9,7]]},"reference":[{"key":"2021111619113825800_B1","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1089\/cell.2016.0050","article-title":"An overview on current issues and challenges of endothelial progenitor cell-based neovascularization in patients with diabetic foot ulcer","volume":"19","author":"Das","year":"2017","journal-title":"Cell Reprogram."},{"key":"2021111619113825800_B2","doi-asserted-by":"publisher","first-page":"e132","DOI":"10.1093\/cid\/cis460","article-title":"2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections","volume":"54","author":"Lipsky","year":"2012","journal-title":"Clin. 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