{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:13:32Z","timestamp":1791231212362,"version":"4.1.0"},"reference-count":42,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T00:00:00Z","timestamp":1715904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Ministry of Health of Ukraine","award":["state registration no. 0123U101055"],"award-info":[{"award-number":["state registration no. 0123U101055"]}]},{"DOI":"10.13039\/501100004742","name":"National Academy of Sciences of Ukraine","doi-asserted-by":"publisher","award":["state registration no. 0123U100516"],"award-info":[{"award-number":["state registration no. 0123U100516"]}],"id":[{"id":"10.13039\/501100004742","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["The International Journal of Lower Extremity Wounds"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:p>\n                    Plasminogen (Pg) is currently considered a master regulator of wound healing, but the molecular mechanisms of its efficacy in improving impaired closure of chronic skin ulcers in type 2 diabetes patients remain unclear. Here, we investigated wound healing effects of autologous plasma-derived Pg in diabetes patients with chronic foot ulcers and evaluated Pg-induced changes in levels of key protein markers related to wound repair. Type 2 diabetes patients with chronic wounds of lower extremities were included in the study and received topical applications of Pg in a dose of 1.0\u2005mg\/mL every 2 days during 20 days, in addition to the standard wound management treatment. Patients treated only according to conventional protocol served as a control. Wound closure rates were monitored by digital planimetry of wound areas. Plasminogen supplementary treatment significantly accelerated relative wound closure as compared with diabetes patients from the control group (24\u2009\u00b1\u20094 days vs 120\u2009\u00b1\u200917 days, respectively,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u2009&lt;\u2009.01). As shown by Western blot, Pg application reduced expression of protein regulators of hypoxia events, angiogenesis, and autophagy such as hypoxia-inducible factor-1\u03b1 (by 6.3-folds,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u2009&lt;\u2009.01), angiostatins (by 2.5-folds,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u2009&lt;\u2009.05), and autophagy marker LC3-II\/LC3-I (by 8.6-folds,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u2009&lt;\u2009.05), while increasing vascular endothelial growth factor level by 1.9-folds (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u2009&lt;\u2009.05). Gelatin zymography showed that Pg-supplemented therapy decreased activity of matrix metalloproteinase-9 (MMP-9) by 3.5-folds at the end of treatment period (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u2009&lt;\u2009.01). We report here for the first time that topically applied plasma-derived Pg has a pronounced beneficial effect in promoting foot ulcer healing in patients with type 2 diabetes through preventing hypoxia-induced signaling, reducing autophagy flux, diminishing excessive MMP activity, and enhancing angiogenesis.\n                  <\/jats:p>","DOI":"10.1177\/15347346241256025","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T10:49:40Z","timestamp":1715942980000},"page":"568-578","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Topical Application of Autologous Plasma-Derived Plasminogen Accelerates Healing of Chronic Foot Ulcers in Type 2 Diabetes Patients"],"prefix":"10.1177","volume":"25","author":[{"given":"Oleg","family":"Petrenko","sequence":"first","affiliation":[{"name":"Bogomolets National Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergiy","family":"Badziukh","sequence":"additional","affiliation":[{"name":"Bogomolets National Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Korsa","sequence":"additional","affiliation":[{"name":"Department of Enzyme Chemistry &amp; Biochemistry, Palladin Institute of Biochemistry of NAS of Ukraine, Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ihor","family":"Kolosovych","sequence":"additional","affiliation":[{"name":"Bogomolets National Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2063-4636","authenticated-orcid":false,"given":"Artem","family":"Tykhomyrov","sequence":"additional","affiliation":[{"name":"Department of Enzyme Chemistry &amp; Biochemistry, Palladin Institute of Biochemistry of NAS of Ukraine, Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2024,5,17]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/socsci11040149"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells11152439"},{"issue":"7","key":"e_1_3_3_4_2","first-page":"665","article-title":"Cutaneous wound: an update from physiopathology to current therapies","volume":"11","author":"Gushiken LFS","year":"2021","unstructured":"Gushiken LFS, Beserra FP, Bastos JK, Jackson CJ, Pellizzon CH. 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