{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:52:08Z","timestamp":1790833928959,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T00:00:00Z","timestamp":1634860800000},"content-version":"vor","delay-in-days":294,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["20-15-00390"],"award-info":[{"award-number":["20-15-00390"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>An understanding of the consequences of oxidative\/halogenative stress triggered by neutrophil activation is impossible without considering NETosis. NETosis, formation of neutrophil extracellular traps (NETs), is known to promote microthrombus formation and impair wound healing in type 2 diabetes mellitus (T2DM) patients. Therefore, there is a need to search for drugs and treatment approaches that could prevent excessive NET formation. We aimed to evaluate the effect of vitamin D3 in combination with omega\u20103 polyunsaturated fatty acids (vitamin D3\/omega\u20103 PUFAs) on NETosis in T2DM patients with purulent necrotizing lesions of the lower extremities. Patients and healthy subjects had vitamin D3 deficiency. Patients received, beyond standard treatment, 6000\u2009IU of vitamin D3 and 480\u2009mg of omega\u20103 PUFAs, and healthy subjects 1000\u2009IU of vitamin D3 and 240\u2009mg of omega\u20103 PUFAs daily for seven days. Neutrophil activation in ex vivo blood by phorbol\u201012\u2010myristate\u201013\u2010acetate (PMA) was used as a NETosis model. The percentage of blood NETs relative to leukocytes (NET<jats:sub>background<\/jats:sub>) before vitamin D3\/omega\u20103 PUFA supplementation was 3.2%\u20104.9% in healthy subjects and 1.7%\u201010.8% in patients. These values rose, respectively, to 7.7%\u20109.1% and 4.0%\u201017.9% upon PMA\u2010induced NETosis. In addition, the leukocyte count decreased by 700\u20101300 per 1\u2009<jats:italic>\u03bc<\/jats:italic>L in healthy subjects and 700\u20104000 per 1\u2009<jats:italic>\u03bc<\/jats:italic>L in patients. For both patients and healthy subjects, taking vitamin D3\/omega\u20103 PUFAs had no effect on NET<jats:sub>background<\/jats:sub> but completely inhibited PMA\u2010induced NET formation, though neutrophils exhibited morphological features of activation. Also, leukocyte loss was reduced (to 500 per 1\u2009<jats:italic>\u03bc<\/jats:italic>L). For patients on standard treatment alone, changes occurred neither in background NETs and leukocytes nor in their amount after PMA stimulation. The decreased ability of neutrophils to generate NETs, which can be achieved by vitamin D3\/omega\u20103 PUFA supplementation, could have a positive effect on wound healing in T2DM patients and reduce the incidence and severity of complications.<\/jats:p>","DOI":"10.1155\/2021\/8089696","type":"journal-article","created":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T22:25:40Z","timestamp":1634941540000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Effect of Vitamin D3 in combination with Omega\u20103 Polyunsaturated Fatty Acids on NETosis in Type 2 Diabetes Mellitus Patients"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5170-9824","authenticated-orcid":false,"given":"Liliya Yu.","family":"Basyreva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatyana V.","family":"Vakhrusheva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoya V.","family":"Letkeman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry I.","family":"Maximov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgeniya A.","family":"Fedorova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5245-2285","authenticated-orcid":false,"given":"\u041eleg M.","family":"Panasenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgeny M.","family":"Ostrovsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey A.","family":"Gusev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,22]]},"reference":[{"key":"e_1_2_11_1_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12440"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1204697"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1092385"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.1134\/S0006297920100065"},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0065-2571(85)90049-4"},{"key":"e_1_2_11_6_2","first-page":"27","article-title":"Halogenizing stress and its biomarkers","author":"Panasenko O. 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