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Of the many sources of ROS<\/jats:styled-content>, the enzyme xanthine oxidase (XO<\/jats:styled-content>) has been linked to overproduction of ROS<\/jats:styled-content> in diabetic environment, and studies have shown that treatment with XO<\/jats:styled-content> inhibitors decreases XO<\/jats:styled-content> overactivity and XO<\/jats:styled-content>\u2010generated ROS<\/jats:styled-content>. This study evaluates the role of XO<\/jats:styled-content> in the diabetic wound and the impact of specifically inhibiting its activity on wound healing. Treatment of diabetic wounds with siXDH<\/jats:styled-content> (xanthine dehydrogenase siRNA<\/jats:styled-content>) decreased XDH mRNA<\/jats:styled-content> expression by 51.6%, XO<\/jats:styled-content> activity by 35.9%, ROS<\/jats:styled-content> levels by 78.1%, pathologic wound burden by 31.5%, and accelerated wound healing by 7 days (23.3%). Polymerase chain reaction analysis showed that increased XO<\/jats:styled-content> activity in wild\u2010type wound may be due to XDH<\/jats:styled-content> to XO<\/jats:styled-content> conversion and\/or XO<\/jats:styled-content> phosphorylation, but not to gene transcription, whereas increased XO<\/jats:styled-content> activity in diabetic wounds may also be from gene transcription. These results suggest that XO<\/jats:styled-content> may be responsible for large proportion of elevated oxidative stress in the diabetic wound environment and that normalizing the metabolic activity of XO<\/jats:styled-content> using targeted delivery of siXDH<\/jats:styled-content> may decrease overproduction of ROS<\/jats:styled-content> and accelerate wound healing in diabetic patients.<\/jats:p>","DOI":"10.1111\/wrr.12249","type":"journal-article","created":{"date-parts":[[2015,1,9]],"date-time":"2015-01-09T09:47:26Z","timestamp":1420796846000},"page":"14-21","source":"Crossref","is-referenced-by-count":29,"title":["Normalizing dysfunctional purine metabolism accelerates diabetic wound healing"],"prefix":"10.1111","volume":"23","author":[{"given":"Andrew L.","family":"Weinstein","sequence":"first","affiliation":[{"name":"Plastic Surgery NYU Langone Medical Center New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank D.","family":"Lalezarzadeh","sequence":"additional","affiliation":[{"name":"Plastic Surgery NYU Langone Medical Center New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc A.","family":"Soares","sequence":"additional","affiliation":[{"name":"Plastic Surgery NYU Langone Medical Center New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre B.","family":"Saadeh","sequence":"additional","affiliation":[{"name":"Plastic Surgery NYU Langone Medical Center New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel J.","family":"Ceradini","sequence":"additional","affiliation":[{"name":"Plastic Surgery NYU Langone Medical Center New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,2,26]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524-475X.2009.00543.x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/414813a"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M707451200"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.3109\/07388551.2010.527823"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.4.1118"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2006.12.029"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1385\/CBB:43:2:289"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.35.3.746"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1067-1927.2004.12404.x"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3302986"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524-475X.2010.00638.x"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005650-198903001-00015"},{"key":"e_1_2_6_14_1","unstructured":"Centers for Disease Control and Prevention.2011 National Diabetes Fact Sheet.2011. 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