{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,22]],"date-time":"2026-03-22T23:31:07Z","timestamp":1774222267549,"version":"3.50.1"},"reference-count":41,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2025,11,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Excessive oxidative stress and inflammation in human umbilical vein endothelial cells (HUVECs) are significant barriers to wound healing in diabetic foot ulcers (DFUs). Umbilical cord mesenchymal stem cells (UCMSCs)\u2010derived exosomal circular RNA homeodomain\u2010interacting protein kinase three (circHIPK3) exerts protective effects on HUVECs under high\u2010glucose (HG) conditions. Our objective was to elucidate the downstream mechanisms through which UCMSCs\u2010derived exosomal circHIPK3 modulates oxidative stress and inflammation in cellular and mice models of DFU. The type II diabetic db\/db mice model, HG\u2010induced HUVECs, and HG\u2010treated human dermal microvascular endothelial cells (HDMECs) were used to investigate the mechanism of UCMSCs\u2010derived exosomal circHIPK3. HG induced oxidative stress and inflammation in HUVECs, which were attenuated by UCMSCs\u2010derived exosomal circHIPK3. Next, UCMSCs\u2010derived exosomal circHIPK3 reduced HG\u2010induced HUVECs' oxidative stress and inflammation by downregulating high mobility group box\u00a01 (HMGB1). Furthermore, up\u2010frameshift protein 1 (UPF1) reduced the stability of HMGB1 mRNA through direct interaction. Additionally, UCMSCs\u2010derived exosomal circHIPK3 alleviated HG\u2010induced oxidative stress and inflammation in HUVECs by upregulating UPF1 expression. UPF1 protected HUVECs from HG\u2010induced oxidative stress and inflammation by decreasing HMGB1 mRNA stability. UCMSCs\u2010derived exosomal circHIPK3 also enhanced wound healing in a DFU mice model and reduced oxidative stress and inflammation in HG\u2010treated HDMECs. Overall, UCMSCs\u2010derived exosomal circHIPK3 suppressed HG\u2010stimulated oxidative stress and inflammation, thereby promoting wound healing in both cellular and animal DFU models through the UPF1\/HMGB1 axis. These findings suggested that the UCMSCs\u2010derived exosomal circHIPK3\/UPF1\/HMGB1 axis represents a promising therapeutic target for treating DFU.<\/jats:p>","DOI":"10.1096\/fj.202501580rr","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:44:57Z","timestamp":1761698697000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>UCMSCs<\/scp>\n                    \u2010Derived Exosomal\n                    <scp>circHIPK3<\/scp>\n                    Restrains Oxidative Stress and Inflammation by Downregulating the Stability of\n                    <scp>HMGB1 mRNA<\/scp>\n                    via Recruiting\n                    <scp>UPF1<\/scp>\n                    in Diabetes Foot Ulcer"],"prefix":"10.1096","volume":"39","author":[{"given":"Nan\u2010Fang","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Burn &amp; Skin Repair Surgery Hainan General Hospital (Affiliated Hainan Hospital of Hainan Medical University)  Haikou Hainan Province People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shao\u2010Wen","family":"Weng","sequence":"additional","affiliation":[{"name":"Department of Gastrointestine Surgery 1 Hainan General Hospital (Affiliated Hainan Hospital of Hainan Medical University)  Haikou Hainan Province People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shi\u2010Shuai","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Burn &amp; Skin Repair Surgery Hainan General Hospital (Affiliated Hainan Hospital of Hainan Medical University)  Haikou Hainan Province People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei\u2010Cheng","family":"Xu","sequence":"additional","affiliation":[{"name":"Affiliated Clinical College of Hainan Medical University  Haikou Hainan Province People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia","family":"Fu","sequence":"additional","affiliation":[{"name":"Affiliated Clinical College of Hainan Medical University  Haikou Hainan Province People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5441-0059","authenticated-orcid":false,"given":"Zun\u2010Hong","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Burn &amp; Skin Repair Surgery Hainan General Hospital (Affiliated Hainan Hospital of Hainan Medical University)  Haikou Hainan Province People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,10,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.10578"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13047-020-00383-2"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.13569"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.00421"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2022.119437"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202103317"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2022.10.038"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.2174\/1574888X16666210907164046"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-020-01852-y"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2022.829868"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-023-03490-6"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-019-0158-7"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/21655979.2022.2031395"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2018.11.041"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/dme.14968"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.52586\/4925"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/15592294.2023.2293409"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-018-5171-8"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-020-01286-3"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-022-03177-8"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-022-00988-y"},{"issue":"4","key":"e_1_2_8_23_1","first-page":"384","article-title":"Empagliflozin Alleviates Renal Inflammation and Oxidative Stress in Streptozotocin\u2010Induced Diabetic Rats Partly by Repressing HMGB1\u2010TLR4 Receptor Axis","volume":"22","author":"Ashrafi Jigheh Z.","year":"2019","journal-title":"Iranian Journal of Basic Medical Sciences"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27217311"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dsx.2018.06.026"},{"issue":"9","key":"e_1_2_8_26_1","article-title":"Verbascoside Protects Gingival Cells Against High Glucose\u2010Induced Oxidative Stress via PKC\/HMGB1\/RAGE\/NFkappaB Pathway","volume":"10","author":"Hsieh P. 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