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Circular RNAs (circRNAs) have emerged as important regulators in diabetic complications, but their roles in DPN remain poorly understood. RNA sequencing (RNA\u2010Seq) and Weighted Gene Co\u2010Expression Network Analysis (WGCNA) were performed to identify DPN\u2010associated circRNAs in rat sciatic nerves. Multi\u2010omics approaches, including proteomics and metabolomics, were applied to characterize the downstream pathways of circ_0000756. Functional studies in Schwann cells assessed oxidative stress, apoptosis, and inflammatory responses, while a DPN rat model was used to validate in\u00a0vivo effects. Circ_0000756 was significantly upregulated in DPN, acting as an miR\u20107b decoy to inhibit NRF2\/ARE pathway activation. This led to enhanced oxidative stress, Schwann cell damage, and amplification of metabolic memory effects. Knockdown of circ_0000756 reduced oxidative stress and apoptosis in Schwann cells and mitigated nerve damage in DPN models. Circ_0000756 drives DPN progression by disrupting the miR\u20107b\/NRF2\/ARE axis, highlighting its potential as a therapeutic target for this challenging diabetic complication.<\/jats:p>","DOI":"10.1096\/fj.202501968r","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T08:40:00Z","timestamp":1761813600000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Circ_0000756 Mediates Oxidative Stress and Metabolic Memory in Diabetic Neuropathy via\n                    <scp>miR<\/scp>\n                    \u20107b Suppression of\n                    <scp>NRF2<\/scp>\n                    \/\n                    <scp>ARE<\/scp>\n                    Pathway"],"prefix":"10.1096","volume":"39","author":[{"given":"Ji","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Endocrinology Jishou University of Huaihua Hospital  Huaihua P. R. China"},{"name":"Department of Endocrinology, Yuebei People's Hospital Shantou University Medical College  Shaoguan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingqing","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Xiangya Hospital of Central South University  Changsha P. R. China"},{"name":"National Clinical Research Center for Geriatric Disorders Xiangya Hospital of Central South University  Changsha P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyuxi","family":"Chen","sequence":"additional","affiliation":[{"name":"Yali High School International Department  Changsha P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinxin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Hunan University of Medicine General Hospital  Huaihua Hunan Province P. R. 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