Nan Jia, Kangling Xie, Cui Li, Yangjie Li, Yujiao Zong, Jiahao Li, Fan Hu, Ying Cai
{"title":"Circular RNA-Directed Therapeutic Strategy for Cold-Induced Diabetic Macrovascular Disease.","authors":"Nan Jia, Kangling Xie, Cui Li, Yangjie Li, Yujiao Zong, Jiahao Li, Fan Hu, Ying Cai","doi":"10.1177/15230864251380269","DOIUrl":null,"url":null,"abstract":"<p><p><b><i>Aims:</i></b> This study aims to elucidate the molecular mechanisms underlying the alleviation of cold-climate-induced diabetic macrovascular disease (DM-MVD) by targeting hsa_circ_0010154 with gold nanoparticles (AuNPs)-mediated antisense oligonucleotides (ASOs) delivery, combined with aerobic exercise, and to explore the therapeutic effects on glucose and lipid metabolism, inflammation, and oxidative stress. <b><i>Results:</i></b> Significant upregulation of hsa_circ_0010154 in DM-MVD was confirmed through bioinformatics analysis and qRT-PCR validation. The constructed gold nanoparticles-mediated antisense oligonucleotides delivery (AuNPs@ASO) complex exhibited efficient reactive oxygen species-responsive release and effective cellular uptake. Silencing hsa_circ_0010154 led to improved endothelial cell function, reduced inflammation markers, enhanced lipid metabolism, and reduced oxidative stress responses. <i>In vivo</i> studies demonstrated improved cardiac function, vascular remodeling, and enhanced antioxidant enzyme activity. <b><i>Innovation:</i></b> This study introduces a novel approach utilizing AuNPs@ASO targeting hsa_circ_0010154 in conjunction with aerobic exercise to address the complex pathophysiology of cold-climate-induced DM-MVD, presenting a targeted, low-toxicity therapeutic strategy with promising translational potential. <b><i>Conclusion:</i></b> The combined treatment of AuNPs@ASO and aerobic exercise, targeting hsa_circ_0010154, effectively modulates critical pathological pathways involved in DM-MVD, offering a precise and innovative approach for tackling this condition, with implications for clinical translation. <i>Antioxid. Redox Signal.</i> 00, 000-000.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":6.1000,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Antioxidants & redox signaling","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1177/15230864251380269","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Aims: This study aims to elucidate the molecular mechanisms underlying the alleviation of cold-climate-induced diabetic macrovascular disease (DM-MVD) by targeting hsa_circ_0010154 with gold nanoparticles (AuNPs)-mediated antisense oligonucleotides (ASOs) delivery, combined with aerobic exercise, and to explore the therapeutic effects on glucose and lipid metabolism, inflammation, and oxidative stress. Results: Significant upregulation of hsa_circ_0010154 in DM-MVD was confirmed through bioinformatics analysis and qRT-PCR validation. The constructed gold nanoparticles-mediated antisense oligonucleotides delivery (AuNPs@ASO) complex exhibited efficient reactive oxygen species-responsive release and effective cellular uptake. Silencing hsa_circ_0010154 led to improved endothelial cell function, reduced inflammation markers, enhanced lipid metabolism, and reduced oxidative stress responses. In vivo studies demonstrated improved cardiac function, vascular remodeling, and enhanced antioxidant enzyme activity. Innovation: This study introduces a novel approach utilizing AuNPs@ASO targeting hsa_circ_0010154 in conjunction with aerobic exercise to address the complex pathophysiology of cold-climate-induced DM-MVD, presenting a targeted, low-toxicity therapeutic strategy with promising translational potential. Conclusion: The combined treatment of AuNPs@ASO and aerobic exercise, targeting hsa_circ_0010154, effectively modulates critical pathological pathways involved in DM-MVD, offering a precise and innovative approach for tackling this condition, with implications for clinical translation. Antioxid. Redox Signal. 00, 000-000.
期刊介绍:
Antioxidants & Redox Signaling (ARS) is the leading peer-reviewed journal dedicated to understanding the vital impact of oxygen and oxidation-reduction (redox) processes on human health and disease. The Journal explores key issues in genetic, pharmaceutical, and nutritional redox-based therapeutics. Cutting-edge research focuses on structural biology, stem cells, regenerative medicine, epigenetics, imaging, clinical outcomes, and preventive and therapeutic nutrition, among other areas.
ARS has expanded to create two unique foci within one journal: ARS Discoveries and ARS Therapeutics. ARS Discoveries (24 issues) publishes the highest-caliber breakthroughs in basic and applied research. ARS Therapeutics (12 issues) is the first publication of its kind that will help enhance the entire field of redox biology by showcasing the potential of redox sciences to change health outcomes.
ARS coverage includes:
-ROS/RNS as messengers
-Gaseous signal transducers
-Hypoxia and tissue oxygenation
-microRNA
-Prokaryotic systems
-Lessons from plant biology