{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T16:22:33Z","timestamp":1787847753708,"version":"build-2784847793"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      This study aimed to evaluate the therapeutic effect of IR-61, a novel mitochondrial heptamethine cyanine dye with antioxidant effects, on diabetes mellitus-induced erectile dysfunction (DMED). Eight-week-old male Sprague\u2013Dawley rats were intraperitoneally injected with streptozotocin (STZ) to induce type 1 diabetes. Eight weeks after STZ injection, all rats were divided into three groups: the control group, DM group, and DM + IR-61 group. In the DM + IR-61 group, the rats were administered IR-61 (1.6 mg kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      ) twice a week by intravenous injection. At week 13, erectile function was evaluated by determining the ratio of the maximal intracavernous pressure to mean arterial pressure, and the penises were then harvested for fluorescent imaging, transmission electron microscopy, histological examinations, and Western blot analysis. Whole-body imaging suggested that IR-61 was highly accumulated in the penis after intravenous injection. IR-61 treatment significantly improved the maximal ICP of diabetic rats. Additionally, IR-61 ameliorated diabetes-induced inflammation, apoptosis, and phenotypic transition of corpus cavernosum smooth muscle cells (CCSMCs) in penile tissue. IR-61 also attenuated mitochondrial damage, reduced reactive oxygen species production in the corpus cavernosum and upregulated sirtuin1 (SIRT1), sirtuin3 (SIRT3), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and heme oxygenase expression in penile tissue. In conclusion, IR-61 represents a potential therapeutic option for DMED by protecting the mitochondria of CCSMCs, which may be mediated by activation of the SIRT1, SIRT3, and Nrf2 pathways.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/aja.aja_69_20","type":"journal-article","created":{"date-parts":[[2021,1,5]],"date-time":"2021-01-05T10:22:08Z","timestamp":1609842128000},"page":"249-258","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":12,"title":["The near-infrared dye IR-61 restores erectile function in a streptozotocin-induced diabetes modelvia mitochondrial protection"],"prefix":"10.4103","volume":"23","author":[{"given":"Xiao-Feng","family":"Yue","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong-Xing","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Wu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin-Yong","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Long","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue-Ru","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Wei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gu-Fang","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zu-Juan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Meng","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Bing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-5-20240829","doi-asserted-by":"crossref","first-page":"E2731","DOI":"10.1073\/pnas.1403471111","article-title":"Inhibition of Ninjurin 1 restores erectile function through dual angiogenic and neurotrophic effects in the diabetic mouse","volume":"111","author":"Yin","year":"2014","journal-title":"Proc Natl Aca Sci U S A"},{"key":"R2-5-20240829","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.2337\/diacare.26.4.1093","article-title":"Do impotent men with diabetes have more severe erectile dysfunction and worse quality of life than the general population of impotent patients.Results from the Exploratory Comprehensive Evaluation of Erectile Dysfunction (ExCEED) database?","volume":"26","author":"Penson","year":"2003","journal-title":"Diabetes Care"},{"key":"R3-5-20240829","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1111\/jcmm.12480","article-title":"Antioxidant icariside II combined with insulin restores erectile function in streptozotocin-induced type 1 diabetic rats","volume":"19","author":"Wang","year":"2015","journal-title":"J Cell Mol Med"},{"key":"R4-5-20240829","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.diabet.2011.09.003","article-title":"Erectile dysfunction and diabetes: a review of the current evidence-based medicine and a synthesis of the main available therapies","volume":"38","author":"Ph\u00e9","year":"2012","journal-title":"Diabetes Metab"},{"key":"R5-5-20240829","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1016\/S0022-5347(05)67111-X","article-title":"Reduction of endothelial and smooth muscle density in the corpora cavernosa of the streptozotocin induced diabetic rat","volume":"164","author":"Burchardt","year":"2000","journal-title":"J Urol"},{"key":"R6-5-20240829","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/S0094-0143(21)00692-3","article-title":"The penis as a vascular organ.The importance of corporal smooth muscle tone in the control of erection","volume":"22","author":"Christ","year":"1995","journal-title":"Urol Cli North Am"},{"key":"R7-5-20240829","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.cellsig.2018.08.019","article-title":"Smooth muscle cell-driven vascular diseases and molecular mechanisms of VSMC plasticity","volume":"52","author":"Frismantiene","year":"2018","journal-title":"Cell Signal"},{"key":"R8-5-20240829","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1159\/000477388","article-title":"Losartan Preserves Erectile function by suppression of apoptosis and fibrosis of corpus cavernosum and corporal veno-occlusive dysfunction in diabetic rats","volume":"42","author":"Li","year":"2017","journal-title":"Cell Physiol Biochem"},{"key":"R9-5-20240829","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1016\/j.eururo.2008.01.032","article-title":"Chronic treatment with a type 5 phosphodiesterase inhibitor suppresses apoptosis of corporal smooth muscle by potentiating Akt signalling in a rat model of diabetic erectile dysfunction","volume":"53","author":"Park","year":"2008","journal-title":"Eur Urol"},{"key":"R10-5-20240829","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.urology.2013.02.045","article-title":"Long-term oral administration of 5a-reductase inhibitor attenuates erectile function by inhibiting autophagy and promoting apoptosis of smooth muscle cells in corpus cavernosum of aged rats","volume":"82","author":"Zhang","year":"2013","journal-title":"Urology"},{"key":"R11-5-20240829","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1016\/j.urology.2012.12.068","article-title":"Effect of chronic low-dose tadalafil on penile cavernous tissues in diabetic rats","volume":"81","author":"Mostafa","year":"2013","journal-title":"Urology"},{"key":"R12-5-20240829","doi-asserted-by":"crossref","first-page":"H346","DOI":"10.1152\/ajpheart.00227.2014","article-title":"Cardiac, skeletal, and smooth muscle mitochondrial respiration: are all mitochondria created equal?","volume":"307","author":"Park","year":"2014","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"R13-5-20240829","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.bbrc.2017.10.122","article-title":"Role of ROS-TRPM7-ERK1\/2 axis in high concentration glucose-mediated proliferation and phenotype switching of rat aortic vascular smooth muscle cells","volume":"494","author":"Yang","year":"2017","journal-title":"Biochem Bioph Res Co"},{"key":"R14-5-20240829","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.atherosclerosis.2017.06.002","article-title":"Palmitate induces VSMC apoptosis via toll like receptor (TLR)4\/ROS\/p53 pathway","volume":"263","author":"Zhang","year":"2017","journal-title":"Atherosclerosis"},{"key":"R15-5-20240829","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1007\/s00441-016-2494-7","article-title":"Beneficial effect of PEDF-transfected ADSCs on erectile dysfunction in a streptozotocin-diabetic rat model","volume":"366","author":"Lu","year":"2016","journal-title":"Cell Tissue Res"},{"key":"R16-5-20240829","doi-asserted-by":"crossref","first-page":"623","DOI":"10.33549\/physiolres.934129","article-title":"Role of oxidative stress, adiponectin and endoglin in the pathophysiology of erectile dysfunction in diabetic and non-diabetic men","volume":"68","author":"Trebatick\u00fd","year":"2019","journal-title":"Physiol Res"},{"key":"R17-5-20240829","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1016\/j.bbadis.2016.10.020","article-title":"Mitochondria as a centrally positioned hub in the innate immune response","volume":"1863","author":"Sandhir","year":"2017","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"R18-5-20240829","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1089\/ars.2017.7313","article-title":"Mitochondria, the NLRP3 inflammasome, and sirtuins in type 2 diabetes: new therapeutic targets","volume":"29","author":"Rovira-Llopis","year":"2018","journal-title":"Antioxid Redox Signal"},{"key":"R19-5-20240829","doi-asserted-by":"crossref","first-page":"e3074","DOI":"10.1038\/cddis.2017.470","article-title":"NLRP3 inflammasome activation contributes to VSMC phenotypic transformation and proliferation in hypertension","volume":"8","author":"Sun","year":"2017","journal-title":"Cell Death Dis"},{"key":"R20-5-20240829","doi-asserted-by":"crossref","first-page":"8397","DOI":"10.1002\/adfm.201600996","article-title":"Development of therapeutic small-molecule fluorophore for cell transplantation","volume":"26","author":"Wang","year":"2016","journal-title":"Adv Funct Mater"},{"key":"R21-5-20240829","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.bbrc.2018.10.036","article-title":"Probucol improves erectile function via activation of Nrf2 and coordinates the HO-1\/DDAH\/PPAR-\u03b3\/eNOS pathways in streptozotocin-induced diabetic rats","volume":"507","author":"Hu","year":"2018","journal-title":"Biochem Bioph Res Co"},{"key":"R22-5-20240829","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1161\/HYPERTENSIONAHA.116.07518","article-title":"Internal pudental artery dysfunction in diabetes mellitus is mediated by NOX1-Derived ROS-, Nrf2-, and Rho kinase-dependent mechanisms","volume":"68","author":"Alves-Lopes","year":"2016","journal-title":"Hypertension"},{"key":"R23-5-20240829","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.juro.2012.12.001","article-title":"Protective effects of hydrogen-rich saline against erectile dysfunction in a streptozotocin induced diabetic rat model","volume":"190","author":"Fan","year":"2013","journal-title":"J Urol"},{"key":"R24-5-20240829","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1038\/ijir.2012.16","article-title":"Characterization of corpus cavernosum smooth muscle cell phenotype in diabetic rats with erectile dysfunction","volume":"24","author":"Wei","year":"2012","journal-title":"Int J Impot Res"},{"key":"R25-5-20240829","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1111\/andr.12375","article-title":"Maintenance of the contractile phenotype in corpus cavernosum smooth muscle cells by Myocardin gene therapy ameliorates erectile dysfunction in bilateral cavernous nerve injury rats","volume":"5","author":"Zhang","year":"2017","journal-title":"Andrology"},{"key":"R26-5-20240829","doi-asserted-by":"crossref","first-page":"6354","DOI":"10.7150\/thno.34008","article-title":"Transplantation of induced pluripotent stem cell-derived mesenchymal stem cells improved erectile dysfunction induced by cavernous nerve injury","volume":"9","author":"Chen","year":"2019","journal-title":"Theranostics"},{"key":"R27-5-20240829","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1159\/000486919","article-title":"Angiotensin II silencing alleviates erectile dysfunction through down-regulating the Rhoa\/Rho kinase signaling pathway in rats with diabetes mellitus","volume":"45","author":"Zhang","year":"2018","journal-title":"Cell Physiol Biochem"},{"key":"R28-5-20240829","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1038\/nrurol.2014.278","article-title":"Understanding and targeting the Rho kinase pathway in erectile dysfunction","volume":"11","author":"Sopko","year":"2014","journal-title":"Nat Rev Urol"},{"key":"R29-5-20240829","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1161\/HYPERTENSIONAHA.112.195644","article-title":"Atorvastatin inhibits myocardin expression in vascular smooth muscle cells","volume":"60","author":"Li","year":"2012","journal-title":"Hypertension"},{"key":"R30-5-20240829","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1111\/and.12261","article-title":"Myocardin restores erectile function in diabetic rats: phenotypic modulation of corpus cavernosum smooth muscle cells","volume":"47","author":"He","year":"2015","journal-title":"Andrologia"},{"key":"R31-5-20240829","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/s41569-018-0064-2","article-title":"Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty","volume":"15","author":"Ferrucci","year":"2018","journal-title":"Nat Rev Cardiol"},{"key":"R32-5-20240829","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1139\/cjpp-2017-0778","article-title":"Depression induced by chronic stress leads to penile cavernosal dysfunction: protective effect of anti-TNF-\u03b1 treatment","volume":"96","author":"Demirta\u015f \u015eahin","year":"2018","journal-title":"Can J Physiol Pharm"},{"key":"R33-5-20240829","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s00395-017-0663-9","article-title":"Role of NLRP3 inflammasome in the pathogenesis of cardiovascular diseases","volume":"113","author":"Liu","year":"2018","journal-title":"Basic Res Cardiol"},{"key":"R34-5-20240829","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.molimm.2018.09.010","article-title":"The role of mitochondria in NLRP3 inflammasome activation","volume":"103","author":"Liu","year":"2018","journal-title":"Mol Immunol"},{"key":"R35-5-20240829","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.7150\/ijbs.33568","article-title":"Role of pyroptosis in cardiovascular diseases and its therapeutic implications","volume":"15","author":"Zeng","year":"2019","journal-title":"Int J Biol Sci"},{"key":"R36-5-20240829","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1016\/j.celrep.2018.10.103","article-title":"The mitochondrial apoptotic effectors BAX\/BAK activate caspase-3 and -7 to trigger NLRP3 inflammasome and caspase-8 driven IL-1\u03b2 activation","volume":"25","author":"Vince","year":"2018","journal-title":"Cell Rep"},{"key":"R37-5-20240829","doi-asserted-by":"crossref","first-page":"2269","DOI":"10.1159\/000486061","article-title":"NLRP3 gene deletion attenuates angiotensin II-Induced phenotypic transformation of vascular smooth muscle cells and vascular remodeling","volume":"44","author":"Ren","year":"2017","journal-title":"Cell Physiol Biochem"},{"key":"R38-5-20240829","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/s41419-019-1400-0","article-title":"Altered mitochondrial quality control in Atg7-deficient VSMCs promotes enhanced apoptosis and is linked to unstable atherosclerotic plaque phenotype","volume":"10","author":"Nahapetyan","year":"2019","journal-title":"Cell Death Dis"},{"key":"R39-5-20240829","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.immuni.2012.01.009","article-title":"Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis","volume":"36","author":"Shimada","year":"2012","journal-title":"Immunity"},{"key":"R40-5-20240829","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1111\/jsm.12447","article-title":"Assessment of androgen replacement therapy for erectile function in rats with type 2 diabetes mellitus by examining nitric oxide-related and inflammatory factors","volume":"11","author":"Kataoka","year":"2014","journal-title":"J Sex Med"},{"key":"R41-5-20240829","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1038\/aja.2013.60","article-title":"Resveratrol, an activator of SIRT1, restores erectile function in streptozotocin-induced diabetic rats","volume":"15","author":"Yu","year":"2013","journal-title":"Asian J Androl"},{"key":"R42-5-20240829","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1111\/jsm.13035","article-title":"Effects of aging and cardiovascular disease risk factors on the expression of sirtuins in the human corpus cavernosum","volume":"12","author":"Freitas","year":"2015","journal-title":"J Sex Med"},{"key":"R43-5-20240829","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.freeradbiomed.2016.12.030","article-title":"Epigenetic regulation of redox signaling in diabetic retinopathy: role of Nrf2","volume":"103","author":"Kowluru","year":"2017","journal-title":"Free Radic Biol Med"},{"key":"R44-5-20240829","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1002\/tox.22736","article-title":"Chlorpyrifos activates cell pyroptosis and increases susceptibility on oxidative stress-induced toxicity by miR-181\/SIRT1\/PGC-1\u03b1\/Nrf2 signaling pathway in human neuroblastoma SH-SY5Y cells: implication for association between chlorpyrifos and Parkinson's disease","volume":"34","author":"Zhao","year":"2019","journal-title":"Environ Toxicol"},{"key":"R45-5-20240829","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.toxlet.2019.08.024","article-title":"The protective effect of lithocholic acid on the intestinal epithelial barrier is mediated by the vitamin D receptor via a SIRT1\/Nrf2 and NF-\u03baB dependent mechanism in Caco-2 cells","volume":"316","author":"Yao","year":"2019","journal-title":"Toxicol Lett"},{"key":"R46-5-20240829","doi-asserted-by":"crossref","first-page":"104276","DOI":"10.1016\/j.phrs.2019.104276","article-title":"MicroRNA-128-3p aggravates doxorubicin-induced liver injury by promoting oxidative stress via targeting Sirtuin-1","volume":"146","author":"Zhao","year":"2019","journal-title":"Pharmacol Res"}],"container-title":["Asian Journal of Andrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/aja.aja_69_20","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T15:35:55Z","timestamp":1787844955000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/aja.aja_69_20"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5]]},"references-count":46,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021]]}},"URL":"https:\/\/doi.org\/10.4103\/aja.aja_69_20","relation":{},"ISSN":["1008-682X"],"issn-type":[{"value":"1008-682X","type":"print"}],"subject":[],"published":{"date-parts":[[2021,5]]}}}