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Vitamin D deficiency is highly prevalent among diabetic populations, and accumulating evidence indicates its potential involvement in the pathogenesis and prognosis of DFUs. This review comprehensively explores the diverse roles of vitamin D in DFUs, encompassing its molecular mechanisms such as immunomodulation, promotion of angiogenesis, neuroprotection, and induction of antimicrobial peptides, as well as the metabolic characteristics associated with various vitamin D forms and compromised vitamin D receptor (VDR) signaling pathways. Although robust observational studies have established an association between vitamin D deficiency and adverse outcomes in DFUs, the clinical validation of supplementation efficacy through randomized controlled trials (RCTs) remains constrained by limitations such as small sample sizes, heterogeneity in study protocols, and insufficient long-term follow-up. This highlights the critical need for large-scale, high-quality studies to ascertain optimal treatment regimens and to cater to individualized patient requirements, particularly for individuals with obesity or those with renal impairments. Innovative strategies, such as the topical administration of vitamin D through intelligent delivery systems leveraging advanced biomaterials like nanofibers and hydrogels, exhibit substantial preclinical potential in enhancing stability, achieving targeted controlled release, and augmenting local biological effects, including the induction of antimicrobial peptides. Nevertheless, significant challenges persist in conclusively establishing clinical efficacy, comprehensively elucidating the underlying mechanisms, ensuring the safe translation of novel delivery systems, and developing personalized therapeutic strategies. The future success of these interventions hinges on meticulous research and interdisciplinary collaboration to seamlessly integrate validated vitamin D-based interventions into a comprehensive multidisciplinary management framework for DFUs, thereby holding promise for improving the clinical outcomes of this debilitating condition.<\/jats:p>","DOI":"10.3390\/ijms26125719","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T09:51:22Z","timestamp":1750067482000},"page":"5719","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Multi-Dimensional Role of Vitamin D in the Pathophysiology and Treatment of Diabetic Foot Ulcers: From Molecular Mechanisms to Clinical Translation"],"prefix":"10.3390","volume":"26","author":[{"given":"Weiwei","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu 610041, China"},{"name":"Innovation Research Center for Diabetic Foot, Diabetic Foot Care Center, West China Hospital of Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengqiu","family":"Chen","sequence":"additional","affiliation":[{"name":"Innovation Research Center for Diabetic Foot, Diabetic Foot Care Center, West China Hospital of Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuxia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Research Core Facilities, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6634-1241","authenticated-orcid":false,"given":"Xingwu","family":"Ran","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu 610041, China"},{"name":"Innovation Research Center for Diabetic Foot, Diabetic Foot Care Center, West China Hospital of Sichuan University, Chengdu 610041, China"},{"name":"Center for High Altitude Medicine, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e3654","DOI":"10.1002\/dmrr.3654","article-title":"Definitions and criteria for diabetes-related foot disease (IWGDF 2023 update)","volume":"40","author":"Bus","year":"2024","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1080\/07853890.2016.1231932","article-title":"Global epidemiology of diabetic foot ulceration: A systematic review and meta-analysis","volume":"49","author":"Zhang","year":"2016","journal-title":"Ann. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"964","DOI":"10.2337\/dc19-1614","article-title":"Global Disability Burdens of Diabetes-Related Lower-Extremity Complications in 1990 and 2016","volume":"43","author":"Zhang","year":"2020","journal-title":"Diabetes Care"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"209","DOI":"10.2337\/dci22-0043","article-title":"Etiology, Epidemiology, and Disparities in the Burden of Diabetic Foot Ulcers","volume":"46","author":"McDermott","year":"2022","journal-title":"Diabetes Care"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"340","DOI":"10.21037\/atm.2017.07.01","article-title":"Prevalence of diabetic foot ulceration and associated risk factors: An old and still major public health problem in Khartoum, Sudan?","volume":"5","author":"Almobarak","year":"2017","journal-title":"Ann. Transl. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1089\/wound.2017.0743","article-title":"Publicly Reported Wound Healing Rates: The Fantasy and the Reality","volume":"7","author":"Fife","year":"2018","journal-title":"Adv. Wound Care"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2367","DOI":"10.1056\/NEJMra1615439","article-title":"Diabetic Foot Ulcers and Their Recurrence","volume":"376","author":"Armstrong","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1001\/jama.2023.10578","article-title":"Diabetic Foot Ulcers: A Review","volume":"330","author":"Armstrong","year":"2023","journal-title":"JAMA"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Kami\u0144ski, A., Bogacz, A., Niezgoda-Nowak, J.T., Podralska, M., G\u00f3rska, A., Soczawa, M., and Czerny, B. (2025). The VDR rs1544410 and rs11568820 Variants and the Risk of Osteoporosis in the Polish Population. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26020481"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1210\/er.2018-00126","article-title":"Skeletal and Extraskeletal Actions of Vitamin D: Current Evidence and Outstanding Questions","volume":"40","author":"Bouillon","year":"2019","journal-title":"Endocr. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Zhu, W., Zhu, Y., Zhang, S., Zhang, W., Si, Z., Bai, Y., Wu, Y., Fu, Y., Zhang, Y., and Zhang, L. (2023). 1,25-Dihydroxyvitamin D regulates macrophage activation through FBP1\/PKR and ameliorates arthritis in TNF-transgenic mice. J. Steroid Biochem. Mol. Biol., 228.","DOI":"10.1016\/j.jsbmb.2023.106251"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Ma, Y., Gong, Y., Wu, Y., Li, Y., Fu, R., Zhang, X., Zhao, Q., and Zhi, X. (2024). 1,25(OH)2D3 improves diabetic wound healing by modulating inflammation and promoting angiogenesis. J. Steroid Biochem. Mol. Biol., 239.","DOI":"10.1016\/j.jsbmb.2024.106477"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Vaccaro, J.A., Qasem, A., and Naser, S.A. (2022). Cathelicidin Mediates an Anti-Inflammatory Role of Active Vitamin D (Calcitriol) During M. paratuberculosis Infection. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.875772"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1111\/jdi.13776","article-title":"Association between vitamin D status and diabetic foot in patients with type 2 diabetes mellitus","volume":"13","author":"Tang","year":"2022","journal-title":"J. Diabetes Investig."},{"key":"ref_15","first-page":"21932","article-title":"The correlation between serum vitamin D status and the occurrence of diabetic foot ulcers: A comprehensive systematic review and meta-analysis","volume":"14","author":"Tang","year":"2024","journal-title":"Sci. Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Atoum, M.F., Al Shdaifat, A., Al Hourani, H., Al Hyari, M., Zahran, R., and Abu Shaikh, H. (2023). Relationship of Serum Vitamin D Levels With Diabetic Foot in Patients With Type 2 Diabetes Mellitus: A Cross-Sectional Study. Int. J. Low. Extremity Wounds, 15347346231205641.","DOI":"10.1177\/15347346231205641"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1002\/jcb.240590107","article-title":"1,25-dihydroxyvitamin D3: A novel agent for enhancing wound healing","volume":"59","author":"Tian","year":"1995","journal-title":"J. Cell. Biochem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1093\/postmj\/qgae107","article-title":"Effects of vitamin D supplementation on diabetic foot ulcer healing: A meta-analysis","volume":"101","author":"Wu","year":"2025","journal-title":"Postgrad. Med. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1038\/s41574-021-00593-z","article-title":"The health effects of vitamin D supplementation: Evidence from human studies","volume":"18","author":"Bouillon","year":"2022","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Delrue, C., and Speeckaert, M.M. (2023). Vitamin D and Vitamin D-Binding Protein in Health and Disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054642"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1093\/clinchem\/hvad151","article-title":"Functional Assessment of Vitamin D Status by a Novel Metabolic Approach: The Low Vitamin D Profile Concept","volume":"69","author":"Herrmann","year":"2023","journal-title":"Clin. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1080\/10408363.2023.2212765","article-title":"Advances and challenges in the measurement of 1,25-dihydroxyvitamin D: A comprehensive review","volume":"60","author":"Jin","year":"2023","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e163627","DOI":"10.1172\/JCI163627","article-title":"A parathyroid hormone\/salt-inducible kinase signaling axis controls renal vitamin D activation and organismal calcium homeostasis","volume":"133","author":"Yoon","year":"2023","journal-title":"J. Clin. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e179882","DOI":"10.1172\/JCI179882","article-title":"Intestinal Cyp24a1 regulates vitamin D locally independent of systemic regulation by renal Cyp24a1 in mice","volume":"135","author":"Fuchs","year":"2024","journal-title":"J. Clin. Investig."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/s11154-016-9353-4","article-title":"Targeting the vitamin D endocrine system (VDES) for the management of inflammatory and malignant skin diseases: An historical view and outlook","volume":"17","author":"Reichrath","year":"2016","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1038\/labinvest.2017.3","article-title":"Vitamin D signaling and melanoma: Role of vitamin D and its receptors in melanoma progression and management","volume":"97","author":"Slominski","year":"2017","journal-title":"Lab. Investig."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.freeradbiomed.2020.05.016","article-title":"CYP11A1-derived vitamin D3 products protect against UVB-induced inflammation and promote keratinocytes differentiation","volume":"155","author":"Chaiprasongsuk","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Bikle, D.D., and Schwartz, J. (2019). Vitamin D Binding Protein, Total and Free Vitamin D Levels in Different Physiological and Pathophysiological Conditions. Front. Endocrinol., 10.","DOI":"10.3389\/fendo.2019.00317"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1093\/clinchem\/hvae202","article-title":"Measurement of Serum Free Vitamin D Concentrations: Importance, Challenges, and the Emerging Role of Mass Spectrometry","volume":"71","author":"Alexandridou","year":"2025","journal-title":"Clin. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Rozmus, D., Ciesielska, A., P\u0142omi\u0144ski, J., Grzybowski, R., Fiedorowicz, E., Kordulewska, N., Savelkoul, H., Kostyra, E., and Cie\u015bli\u0144ska, A. (2020). Vitamin D Binding Protein (VDBP) and Its Gene Polymorphisms-The Risk of Malignant Tumors and Other Diseases. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21217822"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1002\/jmv.26409","article-title":"The role of DBP gene polymorphisms in the prevalence of new coronavirus disease 2019 infection and mortality rate","volume":"93","author":"Hekim","year":"2021","journal-title":"J. Med. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Rozmus, D., P\u0142omi\u0144ski, J., Augustyn, K., and Cie\u015bli\u0144ska, A. (2022). rs7041 and rs4588 Polymorphisms in Vitamin D Binding Protein Gene (VDBP) and the Risk of Diseases. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23020933"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.gene.2017.09.008","article-title":"Association of vitamin D and vitamin D binding protein (DBP) gene polymorphism with susceptibility of type 2 diabetes mellitus in Bangladesh","volume":"636","author":"Rahman","year":"2017","journal-title":"Gene"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Setayesh, L., Casazza, K., Moradi, N., Mehranfar, S., Yarizadeh, H., Amini, A., Yekaninejad, M.S., and Mirzaei, K. (2021). Association of vitamin D-binding protein and vitamin D3 with insulin and homeostatic model assessment (HOMA-IR) in overweight and obese females. BMC Res. Notes, 14.","DOI":"10.1186\/s13104-021-05608-6"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Bastyte, D., Tamasauskiene, L., Stakaitiene, I., Briede, K., Ugenskiene, R., Valiukeviciene, S., and Gradauskiene, B. (2024). Relation of T Cell Profile with Vitamin D Receptor and Vitamin D-Binding Protein Gene Polymorphisms in Atopy. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25169021"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Asghari, G., Yuzbashian, E., Nikparast, A., Najd Hassan Bonab, L., Mahdavi, M., Daneshpour, M.S., Hosseinpanah, F., and Mirmiran, P. (2022). Impact of daily vitamin D3 supplementation on the risk of vitamin D deficiency with the interaction of rs2282679 in vitamin D binding protein gene (GC) among overweight and obese children and adolescents: A one-year randomized controlled trial. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.1061496"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s13098-023-01002-3","article-title":"Level of 25-hydroxyvitamin D and vitamin D receptor in diabetic foot ulcer and factor associated with diabetic foot ulcers","volume":"15","author":"Tang","year":"2023","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.2147\/DMSO.S303018","article-title":"Vitamin D\/VDR Protects Against Diabetic Kidney Disease by Restoring Podocytes Autophagy","volume":"14","author":"Song","year":"2021","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2639","DOI":"10.2337\/db21-0205","article-title":"VDR\/Atg3 Axis Regulates Slit Diaphragm to Tight Junction Transition via p62-Mediated Autophagy Pathway in Diabetic Nephropathy","volume":"70","author":"Wang","year":"2021","journal-title":"Diabetes"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Hou, X., Xu, F., Zhang, C., Shuai, J., Huang, Z., Liang, Y., and Xu, X. (2020). Dexmedetomidine exerts neuroprotective effects during high glucose-induced neural injury by inhibiting miR-125b. Biosci. Rep., 40.","DOI":"10.1042\/BSR20200394"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.4239\/wjd.v13.i12.1140","article-title":"Single nucleotide variations in the development of diabetic foot ulcer: A narrative review","volume":"13","author":"Hu","year":"2022","journal-title":"World J. Diabetes"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1177\/1534734620977599","article-title":"Genetic Polymorphisms and the Risk of Diabetic Foot: A Systematic Review and Meta-Analyses","volume":"21","author":"Zhao","year":"2022","journal-title":"Int. J. Low Extrem. Wounds"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.gene.2016.11.012","article-title":"Vitamin D receptor gene FokI variant in diabetic foot ulcer and its relation with oxidative stress","volume":"599","author":"Soroush","year":"2017","journal-title":"Gene"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"8627","DOI":"10.1007\/s11033-022-07698-2","article-title":"The vitamin D receptor gene variants, ApaI, TaqI, BsmI, and FokI in diabetic foot ulcer and their association with oxidative stress","volume":"49","author":"Klashami","year":"2022","journal-title":"Mol. Biol. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e70027","DOI":"10.1111\/iwj.70027","article-title":"Association of vitamin D status and vitamin D receptor polymorphism in diabetic foot ulcer patients: A prospective observational study in a South-Indian tertiary healthcare facility","volume":"21","author":"Kurian","year":"2024","journal-title":"Int. Wound J."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Gonzalez-Curiel, I., Trujillo, V., Montoya-Rosales, A., Rincon, K., Rivas-Calderon, B., deHaro-Acosta, J., Marin-Luevano, P., Lozano-Lopez, D., Enciso-Moreno, J.A., and Rivas-Santiago, B. (2014). 1,25-dihydroxyvitamin D3 induces LL-37 and HBD-2 production in keratinocytes from diabetic foot ulcers promoting wound healing: An in vitro model. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0111355"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.2217\/nnm-2018-0011","article-title":"1\u03b1,25-dihydroxyvitamin D3-eluting nanofibrous dressings induce endogenous antimicrobial peptide expression","volume":"13","author":"Jiang","year":"2018","journal-title":"Nanomedicine"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"tkac051","DOI":"10.1093\/burnst\/tkac051","article-title":"Macrophage polarization in diabetic wound healing","volume":"10","author":"Wu","year":"2022","journal-title":"Burns Trauma"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"6917","DOI":"10.1002\/jcp.27450","article-title":"Active vitamin D regulates macrophage M1\/M2 phenotypes via the STAT-1-TREM-1 pathway in diabetic nephropathy","volume":"234","author":"Zhang","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4685","DOI":"10.4251\/wjgo.v16.i12.4685","article-title":"Vitamin D 1,25-Dihydroxyvitamin D3 reduces lipid accumulation in hepatocytes by inhibiting M1 macrophage polarization","volume":"16","author":"Luo","year":"2024","journal-title":"World J. Gastrointest. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"108668","DOI":"10.1016\/j.exer.2021.108668","article-title":"Topical calcitriol application promotes diabetic corneal wound healing and reinnervation through inhibiting NLRP3 inflammasome activation","volume":"209","author":"Wang","year":"2021","journal-title":"Exp. Eye Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e70108","DOI":"10.1096\/fj.202401489R","article-title":"Paricalcitol ameliorates diabetic nephropathy by promoting EETs and M2 macrophage polarization and inhibiting inflammation by regulating VDR\/CYP2J2 axis","volume":"38","author":"Tang","year":"2024","journal-title":"Faseb J."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Hwang, J., You, H., Kwon, D.H., Son, Y., Lee, G.Y., and Han, S.N. (2023). Transcriptome analysis of T cells from Ldlr(-\/-) mice and effects of in vitro vitamin D treatment. J. Nutr. Biochem.","DOI":"10.1016\/j.jnutbio.2023.109510"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.arcmed.2020.03.006","article-title":"Host Defense Peptide RNase 7 Is Down-regulated in the Skin of Diabetic Patients with or without Chronic Ulcers, and its Expression is Altered with Metformin","volume":"51","author":"Trujillo","year":"2020","journal-title":"Arch. Med. Res."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Gottlieb, C., Henrich, M., Liu, P.T., Yacoubian, V., Wang, J., Chun, R., and Adams, J.S. (2023). High-Throughput CAMP Assay (HiTCA): A Novel Tool for Evaluating the Vitamin D-Dependent Antimicrobial Response. Nutrients, 15.","DOI":"10.3390\/nu15061380"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1080\/14787210.2023.2151439","article-title":"Vitamin D attenuates biofilm-associated infections via immunomodulation and cathelicidin expression: A narrative review","volume":"21","author":"Benson","year":"2023","journal-title":"Expert. Rev. Anti. Infect. Ther."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Lowry, M.B., Guo, C., Zhang, Y., Fantacone, M.L., Logan, I.E., Campbell, Y., Zhang, W., Le, M., Indra, A.K., and Ganguli-Indra, G. (2020). A mouse model for vitamin D-induced human cathelicidin antimicrobial peptide gene expression. J. Steroid Biochem. Mol. Biol., 198.","DOI":"10.1016\/j.jsbmb.2019.105552"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1017\/S0007114512000578","article-title":"Prevalence and severity of vitamin D deficiency in patients with diabetic foot infection","volume":"109","author":"Tiwari","year":"2013","journal-title":"Br. J. Nutr."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1017\/S0007114514003018","article-title":"Vitamin D deficiency is associated with inflammatory cytokine concentrations in patients with diabetic foot infection","volume":"112","author":"Tiwari","year":"2014","journal-title":"Br. J. Nutr."},{"key":"ref_60","first-page":"474","article-title":"Evaluation of Serum Vitamin D Levels in Diabetic Foot Infections: A Cross-Sectional Study in a Tertiary Care Center in South India","volume":"44","author":"Kumar","year":"2019","journal-title":"Iran. J. Med. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.jsbmb.2018.11.013","article-title":"Vitamin D attenuates rhinovirus-induced expression of intercellular adhesion molecule-1 (ICAM-1) and platelet-activating factor receptor (PAFR) in respiratory epithelial cells","volume":"187","author":"Greiller","year":"2019","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e23003","DOI":"10.1016\/j.heliyon.2023.e23003","article-title":"Identification of angiogenesis-related genes in diabetic foot ulcer using machine learning algorithms","volume":"9","author":"Wang","year":"2023","journal-title":"Heliyon"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"13735","DOI":"10.2147\/IJN.S497041","article-title":"Nanoscale Systems for Local Activation of Hypoxia-Inducible Factor-1 Alpha: A New Approach in Diabetic Wound Management","volume":"19","author":"Saber","year":"2024","journal-title":"Int. J. Nanomed."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Kim, D.H., Meza, C.A., Clarke, H., Kim, J.S., and Hickner, R.C. (2020). Vitamin D and Endothelial Function. Nutrients, 12.","DOI":"10.3390\/nu12020575"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.1002\/ppul.25418","article-title":"Role of vitamin D-vitamin D receptor signaling on hyperoxia-induced bronchopulmonary dysplasia in neonatal rats","volume":"56","author":"Wang","year":"2021","journal-title":"Pediatr. Pulmonol."},{"key":"ref_66","first-page":"763","article-title":"Hypoxia Mediates Runt-Related Transcription Factor 2 Expression via Induction of Vascular Endothelial Growth Factor in Periodontal Ligament Stem Cells","volume":"42","author":"Xu","year":"2019","journal-title":"Mol. Cells"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"S137","DOI":"10.33549\/physiolres.933823","article-title":"Vitamin D upregulates endothelin-1, ETBR, eNOS mRNA expression and attenuates vascular remodelling and ischemia in kidney fibrosis model in mice","volume":"67","author":"Arfian","year":"2018","journal-title":"Physiol. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"455","DOI":"10.2147\/IJN.S152822","article-title":"Nanomedical studies of the restoration of nitric oxide\/peroxynitrite balance in dysfunctional endothelium by 1,25-dihydroxy vitamin D3\u2014Clinical implications for cardiovascular diseases","volume":"13","author":"Khan","year":"2018","journal-title":"Int. J. Nanomed."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1159\/000515512","article-title":"Protective Effects of 1,25 Dihydroxyvitamin D3 against High-Glucose-Induced Damage in Human Umbilical Vein Endothelial Cells Involve Activation of Nrf2 Antioxidant Signaling","volume":"58","author":"Wu","year":"2021","journal-title":"J. Vasc. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/bs.vh.2022.09.004","article-title":"Mechanisms of action of vitamin D in delaying aging and preventing disease by inhibiting oxidative stress","volume":"121","author":"Miao","year":"2023","journal-title":"Vitam. Horm."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1159\/000448713","article-title":"Hyperglycemia and Advanced Glycation End Products Regulate miR-126 Expression in Endothelial Progenitor Cells","volume":"53","author":"Li","year":"2016","journal-title":"J. Vasc. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1007\/s10753-016-0493-1","article-title":"AGEs Decreased SIRT3 Expression and SIRT3 Activation Protected AGEs-Induced EPCs\u2019 Dysfunction and Strengthened Anti-oxidant Capacity","volume":"40","author":"Chang","year":"2017","journal-title":"Inflammation"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Xiong, Y., Zhou, F., Liu, Y., Yi, Z., Wang, X., Wu, Y., and Gong, P. (2021). 1\u03b1,25-Dihydroxyvitamin D3 promotes angiogenesis by alleviating AGEs-induced autophagy. Arch. Biochem. Biophys., 712.","DOI":"10.1016\/j.abb.2021.109041"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.2147\/DDDT.S222244","article-title":"1,25(OH)2D3 Strengthens the Vasculogenesis of Multipotent Mesenchymal Stromal Cells from Rat Bone Marrow by Regulating the PI3K\/AKT Pathway","volume":"14","author":"Ye","year":"2020","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s13098-024-01264-5","article-title":"High glucose-induced injury in human umbilical vein endothelial cells is alleviated by vitamin D supplementation through downregulation of TIPE1","volume":"16","author":"Liu","year":"2024","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_76","first-page":"67","article-title":"The effects of all trans retinoic acid, vitamin D3 and their combination on plasma levels of miRNA-125a-5p, miRNA-34a, and miRNA-126 in an experimental model of diabetes","volume":"12","author":"Sharifzadeh","year":"2022","journal-title":"Avicenna J. Phytomed"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1111\/j.1526-4637.2007.00347.x","article-title":"Painful diabetic neuropathy: Epidemiology, natural history, early diagnosis, and treatment options","volume":"9","author":"Veves","year":"2008","journal-title":"Pain. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2623","DOI":"10.1016\/j.neuron.2023.05.003","article-title":"New perspectives in diabetic neuropathy","volume":"111","author":"Eid","year":"2023","journal-title":"Neuron"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1007\/s001250051443","article-title":"A vitamin D3 derivative (CB1093) induces nerve growth factor and prevents neurotrophic deficits in streptozotocin-diabetic rats","volume":"42","author":"Riaz","year":"1999","journal-title":"Diabetologia"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Lu, X., Chen, Z., Lu, J., and Watsky, M.A. (2023). Effects of 1,25-Vitamin D3 and 24,25-Vitamin D3 on Corneal Nerve Regeneration in Diabetic Mice. Biomolecules, 13.","DOI":"10.3390\/biom13121754"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.3945\/jn.117.250209","article-title":"Vitamin D in the Spectrum of Prediabetes and Cardiovascular Autonomic Dysfunction","volume":"147","author":"Dimova","year":"2017","journal-title":"J. Nutr."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"4321","DOI":"10.1113\/JP279961","article-title":"Vitamin D is an endogenous partial agonist of the transient receptor potential vanilloid 1 channel","volume":"598","author":"Long","year":"2020","journal-title":"J. Physiol."},{"key":"ref_83","first-page":"229","article-title":"Investigation of antinociceptive effects of vitamin D and EB1089 in rats","volume":"34","year":"2022","journal-title":"Agri"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1002\/ejp.2017","article-title":"Role of Src kinase in regulating protein kinase C mediated phosphorylation of TRPV1","volume":"26","author":"Robilotto","year":"2022","journal-title":"Eur. J. Pain"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BCJ20200331","article-title":"Calcitriol increases frataxin levels and restores mitochondrial function in cell models of Friedreich Ataxia","volume":"478","author":"Britti","year":"2021","journal-title":"Biochem. J."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1093\/jnen\/nlad047","article-title":"Vitamin D alleviates neuronal injury in cerebral ischemia-reperfusion via enhancing the Nrf2\/HO-1 antioxidant pathway to counteract NLRP3-mediated pyroptosis","volume":"82","author":"Qiao","year":"2023","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"111585","DOI":"10.1016\/j.diabres.2024.111585","article-title":"Vitamin D deficiency increases the risk of diabetic peripheral neuropathy in elderly type 2 diabetes mellitus patients by predominantly increasing large-fiber lesions","volume":"209","author":"Fei","year":"2024","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e3679","DOI":"10.1002\/dmrr.3679","article-title":"Vitamin D and diabetic peripheral neuropathy: A multi-centre nerve conduction study among Chinese patients with type 2 diabetes","volume":"39","author":"Pang","year":"2023","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e3361","DOI":"10.1002\/dmrr.3361","article-title":"Vitamin D deficiency is associated with painful diabetic neuropathy","volume":"37","author":"Alam","year":"2021","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.clinthera.2022.03.012","article-title":"Vitamin D in the Prevention and Treatment of Diabetic Neuropathy","volume":"44","author":"Putz","year":"2022","journal-title":"Clin. Ther."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1097\/01.ASW.0000559614.90819.45","article-title":"25-Hydroxyvitamin D Deficiency: Impacting Deep-Wound Infection and Poor Healing Outcomes in Patients With Diabetes","volume":"32","author":"Smart","year":"2019","journal-title":"Adv. Skin. Wound Care"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1111\/jdi.13917","article-title":"Association of vitamin\u2009D status with all-cause mortality and outcomes among Chinese individuals with diabetic foot ulcers","volume":"14","author":"Tang","year":"2023","journal-title":"J. Diabetes Investig."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.clnesp.2023.01.011","article-title":"Vitamin D as adjuvant therapy for diabetic foot ulcers: Systematic review and meta-analysis approach","volume":"54","author":"Kinesya","year":"2023","journal-title":"Clin. Nutr. ESPEN"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/j.jdiacomp.2016.06.017","article-title":"The effects of vitamin D supplementation on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double-blind, placebo-controlled trial","volume":"31","author":"Razzaghi","year":"2017","journal-title":"J. Diabetes Complications"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2701","DOI":"10.26452\/ijrps.v11i2.2290","article-title":"To study the effect of oral vitamin D supplements on wound healing in patient with diabetic foot ulcer and its effect on lipid metabolism","volume":"11","author":"Kamble","year":"2020","journal-title":"Int. J. Res. Pharm. Sci."},{"key":"ref_96","first-page":"164","article-title":"Comparative effect of two different doses of vitamin D on diabetic foot ulcer and inflammatory indices among the type 2 diabetic patients a randomized clinical trial","volume":"8","author":"MoeinTavakkoli","year":"2017","journal-title":"Iran. J. Diabetes Obes."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Halschou-Jensen, P.M., Sauer, J., Bouchelouche, P., Fabrin, J., Brorson, S., and Ohrt-Nissen, S. (2021). Improved Healing of Diabetic Foot Ulcers After High-dose Vitamin D: A Randomized Double-blinded Clinical Trial. Int. J. Low Extrem. Wounds, 15347346211020268.","DOI":"10.1177\/15347346211020268"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"459","DOI":"10.23736\/S2724-5985.21.02955-7","article-title":"The enigma of vitamin D supplementation in aging with obesity","volume":"68","author":"Perna","year":"2022","journal-title":"Minerva Gastroenterol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1093\/ndt\/gfx080","article-title":"Clinical practice recommendations for treatment with active vitamin D analogues in children with chronic kidney disease Stages 2-5 and on dialysis","volume":"32","author":"Shroff","year":"2017","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_100","first-page":"95","article-title":"Cost-effectiveness analysis of intravenous paricalcitol vs. oral calcitriol in the treatment of hyperparathyroidism secondary to chronic kidney disease","volume":"45","author":"Cardoso","year":"2023","journal-title":"J. Bras. Nefrol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1039\/c6pp00280c","article-title":"Challenge and perspective: The relevance of ultraviolet (UV) radiation and the vitamin D endocrine system (VDES) for psoriasis and other inflammatory skin diseases","volume":"16","author":"Reichrath","year":"2017","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Gisondi, P., Gracia-Caza\u00f1a, T., Kurzen, H., and Galv\u00e1n, J. (2024). Calcipotriol\/Betamethasone Dipropionate for the Treatment of Psoriasis: Mechanism of Action and Evidence of Efficacy and Safety versus Topical Corticosteroids. J. Clin. Med., 13.","DOI":"10.3390\/jcm13154484"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Lu, X., Chen, Z., Lu, J., and Watsky, M. (2023). Effects of Topical 1,25 and 24,25 Vitamin D on Diabetic, Vitamin D Deficient and Vitamin D Receptor Knockout Mouse Corneal Wound Healing. Biomolecules, 13.","DOI":"10.3390\/biom13071065"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.ijbiomac.2021.03.108","article-title":"Vitamin D3-loaded electrospun cellulose acetate\/polycaprolactone nanofibers: Characterization, in-vitro drug release and cytotoxicity studies","volume":"181","author":"Wsoo","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/s13534-020-00155-8","article-title":"A promising wound dressing based on alginate hydrogels containing vitamin D3 cross-linked by calcium carbonate\/d-glucono-\u03b4-lactone","volume":"10","author":"Ehterami","year":"2020","journal-title":"Biomed. Eng. Lett."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"20417314221122089","DOI":"10.1177\/20417314221122089","article-title":"Controlled vitamin D delivery with injectable hyaluronic acid-based hydrogel for restoration of tendinopathy","volume":"13","author":"Kim","year":"2022","journal-title":"J. Tissue Eng."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1007\/s10068-024-01806-7","article-title":"Rice flour-based filled hydrogel: An effective vitamin D encapsulation system as influenced by rice flour variety","volume":"34","author":"Kim","year":"2025","journal-title":"Food Sci. Biotechnol."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Brahmbhatt, A., NievesTorres, E., Yang, B., Edwards, W.D., Roy Chaudhury, P., Lee, M.K., Kong, H., Mukhopadhyay, D., Kumar, R., and Misra, S. (2014). The role of Iex-1 in the pathogenesis of venous neointimal hyperplasia associated with hemodialysis arteriovenous fistula. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0102542"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Cai, C., Kilari, S., Zhao, C., Singh, A.K., Simeon, M.L., Misra, A., Li, Y., Takahashi, E., Kumar, R., and Misra, S. (2021). Adventitial delivery of nanoparticles encapsulated with 1\u03b1, 25-dihydroxyvitamin D3 attenuates restenosis in a murine angioplasty model. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-84444-x"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2377960818789027","DOI":"10.1177\/2377960818789027","article-title":"Diabetic Foot Ulcers and Vitamin D Status: A Literature Review","volume":"4","author":"Macido","year":"2018","journal-title":"SAGE Open Nurs."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1579631","DOI":"10.1080\/2000625X.2019.1579631","article-title":"Serum vitamin D and diabetic foot complications","volume":"10","author":"Greenhagen","year":"2019","journal-title":"Diabet. Foot Ankle"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"512","DOI":"10.2174\/1573399816999201012195735","article-title":"Vitamin D Supplementation in Diabetic Foot Ulcers: A Current Perspective","volume":"17","author":"Kurian","year":"2021","journal-title":"Curr. Diabetes Rev."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Liu, L., Zhang, F., Jamali, M., Guimar\u00e3es, N.S., Radkhah, N., Jamilian, P., and Wang, Q. (2024). The role of vitamin D in diabetic foot ulcer; an umbrella review of meta-analyses. Front. 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