{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T14:59:25Z","timestamp":1785509965815,"version":"3.56.0"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>\n                    Chronic prostatitis\/chronic pelvic pain syndrome (CP\/CPPS) is a prevalent genitourinary disease that has gradually become recognized as a potential autoimmune disease. Our previous research revealed that a high-glucose diet exacerbated experimental autoimmune prostatitis (EAP), a widely used animal model of CP\/CPPS. However, its effects on the metabolism of EAP mice remain unknown. Here, we applied non-targeted metabolomics analysis of feces and enzyme-linked immunosorbent assays to identify differential metabolites in EAP mice with and without high-glucose feeding. Metabolomics analysis demonstrated significant enrichment of the vitamin digestion and absorption pathway. Glucose-fed EAP mice exhibited increased fecal excretion and reduced absorption of 1,25-dihydroxyvitamin D3 (DHVD3) into the bloodstream, accompanied by decreased expression of the vitamin D receptor (VDR) in prostate tissue.\n                    <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n                    experiments, proteomic sequencing, western blot, and flow cytometry analyses demonstrated that DHVD3 suppressed T helper 17 (Th17) cell differentiation by activating the VDR\/extracellular signal-regulated kinase (ERK) pathway. DHVD3 supplementation ameliorated Th17 responses and EAP severity in glucose-fed mice, whereas the administration of the VDR antagonist MeTC7 reversed these effects. We concluded that high-glucose feeding aggravates EAP through DHVD3\/VDR\/ERK axis-mediated Th17 differentiation. VD3 supplementation may benefit CP\/CPPS patients consuming a high-sugar diet.\n                  <\/jats:p>","DOI":"10.4103\/aja202587","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T14:01:21Z","timestamp":1785506481000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["A high-glucose diet aggravates experimental autoimmune prostatitis via DHVD3\/VDR\/ERK axis-mediated Th17 differentiation"],"prefix":"10.4103","author":[{"given":"Di","family":"Niu","sequence":"first","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China"},{"name":"Institute of Urology, Anhui Medical University, Hefei 230022, China"},{"name":"Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei 230022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao-Yu","family":"Yue","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China"},{"name":"Institute of Urology, Anhui Medical University, Hefei 230022, China"},{"name":"Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei 230022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China"},{"name":"Institute of Urology, Anhui Medical University, Hefei 230022, China"},{"name":"Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei 230022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-Ao","family":"Wei","sequence":"additional","affiliation":[{"name":"Clinical Medical College, Anhui Medical University, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Yi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China"},{"name":"Institute of Urology, Anhui Medical University, Hefei 230022, China"},{"name":"Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei 230022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China"},{"name":"Institute of Urology, Anhui Medical University, Hefei 230022, China"},{"name":"Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei 230022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He-Xi","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China"},{"name":"Institute of Urology, Anhui Medical University, Hefei 230022, China"},{"name":"Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei 230022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-Zhao","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China"},{"name":"Institute of Urology, Anhui Medical University, Hefei 230022, China"},{"name":"Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei 230022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"R1-20260731","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1111\/bju.13101","article-title":"Diagnosis and treatment of chronic bacterial prostatitis and chronic prostatitis\/chronic pelvic pain syndrome: a consensus guideline","volume":"116","author":"Rees","year":"2015","journal-title":"BJU Int"},{"key":"R2-20260731","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1016\/j.biopha.2017.08.016","article-title":"Comprehensive overview of prostatitis","volume":"94","author":"Khan","year":"2017","journal-title":"Biomed Pharmacother"},{"key":"R3-20260731","doi-asserted-by":"crossref","first-page":"898","DOI":"10.3389\/fimmu.2017.00898","article-title":"Immunological mechanisms underlying chronic pelvic pain and prostate inflammation in chronic pelvic pain syndrome","volume":"8","author":"Breser","year":"2017","journal-title":"Front Immunol"},{"key":"R4-20260731","doi-asserted-by":"crossref","first-page":"e12922","DOI":"10.1111\/and.12922","article-title":"Establishment of experimental autoimmune prostatitis model by T2 peptide in aluminium hydroxide adjuvant","volume":"50","author":"Zhang","year":"2018","journal-title":"Andrologia"},{"key":"R5-20260731","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/j.cell.2006.07.035","article-title":"The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells","volume":"126","author":"Ivanov","year":"2006","journal-title":"Cell"},{"key":"R6-20260731","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1111\/bju.15117","article-title":"Patients with chronic prostatitis\/chronic pelvic pain syndrome show T helper type 1 (Th1) and Th17 self-reactive immune responses specific to prostate and seminal antigens and diminished semen quality","volume":"126","author":"Motrich","year":"2020","journal-title":"BJU Int"},{"key":"R7-20260731","doi-asserted-by":"crossref","first-page":"14099","DOI":"10.1111\/jcmm.16021","article-title":"Single-cell multi-omics analysis presents the landscape of peripheral blood T-cell subsets in human chronic prostatitis\/chronic pelvic pain syndrome","volume":"24","author":"Zhang","year":"2020","journal-title":"J Cell Mol Med"},{"key":"R8-20260731","doi-asserted-by":"crossref","first-page":"e0125623","DOI":"10.1371\/journal.pone.0125623","article-title":"IL17 mediates pelvic pain in experimental autoimmune prostatitis (EAP)","volume":"10","author":"Murphy","year":"2015","journal-title":"PLoS One"},{"key":"R9-20260731","doi-asserted-by":"crossref","first-page":"14006","DOI":"10.1096\/fj.201902910RRR","article-title":"CaMK4-dependent phosphorylation of Akt\/mTOR underlies Th17 excessive activation in experimental autoimmune prostatitis","volume":"34","author":"Zhan","year":"2020","journal-title":"Faseb J"},{"key":"R10-20260731","doi-asserted-by":"crossref","first-page":"52","DOI":"10.3109\/10408363.2015.1084990","article-title":"Sugar consumption, metabolic disease and obesity: the state of the controversy","volume":"53","author":"Stanhope","year":"2016","journal-title":"Crit Rev Clin Lab Sci"},{"key":"R11-20260731","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.molmed.2019.08.003","article-title":"The sweet kiss breaching immunological self-tolerance","volume":"25","author":"Galgani","year":"2019","journal-title":"Trends Mol Med"},{"key":"R12-20260731","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1016\/j.jid.2020.01.020","article-title":"Short-term exposure to a Western diet induces psoriasiform dermatitis by promoting accumulation of IL-17A-producing \u03b3\u03b4 T cells","volume":"140","author":"Shi","year":"2020","journal-title":"J Invest Dermatol"},{"key":"R13-20260731","doi-asserted-by":"crossref","first-page":"5026","DOI":"10.4049\/jimmunol.1101817","article-title":"Epidermal CCR6+ \u03b3\u03b4 T cells are major producers of IL-22 and IL-17 in a murine model of psoriasiform dermatitis","volume":"187","author":"Mabuchi","year":"2011","journal-title":"J Immunol"},{"key":"R14-20260731","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.immuni.2019.08.001","article-title":"High glucose intake exacerbates autoimmunity through reactive-oxygen-species-mediated TGF-\u03b2 cytokine activation","volume":"51","author":"Zhang","year":"2019","journal-title":"Immunity"},{"key":"R15-20260731","doi-asserted-by":"crossref","first-page":"eaay6218","DOI":"10.1126\/scitranslmed.aay6218","article-title":"Dietary simple sugars alter microbial ecology in the gut and promote colitis in mice","volume":"12","author":"Khan","year":"2020","journal-title":"Sci Transl Med"},{"key":"R16-20260731","doi-asserted-by":"crossref","first-page":"17020","DOI":"10.1038\/celldisc.2017.20","article-title":"Long-term consumption of caffeine-free high sucrose cola beverages aggravates the pathogenesis of EAE in mice","volume":"3","author":"Cao","year":"2017","journal-title":"Cell Discov"},{"key":"R17-20260731","doi-asserted-by":"crossref","first-page":"111682","DOI":"10.1016\/j.intimp.2024.111682","article-title":"High glucose intake exacerbates experimental autoimmune prostatitis through mitochondrial reactive oxygen species-dependent TGF-\u03b2 activation-mediated Th17 differentiation","volume":"130","author":"Niu","year":"2024","journal-title":"Int Immunopharmacol"},{"key":"R18-20260731","doi-asserted-by":"crossref","first-page":"112669","DOI":"10.1016\/j.intimp.2024.112669","article-title":"Alcohol intake exacerbates experimental autoimmune prostatitis through gut microbiota driving cholesterol biosynthesis-mediated Th17 differentiation","volume":"139","author":"Du","year":"2024","journal-title":"Int Immunopharmacol"},{"key":"R19-20260731","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1016\/j.juro.2011.11.116","article-title":"Role of mast cells in male chronic pelvic pain","volume":"187","author":"Done","year":"2012","journal-title":"J Urol"},{"key":"R20-20260731","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1002\/pros.23252","article-title":"Chronic pelvic pain development and prostate inflammation in strains of mice with different susceptibility to experimental autoimmune prostatitis","volume":"77","author":"Breser","year":"2017","journal-title":"Prostate"},{"key":"R21-20260731","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/ni0111-5","article-title":"Diet, gut microbiota and immune responses","volume":"12","author":"Maslowski","year":"2011","journal-title":"Nat Immunol"},{"key":"R22-20260731","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.3390\/nu10111656","article-title":"Vitamin D: nutrient, hormone, and immunomodulator","volume":"10","author":"Sassi","year":"2018","journal-title":"Nutrients"},{"key":"R23-20260731","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.jsbmb.2015.01.011","article-title":"Critical roles of intestinal epithelial vitamin D receptor signaling in controlling gut mucosal inflammation","volume":"148","author":"Li","year":"2015","journal-title":"J Steroid Biochem Mol Biol"},{"key":"R24-20260731","doi-asserted-by":"crossref","first-page":"276","DOI":"10.4274\/jcrpe.2766","article-title":"Regulatory T cells and vitamin D status in children with chronic autoimmune thyroiditis","volume":"8","author":"\u015e\u0131klar","year":"2016","journal-title":"J Clin Res Pediatr Endocrinol"},{"key":"R25-20260731","doi-asserted-by":"crossref","first-page":"12222","DOI":"10.1074\/jbc.M114.621839","article-title":"The active form of vitamin D transcriptionally represses Smad7 signaling and activates extracellular signal-regulated kinase (ERK) to inhibit the differentiation of a inflammatory T helper cell subset and suppress experimental autoimmune encephalomyelitis","volume":"290","author":"Nanduri","year":"2015","journal-title":"J Biol Chem"},{"key":"R26-20260731","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1007\/s11882-013-0404-6","article-title":"Role of \u201cWestern diet\u201d in inflammatory autoimmune diseases","volume":"14","author":"Manzel","year":"2014","journal-title":"Curr Allergy Asthma Rep"},{"key":"R27-20260731","doi-asserted-by":"crossref","first-page":"988481","DOI":"10.3389\/fimmu.2022.988481","article-title":"Excessive intake of sugar: an accomplice of inflammation","volume":"13","author":"Ma","year":"2022","journal-title":"Front Immunol"},{"key":"R28-20260731","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.abb.2012.01.013","article-title":"Vitamin D 25-hydroxylase \u2013 four decades of searching, are we there yet?","volume":"523","author":"Zhu","year":"2012","journal-title":"Arch Biochem Biophys"},{"key":"R29-20260731","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1080\/10408398.2012.688897","article-title":"Vitamin D bioavailability: state of the art","volume":"55","author":"Borel","year":"2015","journal-title":"Crit Rev Food Sci Nutr"},{"key":"R30-20260731","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1111\/sji.12512","article-title":"Immunomodulatory and immunosuppressive roles of 1\u03b1,25(OH)2D3 in autoimmune diseases","volume":"85","author":"Alhassan Mohammed","year":"2017","journal-title":"Scand J Immunol"},{"key":"R31-20260731","first-page":"CD008422","article-title":"Vitamin D for the management of multiple sclerosis","volume":"9","author":"Jagannath","year":"2018","journal-title":"Cochrane Database Syst Rev"},{"key":"R32-20260731","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.3390\/jcm8091319","article-title":"Vitamin D deficiency is associated with increased disease activity in patients with inflammatory bowel disease","volume":"8","author":"Hausmann","year":"2019","journal-title":"J Clin Med"},{"key":"R33-20260731","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1111\/1756-185X.13676","article-title":"Association between circulating 25-hydroxyvitamin D and systemic lupus erythematosus: a systematic review and meta-analysis","volume":"22","author":"Guan","year":"2019","journal-title":"Int J Rheum Dis"},{"key":"R34-20260731","doi-asserted-by":"crossref","first-page":"7861","DOI":"10.1073\/pnas.93.15.7861","article-title":"1,25-Dihydroxyvitamin D3 reversibly blocks the progression of relapsing encephalomyelitis, a model of multiple sclerosis","volume":"93","author":"Cantorna","year":"1996","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R35-20260731","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1093\/jn\/128.1.68","article-title":"1,25-Dihydroxycholecalciferol inhibits the progression of arthritis in murine models of human arthritis","volume":"128","author":"Cantorna","year":"1998","journal-title":"J Nutr"},{"key":"R36-20260731","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/sji.12403","article-title":"The active metabolite of vitamin D3 as a potential immunomodulator","volume":"83","author":"Szymczak","year":"2016","journal-title":"Scand J Immunol"},{"key":"R37-20260731","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1002\/jcb.10580","article-title":"The targets of vitamin D depend on the differentiation and activation status of CD4 positive T cells","volume":"89","author":"Mahon","year":"2003","journal-title":"J Cell Biochem"},{"key":"R38-20260731","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1002\/1521-4141(200002)30:2<498::AID-IMMU498>3.0.CO;2-Q","article-title":"Inhibition of Th1 development and treatment of chronic-relapsing experimental allergic encephalomyelitis by a non-hypercalcemic analogue of 1,25-dihydroxyvitamin D3","volume":"30","author":"Mattner","year":"2000","journal-title":"Eur J Immunol"},{"key":"R39-20260731","first-page":"13","article-title":"Immunomodulatory role of vitamin D: a review","author":"Skrobot","journal-title":"Adv Exp Med Biol 2018"},{"key":"R40-20260731","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1111\/imm.12776","article-title":"1,25-dihydroxyvitamin D3-induced dendritic cells suppress experimental autoimmune encephalomyelitis by increasing proportions of the regulatory lymphocytes and reducing T helper type 1 and type 17 cells","volume":"152","author":"Xie","year":"2017","journal-title":"Immunology"},{"key":"R41-20260731","first-page":"146430","article-title":"Calcitriol alleviates global cerebral ischemia-induced cognitive impairment by reducing apoptosis regulated by VDR\/ERK signaling pathway in rat hippocampus","author":"Guo","journal-title":"Brain Res 2019"},{"key":"R42-20260731","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1159\/000453135","article-title":"Roles of 1,25(OH)2D3 and vitamin D receptor in the pathogenesis of rheumatoid arthritis and systemic lupus erythematosus by regulating the activation of CD4+ T cells and the PKC\u03b4\/ERK signaling pathway","volume":"40","author":"He","year":"2016","journal-title":"Cell Physiol Biochem"}],"container-title":["Asian Journal of Andrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/aja202587","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T14:01:27Z","timestamp":1785506487000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/aja202587"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,31]]},"references-count":42,"URL":"https:\/\/doi.org\/10.4103\/aja202587","relation":{},"ISSN":["1745-7262","1008-682X"],"issn-type":[{"value":"1745-7262","type":"print"},{"value":"1008-682X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,31]]},"assertion":[{"value":"2025-02-18","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-13","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}