{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T21:16:14Z","timestamp":1788297374568,"version":"build-2803163510"},"reference-count":30,"publisher":"American Chemical Society (ACS)","issue":"1","license":[{"start":{"date-parts":[[2015,10,29]],"date-time":"2015-10-29T00:00:00Z","timestamp":1446076800000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["1R01DK087806"],"award-info":[{"award-number":["1R01DK087806"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["1R01DK100974-01"],"award-info":[{"award-number":["1R01DK100974-01"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["U24 DK097154"],"award-info":[{"award-number":["U24 DK097154"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100003025","name":"Interstitial Cystitis Association","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100003025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR000124"],"award-info":[{"award-number":["UL1TR000124"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003625","name":"Ministry of Health and Welfare","doi-asserted-by":"publisher","award":["HI13C0015"],"award-info":[{"award-number":["HI13C0015"]}],"id":[{"id":"10.13039\/501100003625","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2009-93144"],"award-info":[{"award-number":["2009-93144"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2011-0029572"],"award-info":[{"award-number":["2011-0029572"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2012011362"],"award-info":[{"award-number":["2012011362"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Ministry for Health, Welfare and Family Affairs","doi-asserted-by":"publisher","award":["A090715"],"award-info":[{"award-number":["A090715"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Steven Spielberg Discovery Fund in Prostate Cancer Research","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,1,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Interstitial cystitis\/painful bladder syndrome (IC) is a chronic syndrome of unknown etiology that presents with bladder pain, urinary frequency, and urgency. The lack of specific biomarkers and a poor understanding of underlying molecular mechanisms present challenges for disease diagnosis and therapy. The goals of this study were to identify noninvasive biomarker candidates for IC from urine specimens and to potentially gain new insight into disease mechanisms using a nuclear magnetic resonance (NMR)-based global metabolomics analysis of urine from female IC patients and controls. Principal component analysis (PCA) suggested that the urinary metabolome of IC and controls was clearly different, with 140 NMR peaks significantly altered in IC patients (FDR &amp;lt; 0.05) compared to that in controls. On the basis of strong correlation scores, fifteen metabolite peaks were nominated as the strongest signature of IC. Among those signals that were higher in the IC group, three peaks were annotated as tyramine, the pain-related neuromodulator. Two peaks were annotated as 2-oxoglutarate. Levels of tyramine and 2-oxoglutarate were significantly elevated in urine specimens of IC subjects. An independent analysis using mass spectrometry also showed significantly increased levels of tyramine and 2-oxoglutarate in IC patients compared to controls. Functional studies showed that 2-oxoglutarate, but not tyramine, retarded growth of normal bladder epithelial cells. These preliminary findings suggest that analysis of urine metabolites has promise in biomarker development in the context of IC.<\/jats:p>","DOI":"10.1021\/pr5007729","type":"journal-article","created":{"date-parts":[[2014,10,29]],"date-time":"2014-10-29T17:25:45Z","timestamp":1414603545000},"page":"541-548","source":"Crossref","is-referenced-by-count":33,"title":["Urinary Metabolite Profiling\nCombined with Computational\nAnalysis Predicts Interstitial Cystitis-Associated Candidate Biomarkers"],"prefix":"10.1021","volume":"14","author":[{"given":"He","family":"Wen","sequence":"first","affiliation":[{"name":"Seoul National University , , ,","place":["Seoul, Korea, 151-724"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tack","family":"Lee","sequence":"additional","affiliation":[{"name":"Inha University College of Medicine , , ,","place":["Incheon, Korea, 400-771"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungyong","family":"You","sequence":"additional","affiliation":[{"name":"Cedars-Sinai Medical Center , , , ,","place":["Los Angeles, California, United States, 90048"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo-Hwan","family":"Park","sequence":"additional","affiliation":[{"name":"Inha University College of Medicine , , ,","place":["Incheon, Korea, 400-771"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hosook","family":"Song","sequence":"additional","affiliation":[{"name":"Inha University College of Medicine , , ,","place":["Incheon, Korea, 400-771"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karyn S.","family":"Eilber","sequence":"additional","affiliation":[{"name":"Cedars-Sinai Medical Center , , , ,","place":["Los Angeles, California, United States, 90048"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer T.","family":"Anger","sequence":"additional","affiliation":[{"name":"Cedars-Sinai Medical Center , , , ,","place":["Los Angeles, California, United States, 90048"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Freeman","sequence":"additional","affiliation":[{"name":"Cedars-Sinai Medical Center , , , ,","place":["Los Angeles, California, United States, 90048"]},{"name":"University of California Los Angeles , , , ,","place":["Los Angeles, California, United States, 90095"]},{"name":"Harvard Medical School , , , ,","place":["Boston, Massachusetts, United States, 02115"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunghyouk","family":"Park","sequence":"additional","affiliation":[{"name":"Seoul National University , , ,","place":["Seoul, Korea, 151-724"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayoung","family":"Kim","sequence":"additional","affiliation":[{"name":"Cedars-Sinai Medical Center , , , ,","place":["Los Angeles, California, United States, 90048"]},{"name":"University of California Los Angeles , , , ,","place":["Los Angeles, California, United States, 90095"]},{"name":"Harvard Medical School , , , ,","place":["Boston, Massachusetts, United States, 02115"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2014,10,29]]},"reference":[{"key":"2026090116332482700_cit1","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1007\/s00192-005-1301-x","article-title":"International\nConsultation on IC \u2013 Rome, September 2004\/Forging an International\nConsensus: progress in painful bladder syndrome\/interstitial cystitis.\nReport and abstracts","volume":"16","author":"Hanno","year":"2005","journal-title":"Int. Urogynecol. J. Pelvic\nFloor Dysfunct."},{"key":"2026090116332482700_cit2","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1097\/01.ju.0000158452.15915.e2","article-title":"Psychophysical\nevidence of hypersensitivity in subjects with interstitial cystitis","volume":"173","author":"Ness","year":"2005","journal-title":"J. Urol."},{"key":"2026090116332482700_cit3","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/j.eururo.2003.11.021","article-title":"Primary\nevaluation of patients suspected of having interstitial cystitis (IC)","volume":"45","author":"Nordling","year":"2004","journal-title":"Eur. Urol."},{"key":"2026090116332482700_cit4","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1097\/00042307-200201000-00013","article-title":"Interstitial cystitis","volume":"12","author":"Warren","year":"2002","journal-title":"Curr.\nOpin. Urol."},{"key":"2026090116332482700_cit5","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1016\/S0022-5347(17)40201-1","article-title":"Clinical features and\nspectrum of light microscopic changes in interstitial\ncystitis","volume":"143","author":"Johansson","year":"1990","journal-title":"J. Urol."},{"key":"2026090116332482700_cit6","doi-asserted-by":"crossref","first-page":"2162","DOI":"10.1016\/j.juro.2011.03.064","article-title":"AUA guideline for the diagnosis and treatment of interstitial\ncystitis\/bladder pain syndrome","volume":"185","author":"Hanno","year":"2011","journal-title":"J. Urol."},{"key":"2026090116332482700_cit7","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1016\/j.urology.2005.04.011","article-title":"What is the value\nof cystoscopy with hydrodistension\nfor interstitial cystitis?","volume":"66","author":"Ottem","year":"2005","journal-title":"Urology"},{"key":"2026090116332482700_cit8","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.1016\/S0022-5347(01)63178-1","article-title":"The role of\nurinary potassium in the pathogenesis and diagnosis of interstitial\ncystitis","volume":"159","author":"Parsons","year":"1998","journal-title":"J. Urol."},{"key":"2026090116332482700_cit9","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.aca.2010.10.035","article-title":"Recent and\npotential\ndevelopments in the analysis of urine: a review","volume":"684","author":"Ryan","year":"2011","journal-title":"Anal. Chim. Acta"},{"key":"2026090116332482700_cit10","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.jpba.2013.09.025","article-title":"NMR metabolomics of human blood and\nurine in disease research","volume":"93","author":"Duarte","year":"2014","journal-title":"J. Pharm. Biomed.\nAnal."},{"key":"2026090116332482700_cit11","doi-asserted-by":"crossref","first-page":"823","DOI":"10.2174\/0929867320666131119124056","article-title":"Metabolomics\nand the diagnosis of human diseases\u2500a guide to the markers\nand pathophysiological pathways affected","volume":"21","author":"Medina","year":"2014","journal-title":"Curr.\nMed. Chem."},{"key":"2026090116332482700_cit12","doi-asserted-by":"crossref","first-page":"S54","DOI":"10.1002\/mrc.2530","article-title":"MR metabolomics\nof fecal extracts:\napplications in the study of bowel diseases","volume":"47","author":"Bezabeh","year":"2009","journal-title":"Magn. Reson. Chem."},{"key":"2026090116332482700_cit13","doi-asserted-by":"crossref","first-page":"e16641","DOI":"10.1371\/journal.pone.0016641","article-title":"An effective\nassessment of simvastatin-induced toxicity with NMR-based metabonomics\napproach","volume":"6","author":"Yang","year":"2011","journal-title":"PLoS One"},{"key":"2026090116332482700_cit14","doi-asserted-by":"crossref","first-page":"W127","DOI":"10.1093\/nar\/gks374","article-title":"MetaboAnalyst 2.0\u2500a comprehensive server for\nmetabolomic data analysis","volume":"40","author":"Xia","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"2026090116332482700_cit15","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1093\/bioinformatics\/btr392","article-title":"MetATT: a web-based metabolomics\ntool for analyzing time-series and two-factor datasets","volume":"27","author":"Xia","year":"2011","journal-title":"Bioinformatics"},{"key":"2026090116332482700_cit16","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1007\/s11626-010-9350-y","article-title":"An hTERT-immortalized human urothelial cell line that\nresponds to anti-proliferative factor","volume":"47","author":"Kim","year":"2011","journal-title":"In Vitro\nCell. Dev. Biol.: Anim."},{"key":"2026090116332482700_cit17","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.18632\/oncotarget.1744","article-title":"Diagnosis\nof bladder cancer and prediction of survival by urinary\nmetabolomics","volume":"5","author":"Jin","year":"2014","journal-title":"Oncotarget"},{"key":"2026090116332482700_cit18","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1111\/j.1526-4610.2012.02168.x","article-title":"Pathogenesis of migraine:\nrole of neuromodulators","volume":"52","author":"D\u2019Andrea","year":"2012","journal-title":"Headache"},{"key":"2026090116332482700_cit19","doi-asserted-by":"crossref","first-page":"565","DOI":"10.3109\/00365521.2012.660539","article-title":"Alpha-ketoglutarate (AKG) inhibits\nproliferation of colon adenocarcinoma cells in normoxic conditions","volume":"47","author":"Rzeski","year":"2012","journal-title":"Scand. J. Gastroenterol."},{"key":"2026090116332482700_cit20","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1111\/j.1349-7006.2009.01249.x","article-title":"Antitumor effects of 2-oxoglutarate\nthrough inhibition of angiogenesis in a murine tumor model","volume":"100","author":"Matsumoto","year":"2009","journal-title":"Cancer Sci."},{"key":"2026090116332482700_cit21","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1007\/s00216-012-6269-z","article-title":"Simultaneous determination\nof sixteen underivatized biogenic amines in human urine by HPLC\u2013MS\/MS","volume":"405","author":"Gosetti","year":"2013","journal-title":"Anal. Bioanal. Chem."},{"key":"2026090116332482700_cit22","doi-asserted-by":"crossref","first-page":"25","DOI":"10.4088\/JCP.11096su1c.04","article-title":"The transdermal\ndelivery system of monoamine oxidase inhibitors","volume":"73","author":"VanDenBerg","year":"2012","journal-title":"J. Clin. Psychiatry"},{"key":"2026090116332482700_cit23","doi-asserted-by":"crossref","first-page":"S89","DOI":"10.1007\/s10072-004-0260-1","article-title":"Contributions of\nbiochemistry to the pathogenesis of primary headaches","volume":"25","author":"D\u2019Andrea","year":"2004","journal-title":"Neurol. Sci."},{"key":"2026090116332482700_cit24","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/0304-3959(93)90204-3","article-title":"Tyramine conjugation\ndeficit in patients with chronic idiopathic temporomandibular joint\nand orofacial pain","volume":"54","author":"Aghabeigi","year":"1993","journal-title":"Pain"},{"key":"2026090116332482700_cit25","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1189\/jlb.0912433","article-title":"Biogenic amines\nactivate blood leukocytes via trace amine-associated receptors TAAR1\nand TAAR2","volume":"93","author":"Babusyte","year":"2013","journal-title":"J. Leukocte Biol."},{"key":"2026090116332482700_cit26","doi-asserted-by":"crossref","first-page":"pe38","DOI":"10.1126\/scisignal.2002353","article-title":"Intracellular signaling and the origins\nof the sensations\nof itch and pain","volume":"4","author":"Han","year":"2011","journal-title":"Sci. Signaling"},{"key":"2026090116332482700_cit27","first-page":"417","article-title":"The basic neurophysiologic concept of lower urinary\ntract function\u2500the role of vanilloid TRPV1 receptors of urinary\nbladder afferent nerve endings","volume":"21","author":"Juszczak","year":"2012","journal-title":"Adv. Clin. Exp.\nMed."},{"key":"2026090116332482700_cit28","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1002\/nau.20837","article-title":"Neural control of the\nlower urinary tract: peripheral and spinal\nmechanisms","volume":"29","author":"Birder","year":"2010","journal-title":"Neurourol. Urodyn."},{"key":"2026090116332482700_cit29","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1038\/nrd3456","article-title":"Transient receptor\npotential channels as therapeutic targets","volume":"10","author":"Moran","year":"2011","journal-title":"Nat.\nRev. Drug Discovery"},{"key":"2026090116332482700_cit30","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S0090-4295(99)00492-6","article-title":"Muscarinic\nreceptor antagonists in the treatment of overactive bladder","volume":"55","author":"Chapple","year":"2000","journal-title":"Urology"}],"container-title":["Journal of Proteome Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/pr5007729","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/14\/1\/541\/16231533\/pr5007729.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/14\/1\/541\/16231533\/pr5007729.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T20:33:31Z","timestamp":1788294811000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jprobs\/article\/14\/1\/541\/1518938\/Urinary-Metabolite-Profiling-Combined-with"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,10,29]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2014,10,29]]},"published-print":{"date-parts":[[2015,1,2]]}},"URL":"https:\/\/doi.org\/10.1021\/pr5007729","relation":{},"ISSN":["1535-3893","1535-3907"],"issn-type":[{"value":"1535-3893","type":"print"},{"value":"1535-3907","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,10,29]]}}}