{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:03:32Z","timestamp":1791241412651,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T00:00:00Z","timestamp":1692230400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurourology and Urodynamics"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction and Objective<\/jats:title><jats:p>Interstitial cystitis and bladder pain syndrome (IC\/BPS) presents with symptoms of debilitating bladder pain and is typically a diagnosis of exclusion. The cystoscopic detection of Hunner's lesions increases the likelihood of detecting tissue inflammation on bladder biopsy and increases the odds of therapeutic success with anti\u2010inflammatory drugs. However, the identification of this subgroup remains challenging with the current lack of surrogate biomarkers of IC\/BPS. On the path towards identifying biomarkers of IC\/BPS, we modeled the dynamic evolution of inflammation in an experimental IC\/BPS rodent model using computational biological network analysis of inflammatory mediators (cytokines and chemokines) released into urine. The use of biological network analysis allows us to identify urinary proteins that could be drivers of inflammation and could therefore serve as therapeutic targets for the treatment of IC\/BPS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Rats subjected to cyclophosphamide (CYP) injection (150\u2009mg\/kg) were used as an experimental model for acute IC\/BPS (<jats:italic>n<\/jats:italic>\u2009=\u20098). Urine from each void was collected from the rats over a 12\u2010h period and was assayed for 13 inflammatory mediators using Luminex\u2122. Time\u2010interval principal component analysis (TI\u2010PCA) and dynamic network analysis (DyNA), two biological network algorithms, were used to identify biomarkers of inflammation characteristic of IC\/BPS over time.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to vehicle\u2010treated rats, nearly all inflammatory mediators were elevated significantly (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) in the urine of CYP treated rats. TI\u2010PCA highlighted that GRO\u2010KC, IL\u20105, IL\u201018, and MCP\u20101 account for the greatest variance in the inflammatory response. At early time points, DyNA indicated a positive correlation between IL\u20104 and IL\u20101\u03b2 and between TNF\u2010\u03b1 and IL\u20101\u03b2. Analysis of TI\u2010PCA and DyNA at later time points showed the emergence of IL\u20105, IL\u20106, and IFN\u03b3 as additional key mediators of inflammation. Furthermore, DyNA network complexity rose and fell before peaking at 9.5\u2009h following CYP treatment. This pattern of inflammation may mimic the fluctuating severity of inflammation associated with IC\/BPS flares.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Computational analysis of inflammation networks in experimental IC\/BPS analysis expands on the previously accepted inflammatory signatures of IC by adding IL\u20105, IL\u201018, and MCP\u20101 to the prior studies implicating IL\u20106 and GRO as IC\/BPS biomarkers. This analysis supports a complex evolution of inflammatory networks suggestive of the rise and fall of inflammation characteristic of IC\/BPS flares.<\/jats:p><\/jats:sec>","DOI":"10.1002\/nau.25267","type":"journal-article","created":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T21:57:14Z","timestamp":1692568634000},"page":"1839-1848","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Temporally complex inflammatory networks in an animal model reveal signatures for interstitial cystitis and bladder pain syndrome phenotype"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8990-9509","authenticated-orcid":false,"given":"Ashti M.","family":"Shah","sequence":"first","affiliation":[{"name":"University of Pittsburgh School of Medicine Pittsburgh Pennsylvania 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of Urology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jocelyn","family":"Fitzgerald","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradeep","family":"Tyagi","sequence":"additional","affiliation":[{"name":"Department of Urology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania 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