{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T02:35:37Z","timestamp":1791599737105,"version":"4.3.4"},"reference-count":99,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Institute of Diabetes and Digestive and Kidney Diseases, NIH","award":["R01DK135986"],"award-info":[{"award-number":["R01DK135986"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Radiation cystitis (RC) is a clinically challenging and often progressive complication of pelvic radiotherapy, marked by urothelial injury, vascular dysfunction, chronic inflammation, and fibrotic remodeling. Early diagnosis remains elusive due to nonspecific symptoms and the absence of validated molecular tools. As a biofluid in direct contact with the irradiated bladder, urine offers a unique molecular window into RC pathogenesis. In this review, we synthesize the current landscape of urinary biomarkers associated with the acute, latent, and chronic phases of RC, including inflammatory cytokines, oxidative stress products, epithelial injury markers, extracellular vesicles, microRNAs, proteomic signatures, and metabolomic alterations. We also integrate emerging mechanistic insights such as DNA damage responses, ROS generation, mitochondrial dysfunction, urothelial barrier disruption, senescence-associated secretory phenotypes, hypoxia-driven vascular injury, and profibrotic TGF-\u03b2 signaling, all of which contribute to the release of urinary analytes. By linking phase-specific molecular pathways with corresponding urinary signatures, we highlight opportunities to leverage urine-based measurements for early detection, risk stratification, severity assessment, and therapeutic monitoring. A deeper understanding of the molecular mechanisms shaping urinary biomarker profiles will be essential for advancing precision diagnostics and improving long-term outcomes for patients with radiation cystitis.<\/jats:p>","DOI":"10.3390\/ijms27020565","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T11:13:18Z","timestamp":1767697998000},"page":"565","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Urinary Biomarkers for Radiation Cystitis: Current Insights and Future Directions"],"prefix":"10.3390","volume":"27","author":[{"given":"Rani","family":"Mahyoob","sequence":"first","affiliation":[{"name":"Department of Urology, Corewell Health William Beaumont University Hospital, Royal Oak, MI 48073, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadette M. M.","family":"Zwaans","sequence":"additional","affiliation":[{"name":"Department of Urology, Corewell Health William Beaumont University Hospital, Royal Oak, MI 48073, USA"},{"name":"Department of Urology, William Beaumont School of Medicine, Oakland University, Rochester, MI 48073, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,6]]},"reference":[{"key":"ref_1","unstructured":"Horan, N., and Cooper, J.S. (2025). Radiation Cystitis and Hyperbaric Management. StatPearls, StatPearls."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1038\/nrurol.2010.23","article-title":"Management of radiation cystitis","volume":"7","author":"Smit","year":"2010","journal-title":"Nat. Rev. Urol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1007\/s40265-015-0443-5","article-title":"A Practical Approach to the Management of Radiation-Induced Hemorrhagic Cystitis","volume":"75","author":"Liem","year":"2015","journal-title":"Drugs"},{"key":"ref_4","first-page":"57","article-title":"Challenges and Opportunities in Radiation-induced Hemorrhagic Cystitis","volume":"18","author":"Zwaans","year":"2016","journal-title":"Rev. Urol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1016\/S0022-5347(05)00658-0","article-title":"Radiation induced inflammatory changes in the mouse bladder: The role of cyclooxygenase-2","volume":"175","author":"Jaal","year":"2006","journal-title":"J. Urol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"105089","DOI":"10.1016\/j.ebiom.2024.105089","article-title":"The clinical manifestations and molecular pathogenesis of radiation fibrosis","volume":"103","author":"Fijardo","year":"2024","journal-title":"eBioMedicine"},{"key":"ref_7","first-page":"e28","article-title":"Modeling of radiation cystitis in animals: A systematic review","volume":"3","author":"Zwaans","year":"2016","journal-title":"Bladder"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/gm268","article-title":"Genetics and genomics of radiotherapy toxicity: Towards prediction","volume":"3","author":"West","year":"2011","journal-title":"Genome Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1111\/bju.16140","article-title":"Haemorrhagic cystitis: A review of management strategies and emerging treatments","volume":"132","author":"Li","year":"2023","journal-title":"BJU Int."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"159","DOI":"10.4103\/0970-1591.65380","article-title":"Hemorrhagic cystitis: A challenge to the urologist","volume":"26","author":"Manikandan","year":"2010","journal-title":"Indian. J. Urol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nrneph.2014.247","article-title":"Proteomic biomarkers in kidney disease: Issues in development and implementation","volume":"11","author":"Mischak","year":"2015","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Zwaans, B.M.M., Nicolai, H.E., Chancellor, M.B., and Lamb, L.E. (2020). Prostate cancer survivors with symptoms of radiation cystitis have elevated fibrotic and vascular proteins in urine. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0241388"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e48225","DOI":"10.2196\/48225","article-title":"Correlation Between Electronic Patient-Reported Outcomes and Biological Markers of Key Parameters in Acute Radiation Cystitis Among Patients with Prostate Cancer (RABBIO): Prospective Observational Study","volume":"10","author":"Helissey","year":"2024","journal-title":"JMIR Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.21873\/invivo.14004","article-title":"Urinary Metabolites as Biomarkers of Early Radiation Cystitis in Patients with Prostate Cancer Undergoing Radiotherapy","volume":"39","author":"Shiraishi","year":"2025","journal-title":"In Vivo"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.eururo.2010.03.014","article-title":"Urinary incontinence, overactive bladder, and other lower urinary tract symptoms: A longitudinal population-based survey in men aged 45\u2013103 years","volume":"58","author":"Malmsten","year":"2010","journal-title":"Eur. Urol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"718147","DOI":"10.1155\/2014\/718147","article-title":"A new method to make 24-hour urine collection more convenient: A validity study","volume":"2014","author":"Nabavizadeh","year":"2014","journal-title":"Int. J. Nephrol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e12093","DOI":"10.1002\/jev2.12093","article-title":"Urinary extracellular vesicles: A position paper by the Urine Task Force of the International Society for Extracellular Vesicles","volume":"10","author":"Erdbrugger","year":"2021","journal-title":"J. Extracell. Vesicles"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"206","DOI":"10.12659\/MSMBR.910087","article-title":"Correlation Between First Morning Single Void and 24-Hour Urines: The Reliability to Quantify Niacin Status","volume":"24","author":"Soldi","year":"2018","journal-title":"Med. Sci. Monit. Basic. Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Orysiak, J., Mlynarczyk, M., and Tomaszewski, P. (2022). Hydration Status in Men Working in Different Thermal Environments: A Pilot Study. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19095627"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"89","DOI":"10.11613\/BM.2014.011","article-title":"Preanalytical requirements of urinalysis","volume":"24","author":"Delanghe","year":"2014","journal-title":"Biochem. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2186","DOI":"10.1515\/cclm-2023-0327","article-title":"Urine transfer devices may impact urinary particle results: A pre-analytical study","volume":"61","author":"Debunne","year":"2023","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.jtho.2021.01.1616","article-title":"Biomarker Discovery and Validation: Statistical Considerations","volume":"16","author":"Ou","year":"2021","journal-title":"J. Thorac. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"100493","DOI":"10.1016\/j.conctc.2019.100493","article-title":"Biomarker-guided trials: Challenges in practice","volume":"16","author":"Antoniou","year":"2019","journal-title":"Contemp. Clin. Trials Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5977","DOI":"10.1158\/1078-0432.CCR-07-4534","article-title":"Validation of biomarker-based risk prediction models","volume":"14","author":"Taylor","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e053674","DOI":"10.1136\/bmjopen-2021-053674","article-title":"Biomarker discovery studies for patient stratification using machine learning analysis of omics data: A scoping review","volume":"11","author":"Glaab","year":"2021","journal-title":"BMJ Open"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1111\/bju.12291","article-title":"Chemical- and radiation-induced haemorrhagic cystitis: Current treatments and challenges","volume":"112","author":"Payne","year":"2013","journal-title":"BJU Int."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Lamb, L.E., Janicki, J.J., Bartolone, S.N., Peters, K.M., and Chancellor, M.B. (2017). Development of an interstitial cystitis risk score for bladder permeability. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0185686"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e00327-18","DOI":"10.1128\/IAI.00327-18","article-title":"Urine Cytokine and Chemokine Levels Predict Urinary Tract Infection Severity Independent of Uropathogen, Urine Bacterial Burden, Host Genetics, and Host Age","volume":"86","author":"Armbruster","year":"2018","journal-title":"Infect. Immun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"S148","DOI":"10.1002\/nau.24380","article-title":"Can radiation-induced lower urinary tract disease be ameliorated in patients treated for pelvic organ cancer: ICI-RS 2019?","volume":"39","author":"Bosch","year":"2020","journal-title":"Neurourol. Urodyn."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.21037\/tcr-20-2589","article-title":"Urological complications after radiation therapy-nothing ventured, nothing gained: A Narrative Review","volume":"10","author":"Chorbinska","year":"2021","journal-title":"Transl. Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/pro6.1215","article-title":"Clinical Guidelines for the Prevention and Treatment of Radiation-induced Bladder Injury","volume":"8","author":"Wang","year":"2024","journal-title":"Precis. Radiat. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1038\/nature08467","article-title":"The DNA-damage response in human biology and disease","volume":"461","author":"Jackson","year":"2009","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Mota, S., Ward, E.P., Bartolone, S.N., Chancellor, M.B., and Zwaans, B.M.M. (2024). Identification of Molecular Mechanisms in Radiation Cystitis: Insights from RNA Sequencing. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25052632"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1016\/j.pain.2014.05.029","article-title":"Inflammation and inflammatory control in interstitial cystitis\/bladder pain syndrome: Associations with painful symptoms","volume":"155","author":"Schrepf","year":"2014","journal-title":"Pain"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s40122-023-00559-1","article-title":"Glycosaminoglycan Replacement Therapy with Intravesical Instillations of Combined Hyaluronic Acid and Chondroitin Sulfate in Patients with Recurrent Cystitis, Post-radiation Cystitis and Bladder Pain Syndrome: A Narrative Review","volume":"13","author":"Poletajew","year":"2024","journal-title":"Pain Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.canlet.2011.12.012","article-title":"Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury","volume":"327","author":"Azzam","year":"2012","journal-title":"Cancer Lett."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1111\/bju.14516","article-title":"Current management of radiation cystitis: A review and practical guide to clinical management","volume":"123","author":"Pascoe","year":"2019","journal-title":"BJU Int."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5589","DOI":"10.7314\/APJCP.2015.16.14.5589","article-title":"Radiation Induced Cystitis and Proctitis\u2014Prediction, Assessment and Management","volume":"16","author":"Mallick","year":"2015","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1007\/s00432-015-1974-6","article-title":"Radiation-induced fibrosis: Mechanisms and implications for therapy","volume":"141","author":"Straub","year":"2015","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1126\/science.1082504","article-title":"Tumor response to radiotherapy regulated by endothelial cell apoptosis","volume":"300","author":"Paris","year":"2003","journal-title":"Science"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Helissey, C., Cavallero, S., Brossard, C., Dusaud, M., Chargari, C., and Francois, S. (2020). Chronic Inflammation and Radiation-Induced Cystitis: Molecular Background and Therapeutic Perspectives. Cells, 10.","DOI":"10.3390\/cells10010021"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1038\/nrc1950","article-title":"Preventing or reducing late side effects of radiation therapy: Radiobiology meets molecular pathology","volume":"6","author":"Bentzen","year":"2006","journal-title":"Nat. Rev. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41392-021-00762-6","article-title":"Wnt\/beta-catenin signalling: Function, biological mechanisms, and therapeutic opportunities","volume":"7","author":"Liu","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"L1006","DOI":"10.1152\/ajplung.00015.2014","article-title":"Matrix metalloproteinase-9 activates TGF-beta and stimulates fibroblast contraction of collagen gels","volume":"306","author":"Kobayashi","year":"2014","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.radonc.2004.08.021","article-title":"The radiation-induced fibroatrophic process: Therapeutic perspective via the antioxidant pathway","volume":"73","author":"Delanian","year":"2004","journal-title":"Radiother. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Klee, N.S., McCarthy, C.G., Lewis, S., McKenzie, J.L., Vincent, J.E., and Webb, R.C. (2018). Urothelial Senescence in the Pathophysiology of Diabetic Bladder Dysfunction-A Novel Hypothesis. Front. Surg., 5.","DOI":"10.3389\/fsurg.2018.00072"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1038\/s41385-022-00565-0","article-title":"The urothelium: A multi-faceted barrier against a harsh environment","volume":"15","author":"Jafari","year":"2022","journal-title":"Mucosal Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11934-024-01238-0","article-title":"Advancements in Understanding and Managing Radiation Cystitis: A Comprehensive Review","volume":"26","author":"Neckonoff","year":"2024","journal-title":"Curr. Urol. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"789","DOI":"10.2147\/JIR.S275570","article-title":"Serum and Urine Interleukin-6 and Interleukin-8 Levels Do Not Differentiate Acute Pyelonephritis from Lower Urinary Tract Infections in Children","volume":"13","year":"2020","journal-title":"J. Inflamm. Res."},{"key":"ref_50","first-page":"278715","article-title":"Chemokines as potential markers in pediatric renal diseases","volume":"2014","author":"Pereira","year":"2014","journal-title":"Dis. Markers"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Yu, W.R., Jiang, Y.H., Jhang, J.F., and Kuo, H.C. (2022). Use of Urinary Cytokine and Chemokine Levels for Identifying Bladder Conditions and Predicting Treatment Outcomes in Patients with Interstitial Cystitis\/Bladder Pain Syndrome. Biomedicines, 10.","DOI":"10.3390\/biomedicines10051149"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Liu, Y., Xu, K., Xiang, Y., Ma, B., Li, H., Li, Y., Shi, Y., Li, S., and Bai, Y. (2023). Role of MCP-1 as an inflammatory biomarker in nephropathy. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1303076"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1681\/ASN.2004080658","article-title":"Urine chemokines as biomarkers of human systemic lupus erythematosus activity","volume":"16","author":"Rovin","year":"2005","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Singh, R., Verma, A., Aljabari, S., and Vasylyeva, T.L. (2017). Urinary biomarkers as indicator of chronic inflammation and endothelial dysfunction in obese adolescents. BMC Obes., 4.","DOI":"10.1186\/s40608-017-0148-2"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2313171","DOI":"10.1080\/0886022X.2024.2313171","article-title":"Assessment of urine CCL2 as a potential diagnostic biomarker for acute kidney injury and septic acute kidney injury in intensive care unit patients","volume":"46","author":"Peng","year":"2024","journal-title":"Ren. Fail."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1002\/cncy.22767","article-title":"Urinary IL-6 and IL-8 as predictive markers in bladder urothelial carcinoma: A pilot study","volume":"132","author":"VandenBussche","year":"2024","journal-title":"Cancer Cytopathol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e769","DOI":"10.1097\/01.JU.0001109984.67114.74.17","article-title":"Radiation Cystitis and Urine Inflammatory Biomarkers Pre And Post Hyperbaric Oxygen Therapy: A Pilot Study","volume":"213","author":"Bellemare","year":"2025","journal-title":"J. Urol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"101783","DOI":"10.1016\/j.adro.2025.101783","article-title":"Induction of Cytoplasmic dsDNA and cGAS-STING Immune Signaling After Exposure of Breast Cancer Cells to X-ray or High-Energetic Carbon Ions","volume":"10","author":"Totis","year":"2025","journal-title":"Adv. Radiat. Oncol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20081386","article-title":"How mitochondria produce reactive oxygen species","volume":"417","author":"Murphy","year":"2009","journal-title":"Biochem. J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1159\/000489450","article-title":"Upregulation of NOX2 and NOX4 Mediated by TGF-beta Signaling Pathway Exacerbates Cerebral Ischemia\/Reperfusion Oxidative Stress Injury","volume":"46","author":"Lou","year":"2018","journal-title":"Cell Physiol. Biochem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2606928","DOI":"10.1155\/2022\/2606928","article-title":"Reactive Oxygen Species Bridge the Gap between Chronic Inflammation and Tumor Development","volume":"2022","author":"Yu","year":"2022","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Jiang, Y.H., Jhang, J.F., Ho, H.C., Chiou, D.Y., and Kuo, H.C. (2022). Urine Oxidative Stress Biomarkers as Novel Biomarkers in Interstitial Cystitis\/Bladder Pain Syndrome. Biomedicines, 10.","DOI":"10.3390\/biomedicines10071701"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1038\/s12276-022-00894-x","article-title":"Mitochondrial PARP1 regulates NAD(+)-dependent poly ADP-ribosylation of mitochondrial nucleoids","volume":"54","author":"Lee","year":"2022","journal-title":"Exp. Mol. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2651","DOI":"10.1158\/0008-5472.CAN-19-1527","article-title":"Secretion of Acid Sphingomyelinase and Ceramide by Endothelial Cells Contributes to Radiation-Induced Intestinal Toxicity","volume":"80","author":"Leonetti","year":"2020","journal-title":"Cancer Res."},{"key":"ref_65","unstructured":"National Library of Medicine (2025, October 31). Study of Serum and Urinary Biomarkers and Radiation Cystitis in Patients Treated with Radiotherapy for Localized Prostate Cancer (RABBIO), Available online: https:\/\/www.clinicaltrials.gov\/study\/NCT05246774."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e774","DOI":"10.1097\/01.JU.0001109984.67114.74.28","article-title":"Paired Urine and Serum Extracellular Vesicle Proteomics Identify Pre-Radiotherapy Biomarkers Of Late Radiation Cystitis Risk In Prostate Cancer Patients","volume":"213","author":"Molony","year":"2025","journal-title":"J. Urol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e00007","DOI":"10.1097\/JU9.0000000000000009","article-title":"Postradiotherapy Urinary Extracellular Vesicle Concentrations Predict Late Bladder Toxicity in Patients with Prostate Cancer","volume":"1","author":"Molony","year":"2023","journal-title":"JU Open Plus"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"C1439","DOI":"10.1152\/ajpcell.00349.2023","article-title":"Exploring the role of urinary extracellular vesicles in kidney physiology, aging, and disease progression","volume":"325","author":"Grange","year":"2023","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"217931","DOI":"10.1016\/j.canlet.2025.217931","article-title":"Extracellular vesicle proteomics identify neutrophils as potential mediators of bladder radiotoxicity in prostate cancer","volume":"631","author":"Molony","year":"2025","journal-title":"Cancer Lett."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1186\/s12964-024-01845-x","article-title":"Ionizing radiation effects on blood-derived extracellular vesicles: Insights into miR-34a-5p-mediated cellular responses and biomarker potential","volume":"22","author":"Huber","year":"2024","journal-title":"Cell Commun. Signal"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Walbrecq, G., Margue, C., Behrmann, I., and Kreis, S. (2020). Distinct Cargos of Small Extracellular Vesicles Derived from Hypoxic Cells and Their Effect on Cancer Cells. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21145071"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1007\/s13402-025-01042-z","article-title":"Pathways and outputs orchestrated in tumor microenvironment cells by hypoxia-induced tumor-derived exosomes in pan-cancer","volume":"48","author":"Capik","year":"2025","journal-title":"Cell. Oncol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/s41420-021-00670-2","article-title":"MicroRNA in extracellular vesicles regulates inflammation through macrophages under hypoxia","volume":"7","author":"Li","year":"2021","journal-title":"Cell Death Discov."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Pomatto, M.A.C., Gai, C., Bussolati, B., and Camussi, G. (2017). Extracellular Vesicles in Renal Pathophysiology. Front. Mol. Biosci., 4.","DOI":"10.3389\/fmolb.2017.00037"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e38362","DOI":"10.2196\/38362","article-title":"Correlation Between Serum and Urine Biomarkers and the Intensity of Acute Radiation Cystitis in Patients Treated with Radiation Therapy for Localized Prostate Cancer: Protocol for the Radiotoxicity Bladder Biomarkers (RABBIO) Study","volume":"12","author":"Helissey","year":"2023","journal-title":"JMIR Res. Protoc."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Konoshenko, M.Y., Bryzgunova, O.E., Lekchnov, E.A., Amelina, E.V., Yarmoschuk, S.V., Pak, S.V., and Laktionov, P.P. (2020). The Influence of Radical Prostatectomy on the Expression of Cell-Free MiRNA. Diagnostics, 10.","DOI":"10.3390\/diagnostics10080600"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.urolonc.2024.06.017","article-title":"Influence of radical prostatectomy on miRNA dynamics in urine extracellular vesicles","volume":"42","author":"Shutko","year":"2024","journal-title":"Urol. Oncol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s12032-025-02730-4","article-title":"The influence of maximal androgen blockade and radical prostatectomy on urinary extracellular vesicle miRNA expression","volume":"42","author":"Shutko","year":"2025","journal-title":"Med. Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Ljungstrom, M., and Oltra, E. (2025). Methods for Extracellular Vesicle Isolation: Relevance for Encapsulated miRNAs in Disease Diagnosis and Treatment. Genes, 16.","DOI":"10.20944\/preprints202502.0195.v1"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1681\/ASN.2020081142","article-title":"Comparing Approaches to Normalize, Quantify, and Characterize Urinary Extracellular Vesicles","volume":"32","author":"Blijdorp","year":"2021","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/nrneph.2017.148","article-title":"Isolation and characterization of urinary extracellular vesicles: Implications for biomarker discovery","volume":"13","author":"Merchant","year":"2017","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e14","DOI":"10.1097\/MCG.0b013e31819f5652","article-title":"Urine-based detection of intestinal tight junction loss","volume":"44","author":"Thuijls","year":"2010","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1535750","DOI":"10.1080\/20013078.2018.1535750","article-title":"Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines","volume":"7","author":"Thery","year":"2018","journal-title":"J. Extracell. Vesicles"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Li, Y., Bansal, S., Sridharan, V., Bansal, S., Jayatilake, M.M., Fernandez, J.A., Griffin, J.H., Boerma, M., and Cheema, A.K. (2023). Urinary Metabolomics for the Prediction of Radiation-Induced Cardiac Dysfunction. Metabolites, 13.","DOI":"10.3390\/metabo13040525"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"103214","DOI":"10.1016\/j.eclinm.2025.103214","article-title":"Radiation-induced cystitis treated with hyperbaric oxygen therapy (RICH-ART): Long-term follow-up of a randomised controlled, phase 2\u20133 trial","volume":"83","author":"Oscarsson","year":"2025","journal-title":"eClinicalMedicine"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Kuret, T., Sterle, I., Romih, R., and Veranic, P. (2024). Matched serum- and urine-derived biomarkers of interstitial cystitis\/bladder pain syndrome. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0309815"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/iju.12311","article-title":"Potential urine and serum biomarkers for patients with bladder pain syndrome\/interstitial cystitis","volume":"21","author":"Kuo","year":"2014","journal-title":"Int. J. Urol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s40697-016-0095-8","article-title":"Consecutive first-morning urine samples to measure change in the albumin-to-creatinine ratio: A pilot study of a home urine collection protocol","volume":"3","author":"Sontrop","year":"2016","journal-title":"Can. J. Kidney Health Dis."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.urology.2021.05.005","article-title":"Diagnostic Utility of Serum and Urinary Metabolite Analysis in Patients with Interstitial Cystitis\/Painful Bladder Syndrome","volume":"157","author":"Kim","year":"2021","journal-title":"Urology"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1093\/aje\/kwu067","article-title":"Fibrosis-related biomarkers and risk of total and cause-specific mortality: The cardiovascular health study","volume":"179","author":"Agarwal","year":"2014","journal-title":"Am. J. Epidemiol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1089\/ars.2015.6317","article-title":"Clinical Relevance of Biomarkers of Oxidative Stress","volume":"23","author":"Frijhoff","year":"2015","journal-title":"Antioxid. Redox Signal"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e70007","DOI":"10.1002\/rmv.70007","article-title":"Clinical Relevance of Oxidative Stress Biomarkers in Human Flavivirus Infections as Predictors of Disease Progression and Severity","volume":"34","author":"Hermans","year":"2024","journal-title":"Rev. Med. Virol."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Chang, H.H., Wu, S.B., and Tsai, C.C. (2024). A Review of Pathophysiology and Therapeutic Strategies Targeting TGF-beta in Graves\u2019 Ophthalmopathy. Cells, 13.","DOI":"10.3390\/cells13171493"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"174510","DOI":"10.1016\/j.ejphar.2021.174510","article-title":"TGF-beta-induced fibrosis: A review on the underlying mechanism and potential therapeutic strategies","volume":"911","author":"Ong","year":"2021","journal-title":"Eur. J. Pharmacol."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Zheng, G., and Harris, D.C.H. (2021). Editorial: TGF-beta in Human Disease: Friend or Foe?. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.739172"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Chung, J., Huda, M.N., Shin, Y., Han, S., Akter, S., Kang, I., Ha, J., Choe, W., Choi, T.G., and Kim, S.S. (2021). Correlation between Oxidative Stress and Transforming Growth Factor-Beta in Cancers. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222413181"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1080\/14737159.2025.2534962","article-title":"Regulation of biomarker analysis: What can be translated in the clinic?","volume":"25","author":"Diamantopoulos","year":"2025","journal-title":"Expert. Rev. Mol. Diagn."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1681\/ASN.2009030321","article-title":"Common sense approaches to urinary biomarker study design","volume":"20","author":"Knepper","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1080\/14737159.2016.1199962","article-title":"The importance of predictive biomarkers in oncology drug development","volume":"16","author":"Jorgensen","year":"2016","journal-title":"Expert. Rev. Mol. Diagn."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/2\/565\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T11:14:36Z","timestamp":1767698076000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/2\/565"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,6]]},"references-count":99,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["ijms27020565"],"URL":"https:\/\/doi.org\/10.3390\/ijms27020565","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,6]]}}}