{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:23:33Z","timestamp":1792686213541,"version":"4.5.0"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,11,21]],"date-time":"2017-11-21T00:00:00Z","timestamp":1511222400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,11,21]],"date-time":"2017-11-21T00:00:00Z","timestamp":1511222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cystitis cystica et glandularis (CCEG) is a chronic cystitis that causes extreme agony in affected patients. However, there are lack of effective conservative treatments. In this study, it is evident that intravesicular sodium hyaluronate (SH) therapy significantly improved the clinical symptoms of CCEG patients and ameliorated the bladder mucosal inflammation and cell proliferation characteristics of the disease. Immunohistochemical staining showed that the staining intensities of hyaluronidase (HYAL 1\/2), CD44, IL-6 and phosphorylated signal transducer and activator of transcription 3 (p-Stat3) in bladder mucosal tissue were significantly increased in CCEG patients compared with control patients and that intravesicular SH treatment suppressed these protein expression. We established a CCEG rat model by treating rats with <jats:italic>E<\/jats:italic>. <jats:italic>coli<\/jats:italic> intravesicularly, and we found that HYAL 1\/2 and CD44 expression levels were significantly increased in the <jats:italic>E<\/jats:italic>. <jats:italic>coli<\/jats:italic> group compared with the NC group. Activation of the IL-6\/JAK2\/Stat3 pathway and the expression levels of the downstream pro-apoptotic proteins Mcl-1 and Bcl-xL were also significantly increased in the <jats:italic>E<\/jats:italic>. <jats:italic>coli<\/jats:italic> group compared with the NC group. The above changes were significantly mitigated by intravesicular SH treatment. Therefore, SH may serve as an effective therapy for CCEG by inhibiting bladder mucosal inflammation and proliferation.<\/jats:p>","DOI":"10.1038\/s41598-017-16088-9","type":"journal-article","created":{"date-parts":[[2017,11,15]],"date-time":"2017-11-15T10:48:14Z","timestamp":1510742894000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Intravesicular administration of sodium hyaluronate ameliorates the inflammation and cell proliferation of cystitis cystica et glandularis involving interleukin-6\/JAK2\/Stat3 signaling pathway"],"prefix":"10.1038","volume":"7","author":[{"given":"Yongliang","family":"Ni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaohua","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxuan","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haixin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Guang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangxia","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoubin","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6493-799X","authenticated-orcid":false,"given":"Benkang","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,11,21]]},"reference":[{"key":"16088_CR1","doi-asserted-by":"publisher","first-page":"1847","DOI":"10.1148\/rg.266065126","volume":"26","author":"JJ Wong-You-Cheong","year":"2006","unstructured":"Wong-You-Cheong, J. J., Woodward, P. J., Manning, M. A. & Davis, C. J. From the archives of the AFIP: Inflammatory and nonneoplastic bladder masses: radiologic-pathologic correlation. Radiographics: a review publication of the Radiological Society of North America, Inc \n                           26, 1847\u20131868, https:\/\/doi.org\/10.1148\/rg.266065126 (2006).","journal-title":"Radiographics: a review publication of the Radiological Society of North America, Inc"},{"key":"16088_CR2","first-page":"187","volume":"50","author":"D Garcia Rojo","year":"1997","unstructured":"Garcia Rojo, D. et al. [Transformation of glandular cystitis into bladder transitional carcinoma with adenocarcinoma areas]. Archivos espanoles de urologia \n                           50, 187\u2013189 (1997).","journal-title":"Archivos espanoles de urologia"},{"key":"16088_CR3","first-page":"254","volume":"54","author":"M Medina Perez","year":"2001","unstructured":"Medina Perez, M., Valero Puerta, J. A., Valpuesta Fernandez, I. & Sanchez Gonzalez, M. [Bladder adenocarcinoma with glandular cystitis areas]. Archivos espanoles de urologia \n                           54, 254\u2013256 (2001).","journal-title":"Archivos espanoles de urologia"},{"key":"16088_CR4","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1016\/j.urology.2007.11.079","volume":"71","author":"AK Smith","year":"2008","unstructured":"Smith, A. K., Hansel, D. E. & Jones, J. S. Role of cystitis cystica et glandularis and intestinal metaplasia in development of bladder carcinoma. Urology \n                           71, 915\u2013918, https:\/\/doi.org\/10.1016\/j.urology.2007.11.079 (2008).","journal-title":"Urology"},{"key":"16088_CR5","doi-asserted-by":"publisher","first-page":"1662","DOI":"10.3892\/ol.2014.2360","volume":"8","author":"X Yi","year":"2014","unstructured":"Yi, X. et al. Cystitis glandularis: A controversial premalignant lesion. Oncology letters \n                           8, 1662\u20131664, https:\/\/doi.org\/10.3892\/ol.2014.2360 (2014).","journal-title":"Oncology letters"},{"key":"16088_CR6","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1111\/his.12661","volume":"67","author":"J Gordetsky","year":"2015","unstructured":"Gordetsky, J. & Epstein, J. I. Intestinal metaplasia of the bladder with dysplasia: a risk factor for carcinoma? Histopathology \n                           67, 325\u2013330, https:\/\/doi.org\/10.1111\/his.12661 (2015).","journal-title":"Histopathology"},{"key":"16088_CR7","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1007\/BF02832021","volume":"24","author":"Z Chen","year":"2004","unstructured":"Chen, Z., Ye, Z. & Zeng, W. Clinical investigation on the correlation between lower urinary tract infection and cystitis glandularis. Journal of Huazhong University of Science and Technology. Medical sciences\u2009=\u2009Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban=Huazhong keji daxue xuebao. Yixue Yingdewen ban \n                           24, 303\u2013304 (2004).","journal-title":"Medical sciences=Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban=Huazhong keji daxue xuebao. Yixue Yingdewen ban"},{"key":"16088_CR8","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.17435","author":"YY Xu","year":"2017","unstructured":"Xu, Y. Y. et al. Regulation of CD44v6 expression in gastric carcinoma by the IL-6\/STAT3 signaling pathway and its clinical significance. Oncotarget. https:\/\/doi.org\/10.18632\/oncotarget.17435 (2017).","journal-title":"Oncotarget"},{"key":"16088_CR9","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2017.03.012","author":"Z Culig","year":"2017","unstructured":"Culig, Z. & Puhr, M. Interleukin-6 and prostate cancer: Current developments and unsolved questions. Molecular and cellular endocrinology. https:\/\/doi.org\/10.1016\/j.mce.2017.03.012 (2017).","journal-title":"Molecular and cellular endocrinology"},{"key":"16088_CR10","doi-asserted-by":"publisher","first-page":"2020","DOI":"10.1158\/1078-0432.CCR-0437-03","volume":"10","author":"K Dvorakova","year":"2004","unstructured":"Dvorakova, K. et al. Increased expression and secretion of interleukin-6 in patients with Barrett\u2019s esophagus. Clinical cancer research: an official journal of the American Association for Cancer Research \n                           10, 2020\u20132028 (2004).","journal-title":"Clinical cancer research: an official journal of the American Association for Cancer Research"},{"key":"16088_CR11","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1016\/j.bpg.2008.03.003","volume":"22","author":"JF Flejou","year":"2008","unstructured":"Flejou, J. F. Histological assessment of oesophageal columnar mucosa. Best practice & research. Clinical gastroenterology \n                           22, 671\u2013686, https:\/\/doi.org\/10.1016\/j.bpg.2008.03.003 (2008).","journal-title":"Clinical gastroenterology"},{"issue":"Suppl 1","key":"16088_CR12","doi-asserted-by":"publisher","first-page":"11","DOI":"10.5301\/uro.5000184","volume":"83","author":"CH Klingler","year":"2016","unstructured":"Klingler, C. H. Glycosaminoglycans: how much do we know about their role in the bladder. Urologia \n                           83(Suppl 1), 11\u201314, https:\/\/doi.org\/10.5301\/uro.5000184 (2016).","journal-title":"Urologia"},{"key":"16088_CR13","doi-asserted-by":"publisher","first-page":"638","DOI":"10.3978\/j.issn.2223-4683.2015.11.04","volume":"4","author":"M Cervigni","year":"2015","unstructured":"Cervigni, M. Interstitial cystitis\/bladder pain syndrome and glycosaminoglycans replacement therapy. Translational andrology and urology \n                           4, 638\u2013642, https:\/\/doi.org\/10.3978\/j.issn.2223-4683.2015.11.04 (2015).","journal-title":"Translational andrology and urology"},{"issue":"S26","key":"16088_CR14","first-page":"S28","volume":"22","author":"N Fiander","year":"2013","unstructured":"Fiander, N. Painful bladder syndrome and interstitial cystitis: treatment options. British journal of nursing \n                           22(S26), S28\u201333 (2013).","journal-title":"British journal of nursing"},{"key":"16088_CR15","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1177\/1756287215621234","volume":"8","author":"M Lazzeri","year":"2016","unstructured":"Lazzeri, M. et al. Managing chronic bladder diseases with the administration of exogenous glycosaminoglycans: an update on the evidence. Therapeutic advances in urology \n                           8, 91\u201399, https:\/\/doi.org\/10.1177\/1756287215621234 (2016).","journal-title":"Therapeutic advances in urology"},{"key":"16088_CR16","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.actbio.2015.02.030","volume":"19","author":"P Rooney","year":"2015","unstructured":"Rooney, P., Srivastava, A., Watson, L., Quinlan, L. R. & Pandit, A. Hyaluronic acid decreases IL-6 and IL-8 secretion and permeability in an inflammatory model of interstitial cystitis. Acta biomaterialia \n                           19, 66\u201375, https:\/\/doi.org\/10.1016\/j.actbio.2015.02.030 (2015).","journal-title":"Acta biomaterialia"},{"key":"16088_CR17","doi-asserted-by":"publisher","first-page":"201","DOI":"10.3389\/fimmu.2015.00201","volume":"6","author":"S Misra","year":"2015","unstructured":"Misra, S., Hascall, V. C., Markwald, R. R. & Ghatak, S. Interactions between Hyaluronan and Its Receptors (CD44, RHAMM) Regulate the Activities of Inflammation and Cancer. Frontiers in immunology \n                           6, 201, https:\/\/doi.org\/10.3389\/fimmu.2015.00201 (2015).","journal-title":"Frontiers in immunology"},{"key":"16088_CR18","doi-asserted-by":"publisher","first-page":"1852","DOI":"10.1002\/jcb.24054","volume":"113","author":"GM Campo","year":"2012","unstructured":"Campo, G. M. et al. The inhibition of hyaluronan degradation reduced pro-inflammatory cytokines in mouse synovial fibroblasts subjected to collagen-induced arthritis. Journal of cellular biochemistry \n                           113, 1852\u20131867, https:\/\/doi.org\/10.1002\/jcb.24054 (2012).","journal-title":"Journal of cellular biochemistry"},{"key":"16088_CR19","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-016-2756-5","volume":"16","author":"D Oldenburg","year":"2016","unstructured":"Oldenburg, D. et al. CD44 and RHAMM are essential for rapid growth of bladder cancer driven by loss of Glycogen Debranching Enzyme (AGL). BMC cancer \n                           16, 713, https:\/\/doi.org\/10.1186\/s12885-016-2756-5 (2016).","journal-title":"BMC cancer"},{"key":"16088_CR20","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.cyto.2014.07.006","volume":"70","author":"L Vistejnova","year":"2014","unstructured":"Vistejnova, L. et al. Low molecular weight hyaluronan mediated CD44 dependent induction of IL-6 and chemokines in human dermal fibroblasts potentiates innate immune response. Cytokine \n                           70, 97\u2013103, https:\/\/doi.org\/10.1016\/j.cyto.2014.07.006 (2014).","journal-title":"Cytokine"},{"key":"16088_CR21","doi-asserted-by":"publisher","first-page":"14728","DOI":"10.1074\/jbc.M003965200","volume":"276","author":"T Vincent","year":"2001","unstructured":"Vincent, T., Jourdan, M., Sy, M. S., Klein, B. & Mechti, N. Hyaluronic acid induces survival and proliferation of human myeloma cells through an interleukin-6-mediated pathway involving the phosphorylation of retinoblastoma protein. The Journal of biological chemistry \n                           276, 14728\u201314736, https:\/\/doi.org\/10.1074\/jbc.M003965200 (2001).","journal-title":"The Journal of biological chemistry"},{"key":"16088_CR22","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/j.canlet.2016.04.013","volume":"376","author":"B Hu","year":"2016","unstructured":"Hu, B. et al. HIC1 attenuates invasion and metastasis by inhibiting the IL-6\/STAT3 signalling pathway in human pancreatic cancer. Cancer letters \n                           376, 387\u2013398, https:\/\/doi.org\/10.1016\/j.canlet.2016.04.013 (2016).","journal-title":"Cancer letters"},{"key":"16088_CR23","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.cellsig.2017.01.017","volume":"32","author":"Z Quan","year":"2017","unstructured":"Quan, Z. et al. Interleukin 6 induces cell proliferation of clear cell renal cell carcinoma by suppressing hepaCAM via the STAT3-dependent up-regulation of DNMT1 or DNMT3b. Cellular signalling \n                           32, 48\u201358, https:\/\/doi.org\/10.1016\/j.cellsig.2017.01.017 (2017).","journal-title":"Cellular signalling"},{"key":"16088_CR24","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1007\/s11596-007-0615-y","volume":"27","author":"X Liu","year":"2007","unstructured":"Liu, X., Chen, Z. & Ye, Z. Etiological study on cystitis glandularis caused by bacterial infection. Journal of Huazhong University of Science and Technology. Medical sciences\u2009=\u2009Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban\u2009=\u2009Huazhong keji daxue xuebao. Yixue Yingdewen ban \n                           27, 678\u2013680, https:\/\/doi.org\/10.1007\/s11596-007-0615-y (2007).","journal-title":"Medical sciences\u2009=\u2009Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban\u2009=\u2009Huazhong keji daxue xuebao. Yixue Yingdewen ban"},{"key":"16088_CR25","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1111\/iju.12752","volume":"22","author":"N Yildiz","year":"2015","unstructured":"Yildiz, N. et al. Intravesical hyaluronic acid treatment improves bacterial cystitis and reduces cystitis-induced hypercontractility in rats. International journal of urology: official journal of the Japanese Urological Association \n                           22, 598\u2013603, https:\/\/doi.org\/10.1111\/iju.12752 (2015).","journal-title":"International journal of urology: official journal of the Japanese Urological Association"},{"key":"16088_CR26","first-page":"102","volume":"17","author":"HY Lin","year":"2001","unstructured":"Lin, H. Y. et al. Cystitis glandularis mimics bladder cancer\u2013three case reports and literature review. The Kaohsiung journal of medical sciences \n                           17, 102\u2013106 (2001).","journal-title":"The Kaohsiung journal of medical sciences"},{"key":"16088_CR27","doi-asserted-by":"publisher","first-page":"E708","DOI":"10.5489\/cuaj.359","volume":"7","author":"A Li","year":"2013","unstructured":"Li, A. et al. Clinical character of cystitis glandularis accompanied with upper urinary tract obstruction. Canadian Urological Association journal\u2009=\u2009Journal de l\u2019Association des urologues du Canada \n                           7, E708\u2013710, https:\/\/doi.org\/10.5489\/cuaj.359 (2013).","journal-title":"Canadian Urological Association journal\u2009=\u2009Journal de l\u2019Association des urologues du Canada"},{"key":"16088_CR28","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1016\/j.juro.2011.12.021","volume":"187","author":"A Riaz","year":"2012","unstructured":"Riaz, A., Casalino, D. D. & Dalton, D. P. Cystitis cystica and cystitis glandularis causing ureteral obstruction. The Journal of urology \n                           187, 1059\u20131060, https:\/\/doi.org\/10.1016\/j.juro.2011.12.021 (2012).","journal-title":"The Journal of urology"},{"key":"16088_CR29","doi-asserted-by":"publisher","first-page":"55","DOI":"10.2739\/kurumemedj.37.55","volume":"37","author":"S Noda","year":"1990","unstructured":"Noda, S. & Eto, K. Histopathological studies on the cystic formation of the human urothelium. The Kurume medical journal \n                           37, 55\u201365 (1990).","journal-title":"The Kurume medical journal"},{"key":"16088_CR30","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1111\/iju.13121","volume":"23","author":"N Takizawa","year":"2016","unstructured":"Takizawa, N. et al. Novel strategy for cystitis glandularis: Oral treatment with cyclooxygenase-2 inhibitor. International journal of urology: official journal of the Japanese Urological Association \n                           23, 706\u2013708, https:\/\/doi.org\/10.1111\/iju.13121 (2016).","journal-title":"International journal of urology: official journal of the Japanese Urological Association"},{"key":"16088_CR31","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1159\/000343517","volume":"6","author":"I Raymond","year":"2012","unstructured":"Raymond, I. et al. The clinical effectiveness of intravesical sodium hyaluronate (cystistat(R)) in patients with interstitial cystitis\/painful bladder syndrome and recurrent urinary tract infections. Current urology \n                           6, 93\u201398, https:\/\/doi.org\/10.1159\/000343517 (2012).","journal-title":"Current urology"},{"key":"16088_CR32","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1007\/s00192-010-1294-y","volume":"22","author":"PF Engelhardt","year":"2011","unstructured":"Engelhardt, P. F., Morakis, N., Daha, L. K., Esterbauer, B. & Riedl, C. R. Long-term results of intravesical hyaluronan therapy in bladder pain syndrome\/interstitial cystitis. International urogynecology journal \n                           22, 401\u2013405, https:\/\/doi.org\/10.1007\/s00192-010-1294-y (2011).","journal-title":"International urogynecology journal"},{"key":"16088_CR33","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1111\/j.1464-410X.2011.10550.x","volume":"109","author":"Y Shao","year":"2012","unstructured":"Shao, Y., Lu, G. L. & Shen, Z. J. Comparison of intravesical hyaluronic acid instillation and hyperbaric oxygen in the treatment of radiation-induced hemorrhagic cystitis. BJU international \n                           109, 691\u2013694, https:\/\/doi.org\/10.1111\/j.1464-410X.2011.10550.x (2012).","journal-title":"BJU international"},{"key":"16088_CR34","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1007\/s10156-013-0609-6","volume":"19","author":"M Torella","year":"2013","unstructured":"Torella, M. et al. Intravesical therapy in recurrent cystitis: a multi-center experience. Journal of infection and chemotherapy: official journal of the Japan Society of Chemotherapy \n                           19, 920\u2013925, https:\/\/doi.org\/10.1007\/s10156-013-0609-6 (2013).","journal-title":"Journal of infection and chemotherapy: official journal of the Japan Society of Chemotherapy"},{"key":"16088_CR35","doi-asserted-by":"publisher","first-page":"e3031","DOI":"10.1371\/journal.pone.0003031","volume":"3","author":"F Wang","year":"2008","unstructured":"Wang, F. et al. HYAL1 and HYAL2 inhibit tumour growth in vivo but not in vitro. PloS one \n                           3, e3031, https:\/\/doi.org\/10.1371\/journal.pone.0003031 (2008).","journal-title":"PloS one"},{"key":"16088_CR36","doi-asserted-by":"publisher","first-page":"1429","DOI":"10.1111\/j.1742-4658.2011.08071.x","volume":"278","author":"S Misra","year":"2011","unstructured":"Misra, S. et al. Hyaluronan-CD44 interactions as potential targets for cancer therapy. The FEBS journal \n                           278, 1429\u20131443, https:\/\/doi.org\/10.1111\/j.1742-4658.2011.08071.x (2011).","journal-title":"The FEBS journal"},{"key":"16088_CR37","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1016\/j.bcp.2010.04.024","volume":"80","author":"GM Campo","year":"2010","unstructured":"Campo, G. M. et al. Small hyaluronan oligosaccharides induce inflammation by engaging both toll-like-4 and CD44 receptors in human chondrocytes. Biochemical pharmacology \n                           80, 480\u2013490, https:\/\/doi.org\/10.1016\/j.bcp.2010.04.024 (2010).","journal-title":"Biochemical pharmacology"},{"key":"16088_CR38","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.ccr.2009.01.001","volume":"15","author":"S Grivennikov","year":"2009","unstructured":"Grivennikov, S. et al. IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer. Cancer cell \n                           15, 103\u2013113, https:\/\/doi.org\/10.1016\/j.ccr.2009.01.001 (2009).","journal-title":"Cancer cell"},{"key":"16088_CR39","doi-asserted-by":"publisher","first-page":"9862","DOI":"10.1073\/pnas.1307575110","volume":"110","author":"B Hu","year":"2013","unstructured":"Hu, B. et al. Microbiota-induced activation of epithelial IL-6 signaling links inflammasome-driven inflammation with transmissible cancer. Proceedings of the National Academy of Sciences of the United States of America \n                           110, 9862\u20139867, https:\/\/doi.org\/10.1073\/pnas.1307575110 (2013).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"16088_CR40","doi-asserted-by":"publisher","first-page":"2461","DOI":"10.1016\/S0022-5347(05)65005-7","volume":"167","author":"DR Erickson","year":"2002","unstructured":"Erickson, D. R. et al. A comparison of multiple urine markers for interstitial cystitis. The Journal of urology \n                           167, 2461\u20132469 (2002).","journal-title":"The Journal of urology"},{"key":"16088_CR41","doi-asserted-by":"publisher","first-page":"1449","DOI":"10.1007\/s00192-007-0354-4","volume":"18","author":"LK Daha","year":"2007","unstructured":"Daha, L. K., Lazar, D., Simak, R. & Pfluger, H. Is there a relation between urinary interleukin-6 levels and symptoms before and after intra-vesical glycosaminoglycan substitution therapy in patients with bladder pain syndrome\/interstitial cystitis? International urogynecology journal and pelvic floor dysfunction \n                           18, 1449\u20131452, https:\/\/doi.org\/10.1007\/s00192-007-0354-4 (2007).","journal-title":"International urogynecology journal and pelvic floor dysfunction"},{"key":"16088_CR42","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1016\/j.ccr.2011.03.009","volume":"19","author":"M Lesina","year":"2011","unstructured":"Lesina, M. et al. Stat3\/Socs3 activation by IL-6 transsignaling promotes progression of pancreatic intraepithelial neoplasia and development of pancreatic cancer. Cancer cell \n                           19, 456\u2013469, https:\/\/doi.org\/10.1016\/j.ccr.2011.03.009 (2011).","journal-title":"Cancer cell"},{"key":"16088_CR43","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.ccr.2009.01.009","volume":"15","author":"J Bromberg","year":"2009","unstructured":"Bromberg, J. & Wang, T. C. Inflammation and cancer: IL-6 and STAT3 complete the link. Cancer cell \n                           15, 79\u201380, https:\/\/doi.org\/10.1016\/j.ccr.2009.01.009 (2009).","journal-title":"Cancer cell"},{"key":"16088_CR44","doi-asserted-by":"publisher","first-page":"F1038","DOI":"10.1152\/ajprenal.00110.2009","volume":"297","author":"BP Cheppudira","year":"2009","unstructured":"Cheppudira, B. P. et al. Involvement of JAK-STAT signaling\/function after cyclophosphamide-induced bladder inflammation in female rats. American journal of physiology. Renal physiology \n                           297, F1038\u20131044, https:\/\/doi.org\/10.1152\/ajprenal.00110.2009 (2009).","journal-title":"American journal of physiology. Renal physiology"},{"key":"16088_CR45","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1089\/adt.2010.0348","volume":"9","author":"N Fursov","year":"2011","unstructured":"Fursov, N., Gates, I. V., Panavas, T., Giles-Komar, J. & Powers, G. Development and utilization of activated STAT3 detection assays for screening a library of secreted proteins. Assay and drug development technologies \n                           9, 420\u2013429, https:\/\/doi.org\/10.1089\/adt.2010.0348 (2011).","journal-title":"Assay and drug development technologies"},{"key":"16088_CR46","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1158\/0008-5472.CAN-14-3558","volume":"76","author":"P Yue","year":"2016","unstructured":"Yue, P. et al. Hydroxamic Acid and Benzoic Acid-Based STAT3 Inhibitors Suppress Human Glioma and Breast Cancer Phenotypes In Vitro and In Vivo. Cancer research \n                           76, 652\u2013663, https:\/\/doi.org\/10.1158\/0008-5472.CAN-14-3558 (2016).","journal-title":"Cancer research"},{"key":"16088_CR47","doi-asserted-by":"publisher","first-page":"2570","DOI":"10.1002\/ijc.29923","volume":"138","author":"K Banerjee","year":"2016","unstructured":"Banerjee, K. & Resat, H. Constitutive activation of STAT3 in breast cancer cells: A review. International journal of cancer \n                           138, 2570\u20132578, https:\/\/doi.org\/10.1002\/ijc.29923 (2016).","journal-title":"International journal of cancer"},{"key":"16088_CR48","doi-asserted-by":"publisher","first-page":"12297","DOI":"10.3390\/ijms140612297","volume":"14","author":"D Kunze","year":"2013","unstructured":"Kunze, D., Erdmann, K., Froehner, M., Wirth, M. P. & Fuessel, S. Enhanced inhibition of bladder cancer cell growth by simultaneous knockdown of anti-apoptotic Bcl-xL and survivin in combination with chemotherapy. International journal of molecular sciences \n                           14, 12297\u201312312, https:\/\/doi.org\/10.3390\/ijms140612297 (2013).","journal-title":"International journal of molecular sciences"},{"key":"16088_CR49","doi-asserted-by":"publisher","first-page":"30887","DOI":"10.18632\/oncotarget.5134","volume":"6","author":"M Wu","year":"2015","unstructured":"Wu, M. et al. URGCP\/URG4 promotes apoptotic resistance in bladder cancer cells by activating NF-kappaB signaling. Oncotarget \n                           6, 30887\u201330901, https:\/\/doi.org\/10.18632\/oncotarget.5134 (2015).","journal-title":"Oncotarget"},{"key":"16088_CR50","doi-asserted-by":"publisher","first-page":"1302","DOI":"10.4143\/crt.2015.381","volume":"48","author":"ST Tan","year":"2016","unstructured":"Tan, S. T., Liu, S. Y. & Wu, B. TRIM29 Overexpression Promotes Proliferation and Survival of Bladder Cancer Cells through NF-kappaB Signaling. Cancer research and treatment: official journal of Korean Cancer Association \n                           48, 1302\u20131312, https:\/\/doi.org\/10.4143\/crt.2015.381 (2016).","journal-title":"Cancer research and treatment: official journal of Korean Cancer Association"},{"key":"16088_CR51","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1007\/s00380-011-0219-0","volume":"28","author":"SH Zhao","year":"2013","unstructured":"Zhao, S. H. et al. Effect of ouabain on myocardial ultrastructure and cytoskeleton during the development of ventricular hypertrophy. Heart and vessels \n                           28, 101\u2013113, https:\/\/doi.org\/10.1007\/s00380-011-0219-0 (2013).","journal-title":"Heart and vessels"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-16088-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-16088-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-16088-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T13:53:39Z","timestamp":1671803619000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-16088-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,21]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["16088"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-16088-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,21]]},"assertion":[{"value":"16 June 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 November 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 November 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"15892"}}