{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T21:03:57Z","timestamp":1776373437024,"version":"3.51.2"},"reference-count":41,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T00:00:00Z","timestamp":1666656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010792","name":"Tungs\u2019 Taichung MetroHarbor Hospital","doi-asserted-by":"publisher","award":["TTMHH-R1110029"],"award-info":[{"award-number":["TTMHH-R1110029"]}],"id":[{"id":"10.13039\/100010792","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>The study aimed to investigate the therapeutic impact of intravesical instillation of dehydrated human amnion-chorion membrane (HACM) extracts based on the primary pathological feature of interstitial cystitis (IC). We divided 15 female Sprague-Dawley rats into three groups: sham control, IC, and treatment group. IC was induced by 400-\u00b5L lipopolysaccharide (1 \u00b5g\/\u00b5L), and it was replaced with normal saline in the sham control group. After IC induction, 300 \u00b5L dehydrated HACM extracts (3 mg\/kg) were instilled into rats\u2019 urinary bladder weekly for 3 weeks. General histology, inflammatory cytokines, NF-\u03baB, oxidative markers, and western blots results were examined. The urothelial denudation, mast-cell infiltration, and tissues fibrosis were all ameliorated. The elevated TNF-\u03b1, IL-1\u03b2, IL-6, IL-8, and NF-\u03baB were all down-regulated by dehydrated HACM extracts (p &lt; 0.05). For reactive oxygen species, increased malondialdehyde, decreased superoxide dismutase, and decreased glutathione peroxidase were all reversed (p &lt; 0.05). In apoptosis of IC, elevated Bax and suppressed Bcl-2 were improved (p &lt; 0.05) after instillation. In fibrosis, dysregulated TGF\u03b2\/R-Smads\/Snail was corrected by the instillation of dehydrated HACM (p &lt; 0.05). In conclusion, dehydrated HACM extracts could be a powerful remedy in treating IC by reconstructing the damaged urothelium, reducing mast-cell infiltration and inflammatory reactions, and ameliorating fibrotic changes.<\/jats:p>","DOI":"10.3390\/life12111693","type":"journal-article","created":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T23:50:28Z","timestamp":1666741828000},"page":"1693","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Dehydrated Human Amnion-Chorion Membrane Extracts Can Ameliorate Interstitial Cystitis in Rats by Down-Regulating Inflammatory Cytokines and Protein Coding Genes: A Preclinical Study"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2251-3379","authenticated-orcid":false,"given":"Che-Hsueh","family":"Yang","sequence":"first","affiliation":[{"name":"Division of Urology, Department of Surgery, Tungs\u2019 Taichung MetroHarbor Hospital, Taichung 435, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min-Che","family":"Tung","sequence":"additional","affiliation":[{"name":"Division of Urology, Department of Surgery, Tungs\u2019 Taichung MetroHarbor Hospital, Taichung 435, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Sheng","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Urology, Department of Surgery, Tungs\u2019 Taichung MetroHarbor Hospital, Taichung 435, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9809-7442","authenticated-orcid":false,"given":"Chao-Yu","family":"Hsu","sequence":"additional","affiliation":[{"name":"Division of Urology, Department of Surgery, Tungs\u2019 Taichung MetroHarbor Hospital, Taichung 435, Taiwan"},{"name":"PhD Program in Translational Medicine, Rong Hsing Research Center for Transitional Medicine, National Chung Hsing University, Taichung 402, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivan","family":"Akhrymuk","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kok-Tong","family":"Tan","sequence":"additional","affiliation":[{"name":"Division of General Surgery, Department of Surgery, Tungs\u2019 Taichung MetroHarbor Hospital, Taichung 435, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yen-Chuan","family":"Ou","sequence":"additional","affiliation":[{"name":"Division of Urology, Department of Surgery, Tungs\u2019 Taichung MetroHarbor Hospital, Taichung 435, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chi-Chien","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Science, The iEGG and Animal Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan"},{"name":"Department of Biotechnology, Asia University, Taichung 413, Taiwan"},{"name":"Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 406, Taiwan"},{"name":"Department of Medical Research, Taichung Veterans General Hospital, Taichung 407, Taiwan"},{"name":"Department of Pharmacology, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1002\/nau.20687","article-title":"Status of international consensus on interstitial cystitis\/bladder pain syndrome\/painful bladder syndrome: 2008 snapshot","volume":"28","author":"Hanno","year":"2009","journal-title":"Neurourol. Urodyn."},{"key":"ref_2","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 cystitis\/bladder pain syndrome","volume":"185","author":"Hanno","year":"2011","journal-title":"J. Urol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1016\/j.juro.2015.01.086","article-title":"Diagnosis and Treatment of Interstitial Cystitis\/Bladder Pain Syndrome: AUA Guideline Amendment","volume":"193","author":"Hanno","year":"2015","journal-title":"J. Urol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.eururo.2007.09.019","article-title":"Diagnostic criteria, classification, and nomenclature for painful bladder syndrome\/interstitial cystitis: An ESSIC proposal","volume":"53","author":"Nordling","year":"2008","journal-title":"Eur Urol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.juro.2011.10.040","article-title":"Comparison of an Interstitial Cystitis\/Bladder Pain Syndrome Clinical Cohort with Symptomatic Community Women from the RAND Interstitial Cystitis Epidemiology Study","volume":"187","author":"Konkle","year":"2012","journal-title":"J. Urol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.juro.2012.08.088","article-title":"The prevalence and overlap of interstitial cystitis\/bladder pain syndrome and chronic prostatitis\/chronic pelvic pain syndrome in men: Results of the RAND Interstitial Cystitis Epidemiology male study","volume":"189","author":"Suskind","year":"2013","journal-title":"J. Urol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1111\/iju.14234","article-title":"Clinical guidelines for interstitial cystitis\/bladder pain syndrome","volume":"27","author":"Homma","year":"2020","journal-title":"Int. J. Urol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S0022-5347(05)64847-1","article-title":"Prevalence of symptoms related to interstitial cystitis in women: A population based study in Finland","volume":"168","author":"Leppilahti","year":"2002","journal-title":"J. Urol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e293","DOI":"10.3346\/jkms.2021.36.e293","article-title":"Prevalence of Bladder Pain Syndrome-like Symptoms: A Population-based Study in Korea","volume":"36","author":"Lee","year":"2021","journal-title":"J. Korean Med. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.urology.2016.08.029","article-title":"Urothelial functional protein and sensory receptors in patients with interstitial cystitis\/bladder pain syndrome with and without Hunner\u2019s lesion","volume":"98","author":"Jhang","year":"2016","journal-title":"Urology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.1016\/j.urology.2006.03.084","article-title":"The Role of the Urinary Epithelium in the Pathogenesis of Interstitial Cystitis\/Prostatitis\/Urethritis","volume":"69","author":"Parsons","year":"2007","journal-title":"Urology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1016\/S0022-5347(05)67873-1","article-title":"Recruitment, distribution and phenotypes of mast cells in interstitial cystitis","volume":"163","author":"Peeker","year":"2000","journal-title":"J. Urol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S0090-4295(01)01129-3","article-title":"Mast cell involvement in interstitial cystitis: A review of human and experimental evidence","volume":"57","author":"Theoharides","year":"2001","journal-title":"Urology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S24","DOI":"10.1016\/j.urology.2006.08.1108","article-title":"Neural Upregulation in Interstitial Cystitis","volume":"69","author":"Nazif","year":"2007","journal-title":"Urology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1080\/14656566.2018.1491968","article-title":"An evaluation of the pharmacotherapy for interstitial cystitis","volume":"19","author":"Giusto","year":"2018","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1159\/000447863","article-title":"Systematic Review and Meta-Analysis of Intravesical Hyaluronic Acid and Hyaluronic Acid\/Chondroitin Sulfate Instillation for Interstitial Cystitis\/Painful Bladder Syndrome","volume":"39","author":"Pyo","year":"2016","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1002\/nau.23091","article-title":"A randomized, open-label, multicenter study of the efficacy and safety of intravesical hyaluronic acid and chondroitin sulfate versus dimethyl sulfoxide in women with bladder pain syndrome\/interstitial cystitis","volume":"36","author":"Cervigni","year":"2016","journal-title":"Neurourol. Urodyn."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1007\/s10103-018-02713-0","article-title":"Observation and mechanism study of bladder wound healing after transurethral holmium laser resection of bladder tumor","volume":"34","author":"Han","year":"2019","journal-title":"Lasers Med. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.ejphar.2014.02.013","article-title":"Evaluation of selective cannabinoid CB1 and CB2 receptor agonists in a mouse model of lipopolysaccharide-induced interstitial cystitis","volume":"729","author":"Tambaro","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"163","DOI":"10.5213\/inj.1734898.449","article-title":"Comparison of 5 Different Rat Models to Establish a Standard Animal Model for Research into Interstitial Cystitis","volume":"21","author":"Song","year":"2017","journal-title":"Int. Neurourol. J."},{"key":"ref_21","first-page":"e14724","article-title":"Choice of cystometric technique impacts detrusor contractile dynamics in wistar rats","volume":"9","author":"Hoey","year":"2021","journal-title":"Physiol. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/S0090-4295(00)00918-3","article-title":"Significance of hematuria in patients with interstitial cystitis: Review of radiographic and endoscopic findings","volume":"57","author":"Gomes","year":"2001","journal-title":"Urology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.juro.2015.06.112","article-title":"The Role of Glomerulations in Bladder Pain Syndrome: A Review","volume":"195","author":"Wennevik","year":"2015","journal-title":"J. Urol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1097\/JU.0000000000001811","article-title":"Features of Various Bladder Lesions and Their Impact on Clinical Symptoms and Recurrence in Interstitial Cystitis","volume":"206","author":"Shin","year":"2021","journal-title":"J. Urol."},{"key":"ref_25","first-page":"526","article-title":"Tumor necrosis factor-\u03b1\u2013and interleukin-6\u2013triggered mast cell development from mouse spleen cells","volume":"89","author":"Hu","year":"1997","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Wang, X., Liu, W., O\u2019Donnell, M., Lutgendorf, S., Bradley, C., Schrepf, A., Liu, L., Kreder, K., and Luo, Y. (2016). Evidence for the Role of Mast Cells in Cystitis-Associated Lower Urinary Tract Dysfunction: A Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network Animal Model Study. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0168772"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1002\/nau.23365","article-title":"Digital quantitative analysis of mast cell infiltration in interstitial cystitis","volume":"37","author":"Akiyama","year":"2017","journal-title":"Neurourol. Urodyn."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Lu, K., Wei, S., Wang, Z., Wu, K., Jiang, J., Yan, Z., and Cheng, Y. (2021). Identification of novel biomarkers in Hunner\u2019s interstitial cystitis using the CIBERSORT, an algorithm based on machine learning. BMC Urol., 21.","DOI":"10.1186\/s12894-021-00875-8"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3143","DOI":"10.2147\/IJGM.S351287","article-title":"Integrated Analysis of Microarray Studies to Identify Novel Diagnostic Markers in Bladder Pain Syndrome\/Interstitial Cystitis with Hunner Lesion","volume":"15","author":"Cheng","year":"2022","journal-title":"Int. J. Gen. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.1016\/j.juro.2015.01.036","article-title":"Are mast cells still good biomarkers for bladder pain syndrome\/interstitial cystitis?","volume":"193","author":"Gamper","year":"2015","journal-title":"J. Urol."},{"key":"ref_31","first-page":"586","article-title":"Bladder pain syndrome-does detrusor mastocytosis predict symptomatic improvement following bladder hydrodistention under anesthesia?","volume":"160","author":"Shenhar","year":"2021","journal-title":"Harefuah"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.1016\/S0022-5347(01)62224-9","article-title":"Potential role of rel\/nuclear factor-kappaB in the pathogenesis of interstitial cystitis","volume":"160","author":"Ghoniem","year":"1998","journal-title":"J. Urol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1007\/s00240-003-0339-9","article-title":"NF-kappaB-dependent gene expression of proinflammatory cytokines in T24 cells: Possible role in interstitial cystitis","volume":"31","author":"Bajwa","year":"2003","journal-title":"Urol Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6910","DOI":"10.1038\/sj.onc.1203238","article-title":"Control of apoptosis by Rel\/NF-kappaB transcription factors","volume":"18","author":"Barkett","year":"1999","journal-title":"Oncogene"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2977","DOI":"10.1016\/j.bbamcr.2016.09.012","article-title":"Activation of apoptosis signalling pathways by reactive oxygen species","volume":"1863","year":"2016","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Cell Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1177\/1756287211398255","article-title":"Role of inflammation in bladder function and interstitial cystitis","volume":"3","author":"Grover","year":"2011","journal-title":"Ther. Adv. Urol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1007\/s001920070019","article-title":"Complete Transurethral Resection of Ulcers in Classic Interstitial Cystitis","volume":"11","author":"Peeker","year":"2000","journal-title":"Int. Urogynecology J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1358\/mf.2003.25.2.723680","article-title":"Transforming growth factor-beta1 promotes contraction of collagen gel by cardiac fibroblasts through their differentiation into myofibroblasts","volume":"25","author":"LLijnen","year":"2003","journal-title":"Methods Find. Exp. Clin. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Akiyama, Y. (2021). Biomarkers in Interstitial Cystitis\/Bladder Pain Syndrome with and without Hunner Lesion: A Review and Future Perspectives. Diagnostics, 11.","DOI":"10.3390\/diagnostics11122238"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/s41598-020-80589-3","article-title":"Relationship between the frequency of electrocautery of Hunner lesions and changes in bladder capacity in patients with Hunner type interstitial cystitis","volume":"11","author":"Akiyama","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Trama, F., Illiano, E., Marchesi, A., Brancorsini, S., Crocetto, F., Pandolfo, S.D., Zucchi, A., and Costantini, E. (2021). Use of Intravesical Injections of Platelet-Rich Plasma for the Treatment of Bladder Pain Syndrome: A Comprehensive Literature Review. Antibiotics, 10.","DOI":"10.3390\/antibiotics10101194"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/12\/11\/1693\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:02:04Z","timestamp":1760144524000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/12\/11\/1693"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,25]]},"references-count":41,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["life12111693"],"URL":"https:\/\/doi.org\/10.3390\/life12111693","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,25]]}}}