{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T18:56:59Z","timestamp":1770749819631,"version":"3.50.0"},"reference-count":39,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T00:00:00Z","timestamp":1639008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"San Diego Spina Bifida Association","award":["No grant number"],"award-info":[{"award-number":["No grant number"]}]},{"name":"Adult and Pediatric Urology of University of California San Diego (UC San Diego)","award":["No grant number"],"award-info":[{"award-number":["No grant number"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Acrolein is a metabolite of cyclophosphamide (CYP), an alkylating agent used for a wide range of benign and malignant diseases. CYP treatments are known to trigger hemorrhagic cystitis in patients and animals. Significant effort has been made to prevent CYP\/acrolein-induced cystitis, while still maintaining its therapeutic benefits. As a result, supplementary therapeutic options to mediate the protective role against CYP\/acrolein and lower doses of CYP are currently given to targeted patients, as compared to past treatments. There is still a need to further study the effects of the repeated low-dose CYP\/acrolein on the pathophysiology of the urinary bladder. In our study, a one-time treatment of acrolein and repeated low-dose acrolein triggered the thickening of the smooth muscle and lamina propria in the urinary bladder of C57BL\/6J mice, respectively. The first dose of acrolein did not trigger voiding dysfunction, but the second dose triggered high-volume low-frequency voiding. Interestingly, our new scoring criteria and concurrent behavioral assessment revealed that mice with repeated low-dose acrolein had a wider opening of eyes in response to mechanical stimuli. Our study suggests that clinical symptoms among patients undergoing prolonged low-dose CYP may differ from previously reported symptoms of CYP-induced hemorrhagic cystitis.<\/jats:p>","DOI":"10.3390\/cells10123477","type":"journal-article","created":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T21:52:32Z","timestamp":1639086752000},"page":"3477","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Repeated Low-Dose Acrolein Triggers Irreversible Lamina Propria Edema in Urinary Bladder, Transient Voiding Behavior and Widening of Eyes to Mechanical Stimuli"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6574-8656","authenticated-orcid":false,"given":"Sanghee","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Urology, University of California San Diego, San Diego, CA 92093, USA"},{"name":"Pediatric Urology, Rady Children\u2019s Hospital San Diego (RCHSD), San Diego, CA 92129, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiwoo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Urology, University of California San Diego, San Diego, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chandresh","family":"Khimji","sequence":"additional","affiliation":[{"name":"Department of Urology, University of California San Diego, San Diego, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaebeom","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Urology, University of California San Diego, San Diego, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shelle","family":"Malkmus","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pharmacology, University of California San Diego, San Diego, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Albo","sequence":"additional","affiliation":[{"name":"Department of Urology, University of California San Diego, San Diego, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tony","family":"Yaksh","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pharmacology, University of California San Diego, San Diego, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Chiang","sequence":"additional","affiliation":[{"name":"Department of Urology, University of California San Diego, San Diego, CA 92093, USA"},{"name":"Pediatric Urology, Rady Children\u2019s Hospital San Diego (RCHSD), San Diego, CA 92129, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2655","DOI":"10.1056\/NEJMoa055120","article-title":"Cyclophosphamide versus placebo in scleroderma lung disease","volume":"354","author":"Tashkin","year":"2006","journal-title":"N. 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