{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T19:12:59Z","timestamp":1780341179300,"version":"3.54.1"},"reference-count":21,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T00:00:00Z","timestamp":1706659200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T00:00:00Z","timestamp":1706659200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS\u20102023\u201000208601"],"award-info":[{"award-number":["RS\u20102023\u201000208601"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2024,6]]},"abstract":"\n Background and Objectives<\/jats:title>\n Botulinum neurotoxin (BoNT) is a substance used to treat chronic sialorrhea, muscle dystonia, and is used in cosmetic applications. Measuring the potency of BoNT is crucial because it acts even with a small amount. However, the current methods for measuring the potency of BoNT involve using two\u2010dimensional neuroblastoma cell line\u2010based methods. In this study, we aimed to develop a new method to measure the potency of BoNT using a three\u2010dimensional organoid culture system.<\/jats:p>\n <\/jats:sec>\n \n Materials and Method<\/jats:title>\n We established the optimal conditions for coculturing N2a neuronal cells with murine salivary gland organoids (SGOs). After determining the appropriate chemical concentrations, we treated the SGOs cocultured with N2a cells with BoNT type A (BoNT\/A). We confirmed the expression of salivary gland\u2010related genes and proteins using real\u2010time polymerase chain reaction (PCR) and immunofluorescence staining.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The SGOs cocultured with N2a cells showed that the dendrites or axons of neuronal cells were in contact with the outermost layer of the SGOs. When we applied acetylcholine and neostigmine to the coculture systems, the mRNA expression of\n Aqp5<\/jats:italic>\n and\n Bhlha15<\/jats:italic>\n , associated with salivary gland secretory cells, increased. However, this effect was reversed when BoNT\/A was applied, as confirmed through real\u2010time PCR.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n We found that the coculture system of SGOs and N2a neuronal cells can potentially serve as a potency testing platform for BoNT.<\/jats:p>\n <\/jats:sec>\n \n Level of Evidence<\/jats:title>\n \n NA\n Laryngoscope<\/jats:italic>\n , 134:2697\u20132704, 2024\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/lary.31312","type":"journal-article","created":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T09:19:04Z","timestamp":1706692744000},"page":"2697-2704","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Usefulness of Salivary Gland Organoids for Evaluation of the Potency of Botulinum Neurotoxin"],"prefix":"10.1002","volume":"134","author":[{"given":"Yeo\u2010Jun","family":"Yoon","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Gangnam Severance Hospital Yonsei University College of Medicine Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9757-6414","authenticated-orcid":false,"given":"Jae\u2010Yol","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Gangnam Severance Hospital Yonsei University College of Medicine Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,1,31]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"761","article-title":"Botulinum toxin: from poison to remedy","volume":"18","author":"Kessler KR","year":"1997","journal-title":"Neurotoxicology"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrurol.2015.193"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sdentj.2014.10.001"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.19.2.298-314.2006"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0101638"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.4062\/biomolther.2019.200"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41578-021-00279-y"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-30934-z"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.4161\/org.25224"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1192046"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.32167"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.5966\/sctm.2016-0083"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034516685036"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.26620"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201708051"},{"key":"e_1_2_7_17_1","first-page":"9","article-title":"3D organoid culture from adult salivary gland tissues as an modeling of salivary gland morphogenesis. Front cell","volume":"9","author":"Kim D","year":"2021","journal-title":"Dev Biol"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40659"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-022-01007-6"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.106695"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-022-02561-5"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.13475"}],"container-title":["The Laryngoscope"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/lary.31312","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/lary.31312","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/lary.31312","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T01:41:03Z","timestamp":1771378863000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/lary.31312"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,31]]},"references-count":21,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1002\/lary.31312"],"URL":"https:\/\/doi.org\/10.1002\/lary.31312","archive":["Portico"],"relation":{},"ISSN":["0023-852X","1531-4995"],"issn-type":[{"value":"0023-852X","type":"print"},{"value":"1531-4995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,31]]},"assertion":[{"value":"2023-12-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}