{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T18:30:28Z","timestamp":1792521028848,"version":"4.5.0"},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T00:00:00Z","timestamp":1691971200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T00:00:00Z","timestamp":1691971200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071045"],"award-info":[{"award-number":["82071045"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271158"],"award-info":[{"award-number":["82271158"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Cinchonine (CN) and its isomer cinchonidine (CD), two of the common cinchona alkaloids, are wildly used as antimalarial drugs. However, the effects of CN and CD on the auditory system are unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Molecular docking and molecular dynamics (MD) simulation were used for predicting effective drugs. The CCK\u20108 assay was conducted for assessing cell viability in House Ear Institute\u2010Organ of Corti 1 (HEI\u2010OC1) cells. MitoSox Red staining revealed reactive oxygen species (ROS) amounts. TMRM staining was used to assess the mitochondrial membrane potential (\u0394\u03a8m). Immunofluorescence staining of myosin 7a was used to examine hair cells (HCs) in cisplatin\u2010treated neonatal mouse cochlear explants, while TUJ\u20101 immunostaining was used for the detection of spiral ganglion neurons (SGNs). Cleaved caspase\u20103 and TUNEL immunostaining were utilized for apoptosis assessment. Immunoblot was carried out to detect PI3K\u2010AKT signaling effectors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Pretreatment with CN or CD significantly increased cell viability and reduced mitochondrial dysfunction and ROS accumulation in cisplatin\u2010treated HEI\u2010OC1 cells. Immunofluorescent staining of cochlear explants showed that CN and CD attenuated cisplatin\u2010induced damage to SGNs and HCs. Immunoblot revealed that CN and CD downregulated the expression of cleaved caspase\u20103 and activated PI3K\u2010AKT signaling in cisplatin\u2010injured HEI\u2010OC1 cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>CD and CN can reduce ototoxicity caused by cisplatin and might help treat cisplatin\u2010associated hearing loss.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.14403","type":"journal-article","created":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T05:18:07Z","timestamp":1691990287000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Cinchonine and cinchonidine alleviate cisplatin\u2010induced ototoxicity by regulating\n                    <scp>PI3K\u2010AKT<\/scp>\n                    signaling"],"prefix":"10.1111","volume":"30","author":[{"given":"Dongmei","family":"Tang","sequence":"first","affiliation":[{"name":"ENT Institute and Department of Otorhinolaryngology, Eye &amp; ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, NHC Key Laboratory of Hearing Medicine Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery First Affiliated Hospital of Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingfang","family":"Wu","sequence":"additional","affiliation":[{"name":"ENT Institute and Department of Otorhinolaryngology, Eye &amp; ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, NHC Key Laboratory of Hearing Medicine Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimeng","family":"Li","sequence":"additional","affiliation":[{"name":"ENT Institute and Department of Otorhinolaryngology, Eye &amp; ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, NHC Key Laboratory of Hearing Medicine Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cai","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery First Affiliated Hospital of Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyun","family":"Qiao","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery The Second Affiliated Hospital of Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery First Affiliated Hospital of Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery First Affiliated Hospital of Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanhuan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery First Affiliated Hospital of Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery First Affiliated Hospital of Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2248-2237","authenticated-orcid":false,"given":"Yingzi","family":"He","sequence":"additional","affiliation":[{"name":"ENT Institute and Department of Otorhinolaryngology, Eye &amp; 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