{"created":"2023-05-15T10:01:53.503163+00:00","id":6568,"links":{},"metadata":{"_buckets":{"deposit":"9db04ec5-df83-4a5e-bfb5-ca593cb29b51"},"_deposit":{"created_by":5,"id":"6568","owner":"5","owners":[5],"pid":{"revision_id":0,"type":"depid","value":"6568"},"status":"published"},"_oai":{"id":"oai:miyazaki-u.repo.nii.ac.jp:00006568","sets":["72","72:30"]},"author_link":["33941","33949","33959","33946","33940","33966","33952","33968","33967","33950","33947","33948","33942","33958","33960","33964","33956","33965","33945","33951","33943","33963","33957","33969","33961","33953","33944","33954","33955","33970"],"control_number":"6568","item_10001_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2022-09-16","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"113698","bibliographicVolumeNumber":"155","bibliographic_titles":[{"bibliographic_title":"Biomedicine & pharmacotherapy"}]}]},"item_10001_description_19":{"attribute_name":"フォーマット","attribute_value_mlt":[{"subitem_description":"application/pdf","subitem_description_type":"Other"}]},"item_10001_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Niemann-Pick disease type C （NPC） is a fatal disorder with abnormal intracellular cholesterol trafficking resulting in neurodegeneration and hepatosplenomegaly. A cyclic heptasaccharide with different degrees of substitution of 2-hydroxypropyl groups, 2-hydroxypropyl-β-cyclodextrin （HP-β-CD）, acts as a strong cholesterol solubilizer and is under investigation for treating this disease in clinical trials, but its physicochemical properties and ototoxicity remain a concern. Here, we evaluated the potential of mono-6-O-α-maltosyl-γ-CD （G2-γ-CD）, a single-maltose-branched cyclic octasaccharide with a larger cavity than HP-β-CD, for treating NPC. We identified that G2-γ-CD ameliorated NPC manifestations in model mice and showed lower ototoxicity in mice than HP-β-CD. To investigate the molecular mechanisms of action behind the differential ototoxicity of these CDs, we performed cholesterol solubility analysis, proton nuclear magnetic resonance spectroscopy, and molecular modeling, and estimated that the cholesterol inclusion mode of G2-γ-CD maintained solely the 1:1 inclusion complex, whereas that of HP-β-CD shifted to the highly-soluble 2:1 complex at higher concentrations. We predicted the associations of these differential complexations of CDs with cholesterol with the profile of disease attenuation and of the auditory cell toxicity using specific cell models. We proposed that G2-γ-CD can serve as a fine-tuned cholesterol solubilizer for treating NPC, being highly biocompatible and physicochemically suitable for clinical application.","subitem_description_type":"Abstract"}]},"item_10001_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Elsevier"}]},"item_10001_relation_13":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"36116252","subitem_relation_type_select":"PMID"}}]},"item_10001_relation_14":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1016/j.biopha.2022.113698","subitem_relation_type_select":"DOI"}}]},"item_10001_rights_15":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"© 2022 The Authors. Published by Elsevier Masson SAS."}]},"item_10001_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"1950-6007","subitem_source_identifier_type":"ISSN"}]},"item_10001_version_type_20":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Yamada, Yusei","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"33941","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Miwa, Toru","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"33942","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Nakashima, Masaki","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"33943","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Shirakawa, Aina","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"33944","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ishii, Akira","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"33945","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Namba, Nanami","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"33946","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kondo, Yuki","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"33947","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Takeo, Toru","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"33948","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Nakagata, Naomi","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"33949","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Motoyama, Keiichi","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"33950","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Higashi, Taishi","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"33951","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Arima, Hidetoshi","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"33952","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kurauchi, Yuki","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"33953","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Seki, Takahiro","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"33954","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Katsuki, Hiroshi","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"33955","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Okada, Yasuyo","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"33956","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ichikawa, Atsushi","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"33957","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Higaki, Katsumi","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"33958","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Hayashi, Ken","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"33959","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Minami, Kentaro","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"33960","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Yoshikawa, Naoki","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"33961","nameIdentifierScheme":"WEKO"}]},{"creatorAffiliations":[{"affiliationNameIdentifiers":[{"affiliationNameIdentifier":"0000000106573887","affiliationNameIdentifierScheme":"ISNI","affiliationNameIdentifierURI":"https://isni.org/isni/0000000106573887"}],"affiliationNames":[{"affiliationName":"宮崎大学","affiliationNameLang":"ja"},{"affiliationName":"University of Miyazaki","affiliationNameLang":"en"}]}],"creatorNames":[{"creatorName":"池田, 龍二","creatorNameLang":"ja"},{"creatorName":"イケダ, リュウジ","creatorNameLang":"ja-Kana"},{"creatorName":"Ikeda, Ryuji","creatorNameLang":"en"}],"familyNames":[{"familyName":"池田","familyNameLang":"ja"},{"familyName":"イケダ","familyNameLang":"ja-Kana"},{"familyName":"Ikeda","familyNameLang":"en"}],"givenNames":[{"givenName":"龍二","givenNameLang":"ja"},{"givenName":"リュウジ","givenNameLang":"ja-Kana"},{"givenName":"Ryuji","givenNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"33940","nameIdentifierScheme":"WEKO"},{"nameIdentifier":"50398278","nameIdentifierScheme":"e-Rad_Researcher","nameIdentifierURI":"https://kaken.nii.ac.jp/ja/search/?qm=50398278"}]},{"creatorNames":[{"creatorName":"Ishikawa, Yoshihide","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"33963","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kajii, Tomohito","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"33964","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Tachii, Kyoko","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"33965","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Takeda, Hiroki","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"33966","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Orita, Yorihisa","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"33967","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Matsuo, Muneaki","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"33968","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Irie, Tetsumi","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"33969","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ishitsuka, Yoichi","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"33970","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2022-10-17"}],"displaytype":"detail","filename":"1-s2.0-S0753332222010873-main.pdf","filesize":[{"value":"8.8 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"本文","url":"https://miyazaki-u.repo.nii.ac.jp/record/6568/files/1-s2.0-S0753332222010873-main.pdf"},"version_id":"ee2a6dad-696d-428c-a344-cbf9bd48e68e"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"Cholesterol","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Cyclodextrin","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Niemann–Pick disease type C","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Ototoxicity","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Physicochemical property","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Solubilization","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"Fine-tuned cholesterol solubilizer, mono-6-O-α-D-maltosyl-γ-cyclodextrin, ameliorates experimental Niemann-Pick disease type C without hearing loss.","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Fine-tuned cholesterol solubilizer, mono-6-O-α-D-maltosyl-γ-cyclodextrin, ameliorates experimental Niemann-Pick disease type C without hearing loss.","subitem_title_language":"en"}]},"item_type_id":"10001","owner":"5","path":["72","30"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2022-10-17"},"publish_date":"2022-10-17","publish_status":"0","recid":"6568","relation_version_is_last":true,"title":["Fine-tuned cholesterol solubilizer, mono-6-O-α-D-maltosyl-γ-cyclodextrin, ameliorates experimental Niemann-Pick disease type C without hearing loss."],"weko_creator_id":"5","weko_shared_id":-1},"updated":"2024-11-29T01:07:55.080708+00:00"}