{"created":"2025-06-12T00:49:39.290599+00:00","id":2000344,"links":{},"metadata":{"_buckets":{"deposit":"7c616a68-6e29-41c1-8d6a-1e338b2740cd"},"_deposit":{"created_by":20,"id":"2000344","owner":"20","owners":[20],"pid":{"revision_id":0,"type":"depid","value":"2000344"},"status":"published"},"_oai":{"id":"oai:muroran-it.repo.nii.ac.jp:02000344","sets":["41:227"]},"author_link":[],"item_1716854901627":{"attribute_name":"日付","attribute_value_mlt":[{"subitem_date_issued_datetime":"2026-03-01","subitem_date_issued_type":"Available"}]},"item_81_date_granted_17":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2025-03-24"}]},"item_81_degree_grantor_10":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"室蘭工業大学"},{"subitem_degreegrantor_language":"en","subitem_degreegrantor_name":"Muroran Institute of Technology"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"10103","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_81_degree_name_11":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（工学）","subitem_degreename_language":"ja"}]},"item_81_description_7":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"血清アミロイド A (SAA) は、アミロイドーシスの研究中に発見された最も重要なアミロ\nイド前駆体タンパク質の 1 つであるが、その凝集メカニズムはまだ十分に解明されていな\nい。SAA の凝集は AA アミロイドーシスの発症における重要なステップであるため、アミ\nロイド阻害剤はその発症を研究するためのツールとして使用できる。以前、当研究室では量\n子ドット (QD) 蛍光イメージング技術を基にアミロイド β (Aβ) 凝集阻害剤をスクリー\nニングする微量ハイスループットスクリーニング（MSHTS） システムを報告した。本研究で\nは、リン酸緩衝生理食塩水中のヒト SAA (hSAA) の凝集を報告し、蛍光顕微鏡と共焦点顕\n微鏡を使用して QD による hSAA 凝集の可視化に成功した。2 次元および3 次元画像解析に\nより、40 μM のhSAA で大量の凝集が観察され、これがin vitro における凝集の最適濃度\nであることが確認された。この発見の正確さは、チオフラビン T アッセイによって検証さ\nれた。透過型電子顕微鏡の結果から、QD が hSAA 凝集に均一に結合することが示された。\nhSAA 凝集阻害活性はロスマリン酸 (RA) によっても評価された。その結果は、Aβ 凝集に\n対して高い阻害活性を示す化合物である RA が、40 μM hSAA に対しても高い阻害活性を示\nした。これらの結果は、MSHTS システムが hSAA 凝集体の可視化と高活性阻害剤のスクリ\nーニングに効果的なツールであることを示した。\nそこで、MSHTS システムを用いて、Perilla frutescens var. crispa およびSanguisorba\ntenuijfolia var. alba 抽出物のmSAA 凝集に対する阻害活性を評価した。その結果、両抽\n出物はAβ 凝集に対して高い阻害活性を示し、50 μM のmSAA 凝集に対しても高い阻害活性\nを示した。また、1%のPerilla frutescens var. crispa およびSanguisorba tenuijfolia\nvar. alba 抽出物をマウスに投与し、臓器へのSAA 沈着を評価したところ、両抽出物を与え\nたマウスではコントロールに比べて臓器のアミロイド沈着量が低下した。これらの結果は、\nPerilla frutescens var. crispa およびSanguisorba tenuijfolia var. alba の食餌摂取\nがSAA 凝集に対する阻害効果を持ち、臓器におけるSAA 沈着を抑制することを示唆した。\n結論として、これらの抽出物はAA アミロイドーシスの予防において有望な可能性を持つが、\nその効果と作用機序をより深く理解するためには、さらなる臨床研究が必要である。","subitem_description_language":"ja","subitem_description_type":"Abstract"},{"subitem_description":"Serum amyloid A (SAA) is one of the most important precursor amyloid proteins\ndiscovered during the study of amyloidosis, but its underlying aggregation\nmechanism has not yet been well elucidated. Since SAA aggregation is a key step in\nthe pathogenesis of AA amyloidosis, amyloid inhibitors can be used as a tool to\nstudy its pathogenesis. A novel microliterscale high-throughput screening (MSHTS)\nsystem for screening amyloid β (Aβ) aggregation inhibitors was previously\nreported, utilizing quantum dot (QD) fluorescence imaging technology. In this study,\nI reported the aggregation of human SAA (hSAA) in phosphate-buffered saline, in\nwhich I successfully visualized hSAA aggregation by QD using fluorescence\nmicroscopy and confocal microscopy. Two-dimensional (2D) and three-dimensional (3D)\nimage analyses revealed large amount of aggregation at 40 μM hSAA, identified as\nthe optimal concentration for aggregation in vitro. The accuracy of this finding\nwas verified by a Thioflavin T (ThT) assay. The transmission electron microscopy\n(TEM) results showed that QD was uniformly bound to hSAA aggregation. hSAA\naggregation inhibitory activity was also evaluated by rosmarinic acid (RA). The\nresults showed that RA, which is a compound with high inhibitory activity against\nAβ aggregation, also exhibited high inhibitory activity against 40 μM hSAA. These\nresults indicate that the MSHTS system is an effective tool for visualizing hSAA\naggregation and for screening highly active inhibitors.\nTherefore, I evaluated the inhibitory activity of Perilla frutescens var. crispa\nand Sanguisorba tenuijfolia var. alba extracts on mSAA aggregation using the MSHTS\nsystem. The results showed that Perilla frutescens var. crispa and Sanguisorba\ntenuijfolia var. alba extracts had high inhibitory activity against Aβ aggregation\nand also showed high inhibitory activity against 50 μM mSAA aggregation. I\nevaluated the deposition of SAA in the organs of mice by feeding them 1% Perilla\nfrutescens var. crispa and Sanguisorba tenuijfolia var. alba extracts. The amount\nof amyloid deposition in the organs of mice fed with both extracts was lower than\nthat of the control group. These results indicate that dietary intake of Perilla\nfrutescens var. crispa and Sanguisorba tenuijfolia var. alba extracts inhibited\nthe deposition of SAA in organs. In conclusion, the potential application of the\nPerilla frutescens var. crispa and Sanguisorba tenuijfolia var. alba in the\nprevention of AA amyloidosis are promising, but further clinical studies are needed\nto fully understand their benefits and mechanisms of action.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_81_dissertation_number_13":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第548号"}]},"item_81_text_12":{"attribute_name":"学位の種別","attribute_value_mlt":[{"subitem_text_language":"ja","subitem_text_value":"課程博士"}]},"item_81_text_14":{"attribute_name":"報告番号","attribute_value_mlt":[{"subitem_text_language":"ja","subitem_text_value":"甲第548号"}]},"item_81_text_15":{"attribute_name":"学位記番号","attribute_value_mlt":[{"subitem_text_language":"ja","subitem_text_value":"博甲第548号"}]},"item_81_text_16":{"attribute_name":"研究科・専攻","attribute_value_mlt":[{"subitem_text_language":"ja","subitem_text_value":"工学研究科"}]},"item_81_version_type_24":{"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_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"embargoed access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_f1cf"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorAffiliations":[{"affiliationNames":[{"affiliationName":"室蘭工業大学","affiliationNameLang":"ja"},{"affiliationName":"Muroran Institute of Technology","affiliationNameLang":"en"}]}],"creatorNames":[{"creatorName":"Liangquan, Shi","creatorNameLang":"en"}],"familyNames":[{"familyName":"Liangquan","familyNameLang":"en"}],"givenNames":[{"givenName":"Shi","givenNameLang":"en"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2026-03-01"}],"filename":"A548.pdf","filesize":[{"value":"2 MB"}],"format":"application/pdf","url":{"objectType":"fulltext","url":"https://muroran-it.repo.nii.ac.jp/record/2000344/files/A548.pdf"},"version_id":"3f99b439-9865-42d5-8cc3-e06afc77fa77"},{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2025-06-12"}],"filename":"A548_summary.pdf","filesize":[{"value":"119 KB"}],"format":"application/pdf","url":{"objectType":"abstract","url":"https://muroran-it.repo.nii.ac.jp/record/2000344/files/A548_summary.pdf"},"version_id":"f6fa0631-9c9b-423a-8191-5b044e75b77c"}]},"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":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"In vitro evaluation of the aggregation and inhibitory activity of human serum amyloid A, and verification of the suppressive effects of Perilla frutescence var. crispa and Sanguisorba tenuijfolia var. alba on mouse AA amyloidosis","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"In vitro evaluation of the aggregation and inhibitory activity of human serum amyloid A, and verification of the suppressive effects of Perilla frutescence var. crispa and Sanguisorba tenuijfolia var. alba on mouse AA amyloidosis","subitem_title_language":"en"},{"subitem_title":"ヒト血清アミロイドA の凝集および阻害活性のin vitro 評価、お よびPerilla frutescence var. crispa とSanguisorba tenuijfolia var. alba によるマウスAA アミロイドーシス抑制効果の検証","subitem_title_language":"ja"}]},"item_type_id":"81","owner":"20","path":["227"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2025-06-12"},"publish_date":"2025-06-12","publish_status":"0","recid":"2000344","relation_version_is_last":true,"title":["In vitro evaluation of the aggregation and inhibitory activity of human serum amyloid A, and verification of the suppressive effects of Perilla frutescence var. crispa and Sanguisorba tenuijfolia var. alba on mouse AA amyloidosis"],"weko_creator_id":"20","weko_shared_id":-1},"updated":"2025-06-12T00:56:08.126290+00:00"}