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口腔マイクロバイオームの新機能:「副代謝系」の解明による口腔と全身の健康増進戦略

Research Project

Project/Area Number 23K21499
Project/Area Number (Other) 21H03151 (2021-2023)
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeMulti-year Fund (2024)
Single-year Grants (2021-2023)
Section一般
Review Section Basic Section 57080:Social dentistry-related
Research InstitutionTohoku University

Principal Investigator

高橋 信博  東北大学, 歯学研究科, 教授 (60183852)

Co-Investigator(Kenkyū-buntansha) 佐藤 拓一  新潟大学, 医歯学系, 教授 (10303132)
鷲尾 純平  東北大学, 歯学研究科, 准教授 (20400260)
坂本 光央  国立研究開発法人理化学研究所, バイオリソース研究センター, 専任研究員 (50321766)
Project Period (FY) 2021-04-01 – 2025-03-31
Project Status Granted (Fiscal Year 2024)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2024: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2023: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2022: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2021: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
Keywords口腔マイクロバイオーム / 副代謝系 / 硝酸塩代謝 / アルコール代謝 / ポリアミン代謝
Outline of Research at the Start

近年、口腔マイクロバイオーム(口腔細菌叢)と全身の健康を紐づけるものとして、口腔マイクロバイオームが持つ「見過ごされていた代謝系(副代謝系という)」が注目されている。本研究では、
1. 口腔マイクロバイオームの持つ「高血圧、がん、老化」に関わる「アルコール代謝、硝酸塩代謝、ポリアミン代謝」といった副代謝系の存在を明らかにする。
2. 副代謝系を持つ細菌を特定し、副代謝系の仕組みを明らかにする。
3. 副代謝遺伝子の網羅的解析によって、個人の持つ副代謝系の多寡と全身の健康状態との関連を探る。
4. 副代謝系を活用した健康増進戦略を提案し、口腔からの全身の健康への貢献を目指す。

Outline of Annual Research Achievements

1. 「副代謝系(エタノール代謝系)」の活性測定と細菌の同定
代表的「副代謝系」である口腔マイクロバイオームのエタノール代謝は、アルコール飲料等に含まれるエタノールを発がん性の高いアセトアルデヒドに変換し、口腔・咽頭における発がん因子の一つと考えられている。そこで、ボランティアを募り、研究倫理審査に基いてインフォームドコンセントを得たのち、口腔マイクロバイオーム(プラーク)を採取し、試料の1/2量にエタノールを加え、37℃、30分間代謝させた。代謝産物を同定・定量したところ、口腔マイクロバイオームによるエタノールからのアセトアルデヒド産生活性は個人差が大きいことが分かった。さらに、ほとんどの口腔マイクロバイオームはアセトアルデヒド分解活性も持つことが新たに明らかになった。試料の残り1/2量を血液寒天平板に播種し、エタノール産生能、アセトアルデヒド分解能を持つコロニーを検出し、菌種を同定した。これらの結果は学会にて発表し、さらに、現在、論文として投稿準備中である。
2. 「副代謝系(硝酸塩代謝系)」活性測定と細菌の同定
葉物野菜に多く含まれる硝酸塩は口腔マイクロバイオームによって亜硝酸塩に代謝され、亜硝酸塩は小腸より血液循環に吸収されて全身の血管を拡張することで高血圧を予防すると考えられている。そこで、口腔マイクロバイオームによる硝酸塩代謝活性についても並行して行い、全ての口腔マイクロバイオーム試料において硝酸塩代謝による亜硝酸産生活性が存在するものの、その個人差は大きいことが明らかになった。加えて、産生された亜硝酸塩は口腔マイクロバイオームによってさらに代謝分解されることが明らかになり、これらの活性を持つ細菌の同定と、その中の代表的細菌を用いた代謝系および代謝調節機構について現在、研究を進めている。これらの結果は学会にて発表し、現在、その一部は論文として投稿中である。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

口腔マイクロバイオームの主要な「副代謝系」として「エタノール代謝」と「硝酸塩代謝」があるが、その両者において実際の口腔マイクロバイオームにてその存在が確認され、さらに、それぞれの代謝産物であるアセトアルデヒドと亜硝酸塩をさらに代謝する活性も確認された。また、これらの代謝活性を持つ口腔細菌が特定され、代謝系や代謝制御の詳細について明らかになりつつあることから、おおむね順調に進展しているものと判断した。

Strategy for Future Research Activity

口腔マイクロバイオームの主要な「副代謝系」として「エタノール代謝」と「硝酸塩代謝」について、口腔マイクロバイオームはエタノールからのアセトアルデヒド産生活性だけではなくアセトアルデヒド分解活性を、硝酸塩からの亜硝酸塩産生活性だけではなく亜硝酸塩分解活性を持つことが明らかになった。このことは、口腔マイクロバイオームによる産生と分解のバランスが全身の疾患(アセトアルデヒドによる発がん性)及び健康(亜硝酸塩による高血圧予防)をコントロールしている可能性を示す。そこで、これらの産生と分解のバランスが何によって決定されるのかについて、口腔マイクロバイオームの細菌構成の違いや口腔環境の違い等に着目して、本研究を推進して行くこととした。

Report

(3 results)
  • 2023 Annual Research Report
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (101 results)

All 2024 2023 2022 2021 Other

All Int'l Joint Research (7 results) Journal Article (32 results) (of which Int'l Joint Research: 14 results,  Peer Reviewed: 32 results,  Open Access: 28 results) Presentation (60 results) (of which Int'l Joint Research: 24 results,  Invited: 23 results) Book (2 results)

  • [Int'l Joint Research] FISABIO Foundation(スペイン)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] 四川大学華西口腔医学院/香港大学(中国)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] FISABIO Foundation(スペイン)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] 四川大学華西口腔医学院(中国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] アイルランガ大学(インドネシア)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] FISABIO Foundation(スペイン)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] 四川大学華西口腔医学院(中国)

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Application of omics technologies in cariology research: A critical review with bibliometric analysis2024

    • Author(s)
      Zhang J.S, Huang S, Chen Z, Chu C.-H, Takahashi N, Yu O.Y
    • Journal Title

      Journal of Dentistry

      Volume: 141 Pages: 104801-104801

    • DOI

      10.1016/j.jdent.2023.104801

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Electrochemical difference between single- and poly-crystalline LaF3 for a compact and low-price fluoride ion sensor2024

    • Author(s)
      Kanda K, Yamada T, Yanagida Y, Kubota Y, Matsushita N, Mayanagi G, Washio J, Takahashi N
    • Journal Title

      Electroanalysis

      Volume: 36 Issue: 4

    • DOI

      10.1002/elan.202300318

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fluoride ion sensor based on LaF<sub>3</sub> nanocrystals prepared by low-temperature process2023

    • Author(s)
      Yamada T, Kanda K, Yanagida Y, Mayanagi G, Washio, J Takahashi N
    • Journal Title

      Journal of the Ceramic Society of Japan

      Volume: 131 Issue: 3 Pages: 31-36

    • DOI

      10.2109/jcersj2.22127

    • ISSN
      1348-6535, 1882-0743
    • Year and Date
      2023-03-01
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Green Tea-Derived Catechins Suppress the Acid Productions of Streptococcus mutans and Enhance the Efficiency of Fluoride2023

    • Author(s)
      Han S, Washio J, Abiko Y, Zhang L, Takahashi N
    • Journal Title

      Caries Res

      Volume: 57(3) Issue: 3 Pages: 255-264

    • DOI

      10.1159/000534055

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Chapter 11: Future Perspectives in the Study of Dental Caries.2023

    • Author(s)
      Takahashi N
    • Journal Title

      Monogr Oral Sci

      Volume: 31 Pages: 221-233

    • DOI

      10.1159/000530612

    • ISBN
      9783318071658, 9783318071665
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In situ detection of endogenous proteolytic activity and the effect of inhibitors on tooth root surface.2023

    • Author(s)
      Sakurai I, Mayanagi G, Yamada S, Takahashi N.
    • Journal Title

      Journal of Dentistry.

      Volume: 印刷中 Pages: 104471-104471

    • DOI

      10.1016/j.jdent.2023.104471

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Questionnaire survey on the satisfaction of SimEx dental education system2023

    • Author(s)
      Hong Guang、Hung Chun-Cheng、Mayanagi Gen、Nishioka Takashi、Sun Lu、Lai Eddie Hsiang-Hua、Lan Ting-Hsun、Sasaki Keiichi、Takahashi Nobuhiro
    • Journal Title

      Journal of Dental Sciences

      Volume: 18 Issue: 2 Pages: 840-847

    • DOI

      10.1016/j.jds.2023.01.028

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Li C. Glycolysis-Related Gene Analyses Indicate That DEPDC1 Promotes the Malignant Progression of Oral Squamous Cell Carcinoma via the WNT/β-Catenin Signaling Pathway2023

    • Author(s)
      Huang G, Chen S, Washio J, Paka Lubamba G, Takahashi N
    • Journal Title

      Int J Mol Sci.

      Volume: 24(3) Issue: 3 Pages: 1992-1992

    • DOI

      10.3390/ijms24031992

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effectiveness of an actuator-driven pulsed water jet for removal of softened carious dentin2022

    • Author(s)
      YOKOYAMA-SATO Yuka、NISHIOKA Takashi、NAGANUMA Yukihiro、TAKAHASHI Masatoshi、NAKAGAWA Atsuhiro、YODA Nobuhiro、SASAKI Keiichi、TAKAHASHI Nobuhiro、TOMINAGA Teiji、IIKUBO Masahiro
    • Journal Title

      Dental Materials Journal

      Volume: 41 Issue: 4 Pages: 527-533

    • DOI

      10.4012/dmj.2021-234

    • ISSN
      0287-4547, 1881-1361
    • Year and Date
      2022-07-25
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Facile Fabrication of All-solid-state Ion-selective Electrodes by Laminating and Drop-casting for Multi-sensing2022

    • Author(s)
      Okubo S, Ozeki Y, Yamada T, Saito K, Ishihara N, Yanagida Y, Mayanagi G, Washio J, Takahashi N
    • Journal Title

      Electrochemistry

      Volume: 90 Issue: 7 Pages: 077001-077001

    • DOI

      10.5796/electrochemistry.22-00020

    • ISSN
      1344-3542, 2186-2451
    • Year and Date
      2022-07-06
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A water-soluble glass-based temporary restorative resin inhibited bacteria-induced pH reductions at the bacteria-material interface2022

    • Author(s)
      MAYANAGI Gen、YUFANG Luo、HOSHINO Tomohiro、TAKAHASHI Nobuhiro
    • Journal Title

      Dental Materials Journal

      Volume: 41 Issue: 1 Pages: 95-100

    • DOI

      10.4012/dmj.2021-129

    • NAID

      130008150327

    • ISSN
      0287-4547, 1881-1361
    • Year and Date
      2022-01-25
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Combined Treatment with Fluoride and Antimicrobial Peptide GH12 Efficiently Controls Caries in vitro and in vivo2022

    • Author(s)
      Wang Y, Zeng Y, Feng Z, Li Z, Jiang X, Han S, Washio J, Takahashi N, Zhang L
    • Journal Title

      Caries Res.

      Volume: 56(5-6) Issue: 5-6 Pages: 524-534

    • DOI

      10.1159/000528057

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Profiling of the microbiota of breast milk before and after feeding with an artificial nipple2022

    • Author(s)
      Sano Hiroto、Wakui Anna、Kawachi Miho、Maruyama Shingo、Moriyama Sachie、Nishikata Mayumi、Washio Jumpei、Abiko Yuki、Mayanagi Gen、Sakashita Reiko、Tanaka Kaori、Takahashi Nobuhiro、Sato Takuichi
    • Journal Title

      Journal of Oral Biosciences

      Volume: 64 Issue: 4 Pages: 431-436

    • DOI

      10.1016/j.job.2022.09.004

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Profiling of the microbiota in the remaining sports drink and orange juice in plastic bottles after direct drinking2022

    • Author(s)
      Kawachi Miho、Wakui Anna、Kaku Nagara、Takahashi Nanase、Maruyama Shingo、Washio Jumpei、Abiko Yuki、Mayanagi Gen、Tanaka Kaori、Takahashi Nobuhiro、Sato Takuichi
    • Journal Title

      Journal of Oral Biosciences

      Volume: 64 Issue: 4 Pages: 437-444

    • DOI

      10.1016/j.job.2022.08.003

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] All-solid-state Fluoride Ion-selective Electrode using LaF3 Single Crystal with Poly(3,4-ethylenedioxythiophene) as Solid Contact Layer.2022

    • Author(s)
      Yamada T, Kanda k, Yanagida Y, Mayanagi G, Washio J, Takahashi N
    • Journal Title

      Electroanalysis

      Volume: 印刷中 Issue: 4

    • DOI

      10.1002/elan.202200103

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development and evaluation of a chewing gum containing antimicrobial peptide GH12 for caries prevention2022

    • Author(s)
      Jiang X, Wang Y, Li X, Feng Z, Zeng Y, Han S, Takahashi N, Zhang L
    • Journal Title

      Eur J Oral Sci.

      Volume: 130(5) Issue: 5

    • DOI

      10.1111/eos.12887

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Investigation of drug resistance of caries-related streptococci to antimicrobial peptide GH122022

    • Author(s)
      Li X, Wang Y, Jiang X, Zeng Y, Zhao X, Washio J, Takahashi N, Zhang L
    • Journal Title

      Front Cell Infect Microbiol.

      Volume: 12 Pages: 991938-991938

    • DOI

      10.3389/fcimb.2022.991938

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Microbiota profiles on the surface of non-woven fabric masks after wearing2022

    • Author(s)
      Maruyama Shingo、Sano Hiroto、Wakui Anna、Kawachi Miho、Kaku Nagara、Takahashi Nanase、Miyazawa Misato、Abe Takashi、Sato Aya、Washio Jumpei、Abiko Yuki、Mayanagi Gen、Tanaka Kaori、Takahashi Nobuhiro、Sato Takuichi
    • Journal Title

      Journal of Oral Biosciences

      Volume: 64 Issue: 3 Pages: 376-379

    • DOI

      10.1016/j.job.2022.07.002

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Quantification of Porphyromonas gingivalis Bacteria in Final Trimester of Pregnant Women According to Their Oral Health Status2022

    • Author(s)
      Roestamadji Retno I, Tedjosasongko Udijanto, Indrastie Nuraini, Diyatri Indeswati, Surboyo Meircurius DC, Sudarmo Subijanto M, Santoso Budi, Takahashi N
    • Journal Title

      Eur Journal of Gen Dent.

      Volume: 11(3) Issue: 03 Pages: 201-206

    • DOI

      10.1055/s-0042-1759755

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A detection and analysis of Fusobacterium utilizing changes in the magnetic properties of magnetic nanoparticles-antibody-antigen aggregates2022

    • Author(s)
      S. Yabukami, T. Murayama, S. Takahashi, S. Ohno, J. Washio, N. Takahashi
    • Journal Title

      IEEE Transactions on Magnetics

      Volume: 58 Issue: 8 Pages: 5300306-5300306

    • DOI

      10.1109/tmag.2022.3161508

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oral Microbiome Profiles and Inflammation in Pregnant Women Who Used Orthodontic Appliances2022

    • Author(s)
      Kurniawan FKD, Roestamadji RI, Takahashi N, Tedjosasongko U, Narmada IB, Surboyo MDC, Diyatri I
    • Journal Title

      Dent J (Basel).

      Volume: 10(7) Issue: 7 Pages: 118-118

    • DOI

      10.3390/dj10070118

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Importance of Nitrate Reduction for Oral Health2022

    • Author(s)
      Rosier B.T.、Takahashi N.、Zaura E.、Krom B.P.、Martinez-Espinosa R.M.、van Breda S.G.J.、Marsh P.D.、Mira A.
    • Journal Title

      Journal of Dental Research

      Volume: - Issue: 8 Pages: 002203452210809-002203452210809

    • DOI

      10.1177/00220345221080982

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Influence of alcohol sensitivity on bone metastases and skeletal-related events in primary operable breast cancer: A retrospective cohort study2022

    • Author(s)
      Tanda N, Tada H, Washio J, Takahashi N, Ishida T, Koseki T
    • Journal Title

      PLoS One.

      Volume: 17(6) Issue: 6 Pages: e0269335-e0269335

    • DOI

      10.1371/journal.pone.0269335

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rewired Cellular Metabolic Profiles in Response to Metformin under Different Oxygen and Nutrient Conditions2022

    • Author(s)
      Liu Shan、Washio Jumpei、Sato Satoko、Abiko Yuki、Shinohara Yuta、Kobayashi Yuri、Otani Haruki、Sasaki Shiori、Wang Xiaoyi、Takahashi Nobuhiro
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 2 Pages: 989-989

    • DOI

      10.3390/ijms23020989

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hypoxically cultured cells of oral squamous cell carcinoma increased their glucose metabolic activity under normoxic conditions2021

    • Author(s)
      Shinohara Yuta、Washio Jumpei、Kobayashi Yuri、Abiko Yuki、Sasaki Keiichi、Takahashi Nobuhiro
    • Journal Title

      PLOS ONE

      Volume: 16 Issue: 10 Pages: e0254966-e0254966

    • DOI

      10.1371/journal.pone.0254966

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bifacial biological effects of ethanol: acetaldehyde production by oral Streptococcus species and the antibacterial effects of ethanol against these bacteria2021

    • Author(s)
      Tagaino Ryo、Washio Jumpei、Otani Haruki、Sasaki Keiichi、Takahashi Nobuhiro
    • Journal Title

      Journal of Oral Microbiology

      Volume: 13 Issue: 1 Pages: 1937884-1937884

    • DOI

      10.1080/20002297.2021.1937884

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effectiveness and safety of a new dental plaque removal device utilizing micro mist spray for removing oral biofilm in vitro2021

    • Author(s)
      Hihara Hiroki、Tagaino Ryo、Washio Jumpei、Laosuwan Kittipong、Wicaksono Dimas Prasetianto、Izumita Kuniyuki、Koide Rie、Takahashi Nobuhiro、Sasaki Keiichi
    • Journal Title

      BMC Oral Health

      Volume: 21 Issue: 1 Pages: 286-286

    • DOI

      10.1186/s12903-021-01647-4

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Profiling system of oral microbiota utilizing polymerase chain reaction-restriction fragment length polymorphism analysis2021

    • Author(s)
      Sano H, Wakui A, Kawachi M, Washio J, Abiko Y, Mayanagi G, Yamaki K, Tanaka K, Takahashi N, Sato T
    • Journal Title

      Journal of Oral Biosciences

      Volume: 63 Issue: 3 Pages: 292-297

    • DOI

      10.1016/j.job.2021.05.003

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Profiling of microbiota at the mouth of bottles and in remaining tea after drinking directly from plastic bottles of tea2021

    • Author(s)
      Wakui A*, Sano H*, Hirabuki Y*, Kawachi M, Aida A, Washio J, Abiko Y, Mayanagi G, Yamaki K, Tanaka K, Takahashi N, Sato T
    • Journal Title

      Dentistry Journal

      Volume: 9 Issue: 6 Pages: 58-58

    • DOI

      10.3390/dj9060058

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Green Tea-Derived Epigallocatechin Gallate Inhibits Acid Production and Promotes the Aggregation of Streptococcus mutans and Non-Mutans Streptococci2021

    • Author(s)
      Han Sili、Abiko Yuki、Washio Jumpei、Luo Yufang、Zhang Linglin、Takahashi Nobuhiro
    • Journal Title

      Caries Research

      Volume: 55 Issue: 3 Pages: 205-214

    • DOI

      10.1159/000515814

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Bacterial amounts and compositions in liquid baby formula and a baby drink consumed with an artificial nipple.2021

    • Author(s)
      Wakui A, Sano H, Kawachi M, Aida A, Takenaka Y, Yonezawa A, Nakahata N, Moriyama S, Nishikata M, Washio J, Abiko Y, Mayanagi G, Yamaki K, Sakashita R, Tanaka K, Takahashi N, Sato T
    • Journal Title

      J Oral Biosci.

      Volume: 印刷中 Issue: 2 Pages: 161-168

    • DOI

      10.1016/j.job.2021.03.001

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of the COVID‐19 pandemic on dental clinical training and future prospects2021

    • Author(s)
      Nishioka Takashi、Mayanagi Gen、Iwamatsu‐Kobayashi Yoko、Hong Guang
    • Journal Title

      Journal of Dental Education

      Volume: 85 Issue: S3 Pages: 1999-2001

    • DOI

      10.1002/jdd.12562

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Propofol affected on the glucose metabolism in liver cells2024

    • Author(s)
      Shiori Sasaki, Jumpei Washio, Haruki Otani, Shan Liu, Satoko Sato, Kentaro Mizuta and Nobuhiro Takahashi
    • Organizer
      The 102nd IADR General Session & Exhibition
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Nutritional conditions for cell growth affect anticancer drug sensitivity.2024

    • Author(s)
      Ayano Igarashi, Jumpei Washio, Satoko Sato, Hiromitsu Morishima, Kensuke Yamauchi, Nobuhiro Takahashi
    • Organizer
      The 102nd IADR General Session & Exhibition
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 緑茶カテキンEGCGの抗菌効果について:齲蝕関連細菌と歯周病関連細菌の比較2023

    • Author(s)
      樋口真由、安彦友希、鷲尾純平、髙橋信博
    • Organizer
      第13回口腔保健用機能性食品研究会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Profiling of microbiota of bottled beverages: storage under different temperatures2023

    • Author(s)
      A. WAKUI, M. KAWACHI, Y. ABIKO, J. WASHIO, N.TAKAHASHI, T. SATO
    • Organizer
      The 71st Annual Meeting of Japanese Association for Dental Research
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effects of butyrate on morphology and proliferation of OSCC cells2023

    • Author(s)
      G. HUANG, J.WASHIO, H. OTANI, N. TAKAHASHI
    • Organizer
      The 71st Annual Meeting of Japanese Association for Dental Research
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Antimicrobial effect of green tea catechins on periodontal disease-associated bacteria2023

    • Author(s)
      Mayu Higuchi, Yuki Abiko, Jumpei Washio, Nobuhiro Takahashi
    • Organizer
      The 71st Annual Meeting of Japanese Association for Dental Research
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 細胞増殖の栄養環境は、口腔がん細胞の増殖、糖代謝能、および抗がん剤感受性に影響する2023

    • Author(s)
      五十嵐彩乃, 鷲尾純平, 森島浩允, 山内健介, 髙橋信博
    • Organizer
      第68回日本口腔外科学会総会・学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 細菌性代謝産物の酪酸が歯肉線維芽細胞の機能に与える影響2023

    • Author(s)
      大谷 栄毅, 鷲尾 純平, 國富 葵, 佐々木 詩織, 大橋 一正, 山田 聡, 高橋 信博
    • Organizer
      第66回秋季日本歯周病学会学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 改・口腔マイクロバイオームとわたしたちの健康2023

    • Author(s)
      鷲尾純平
    • Organizer
      第81回 東北大学歯学会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 歯周病関連細菌に由来する酪酸が歯周組織細胞機能に与える影響2023

    • Author(s)
      大谷 栄毅, 鷲尾 純平, 佐藤 聡子, 佐々木 詩織, 山田 聡, 高橋 信博
    • Organizer
      第65回歯科基礎医学会学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 静脈麻酔薬プロポフォールが肝細胞の糖代謝活性に及ぼす影響2023

    • Author(s)
      佐々木 詩織, 鷲尾 純平, 大谷 栄毅, 佐藤 聡子, 水田 健太郎, 高橋 信博
    • Organizer
      第65回歯科基礎医学会学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 口腔Actinomyces属及びSchaalia属の亜硝酸塩産生活性と活性に対する環境要因の影響2023

    • Author(s)
      大竹 知菜, 鷲尾 純平, 安彦 友希, 五十嵐 薫, 高橋 信博
    • Organizer
      第65回歯科基礎医学会学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 口腔マイクロバイオームは発がん性物質アセトアルデヒドの分解にも関与する アセトアルデヒド産生能・分解能の簡易スクリーニング法の確立2023

    • Author(s)
      佐藤 知佳, 互野 亮, 鷲尾 純平, 安彦 友希, 五十嵐 薫, 高橋 信博
    • Organizer
      第65回歯科基礎医学会学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 歯周病菌由来酪酸の増殖・代謝抑制作用は正常細胞とOSSC細胞で異なる(Inhibitory effects of periodontal pathogen-derived butyrate on proliferation and metabolism differ between normal and OSSC cells)2023

    • Author(s)
      Huang Guangzhao, Washio Jumpei, Otani Haruki, Sato Satoko, Takahashi Nobuhiro
    • Organizer
      第65回歯科基礎医学会学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] A new perspective on the biochemical and ecological characteristics of fungi. - How do they survive in the anaerobic environment of the oral cavity? -2023

    • Author(s)
      Haneen Raafat Fathi Mousa, Yuki Abiko, Jumpei Washio, Nobuhiro Takahashi
    • Organizer
      第65回歯科基礎医学会学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 口腔細菌に対する緑茶カテキンの抗菌効果2023

    • Author(s)
      樋口真由, 安彦友希, 鷲尾純平, 高橋信博
    • Organizer
      『革新的食学拠点』令和5年度第3回合同ミーティング
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Profiling of the Microbiota on the Surfaces of Non-woven Fabric Masks after Wearing and Smartphone Touchscreens2023

    • Author(s)
      Anna Wakui, Miho Kawachi, Nanase Takahashi, Takashi Abe, Shingo Maruyama, Nagara Kaku, Misato Miyazawa, Aya Sato, Manami Imai, Hikaru Arai1, Kaori Tanaka, Yuki Abiko, Jumpei Washio, Nobuhiro Takahashi, Takuichi Sato
    • Organizer
      Interface Summer Seminar 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Profiling of the Microbiota in the Remaining Green Tea Drinks in Plastic Bottles2023

    • Author(s)
      Miho Kawachi, Anna Wakui, Nagara Kaku, Nanase Takahashi, Misato Miyazawa, Takashi Abe, Aya Sato, Manami Imai, Hikaru Arai, Haruna Sato, Yuki Kato, Rika Okabe, Yuka Naruse, Nao Sato, Kaori Tanaka, Mayu Higuchi, Yuki Abiko, Jumpei Washio, Nobuhiro Takahashi, Takuichi Sato
    • Organizer
      Interface Summer Seminar 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒト母乳と新生児口腔細菌叢との関連2023

    • Author(s)
      涌井杏奈,河内美帆,安彦友希,鷲尾純平,高橋信博,佐藤拓一
    • Organizer
      『革新的食学拠点』令和5年度第2回合同ミーティング
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Oral Neisseria and nitrate suppress pH-decrease in the oral microbiome2023

    • Author(s)
      Jumpei Washio, Kazuko Ezoe, Satoko Sato, Yuki Abiko and Nobuhiro Takahashi
    • Organizer
      The 101st IADR General Session & Exhibition
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 細菌代謝産物「酪酸」がヒトの健康に及ぼす影響 ?口腔内と腸内では異なるそのイメージ-2023

    • Author(s)
      大谷栄毅, 鷲尾純平, 佐藤聡子, 山田聡, 髙橋信博
    • Organizer
      『革新的食学拠点』令和5年度第1回合同ミーティング
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 緑茶カテキンの歯周病関連細菌に対する抗菌作用:アミノ酸代謝活性抑制および菌体凝集作用について2023

    • Author(s)
      樋口真由,安彦友希,鷲尾純平,高橋信博
    • Organizer
      第72回日本口腔衛生学会学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] ペットボトル飲料物の保管に関する食品科学的・細菌学的研究2023

    • Author(s)
      河内美帆,涌井杏奈,賀来ながら,高橋七瀬,宮沢美里,佐藤 彩,阿部峰士,今井真奈美,佐藤遥菜,加藤優希,岡部璃佳,成瀬悠香,佐藤奈緒,鷲尾純平,佐藤拓一
    • Organizer
      第72回日本口腔衛生学会学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 搾乳母乳と新生児口腔内細菌叢との連関2023

    • Author(s)
      涌井杏奈,河内美帆,佐野拓人,坂下玲子,鷲尾純平,高橋信博,佐藤拓一
    • Organizer
      第72回日本口腔衛生学会学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] ミニシンポジウム5:口腔マイクロバイオームの復元力(レジリエンス)から考える新たな齲蝕予防戦略2023

    • Author(s)
      高橋信博
    • Organizer
      第72回日本口腔衛生学会学術大会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 口ミニシンポジウム5:腔マイクロバイオームの酸産生抑制代謝産物(硝酸塩・亜硝酸塩代謝)2023

    • Author(s)
      鷲尾純平
    • Organizer
      第72回日本口腔衛生学会学術大会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 母乳と新生児口腔内細菌叢との関連2023

    • Author(s)
      涌井杏奈,佐野拓人,河内美帆,丸山伸吾,安彦友希,鷲尾純平,高橋信博,佐藤拓一
    • Organizer
      第12回口腔保健用機能性食品研究会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 飲みかけの緑茶ペットボトルの細菌について2023

    • Author(s)
      今井真奈美,佐藤遥菜,河内美帆,賀来ながら,涌井杏奈,高橋七瀬,宮沢美里,佐藤 彩,阿部峰士,加藤優希,岡部璃佳,成瀬悠香,佐藤奈緒,丸山伸吾,佐野拓人,樋口真由、安彦友希,鷲尾純平,高橋信博,佐藤拓一
    • Organizer
      第12回口腔保健用機能性食品研究会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 緑茶カテキンの歯周病関連細菌に対する抗菌作用2023

    • Author(s)
      樋口真由,安彦友希,鷲尾純平,髙橋信博
    • Organizer
      第12回口腔保健用機能性食品研究会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Identification of health-related nitrite-producing bacteria and the regulatory mechanism of their nitrite production2023

    • Author(s)
      Jumpei Washio, Kazuko Ezoe, Yuki Abiko, Tomona Otake, Dimas Prasetianto Wicaksono and Nobuhiro Takahashi
    • Organizer
      CA+inD International Symposium, 2023
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The creation of SHOKU-gaku (Transdisciplinary Science of Eating, Food, and Nutrition for Health and Wellbeing) and its goals: with an example of food function enhancement by the oral microbiome.2022

    • Author(s)
      Nobuhiro Takahashi, Jumpei Washio.
    • Organizer
      The 22nd IUNS-ICN (International Union of Nutrition Science-International Congress of Nutrition)
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Growth promotion factors of ECC-associated bacterium, Scardovia wiggsiae.2022

    • Author(s)
      Kameda M, Abiko Y, Washio J, Takahashi N
    • Organizer
      2022FJMU-HKU-TU International Online Symposium on Oral Health Sciences
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] New Challenges for Tohoku University Graduate School of Dentistry.2022

    • Author(s)
      Nobuhiro Takahashi
    • Organizer
      The Creation of Shoku-gaku (Transdisciplinary Science of Eating, Food, and Nutrition for Health and Wellbeing)
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Scardovia wiggsiae の増殖促進因子の検討2022

    • Author(s)
      亀田 真衣,安彦 友希,鷲尾 純平,佐藤 聡子,高橋 信博
    • Organizer
      第64回歯科基礎医学会学術大会
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
  • [Presentation] How oral bacteria contribute to the onset of periodontitis?―Bacterial effects on the glucose metabolic activity of host cells.2022

    • Author(s)
      Otani H,Washio J,Liu S,Sasaki S,Yamada S,Takahashi N
    • Organizer
      第64回歯科基礎医学会学術大会
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Invited
  • [Presentation] 口腔細菌によるがん性物質アセトアルデヒド”の産生?飲酒や食事との関連性?2022

    • Author(s)
      互野亮
    • Organizer
      令和4年度第3回『革新的食学拠点』ミーティング
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Effectiveness and safety of the Micro Scale Mist spray for removing oral biofilm in vitro2022

    • Author(s)
      Hihara H, Tagaino R, Washio J, Izumita K, Koide R, Takahashi N, Sasaki K
    • Organizer
      Interface Summer Seminar 2022
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Rewired cellular metabolic profiles in response to metformin under different oxygen and nutrient conditions2022

    • Author(s)
      Liu S, Washio J, Sato S, Abiko Y, Shinohara Y, Kobayashi Y, Otani H, Sasaki S, Wang X, Takahashi N
    • Organizer
      Interface Summer Seminar 2022
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 歯科訪問診療における水質管理方策の検討2022

    • Author(s)
      伏見 国拡, 山田 将博, 渡辺 隼, 鷲尾 純平, 高橋 信博, 江草 宏
    • Organizer
      第79回 東北大学歯学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Oral Environmental Factors Regulated Nitrate/Nitrite Metabolism of Oral Neisseria2022

    • Author(s)
      Jumpei Washio, Kazuko Ezoe and Nobuhiro Takahashi
    • Organizer
      2022 International Association of Dental Research General Session &Exhibition Virtual Experience
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 飲みかけのペットボトル飲料物から検出される細菌の量・構成(第 4 報)、緑茶についての解析2022

    • Author(s)
      宮沢美里,河内美帆,涌井杏奈,臼田紫乃,今井真奈美,坂井ふたば,佐藤遥菜,加藤優希,佐藤 彩,高橋七瀬,賀来ながら,樋口真由,鷲尾純平,安彦友希,眞柳 弦,高橋信博,佐藤拓一
    • Organizer
      第11回口腔保健用機能性食品研究会
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Invited
  • [Presentation] The antimicrobial properties of green tea derived-catechins and their combined effect with fluoride on Streptococcus mutans2022

    • Author(s)
      Han S, Washio J, Abiko Y, Zhang L, Takahashi N
    • Organizer
      第11回口腔保健用機能性食品研究会
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Invited
  • [Presentation] Metabolic functions of the oral microbiome: How does the oral microbiome function and contribute to our health?2022

    • Author(s)
      Washio J, Mayanagi G, Abiko Y, Tagaino R, Dimas Prasetianto Wicaksono, Domon H, Ezoe K, Sato S, Takahashi N
    • Organizer
      International Symposium for Interface Oral Health Science 2022 (IOHS)
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Shoku-gaku: Transdisciplinary Science of Eating, Food, and Nutrition? Promoting lifelong health and wellbeing through right eating and right food ?2022

    • Author(s)
      Takahashi N
    • Organizer
      International Symposium for Interface Oral Health Science 2022 (IOHS)
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A novel ECC-related bacterium, Scardovia wiggsiae, has a unique carbohydrate metabolism with fluoride resistance2022

    • Author(s)
      Kameda M, Abiko Y, Washio J, Takahashi N
    • Organizer
      International Symposium for Interface Oral Health Science 2022 (IOHS)
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Profiling of Microbiota in Sport-Drink and Orange Juice of Plastic Bottle After Drinking Directly From Plastic Bottles2022

    • Author(s)
      Kawachi M, Wakui A, Washio J, Abiko Y, Mayanagi G, Takahashi N, Sato T
    • Organizer
      International Symposium for Interface Oral Health Science 2022 (IOHS)
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Profiling of Microbiota in Liquid Baby Formula and a Baby Drink Consumed with an Artificial Nipple2022

    • Author(s)
      Wakui A, Kawachi M, Nishikata M, Washio J, Abiko Y, Mayanagi G, Takahashi N, Sato T
    • Organizer
      International Symposium for Interface Oral Health Science 2022 (IOHS)
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Bifacial aspects of ethanol: antibacterial effect and carcinogenic effect by metabolism to acetaldehyde depend on ethanol concentration2022

    • Author(s)
      Tagaino R, Washio J, Sasaki K, Takahashi N
    • Organizer
      International Symposium for Interface Oral Health Science 2022 (IOHS)
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effect of rapid increases in oxygen levels on glucose metabolism of cancer cells2022

    • Author(s)
      Shinohara Y, Washio J, Kobayashi Y, Abiko Y, Morishima H, Sasaki K, Takahashi N
    • Organizer
      International Symposium for Interface Oral Health Science 2022 (IOHS)
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 口腔細菌によるがん性物質アセトアルデヒド”の産生ー飲酒や食事との関連性ー2022

    • Author(s)
      互野亮
    • Organizer
      令和4年度第3回『革新的食学拠点』ミーティング
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] ?腔と全?の健康に関わる?腔バイオフィルムの代謝機能2021

    • Author(s)
      髙橋信博, 鷲尾純平
    • Organizer
      第94回日本細菌学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Oral microbiome metabolism in oral and systemic health/disease2021

    • Author(s)
      Nobuhiro Takahashi
    • Organizer
      Kaohsiung Medical University (KMU) Research Day
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Oxygen dependent anti-cancer effect of metformin: growth and glucose metabolism2021

    • Author(s)
      Shan Liu, Jumpei Washio, Nobuhiro Takahashi
    • Organizer
      The 99h IADR General Session & Exhibition
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Porphyromonas gingivalis inhibit the glucose metabolic activity of host cells2021

    • Author(s)
      Haruki Otani, Jumpei Washio, Satoru Yamada and Nobuhiro Takahashi
    • Organizer
      The 99h IADR General Session & Exhibition
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] The antimicrobial properties of green tea derived-catechins on Streptococcus mutans2021

    • Author(s)
      Han S, Washio J, Abiko Y, Zhang L, Takahashi N
    • Organizer
      The 99h IADR General Session & Exhibition
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 根面う蝕モデル 酸による根面内在性タンパク分解酵素の活性化(Root caries model: Acid-induced activation of endogenous proteases embedded in root surfaces)2021

    • Author(s)
      櫻井 泉, 真柳 弦, 山田 聡, 高橋 信博
    • Organizer
      第63回歯科基礎医学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 口腔Neisseria属による亜硝酸産生活性と環境因子による影響(The Nitrite producing activity of oral Neisseria and the effect of environmental factors)2021

    • Author(s)
      鷲尾 純平, 江副 和子, 佐藤 聡子, 安彦 友希, 小峰 英也, 柴田 怜, 田花 航平, 毛 雪竹, 高橋 信博
    • Organizer
      第63回歯科基礎医学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 小児齲蝕の発症機序と 生物学的要因2021

    • Author(s)
      高橋信博
    • Organizer
      第70回日本口腔衛生学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Oral Microbiome in Health and Diseases2021

    • Author(s)
      Nobuhiro Takahashi
    • Organizer
      Zhejiang University International Workshop
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 口腔内ビフィズス菌の糖代謝 ーう蝕との関連ー2021

    • Author(s)
      安彦 友希, 馬目 歩実, 亀田 真衣, 鷲尾 純平, 髙橋 信博
    • Organizer
      令和3年度第3回・『革新的食学拠点』ミーティング
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Book] 歯科衛生学辞典第2版2024

    • Author(s)
      眞木吉信ほか
    • Total Pages
      20
    • Publisher
      永末書店
    • ISBN
      9784816014390
    • Related Report
      2023 Annual Research Report
  • [Book] ポリフェノールの機能と多角的応用2022

    • Author(s)
      鷲尾純平、安彦友希、髙橋信博
    • Total Pages
      333
    • Publisher
      シーエムシー出版
    • ISBN
      9784781316871
    • Related Report
      2021 Annual Research Report

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Published: 2021-04-28   Modified: 2024-12-25  

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