Nakazawa, Yosuke

写真a

Affiliation

Faculty of Pharmacy, Department of Pharmacy 衛生化学講座 (Shiba-Kyoritsu)

Position

Assistant Professor/Senior Assistant Professor

Career 【 Display / hide

  • 2005.04
    -
    2009.03

    Faculity of pahrmacy, setsunan university, 助手

  • 2009.04
    -
    2012.03

    慶應義塾大学薬学部, 助手

  • 2012.04
    -
    2019.03

    慶應義塾大学薬学部, 助教

  • 2016.09
    -
    2017.08

    The University of Auckland, Faculty of Medical and Health Sciences, Visiting Researcher

  • 2019.04
    -
    Present

    Fuculty of Pharmacy, Keio University, Senior Lecturer

Licenses and Qualifications 【 Display / hide

  • 薬剤師, 2003.04

  • 健康食品管理士, 2019.01

 

Papers 【 Display / hide

  • Oral Formulation Based on Irbesartan Nanocrystals Improve Drug Solubility, Absorbability, and Efficacy.

    Nagai N, Ogata F, Ike A, Shimomae Y, Osako H, Nakazawa Y, Yamamoto N, Kawasaki N

    Pharmaceutics (Pharmaceutics)  14 ( 2 )  2022.02

    Research paper (scientific journal), Accepted

     View Summary

    We previously reported that the bioavailability (BA) of irbesartan (IRB), a BSC class II drug, was improved by preparing nanocrystalline suspensions. However, nanocrystalline suspensions have chemical and physical instabilities and must be converted into tablets through drying approaches in order to overcome such instabilities. In this study, we attempted to design a molded tablet based on nanocrystalline IRB suspensions (IRB-NP tablet) and investigated the effects of this IRB-NP tablet on blood pressure (BP) in a stroke-prone spontaneously hypertensive (SHR-SP) rat. The IRB-NP tablet (with a hardness of 42.6 N) was developed by combining various additives (methylcellulose, 2-hydroxypropyl-β-cyclodextrin HPβCD, D-mannitol, polyvinylpyrrolidone, and gum arabic) followed by bead-milling and freeze-drying treatments. The mean particle size in the redispersions of the IRB-NP tablet was approximately 118 nm. The solubility and intestinal absorption of IRB in the IRB-NP tablet were significantly enhanced in comparison with the microcrystalline IRB tablet (IRB-MP tablet), and both solubility and clathrin-dependent endocytosis helped improve the low BA of the IRB. In addition, the BP-reducing effect of the IRB-NP tablet was significantly higher than that of the IRB-MP tablet. These results provide useful information for the preservation of nanocrystalline suspensions of BCS class II drugs, such as IRB.

  • Novel Mechanism by a Bis-Pyridinium Fullerene Derivative to Induce Apoptosis by Enhancing the MEK-ERK Pathway in a Reactive Oxygen Species-Independent Manner in BCR-ABL-Positive Chronic Myeloid Leukemia-Derived K562 Cells

    Sumi K., Tago K., Nakazawa Y., Takahashi K., Ohe T., Mashino T., Funakoshi-Tago M.

    International Journal of Molecular Sciences (International Journal of Molecular Sciences)  23 ( 2 )  2022.01

    Research paper (scientific journal), Accepted,  ISSN  16616596

     View Summary

    In the treatment of breakpoint cluster region-Abelson (BCR-ABL)-positive chronic myeloid leukemia (CML) using BCR-ABL inhibitors, the appearance of a gatekeeper mutation (T315I) in BCR-ABL is a serious issue. Therefore, the development of novel drugs that overcome acquired resistance to BCR-ABL inhibitors by CML cells is required. We previously demonstrated that a bis-pyridinium fullerene derivative (BPF) induced apoptosis in human chronic myeloid leukemia (CML)-derived K562 cells partially through the generation of reactive oxygen species (ROS). We herein show that BPF enhanced the activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-extracellular signal-regulated kinase (MEK-ERK) pathway in a ROS-independent manner. BPF-induced apoptosis was attenuated by trametinib, suggesting the functional involvement of the MEK-ERK pathway in apoptosis in K562 cells. In addition, the constitutive activation of the MEK-ERK pathway by the enforced expression of the BRAFV600E mutant significantly increased the sensitivity of K562 cells to BPF. These results confirmed for the first time that BPF induces apoptosis in K562 cells through dual pathways—ROS production and the activation of the MEK-ERK pathway. Furthermore, BPF induced cell death in transformed Ba/F3 cells expressing not only BCR-ABL but also T315I mutant through the activation of the MEK-ERK pathway. These results indicate that BPF is as an effective CML drug that overcomes resistance to BCR-ABL inhibitors.

  • A bis-pyridinium fullerene derivative induces apoptosis through the generation of ROS in BCR-ABL-positive leukemia cells.

    Sumi K, Tago K, Nakazawa Y, Takahashi K, Ohe T, Mashino T, Funakoshi-Tago M

    European journal of pharmacology (European Journal of Pharmacology)  916   174714 2021.12

    Research paper (scientific journal), Accepted,  ISSN  0014-2999

     View Summary

    A fusion protein, Breakpoint cluster region-Abelson (BCR-ABL) is responsible for the development of chronic myeloid leukemia (CML) and acute lymphocytic leukemia (ALL). Inhibitors against BCR-ABL are effective for the treatment of leukemia; however, a gatekeeper mutation (T315I) in BCR-ABL results in resistance to these inhibitors, which markedly impedes their efficacy. We herein demonstrated that a bis-pyridinium fullerene derivative (BPF) significantly induced apoptosis in human CML-derived K562 cells and ALL-derived SUP-B15 cells via the generation of reactive oxygen species (ROS). BPF reduced the expression of Bcr-Abl mRNA by inhibiting expression of c-Myc through ROS production. BPF also accelerated protein degradation of BCR-ABL through ROS production. Furthermore, BPF down-regulated the expression of not only BCR-ABL but also T315I-mutated BCR-ABL in ROS-dependent manner. As a result, BPF effectively induced apoptosis in transformed Ba/F3 cells expressing both BCR-ABL and T315I-mutated BCR-ABL. Collectively, these results indicate the potential of BPF as an effective leukemia drug that overcomes resistance to BCR-ABL inhibitors.

  • Capsaicin attenuates TGFβ2-induced epithelial-mesenchymal-transition in lens epithelial cells in vivo and in vitro

    Sugiyama Y., Nakazawa Y., Sakagami T., Kawata S., Nagai N., Yamamoto N., Funakoshi-Tago M., Tamura H.

    Experimental Eye Research (Experimental Eye Research)  213   108840 2021.12

    Research paper (scientific journal), Accepted,  ISSN  00144835

     View Summary

    Posterior capsule opacification (PCO), the most common complication of cataract surgery occurring in 20–50% of patients after 2–5 years of cataract surgery, is a major problem in the aging society. The epithelial-mesenchymal transition (EMT) of lens epithelial cells after cataract surgery has been proposed as a major cause of PCO. Capsaicin, widely used as a food additive and analgesic agent, is a major pungent ingredient in red pepper. Although the effect of capsaicin on EMT has been reported in cancer cells, the biological reaction of capsaicin was unique in each cell type, and there have been no reports describing its effects on EMT earlier. In this study, we demonstrated that treatment with capsaicin inhibited TGFβ2-induced EMT in vitro lens epithelial cells and ex vivo explant lens epithelial cells. Furthermore, eye drops of capsaicin inhibited the PCO model mice in vivo. Finally, we showed that capsaicin inhibited non-canonically induced Smad2/3 activation via suppression of EGFR activation and ERK phosphorylation. Our findings indicate that capsaicin and its derivatives are good candidate compounds for preventing PCO after cataract surgery.

  • Regulation of the membrane trafficking of the mechanosensitive ion channels trpv1 and trpv4 by zonular tension, osmotic stress and activators in the mouse lens

    Nakazawa Y., Petrova R.S., Sugiyama Y., Nagai N., Tamura H., Donaldson P.J.

    International Journal of Molecular Sciences (International Journal of Molecular Sciences)  22 ( 23 )  2021.12

    Accepted,  ISSN  16616596

     View Summary

    Lens water transport generates a hydrostatic pressure gradient that is regulated by a dual-feedback system that utilizes the mechanosensitive transient receptor potential vanilloid (TRPV) channels, TRPV1 and TRPV4, to sense changes in mechanical tension and extracellular osmolarity. Here, we investigate whether the modulation of TRPV1 or TRPV4 activity dynamically affects their membrane trafficking. Mouse lenses were incubated in either pilocarpine or tropicamide to alter zonular tension, exposed to osmotic stress, or the TRPV1 and TRPV4 activators capsaicin andGSK1016790A (GSK101), and the effect on the TRPV1 and TRPV4 membrane trafficking in peripheral fiber cells visualized using confocal microscopy. Decreases in zonular tension caused the removal of TRPV4 from the membrane of peripheral fiber cells. Hypotonic challenge had no effect on TRPV1, but increased the membrane localization of TRPV4. Hypertonic challenge caused the insertion of TRPV1 and the removal of TRPV4 from the membranes of peripheral fiber cells. Capsaicin caused an increase in TRPV4 membrane localization, but had no effect on TRPV1; while GSK101 decreased the membrane localization of TRPV4 and increased the membrane localization of TRPV1. These reciprocal changes in TRPV1/4 membrane localization are consistent with the channels acting as mechanosensitive transducers of a dual‐feedback pathway that regulates lens water transport.

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Papers, etc., Registered in KOARA 【 Display / hide

Reviews, Commentaries, etc. 【 Display / hide

  • TRPV channels in the Lens

    Yosuke Nakazawa

    Ganka (金原出版株式会社)  64 ( 4 ) 317 - 323 2022.04

    Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media), Single Work, Lead author, Corresponding author

  • Animal Models to Fight the Cataract

    Yosuke Nakazawa

    The journal of the Japanese Society for Cataract Research (The Japanese Society for Cataract )  33 ( 1 ) 37 - 40 2021.06

    Article, review, commentary, editorial, etc. (scientific journal), Single Work

  • Look back on the eye with basic research, clinical science and drug repositioning

    Kosano H., Nakazawa Y., Hara H.

    Yakugaku Zasshi (Yakugaku Zasshi)  141 ( 1 ) 33 - 34 2021.01

    ISSN  00316903

  • Eye diseases with aging ―For keeping high QOV (Quality of Vision)―

    Nakazawa Y., Nagai N.

    Yakugaku Zasshi (Yakugaku Zasshi)  56 ( 12 ) 1305 - 1306 2021

    ISSN  00316903

  • フィレンシンによるアクアポリン0(AQP0)の機能解析.

    中澤洋介.

    日本白内障学会誌 (日本白内障学会)  26   28-29 2014.06

    Article, review, commentary, editorial, etc. (scientific journal), Single Work

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Presentations 【 Display / hide

  • ビスピリジニウム型フラーレン誘導体によるBCR-ABL陽性K562細胞のアポトーシス誘導機構の解明

    鷲見和也、多胡憲治、中澤洋介、高橋恭子、大江知之、増野匡彦、多胡めぐみ

    日本薬学会第142年会, 

    2022.03

    Oral presentation (general)

  • Discovery of the Ion channels in the Lens

    Yosuke Nakazawa

    第60回日本白内障学会総会/第47回水晶体研究会, 

    2021.11

    Symposium, workshop panel (nominated)

  • 温度の違いがヒト水晶体中ミトコンドリア機能へ及ぼす影響:高環境温度はエーティーピーの過剰産生を誘発する

    長井紀章、武田峻、出口粧央里、山本直樹、中澤洋介、高田匠、宮田佳樹、平松範子、永田万由美、久保江理、佐々木洋

    第60回日本白内障学会総会/第47回水晶体研究会, 

    2021.11

    Oral presentation (general)

  • 培養温度の違いによるヒト不死化水晶体上皮細胞の遺伝子・蛋白質への影響

    山本直樹、平松範子、長井紀章、中澤洋介、高田匠、宮田佳樹、武田峻、永田万由美、松島博之、久保江理、佐々木洋

    第60回日本白内障学会総会/第47回水晶体研究会, 

    2021.11

    Oral presentation (general)

  • TRPV1 activation can prevent posterior capsule opacification

    中澤洋介、杉山裕紀、阪上瞳子、河田沙良、長井紀章、山本直樹、多胡めぐみ、田村悦臣

    第60回日本白内障学会総会/第47回水晶体研究会, 

    2021.11

    Oral presentation (general)

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • 老眼発症機序の解明とTRPVチャネルを標的とした抗老眼薬創製の基盤研究

    2020.04
    -
    2023.03

    文部科学省, 科学研究費補助金(文部科学省・日本学術振興会), Yosuke Nakazawa, Research grant, Principal investigator

  • Roles for the mechanosensitive channels (TRPV1 and TRPV4) in the initiation of presb yopia and development of cataract

    2020.04
    -
    2022.03

    JSPS-NZRS, Bilateral joint research project between Japan and New Zealand, Yosuke Nakazawa, Research grant, Principal investigator

  • 老眼発症遅延薬の開発を見据えて:老眼発症メカニズムの解明と老眼モデル動物の開発

    2018.09
    -
    2019.08

    Japan Health Foundation, Yosuke Nakazawa, Research grant, Principal investigator

  • アクアポリン0およびアクアポリン5の機能解明とこれらを標的とした新規抗白内 障薬の創生

    2016.09
    -
    2017.08

    公益財団法人 持田記念医学薬学振興財団, Research grant, No Setting

  • 新規白内障治療薬の開発を目指したアクアポリン0の機能解明

    2016.04
    -
    2018.03

    文部科学省, Grant-in-Aid for Scientific Research, Yosuke Nakazawa, Research grant, Principal investigator

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Awards 【 Display / hide

  • 日本薬学会2019年度関東支部 奨励賞

    中澤洋介, 2019.09, 公益社団法人日本薬学会関東支部, 抗白内障薬/抗老眼薬の創製を見据えて:水晶体透明性維持機構の解明と疾患予防の基盤研究

    Type of Award: Award from publisher, newspaper, foundation, etc.

  • 日本白内障学会 学術賞

    中澤洋介, 2014.09, Japanese Society for Cataract Research, 水晶体のアクアポリン0の役割および機能に関する新しい知見

  • 2019年度 助成研究発表会 優秀賞

    2019.11, Japan Health Fundation

    Type of Award: Award from Japanese society, conference, symposium, etc.

  • Imaging competion Winner 2019

    2019.07, Vector Laboratories社, lens E10 section

    Type of Award: Award from publisher, newspaper, foundation, etc.

  • Young Investigator Awards

    Yosuke Nakazawa, Rosica S. Petrova, Hiroomi Tamura, Paul J. Donaldson, 2017.12, National Foundation for Eye Research, The subcellular expression patterns of the mechano-sensitive channels TRPV1/4 in the mouse lens are modulated by changes in zonular tension

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Other 【 Display / hide

  • 日本薬学会 第141年会 一般シンポジウム オーガナイザー

    2021年03月

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    日本薬学会 第141年会
    一般シンポジウム オーガナイザー

    [S20] 老化と眼疾患ーいつまでも健康な視機能をー

  • 日本薬学会 第140年会 一般シンポジウム オーガナイザー

    2020年03月

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    日本薬学会 第140年会
    一般シンポジウム オーガナイザー

    今いちど,眼科領域の進歩を考える ―基礎,臨床,そしてドラッグリポジショニングについて―

  • Conference President, The 44th Annual meeting of the Japanese Society for Crystalline Lens Research.

    2018年07月

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    Conference President,
    The 44th Annual meeting of the Japanese Society for Crystalline Lens Research.

 

Courses Taught 【 Display / hide

  • SPECIAL PRACTICE IN TISSUE CULTURE AND GENE TECHNOLOGY

    2022

  • SEMINAR: (HYGIENIC CHEMISTRY)

    2022

  • RESEARCH FOR BACHELOR'S THESIS 1

    2022

  • RESEARCH APPARATUS LABORATORY COURSE

    2022

  • PRACTICAL NUTRITIONAL INFORMATION

    2022

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Committee Experiences 【 Display / hide

  • 2018.07

    大会長, 第44回 水晶体研究会 

  • 2022.04
    -
    Present

    理事, 日本老視学会

  • 2021.11
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    Present

    The Journal of The Japanese Society for Cataract Research, Editor-in-Chief, 日本白内障学会

  • 2021.04
    -
    Present

    評議員, 日本眼薬理学会

  • 2019.07
    -
    Present

    評議員, 白内障学会

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