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小暮健太朗

徳島大学

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2024年4月26日更新

職名: 教授
電話: 088-633-7248
電子メール: kogure@tokushima-u.ac.jp
学歴: 1989/3: 徳島大学薬学部卒業
1991/3: 徳島大学大学院薬学研究科博士前期課程修了
1994/3: 徳島大学大学院薬学研究科博士後期課程修了博士(薬学)学位取得
学位: 博士(薬学) (徳島大学)
職歴・経歴: 1994/4: 富山医科薬科大学薬学部教務職員
1994/10: 富山医科薬科大学薬学部助手
1998/3: 徳島大学薬学部助手
2003/4: 科学技術振興機構 CREST 博士研究員
2005/1: 北海道大学大学院薬学研究科寄附講座講師
2006/4: 北海道大学大学院薬学研究院特任講師(組織改組に伴う変更)
2007/4: 京都薬科大学薬品物理化学分野教授
2016/1: 徳島大学大学院医歯薬学研究部(薬学系)衛生薬学分野教授

専門分野・研究分野: 生物物理化学 (Biophysical Chemistry)
薬物送達学
衛生薬学

研究者総覧で最新データを確認する

2024年4月26日更新

専門分野・研究分野: 生物物理化学 (Biophysical Chemistry)
薬物送達学
衛生薬学
担当経験のある授業科目: コアDDS講義 (学部)
健康生命薬学特論 (大学院)
先端医療薬学 (学部)
創薬研究実践特論 (大学院)
創薬科学演習 (大学院)
医療における人間学 (学部)
基礎医療薬学 (学部)
学術論文作成法 (学部)
専攻公開ゼミナール (大学院)
環境薬学 (学部)
研究体験演習 (学部)
研究倫理WS (学部)
社会医学・疫学・医学統計概論 (大学院)
社会薬学 (学部)
英語プレゼン実践講座 (学部)
薬学科学特論Ⅰ (大学院)
薬科学演習1 (大学院)
薬科学特別研究 (大学院)
衛生化学実習 (学部)
衛生薬学1(栄養) (学部)
衛生薬学2(疾病) (学部)
資源・環境共通演習 (大学院)
指導経験: 1人 (博士)

研究者総覧で最新データを確認する

2024年4月26日更新

専門分野・研究分野: 生物物理化学 (Biophysical Chemistry)
薬物送達学
衛生薬学

研究テーマ: 1) 抗酸化物質の作用発現機構解明とその誘導体による生活習慣病治療, 微弱電流による細胞生理の制御メカニズムの解明

著書

小暮健太朗 :
ビタミン・バイオファクター総合事典, --- 1.3. ビタミンE 1.3.7 生理学・薬理学(抗酸化作用) ---,
朝倉書店, 東京, 2021年7月. 田中保, 小暮健太朗 :
3.6. 活性リン脂質 3.6.1. はじめに,
朝倉書店, 2021年7月. 小暮健太朗 :
第3章1節脂質型キャリア,
丸善出版, 2018年12月. 濱進, 板倉祥子, 小暮健太朗 :
がん微小環境をターゲットとしたDDS技術開発,
株式会社技術情報協会, 2017年5月. 眞岡孝至, 小暮健太朗 :
第22章アスタキサンチン,
2016年. 後藤了, 小暮健太朗, 土屋浩一郎, 尾関哲也 :
エピソード物理化学,
2011年3月. 福澤健治, 小暮健太朗, 真鍋幸恵, 德村彰 :
ビタミンE研究の進歩 XII, --- α-トコフェロールジカルボン酸誘導体の抗ガン作用 ---,
共立出版株式会社, 東京, 2007年. 真鍋幸恵, 小暮健太朗, 森田健之, 德村彰, 福澤健治 :
ビタミンE研究の進歩 XI, --- 抗ガン作用の増強を指向したビタミンEコハク酸ベシクル ---,
共立出版株式会社, 東京, 2004年. 福澤健治, 小暮健太朗, 中島佐和, 土江明子, 德村彰 :
ビタミンE研究の進歩 XI, --- リン脂質酸化二次産物による血管平滑筋細胞のアポトーシス誘導とビタミンEによる抑制作用 ---,
共立出版株式会社, 東京, 2004年. 小暮健太朗, 德村彰, 福澤健治 :
ビタミンE研究の進歩 X, --- α-トコフェロールコハク酸誘導アポトーシスの誘導機構 ---,
共立出版株式会社, 東京, 2002年. 濱進, 小暮健太朗, 森田元喜, 德村彰, 福澤健治 :
ビタミンE研究の進歩 X, --- ラット血管平滑筋細胞におけるα-トコフェロールコハク酸の一酸化窒素(NO)産生促進作用にはプロテインキナーゼCが関与する ---,
共立出版株式会社, 東京, 2002年.

論文

Naoshi Yamazaki, Ohtsuka Chiho and Kentaro Kogure :
Weak electric current increases ceramide levels by inducing ceramide synthase expression,
Journal of Asian Association of Schools of Pharmacy, Vol.13, 1-5, 2024. Seiko Nakamura, Mizune Ohzono, Karen Yanagi and Kentaro Kogure :
Development of an effective psoriasis treatment by combining tacrolimus-encapsulated liposomes and iontophoresis,
Biological & Pharmaceutical Bulletin, Vol.47, No.1, 196-203, 2023.

(要約): Psoriasis is a chronic T-cell-mediated autoimmune skin disease. Tacrolimus (FK506) is commonly used treatment for psoriasis. However, since the molecular weight of FK506 is more than 500 Da, its skin penetration is limited, so that there is a need to improve the penetrability of FK506 to allow for more effective treatment. To this end, we employed iontophoresis (ItP), which is a physical, intradermal drug delivery technology that relies on the use of weak electric current. Previous findings suggest that activation of cell signaling by the weak electric current applied during ItP may affect the expression of inflammatory cytokines, leading to aggravation of psoriasis. In this study, we analyzed the effect of ItP on the expression of various inflammatory cytokines in the skin, and subsequently examined the therapeutic effect of ItP using negatively-charged liposomes encapsulating FK506 (FK-Lipo) in a rat psoriasis model induced by imiquimod. We found that ItP (0.34 mA/cm, 1 h) did not affect mRNA levels of inflammatory cytokines or epidermis thickness, indicating that ItP is a safe technology for psoriasis treatment. ItP of FK-Lipo suppressed the expression of inflammatory cytokines induced by imiquimod treatment to a greater extent than skin treated with FK506 ointment for 1 h. Furthermore, epidermis thickening was significantly suppressed only by ItP of FK-Lipo. Taken together, results of this study demonstrate the successful development of an efficient treatment for psoriasis by combining FK-Lipo and ItP, without disease aggravation associated with the weak electric current.
(徳島大学機関リポジトリ): ● Metadata: 118787
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/bpb.b23-00667
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38246645; ● Search Scopus @ Elsevier (PMID): 38246645; ● Search Scopus @ Elsevier (DOI): 10.1248/bpb.b23-00667

(徳島大学機関リポジトリ: 118787, DOI: 10.1248/bpb.b23-00667, PubMed: 38246645) Manobendro Nath Ray, Michiko Kiyofuji, Mizune Ohzono and Kentaro Kogure :
Vitamin E succinate mediated apoptosis by juxtaposing endoplasmic reticulum and mitochondria,
Biochimica et Biophysica Acta (BBA) - General Subjects, Vol.1867, No.12, 130485, 2023.

(要約): Vitamin E succinate (VES) is an esterified form of natural α-tocopherol, has turned out to be novel anticancer agent. However, its anticancer mechanisms have not been illustrated. Previously, we reported VES mediated Ca release from the endoplasmic reticulum (ER) causes mitochondrial Ca overload, leading to mitochondrial depolarization and apoptosis. Here, we elucidated the mechanism of VES-induced Ca transfer from ER to mitochondria by investigating the role of VES in ER-mitochondria contact formation. Transmission electron microscopic observation confirms VES mediated ER-mitochondria contact while fluorescence microscopic analysis revealed that VES increased mitochondria-associated ER membrane (MAM) formation. Pre-treatment with the inositol 1,4,5-triphosphate receptor (IPR) antagonist 2-aminoethyl diphenylborinate (2-APB) decreased VES-induced MAM formation, suggesting the involvement of VES-induced Ca efflux from ER in MAM formation. The ER IPR receptor is known to interact with voltage-dependent anion channels (VDAC) via the chaperone glucose-regulated protein 75 kDa (GRP75) to bring ER and mitochondria nearby. Although we revealed that VES treatment does not affect GRP75 protein level, it increases GRP75 localization in the MAM. In addition, the inhibition of Ca release from ER by 2-APB decreases GRP75 localization in the MAM, suggesting the possibility of Ca-induced conformational change of GRP75 that promotes formation of the IPR-GRP75-VDAC complex and thereby encourages MAM formation. This study identifies the mechanism of VES-induced enhanced Ca transfer from ER to mitochondria, which causes mitochondrial Ca overload leading to apoptosis.
(キーワード): alpha-Tocopherol / Mitochondria / Endoplasmic Reticulum / Apoptosis
(徳島大学機関リポジトリ): ● Metadata: 118618
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bbagen.2023.130485
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37838355; ● Search Scopus @ Elsevier (PMID): 37838355; ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbagen.2023.130485

(徳島大学機関リポジトリ: 118618, DOI: 10.1016/j.bbagen.2023.130485, PubMed: 37838355) Shinya Inoue, Yasufumi Ohshima and Kentaro Kogure :
Non-invasive intradermal delivery of hyaluronic acid via iontophoresis,
Biological & Pharmaceutical Bulletin, Vol.46, No.11, 1635-1638, 2023.

(要約): Hyaluronic acid (HA) is a hydrophilic supra-macromolecule, with a molecular weight (MW) 1000000<. HA is recognized as a biomaterial for skin moisturization. HA solution is typically injected into the skin using a needle. However, needle injection is invasive and does not result in homogeneous distribution of HA over a large area of skin. Therefore, non-invasive and effective technologies for homogenous intradermal delivery of HA are needed. Recently, we demonstrated the use of iontophoresis (ItP) for non-invasive intradermal delivery of various macromolecules, such as small interfering RNA (siRNA) (MW: 12000) and antibodies (MW: 150000). Based on our previous studies, we hypothesized that HA can also be delivered non-invasively into the skin by ItP. In this study, we applied ItP to fluorescence-labeled HA (MW: 600000-1120000 and 1200000-1600000) on rat dorsal skin. Following treatment, fluorescence was observed to be widely distributed in the skin, demonstrating successful intradermal delivery of HA via ItP. In addition, the relative moisture content and elasticity of skin treated with ItP/HA was temporarily higher than that of control skin. This is the first report demonstrating successful non-invasive intradermal delivery of HA and improvement of skin conditions by high-molecular weight HA delivered by ItP. In conclusion, ItP would be a useful technology for non-invasive intradermal delivery of high-molecular weight HA for treatment of skin diseases and cosmetology applications.
(キーワード): Animals / Rats / Hyaluronic Acid / Iontophoresis / Skin / Administration, Cutaneous / Skin Absorption / Skin Diseases
(徳島大学機関リポジトリ): ● Metadata: 118568
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/bpb.b23-00408
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37914367; ● Search Scopus @ Elsevier (PMID): 37914367; ● Search Scopus @ Elsevier (DOI): 10.1248/bpb.b23-00408

(徳島大学機関リポジトリ: 118568, DOI: 10.1248/bpb.b23-00408, PubMed: 37914367) Tabassum Ara and Kentaro Kogure :
Nanoparticles Encapsulated γ-Oryzanol as a Natural Prodrug of Ferulic Acid for the Treatment of Oxidative Liver Damage,
Biological & Pharmaceutical Bulletin, Vol.46, No.10, 1403-1411, 2023.

(要約): Antioxidants are promising therapeutics for treating oxidative stress-mediated liver diseases. Previously, we studied a potent natural antioxidant, ferulic acid, and developed a liposomal formulation of ferulic acid (ferulic-lipo) to improve its solubility. Ferulic-lipo significantly attenuated oxidative damage in the liver by inhibiting reactive oxygenase species (ROS). However, antioxidative liposomes must be less reactive with ROS prior to reaching the target sites to effectively neutralize existing ROS. But ferulic-lipo tends to be oxidized before reaching the liver. Besides, γ-oryzanol has been reported to decompose into ferulic acid in vivo; accordingly, we hypothesized that γ-oryzanol could be employed as a natural prodrug of ferulic acid to improve stability and antioxidative effectiveness. Therefore, in this study, we prepared a liposomal formulation of γ-oryzanol (γ-ory-lipo) and investigated its therapeutic effects in a CCl-induced rat model of liver injury. We found that γ-ory-lipo has a higher chemical stability than does free γ-oryzanol. Although the antioxidative effect of γ-ory-lipo was lower than that of ferulic-lipo, pretreatment of the HepG2 cells with γ-ory-lipo improved the viability of CCl-treated cells to a similar level as treatment with ferulic-lipo. γ-Oryzanol was shown to be converted into ferulic acid in vitro and in vivo. Furthermore, intravenous administration of γ-ory-lipo exhibited a similar effectiveness as ferulic-lipo against CCl-induced hepatotoxicity, which should be the due to the conversion of γ-oryzanol into ferulic acid. These findings demonstrated that γ-ory-lipo could be a good natural prodrug of ferulic acid for eradicating its stability problem.
(キーワード): Rats / Animals / Prodrugs / Reactive Oxygen Species / Oxidative Stress / Antioxidants / Phenylpropionates / Liver Diseases / Nanoparticles
(徳島大学機関リポジトリ): ● Metadata: 118472
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/bpb.b23-00181
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37779041; ● Search Scopus @ Elsevier (PMID): 37779041; ● Search Scopus @ Elsevier (DOI): 10.1248/bpb.b23-00181

(徳島大学機関リポジトリ: 118472, DOI: 10.1248/bpb.b23-00181, PubMed: 37779041) Tatsuya Fukuta, Akina Nishikawa, Ami Hiramachi, Sachika Yamashita and Kentaro Kogure :
Development of functional chimeric nanoparticles by membrane fusion of small extracellular vesicles and drug-encapsulated liposomes,
Biological & Pharmaceutical Bulletin, Vol.46, No.8, 1098-1104, 2023.

(要約): Since small extracellular vesicle (sEVs) are involved in cell-to-cell communication via transfer of certain bioactive molecules and have the capability to overcome biological barriers against drug transport, their use as a drug delivery system (DDS) has been demonstrated in treatment of a diverse range of diseases. However, some issues in drug encapsulation have been pointed out, including low encapsulation efficiency and poor reproducibility. It was previously reported that liposomes containing phosphatidylserine (PS) can fuse together in the presence of calcium ion, which allows for drug encapsulation into the resultant liposomes (i.e., calcium fusion method). On the other hand, PS is reportedly present in lipid membrane of sEVs as a distinct lipid composition. We therefore hypothesized that PS-mediated membrane fusion of sEVs with PS-liposomes encapsulating therapeutic agents via the calcium fusion method can be applied to convenient drug encapsulation into sEVs. Membrane fusion of PS-liposomes and sEVs derived from murine melanoma B16F1 cells (B16-sEVs) was firstly confirmed. The obtained nanoparticles, termed chimeric nanoparticles (CM-NP), showed comparable cellular uptake to B16-sEVs into B16F1 cells. Moreover, CM-NP encapsulating an anticancer drug doxorubicin (DOX) (CM-NP-DOX) could be prepared by membrane fusion of PS-liposomes encapsulating DOX (PS-Lipo-DOX) and B16-sEVs. CM-NP-DOX exhibited a superior anticancer effect on B16F1 cells in vitro compared with PS-Lipo-DOX. These findings suggest that the calcium fusion method could be applied for membrane fusion of sEVs and PS-liposomes, and that this approach would likely be useful for efficient drug encapsulation into sEVs, as well as increasing liposome functionality.
(キーワード): Animals / Mice / Liposomes / Calcium / Membrane Fusion / Reproducibility of Results / Doxorubicin / Nanoparticles / Extracellular Vesicles / Lipids
(徳島大学機関リポジトリ): ● Metadata: 118301
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/bpb.b23-00135
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37532560; ● Search Scopus @ Elsevier (PMID): 37532560; ● Search Scopus @ Elsevier (DOI): 10.1248/bpb.b23-00135

(徳島大学機関リポジトリ: 118301, DOI: 10.1248/bpb.b23-00135, PubMed: 37532560) Kohki Michiue, Kentaro Takayama, Atsuhiko Taniguchi, Yoshio Hayashi and Kentaro Kogure :
Increasing Skeletal Muscle Mass in Mice by Non-Invasive Intramuscular Delivery of Myostatin Inhibitory Peptide by Iontophoresis,
Pharmaceuticals, Vol.16, 397, 2023.

(要約): Sarcopenia is a major public health issue that affects older adults. Myostatin inhibitory-D-peptide-35 (MID-35) can increase skeletal muscle and is a candidate therapeutic agent, but a non-invasive and accessible technology for the intramuscular delivery of MID-35 is required. Recently, we succeeded in the intradermal delivery of various macromolecules, such as siRNA and antibodies, by iontophoresis (ItP), a non-invasive transdermal drug delivery technology that uses weak electricity. Thus, we expected that ItP could deliver MID-35 non-invasively from the skin surface to skeletal muscle. In the present study, ItP was performed with a fluorescently labeled peptide on mouse hind leg skin. Fluorescent signal was observed in both skin and skeletal muscle. This result suggested that the peptide was effectively delivered to skeletal muscle from skin surface by ItP. Then, the effect of MID-35/ItP on skeletal muscle mass was evaluated. The skeletal muscle mass increased 1.25 times with ItP of MID-35. In addition, the percentage of new and mature muscle fibers tended to increase, and ItP delivery of MID-35 showed a tendency to induce alterations in the levels of mRNA of genes downstream of myostatin. In conclusion, ItP of myostatin inhibitory peptide is a potentially useful strategy for treating sarcopenia.
(徳島大学機関リポジトリ): ● Metadata: 118028
(出版サイトへのリンク): ● Publication site (DOI): 10.3390/ph16030397
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36986496; ● Search Scopus @ Elsevier (PMID): 36986496; ● Search Scopus @ Elsevier (DOI): 10.3390/ph16030397

(徳島大学機関リポジトリ: 118028, DOI: 10.3390/ph16030397, PubMed: 36986496) Rabab A. Husseini, Tatsuya Fukuta, Mizune Ohzono, Azza A. Hasan, Nagia El A. Megrab and Kentaro Kogure :
The effect of iontophoretic-delivered polyplex vaccine on melanoma regression,
Biological & Pharmaceutical Bulletin, Vol.46, No.3, 494-504, 2023.

(要約): Although the strategy in cancer vaccination is to provide a therapeutic effect against an established tumor, there is an urgent need to develop prophylactic vaccines for non-viral cancers. In this study, we prepared polyplex nanoparticles through electrostatic interactions between a positively-charged modified tumor associated antigen, namely human derived melanoma gp100 peptide (KVPRNQDWL-RRRR), and a negatively charged cytosine-phosphate-guanosine motif (CpG-ODN) adjuvant. We previously demonstrated successful transdermal delivery of various hydrophilic macromolecules by iontophoresis (IP) using weak electricity. Herein, we investigated the effectiveness of IP in the transdermal delivery of a prophylactic polyplex vaccine. IP was successful in establishing a homogenous distribution of the vaccine throughout skin. Efficacy of the vaccine was demonstrated against melanoma growth. A significant tumor regression effect was observed, which was confirmed by elevated mRNA expression levels of various cytokines, mainly interferon (IFN)-γ, as well as infiltration of cytotoxic CD8 T cells. Additionally, we evaluated the therapeutic effect of the vaccine and we found a significant reduction in tumor burden. Stimulation of systemic immunity was confirmed by upregulation of IFN-γ. This is the first report to demonstrate the use of IP in the transdermal delivery of a prophylactic melanoma vaccine.
(キーワード): Humans / Iontophoresis / CD8-Positive T-Lymphocytes / Melanoma / Cancer Vaccines / Interferon-gamma
(徳島大学機関リポジトリ): ● Metadata: 117908
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/bpb.b22-00873
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36858579; ● Search Scopus @ Elsevier (PMID): 36858579; ● Search Scopus @ Elsevier (DOI): 10.1248/bpb.b22-00873

(徳島大学機関リポジトリ: 117908, DOI: 10.1248/bpb.b22-00873, PubMed: 36858579) Ray Nath Manobendro, Mizune Ohzono, Michiyasu Nakao, Shigeki Sano and Kentaro Kogure :
Only one carbon difference determines the pro-apoptotic activity of α-tocopheryl esters,
The FEBS Journal, Vol.290, 1027-1048, 2023.

(要約): α-Tocopheryl succinate (TS), a redox-silent succinyl ester of natural α-Tocopherol, has emerged as a novel anti-cancer agent. However, the underlying mechanism is unclear. We found that the terminal dicarboxylic moiety of tocopheryl esters contributes to apoptosis induction and thus cytotoxicity. To further examine this relationship, we compared the pro-apoptotic activity of TS, which has four carbon atoms in the terminal dicarboxylic moiety, to that of a newly synthesized, tocopheryl glutarate (Tglu), which has five. Cytotoxicity assays in vitro confirmed that TS stimulated apoptosis, while Tglu was non-cytotoxic. In investigating biological mechanisms leading to these opposing effects, we found that TS caused an elevation of intracellular superoxide, but Tglu did not. TS increased intracellular Ca in cultured cells, suggesting induction of endoplasmic reticulum (ER) stress; however, Tglu did not affect Ca homeostasis. 1,4,5-trisphosphate (IP ) receptor antagonist 2-Aminoethyl diphenylborinate (2-APB) decreased TS-induced intracellular Ca , restored mitochondrial activity and cell viability in TS-treated cells, establishing the ER-mitochondria relationship in apoptosis induction. Moreover, real-time PCR, immunostaining and Western blotting assays revealed that TS downregulated glucose-regulated protein 78 (GRP78), which maintains ER homeostasis and promotes cell survival. Conversely, Tglu upregulates GRP78. Taken together, our results suggest a model in which TS-mediated superoxide production and GRP78 inhibition induce ER stress, which elevates intracellular Ca and depolarizes mitochondria, leading to apoptosis. Because Tglu does not affect superoxide generation and increases GRP78 expression, it inhibits ER stress and is thereby non-cytotoxic. Our research provides insight into the structure-activity relationship of tocopheryl esters regarding the induction of apoptosis.
(徳島大学機関リポジトリ): ● Metadata: 117788
(出版サイトへのリンク): ● Publication site (DOI): 10.1111/febs.16623
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36083714; ● Summary page in Scopus @ Elsevier: 2-s2.0-85138289941

(徳島大学機関リポジトリ: 117788, DOI: 10.1111/febs.16623, PubMed: 36083714, Elsevier: Scopus) A R Husseini, Naoko Abe, Tomoaki Hara, Hiroshi Abe and Kentaro Kogure :
Use of iontophoresis technology for transdermal delivery of a minimal mRNA vaccine as a potential melanoma therapeutic,
Biological & Pharmaceutical Bulletin, Vol.46, No.2, 301-308, 2023.

(要約): mRNA vaccines have attracted considerable attention as a result of the 2019 coronavirus pandemic; however, challenges remain regarding use of mRNA vaccines, including insufficient delivery owing to the high molecular weights and high negative charges associated with mRNA. These characteristics of mRNA vaccines impair intracellular uptake and subsequent protein translation. In the current study, we prepared a minimal mRNA vaccine encoding a tumor associated antigen human gp100 peptide (KVPRNQDWL), as a potential treatment for melanoma. Minimal mRNA vaccines have recently shown promise at improving the translational process, and can be prepared via a simple production method. Moreover, we previously reported the successful use of iontophoresis (IP) technology in the delivery of hydrophilic macromolecules into skin layers, as well as intracellular delivery of small interfering RNA (siRNA). We hypothesized that combining IP technology with a newly synthesized minimal mRNA vaccine can improve both transdermal and intracellular delivery of mRNA. Following IP-induced delivery of a mRNA vaccine, an immune response is elicited resulting in activation of skin resident immune cells. As expected, combining both technologies led to potent stimulation of the immune system, which was observed via potent tumor inhibition in mice bearing melanoma. Additionally, there was an elevation in mRNA expression levels of various cytokines, mainly interferon (IFN)-γ, as well as infiltration of cytotoxic CD8 T cells in the tumor tissue, which are responsible for tumor clearance. This is the first report demonstrating the application of IP for delivery of a minimal mRNA vaccine as a potential melanoma therapeutic.
(キーワード): Animals / Humans / Mice / Cancer Vaccines / CD8-Positive T-Lymphocytes / Iontophoresis / Melanoma / mRNA Vaccines
(徳島大学機関リポジトリ): ● Metadata: 117787
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/bpb.b22-00746
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36724958; ● Search Scopus @ Elsevier (PMID): 36724958; ● Search Scopus @ Elsevier (DOI): 10.1248/bpb.b22-00746

(徳島大学機関リポジトリ: 117787, DOI: 10.1248/bpb.b22-00746, PubMed: 36724958) El-Emam Mohamed Abd Mahran, Ray Nath Manobendro, Mizune Ohzono and Kentaro Kogure :
Heat stress disrupts spermatogenesis via modulation of sperm-specific calcium channels in rats,
Journal of Thermal Biology, Vol.112, 103465, 2023.

(要約): Heat is a detrimental environmental stressor that disrupts spermatogenesis and results in male infertility. Previous investigations have shown that heat stress reduces the motility, number, and fertilization ability of living spermatozoa. Sperm hyperactivation, capacitation, acrosomal reaction, and chemotaxis towards the ova are regulated by the cation channel of sperm (CatSper). This sperm-specific ion channel triggers the influx of calcium ions into sperm cells. The aim of this study in rats was to investigate whether heat treatment affected the expression levels of CatSper-1 and -2, together with the sperm parameters, testicular histology and weight. The rats were exposed to heat stress for 6 days and the cauda epididymis and testis were collected 1, 14, and 35 days after heat treatment to measure sperm parameters, gene and protein expression, testicular weight, and histology. Interestingly, we found that heat treatment caused a notable downregulation of CatSper-1 and -2 expression at all three time points. In addition, there were significant reductions in sperm motility and number and an increase in the percentage of abnormal sperm at 1 and 14 days, with cessation of sperm production at 35 days. Furthermore, expression of the steroidogenesis regulator, 3 beta-hydroxysteroid dehydrogenase (3β-HSD) was upregulated in the 1-, 14- and 35-day samples. Heat treatment also upregulated the expression of the apoptosis regulator, BCL2-associated X protein (BAX), decreased testicular weight, and altered testicular histology. Therefore, our data showed for the first time that heat stress downregulated CatSper-1 and -2 in the rat testis, and that this may be a mechanism involved in heat stress-induced impairment of spermatogenesis.
(キーワード): Male / Rats / Animals / Calcium Channels / Semen / Sperm Motility / Spermatozoa / Spermatogenesis / Testis / Calcium
(徳島大学機関リポジトリ): ● Metadata: 117909
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.jtherbio.2023.103465
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36796910; ● Search Scopus @ Elsevier (PMID): 36796910; ● Search Scopus @ Elsevier (DOI): 10.1016/j.jtherbio.2023.103465

(徳島大学機関リポジトリ: 117909, DOI: 10.1016/j.jtherbio.2023.103465, PubMed: 36796910) Ara Tabassum, Satoko Ono, M Hasan, Mizune Ohzono and Kentaro Kogure :
Protective effects of liposomes encapsulating ferulic acid against CCl4-induced oxidative liver damage in vivo rat model,
Journal of Clinical Biochemistry and Nutrition, Vol.72, No.1, 46-53, 2023.

(要約): Antioxidants are useful for the treatment of oxidative stress mediated liver damage. A naturally occurring antioxidant γ-oryzanol is rapidly hydrolyzed to its active hydrophobic metabolite, ferulic acid, inside the body. Limitations associated with the hydrophobicity of ferulic acid can be overcome by encapsulating in a liposomal formulation. As intravenously administered nanoparticles (including liposomes) can effectively reach the liver, such systems may be suitable drug delivery carriers to treat liver injury. In this study, we prepared a liposomal formulation of ferulic acid (ferulic-lipo) and examined its effects on liver damage induced by CCl. Ferulic-lipo were ~100 nm in size and drug encapsulation efficiency was about 92%. Ferulic-lipo showed potent scavenging efficacy against hydroxyl radical compared to α-tocopherol liposomes. Ferulic-lipo significantly prevented CCl-mediated cytotoxicity in human hepatocarcinoma cells. Furthermore, intravenous administration of ferulic-lipo significantly reduced alanine aminotransferase and aspartate amino transferase levels in a rat model of liver injury. CCl-mediated reactive oxygen species generation in liver was also reduced by intravenous administration of ferulic-lipo. Hepatoprotective effects of ferulic-lipo were demonstrated by histological observation of CCl-induced liver tissue damage. Therefore, ferulic-lipo exhibit potent antioxidative capacity and were suggested to be an effective formulation for prevention of oxidative damage of liver tissue.
(徳島大学機関リポジトリ): ● Metadata: 117266
(出版サイトへのリンク): ● Publication site (DOI): 10.3164/jcbn.22-37
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36777075; ● Search Scopus @ Elsevier (PMID): 36777075; ● Search Scopus @ Elsevier (DOI): 10.3164/jcbn.22-37

(徳島大学機関リポジトリ: 117266, DOI: 10.3164/jcbn.22-37, PubMed: 36777075) Morito Katsuya, Shimizu Ryota, Ali Hanif, Shimada Akina, Miyazaki Tohru, Takahashi Naoko, Rahman Motiur M., Tsuji Kazuki, Shimozawa Nobuyuki, Michiyasu Nakao, Shigeki Sano, Momoyo Azuma, Nanjundan Meera, Kentaro Kogure and Tamotsu Tanaka :
Molecular species profiles of plasma ceramides in different clinical types of X-linked adrenoleukodystrophy,
The Journal of Medical Investigation : JMI, Vol.70, No.3.4, 403-410, 2023.

(要約): X-linked adrenoleukodystrophy (X-ALD) is a genetic disorder associated with peroxisomal dysfunction. Patients with this rare disease accumulate very long-chain fatty acids (VLCFAs) in their bodies because of impairment of peroxisomal VLCFA ?-oxidation. Several clinical types of X-ALD, ranging from mild (axonopathy in the spinal cord) to severe (cerebral demyelination), are known. However, the molecular basis for this phenotypic variability remains largely unknown. In this study, we determined plasma ceramide (CER) profile using liquid chromatography-tandem mass spectrometry. We characterized the molecular species profile of CER in the plasma of patients with mild (adrenomyeloneuropathy;AMN) and severe (cerebral) X-ALD. Eleven X-ALD patients (five cerebral, five AMN, and one carrier) and 10 healthy volunteers participated in this study. Elevation of C26:0 CER was found to be a common feature regardless of the clinical types. The level of C26:1 CER was significantly higher in AMN but not in cerebral type, than that in healthy controls. The C26:1 CER level in the cerebral type was significantly lower than that in the AMN type. These results suggest that a high level of C26:0 CER, along with a control level of C26:1 CER, is a characteristic feature of the cerebral type X-ALD. J. Med. Invest. 70 : 403-410, August, 2023.
(キーワード): Humans / Adrenoleukodystrophy / Ceramides
(徳島大学機関リポジトリ): ● Metadata: 118324
(出版サイトへのリンク): ● Publication site (DOI): 10.2152/jmi.70.403
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37940524; ● Search Scopus @ Elsevier (PMID): 37940524; ● Search Scopus @ Elsevier (DOI): 10.2152/jmi.70.403

(徳島大学機関リポジトリ: 118324, DOI: 10.2152/jmi.70.403, PubMed: 37940524) Misaki Yamasaki, Yuika Seto, Mizune Ohzono, Michiyasu Nakao, Akira Shigenaga, Akira Otaka, Shigeki Sano and Kentaro Kogure :
Development of a novel tocopheryl ester for suppression of lipid accumulation without cytotoxicity by optimization of dicarboxylic ester moiety,
Biochemistry and Biophysics Reports, Vol.31, 101329, 2022.

(徳島大学機関リポジトリ): ● Metadata: 117361
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bbrep.2022.101329
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrep.2022.101329

(徳島大学機関リポジトリ: 117361, DOI: 10.1016/j.bbrep.2022.101329) Shintaroh Yoneda, Tatsuya Fukuta, Mizune Ohzono and Kentaro Kogure :
Enhancement of cerebroprotective effects of lipid nanoparticles encapsulating FK506 on cerebral ischemia/reperfusion injury by particle size regulation,
Biochemical and Biophysical Research Communications, Vol.611, 53-59, 2022.

(要約): Delivery of cerebroprotective agents using liposomes has been demonstrated to be useful for treating cerebral ischemia/reperfusion (I/R) injury. We previously reported that intravenous administration of liposomes with diameters of 100 nm showed higher accumulation in the I/R region compared with larger liposomes (>200 nm) by passage through the disintegrated blood-brain barrier, suggesting a size-dependence for liposome-mediated drug delivery. Based on these findings, we hypothesized that regulation of liposomal particle size (<100 nm) may enhance the therapeutic efficacy of encapsulated drugs on cerebral I/R injury. Herein, we prepared lipid nanoparticles (LNP) with particle sizes <100 nm by the microfluidics method and compared their therapeutic potential with LNP exhibiting sizes >100 nm in cerebral I/R model rats. Intravenously administered smaller LNP (ca. 60 nm) exhibited wider accumulation and diffusivity in the brain parenchyma of the I/R region compared with larger LNP (>100 nm). Importantly, treatment with LNP encapsulating the cerebroprotective agent FK506 (FK-LNP) with particle sizes <100 nm showed greater cerebroprotective effects than FK-LNP with sizes >100 nm, and also significantly ameliorated brain injury. These results suggest that particle size regulation of LNP to sizes <100 nm can enhance the therapeutic effect of encapsulated drugs for treatment of cerebral I/R injury, and that FK-LNP could be a promising cerebroprotective agent.
(キーワード): Animals / Brain Ischemia / Liposomes / Nanoparticles / Neuroprotective Agents / Particle Size / Rats / Rats, Wistar / Reperfusion Injury / Tacrolimus
(徳島大学機関リポジトリ): ● Metadata: 117238
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bbrc.2022.04.080
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35477093; ● Search Scopus @ Elsevier (PMID): 35477093; ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrc.2022.04.080

(徳島大学機関リポジトリ: 117238, DOI: 10.1016/j.bbrc.2022.04.080, PubMed: 35477093) S Hama, T Nishi, E Isono, S Itakura, Y Yoshikawa, A Nishimoto, S Suzuki, N Kirimura, H Todo and Kentaro Kogure :
Intraperitoneal administration of nanoparticles containing tocopheryl succinate prevents peritoneal dissemination,
Cancer Science, Vol.113, No.5, 1779-1788, 2022.

(要約): Intraperitoneal administration of anticancer nanoparticles is a rational strategy for preventing peritoneal dissemination of colon cancer due to the prolonged retention of nanoparticles in the abdominal cavity. However, instability of nanoparticles in body fluids causes inefficient retention, reducing its anticancer effects. We have previously developed anticancer nanoparticles containing tocopheryl succinate, which showed high in vivo stability and multifunctional anticancer effects. In the present study, we have demonstrated that peritoneal dissemination derived from colon cancer was prevented by intraperitoneal administration of tocopheryl succinate nanoparticles. The biodistribution of tocopheryl succinate nanoparticles was evaluated using inductively coupled plasma mass spectroscopy and imaging analysis in mice administered quantum dot encapsulated tocopheryl succinate nanoparticles. Intraperitoneal administration of tocopheryl succinate nanoparticles showed longer retention in the abdominal cavity than by its intravenous (i.v.) administration. Moreover, due to effective biodistribution, tumor growth was prevented by intraperitoneal administration of tocopheryl succinate nanoparticles. Furthermore, the anticancer effect was attributed to the inhibition of cancer cell proliferation and improvement of the intraperitoneal microenvironment, such as decrease in the levels of vascular endothelial growth factor A, interleukin 10, and M2-like phenotype of tumor-associated macrophages. Collectively, intraperitoneal administration of tocopheryl succinate nanoparticles is expected to have multifaceted antitumor effects against colon cancer with peritoneal dissemination.
(キーワード): Animals / Colonic Neoplasms / Humans / Mice / Nanoparticles / Succinates / Tissue Distribution / Tumor Microenvironment / Vascular Endothelial Growth Factor A / alpha-Tocopherol
(徳島大学機関リポジトリ): ● Metadata: 117424
(出版サイトへのリンク): ● Publication site (DOI): 10.1111/cas.15321
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35253340; ● Search Scopus @ Elsevier (PMID): 35253340; ● Search Scopus @ Elsevier (DOI): 10.1111/cas.15321

(徳島大学機関リポジトリ: 117424, DOI: 10.1111/cas.15321, PubMed: 35253340) S Hama, N Kirimura, A Obara, H Takatsu and Kentaro Kogure :
Tocopheryl phosphate inhibits rheumatoid arthritis-related gene expression in vitro and ameliorates arthritic symptoms in mice,
Molecules, Vol.27, No.4, 1425, 2022.

(要約): Anti-rheumatoid arthritis (RA) effects of α-tocopherol (α-T) have been shown in human patients in a double-blind trial. However, the effects of α-T and its derivatives on fibroblast-like synoviocytes (FLS) during the pathogenesis of RA remain unclear. In the present study, we compared the expression levels of genes related to RA progression in FLS treated with α-T, succinic ester of α-T (TS), and phosphate ester of α-T (TP), as determined via RT-PCR. The mRNA levels of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), matrix metalloproteinase (MMP)-3, and MMP-13 were reduced by treatment with TP without cytotoxicity, while α-T and TS did not show such effects. Furthermore, intraperitoneal injection of TP ameliorated the edema of the foot and joint and improved the arthritis score in laminarin-induced RA model mice. Therefore, TP exerted anti-RA effects through by inhibiting RA-related gene expression.
(キーワード): Animals / Antirheumatic Agents / Arthritis, Rheumatoid / Cytokines / Gene Expression Regulation / Glucans / Humans / Matrix Metalloproteinase 13 / Matrix Metalloproteinase 3 / Mice / alpha-Tocopherol
(徳島大学機関リポジトリ): ● Metadata: 117569
(出版サイトへのリンク): ● Publication site (DOI): 10.3390/molecules27041425
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35209214; ● Search Scopus @ Elsevier (PMID): 35209214; ● Search Scopus @ Elsevier (DOI): 10.3390/molecules27041425

(徳島大学機関リポジトリ: 117569, DOI: 10.3390/molecules27041425, PubMed: 35209214) M Hasan, Tatsuya Fukuta, Shinya Inoue, Hinako Mori, Mayuko Kagawa and Kentaro Kogure :
Iontophoresis-mediated direct delivery of nucleic acid therapeutics, without use of carriers, to internal organs via non-blood circulatory pathways,
Journal of Controlled Release, Vol.343, 392-399, 2022.

(要約): Nanoparticle drug carriers have been employed to achieve systemic delivery of nucleic acid therapeutics, including small interfering RNA (siRNA); however, non-specific distribution and immune-related events often cause undesired adverse effects. Thus, there is a need for a new technology capable of specifically delivering nucleic acid therapeutics to desired sites. We demonstrated the utility of iontophoresis (IP) using weak electric current (0.3-0.5 mA/cm) as a local drug delivery technology. Our previous studies revealed that IP allows for transdermal permeation of nucleic acid therapeutics via induction of intercellular junction cleavage initiated by Ca influx-mediated cellular signaling activation, and subsequent cytoplasmic delivery through a unique endocytosis process in both skin and other cells. Based on these findings, we hypothesized that IP may enable direct delivery of nucleic acid therapeutics to internal organs through non-blood circulatory pathways without the use of delivery carriers. Permeation of fluorescent-labeled nucleic acids administered via IP applied to the surface of the liver and pancreas was observed in both organs, but not with topical application. IP-mediated local delivery of siRNA into the liver and pancreas significantly suppressed target mRNA expression in each organ. Moreover, IP administration of therapeutic siRNA against the molecules responsible for liver steatosis and fibrosis significantly inhibited lipid accumulation and fibrotic hepatic damage in individual model mice. These findings suggest that IP may be a useful technology to directly deliver nucleic acid therapeutics to internal organs without use of drug delivery carriers via non-blood circulatory pathways.
(キーワード): Administration, Cutaneous / Animals / Drug Carriers / Drug Delivery Systems / Iontophoresis / Mice / Nucleic Acids / RNA, Small Interfering
(徳島大学機関リポジトリ): ● Metadata: 117237
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.jconrel.2022.01.052
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35131371; ● Search Scopus @ Elsevier (PMID): 35131371; ● Search Scopus @ Elsevier (DOI): 10.1016/j.jconrel.2022.01.052

(徳島大学機関リポジトリ: 117237, DOI: 10.1016/j.jconrel.2022.01.052, PubMed: 35131371) A Khatun, M Hasan, E M A Mahran, Tatsuya Fukuta, Miyuki Mimura, Riho Tashima, S Yoneda, Shintaroh Yoshimi and Kentaro Kogure :
Effective Anticancer Therapy by Combination of Nanoparticles Encapsulating Chemotherapeutic Agents and Weak Electric Current,
Biological & Pharmaceutical Bulletin, Vol.45, No.2, 194-199, 2022.

(要約): Delivery of medicines using nanoparticles via the enhanced permeability and retention (EPR) effect is a common strategy for anticancer chemotherapy. However, the extensive heterogeneity of tumors affects the applicability of the EPR effect, which needs to overcome for effective anticancer therapy. Previously, we succeeded in the noninvasive transdermal delivery of nanoparticles by weak electric current (WEC) and confirmed that WEC regulates the intercellular junctions in the skin by activating cell signaling pathways (J. Biol. Chem., 289, 2014, Hama et al.). In this study, we applied WEC to tumors and investigated the EPR effect with polyethylene glycol (PEG)-modified doxorubicin (DOX) encapsulated nanoparticles (DOX-NP) administered via intravenous injection into melanoma-bearing mice. The application of WEC resulted in a 2.3-fold higher intratumor accumulation of nanoparticles. WEC decreased the amount of connexin 43 in tumors while increasing its phosphorylation; therefore, the enhancing of intratumor delivery of DOX-NP is likely due to the opening of gap junctions. Furthermore, WEC combined with DOX-NP induced a significant suppression of tumor growth, which was stronger than with DOX-NP alone. In addition, WEC alone showed tumor growth inhibition, although it was not significant compared with non-treated group. These results are the first to demonstrate that effective anticancer therapy by combination of nanoparticles encapsulating chemotherapeutic agents and WEC.
(キーワード): Animals / Antineoplastic Agents / Doxorubicin / Drug Delivery Systems / Electrochemical Techniques / Male / Melanoma / Mice / Mice, Inbred C57BL / Nanoparticles / Neoplasms, Experimental / Xenograft Model Antitumor Assays
(徳島大学機関リポジトリ): ● Metadata: 117236
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/bpb.b21-00714
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35110506; ● Search Scopus @ Elsevier (PMID): 35110506; ● Search Scopus @ Elsevier (DOI): 10.1248/bpb.b21-00714

(徳島大学機関リポジトリ: 117236, DOI: 10.1248/bpb.b21-00714, PubMed: 35110506) Yuma Hirata, Riho Tashima, N Mitsuhashi, S Yoneda, M Ozono, Tatsuya Fukuta, E Majima and Kentaro Kogure :
A simple, fast, and orientation-controllable technology for preparing antibody-modified liposomes,
International Journal of Pharmaceutics, Vol.607, 120966, 2021.

(要約): Modification with antibodies is a useful strategy for the delivery of nanoparticles to target cells. However, the complexity of the required chemical modifications makes them time-consuming and low efficiency, and the orientation of the antibody is challenging to control. To develop a simple, fast, effective, and orientation-controllable technology, we employed staphylococcal protein A, which can bind to the Fc region of antibodies, as a tool for conjugating antibodies to nanoparticles. Specifically, we modified the C-domain dimer of protein A to contain a lysine cluster to create a molecule, DPACK, that would electrostatically bind to anionic liposomes. Using this protein, antibody-modified liposomes can be prepared in 35 min with two steps: (1) interaction of DPACK with liposomes and (2) interaction of an antibody with DPACK-modified liposomes. Binding efficiencies of DPACK with liposomes and IgG with DPACK-modified liposomes were 75% and 72-84%, respectively. Uptake of liposomes modified with anti-epidermal growth factor receptor (EGFR) antibodies via DPACK by EGFR-expressing cancer cells was significantly higher than that of unmodified liposomes, and the liposomes accumulated in tumors and colocalized with EGFR. This simple, fast, effective and orientation-controllable technology for preparing antibody-modified liposomes will be useful for active targeting drug delivery.
(徳島大学機関リポジトリ): ● Metadata: 116134
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ijpharm.2021.120966
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34352337; ● Search Scopus @ Elsevier (PMID): 34352337; ● Search Scopus @ Elsevier (DOI): 10.1016/j.ijpharm.2021.120966

(徳島大学機関リポジトリ: 116134, DOI: 10.1016/j.ijpharm.2021.120966, PubMed: 34352337) Atsushi Nakayama, Tenta Nakamura, Tabassum Ara, tatsuya fukuta, Sangita Karanjit, Takeshi Harada, Asuka Oda, Hideo Sato, Masahiro Abe, Kentaro Kogure and Kosuke Namba :
Development of a novel antioxidant based on a dimeric dihydroisocoumarin derivative,
Tetrahedron Letters, Vol.74, 153176, 2021.

(徳島大学機関リポジトリ): ● Metadata: 116179
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.tetlet.2021.153176
(文献検索サイトへのリンク): ● Summary page in Scopus @ Elsevier: 2-s2.0-85107022552

(徳島大学機関リポジトリ: 116179, DOI: 10.1016/j.tetlet.2021.153176, Elsevier: Scopus) S Hama, M Sakai, S Itakura, E Majima and Kentaro Kogure :
Rapid modification of antibodies on the surface of liposomes composed of high-affinity protein A-conjugated phospholipid for selective drug delivery,
Biochemistry and Biophysics Reports, Vol.27, 101067, 2021.

(要約): Antibody-modified liposomes, immuno-liposomes, can selectively deliver encapsulated drug 'cargos' to cells via the interaction of cell surface proteins with antibodies. However, chemical modification of both the antibodies and phospholipids is required for the preparation of immuno-liposomes for each target protein using conventional methods, which is time-consuming. In the present study, we demonstrated that high-affinity protein A- (Protein A-R28: PAR28) displaying liposomes prepared by the post-insertion of PAR28-conjugated phospholipid through polyethylene glycol (PEG)-linkers (PAR28-PEG-lipo) can undergo rapid modification of antibodies on their surface, and the liposomes can be delivered to cells based on their modified antibodies. Anti-CD147 and anti-CD31 antibodies could be modified with PAR28-PEG-lipo within 1 h, and each liposome was specifically taken up by CD147- and CD31-positive cells, respectively. The cellular amounts of doxorubicin delivered by anti-CD147 antibody-modified PAR28-PEG-lipo were significantly higher than those of isotype control antibody-modified liposomes. PAR28-PEG-lipo can easily and rapidly undergo modification of various antibodies on their surface, which then makes them capable of selective drug delivery dependent on the antibodies.
(徳島大学機関リポジトリ): ● Metadata: 116683
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bbrep.2021.101067
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34258398; ● Search Scopus @ Elsevier (PMID): 34258398; ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrep.2021.101067

(徳島大学機関リポジトリ: 116683, DOI: 10.1016/j.bbrep.2021.101067, PubMed: 34258398) Tatsuya Fukuta, Daichi Tanaka, Shinya Inoue, Kohki Michiue and Kentaro Kogure :
Overcoming thickened pathological skin in psoriasis via iontophoresis combined with tight junction-opening peptide AT1002 for intradermal delivery of NF-κB decoy oligodeoxynucleotide,
International Journal of Pharmaceutics, Vol.602, 120601, 2021.

(要約): Transdermal delivery of nucleic acid therapeutics has been demonstrated to be effective for psoriasis treatment. We previously reported the utility of iontophoresis (IP) using weak electric current (0.3-0.5 mA/cm) for intradermal delivery of nucleic acid therapeutics via weak electricity-mediated intercellular junction cleavage, and subsequent exertion of nucleic acid function. However, the thickened pathological skin in psoriasis hampers permeation of IP-administered macromolecules. Thus, approaches are needed to more strongly cleave intercellular spaces and overcome the psoriatic skin barrier. Herein, we applied a combination of tight junction-opening peptide AT1002 with IP, as synergistic effects of weak electricity-mediated intercellular junction cleavage and the tight junction-opening ability of AT1002 may help overcome thickened psoriatic skin and facilitate macromolecule delivery. Pretreatment with IP of an AT1002 analog exhibiting positively-charged moieties before fluorescence-labeled oligodeoxynucleotide IP resulted in the oligodeoxynucleotide permeation into psoriatic skin, whereas IP of the oligodeoxynucleotide alone did not. Moreover, psoriasis-induced upregulation of inflammatory cytokine mRNA levels was significantly suppressed by NF-κB decoy oligodeoxynucleotide IP combined with the AT1002 analog, resulting in amelioration of epidermis hyperplasia. These results suggest that synergistic effects of IP and an AT1002 analog can overcome thickened psoriatic skin and enable intradermal delivery of NF-κB decoy oligodeoxynucleotide for psoriasis treatment.
(キーワード): Humans / Iontophoresis / Oligodeoxyribonucleotides / Oligopeptides / Peptides / Psoriasis / Skin / Tight Junctions
(徳島大学機関リポジトリ): ● Metadata: 116139
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ijpharm.2021.120601
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33905867; ● Search Scopus @ Elsevier (PMID): 33905867; ● Search Scopus @ Elsevier (DOI): 10.1016/j.ijpharm.2021.120601

(徳島大学機関リポジトリ: 116139, DOI: 10.1016/j.ijpharm.2021.120601, PubMed: 33905867) Dai Majima, Ryosuke Mitsuhashi, M Yamasaki, K Kajimoto, Tatsuya Fukuta and Kentaro Kogure :
Suppression of lipid accumulation in 3T3-L1 adipocytes by α-tocopheryl succinate,
Biological & Pharmaceutical Bulletin, Vol.44, No.1, 46-50, 2021.

(要約): Obesity is a pathological state related to various lifestyle-related diseases, such as diabetes and dyslipidemia, that may be prevented through the development of anti-obesity treatments. Lipid accumulation in cells could be affected by vitamin E ester α-tocopheryl succinate (TS), which has various biological activities, such as anti-cancer effect, via activation of cell signaling pathways, although the antioxidative activity of TS is lost due to esterification of the phenolic OH group. In this study, we found for the first time that TS significantly suppressed lipid accumulation in mouse 3T3-L1 adipocytes. TS treatment reduced the amount of triglycerides in the culture medium, and inhibited activity of glycerol-3-phosphate dehydrogenase, a marker of lipid synthesis. Furthermore, TS accelerated lipolysis. Treatment of adipocytes with TS for 24 h induced no significant cytotoxicity. In TS-treated cells, phosphorylation of Akt, which is involved in fatty acid synthesis via sterol regulatory element-binding proteins (SREBP), was prevented, while levels of phosphorylated protein kinase A (PKA) did not change. Taken together, these results suggest that vitamin E ester TS can suppress lipid accumulation in adipocytes by regulating lipid metabolic cell signaling.
(徳島大学機関リポジトリ): ● Metadata: 115369
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/bpb.b20-00573
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33390549; ● Summary page in Scopus @ Elsevier: 2-s2.0-85098660216

(徳島大学機関リポジトリ: 115369, DOI: 10.1248/bpb.b20-00573, PubMed: 33390549, Elsevier: Scopus) Tatsuya Fukuta, Shintaroh Yoshimi and Kentaro Kogure :
Leukocyte-mimetic liposomes penetrate into tumor spheroids and suppress spheroid growth by encapsulated doxorubicin,
Journal of Pharmaceutical Sciences, Vol.110, No.4, 1701-1709, 2020.

(要約): As leukocytes can penetrate into deep regions of a tumor mass, leukocyte-mimetic liposomes (LM-Lipo) containing leukocyte membrane proteins are also expected to penetrate into tumors by exerting properties of those membrane proteins. The aim of the present study was to examine whether LM-Lipo, which were recently demonstrated to actively pass through inflamed endothelial layers, can penetrate into tumor spheroids, and to investigate the potential of LM-Lipo for use as an anticancer drug carrier. We prepared LM-Lipo via intermembrane protein transfer from human leukemia cells; transfer of leukocyte membrane proteins onto the liposomes was determined by Western blotting. LM-Lipo demonstrated a significantly high association with human lung cancer A549 cells compared with plain liposomes, which contributed to effective anti-proliferative action by encapsulated doxorubicin hydrochloride (DOX). Confocal microscopic images showed that LM-Lipo, but not plain liposomes, could efficiently penetrate into A549 tumor spheroids. Moreover, DOX-encapsulated LM-Lipo significantly suppressed tumor spheroid growth. Thus, leukocyte membrane proteins transferred onto LM-Lipo retained their unique function, which allowed for efficient penetration of the liposomes into tumor spheroids, similar to leukocytes. In conclusion, these results suggest that LM-Lipo could be a useful tumor-penetrating drug delivery system for cancer treatment.
(キーワード): Cell Line, Tumor / Doxorubicin / Drug Delivery Systems / Humans / Leukocytes / リポソーム (liposomes) / Lung Neoplasms
(徳島大学機関リポジトリ): ● Metadata: 115754
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.xphs.2020.10.049
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33129835; ● Summary page in Scopus @ Elsevier: 2-s2.0-85096382956

(徳島大学機関リポジトリ: 115754, DOI: 10.1016/j.xphs.2020.10.049, PubMed: 33129835, Elsevier: Scopus) Tatsuya Fukuta, Natsu Nakatani, Shintaroh YONEDA and Kentaro Kogure :
Weak electric current treatment to artificially enhance vascular permeability in embryonated chicken eggs,
Biological & Pharmaceutical Bulletin, Vol.43, No.11, 1729-1734, 2020.

(要約): Technologies that overcome the barrier presented by vascular endothelial cells are needed to facilitate targeted delivery of drugs into tissue parenchyma by intravenous administration. We previously reported that weak electric current treatment (ET: 0.3-0.5 mA/cm) applied onto skin tissue in a transdermal drug delivery technique termed iontophoresis induces cleavage of intercellular junctions that results in permeation of macromolecules such as small interfering RNA and cytosine-phosphate-guanine (CpG) oligonucleotide through the intercellular space. Based on these findings, we hypothesized that application of ET to blood vessels could promote cleavage of intercellular junctions that artificially induces increase in vascular permeability to enhance extravasation of drugs from the vessels into target tissue parenchyma. Here we investigated the effect of ET (0.34 mA/cm) on vascular permeability using embryonated chicken eggs, which have blood vessels in the chorioallantoic membrane (CAM), as an animal model. ET onto the CAM of the eggs significantly increased extravasation of intravenously injected calcein (M.W. 622.6), a low molecular weight compound model, and the macromolecule fluorescein isothiocyanate (FITC)-dextran (M.W. 10000). ET-mediated promotion of penetration of FITC-dextran through vascular endothelial cells was also observed in transwell permeability assay using monolayer of human umbilical vein endothelial cells without induction of obvious cellular damage. Confocal microscopy detected remarkable fluorescence derived from injected FITC-dextran in blood vessel walls. These results in embryonated chicken eggs suggest that ET onto blood vessels could artificially enhance vascular permeability to facilitate extravasation of macromolecules from blood vessels.
(キーワード): Animals / Capillary Permeability / Chickens / Chorioallantoic Membrane / Dextrans / Electric Stimulation / Endothelium, Vascular / Fluorescein-5-isothiocyanate / Human Umbilical Vein Endothelial Cells / Humans / Injections, Intravenous / Microscopy, Confocal
(徳島大学機関リポジトリ): ● Metadata: 115159
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/bpb.b20-00423
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33132318; ● Search Scopus @ Elsevier (PMID): 33132318; ● Search Scopus @ Elsevier (DOI): 10.1248/bpb.b20-00423

(徳島大学機関リポジトリ: 115159, DOI: 10.1248/bpb.b20-00423, PubMed: 33132318) 福田達也, 小暮健太朗 :
脳梗塞部位の血液脳関門の能動的突破を目指したDDS 開発,
薬学雑誌, Vol.140, No.8, 1007-1012, 2020年.

(要約): We previously showed that increased permeability of the blood-brain barrier (BBB) after ischemic stroke enables extravasation of nano-sized liposomes and accumulation in the ischemic region, and that delivery of neuroprotective agents using liposomal drug delivery systems (DDS) is applicable for treating cerebral ischemia/reperfusion (I/R) injury. However, entry of liposomes into the brain parenchyma was limited in the early stages after I/R possibly due to microvascular dysfunction induced by pathological progression. As such, new approaches to overcome the BBB are needed. Leukocytes can pass through inflamed BBB in I/R region due to membrane proteins displayed on their surface. We thus hypothesized that incorporation of leukocyte membrane proteins onto liposomal membranes would impart leukocyte-mimicking functions to liposomes and that leukocyte-mimetic liposomes (LM-Lipo) may pass through inflamed endothelial cells and BBB, similar to leukocytes. LM-Lipo prepared using intermembrane protein transfer from human leukemia cells showed significantly increased association to inflamed human umbilical vein endothelial cells relative to plain liposomes. Moreover, LM-Lipo passed through inflamed endothelial cell layer by regulating intercellular junctions. These results suggest that imparting leukocyte-like properties to liposomes via intermembrane protein transfer would be an effective strategy to overcome inflamed endothelial barriers. In this review, we describe our findings on ischemic stroke treatment using liposomal DDS and the potential of LM-Lipo to overcome inflamed endothelial barriers.
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/yakushi.20-00012-7
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32741858; ● Search Scopus @ Elsevier (PMID): 32741858; ● Search Scopus @ Elsevier (DOI): 10.1248/yakushi.20-00012-7

(DOI: 10.1248/yakushi.20-00012-7, PubMed: 32741858) Rumana Yesmin Hasi, Dai Majima, Katsuya Morito, Hanif Ali, Kentaro Kogure, Meera Nanjundan, Junji Hayashi, Ryushi Kawakami, Kaori Kanemaru and Tamotsu Tanaka :
Isolation of glycosylinositol phosphoceramide and phytoceramide 1-phosphate in plants and their chemical stabilities.,
Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, Vol.1152, 122213, 2020.

(要約): Glycosylinositol phosphoceramide (GIPC) is a sphingophospholipid in plants. Recently, we identified that GIPC is hydrolyzed to phytoceramide 1-phosphate (PC1P) by an uncharacterized phospholipase D activity following homogenization of certain plant tissues. We now developed methods for isolation of GIPC and PC1P from plant tissues and characterized their chemical stabilities. Hydrophilic solvents, namely a lower layer of a mixed solvent system consisting of isopropanol/hexane/water (55:20:25, v/v/v) was efficient solvent for extraction and eluent in column chromatography. GIPC was isolated by Sephadex column chromatography followed by TLC. A conventional method, such as the Bligh and Dyer method, was applicable for PC1P extraction. Specifically, PC1P was isolated by TLC following mild alkali treatment of lipid extracts of plants. The yields of GIPC and PC1P in our methods were both around 50-70%. We found that PC1P is tolerant against heat (up to 125 °C), strong acid (up to 10 M HCl), and mild alkali (0.1 M KOH). In contrast, significant degradation of GIPC occurred at 100 °C and 1.0 M HCl treatment, suggesting the instability of the inositol glycan moiety in these conditions. These data will be useful for further biochemical and nutritional studies on these sphingolipids.
(徳島大学機関リポジトリ): ● Metadata: 115195
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.jchromb.2020.122213
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32615533; ● Search Scopus @ Elsevier (PMID): 32615533; ● Search Scopus @ Elsevier (DOI): 10.1016/j.jchromb.2020.122213

(徳島大学機関リポジトリ: 115195, DOI: 10.1016/j.jchromb.2020.122213, PubMed: 32615533) Tatsuharu Shimokawa, Tatsuya Fukuta, Toshio Inagi and Kentaro Kogure :
Protective effect of high-affinity liposomes encapsulating astaxanthin against corneal disorder in the in vivo rat dry eye disease model,
Journal of Clinical Biochemistry and Nutrition, Vol.66, No.3, 224-232, 2020.

(徳島大学機関リポジトリ): ● Metadata: 114731
(出版サイトへのリンク): ● Publication site (DOI): 10.3164/jcbn.19-102
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.3164/jcbn.19-102

(徳島大学機関リポジトリ: 114731, DOI: 10.3164/jcbn.19-102) Tatsuya Fukuta, Shota Hirai, Tatsusada Yoshida, T Maoka and Kentaro Kogure :
Protective effect of antioxidative liposomes co-encapsulating astaxanthin and capsaicin on CCl₄-induced liver injury,
Biological & Pharmaceutical Bulletin, Vol.43, No.8, 1272-1274, 2020.

(要約): Our previous study reported that co-encapsulation of potent antioxidants astaxanthin (Asx) and capsaisin (Cap) into liposomes brought about synergistically higher antioxidative activity than the calculated additive activity of each single antioxidant encapsulating liposome. Based on the previous computational chemistry analysis, the synergistic effect was revealed to be resulted from intermolecular interactions between Asx, especially 3R,3'R-form of Asx stereoisomer (Asx-R), and Cap, by which changes of electronic states of the polyene moiety of Asx-R were induced. Although liposomes co-encapsulating Asx-R and Cap (Asx-R/Cap-Lipo) at an optimal ratio clearly showed synergistic antioxidative activity in vitro, it is unclear whether the effective antioxidative activity derived from intermolecular interaction between Asx-R and Cap is also exerted in vivo. Therefore, in this study, we investigated therapeutic potential of Asx-R/Cap-Lipo as an antioxidant formulation in vivo. For this purpose, we employed carbon tetrachloride (CCl)-induced acute liver injury rat model, since CCl is known to cause oxidative damage in liver. CCl administration significantly increased the levels of aspartate transaminase (AST) and alanine aminotransferase (ALT). Intravenous combined administration of liposomes encapsulating Asx-R (Asx-R-Lipo) and liposomes encapsulating Cap (Cap-Lipo) significantly decreased CCl-induced increase of AST and ALT levels. Importantly, the treatment with Asx-R/Cap-Lipo tended to show higher protective effect on acute liver injury than combined treatment with Asx-R-Lipo plus Cap-Lipo. These results suggest that co-encapsulated Asx-R and Cap in liposomal membranes could exert more effective antioxidative activities in vivo, and that Asx-R/Cap-Lipo would be a hopeful antioxidant formulation for treating reactive oxygen species-related diseases.
(徳島大学機関リポジトリ): ● Metadata: 114732
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/bpb.b20-00116
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32741949; ● Search Scopus @ Elsevier (PMID): 32741949; ● Search Scopus @ Elsevier (DOI): 10.1248/bpb.b20-00116

(徳島大学機関リポジトリ: 114732, DOI: 10.1248/bpb.b20-00116, PubMed: 32741949) Tatsuya Fukuta, Yasufumi Oshima, Kohki Michiue, Daichi Tanaka and Kentaro Kogure :
Non-invasive delivery of biological macromolecular drugs into the skin by iontophoresis and its application to psoriasis treatment,
Journal of Controlled Release, Vol.323, 323-332, 2020.

(要約): Biological macromolecular drugs, such as antibodies and fusion protein drugs, have been widely employed for the treatment of various diseases. Administration routes are typically via invasive intravenous or subcutaneous injection with needles; the latter is challenging for applications involving inflamed skin (e.g., psoriasis) due to concerns of expansion of inflammation. As a method of non-invasive transdermal drug delivery, we previously demonstrated that iontophoresis (IP) using weak electric current (0.3-0.5 mA/cm) enables transdermal permeation of hydrophilic macromolecules, such as small interfering RNA and nanoparticles into the skin, and subsequent exertion of their functions. The underlying mechanism was revealed to be via intercellular junction cleavage by cellular signaling activation initiated by Ca influx. Based on these findings, in the present study, we hypothesized that non-invasive intradermal delivery of biological macromolecular drugs could be efficiently achieved via IP. Fluorescence of FITC-labeled IgG antibody was broadly observed in the skin after IP administration (0.4 mA/cm for 1 h) and extended from the epidermis to the dermis layer of hairless rats; passive antibody diffusion was not observed. In imiquimod-induced psoriasis model rats, antibodies were also delivered via IP into inflamed skin tissue. Additionally, upregulation of interleukin-6 mRNA levels, which is related to pathological progression of psoriasis, was significantly inhibited by IP of the anti-tumor necrosis factor-α drug etanercept, but not by its subcutaneous injection. Importantly, IP administration of etanercept significantly ameliorated epidermis hyperplasia, a symptom of psoriasis. Taken together, the present study is the first to demonstrate that IP can be applied as a non-invasive and efficient intradermal drug delivery technology for biological macromolecular drugs.
(徳島大学機関リポジトリ): ● Metadata: 114727
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.jconrel.2020.04.044
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32360305; ● Summary page in Scopus @ Elsevier: 2-s2.0-85084069379

(徳島大学機関リポジトリ: 114727, DOI: 10.1016/j.jconrel.2020.04.044, PubMed: 32360305, Elsevier: Scopus) Tatsuya Fukuta, Shota Hirai, Tatsusada Yoshida, T Maoka and Kentaro Kogure :
Enhancement of antioxidative activity of astaxanthin by combination with an antioxidant capable of forming intermolecular interactions,
Free Radical Research, 2020.

(要約): We previously demonstrated that coencapsulation of the potent antioxidant astaxanthin (Asx) and tocotrienols into liposomes results in synergistically higher antioxidative activity than the calculated additive activity of each individual antioxidant-containing liposome, due to intermolecular interactions between terminal ring moieties of the two antioxidants and the polyene chain and the triene moiety. We reported that intermolecular interactions depend on the stereochemistry of Asx, and change the electronic state of the Asx polyene moiety. Based on these findings, we hypothesised that antioxidants that interact with Asx at the terminal ring and polyene moieties may enhance the antioxidative activity. Herein, we selected two candidate antioxidants, capsaicin (Cap) and resveratrol, based on their structures, in which the compounds exhibit similar characteristics to tocotrienols. We evaluated the antioxidative capacities of liposomes coencapsulating Asx and the selected candidates. Based on hydroxyl radical scavenging activity, Cap was found to synergistically enhance the antioxidative activity of Asx at an optimal Asx/Cap ratio. Intermolecular interactions between Asx and Cap are necessary for the synergistic effect, and the Asx stereoisomer 3,3'-form (Asx-) was predicted to most potently interact. Liposomes coencapsulating Asx- and Cap exhibited clear synergistic antioxidative activity at an optimal ratio, whereas liposomes coencapsulating the other Asx stereoisomer and Cap did not demonstrate such activity. Computational chemistry analysis showed that changes in the electronic state of the polyene moiety of Asx- are crucial for the synergistic activity. These results suggest that antioxidants that can change the electronic state of Asx via intermolecular interactions may enhance the function of Asx.
(徳島大学機関リポジトリ): ● Metadata: 114072
(出版サイトへのリンク): ● Publication site (DOI): 10.1080/10715762.2019.1693042
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31718328; ● Summary page in Scopus @ Elsevier: 2-s2.0-85081234098

(徳島大学機関リポジトリ: 114072, DOI: 10.1080/10715762.2019.1693042, PubMed: 31718328, Elsevier: Scopus) Tatsuya Fukuta, Akina Nishikawa and Kentaro Kogure :
Low level electricity increases the secretion of extracellular vesicles from cultured cells,
Biochemistry and Biophysics Reports, Vol.21, 100713, 2020.

(要約): Exosomes, a type of extracellular vesicles, can be collected from the conditioned medium of cultured cells, and are expected to be used in disease therapy and drug delivery systems. However, since the yield of exosomes from conditioned medium is generally low, investigations to develop new methods to increase exosome secretion and to elucidate the secretion mechanism have been performed. Our previous studies demonstrated that activation of intracellular signaling including Rho GTPase and subsequent endocytosis of extraneous molecules in cells could be induced by low level electricity (0.3-0.5 mA/cm). Since exosomes are produced in the process of endocytosis and secreted by exocytosis via certain signaling pathways, we hypothesized that low level electric treatment (ET) would increase exosome secretion from cultured cells via intracellular signaling activation. In the present study, the influence of ET (0.34 mA/cm) on extracellular vesicle (EV) secretion from cultured cells was examined by using murine melanoma and murine fibroblast cells. The results showed that the number of EV particles collected by ultracentrifugation was remarkably increased by ET in both cell lines without cellular toxicity or changes in the particle distribution. Also, protein amounts of the collected EVs were significantly increased in both cells by ET without alteration of expression of representative exosome marker proteins. Moreover, in both cells, the ratio of particle numbers to protein amount was not significantly changed by ET. Rho GTPase inhibition significantly suppressed ET-mediated increase of EV secretion in murine melanoma, indicating that Rho GTPase activation could be involved in ET-mediated EV secretion in the cell. Additionally, there were almost no differences in uptake of each EV into each donor cell regardless of whether the cells had been exposed to ET for EV collection. Taken together, these results suggest that ET could increase EV secretion from both cancer and normal cells without apparent changes in EV quality.
(徳島大学機関リポジトリ): ● Metadata: 114729
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bbrep.2019.100713
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31828227; ● Search Scopus @ Elsevier (PMID): 31828227; ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrep.2019.100713

(徳島大学機関リポジトリ: 114729, DOI: 10.1016/j.bbrep.2019.100713, PubMed: 31828227) Tasuku Torao, Miyuki Mimura, Yasufumi Ohshima, Kohki Fujikawa, Mahadi Hasan, Tatsuharu Shimokawa, Naoshi Yamazaki, Hidenori ANDO, Tatsuhiro Ishida, Tatsuya Fukuta, Tamotsu Tanaka and Kentaro Kogure :
Characteristics of unique endocytosis induced by weak current for cytoplasmic drug delivery,
International Journal of Pharmaceutics, Vol.576, 119010, 2020.

(徳島大学機関リポジトリ): ● Metadata: 114728
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ijpharm.2019.119010
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1016/j.ijpharm.2019.119010

(徳島大学機関リポジトリ: 114728, DOI: 10.1016/j.ijpharm.2019.119010) Susumu Hama, Yuriko Okamura, Kazuho Kamei, Saki Nagao, Mari Hayashi, Maeda Shizuka, Kenji Fukuzawa and Kentaro Kogure :
α-Tocopheryl succinate stabilizes the structure of tumor vessels by inhibiting angiopoietin-2 expression,
Biochemical and Biophysical Research Communications, 2020.

(要約): α-Tocopheryl succinate (TS) is a tocopherol derivative and has multifaceted anti-cancer effects; TS not only causes cancer cell-specific apoptosis but also inhibits tumor angiogenesis. Although TS has the potential to be used as a well-tolerated anti-angiogenic drug, it is still unclear which step of the angiogenic process is inhibited by TS. Here, we show that TS inhibits the expression of angiopoietin (Ang)-2, which induces destabilization of vascular structure in the initial steps of the angiogenic process. In mouse melanoma cells, TS treatment decreased mRNA and extracellular protein levels of Ang-2; however, the mRNA level of Ang-1, which stabilizes the vascular structure, remained unchanged. Furthermore, aorta ring and Matrigel plug angiogenesis assays indicated that the conditioned medium from TS-treated cells (CM-TS) inhibited neovascularization and blood leakage from the existing blood vessels, respectively. Following immunohistochemical staining of the vessels treated with CM-TS, imaging studies showed that the vascular endothelial cells were highly packed with pericytes. In conclusion, we found that TS inhibits Ang-2 expression and, consequently, stabilizes the vascular structure during the initial step of tumor angiogenesis.
(徳島大学機関リポジトリ): ● Metadata: 114071
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bbrc.2019.11.017
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31718795; ● Summary page in Scopus @ Elsevier: 2-s2.0-85075357860

(徳島大学機関リポジトリ: 114071, DOI: 10.1016/j.bbrc.2019.11.017, PubMed: 31718795, Elsevier: Scopus) Katsuya Morito, Ryota Shimizu, Nahoko Kitamura, Si-Bum Park, Shigenobu Kishino, Jun Ogawa, Tatsuya Fukuta, Kentaro Kogure and Tamotsu Tanaka :
Gut microbial metabolites of linoleic acid are metabolized by accelerated peroxisomal β-oxidation in mammalian cells,
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, Vol.1864, No.11, 1619-1628, 2019.

(要約): Microorganisms in animal gut produce unusual fatty acids from the ingested diet. Two types of hydroxy fatty acids (HFAs), 10-hydroxy-cis-12-octadecenoic acid (HYA) and 10-hydroxy-octadecanoic acid (HYB), are linoleic acid (LA) metabolites produced by Lactobacillus plantarum. In this study, we investigated the metabolism of these HFAs in mammalian cells. When Chinese hamster ovary (CHO) cells were cultured with HYA, approximately 50% of the supplemented HYA disappeared from the dish within 24 h. On the other hand, the amount of HYA that disappeared from the dish of peroxisome (PEX)-deficient CHO cells was lower than 20%. Significant amounts of C2- and C4-chain-shortened metabolites of HYA were detected in culture medium of HYA-supplemented CHO cells, but not in medium of PEX-deficient cells. These results suggested that peroxisomal β-oxidation is involved in the disappearance of HYA. The PEX-dependent disappearance was observed in the experiment with HYB, but not with LA. We also found that HYA treatment up-regulates peroxisomal β-oxidation activity of human gastric MKN74 cells and intestinal Caco-2 cells. These results indicate a possibility that HFAs produced from gut bacteria affect lipid metabolism of host via modulation of peroxisomal β-oxidation activity.
(徳島大学機関リポジトリ): ● Metadata: 113682
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bbalip.2019.07.010
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31351225; ● Search Scopus @ Elsevier (PMID): 31351225; ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbalip.2019.07.010

(徳島大学機関リポジトリ: 113682, DOI: 10.1016/j.bbalip.2019.07.010, PubMed: 31351225) Rumana Yesmin Hasi, Makoto Miyagi, Takashi Kida, Tatsuya Fukuta, Kentaro Kogure, Junji Hayashi, Ryushi Kawakami, Kaori Kanemaru and Tamotsu Tanaka :
Quantitative Analysis of Glycosylinositol Phosphoceramide and Phytoceramide 1-Phosphate in Vegetables,
Journal of Nutritional Science and Vitaminology, Vol.65, No.Supplement, S175-S179, 2019.

(要約): Previously, we found an unidentified sphingolipid in cabbage, and determined it as phytoceramide 1-phosphate (PC1P). PC1P is found to be produced from glycosylinositol phosphoceramide (GIPC) by the action of phospholipase D (PLD) activity. Although GIPC is abundant sphingolipid, especially in cruciferous vegetables, amount of daily intake, digestibility and nutritional activity of GIPC are not well understood. Here, we investigated amounts of GIPC and PC1P in vegetables. GIPC was found in all vegetables examined (13 kinds) at levels 3-20 mg/100 g (wet weight). On the other hand, PC1P was present in limited vegetables which show higher GIPC-PLD activity, such as inner cabbage leaves (5.2 mg/100 g). Because PC1P is formed during homogenization by activated GIPC-PLD, level of PC1P in boiled cabbage leaves was very low. Although digestibility of GIPC is unknown at present, a portion of dietary GIPC is considered to be converted to PC1P during mastication by plant-derived GIPC-PLD activity in some vegetables.
(キーワード): Brassica / Ceramides / Glycosphingolipids / Inositol / Phosphates / Phospholipase D / Plant Leaves / Sphingolipids / Vegetables
(徳島大学機関リポジトリ): ● Metadata: 115197
(出版サイトへのリンク): ● Publication site (DOI): 10.3177/jnsv.65.S175
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31619623; ● Summary page in Scopus @ Elsevier: 2-s2.0-85073476996

(徳島大学機関リポジトリ: 115197, DOI: 10.3177/jnsv.65.S175, PubMed: 31619623, Elsevier: Scopus) Hasi Yesmin Rumana, Makoto Miyagi, Katsuya Morito, Toshiki Ishikawa, Maki Kawai-Yamada, Hiroyuki Imai, Tatsuya Fukuta, Kentaro Kogure, Kaori Kanemaru, Junji Hayashi, Ryushi Kawakami and Tamotsu Tanaka :
Glycosylinositol phosphoceramide-specific phospholipase D activity catalyzes transphosphatidylation,
The Journal of Biochemistry, Vol.166, No.5, 441-448, 2019.

(要約): Glycosylinositol phosphoceramide (GIPC) is the most abundant sphingolipid in plants and fungi. Recently, we detected GIPC-specific phospholipase D (GIPC-PLD) activity in plants. Here, we found that GIPC-PLD activity in young cabbage leaves catalyzes transphosphatidylation. The available alcohol for this reaction is a primary alcohol with a chain length below C4. Neither secondary alcohol, tertiary alcohol, choline, serine nor glycerol serves as an acceptor for transphosphatidylation of GIPC-PLD. We also found that cabbage GIPC-PLD prefers GIPC containing two sugars. Neither inositol phosphoceramide, mannosylinositol phosphoceramide nor GIPC with three sugar chains served as substrate. GIPC-PLD will become a useful catalyst for modification of polar head group of sphingophospholipid.
(キーワード): Biocatalysis / Brassica / Ceramides / Inositol / Molecular Structure / Phosphatidylcholines / Phospholipase D / Plant Leaves
(徳島大学機関リポジトリ): ● Metadata: 113685
(出版サイトへのリンク): ● Publication site (DOI): 10.1093/jb/mvz056
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31504617; ● Summary page in Scopus @ Elsevier: 2-s2.0-85073764089

(徳島大学機関リポジトリ: 113685, DOI: 10.1093/jb/mvz056, PubMed: 31504617, Elsevier: Scopus) Tetsuya Suzuki, Yusuke Wakao, Tadashi Watanabe, Mika Hori, Yoshito Ikeda, Hiroyuki Tsuchiya, Kentaro Kogure, Mariko Harada-Shiba, Masahiro Fujimuro and Hiroyuki Kamiya :
No enhancing effects of plasmid-specific histone acetyltransferase recruitment system on transgene expression in vivo,
Nucleosides, Nucleotides & Nucleic Acids, 1-8, 2019.

(要約): Altered levels of histone acetylation are associated with changes in chromosomal gene expression. Thus, the specific acetylation of histones bound to plasmid DNA might increase transgene expression. Previously, the expression of the histone acetyltransferase domain of CREB-binding protein fused to the sequence-dependent DNA binding domain of GAL4 (GAL4-HAT) successfully improved reporter gene expression in cultured cells [ 123, 277-280 (2017)]. In this study, the same approach was applied for transgene expression in mice. The activator and reporter plasmid DNAs bearing the genes for GAL4-HAT and luciferase, respectively, were co-administered into the mouse liver by hydrodynamics-based tail vein injection, and the luciferase activity in serum was measured for two weeks. Unexpectedly, the co-injection of the GAL4-HAT and luciferase plasmid DNAs seemed to decrease, rather than increase, luciferase expression. Moreover, the co-injection apparently reduced the amount of luciferase DNA in the liver. These results indicated that this system is ineffective in vivo and suggested the exclusion of hepatic cells expressing GAL4-HAT.
(出版サイトへのリンク): ● Publication site (DOI): 10.1080/15257770.2019.1638514
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31299884; ● Summary page in Scopus @ Elsevier: 2-s2.0-85068907161

(DOI: 10.1080/15257770.2019.1638514, PubMed: 31299884, Elsevier: Scopus) Tatsuya Fukuta, Shintaroh Yoshimi, Tamotsu Tanaka and Kentaro Kogure :
Leukocyte-mimetic liposomes possessing leukocyte membrane proteins pass through inflamed endothelial cell layer by regulating intercellular junctions,
International Journal of Pharmaceutics, Vol.563, 314-323, 2019.

(要約): Nanoparticles such as liposomes have been applied for the treatment of various diseases such as cancer and inflammatory diseases by utilizing the enhanced permeability and retention effect. However, their entry into inflammation sites is still limited since passive delivery of nanoparticles is often hampered by the presence of endothelial barriers. As leukocytes can pass through the inflamed endothelium via utilizing membrane protein functions, we hypothesized that incorporating leukocyte membrane proteins onto liposomal membranes may impart leukocyte-mimicking functions to liposomes, allowing for their adherence to and active passage through the inflamed endothelium. Herein, we developed leukocyte-mimetic liposomes (LM-Lipo) by leukocyte membrane protein transfer and evaluated their function in vitro. Transfer of membrane proteins from human leukemia cells onto liposomal membranes allowed for significant association of the liposomes with inflamed human endothelial cells, and subsequent passage through inflamed endothelial cell layer. The confocal images showed that LM-Lipo significantly induced vascular endothelial-cadherin displacement. These results indicate that LM-Lipo adhered to and regulated intercellular junctions of inflamed endothelial cell layer, resulting in passage through the layer, by mimicking the function of leukocytes. Furthermore, it is suggested that liposomes possessing leukocyte-like functions could be useful for drug delivery to inflammation sites by overcoming endothelial barriers.
(キーワード): Biomimetics / HL-60 Cells / Human Umbilical Vein Endothelial Cells / Humans / Inflammation / Intercellular Junctions / Leukocytes / Liposomes / Membrane Proteins
(徳島大学機関リポジトリ): ● Metadata: 114730
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ijpharm.2019.04.027
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30978483; ● Search Scopus @ Elsevier (PMID): 30978483; ● Search Scopus @ Elsevier (DOI): 10.1016/j.ijpharm.2019.04.027

(徳島大学機関リポジトリ: 114730, DOI: 10.1016/j.ijpharm.2019.04.027, PubMed: 30978483) Mahadi Hasan, Susumu Hama and Kentaro Kogure :
Low electric treatment activates Rho GTPase via heat shock protein 90 and protein kinase c for intracellular delivery of siRNA,
Scientific Reports, Vol.9, No.1, 4114, 2019.

(要約): Low electric treatment (LET) promotes intracellular delivery of naked siRNA by altering cellular physiology. However, which signaling molecules and cellular events contribute to LET-mediated siRNA uptake are unclear. Here, we used isobaric tags in relative and absolute quantification (iTRAQ) proteomic analysis to identify changes in the levels of phosphorylated proteins that occur during cellular uptake of siRNA promoted by LET. iTRAQ analysis revealed that heat shock protein 90 (Hsp90)α and myristoylated alanine-rich C-kinase substrate (Marcks) were highly phosphorylated following LET of NIH 3T3 cells, but not untreated cells. Furthermore, the levels of phosphorylated Hsp90α and protein kinase C (PKC)γ were increased by LET both with siRNA and liposomes having various physicochemical properties used as model macromolecules, suggesting that PKCγ activated partly by Ca influx as well as Hsp90 chaperone function were involved in LET-mediated cellular siRNA uptake. Furthermore, LET with siRNA induced activation of Rho GTPase via Hsp90 and PKC, which could contribute to cellular siRNA uptake accompanied by actin cytoskeleton remodeling. Collectively, our results suggested that LET-induced Rho GTPase activation via Hsp90 and PKC would participate in actin-dependent cellular uptake of siRNA.
(徳島大学機関リポジトリ): ● Metadata: 114945
(出版サイトへのリンク): ● Publication site (DOI): 10.1038/s41598-019-40904-z
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30858501; ● Summary page in Scopus @ Elsevier: 2-s2.0-85062766468

(徳島大学機関リポジトリ: 114945, DOI: 10.1038/s41598-019-40904-z, PubMed: 30858501, Elsevier: Scopus) Tatsuharu Shimokawa, Mai Yoshida, Tatsuya Fukuta, Tamotsu Tanaka, Toshio Inagi and Kentaro Kogure :
Efficacy of high-affinity liposomal astaxanthin on up-regulation of age-related markers induced by oxidative stress in human corneal epithelial cells,
Journal of Clinical Biochemistry and Nutrition, Vol.64, No.1, 27-35, 2019.

(要約): Decreases in tear volume, unstable tear films and excessive tear evaporation are known to cause desiccation and hyperosmolar stress. These, in turn, induce oxidative stress that is thought to cause dry eye, which is also considered to be age-related disease. We hypothesized that oxidative stress induces up-regulation of age-related markers, and that the antioxidant astaxanthin prepared as a liposomal formulation may be a candidate for the treatment of dry eye. Herein, we examined age-related markers in an dry eye model, and evaluated the efficacy of high-affinity liposomes containing astaxanthin. The dry eye model showed desiccation time-dependent increases in reactive oxygen species. We confirmed the up-regulation of p53, p21 and p16 as a function of desiccation time. Pretreatment with both neutral and slightly-positively-charged astaxanthin liposomal formulations showed significant suppression of up-regulation of all markers, with the positively-charged liposomes exhibiting the greatest efficacy. Furthermore, positively-charged liposomes labeled with fluorescent dyes demonstrated much higher affinity to normal human corneal epithelial cells (HCECs) than neutral liposomes. Taken together, we confirmed the up-regulation of age-related markers, especially p16, in an dry eye model, and demonstrated the potential of high-affinity liposomal astaxanthin for the treatment of dry eye.
(出版サイトへのリンク): ● Publication site (DOI): 10.3164/jcbn.18-27
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30705509; ● Summary page in Scopus @ Elsevier: 2-s2.0-85059761043

(DOI: 10.3164/jcbn.18-27, PubMed: 30705509, Elsevier: Scopus) Misuzu Ishikawa, Shota Hirai, Tatsusada Yoshida, Natsumi Shibuya, Susumu Hama, Yu Takahashi, Tatsuya Fukuta, Tamotsu Tanaka, Shinzo Hosoi and Kentaro Kogure :
Carotenoid Stereochemistry Affects Antioxidative Activity of Liposomes Co-encapsulating Astaxanthin and Tocotrienol,
Chemical & Pharmaceutical Bulletin, Vol.66, No.7, 714-720, 2018.

(要約): We previously found that antioxidative activity of liposomes co-encapsulating astaxanthin (Asx) and tocotrienols (T3s) was higher than the calculated additive activity, which results from intermolecular interactions between both antioxidants (J. Clin. Biochem. Nutr., 59, 2016, Kamezaki et al.). Herein, we conducted experiments to optimize Asx/α-T3 ratio for high antioxidative activity, and tried to elucidate details of intermolecular interaction of Asx with α-T3. Higher activity than calculated additive value was clearly observed at an Asx/α-T3 ratio of 2 : 1, despite two α-T3 would potentially interact with two terminal rings of one Asx. The synthetic Asx used in this study was a mixture of three stereoisomers, 3R,3'R-form (Asx-R), 3S,3'S-form (Asx-S) and 3R,3'S-meso form (Asx-meso). The calculated binding energy of the Asx-S/α-T3 complex was higher than those of Asx-R/α-T3 and Asx-meso/α-T3, suggesting that Asx-S and α-T3 is the most preferable combination for the intermolecular interaction. The optimal Asx-S/α-T3 ratio for antioxidation was shown to be 1 : 2. These results suggest that the Asx stereochemistry affects the intermolecular interaction of Asx/α-T3. Moreover, the absorption spectrum changes of Asx-S upon co-encapsulation with α-T3 in liposomes indicate that the electronic state of Asx-S is affected by intermolecular interactions with α-T3. Further, intermolecular interactions with α-T3 affected the electronic charges on the C9, C10 and C15 atoms in the polyene moiety of Asx-S. In conclusion, the intermolecular interaction of Asx/T3 depends on the Asx stereochemistry, and caused a change in the electronic state of the Asx polyene moiety by the presence of double bond in the T3 triene moiety.
(キーワード): Antioxidants / カロテノイド (carotenoids) / リポソーム (liposomes) / 分子構造 (molecular structure) / Stereoisomerism / Tocotrienols / Xanthophylls
(徳島大学機関リポジトリ): ● Metadata: 113562
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/cpb.c18-00035
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29962454; ● Summary page in Scopus @ Elsevier: 2-s2.0-85049232130

(徳島大学機関リポジトリ: 113562, DOI: 10.1248/cpb.c18-00035, PubMed: 29962454, Elsevier: Scopus) Sheuli Afroz, Ayano Yagi, Kouki Fujikawa, M. Motiur Rahman, Katsuya Morito, Tatsuya Fukuta, Shiro Watanabe, Kazunori Toida, Emi Kiyokage, Taro Shimizu, Tatsuhiro Ishida, Kentaro Kogure, Akira Tokumura and Tamotsu Tanaka :
Lysophosphatidic acid in medicinal herbs enhances prostaglandin E2 and protects against indomethacin-induced gastric cell damage in vivo and in vitro,
Prostaglandins & Other Lipid Mediators, Vol.135, 36-44, 2018.

(要約): Lysophosphatidic acid (LPA) is a bioactive phospholipid that induces diverse biological responses. Recently, we found that LPA ameliorates NSAIDs-induced gastric ulcer in mice. Here, we quantified LPA in 21 medicinal herbs used for treatment of gastrointestinal (GI) disorders. We found that half of them contained LPA at relatively high levels (40-240 μg/g) compared to soybean seed powder (4.6 μg/g), which we previously identified as an LPA-rich food. The LPA in peony (Paeonia lactiflora) root powder is highly concentrated in the lipid fraction that ameliorates indomethacin-induced gastric ulcer in mice. Synthetic 18:1 LPA, peony root LPA and peony root lipid enhanced prostaglandin E production in a gastric cancer cell line, MKN74 cells that express LPA abundantly. These materials also prevented indomethacin-induced cell death and stimulated the proliferation of MKN74 cells. We found that LPA was present in stomach fluids at 2.4 μM, which is an effective LPA concentration for inducing a cellular response in vitro. These results indicated that LPA is one of the active components of medicinal herbs for the treatment of GI disorder and that orally administered LPA-rich herbs may augment the protective actions of endogenous LPA on gastric mucosa.
(徳島大学機関リポジトリ): ● Metadata: 112025
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.prostaglandins.2018.01.003
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29462674; ● Summary page in Scopus @ Elsevier: 2-s2.0-85042401633

(徳島大学機関リポジトリ: 112025, DOI: 10.1016/j.prostaglandins.2018.01.003, PubMed: 29462674, Elsevier: Scopus) Kanako Shiota, Susumu Hama, Toru Yoshitomi, Yukio Nagasaki and Kentaro Kogure :
Prevention of UV-induced Melanin Production by Accumulation of Redox Nanoparticles in the Epidermal Layer via Iontophoresis,
Biological & Pharmaceutical Bulletin, Vol.40, No.6, 941-944, 2017.

(要約): UV rays induce melanin production in the skin, which, from a cosmetic point of view, is problematic. Reactive oxygen species (ROS) generated in the skin upon UV irradiation are thought to be responsible for melanin production. Thus, effective antioxidants are recognized as useful tools for prevention of UV-induced melanin production. Redox nanoparticles (RNPs) containing nitroxide radicals as free radical scavengers were previously developed, and shown to be effective ROS scavengers in the body. RNPs are therefore expected to be useful for effective protection against UV-induced melanin production. However, as the sizes of RNPs are typically larger than the intercellular spaces of the skin, transdermal penetration is difficult. We recently demonstrated effective transdermal delivery and accumulation of nanoparticles in the epidermal layer via faint electric treatment, i.e., iontophoresis, suggesting that iontophoresis of RNPs may be a useful strategy for prevention of UV-induced melanin production in the skin. Herein, we performed iontophoresis of RNPs on the dorsal skin of hairless mice that produce melanin in response to light exposure. RNPs accumulated in the epidermal layer upon application of iontophoresis. Further, the combination of RNPs with iontophoresis decreased UV-induced melanin spots and melanin content in the skin. Taken together, we successfully demonstrated that iontophoresis-mediated accumulation of RNPs in the epidermis prevented melanin production.
(キーワード): Animals / Antioxidants / Cyclic N-Oxides / Epidermis / Iontophoresis / Male / Melanins / Mice, Hairless / Nanoparticles / Oxidation-Reduction / Polymers / Ultraviolet Rays
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/bpb.b17-00155
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28566638; ● Summary page in Scopus @ Elsevier: 2-s2.0-85020052387

(DOI: 10.1248/bpb.b17-00155, PubMed: 28566638, Elsevier: Scopus) Satoko Suzuki, Shoko Itakura, Ryo Matsui, Kayoko Nakayama, Takayuki Nishi, Akinori Nishimoto, Susumu Hama and Kentaro Kogure :
Tumor microenvironment-sensitive liposomes penetrate tumor tissue via attenuated interaction of the extracellular matrix and tumor cells, and accompanying actin depolymerization,
Biomacromolecules, Vol.18, No.2, 535-543, 2017.

(要約): Delivery of anticancer drugs into tumor cores comprised of malignant cancer cells can result in potent therapeutic effects. However, conventional nanoparticle-based drug delivery systems used for cancer therapy often exhibit inefficient tumor-penetrating properties, thus, suggesting the need to improve the functional design of such systems. Herein, we focus on the interactions between cancer cells and the extracellular matrix (ECM) and demonstrate that liposomes modified with slightly acidic pH-sensitive peptide (SAPSp-lipo) can penetrate in vivo tumor tissue and in vitro spheroids comprised of cancer cells and ECM. We previously reported SAPSp-lipo, tumor microenvironment-sensitive liposomes, are effectively delivered to tumor tissue (Hama et al. J Control Release 2015, 206, 67-74). Compared with conventional liposomes, SAPSp-lipo could be delivered to deeper regions within both spheroids and tumor tissues. Furthermore, tumor penetration was found to be promoted at regions where actin depolymerization was induced by SAPSp-lipo and inhibited by the polymerization of actin. In addition, SAPSp-lipo attenuated the interaction between cancer cells and ECM, contributing to the penetration of SAPSp-lipo. These results suggest that SAPSp-lipo penetrates tumors via the interspace route and is accompanied by actin depolymerization. Taken together, SAPSp-lipo demonstrates potential as a novel tumor-penetrable drug carrier for induction of therapeutic effects against malignant cells that comprise tumor cores.
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/acs.biomac.6b01688
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28055201; ● Summary page in Scopus @ Elsevier: 2-s2.0-85012306090

(DOI: 10.1021/acs.biomac.6b01688, PubMed: 28055201, Elsevier: Scopus) Kida Takashi, Itoh Aoi, Kimura Akari, Matsuoka Hisatsugu, Imai Hiroyuki, Kentaro Kogure, Akira Tokumura and Tamotsu Tanaka :
Distribution of glycosylinositol phosphoceramide-specific phospholipase D activity in plants,
The Journal of Biochemistry, Vol.161, No.2, 187-195, 2017.

(要約): Previously, we detected an unknown sphingophospholipid in cabbage leaves and identified it as phytoceramide-1-phosphate (PC1P). We also found an enzyme activity that produces PC1P by glycosylinositol phosphoceramide (GIPC)-specific hydrolysis in cabbage leaves. To characterize the GIPC-specific phospholipase D (GIPC-PLD) activity, we investigated distributions of GIPC-PLD activity in 25 tissues of 10 plants. In most plants, the GIPC-PLD activity was the highest in roots. Young leaves of cabbage and Welsh onion had higher activities than corresponding aged outer leaves. The GIPC-PLD activities in leaves, stems and roots of mung bean were higher in the sprouting stage than in more mature stages. We also examined the distribution of substrate GIPC and product PC1P and found that GIPC was ubiquitously distributed at 50-280 nmol/g (wet wt) in tissues of plants, whereas PC1P was detectable (3-60 nmol/g wet wt.) only in tissues showing considerable GIPC-PLD activity. These results suggest a possibility that GIPC-PLD activity is involved in plant growth.
(キーワード): Brassica / Ceramides / Daucus carota / Glycosphingolipids / Molecular Structure / Phospholipase D / Plant Leaves / Raphanus / Spinacia oleracea
(徳島大学機関リポジトリ): ● Metadata: 117827
(出版サイトへのリンク): ● Publication site (DOI): 10.1093/jb/mvw060
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28175321; ● CiNii @ 国立情報学研究所 (CRID): 1522262180608136704; ● Summary page in Scopus @ Elsevier: 2-s2.0-85015919191

(徳島大学機関リポジトリ: 117827, DOI: 10.1093/jb/mvw060, PubMed: 28175321, CiNii: 1522262180608136704, Elsevier: Scopus) Hyunkyung Jung, Yuri Shimatani, Mahadi Hasan, Kohei Uno, Susumu Hama and Kentaro Kogure :
Development of flexible nanocarriers for siRNA delivery into tumor tissue,
International Journal of Pharmaceutics, Vol.516, No.1-2, 258-265, 2017.

(要約): Various non-viral delivery systems for small interfering RNAs (siRNA) have been developed. Such delivery systems generally exhibit tightly formed spherical structures. While such carriers have demonstrated good transfection activity in mono-layered cell systems, effects against solid tumors are often less apparent and difficult to demonstrate, likely due to the rigid structures of the carriers, which may prevent penetration to deeper regions within tumor tissue. Herein, we developed a flexible nanocarrier (FNC) system that is able to penetrate to deeper regions within tumor tissue. Specifically, we employed previously found flexible polyplexes comprised of siRNA and poly-l-lysine as wick structures for the preparation of FNCs. FNCs were constructed by coating the wick structures with lipids using a liposomal membrane fusion method. The diameters of the resulting FNCs were ca. 170nm, and the shapes were non-spherical. Lipid coating was confirmed using a nuclease resistance assay. Furthermore, FNCs showed significant RNA interference effects, comparable to Lipofectamine 2000, in a mono-layered cell system. To accelerate tumor penetration, the FNC surface was modified with polyethylene glycol (PEG) and the tight junction opener peptide AT1002. Surface-modified FNCs demonstrated effective penetrability into a cancer spheroid. Thus, we developed a novel and unique tumor-penetrable siRNA FNC system.
(キーワード): Animals / Cell Line, Tumor / Gene Transfer Techniques / Lipids / Mice / Nanoparticles / Neoplasms / Particle Size / Polyethylene Glycols / RNA Interference / RNA, Small Interfering / Tissue Distribution / Transfection
(徳島大学機関リポジトリ): ● Metadata: 110902
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ijpharm.2016.11.042
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27871835; ● Summary page in Scopus @ Elsevier: 2-s2.0-84997108932

(徳島大学機関リポジトリ: 110902, DOI: 10.1016/j.ijpharm.2016.11.042, PubMed: 27871835, Elsevier: Scopus) S Afroz, Teru Ikoma, Ayano Yagi, Kentaro Kogure, Akira Tokumura and Tamotsu Tanaka :
Concentrated phosphatidic acid in cereal brans as potential protective agents against indomethacin-induced stomach ulcer.,
Journal of Agricultural and Food Chemistry, Vol.64, No.37, 6950-6957, 2016.

(要約): One of complications associated with long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) is peptic ulcer. Recently, we found that orally administered phosphatidic acid (PA) ameliorated aspirin-induced stomach lesions in mice. In this study, we identified PA-rich food sources and examined the effects of the food materials on indomethacin-induced stomach ulcer. Among examined, buckwheat (Fagopyrum esculentum) bran contained the highest level of PA (188 mg/100 g). PA was the richest phospholipid (25%) in the lipid fraction of the buckwheat bran. Administration of the lipid extracts of buckwheat bran significantly ameliorated indomethacin-induced stomach lesions in mice. In contrast, wheat (Triticum durum) bran lipids (PA, 4%) and soybean (Glycine max) lipids (PA, 3%) were not associated with ameliorative effects. These results indicated that PA-rich lipids can be used as an effective supplement for prevention of NSAID-induced stomach ulcer.
(キーワード): Animals / Edible Grain / Fagopyrum / Gastric Mucosa / Humans / Indomethacin / Male / Mice / Mice, Inbred ICR / Phosphatidic Acids / Plant Extracts / Protective Agents / Seeds / Soybeans / Stomach Ulcer / Triticum
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/acs.jafc.6b02884
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27561232; ● Search Scopus @ Elsevier (PMID): 27561232; ● Search Scopus @ Elsevier (DOI): 10.1021/acs.jafc.6b02884

(DOI: 10.1021/acs.jafc.6b02884, PubMed: 27561232) Mahadi Hasan, Noriko Saito-Tarashima, Koki Fujikawa, Takashi Ohgita, Susumu Hama, Tamotsu Tanaka, Hiroyuki Saito, Noriaki Minakawa and Kentaro Kogure :
The novel functional nucleic acid iRed effectively regulates target genes following cytoplasmic delivery by faint electric treatment,
Science and Technology of Advanced Materials, Vol.17, No.17, 554-562, 2016.

(要約): An intelligent shRNA expression device (iRed) contains the minimum essential components needed for shRNA production in cells, and could be a novel tool to regulate target genes. However, general delivery carriers consisting of cationic polymers/lipids could impede function of a newly generated shRNA via electrostatic interaction in the cytoplasm. Recently, we found that faint electric treatment (fET) of cells enhanced delivery of siRNA and functional nucleic acids into the cytoplasm in the absence of delivery carriers. Here, we examined fET of cells stably expressing luciferase in the presence of iRed encoding anti-luciferase shRNA. Transfection of lipofectamine 2000 (LFN)/iRed lipoplexes showed an RNAi effect, but fET-mediated iRed transfection did not, likely because of the endosomal localization of iRed after delivery. However, fET in the presence of lysosomotropic agent chloroquine significantly improved the RNAi effect of iRed/fET to levels that were higher than those for the LFN/iRed lipoplexes. Furthermore, the amount of lipid droplets in adipocytes significantly decreased following fET with iRed against resistin in the presence of chloroquine. Thus, iRed could be a useful tool to regulate target genes following fET-mediated cytoplasmic delivery with endosomal escape devices.
(徳島大学機関リポジトリ): ● Metadata: 115720
(出版サイトへのリンク): ● Publication site (DOI): 10.1080/14686996.2016.1221726
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27877903; ● Summary page in Scopus @ Elsevier: 2-s2.0-85019070861

(徳島大学機関リポジトリ: 115720, DOI: 10.1080/14686996.2016.1221726, PubMed: 27877903, Elsevier: Scopus) Shoko Itakura, Susumu Hama, Ryo Matsui and Kentaro Kogure :
Effective cytoplasmic release of siRNA from liposomal carriers by controlling the electrostatic interaction of siRNA with a charge-invertible peptide, in response to cytoplasmic pH,
Nanoscale, Vol.8, No.20, 10649-10658, 2016.

(要約): Condensing siRNA with cationic polymers is a major strategy used in the development of siRNA carriers that can avoid degradation by nucleases and achieve effective delivery of siRNA into the cytoplasm. However, ineffective release of siRNA from such condensed forms into the cytoplasm is a limiting step for induction of RNAi effects, and can be attributed to tight condensation of siRNA with the cationic polymers, due to potent electrostatic interactions. Here, we report that siRNA condensed with a slightly acidic pH-sensitive peptide (SAPSP), whose total charge is inverted from positive to negative in response to cytoplasmic pH, is effectively released via electrostatic repulsion of siRNA with negatively charged SAPSP at cytoplasmic pH (7.4). The condensed complex of siRNA and positively-charged SAPSP at acidic pH (siRNA/SAPSP) was found to result in almost complete release of siRNA upon charge inversion of SAPSP at pH 7.4, with the resultant negatively-charged SAPSP having no undesirable interactions with endogenous mRNA. Moreover, liposomes encapsulating siRNA/SAPSP demonstrated knockdown efficiencies comparable to those of commercially available siRNA carriers. Taken together, SAPSP may be very useful as a siRNA condenser, as it facilitates effective cytoplasmic release of siRNA, and subsequent induction of specific RNAi effects.
(出版サイトへのリンク): ● Publication site (DOI): 10.1039/c5nr08365f
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27145993; ● Summary page in Scopus @ Elsevier: 2-s2.0-84971232259

(DOI: 10.1039/c5nr08365f, PubMed: 27145993, Elsevier: Scopus) Chihiro Kamezaki, Ami Nakashima, Asako Yamada, Sachiko Uenishi, Hiroshi Ishibashi, Natsumi Shibuya, Susumu Hama, Shinzo Hosoi, Eiji Yamashita and Kentaro Kogure :
Synergistic antioxidative effect of astaxanthin and tocotrienol by co-encapsulated in liposomes,
Journal of Clinical Biochemistry and Nutrition, Vol.59, No.2, 100-106, 2016.

(要約): Astaxanthin and vitamin E are both effective antioxidants that are frequently used in cosmetics, as food additives, and in to prevent oxidative damage. A combination of astaxanthin and vitamin E would be expected to show an additive anntioxidative effect. In this study, liposomes co-encapsulating astaxanthin and the vitamin E derivatives α-tocopherol (α-T) or tocotrienols (T3) were prepared, and the antioxidative activity of these liposomes toward singlet oxygen and hydroxyl radical was evaluated in vitro. Liposomes co-encapsulating astaxanthin and α-T showed no additive anntioxidative effect, while the actual scavenging activity of liposomes co-encapsulating astaxanthin and T3 was higher than the calculated additive activity. To clarify why this synergistic effect occurs, the most stable structure of astaxanthin in the presence of α-T or α-T3 was calculated. Only α-T3 was predicted to form hydrogen bonding with astaxanthin, and the astaxanthin polyene chain would partially interact with the α-T3 triene chain, which could explain why there was a synergistic effect between astaxanthin and T3 but not α-T. In conclusion, co-encapsulation of astaxanthin and T3 induces synergistic scavenging activity by intermolecular interactions between the two antioxidants.
(徳島大学機関リポジトリ): ● Metadata: 110843
(出版サイトへのリンク): ● Publication site (DOI): 10.3164/jcbn.15-153
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27698536; ● Summary page in Scopus @ Elsevier: 2-s2.0-84988934724

(徳島大学機関リポジトリ: 110843, DOI: 10.3164/jcbn.15-153, PubMed: 27698536, Elsevier: Scopus) Mahadi Hasan, Akinori Nishimoto, Takashi Ohgita, Susumu Hama, Hiromu Kashida, Hiroyuki Asanuma and Kentaro Kogure :
Faint electric treatment-induced rapid and efficient delivery of extraneous hydrophilic molecules into the cytoplasm,
Journal of Controlled Release, Vol.228, 20-25, 2016.

(要約): Effective delivery of extraneous molecules into the cytoplasm of the target cells is important for several drug therapies. Previously, we showed effective in vivo transdermal delivery of naked siRNA into skin cells induced by faint electric treatment (ET) iontophoresis, and significant suppression of target mRNA levels (Kigasawa et al., Int. J. Pharm., 2010). This result indicates that electricity promoted the delivery of siRNA into cytoplasm. In the present study, we analyzed the intracellular delivery of naked anti-luciferase siRNA by faint ET, and found that the luciferase activity of cells expressing luciferase was reduced by in vitro ET like in vivo iontophoresis. Cellular uptake of fluorescent-label siRNA was increased by ET, while low temperature exposure, macropinocytosis inhibitor amiloride and caveolae-mediated endocytosis inhibitor filipin significantly prevented siRNA uptake. These results indicate that the cellular uptake mechanism involved endocytosis. In addition, voltage sensitive fluorescent dye DiBAC4 (3) penetration was increased by ET, and the transient receptor potential channel inhibitor SKF96365 reduced siRNA uptake, suggesting that faint ET reduced membrane potentials by changing intracellular ion levels. Moreover, to analyze cytoplasmic delivery, we used in-stem molecular beacon (ISMB), which fluoresces upon binding to target mRNA in the cytoplasm. Surprisingly, cytoplasmic ISMB fluorescence appeared rapidly and homogeneously after ET, indicating that cytoplasmic delivery is markedly enhanced by ET. In conclusion, we demonstrated for the first time that faint ET can enhance cellular uptake and cytoplasmic delivery of extraneous molecules.
(徳島大学機関リポジトリ): ● Metadata: 110029
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.jconrel.2016.02.048
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26944781; ● Summary page in Scopus @ Elsevier: 2-s2.0-84961631654

(徳島大学機関リポジトリ: 110029, DOI: 10.1016/j.jconrel.2016.02.048, PubMed: 26944781, Elsevier: Scopus) Asako Yamada, Asako Mitsueda, Mahadi Hasan, Miho Ueda, Susumu Hama, Shota Warashina, Takashi Nakamura, Hideyoshi Harashima and Kentaro Kogure :
Tri-membrane nanoparticles produced by combining liposome fusion and a novel patchwork of bicelles to overcome endosomal and nuclear membrane barriers to cargo delivery,
Biomaterials Science, Vol.4, No.3, 439-447, 2016.

(要約): Membrane fusion is a rational strategy for crossing intracellular membranes that present barriers to liposomal nanocarrier-mediated delivery of plasmid DNA into the nucleus of non-dividing cells, such as dendritic cells. Based on this strategy, we previously developed nanocarriers consisting of a nucleic acid core particle coated with four lipid membranes [Akita, et al., Biomaterials, 2009, 30, 2940-2949]. However, including the endosomal membrane and two nuclear membranes, cells possess three intracellular membranous barriers. Thus, after entering the nucleus, nanoparticles coated with four membranes would still have one lipid membrane remaining, and could impede cargo delivery. Until now, coating a core particle with an odd number of lipid membranes was challenging. To produce nanocarriers with an odd number of lipid membranes, we developed a novel coating method involving lipid nano-discs, also known as bicelles, as a material for packaging DNA in a carrier with an odd number of lipid membranes. In this procedure, bicelles fuse to form an outer coating that resembles a patchwork quilt, which allows the preparation of nanoparticles coated with only three lipid membranes. Moreover, the transfection activity of dendritic cells with these three-membrane nanoparticles was higher than that for nanoparticles coated with four lipid membranes. In summary, we developed novel nanoparticles coated with an odd number of lipid membranes using the novel "patchwork-packaging method" to deliver plasmid DNA into the nucleus via membrane fusion.
(出版サイトへのリンク): ● Publication site (DOI): 10.1039/c5bm00327j
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26667208; ● Search Scopus @ Elsevier (PMID): 26667208; ● Search Scopus @ Elsevier (DOI): 10.1039/c5bm00327j

(DOI: 10.1039/c5bm00327j, PubMed: 26667208) Keita Takagi, Takashi Ohgita, Takenori Yamamoto, Yasuo Shinohara and Kentaro Kogure :
Transmission of external environmental pH information to the inside of liposomes via pore-forming proteins embedded within the liposomal membrane,
Chemical & Pharmaceutical Bulletin, Vol.64, No.5, 432-438, 2016.

(要約): Liposomes are closed-membrane vesicles comprised of lipid bilayers, in which the inside of the vesicles is isolated from the external environment. Liposomes are therefore often used as models for biomembranes and as drug delivery carriers. However, materials encapsulated within liposomes often cannot respond to changes in the external environment. The ability of enclosed materials to maintain their responsiveness to changes in the external environment following encapsulation into liposomes would greatly expand the applicability of such systems. We hypothesize that embedding pore-like "access points" into the liposomal membrane could allow for the transmission of information between the internal and external liposomal environments and thus overcome this inherent limitation of conventional liposomes. To investigate this, we evaluated whether a change in the pH of an external solution could be transmitted to the inside of liposomes through the pore-forming protein, yeast voltage-dependent anion channel (VDAC). Transmission of a pH change via VDAC was evaluated using a polyglutamic acid/doxorubicin complex (PGA/Dox) as an internal pH sensor. Upon encapsulation into conventional liposomes, PGA/Dox exhibits no pH sensitivity due to isolation from the external environment. On the other hand, PGA/Dox was found to retain its pH sensitivity upon encapsulation into VDAC-reconstituted liposomes, suggesting that VDAC facilitated the transmission of information on the pH of the external environment to the inside of the liposomes. In conclusion, we successfully demonstrated the transmission of information between the external and internal liposomal environments by a stable pore-like structure embedded into the liposomal membranes, which serve as access points.
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/cpb.c15-00985
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27150475; ● Summary page in Scopus @ Elsevier: 2-s2.0-84969579933

(DOI: 10.1248/cpb.c15-00985, PubMed: 27150475, Elsevier: Scopus) 喜田孝史, 木村朱里, 伊藤葵, 山下量平, 小暮健太朗, 德村彰, 田中保 :
食品に含まれるグリコシルイノシトールホスホセラミドおよびフィトセラミド-1-リン酸,
脂質栄養学, Vol.25, 75-85, 2016年.

(出版サイトへのリンク): ● Publication site (DOI): 10.4010/jln.25.75
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390001205191889280; ● Search Scopus @ Elsevier (DOI): 10.4010/jln.25.75

(DOI: 10.4010/jln.25.75, CiNii: 1390001205191889280) Ryouhei Yamashita, Yumika Tabata, Erina Iga, Michiyasu Nakao, Shigeki Sano, Kentaro Kogure, Akira Tokumura and Tamotsu Tanaka :
Analysis of molecular species profiles of ceramide-1-phosphate and sphingomyelin using MALDI-TOF mass spectrometry,
Lipids, Vol.51, No.2, 263-270, 2016.

(要約): Ceramide-1-phosphate (C1P) is a potential signaling molecule that modulates various cellular functions in animals. It has been known that C1P with different N-acyl lengths induce biological responses differently. However, molecular species profiles of the C1P in animal tissues have not been extensively examined yet. Here, we developed a method for determination of the molecular species of a C1P using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry with Phos-tag, a phosphate capture molecule. The amounts of total C1P in skin, brain, liver, kidney and small intestine of mice were determined to be 344, 151, 198, 96 and 90 pmol/g wet weight, respectively. We found a C1P species having an α-hydroxypalmitoyl residue (h-C1P, 44 pmol/g wet weight) in mouse skin. The h-C1P was detected only in the skin, and not other tissues of mice. The same analysis was applied to sphingomyelin after conversion of sphingomyelin to C1P by Streptomyces chromofuscus phospholipase D. We found that molecular species profiles of sphingomyelin in skin, kidney and small intestine of mice were similar to those of C1P in corresponding tissues. In contrast, molecular species profiles of sphingomyelin in liver and brain were quite different from those of C1P in these tissues, indicating selective synthesis or degradation of C1P in these tissues. The method described here will be useful for detection of changes in molecular species profiles of C1P and sphingomyelin.
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s11745-015-4082-0
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26694604; ● Summary page in Scopus @ Elsevier: 2-s2.0-84957439211

(DOI: 10.1007/s11745-015-4082-0, PubMed: 26694604, Elsevier: Scopus) Yuma Yamada, Hidetaka Akita, Hiroyuki Kamiya, Kentaro Kogure, Takenori Yamamoto, Yasuo Shinohara, Kikuji Yamashita, Hideo Kobayashi, Hiroshi Kikuchi and Hideyoshi Harashima :
MITO-Porter: A liposome-based carrier system for delivery of macromolecules into mitochondria via membrane fusion.,
Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol.1778, No.2, 423-432, 2007.

(要約): Mitochondria are the principal producers of energy in higher cells. Mitochondrial dysfunction is implicated in a variety of human diseases, including cancer and neurodegenerative disorders. Effective medical therapies for such diseases will ultimately require targeted delivery of therapeutic proteins or nucleic acids to the mitochondria, which will be achieved through innovations in the nanotechnology of intracellular trafficking. Here we describe a liposome-based carrier that delivers its macromolecular cargo to the mitochondrial interior via membrane fusion. These liposome particles, which we call MITO-Porters, carry octaarginine surface modifications to stimulate their entry into cells as intact vesicles (via macropinocytosis). We identified lipid compositions for the MITO-Porter which promote both its fusion with the mitochondrial membrane and the release of its cargo to the intra-mitochondrial compartment in living cells. Thus, the MITO-Porter holds promise as an efficacious system for the delivery of both large and small therapeutic molecules into mitochondria.
(キーワード): Animals / Hela Cells / Humans / Liposomes / Male / Membrane Fusion / Microscopy, Fluorescence / Mitochondria, Liver / Rats / Rats, Wistar
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bbamem.2007.11.002
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18054323; ● Search Scopus @ Elsevier (PMID): 18054323; ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbamem.2007.11.002

(DOI: 10.1016/j.bbamem.2007.11.002, PubMed: 18054323) Kentaro Kogure, Sachie Manabe, Ichiro Suzuki, Akira Tokumura and Kenji Fukuzawa :
Cytotoxicity of α-tocopheryl succinate, malonate and oxalate in normal and cancer cells in vitro and their anti-cancer effects on mouse melanoma in vivo,
Journal of Nutritional Science and Vitaminology, Vol.51, No.6, 392-397, 2005.

(要約): alpha-Tocopheryl succinate (TS), which is known to induce apoptosis selectively in cancer cells, has attracted attention as a chemotherapeutic agent. Recently, we found that alpha-tocopheryl malonate (TM) and alpha-tocopheryl oxalate (TO), among the alpha-tocopheryl esters tested, have high apoptogenic activity as well as TS. In this study, we investigated the characteristics of their cytotoxicity on normal cells and cancer cells in vitro, and their anti-cancer effects on mice inoculated with melanoma B16-F1 cells in vivo. The order of in vitro cytotoxicity was TO > or = TM > TS in all cell lines examined. Addition of exogenous superoxide dismutase (SOD) and the antioxidant N-acetyl cysteine (NAC) inhibited TS- and TM- but not TO-induced cell deaths. A selective cytotoxic effect on cancer cells was observed with TS but not with TM or TO. c-Jun N-terminal kinase (JNK) inhibitor II prevented cell death induced by TS but did not prevent cell deaths induced either by TM or TO. Intravenous administration of vesiculated TS and TM to mice inoculated with melanoma B16-F1 cells prevented tumor growth and enhanced the mean survival time, but TO administration killed the mice due to its acute high toxicity. From these results, we discussed the characteristics of their selective cytotoxicity toward tumor cells in vitro and anti-cancer effects in vivo.
(キーワード): Acetylcysteine / Animals / Antineoplastic Agents / Antioxidants / 細胞死 (cell death) / 細胞分裂 (cell division) / Male / Melanoma, Experimental / Mice / Mice, Nude / Mitochondrial Membranes / Neoplasm Transplantation / Superoxide Dismutase / Tocopherols / alpha-Tocopherol
(出版サイトへのリンク): ● Publication site (DOI): 10.3177/jnsv.51.392
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16521697; ● Summary page in Scopus @ Elsevier: 2-s2.0-31444446546

(DOI: 10.3177/jnsv.51.392, PubMed: 16521697, Elsevier: Scopus) Kenji Fukuzawa, Yasuaki Saitoh, Kaori Akai, Kentaro Kogure, Satoru Ueno, Akira Tokumura, Masaki Otagiri and Akira Shibata :
Antioxidant effect of bovine serum albumin on membrane lipid peroxidation induced by iron chelate and superoxide,
Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol.1668, No.1, 145-155, 2005.

(要約): Albumin is supposed to be the major antioxidant circulating in blood. This study examined the prevention of membrane lipid peroxidation by bovine serum albumin (BSA). Lipid peroxidation was induced by the exposing of enzymatically generated superoxide radicals to egg yolk phosphatidylcholine liposomes incorporating lipids with different charges in the presence of chelated iron catalysts. We used three kinds of Fe3+-chelates, which initiated reactions that were dependent on membrane charge: Fe3+-EDTA and Fe3+-EGTA catalyzed peroxidation in positively and negatively charged liposomes, respectively, and Fe3+-NTA, a renal carcinogen, catalyzed the reaction in liposomes of either charge. Fe3+-chelates initiated more lipid peroxidation in liposomes with increased zeta potentials, followed by an increase of their availability for the initiation of the reaction at the membrane surface. BSA inhibits lipid peroxidation by preventing the interaction of iron chelate with membranes, followed by a decrease of its availability in a charge-dependent manner depending on the iron-chelate concentration: one is accompanied and the other is unaccompanied by a change in the membrane charge. The inhibitory effect of BSA in the former at high concentrations of iron chelate would be attributed to its electrostatic binding with oppositely charged membranes. The inhibitory effect in the latter at low concentrations of iron chelate would be caused by BSA binding with iron chelates and keeping them away from membrane surface where lipid peroxidation is initiated. Although these results warrant further in vivo investigation, it was concluded that BSA inhibits membrane lipid peroxidation by decreasing the availability of iron for the initiation of membrane lipid peroxidation, in addition to trapping active oxygens and free radicals.
(キーワード): Animals / Antioxidants / Cattle / Iron Chelating Agents / Lipid Peroxidation / Membrane Lipids / Peptides / Serum Albumin, Bovine / Superoxides
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bbamem.2004.12.006
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15670740; ● Search Scopus @ Elsevier (PMID): 15670740; ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbamem.2004.12.006

(DOI: 10.1016/j.bbamem.2004.12.006, PubMed: 15670740) Kentaro Kogure, Aiko Yamauchi, Akira Tokumura, Kyoko Kondou, Naonobu Tanaka, Yoshihisa Takaishi and Kenji Fukuzawa :
Novel antioxidants isolated from plants of the genera Ferula, Inula, Prangos and Rheum collected in Uzbekistan,
Phytomedicine, Vol.11, No.7-8, 645-651, 2004.

(要約): We examined the effects of 48 compounds isolated from Ferula pallida, F. penninervis, Inula macrophylla, Prangos pabularia, P. tschimganica and Rheum maximowiczii collected in Uzbekistan on ADP/Fe2+-induced lipid peroxidation of egg yolk phosphatidylcholine liposomes. Of those compounds, 23 inhibited ADP/Fe2+-induced lipid peroxidation and nine showed especially strong inhibition of lipid peroxidation. Most compounds that inhibited peroxidation scavenged the 1,1'-diphenyl-2-picrylhydrazyl (DPPH) radical, indicating that the inhibition was due to radical scavenging. However, some compounds did not scavenge DPPH but inhibited lipid peroxidation significantly, suggesting that their inhibitory effect was not due to radical scavenging but to some other mechanism, such as prevention of Fe2+ function. Thus, we found various new antioxidants, some of which had a unique mechanism of action, in Ferula, Inula, Prangos and Rheum plants collected in Uzbekistan as seeds used in medicine.
(キーワード): Antioxidants / Natural products / Ferula / Inula / Prangos / Rheum
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.phymed.2003.09.004
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15636179; ● Search Scopus @ Elsevier (PMID): 15636179; ● Search Scopus @ Elsevier (DOI): 10.1016/j.phymed.2003.09.004

(DOI: 10.1016/j.phymed.2003.09.004, PubMed: 15636179) Kaori Akai, Koichiro Tsuchiya, Akira Tokumura, Kentaro Kogure, Satoru Ueno, Akira Shibata, Toshiaki Tamaki and Kenji Fukuzawa :
Ability of ferric nitrilotriacetate complex with three pH-dependent conformations to induce lipid peroxidation.,
Free Radical Research, Vol.38, No.9, 951-962, 2004.

(出版サイトへのリンク): ● Publication site (DOI): 10.1080/1071576042000261945
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15621713; ● Search Scopus @ Elsevier (PMID): 15621713; ● Search Scopus @ Elsevier (DOI): 10.1080/1071576042000261945

(DOI: 10.1080/1071576042000261945, PubMed: 15621713) Mamoru Okasaka, Yoshihisa Takaishi, Kentaro Kogure, Kenji Fukuzawa, Hirofumi Shibata, Tomihiko Higuti, Gisho Honda, Michiho Ito, Olimjon K. Kodzhimatov and Ozodbek Ashurmetov :
New Stilbene Derivatives from Calligonum leucocladum,
Journal of Natural Products, Vol.67, No.6, 1044-1046, 2004.

(要約): Two new stilbene derivatives, (E)-resveratrol 3-(6' '-galloyl)-O-beta-D-glucopyranoside (1) and (E)-resveratrol 3-(4' '-acetyl)-O-beta-D-xylopyranoside (2), and five known stilbene derivatives (3-7) were isolated from the dried aerial parts of Calligonum leucocladum. Their structures were established on the basis of spectroscopic evidence. Compound 1 showed antioxidant activity and a restorative effect of the inhibition of oxacillin to oxacillin/methicillin-resistant Staphylococcus aureus.
(キーワード): Drug Resistance, Multiple / Glucosides / Methicillin Resistance / Molecular Structure / Oxacillin / Plants, Medicinal / Polygonaceae / Staphylococcus aureus / Stilbenes / Uzbekistan
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/np0304823
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15217293; ● Search Scopus @ Elsevier (PMID): 15217293; ● Search Scopus @ Elsevier (DOI): 10.1021/np0304823

(DOI: 10.1021/np0304823, PubMed: 15217293) Kentaro Kogure, Susumu Hama, Mayumi Kisaki, Hideaki Takemasa, Akira Tokumura, Ichiro Suzuki and Kenji Fukuzawa :
Structural characteristic of terminal dicarboxyric moiety required for apoptogenic activity of α-Tocopheryl esters.,
Biochimica et Biophysica Acta (BBA) - General Subjects, Vol.1672, No.2, 93-99, 2004.

(要約): alpha-Tocopheryl succinate (TS) is known to induce apoptosis in various cells and has attracted attention as a chemotherapeutic agent. Recently, we reported the structural significance of the terminal dicarboxylic moiety for the action of TS [J. Nutr. Sci. Vitaminol. 49 (2003) 310-314]. In this study, to determine details of the relationship between the structure and the function of the terminal ester moiety of alpha-tocopherol (alpha-T), we synthesized four novel esters, alpha-tocopheryl oxalate (TO), alpha-tocopheryl malonate (TM), alpha-tocopheryl pimelate (TP) and alpha-tocopheryl succinate ethyl ester (TSE), and compared their apoptogenic activities with those of TS, alpha-T, gamma-tocopherol (gamma-T) and two commercially available alpha-T derivatives, alpha-tocopheryl nicotinate (TN) and alpha-tocopheryl acetate (TA), in vascular smooth muscle cells and a mouse breast cancer cell line C127I. TO and TM in addition to TS, but not the others, induced apoptosis in both cells. Particularly, TO was the most potent of all alpha-T derivatives used. The addition of exogenous superoxide dismutase (SOD) significantly prevented the apoptosis induced by TM as well as that by TS as reported previously, but did not affect TO-induced apoptosis. These results suggest that O(2)(-) generated exogenously participates in TM-induced apoptosis but not in TO-induced apoptosis. The difference in their apoptotic effects is attributed to structural properties of the terminal dicarboxylic moiety, which has an inflexible plane conformation in TO, while it is highly flexible in TM and TS.
(キーワード): アポトーシス (apoptosis) / Dicarboxylic Acids / Esters / Hydrogen-Ion Concentration / 分子構造 (molecular structure) / alpha-Tocopherol
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bbagen.2004.03.001
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15110091; ● Summary page in Scopus @ Elsevier: 2-s2.0-1942510597

(DOI: 10.1016/j.bbagen.2004.03.001, PubMed: 15110091, Elsevier: Scopus) Ai Suga, Yoshihisa Takaishi, Satoru GOTO, Tatsuo Munakata, Izumi Yamauchi and Kentaro Kogure :
Two lignan dimers from bamboo stems (Phyllostachys edulis),
Phytochemistry, Vol.64, No.5, 991-996, 2003.

(要約): Phyllostadimers A and B, two bis-lignans in which the two lignan units are directly connected by a C-C bond, were isolated from stems of bamboo, Phyllostachys edulis. Their structures were determined on the basis of spectral evidence. In addition, 14 known compounds were also obtained throughout the investigation. Phyllostadimer A significantly inhibited liposomal lipid peroxidation.
(キーワード): Phyllostachys edulis / Gramineae / Lignan dimers / Antioxidant activity
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/S0031-9422(03)00422-9
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 14561516; ● Search Scopus @ Elsevier (PMID): 14561516; ● Search Scopus @ Elsevier (DOI): 10.1016/S0031-9422(03)00422-9

(DOI: 10.1016/S0031-9422(03)00422-9, PubMed: 14561516) Kentaro Kogure, Sawa Nakashima, Akiko Tsuchie, Akira Tokumura and Kenji Fukuzawa :
Temporary membrane distortion of vascular smooth muscle cells is responsible for their apoptosis induced by platelet-activating factor-like oxidized phospholipids and thair degradation product lysophosphatidylcholine.,
Chemistry and Physics of Lipids, Vol.126, No.1, 29-38, 2003.

(要約): To obtain information about the mechanism of apoptosis induced by oxidized low density lipoproteins (oxLDL) in atherosclerotic plaques, we examined the effects of lysophosphatidylcholine (LPC) and platelet-activating factor (PAF)-like lipids (PAF-LL), which can be derived from oxLDL, on rat vascular smooth muscle cells (VSMC). All the lipids with different structures examined induced apoptosis of VSMC, so we studied the mechanism of induction of apoptosis by LPC. LPC-induced apoptosis was inhibited by alpha-tocopherol (alpha-T) and cholesterol (Chol), but not by other antioxidants such as palmitoyl ascorbic acid and PAF receptor antagonist. The cells temporarily became spherical and highly permeable before induction of apoptosis, and their change in shape was prevented by alpha-T and Chol. From these results, we suggest that the apoptosis induced by oxLDL-derived phospholipids in VSMC is caused by temporary membrane distortion, not through specific receptors.
(キーワード): Animals / Aorta / アポトーシス (apoptosis) / Cell Membrane / Cell Membrane Permeability / Cell Size / コレステロール (cholesterol) / Lipoproteins, LDL / Lysophosphatidylcholines / Muscle, Smooth, Vascular / 酸化と還元 (oxidation and reduction) / Phospholipids / Platelet Activating Factor / Rats / alpha-Tocopherol
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/S0009-3084(03)00091-4
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 14580708; ● Summary page in Scopus @ Elsevier: 2-s2.0-0142090711

(DOI: 10.1016/S0009-3084(03)00091-4, PubMed: 14580708, Elsevier: Scopus) Kentaro Kogure, Susumu Hama, Satoru GOTO, Tatsuo Munakata, Akira Tokumura and Kenji Fukuzawa :
alpha-Tocopheryl succinate activates protein kinase C in cellular and cell-free systems,
Journal of Nutritional Science and Vitaminology, Vol.49, No.5, 310-314, 2003.

(要約): The effect of alpha-tocopheryl succinate (TS) on protein kinase C (PKC) activity was examined. TS increased the auto-phosphorylation of PKC in vascular smooth muscle cells. Furthermore TS activated isolated PKC-like phorbol 12-myristate 13-acetate (PMA), although it was required at a significantly higher concentration than PMA for PKC activation. Molecular superimposition of the TS on PMA by computation suggested that TS took an active binding conformation to the PKC-like PMA, but that the conformational population was about 1/1.000. Consequently, we conclude that TS interacts directly with PKC, and activates it by taking an active conformation like PMA.
(キーワード): Animals / Cell-Free System / Enzyme Activation / Models, Molecular / Molecular Conformation / Muscle, Smooth, Vascular / リン酸化 (phosphorylation) / Protein Kinase C / Rats / Tetradecanoylphorbol Acetate / Tocopherols / ビタミンE (vitamin E)
(出版サイトへのリンク): ● Publication site (DOI): 10.3177/jnsv.49.310
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 14703304; ● CiNii @ 国立情報学研究所 (CRID): 1390001206326223360; ● Summary page in Scopus @ Elsevier: 2-s2.0-0242492228

(DOI: 10.3177/jnsv.49.310, PubMed: 14703304, CiNii: 1390001206326223360, Elsevier: Scopus) Kentaro Kogure, Koichiro Tsuchiya, Kazutoyo Abe, Michinori Akasu, Toshiaki Tamaki, Kenji Fukuzawa and Hiroshi Terada :
Direct radical scavenging by the bisbenzylisoquinoline alkaloid cepharanthine.,
Biochimica et Biophysica Acta (BBA) - General Subjects, Vol.1622, No.1, 1-5, 2003.

(要約): Cepharanthine (Ceph) is known as a potent antiperoxidative agent. Recently, we characterized the antiperoxidative effects of Ceph [Biochim. Biophys. Acta 1426 (1999) 133]. However, it was not clear whether the antiperoxidative effect is really due to its direct radical scavenging activity. Therefore, we studied the interaction of Ceph with the hydroxyl radical (*OH) by the electron paramagnetic resonance (EPR) technique. Results showed that Ceph actually scavenged *OH derived by the Fenton reaction. We also found that Ceph radicals were generated on interaction of Ceph with *OH in neutral aqueous solution, but not in acidic solution, consistent with the pH-dependent anti-lipid peroxidation activity of Ceph. Hence, we concluded that anti-lipid peroxidation by Ceph is due to its direct radical scavenging activity.
(キーワード): Alkaloids / Antioxidants / Benzylisoquinolines / Electron Spin Resonance Spectroscopy / Free Radical Scavengers / Hydrogen-Ion Concentration / Hydroxyl Radical / Lipid Peroxidation
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/S0304-4165(03)00095-3
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12829254; ● Search Scopus @ Elsevier (PMID): 12829254; ● Search Scopus @ Elsevier (DOI): 10.1016/S0304-4165(03)00095-3

(DOI: 10.1016/S0304-4165(03)00095-3, PubMed: 12829254) Kentaro Kogure, Sachie Manabe, Susumu Hama, Akira Tokumura and Kenji Fukuzawa :
Potentiation of anti-cancer effect by intravenous administration of vesiculated α-tocopheryl hemisuccinate on mouse melanoma in vivo.,
Cancer Letters, Vol.192, No.1, 19-24, 2003.

(要約): We examined the effect of alpha-tocopheryl hemisuccinate (TS) on the growth of mouse melanoma cells B16-F1 inoculated on the back of hairless mice by two administration procedures of TS, i.p. administration of TS dissolved with dimethyl sulfoxide (TS i.p.) and i.v. administration of TS vesicles (TS-vesicle i.v.). TS i.p. significantly prevented the tumor growth of only half the mice in the group. However, TS-vesicle i.v. almost completely inhibited the tumor growth of all mice. Furthermore, the mean survival of the TS-vesicle i.v. group was 1.4-fold those of the control and TS i.p. groups.
(キーワード): Animals / アポトーシス (apoptosis) / 細胞分裂 (cell division) / Injections, Intraperitoneal / Injections, Intravenous / Male / Melanoma / Mice / Mice, Hairless / Neoplasm Transplantation / Survival Rate / Time Factors / Tocopherols / Tumor Cells, Cultured / ビタミンE (vitamin E)
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/S0304-3835(02)00683-3
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12637149; ● Summary page in Scopus @ Elsevier: 2-s2.0-0037456691

(DOI: 10.1016/S0304-3835(02)00683-3, PubMed: 12637149, Elsevier: Scopus) Kentaro Kogure, Susumu Hama, Sachie Manabe, Akira Tokumura and Kenji Fukuzawa :
High cytotoxicity of α-tocopheryl hemisuccinate to cancer cells is due to failure of their antioxidative defense systems.,
Cancer Letters, Vol.186, No.2, 151-156, 2002.

(要約): Alpha-tocopheryl hemisuccinate (TS) has been reported to induce apoptosis in various cells, and to show higher toxicity to cancer cells than to normal cells. In this study, although TS induced apoptosis in both a mouse breast normal cell line NMuMG and a mouse breast cancer cell line C127I, the latter were more susceptible to TS. TS-induced apoptosis in C127I was inhibited by superoxide dismutase, alpha-tocopherol and butylated hydroxyanisol. From these results, superoxide (O(2)(-)) itself and reactive oxygen species derived from O(2)(-) and/or free radicals are assumed to be associated with TS toxicity, and the high toxicity of TS to cancer cells is suggested to be due to failure of their antioxidative defense systems.
(キーワード): Animals / Antioxidants / Apoptosis / Butylated Hydroxyanisole / Carcinogens / Cell Line / Cell Survival / DNA Fragmentation / Dose-Response Relationship, Drug / Free Radicals / Humans / Mice / Neoplasms / Superoxide Dismutase / Superoxides / Tocopherols / Tumor Cells, Cultured / Vitamin E / alpha-Tocopherol
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/S0304-3835(02)00344-0
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12213284; ● Summary page in Scopus @ Elsevier: 2-s2.0-0037027755

(DOI: 10.1016/S0304-3835(02)00344-0, PubMed: 12213284, Elsevier: Scopus) Kentaro Kogure, Satoru GOTO, Miki Nishimura, Mina Yasumoto, Kazutoyo Abe, Chie Ohiwa, Hironori Sassa, Takenori Kusumi and Hiroshi Terada :
Mechanism of potent antiperoxidative effect of capsaicin,
Biochimica et Biophysica Acta (BBA) - General Subjects, Vol.1573, No.1, 84-92, 2002.

(要約): The effect of a pungent ingredient of red pepper, capsaicin, on lipid peroxidation of rat liver mitochondria (RLM) induced by ADP/Fe(2+) was studied. Capsaicin inhibited the lipid peroxidation significantly, being more effective than the well-known antioxidant alpha-tocopherol. Capsaicin was also found to scavenge 1,1'-diphenyl-2-picrylhydrazyl (DPPH) radicals both in solution and in membranes, especially the latter. Capsaicin was found to scavenge radicals both at/near the membrane surface and in the interior of the membrane. The phenolic OH-group of capsaicin remained intact after reaction with DPPH radicals, indicating that the hydroxyl group is not associated with the radical scavenging reaction. From the results of quantum chemical calculations of various radical intermediates derived from the model compound N-vanillylacetamide, and the findings that vanillin and 8-methyl-6-noneamide were major reaction products of capsaicin with DPPH radicals, it was concluded that the radical scavenging site of capsaicin is the C7-benzyl carbon.
(キーワード): Adenosine Diphosphate / Animals / Antioxidants / Binding Sites / Capsaicin / Electron Spin Resonance Spectroscopy / Free Radical Scavengers / Free Radicals / Lipid Peroxidation / Male / Mitochondria, Liver / Molecular Structure / Oxygen Consumption / Rats / Rats, Wistar / Spectrophotometry
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/S0304-4165(02)00335-5
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12383946; ● Search Scopus @ Elsevier (PMID): 12383946; ● Search Scopus @ Elsevier (DOI): 10.1016/S0304-4165(02)00335-5

(DOI: 10.1016/S0304-4165(02)00335-5, PubMed: 12383946) Akira Tokumura, Junya Shinomiya, Seishi Kishimoto, Tamotsu Tanaka, Kentaro Kogure, Takayuki Sugiura, Kiyoshi Satouchi, Keizo Waku and Kenji Fukuzawa :
Human platelets respond differentially to lysophosphatidic acids having a highly unsaturated fatty acyl group and alkyl ether-linked lysophosphatidic acids,
The Biochemical Journal, Vol.365, No.Pt 3, 617-628, 2002.

(要約): Lysophosphatidic acid (LPA) is a physiological agonist that is produced by lysophospholipase D, phospholipase A(1) and phospholipase A(2) in the blood of animals. It exerts diverse biological actions on a broad range of animal cells. Specific receptors for this important agonist have been characterized. In this investigation, for the first time we prepared LPAs having a highly unsaturated fatty acyl group, such as the eicosapentaenoyl or docosahexaenoyl residue, and their acetylated derivatives. Human platelets aggregated more potently in response to the highly unsaturated acyl-LPAs than to LPAs with a C(18) fatty acyl group, such as an oleoyl group, while alkyl ether-linked LPAs (alkyl-LPA) had much stronger aggregating activity. Two positional isomers of LPAs with an arachidonoyl, eicosapentaenoyl or docosahexaenoyl group had equipotent aggregatory activity as well as the positional isomers of their acetylated analogues, indicating that putative LPA receptors could not distinguish the difference between the positional isomers. We found that platelet preparations from two individuals showed no aggregatory response to alkyl-LPAs, although they contained mRNAs for known LPA receptors in the following order of expression level: endothelial differentiation gene (Edg)-4>Edg-7>Edg-2. We also obtained evidence that 2-(p-amylcinnamoyl)amino-4-chlorobenzoic acid (ONO-RS-082), a phospholipase A(2) inhibitor, potentiated alkyl-LPA-induced platelet aggregation, but inhibited highly unsaturated acyl-LPA-induced platelet aggregation. These results indicated that human platelets express acyl-LPA-selective and alkyl-LPA-selective receptors on their plasma membrane.
(キーワード): Affinity Labels / Aminobenzoic Acids / Animals / Blood Platelets / Cattle / Cinnamates / Dose-Response Relationship, Drug / Fatty Acids, Unsaturated / Gas Chromatography-Mass Spectrometry / Glyceryl Ethers / Humans / Lysophospholipids / 分子構造 (molecular structure) / Nuclear Proteins / Phosphodiesterase Inhibitors / Platelet Aggregation / Receptors, Cell Surface / Receptors, G-Protein-Coupled / Receptors, Lysophosphatidic Acid / Serum Albumin, Bovine / Transcription Factors
(出版サイトへのリンク): ● Publication site (DOI): 10.1042/BJ20020348
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11982483; ● CiNii @ 国立情報学研究所 (CRID): 1570854176748304256; ● Summary page in Scopus @ Elsevier: 2-s2.0-0036683314

(DOI: 10.1042/BJ20020348, PubMed: 11982483, CiNii: 1570854176748304256, Elsevier: Scopus) Kentaro Kogure, Motoki Morita, Susumu Hama, Sawa Nakashima, Akira Tokumura and Kenji Fukuzawa :
Enhancement by α-tocopheryl hemisuccinate of nitric oxide production induced by lypopolysaccharide and interferon-γ through up-regulation of protein kinase C in rat vascular smooth muscle cells.,
European Journal of Biochemistry, Vol.269, No.9, 2367-2372, 2002.

(要約): The effect of alpha-tocopheryl hemisuccinate (TS) on lipopolysaccharide (LPS)/interferon-gamma (IFN)-induced nitric oxide production in rat vascular smooth muscle cells (VSMC) was examined. The LPS/IFN-induced NO production was enhanced by TS but not by the other alpha-tocopherol (alpha-T) derivatives alpha-tocopheryl acetate (TA) and alpha-tocopheryl nicotinate (TN), or alpha-T itself. alpha-T, TA and TN inhibited the enhancement by TS of LPS/IFN-induced NO production. The enhancing effect of TS was observed in the presence of LPS, but not IFN, suggesting that TS participates in the LPS-stimulated signal pathway leading to NO production. Protein kinase C (PKC) inhibitors, but not protein kinase A inhibitors, inhibited the enhancing effect of TS on LPS/IFN-induced NO production. Furthermore, TS enhanced the amount of PKCalpha in VSMC. From these results, we concluded that the enhancing effect of LPS/IFN-induced NO production was caused by upregulation of PKC in VSMC.
(キーワード): Animals / Cyclic AMP-Dependent Protein Kinase Type II / Cyclic AMP-Dependent Protein Kinases / Interferon-gamma / Lipopolysaccharides / Muscle, Smooth, Vascular / 一酸化窒素 (nitric oxide) / Protein Kinase C / Rats / Tocopherols / Up-Regulation / ビタミンE (vitamin E)
(出版サイトへのリンク): ● Publication site (DOI): 10.1046/j.1432-1033.2002.02894.x
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11985620; ● CiNii @ 国立情報学研究所 (CRID): 1571698601676950784; ● Summary page in Scopus @ Elsevier: 2-s2.0-0036091121

(DOI: 10.1046/j.1432-1033.2002.02894.x, PubMed: 11985620, CiNii: 1571698601676950784, Elsevier: Scopus) Akira Tokumura, Kyoko Tominaga, Yasuda Katsuhiko, Hideharu Kanzaki, Kentaro Kogure and Kenji Fukuzawa :
Lack of significant differences in the corrected activity of lysophospholipase D, producer of phospholipid mediator lysophosphatidic acid, in incubated serum from women with and without ovarian tumors,
Cancer, Vol.94, No.1, 141-151, 2002.

(要約): Several studies have shown that lysophosphatidic acid (LPA), a phospholipidic chemical mediator, is relevant to the pathogenesis of ovarian carcinoma. Higher plasma levels of LPA have been reported in patients with ovarian carcinoma than in healthy patients, and LPA is known to activate ovarian carcinoma cells. To determine the reason for the increased plasma LPA levels in ovarian carcinoma patients, we compared the activities of serum lysophospholipase D, a novel LPA-producing metallo-enzyme, in healthy volunteers, patients with benign ovarian tumor, and patients with ovarian carcinoma. Lysophospholipase D activity was assessed by measuring the percentage conversion of [14C]palmitoyl-lysophosphatidylcholine (LPC) added to human serum. The apparent enzyme activities were corrected based on the serum levels of palmitoyl-LPC determined by gas-liquid chromatography after its purification and conversion to fatty acid methyl esters. The apparent activity of lysophospholipase D in serum preparations from four patients with ovarian carcinoma at Stage IV was significantly higher than those from five healthy subjects, five patients with benign ovarian tumors, and fourteen patients with ovarian carcinoma at Stages I (n = 5), II (n = 4), and III (n = 5). The serum levels of LPC, an endogenous substrate of lysophospholipase D, in ovarian carcinoma patients were less than those in patients with benign ovarian tumors. There were no significant differences in the corrected lysophospholipase D activity for the LPC levels in healthy women, patients with benign ovarian tumors, and patients with ovarian carcinoma at various stages. The current results suggest that lysophospholipase D is not associated with the elevated plasma levels of LPA in ovarian carcinoma patients previously reported, although only a limited number of patients were analyzed.
(キーワード): Adult / Aged / Female / Humans / Lysophospholipids / Middle Aged / Neoplasm Staging / Ovarian Neoplasms / Phosphoric Diester Hydrolases / Tumor Markers, Biological
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/cncr.10146
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11815970; ● Summary page in Scopus @ Elsevier: 2-s2.0-0036140653

(DOI: 10.1002/cncr.10146, PubMed: 11815970, Elsevier: Scopus) Kentaro Kogure, Motoki Morita, Sawa Nakashima, Susumu Hama, Akira Tokumura and Kenji Fukuzawa :
Superoxide is responsible for apoptosis in rat vascular smooth muscle cells induced by α-tocopheryl hemisuccinate.,
Biochimica et Biophysica Acta (BBA) - General Subjects, Vol.1528, No.1, 25-30, 2001.

(要約): We investigated the mechanism of cell toxicity of alpha-tocopheryl hemisuccinate (TS). TS concentration- and time-dependently induced the lactate dehydrogenase release and DNA fragmentation of rat vascular smooth muscle cells (VSMC). Exogenous addition of superoxide dismutase, but not catalase, significantly inhibited the cell toxicity of TS. The NADPH-dependent oxidase activity of VSMC was stimulated by TS treatment. The cell toxicity of TS was inhibited by NADPH oxidase inhibitor 4-(2-aminoethyl)-benzenesulfonyl fluoride. Consequently, TS-induced apoptosis of VSMC was suggested to be caused by exogenous O(2)(-) generated via the oxidase system activated with TS.
(キーワード): Animals / Apoptosis / Ascorbic Acid / Catalase / Cells, Cultured / Cytochrome c Group / DNA Fragmentation / Dose-Response Relationship, Drug / Enzyme Activation / L-Lactate Dehydrogenase / Muscle, Smooth, Vascular / NADPH Oxidase / Oxygen / Rats / Superoxide Dismutase / Superoxides / Tocopherols / Vitamin E
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/S0304-4165(01)00168-4
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11514094; ● Search Scopus @ Elsevier (PMID): 11514094; ● Search Scopus @ Elsevier (DOI): 10.1016/S0304-4165(01)00168-4

(DOI: 10.1016/S0304-4165(01)00168-4, PubMed: 11514094) Satoru GOTO, Kentaro Kogure, Kazutoyo Abe, Yukari Kimata, Katsuhiro Kitahama, Eiji Yamashita and Hiroshi Terada :
Efficient radical trapping at the surface and inside the phospholipid membrane is responsible for highly potent antiperoxidative activity of the carotenoid astaxanthin,
Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol.1512, No.2, 251-258, 2001.

(要約): The effects of the carotenoids beta-carotene and astaxanthin on the peroxidation of liposomes induced by ADP and Fe(2+) were examined. Both compounds inhibited production of lipid peroxides, astaxanthin being about 2-fold more effective than beta-carotene. The difference in the modes of destruction of the conjugated polyene chain between beta-carotene and astaxanthin suggested that the conjugated polyene moiety and terminal ring moieties of the more potent astaxanthin trapped radicals in the membrane and both at the membrane surface and in the membrane, respectively, whereas only the conjugated polyene chain of beta-carotene was responsible for radical trapping near the membrane surface and in the interior of the membrane. The efficient antioxidant activity of astaxanthin is suggested to be due to the unique structure of the terminal ring moiety.
(キーワード): Adenosine Diphosphate / Antioxidants / Cardiolipins / Ferrous Compounds / Free Radicals / Hydrogen Bonding / Iron / Kinetics / Lipid Peroxidation / Liposomes / Models, Molecular / Molecular Conformation / Oxidation-Reduction / Phosphatidylcholines / Surface Properties / Xanthophylls / beta Carotene
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/S0005-2736(01)00326-1
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11406102; ● Search Scopus @ Elsevier (PMID): 11406102; ● Search Scopus @ Elsevier (DOI): 10.1016/S0005-2736(01)00326-1

(DOI: 10.1016/S0005-2736(01)00326-1, PubMed: 11406102) Kenji Fukuzawa, Akira Tokumura, Kentaro Kogure, Masahito Iemura, Naoto Gondoh, Masanobu Fujii, Satoru Ueno and Akira Shibata :
A comparative study of the ability of ferric nitrilotriacetate and other iron chelators to assist membrane lipid peroxidation by superoxide radicals,
Chemistry and Physics of Lipids, Vol.110, No.1, 69-84, 2001.

(要約): This study examined some of the variables determining the efficiency of lipid peroxidation in egg yolk phosphatidylcholine liposomes and in microsomes exposed to enzymatically-generated superoxide radicals. The initiation of peroxidation required the presence of preformed lipid peroxides and a chelated metal catalyst. Comparison of the relative effectiveness of four iron chelating agents showed that the chelate must bind to the membrane by coulombic attraction between the charged membrane and a chelate carrying an opposite net charge. Of the chelates tested, only the carcinogenic ferric nitrilotriacetate [corrected] (Fe(3+)-NTA) was an effective catalyst of oxidation of all membranes, whether carrying a net charge, or not. We postulate that the unique catalytic capacity of the ferric nitrilotriacetate [corrected] (Fe(3+)-NTA) can be explained by its existence in two forms at neutral pH, each binding to oppositely charged membranes and initiating their peroxidation. This gives the complex the unique ability to bind to any membrane, which may be a factor in its carcinogenicity.
(キーワード): Animals / Ascorbic Acid / Carcinogens / Ferric Compounds / Hydrogen-Ion Concentration / Iron Chelating Agents / Lipid Peroxidation / Liposomes / Male / Microsomes, Liver / NADP / Nitrilotriacetic Acid / Oxidation-Reduction / Oxygen / Phosphatidylcholines / Rats / Rats, Wistar / Superoxides / Thiobarbituric Acid Reactive Substances
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11245836; ● Search Scopus @ Elsevier (PMID): 11245836

(PubMed: 11245836) Takashi Chikawa, Takaaki Ikata, Shinsuke Katoh, Yoshitaka Hamada, Kentaro Kogure and Kenji Fukuzawa :
Preventive effects of lecithinized superoxide dismutase and methylprednisolone on spinal cord injury in rats, --- Transcriptional regulation of inflammatory and neurotrophic genes ---,
Journal of Neurotrauma, Vol.18, No.1, 93-103, 2001.

(要約): The effects of lecithinized superoxide dismutase (PC-SOD) and/or methylpredisolone (MP) in preventing secondary pathological changes after spinal cord injury (SCI) were investigated in rats with reference to recovery of hindlimb motor function and expression of mRNA of pro-inflammatory and neurotrophic genes. Hindlimb motor function was assessed as the BBB open field locomotor scores. The BBB scores of three groups treated with either PC-SOD (40,000 units/kg), MP (30 mg/kg), or a combination of PC-SOD and MP (PC-SOD+MP) increased with time until 3 days after SCI, and were significantly higher than that of the control group (p < 0.05). Thereafter, the score of the PC-SOD group increased, whereas that of the MP group showed a temporary decrease from day 3 to 5 and then it gradually recovered. The scores in all groups reached a plateau about 18 days after SCI. The PC-SOD+MP group did not show a synergism but a tendency similar to that of the MP group. PC-SOD and MP had down-regulatory effects on mRNA expression of pro-inflammatory substances such as interleukin-1beta (IL-1beta), intercellular adhesion molecule-1 (ICAM-1), and inducible-nitric oxide synthetase (i-NOS) after spinal cord compression at 3, 6, and 24 h, respectively, as judged by a semiquantitative reverse transcription-polymerase chain reaction and on the lipid peroxide (LPO) level 1 h after injury as determined by thiobarbituric acid-reactive substances. The suppression of pro-inflammatory genes expression, especially IL-1beta were greater in the MP group than in the PC-SOD group, while suppression of LPO level was similar in these two groups. PC-SOD+MP treatment augmented the suppression of all three pro-inflammatory genes expression and the decrease of the LPO level. The level of neurotrophin-3 (NT-3) mRNA increased from 6 h after SCI and reached a maximum after 48 h. NT-3 mRNA level was enhanced by PC-SOD treatment, but not by MP treatment. Thus, the effect of MP in suppressing these pro-inflammatory genes expression was more than that of PC-SOD. The difference in motor function in the early and later stage may be partially due to differences in expression of IL-1beta and NT-3 after either treatment, through an IL-1beta-dependent or NT-3-mediated repair response.
(キーワード): Animals / Gene Expression Regulation / Glycerol-3-Phosphate Dehydrogenase (NAD+) / Glycerolphosphate Dehydrogenase / Intercellular Adhesion Molecule-1 / Interleukin-1 / Male / Methylprednisolone / Movement Disorders / Myelitis / Nerve Growth Factors / Neurotrophin 3 / Nitric Oxide Synthase / Phosphatidylcholines / RNA, Messenger / Rats / Rats, Wistar / Recovery of Function / Spinal Cord Injuries / Superoxide Dismutase / Thiobarbituric Acid Reactive Substances / Transcription, Genetic
(出版サイトへのリンク): ● Publication site (DOI): 10.1089/089771501750055802
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11200253; ● Search Scopus @ Elsevier (PMID): 11200253; ● Search Scopus @ Elsevier (DOI): 10.1089/089771501750055802

(DOI: 10.1089/089771501750055802, PubMed: 11200253) Akira Tokumura, T. Sumida, M. Toujima, Kentaro Kogure, Kenji Fukuzawa, Y. Takahashi and S. Yamamoto :
Structural identification of phosphatidylcholines having an oxidatively shortened linoleate residue generated through its oxygenation with soybean or rabbit reticulocyte lipoxygenase.,
Journal of Lipid Research, Vol.41, No.6, 953-962, 2000.

(要約): Phosphatidylcholines (PCs) with platelet-activating factor (PAF)-like biological activities are known to be generated by fragmentation of the sn-2-esterified polyunsaturated fatty acyl group. The reaction is free radical-mediated and triggered by oxidants such as metal ions, oxyhemoglobin, and organic hydroperoxides. In this study, we characterized the PAF-like phospholipids produced on reaction of PC having a linoleate group with lipoxygenase enzymes at low oxygen concentrations. When the oxidized PCs were analyzed by gas chromatography-mass spectrometry, two types of oxidatively fragmented PC were detected. One PC had an sn-2-short chain saturated or unsaturated acyl group (C(8)-C(13)) with an aldehydic terminal; the abundant species were PCs with C(9) and C(13). The other PC had a short chain saturated acyl group (C(6)-C(9)) with a methyl terminal, and the most predominant species was PC with C(8). When the extracts of oxidation products were subjected to catalytic hydrogenation, PCs having saturated acyl groups (C(6)-C(14)) were detected; the most abundant was C(12) species. The less regiospecific formation of PAF-like lipids suggests that they were generated by oxidative fragmentation of PC hydroperoxides formed by non-stereoselective oxygenation of the alkyl radical of esterified linoleate that escaped from the active centers of lipoxygenases. One of the PAF-like PC with an aldehydic terminal was found to be bioactive; it inhibited the production of nitric oxide induced by lipopolysaccharide and interferon-gamma in vascular smooth muscle cells from rat aorta.
(キーワード): Animals / Cells, Cultured / Chromatography, Thin Layer / Gas Chromatography-Mass Spectrometry / Linoleic Acid / Lipoxygenase / Muscle, Smooth, Vascular / Nitric Oxide / Oxidation-Reduction / Oxygen / Phosphatidylcholines / Platelet Activating Factor / Rabbits / Rats / Reticulocytes / Soybeans
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10828088; ● Summary page in Scopus @ Elsevier: 2-s2.0-0033934565

(PubMed: 10828088, Elsevier: Scopus) Kentaro Kogure, Satoru GOTO, Kazutoyo Abe, Chie Ohiwa, Michinori Akasu and Hiroshi Terada :
Potent anti-peroxidation activity of the bisbenzylisoquinoline alkaloid cepharanthine: The amine moiety is responsible for its pH-dependent radical scavenge activity,
Biochimica et Biophysica Acta (BBA) - General Subjects, Vol.1426, No.1, 133-142, 1999.

(要約): The bisbenzylisoquinoline alkaloid cepharanthine, which has been considered to exhibit antiperoxidation activity due to its membrane stabilizing effect, was found to scavenge radicals such as .OH and DPPH (1,1-diphenyl-2-picrylhydrazyl) in solution, and to inhibit lipid peroxidation in mitochondria and liposomes by Fe2+/ADP. The antiperoxidation activity of cepharanthine in rat liver mitochondria initiated by Fe2+/ADP at pH 7.4 was much greater than that of alpha-tocopherol, its half-inhibitory concentration being about 23 microM. However, cepharanthine was effective only at neutral pH values such as pH 7.4, not in a moderately acidic pH region below pH 6.5. Accordingly, the neutral form of the deprotonated amine moiety in the tetrahydroisoquinoline ring is concluded to be responsible for the radical scavenging activity of cepharanthine. There are two amine moieties in the cepharanthine molecule, but we specified the effective amine moiety from the antiperoxidation activities of the imine analogs of cepharanthine.
(キーワード): Alkaloids / Amines / Animals / Antioxidants / Benzylisoquinolines / Bepridil / Biphenyl Compounds / Free Radical Scavengers / Hydrogen-Ion Concentration / Lipid Peroxidation / Male / Membrane Fluidity / Mitochondria, Liver / Picrates / Rats / Rats, Wistar
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/S0304-4165(98)00146-9
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 9878710; ● Search Scopus @ Elsevier (PMID): 9878710; ● Search Scopus @ Elsevier (DOI): 10.1016/S0304-4165(98)00146-9

(DOI: 10.1016/S0304-4165(98)00146-9, PubMed: 9878710) Junji Ichihara, Yasuo Shinohara, Kentaro Kogure and Hiroshi Terada :
Nucleotide sequence of the 5'-flanking region of the rat type II hexokinase gene,
Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression, Vol.1260, No.3, 365-368, 1995.

(要約): In a previous study, we found that the steady state transcript level of type II hexokinase was specifically and remarkably elevated in rat hepatoma AH130 cells. To determine the molecular mechanism of transcriptional control of the type II hexokinase gene, we examined the nucleotide sequence of its 5'-flanking region and analyzed putative transcription factor binding sites. We also examined the type II hexokinase promoter activity by the chloramphenicol acetyltransferase (CAT) assay.
(キーワード): Amino Acid Sequence / Animals / Base Sequence / Chloramphenicol O-Acetyltransferase / Cloning, Molecular / DNA / Hexokinase / Molecular Sequence Data / Promoter Regions, Genetic / Rats / Transcription, Genetic
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/0167-4781(94)00226-S
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 7873617; ● Search Scopus @ Elsevier (PMID): 7873617; ● Search Scopus @ Elsevier (DOI): 10.1016/0167-4781(94)00226-S

(DOI: 10.1016/0167-4781(94)00226-S, PubMed: 7873617) Yasuo Shinohara, Kenji Yamamoto, Kentaro Kogure, Junji Ichihara and Hiroshi Terada :
Steady state transcript levels of the type II hexokinase and type 1 glucose transporter in human tumor cell line,
Cancer Letters, Vol.82, No.1, 27-32, 1994.

MISC

福澤健治, 小暮健太朗, 中島佐和, 土江明子, 德村彰 :
リン脂質酸化二次作物による血管平滑筋細胞のアポトーシス誘導とビタミンEによる抑制作用,
ビタミンE研究の進歩Ⅺ, 115-127, 2004年. 真鍋幸恵, 小暮健太朗, 森田健之, 德村彰, 福澤健治 :
抗ガン作用の増強を志向したビタミンEコハク酸ベシクル,
ビタミンE研究の進歩Ⅺ, 45-49, 2004年. 德村彰, 平尾恵理, 丸山祐史, 小暮健太朗, 福澤健治, 安田勝彦, 神崎秀暢 :
正常および異常妊娠時のヒト血清リゾホスホリパーゼD活性,
脂質生化学研究, Vol.45, No.0, 95-97, 2003年.

(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1570572700727485440

(CiNii: 1570572700727485440) 德村彰, 富永恭子, 小暮健太朗, 福澤健治, 安田勝彦, 刈谷優子, 真島英司 :
生理活性リン脂質LPAを産生するヒト血漿リゾホスホリパーゼDは多機能性ヌクレオチドホスジエステラーゼautotaxinである,
脂質生化学研究, Vol.44, 78-881, 2002年. 德村彰, 富永恭子, 金谷由美, 小暮健太朗, 福澤健治 :
モルモット腹腔洗浄液のリゾホスホリパーゼD活性,
脂質生化学研究, Vol.43, 82-85, 2001年.

(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1570009750154718208

(CiNii: 1570009750154718208) Kenji Fukuzawa, Kentaro Kogure, M Morita, S Hama, S Nakashima and Akira Tokumura :
Enhancement by α-tocopherol hemisuccinate of nitric oxide production induced by lipopolysaccharide and interferon-γ through up-regulation of protein kinase C in rat vascular smooth muscle cells,
Proc.Of the second China-Japan international Conference on Vitamins, 262-267, 2001. 德村彰, 金谷由美, 富永恭子, 小暮健太朗, 福澤健治, 北原真樹, 安田勝彦 :
血清リゾホスホリパーゼDによるリゾホスファチジン酸産生の病態下での変動,
脂質生化学研究, Vol.42, 41-44, 2000年. 德村彰, 四宮淳也, 小暮健太朗, 福澤健治, 田中保, 里内清 :
高度不飽和脂肪酸を有するリゾホスファチジン酸:血漿中での生成と血小板凝集活性,
脂質生化学研究, Vol.41, 193-195, 1999年.

総説・解説

小暮健太朗 :
ビタミンEエステル体の抗肥満薬としての可能性,
バイオインダストリー, Vol.40, No.8, 49-54, 2023年8月. 小暮健太朗 :
微弱電流による薬剤の皮内送達,
化学工学, Vol.36, No.5, 219-222, 2022年5月.

(徳島大学機関リポジトリ): ● Metadata: 117239
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1050574411836978048

(徳島大学機関リポジトリ: 117239, CiNii: 1050574411836978048) Tatsuya Fukuta and Kentaro Kogure :
Biomimetic nanoparticle drug delivery systems to overcome biological barriers for therapeutic applications.,
Chemical & Pharmaceutical Bulletin, Vol.70, No.5, 334-340, May 2022.

(要約): Targeted drug delivery using nanoparticles has been applied for the treatment of diverse diseases, including cancer and inflammatory diseases. Nanoparticle-mediated delivery of therapeutic agents via the enhanced permeability and retention effect generally augments their therapeutic efficiency; however, limitations with passive entry of nanoparticles into diseased sites, due to the presence of biological barriers represented by the endothelial layer, remain to be addressed. To this end, development of nanoparticles with intrinsic characteristics similar to circulatory cells (e.g., leukocytes, platelets) for use as biomimetic drug delivery systems (DDS) has been focused as a means to overcome the issues of conventional DDS. In particular, synthetic biomimetic nanoparticles coated with cellular membranes were recently prepared and shown to actively overcome the inflamed vessels and tumor microenvironment as a result of the functionality of membrane proteins, which allowed secure drug delivery into diseased sites. We recently developed liposomes modified with leukocyte membrane proteins via intermembrane protein transfer, a simple method to reconstitute cellular membrane proteins onto lipid bilayers. The resultant liposomes demonstrated the ability to cross the inflamed endothelial layer and permeate into tumor tissue by mimicking the properties of leukocytes. Thus, biomimetic DDS offer promise as new therapeutic approaches for various diseases by overcoming biological barriers that typically inhibit drug delivery. Herein, we review recent approaches to develop biomimetic DDS using the cell membrane coating method, and highlight our recent findings on leukocyte-mimetic liposomes prepared via intermembrane protein transfer.
(キーワード): Biomimetics / Drug Delivery Systems / Liposomes / Membrane Proteins / Nanoparticle Drug Delivery System
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/cpb.c21-00961
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35491189; ● Search Scopus @ Elsevier (PMID): 35491189; ● Search Scopus @ Elsevier (DOI): 10.1248/cpb.c21-00961

(DOI: 10.1248/cpb.c21-00961, PubMed: 35491189) Mahadi Hasan, Anowara Khatun and Kentaro Kogure :
Iontophoresis of Biological Macromolecular Drugs.,
Pharmaceutics, Vol.14, No.3, 525, Feb. 2022.

(要約): Over the last few decades, biological macromolecular drugs (e.g., peptides, proteins, and nucleic acids) have become a significant therapeutic modality for the treatment of various diseases. These drugs are considered superior to small-molecule drugs because of their high specificity and favorable safety profiles. However, such drugs are limited by their low oral bioavailability and short half-lives. Biological macromolecular drugs are typically administrated via invasive methods, e.g., intravenous or subcutaneous injections, which can be painful and induce needle phobia. Noninvasive transdermal delivery is an alternative administration route for the local and systemic delivery of biological macromolecular drugs. However, a challenge with the noninvasive transdermal delivery of biological macromolecular drugs is the outermost layer of the skin, known as the stratum corneum, which is a physical barrier that restricts the entry of extraneous macromolecules. Iontophoresis (IP) relies on the application of a low level of electricity for transdermal drug delivery, in order to facilitate the skin permeation of hydrophilic and charged molecules. The IP of several biological macromolecular drugs has recently been investigated. Herein, we review the IP-mediated noninvasive transdermal delivery of biological macromolecular drugs, their routes of skin permeation, their underlying mechanisms, and their advance applications.
(徳島大学機関リポジトリ): ● Metadata: 117589
(出版サイトへのリンク): ● Publication site (DOI): 10.3390/pharmaceutics14030525
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35335900; ● Search Scopus @ Elsevier (PMID): 35335900; ● Search Scopus @ Elsevier (DOI): 10.3390/pharmaceutics14030525

(徳島大学機関リポジトリ: 117589, DOI: 10.3390/pharmaceutics14030525, PubMed: 35335900) Tatsuya Fukuta, Naoto Oku and Kentaro Kogure :
Application and utility of liposomal neuroprotective agents and biomimetic nanoparticles for the treatment of ischemic stroke,
Pharmaceutics, Vol.14, No.2, 361, Feb. 2022.

(要約): Ischemic stroke is still one of the leading causes of high mortality and severe disability worldwide. Therapeutic options for ischemic stroke and subsequent cerebral ischemia/reperfusion injury remain limited due to challenges associated with drug permeability through the blood-brain barrier (BBB). Neuroprotectant delivery with nanoparticles, including liposomes, offers a promising solution to address this problem, as BBB disruption following ischemic stroke allows nanoparticles to pass through the intercellular gaps between endothelial cells. To ameliorate ischemic brain damage, a number of nanotherapeutics encapsulating neuroprotective agents, as well as surface-modified nanoparticles with specific ligands targeting the injured brain regions, have been developed. Combination therapy with nanoparticles encapsulating neuroprotectants and tissue plasminogen activator (t-PA), a globally approved thrombolytic agent, has been demonstrated to extend the narrow therapeutic time window of t-PA. In addition, the design of biomimetic drug delivery systems (DDS) employing circulating cells (e.g., leukocytes, platelets) with unique properties has recently been investigated to overcome the injured BBB, utilizing these cells' inherent capability to penetrate the ischemic brain. Herein, we review recent findings on the application and utility of nanoparticle DDS, particularly liposomes, and various approaches to developing biomimetic DDS functionalized with cellular membranes/membrane proteins for the treatment of ischemic stroke.
(徳島大学機関リポジトリ): ● Metadata: 117590
(出版サイトへのリンク): ● Publication site (DOI): 10.3390/pharmaceutics14020361
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35214092; ● Search Scopus @ Elsevier (PMID): 35214092; ● Search Scopus @ Elsevier (DOI): 10.3390/pharmaceutics14020361

(徳島大学機関リポジトリ: 117590, DOI: 10.3390/pharmaceutics14020361, PubMed: 35214092) 小暮健太朗, 福田達也 :
イオントフォレシスによる経皮デリバリー,
Drug Delivery System, Vol.36, No.3, 90-100, 2021年10月.

(要約): イオントフォレシス(IP)は，微弱電流を用いる経皮デリバリー技術であるが，従来その適用は荷電を有する疎水性化合物に限定され，親水性高分子はIPに適用できないと考えられてきた．しかし筆者らは，核酸医薬siRNAなどのIPによる経皮デリバリーに成功した．メカニズム解析の結果，微弱電流処理により，細胞シグナル系が活性化されて皮膚組織細胞間隙が開裂することで，高分子が皮内に浸透可能になること，さらに，エンドサイトーシスが誘起され細胞質まで送達されることが明らかになってきた．また，微弱電流によってエクソソーム分泌が促進されることも見出している．本稿では，最近の知見も交えてIPによる経皮デリバリーについて紹介する．
(キーワード): Iontophoresis / Weak electric current / Transdermal drug delivery
(出版サイトへのリンク): ● Publication site (DOI): 10.2745/dds.36.198
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390289920608691840; ● Search Scopus @ Elsevier (DOI): 10.2745/dds.36.198

(DOI: 10.2745/dds.36.198, CiNii: 1390289920608691840) Mahadi Hasan, Anowara Khatun, Tatsuya Fukuta and Kentaro Kogure :
Noninvasive transdermal delivery of liposomes by weak electric current.,
Advanced Drug Delivery Reviews, Vol.154-155, 227-235, Jun. 2020.

(要約): Noninvasive transdermal drug delivery (NTDD) offers an exciting new method of administration relative to conventional routes, but is associated with some challenges. Liposomes are capable of encapsulating transdermally-unfavorable drugs. However, the horny layer of skin is a significant barrier that limits efficient transdermal delivery of liposomes. Iontophoresis using weak electric current (WEC) represents a NTDD technology. WEC treatment of liposomes applied to the skin surface improves transdermal penetration of encapsulated drugs by cooperative effects. In this review, we provide an overview of the application of WEC/liposomes for transdermal delivery of macromolecules and low molecular weight drugs. We compare the transdermal delivery and therapeutic efficiency of the combined system with conventional routes of administration and their individual use. We discuss a novel perspective on the mechanism of WEC-mediated transdermal delivery of liposomes, which suggests that WEC activates the intracellular signaling pathway for transdermal permeation and induces unique endocytosis in skin cells.
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.addr.2020.06.016
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32589904; ● Search Scopus @ Elsevier (PMID): 32589904; ● Search Scopus @ Elsevier (DOI): 10.1016/j.addr.2020.06.016

(DOI: 10.1016/j.addr.2020.06.016, PubMed: 32589904) 小暮健太朗, 福田達也 :
[Drug Delivery to Various Body Organs via Non-blood Circulatory Pathway].,
薬学雑誌, Vol.140, No.5, 611-615, 2020年.

(要約): Delivery of nucleic acid therapeutics to target body organs requires injection of nanocarriers into the bloodstream. However, as such nanocarriers would also be delivered to non-target organs, low delivery efficiency to target organs and risk of unexpected effects are clear limitations of this technology. We recently applied iontophoresis (IP) for direct delivery of nucleic acid therapeutics to various organs. IP relies on a weak electric current for noninvasive transdermal drug delivery. We found that IP can deliver hydrophilic macromolecules and nanoparticles into the skin. We previously succeeded in transdermal delivery of siRNA, and subsequent knockdown (70%) of target mRNA levels in the skin via IP of siRNA (Int. J. Pharm., 383, 2010, Kigasawa et al.). Moreover, we found that cell signal activation and cleavage of intercellular junctions are induced by IP (J. Biol. Chem., 289, 2014, Hama et al.). We hypothesized that this phenomenon should be observed in not only skin but also other organs, and subsequently carried out IP of nucleic acid therapeutics to various body organs including liver, pancreas and kidney. This technique resulted in delivery of nucleic acid therapeutics into the various target body organs, and subsequent knockdown of target genes. These results suggest that direct delivery to target body organs via non-blood circulatory pathway is possible. This technology may offer a solution to the various limitations associated with current drug delivery systems (DDS).
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/yakushi.19-00218-1
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32378660; ● Search Scopus @ Elsevier (PMID): 32378660; ● Search Scopus @ Elsevier (DOI): 10.1248/yakushi.19-00218-1

(DOI: 10.1248/yakushi.19-00218-1, PubMed: 32378660) 小暮健太朗 :
イオントフォレシスによる核酸医薬の展開-微弱電流による組織細胞生理の制御,
医学のあゆみ, Vol.262, No.2, 153-156, 2017年7月. 小暮健太朗 :
アスタキサンチンのヘマトコッカス培養による生産と機能性研究,
アグリバイオ, Vol.1, 9-13, 2017年4月. 小暮健太朗, 濱進 :
ビタミンE コハク酸の多彩な生理作用と薬学への展開,
ビタミン, Vol.91, 182-187, 2017年3月. 小暮健太朗 :
ナノメディシン送達のための微弱電流による組織細胞生理の制御,
化学工業, Vol.67, No.11, 14-20, 2016年11月.

(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1523951030575326592

(CiNii: 1523951030575326592) Kenji Fukuzawa, Kentaro Kogure, Motoki Morita, Susumu Hama and Akira Tokumura :
Enhancement of Nitric Oxide and Superoxide Generations by α-Tocopheryl Succinate and Its Apoptotic and Anticancer Effects,
Biochemistry (Moscow), Vol.69, No.1, 50-57, Jan. 2004.

(要約): Tocopheryl succinate (TS), a succinyl ester of alpha-tocopherol (alpha-T), has been reported to have various biological activities. In this communication, we review the current findings about TS including our recent studies of its effects on nitric oxide (NO) and superoxide (O2-) generations implicated in cancer and atherosclerosis. First, we investigated the effect of TS on NO production in vascular smooth muscle cells (VSMC) under atherosclerosis-like conditions using lipopolysaccharide (LPS) and interferon-gamma (IFN). TS enhanced LPS/IFN-dependent NO production, but alpha-T itself did not. The enhancement by TS of NO production was inhibited by alpha-T but not by antioxidants such as ascorbic acid and 2[3]-t-butyl-4-hydroxyanisole (BHA). TS enhanced the amount of protein kinase Calpha (PKCalpha) in VSMC, and PKC inhibitors inhibited TS-enhanced NO production, suggesting that the enhancing effect of TS on NO production is caused by up-regulation of PKC. Second, we found that TS induced apoptosis in VSMC associated with increase in O2- generation via NADPH-dependent oxidase. We further observed that a mouse breast cancer cell line C127I was more susceptible for TS-induced apoptosis than a mouse breast normal cell line NmuMG, and that superoxide dismutase, alpha-T, and BHA inhibited TS-caused morphological cell damage in C127I. From these results, O2- itself and/or other reactive oxygen species are assumed to associate with TS-induced cell toxicity, and antioxidative defense systems are supposed to be lowered in cancer cells. Finally, we found that intravenous injection of TS vesicles completely inhibited the growth of melanoma cells B16-F1 inoculated on the back of hairless mice and enhanced their survival time.
(キーワード): Animals / Antineoplastic Agents / アポトーシス (apoptosis) / Humans / Myocytes, Smooth Muscle / 一酸化窒素 (nitric oxide) / Superoxides / Tocopherols / ビタミンE (vitamin E)
(出版サイトへのリンク): ● Publication site (DOI): 10.1023/B:BIRY.0000016351.77553.74
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 14972018; ● Summary page in Scopus @ Elsevier: 2-s2.0-3543145018

(DOI: 10.1023/B:BIRY.0000016351.77553.74, PubMed: 14972018, Elsevier: Scopus) Kentaro Kogure and Kenji Fukuzawa :
Tocopheryl succinate-versatile function due to its unique physicochemical properties,
Journal of Clinical Biochemistry and Nutrition, Vol.35, No.1, 29-34, 2004.

(出版サイトへのリンク): ● Publication site (DOI): 10.3164/jcbn.35.29
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.3164/jcbn.35.29

(DOI: 10.3164/jcbn.35.29) 小暮健太朗, 福澤健治 :
ビタミンEコハク酸 : アポトーシス誘導作用と抗ガン剤としての可能性,
ビタミン, Vol.76, No.4, 224-225, 2002年4月. 土江明子, 德村彰, 小暮健太朗, 福澤健治 :
喫煙が血液中で悪玉リン脂質をつくるー動脈硬化との関連ー,
日本薬学会第122年会講演ハイライト, 22, 2002年. Akira Tokumura, Tuneki Sumida, Masaoki Toujima, Kentaro Kogure and Kenji Fukuzawa :
Platelet-activating factor (PAF)- like oxidized phospholipids: relevance to atherosclerosis,
BioFactors, Vol.13, No.1-4, 29-33, 2000.

(要約): Lipid peroxidation is involved in the pathogenesis of chronic diseases including atherosclerosis. Oxidized lipoprotein has diverse biological activities and is believed to initiate atheroma formation and maturate fatty plaque. The active components of oxidized lipoproteins still remain to be clarified, but a likely candidate is the phosphatidylcholine (PC) having an sn-2-short-chain acyl group with a methyl, hydroxyl, aldehydic or carboxylic terminal. These unique PCs, formed by oxidative fragmentation of the polyunsaturated acyl group of the parent PC in liposomes, low density lipoproteins and blood plasma, induce platelet aggregation through the activation of the receptor for platelet-activating factor (PAF), due to their resemblance in structure with PAF. We have found that PAF-like lipids regulate DNA synthesis and production of nitric oxide independently of the activation of the PAF receptor in vascular smooth muscle cells. Regulation of vascular cell function through two distinct signaling pathways mediated by PAF-like lipids provides new insight into the mechanism of induction of atherosclerosis.
(キーワード): Animals / Arteriosclerosis / DNA (DNA) / Humans / 脂質過酸化 (lipid peroxidation) / Lipoproteins, LDL / Muscle, Smooth, Vascular / Phospholipids / Platelet Activating Factor
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11237195; ● Summary page in Scopus @ Elsevier: 2-s2.0-0034490867

(PubMed: 11237195, Elsevier: Scopus)

講演・発表

Kentaro Kogure :
Non-invasive and effective intradermal delivery of macromolecules by iontophoresis, weak electric current technology,
The 11th Asian association of schools of pharmacey (AASP) conference, Aug. 2023. AMI Hiramachi, Tatsuya Fukuta, Mizune Ohzono and Kentaro Kogure :
Development of a novel DDS carrier having targetability to specific tissues by membrane fusion of exosome and liposome,
13th International congress on membranes and membrane processes (ICOM2023), Jul. 2023. sachika Yamashita, ami hiramachi, Tatsuya Fukuta, Mizune Ohzono, Eiji Majima and Kentaro Kogure :
Antibody modification of exosome-based nanoparticles using improved Protein A to provide targeting ability,
13th International congress on membranes and membrane processes (ICOM2023), Jul. 2023. Misuzu Ishikawa, Tatsusada Yoshida and Kentaro Kogure :
Enhanced antioxidant activity of astaxanthin and tocotrienol through intermolecular interactions in lipid membranes,
13th International congress on membranes and membrane processes (ICOM2023), Jul. 2023. Kentaro Kogure, Tatsuya Fukuta, Shinya Inoue and M Hasan :
Iontophoresis-mediated direct delivery of siRNA to internal organs via non-blood circulatory pathways,
15th International Symposium on Nanomedicine, Dec. 2022. Kentaro Kogure :
Weak Current-mediated delivery of liposomes,
Liposome Research Days 2019, Sep. 2019. Tatsuya Fukuta, Yoshimi Shitaro and Kentaro Kogure :
Development of leukocyte-mimetic liposomes by intermembrane protein transfer to overcome inflamed endothelial cell layer,
Liposome Research Days 2019, Sep. 2019. Mimura Miyuki, Khatun Anowara, Nakatani Natsu, Tatsuya Fukuta and Kentaro Kogure :
Acceleration of the enhanced permeability and retention effect for delivery of nanoparticles by treatment with weak current,
Liposome Research Days 2019, Sep. 2019. Hirai Shota, Tatsuya Fukuta, Tamotsu Tanaka, Takahashi Yu, Yoshida Tatsusada and Kentaro Kogure :
Astaxanthin stereochemistry-dependent synergistic antioxidative activity of liposomes co-encapsulating with capsaicin,
The 9th Bieenial Meeting of Society for Free Radical Research (SFRR)-Asia, Apr. 2019. Kentaro Kogure and Y Nagasaki :
Transdermal delivery of polymer nanoparticles via faint electricity,
ACS Spring 2019 National Meeting, Mar. 2019. Kohki Tachibana, Tamotsu Tanaka, Kentaro Kogure, Tatsuhiro Ishida and Keiichiro Okuhira :
Sphingosine-1-phosphate (S1P) affects the secretion of high density lipoprotein (HDL)-constituent protein,
12th International Symposium on Nanomedicine, Ube, Dec. 2018. Seigi Yamamoto, Noriko Saito-Tarashima, Naoshi Yamazaki, Tatsuya Fukuta, Kentaro Kogure and Noriaki Minakawa :
Development and Evaluation of Photoresponsive DNA Prism with Nucleic Acid Medicine.,
The 45th International Symposium on Nucleic Acids Chemistry (ISNAC 2018), Nov. 2018. susumu Hama, satoko suzuki, shoko itakura and Kentaro Kogure :
Development of a siRNA Carrier Penetrable into the Deep Region of Tumor,
BIT's 9th World Gene Convention-2018, Nov. 2018. Kentaro Kogure, misuzu Ishikawa, shota Hirai, Tatsusada Yoshida, natsumi Shibuya, susumu Hama, yu Takahashi, Tatsuya Fukuta, Tamotsu Tanaka, shinzo hosoi and Kentaro Kogure :
Mechanism of Synergistic Antioxidative Effect of Astaxanthin and Tocotrienol by Co-encapsulated in Liposomal membranes,
The Third International Symposium on Rice Science in Global Health (ISRGH2018), Nov. 2018. Rumana Hasi Yesmin, Makoto Miyagi, Takashi Kida, Tatsuya Fukuta, Kentaro Kogure and Tamotsu Tanaka :
Amounts of glycosylinositol phosphoceramide and phytoceramide 1-phosphate in vegetables,
The Third International Symposium on Rice Science in Global Health (ISRGH2018), Nov. 2018. Dai Majima, Ryosuke Mitsuhashi, Tatsuya Fukuta, Tamotsu Tanaka and Kentaro Kogure :
Tocopheryl succinate liposomes regulate lipid accumulation in 3T3-L1 adipocytes,
The Third International Symposium on Rice Science in Global Health (ISRGH2018), Nov. 2018. susumu Hama, satoko Suzuki, shoko Itakura and Kentaro Kogure :
Tumor-penetrable nanoparticles for delivering drugs into cells in response to tumor microenvironment,
BIT's 8th annual world congress of Nano Science & Technology (Nano-S&T) 2018, Oct. 2018. Tatsuya Fukuta, Tamotsu Tanaka and Kentaro Kogure :
Development of liposomes with leukocyte-like function by intermembrane transfer of leukocyte membrane proteins,
18th Symposium for GeneDesign and Delivery, Jul. 2018. yasufumi Oshima, Tatsuya Fukuta, Tamotsu Tanaka and Kentaro Kogure :
Delivery of antibody into organ and cytoplasm via faint electricity,
18th Symposium for GeneDesign and Delivery, Jul. 2018. Hinako Mori, Tatsuya Fukuta, Tamotsu Tanaka and Kentaro Kogure :
Delivery of nucleic acid medicines into pancreas by faint electricity for treatment of pancreatic diseases,
18th Symposium for GeneDesign and Delivery, Jul. 2018. Kentaro Kogure, Noriko Saito-Tarashima, K Fujikawa, Y Oshima, Tasuku Torao, M Mimura, M Hasan, S Hama, Tamotsu Tanaka, Hiroyuki Saito and Noriaki Minakawa :
Effective cellular delivery of intelligent shRNA expression device by faint electricity.,
The 5th Seminar of pharmaceutial sciences and technology., Sep. 2017. Kentaro Kogure, K Kigasawa, S Hama and K Kajimoto :
Transdermal delivery of liposomes encapsulating functional proteins by iontophoresis,
ILS/LRD Liposome Advances Combined Conference, Sep. 2017. Tamotsu Tanaka, M Md Rahman, E Iga, R Yamashita, R Shimizu, K Tsuji, A Shimada, Michiyasu Nakao, Shigeki Sano and Kentaro Kogure :
Plasma level of ceramide 1-phosphate and its anti-apoptotic activity.,
58th International conference on the bioscience of lipids (ICBL), Sep. 2017. Kentaro Kogure, Noriko Saito-Tarashima, K Fujikawa, Y Oshima, Tasuku Torao, M Mimura, M Hasan, S Hama, Tamotsu Tanaka, Hiroyuki Saito and Noriaki Minakawa :
Effective cellular delivery of intelligent shRNA expression device by faint electricity.,
6th FIP Pharmaceutical Sciences World Congress (PSWC), May 2017. M Md Rahman, A Shimada, Tohru Miyazaki, K Tsuji, Michiyasu Nakao, Shigeki Sano, Kentaro Kogure and Tamotsu Tanaka :
Characterization of the Biological Effects of Ceramide-1-Phosphate.,
第58回日本生化学会中国・四国支部例会, May 2017. Kentaro Kogure, Kohki Fujikawa, M Hasan, S Hama, H Kashida and H Asanuma :
Effective cytoplasmic delivery of functional macromolecules by faint electricity.,
3rd International Conference on Biomaterials Science in Tokyo (ICBS2016) (Tokyo, Japan), Nov. 2016. Kohki Fujikawa, M Hasan, S Hama, Tamotsu Tanaka and Kentaro Kogure :
Faint electric treatment induces cytoplasmic delivery of functional macromolecules via changing endosome property.,
3rd International Conference on Biomaterials Science in Tokyo (ICBS2016) (Tokyo, Japan), Nov. 2016. S Hama, S Itakura, R Matsui and Kentaro Kogure :
Development of liposomal siRNA carriers using slightly acidic pH-sensitive peptide SAPSP for cancer therapy.,
3rd International Conference on Biomaterials Science in Tokyo (ICBS2016) (Tokyo, Japan), Nov. 2016. S Hama, S Itakura and Kentaro Kogure :
Slightly Acidic pH Sensitive Peptide-Modified Nanoparticles for Nucleic Acid Delivery to Cancer Cells.,
BITs 6th Annual World Congress of Nano Science & Technology (Singapore), Oct. 2016. Kentaro Kogure, Kohki Fujikawa, M Hasan and S Hama :
Effective Cytoplasmic Delivery of Macromolecules by Faint Electric Treatment,
12th France-Japan Drug Delivery Systems Symposium (Cernay-la-Ville, France), Oct. 2016. Kentaro Kogure :
Noninvasive and effective transdermal delivery of macromolecular medicines by faint electric treatment.,
32nd International Annual Meeting in Pharmaceutical Sciences held by the Chulalongkorn University Faculty of Pharmaceutical Sciences., Mar. 2016. Kenji Fukuzawa, Kentaro Kogure, Sachie Manabe and Akira Tokumura :
In vitro cytotoxicity of alpha-tocopherol succinate, malonate and oxalate on cancer cells and their in vivo anti-cancer effects on mouse melanoma,
XIII the Biennial Meeting of the Society for Free Radical Research International, Davos, Aug. 2006. Kenji Fukuzawa, Kentaro Kogure, S. Manabe, Ichiro Suzuki and Akira Tokumura :
Selective cytotoxicity to cancer cells of α-tocopheryl succinate analogues in vitro and their anti-cancer effects on mouse melanoma in vivo,
International Interdisciplinary Conference on Vitamins, Coenzymes, and Biofactors 2005, Awaji, Hyogo, Nov. 2005. Kenji Fukuzawa, Kentaro Kogure, M. Morita, S. Hama and Akira Tokumura :
Enhancement by alpha-tocopheryl succinate of superoxide and nitric oxide generations in cultured cells,
International Symposium: Reactive Oxygen and Nitrogen Species: Diagnostic,Preventive and Therapeutic Values, St. Petersburg-Kizhi-St.Petersburg Russia, Jul. 2002. Akira Tokumura, A. Tsuchie, Kentaro Kogure and Kenji Fukuzawa :
Cigarette smoking increases plasma level of phosphatidylcholine having an oxidatively shortened fatty acyl group with a carboxyl terminal,
11th Biennial Scientific Meeting of the International Society for Free Radical Research, Paris, Jul. 2002. Kentaro Kogure, S. Hama, S. Manabe, M. Kisaki, Akira Tokumura and Kenji Fukuzawa :
High toxicity of α-tocopheryl succinate to cancer cells is due to their failed antioxidative deffence system,
11th Biennial Scientific Meeting of the International Society for Free Radical Research, Paris, Jul. 2002. Kenji Fukuzawa, Y. Saitoh, K. Arai, Kentaro Kogure, Akira Tokumura and A. Shibata :
Antioxidant effect of bovine serum albumin on iron-chelate superoxide-dependent membrane lipid peroxidation,
11th Biennial Scientific Meeting of the International Society for Free Radical Research, Paris, Jul. 2002. Kentaro Kogure, S. Hama, S. Manabe, Ichiro Suzuki, M. Shibuya, Akira Tokumura and Kenji Fukuzawa :
Role of terminal structure of a-tocopheryl esters in nitric oxide production and apoptosis,
The 9th Korea-Japan joint symposium of drug design and development, Seoul, May 2002. S. Hama, Kentaro Kogure, S. Manabe, Akira Tokumura and Kenji Fukuzawa :
Anti-cancer effect of a-tocopheryl succinate mediated by apoptosis,
The 9th Korea-Japan joint symposium of drug design and development, Seoul, May 2002. K. Tominaga, 小暮健太朗, 福澤健治, 德村彰 :
Property of secretory phospholipase D which generates bioactive lysophosphatidic acid in guinea-pig peritoneal washing,
The 1st Takeda Science Foundation Symposium on Pharma Sciences:Lipids in Signaling and Related Diseases, 東京, 2001年10月. Kentaro Kogure, M. Morita, S. Nakashima, S. Hama, Akira Tokumura and Kenji Fukuzawa :
Superoxide is responsible for apoptosis in rat vascular smooth muscle cells induced by α-tocopheryl hemisuccinate,
2nd China-Japan International Conference on Vitamins, Shanghai, Oct. 2001. Kenji Fukuzawa, Kentaro Kogure, M. Morita, S. Hama, S. Nakashima and Akira Tokumura :
Enhancement by α-tocopheryl hemisuccinate of nitric oxide production indeced by lipopolysaccharide and interferon-γthrough up-regulation of protein kinase C in rat vascular smooth muscle cells,
2nd China-Japan International Conference on Vitamins, Shanghai, Oct. 2001. 山﨑尚志, 大川亜衣梨, 山本汐里, 枇杷谷有佐, 月本準, 伊藤孝司, 小暮健太朗 :
塩基改変U1 snRNAを用いたカテプシンAスプライス異常の修復,
第62回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2023年10月. 瀬尾明日香, 大高晋之, 山岡哲二, 小暮健太朗 :
ボロン酸基含有ポリマーをコアとするナノ粒子とイオントフォレシスを組み合わせたヌクレオシドの皮内送達,
遺伝子·デリバリー研究会第21回夏期セミナー, 2023年8月. 井上慎也, Mahadi Hasan, 福田達也, 小暮健太朗 :
イオントフォレシスを用いて体内臓器へ直接送達したsiRNAの遺伝子発現抑制効果,
遺伝子·デリバリー研究会第21回夏期セミナー, 2023年8月. 小暮健太朗 :
進化したイオントフォレシスによるデリバリー,
遺伝子·デリバリー研究会第21回夏期セミナー, 2023年8月. 小西晴貴, 小暮健太朗 :
広範囲な皮内薬物送達を可能にする非接触型イオントフォレシス,
第39回日本DDS学会学術集会, 2023年7月. 井上慎也, Mahadi Hasan, 福田達也, 小暮健太朗 :
経皮薬物送達技術イオントフォレシスを用いた肝臓内へのsiRNA送達,
第39回日本DDS学会学術集会, 2023年7月. 瀬尾明日香, 大高晋之, 山岡哲二, 小暮健太朗 :
ボロン酸基含有ポリマーを使用したヌクレオシド封入ナノ粒子のイオントフォレシスによる皮内送達,
第39回日本DDS学会学術集会, 2023年7月. 小暮健太朗, Rabab Ahmed ZeinElAbdin Husseini, Hara Tomoaki, Abe Naoko, Abe Hiroshi :
Use of Iontophoresis Technology for Transdermal Delivery of a Minimal mRNA as a Potential Melanoma Therapeutic,
日本核酸医薬学会第8回年会, 2023年7月. 林生成, 山﨑美沙季, 大園瑞音, 中尾允泰, 佐野茂樹, 小暮健太朗 :
安定性を向上させた新規ビタミン E 誘導体の脂肪蓄積抑制効果,
日本ビタミン学会第 75 回大会, 2023年6月. 瀬戸唯加, 山﨑美沙季, 大園瑞音, 小暮健太朗 :
ビタミン E コハク酸 / ビタミン E 共含有リポソーム投与が肥満モデルマウスの脂肪蓄積に与える影響,
日本ビタミン学会第 75 回大会, 2023年6月. MANOBENDRO NATH RAY, 大園瑞音, 小暮健太朗 :
ビタミン E コハク酸誘導アポトーシスには細胞内 Ca2+ とミトコンドリアが関与する,
日本ビタミン学会第 75 回大会, 2023年6月. 大川亜衣梨, 山本汐里, 枇杷谷有佐, 月本準, 伊藤孝司, 小暮健太朗, 山﨑尚志 :
改変 U1 snRNA を用いたカテプシン A スプライス異常の修復,
第64回日本生化学会中国四国支部例会, 2023年5月. Ara Tabassum, 小暮健太朗 :
γオリザノールを天然プロドラッグとする抗酸化ナノ粒子による酸化ストレス誘発肝障害モデルに対する治療効果の検討,
第76回日本酸化ストレス学会学術集会, 2023年5月. 小暮健太朗 :
電気を利用した生体バリアの透過,
日本薬剤学会第38年会, 2023年5月. 小暮健太朗 :
徳島大学薬学部における 6年制1本化の経緯と研究マインド醸成の取り組み,
日本薬剤学会第38年会, 2023年5月. 小暮健太朗, 井上慎也, Hasan Mahadi, 福田達也 :
イオントフォレシスによる体内臓器へのsiRNA送達,
日本薬剤学会第38年会, 2023年5月. 吉田響, 大園瑞音, 小暮健太朗 :
皮内コラーゲン合成促進を目指したアスコルビン酸封入リポソームのイオントフォレシス,
日本薬剤学会第38年会, 2023年5月. 小西晴貴, 大園瑞音, 小暮健太朗 :
非接触型イオントフォレシスによる高分子薬物の皮内送達,
日本薬剤学会第38年会, 2023年5月. 井上慎也, Mahadi Hasan, 福田達也, 小暮健太朗 :
経皮送達技術イオントフォレシスの体内臓器への応用,
日本薬学会第143年会, 2023年3月. 山﨑美沙季, 瀬戸唯加, 大園瑞音, 中尾允泰, 佐野茂樹, 小暮健太朗 :
ジカルボン酸構造の最適化による安全で脂肪蓄積抑制作用を有する新規ビタミンE誘導体の開発,
日本薬学会第143年会, 2023年3月. 林生成, 山崎美沙季, 大園瑞音, 中尾允泰, 佐野茂樹, 小暮健太朗 :
構造改変によるビタミンE誘導体の安定性の向上と脂肪蓄積抑制効果,
第32回ビタミンE研究会, 2023年1月. 瀬戸唯加, 山崎美沙季, 大園瑞音, 小暮健太朗 :
ビタミンE/ビタミンEコハク酸共含有リポソームが肥満マウスに及ぼす影響,
第32回ビタミンE研究会, 2023年1月. MANOBENDRO NATH RAY, 大園瑞音, 中尾允泰, 佐野茂樹, 小暮健太朗 :
炭素数一つの違いがビタミンE誘導体の細胞毒性を左右する,
第32回ビタミンE研究会, 2023年1月. 小暮健太朗 :
徳島大学における6年制1本化の経緯と目指すところ,
日本学術会議公開シンポジウム「21世紀の新しい人材育成に向け薬学教育はどこへ向かうのか?」, 2022年11月. 山下祥花, 平町愛美, 福田達也, 大園瑞音, 真島英司, 小暮健太朗 :
改変型Protein Aを用いたエクソソームとエクソソーム基盤ナノ粒子の抗体修飾による標的化能の付与,
膜シンポジウム2022, 2022年11月. 平町愛美, 福田達也, 大園瑞音, 小暮健太朗 :
エクソソームとリポソームのキメラナノ粒子構築と脳血管内皮細胞取り込みの検討,
膜シンポジウム2022, 2022年11月. 金山鈴華, 福田達也, 大園瑞音, 小暮健太朗 :
細胞外小胞Exosomeの皮内送達による皮膚炎症抑制の検討,
膜シンポジウム2022, 2022年11月. MANOBENDRO NATH RAY, 大園瑞音, 小暮健太朗 :
ビタミンE誘導体の細胞毒性に寄与する構造特性とそのメカニズムの検討,
膜シンポジウム2022, 2022年11月. 石川みすず, 平井将太, 小暮健太朗 :
脂質膜中に共存する異なる抗酸化物質の分子間相互作用と抗酸化活性,
膜シンポジウム2022, 2022年11月. 小暮健太朗 :
静電的相互作用を利用した種々の脂質膜ナノ粒子の構築,
第43回生体膜と薬物の相互作用シンポジウム, 2022年10月. Ray Manobendro Nath, 大園瑞音, 小暮健太朗 :
ビタミン E 誘導体の細胞毒性を左右する構造特性とメカニズムの検討,
第373回脂溶性ビタミン総合研究委員会, 2022年9月. 小暮健太朗 :
静電的相互作用に基づく脂質膜ナノ粒子の構築,
第3回超分子薬剤学FGシンポジウム, 2022年9月. Tabassum Ara, 大園瑞音, 小暮健太朗 :
抗酸化ナノ粒子によるCCl4誘導酸化ストレス肝障害抑制効果,
フォーラム2022, 2022年8月. 米田晋太朗, 福田達也, 大園瑞音, 小暮健太朗 :
脳保護薬FK506封入脂質ナノ粒子の粒子径制御を介した脳虚血/再灌流治療効果の向上,
遺伝子・デリバリー研究会第21回シンポジウム，第20回夏季セミナー, 2022年8月. Kentaro Kogure, Tatsuya Fukuta, Inoue Shinya and Hasan Mahadi :
Iontophoresis-mediated direct delivery of nucleic acid therapeutics to internal organs via non-blood circulatory pathways,
Premium oral session 7th Annual Meeting of the Nucleic Acids Therapeutics Society of Japan, Aug. 2022. 小暮健太朗, 井上慎也, 福田達也, Mahadi Hasan :
イオントフォレシスによる核酸医薬の肝臓内送達,
第38回日本DDS学会学術集会, 2022年6月. 瀬戸唯加, 山崎美沙季, 大園瑞音, 小暮健太朗 :
ビタミン E によるビタミン E コハク酸の細胞毒性制御と脂肪蓄積抑制,
日本ビタミン学会第74回大会, 2022年6月. 大園瑞音, 山﨑美沙季, 瀬戸唯加, 中尾允泰, 佐野茂樹, 小暮健太朗 :
安全で脂肪蓄積抑制作用を有する新規ビタミンE誘導体の開発,
日本ビタミン学会第74回大会, 2022年6月. 瀬戸唯加, 大園瑞音, 小暮健太朗 :
細胞毒性を制御したビタミンEコハク酸リポソーム製剤による抗肥満効果の検討,
第 372 回脂溶性ビタミン総合研究委員会プログラム, 2022年6月. 田嶋里帆, 平田悠真, 大園瑞音, 福田達也, 真島英司, 小暮健太朗 :
改良型ProteinAを用いたリポソームへの簡便で効率的な抗体修飾法の開発,
日本膜学会第44年会, 2022年6月. 山下祥花, 平町愛美, 福田達也, 大園瑞音, 真島英司, 小暮健太朗 :
改変型Protein Aを用いた抗体修飾によるエクソソーム基盤ナノ粒子への標的化能の付与,
日本膜学会第44年会, 2022年6月. 森戸克弥, 島田明奈, 宮崎徹, 清水良多, 高橋尚子, 東桃代, 下澤伸行, 福田達也, 小暮健太朗, 田中保 :
X連鎖性副腎白質ジストロフィー患者血漿中セラミドの分析とその主要な分子種の動物細胞への取り込みと作用,
第63回日本生化学中国・四国支部例会, 2022年5月. 井上慎也, ハサンマハディ, 福田達也, 小暮健太朗 :
イオントフォレシスによる核酸医薬の肝臓内への直接送達,
日本薬剤学会第37年会, 2022年5月. 吉田響, 大園瑞音, 小暮健太朗 :
皮内コラーゲン合成促進を目指したイオントフォレシスによるパルミトイルアスコルビン酸封入リポソームの皮内送達,
日本薬剤学会第37年会, 2022年5月. 米田晋太朗, 福田達也, 大園瑞音, 小暮健太朗 :
FK506封入脂質ナノ粒子の粒子径制御による脳虚血/再灌流障害に対する治療効果の向上,
日本薬剤学会第37年会, 2022年5月. Ara Tabassum, Ono Satoko, Mizune Ohzono and Kentaro Kogure :
Hepatoprotective effects of ferulic acid liposomal formulation against CCl4-induced oxidative liver damage,
第75回日本酸化ストレス学会学術集会, May 2022. Nath Manobendro Ray, Yamasaki Misaki, Mizune Ohzono and Kentaro Kogure :
Apoptogenic Activity of Tocopheryl Esters Depends on their Structure,
日本薬学会第142年会,, Mar. 2022. 道上巧基, 高山健太郎, 林良雄, 大園瑞音, 小暮健太朗 :
イオントフォレシスによるマイオスタチン阻害ペプチドの筋内送達による筋量増大,
遺伝子・デリバリー研究会第20回シンポジウム, 2021年12月. 小暮健太朗, 田中太智, 井上慎也, 道上巧基, 福田達也 :
タイトジャンクション開裂ペプチドAT1002とイオントフォレシスによる肥厚化乾癬皮膚内へのNF-κBデコイオリゴDNAのデリバリー,
遺伝子・デリバリー研究会第20回シンポジウム, 2021年12月. 小暮健太朗 :
ビタミンEエステル体の生物活性におけるエステル構造の影響,
日本ビタミン学会第73 回大会Part2,, 2021年11月. 平町愛美, 西川明菜, 福田達也, 大園瑞音, 小暮健太朗 :
エクソソームとリポソームの膜融合による組織指向性を有する新規DDSキャリアの構築,
膜シンポジウム2021, 2021年11月. 山下祥花, 福田達也, 大園瑞音, 小暮健太朗 :
改変型Protein Aを用いた抗体修飾によるエクソソームへの標的化能の付与,
膜シンポジウム2021, 2021年11月. 金山鈴華, 福田達也, 大園瑞音, 小暮健太朗 :
ヒト骨髄由来間葉系幹細胞Exosomeの皮内送達による皮膚炎症抑制の試み,
膜シンポジウム2021, 2021年11月. 米田晋太朗, 福田達也, 大園瑞音, 小暮健太朗 :
粒子径制御FK506内封脂質ナノ粒子の構築と脳梗塞部位への送達効率の向上,
第60回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2021年11月. 瀬戸唯加, 山﨑美沙季, 福田達也, 小暮健太朗 :
脂肪細胞に対するトコフェロールおよびトコフェロールコハク酸共含有リポソームの脂肪蓄積抑制効果,
第60回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2021年11月. 大塚ちほ, 虎尾祐, 福田達也, 小暮健太朗 :
微弱電流処理時に生じるセラミド増加のメカニズム解析,
第60回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2021年11月. 山﨑美沙季, 福田達也, 中尾允泰, 佐野茂樹, 小暮健太朗 :
脂肪蓄積抑制作用を有する安全性の高い新規トコフェロールエステル体の開発,
第60回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2021年11月. 小暮健太朗, 大塚ちほ, 虎尾祐, 三村美夕紀, 大園瑞音, 福田達也 :
微弱電流が誘導するユニークなエンドサイトーシスの特性,
第42回生体膜と薬物の相互作用シンポジウム, 2021年10月. 大園瑞音, Nath Manobendoro Ray, 山﨑美沙季, 瀬戸唯加, 中尾允泰, 福田達也, 佐野茂樹, 小暮健太朗 :
ビタミンE誘導体による細胞死誘導機構の解明と安全な抗肥満薬開発への展開,
第42回生体膜と薬物の相互作用シンポジウム, 2021年10月. 福田達也, 吉見真太朗, 小暮健太朗 :
がん組織深部への浸透を目指した白血球模倣リポソームの開発,
第37回日本DDS学会, 2021年6月. 福田達也, 森日向子, 小暮健太朗 :
膵臓がん治療を目指したイオントフォレシスによる膵臓への核酸医薬送達,
日本核酸医薬学会第6年会, 2021年6月. 小暮健太朗, 田中太智, 井上慎也, 道上巧基, 福田達也 :
タイトジャンクション開裂ペプチドAT1002とイオントフォレシスの組み合わせによる肥厚化した乾癬皮膚内へのNF-κBデコイオリゴDNAの送達,
日本核酸医薬学会第6年会, 2021年6月. 小暮健太朗, 瀬戸唯加, 山崎美沙季, 大園瑞音 :
脂肪蓄積抑制作用を有する新規ビタミンEエステル体の開発,
第368 回脂溶性ビタミン総合研究委員会, 2021年6月. 瀬戸唯加, 山崎美沙季, 福田達也, 小暮健太朗 :
ビタミンE コハク酸及びビタミンE 共含有リポソームが脂肪蓄積に及ぼす影響,
日本ビタミン学会第73 回大会, 2021年6月. 山﨑美沙季, 福田達也, 中尾允泰, 佐野茂樹, 小暮健太朗 :
新規ビタミンE エステル体の脂肪細胞に対する脂肪蓄積抑制効果,
日本ビタミン学会第73 回大会, 2021年6月. 小暮健太朗, 下川達張, 福田達也 :
アスタキサンチン含有リポソーム製剤によるドライアイ抑制効果の検討,
第74回日本酸化ストレス学会・第21回日本NO学会合同学術集会, 2021年5月. 福田達也, 小暮健太朗 :
生体バリアの突破を目指した生体膜模倣DDSの開発,
特別企画シンポジウム2「徳島発の最先端研究と薬剤学への展開」. 日本薬剤学会第36年会, 2021年5月. 井上慎也, 福田達也, 小暮健太朗 :
イオントフォレシスによるヒアルロン酸の皮内送達,
日本薬剤学会第36年会, 2021年5月. 山田海斗, 福田達也, 小暮健太朗 :
イオントフォレシスを用いたエクソソームの皮内送達によるがん免疫療法に向けた検討,
日本薬剤学会第36年会, 2021年5月. 米田晋太朗, 福田達也, 小暮健太朗 :
脳虚血/再灌流障害の治療を目指した粒子径制御リポソーム化FK506の構築,
日本薬剤学会第36年会, 2021年5月. 田嶋里帆, 平田悠真, 三橋尚登, 福田達也, 真島英司, 小暮健太朗 :
ProteinA誘導体を用いた抗体修飾リポソームの開発と腫瘍集積性の検討,
日本薬剤学会第36年会, 2021年5月. 福田達也, 吉見真太朗, 小暮健太朗 :
がん組織深部へ浸透可能な白血球模倣リポソームの構築と機能性評価,
日本薬学会第141年会, 2021年3月. 小暮健太朗, 大島康史, 道上巧基, 田中太智, 福田達也 :
イオントフォレシスによる生体高分子医薬の皮内送達と乾癬治療への展開.,
日本薬学会第141年会, 2021年3月. 柳香蓮, 福田達也, 小暮健太朗 :
イオントフォレシスの皮膚生理機能に対する影響の検討,
日本薬学会第141年会, 2021年3月. Ara Tabassum, Ono Satoko, Hasan Mahadi, Mizune Ohzono, Tatsuya Fukuta and Kentaro Kogure :
Protective effects of ferulic acid liposomal formulation on CCl4-induced liver damage,
日本薬学会第142年会, Mar. 2021. 小暮健太朗, 山崎美沙季, 真島大, 福田達也 :
種々のトコフェロールエステルによる脂肪蓄積抑制効果,
第365 回脂溶性ビタミン総合研究委員会, 2020年9月. Rumana Yesmin Hasi, Yoshimichi Takai, Hanif Ali, Kentaro Kogure, Junji Hayashi, Ryushi Kawakami, Mutsumi Aihara, Kaori Kanemaru and Tamotsu Tanaka :
Isolation of glycosylinositol phosphoceramide and phytoceramide 1-phosphate from cabbage leaves and their chemical stabilities.,
日本農芸化学会2020年度中四国支部大会(第57回講演会), Sep. 2020. Rumana Yesmin Hasi, Dai Majima, Katsuya Morito, Hanif Ali, Kentaro Kogure, Junji Hayashi, Ryushi Kawakami, Kaori Kanemaru, Meera Nanjundan, Toshiki Ishikawa and Tamotsu Tanaka :
Methods for isolation of glycosylinositol phosphoceramide and phytoceramide 1-phosphate from plant tissues.,
第93回日本生化学大会, Sep. 2020. 山﨑美沙季, 真島大, 中尾允泰, 佐野茂樹, 福田達也, 小暮健太朗 :
脂肪細胞の脂肪蓄積に対する種々のトコフェロールエステル体の効果,
日本ビタミン学会第72回大会, 2020年9月. 米田晋太朗, 福田達也, 小暮健太朗 :
脳虚血/再灌流部位へのリポソーム集積性に及ぼす粒子径の影響,
第36回日本DDS学会学術集会, 2020年8月. 福田達也, 吉見真太朗, 小暮健太朗 :
血管内皮層突破を目指した白血球模倣リポソームの機能性評価,
第36回日本DDS学会学術集会, 2020年8月. 下川達張, 福田達也, 小暮健太朗 :
ドライアイに対する抗酸化リポソーム製剤の抑制効果の検討,
第73回日本酸化ストレス学会/第20回NO学会合同学術集会, 2020年6月. 福田達也, 小暮健太朗 :
脂質膜中の分子間相互作用による抗酸化化合物の相乗的な活性向上.,
日本膜学会第42年会, 2020年6月. 福田達也, 西川明菜, 小暮健太朗 :
細胞外小胞を用いた新規DDS開発に向けた培養細胞からのエクソソーム分泌促進,
日本膜学会第42年会, 2020年6月. Rumana Yesmin Hasi, Dai Majima, Katsuya Morito, Hanif Ali, Kentaro Kogure, Junji Hayashi, Ryushi Kawakami, Kaori Kanemaru, Meera Nanjundan, Toshiki Ishikawa, Hiroyuki Imai and Tamotsu Tanaka :
Development of methods for isolation of glycosylinositol phosphoceramide and phytoceramide 1-phosphate from plant tissues.,
第62回日本脂質生化学会, May 2020. 山田海斗, 福田達也, 小暮健太朗 :
イオントフォレシスによる細胞外小胞エクソソームの皮内送達,
日本薬剤学会第35年会, 2020年5月. 福田達也, 西川明菜, 小暮健太朗 :
微弱電流処理を利用した細胞外小胞の分泌促進,
日本薬学会第140年会, 2020年3月. 中谷奈津, 福田達也, 小暮健太朗 :
発育鶏卵を用いた微弱電流処理による血管透過性亢進の検討,
日本薬学会第140年会, 2020年3月. 山崎美沙季, 真島大, 三橋亮介, 梶本和昭, 福田達也, 小暮健太朗 :
トコフェロールコハク酸が脂肪細胞の脂肪蓄積に及ぼす影響,
日本薬学会第140年会, 2020年3月. 山崎美沙季, 真島大, 三橋亮介, 梶本和昭, 福田達也, 小暮健太朗 :
脂肪細胞の脂肪蓄積に対するトコフェロールコハク酸の効果,
第31回ビタミンE研究会, 2020年1月. 福田達也, 吉見真太朗, 小暮健太朗 :
血管内皮細胞層を突破可能な白血球模倣ナノ粒子の開発,
日本バイオマテリアル学会第41回大会, 2019年11月. 福田達也, 吉見真太朗, 小暮健太朗 :
炎症血管バリアの突破を可能とする白血球膜タンパク質搭載リポソームの構築,
第58回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2019年11月. 柳香蓮, 福田達也, 小暮健太朗 :
皮膚組織に対する微弱電流処理の影響の検討,
第58回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2019年11月. 米田晋太朗, 中谷奈津, 福田達也, 小暮健太朗 :
脳への微弱電流処理による脳血管透過制御を目指した検討,
第58回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2019年11月. 西川明菜, 福田達也, 小暮健太朗 :
微弱電流処理による細胞外小胞エクソソームの分泌促進,
第58回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2019年11月. 田中保, Rumana Hasi Yesmin, 森戸克弥, 小暮健太朗, 林順司, 川上竜巳, 金丸芳, 今井博之, 石川寿樹 :
グリコシルイノシトールホスホセラミドの単離法の開発,
第12回セラミド研究会学術集会, 2019年10月. 福田達也, 吉見真太朗, 小暮健太朗 :
炎症血管内皮層の突破を目指した白血球ミミックリポソームの構築,
第41回生体膜と薬物の相互作用シンポジウム, 2019年10月. 田中保, 森戸克弥, Rumana Hasi Yesmin, 林順司, 川上竜巳, 金丸芳, 若山睦, 近藤千恵子, 福田達也, 小暮健太朗 :
食品素材に含まれるセラミドの簡便な定量方法,
日本脂質栄養学会第28回大会, 2019年9月. 森戸克弥, 島田明奈, 宮崎徹, 清水良多, 高橋尚子, 下澤伸行, 東桃代, 福田達也, 小暮健太朗, 田中保 :
ヒト血漿の主要なセラミド及びセラミド1-リン酸分子種の動物細胞への取り込みと作用,
第92回日本生化学会大会, 2019年9月. 高橋尚子, 清水良多, 森戸克弥, 東桃代, 下澤伸行, 福田達也, 小暮健太朗, 田中保 :
液体クロマトグラフィー/タンデム質量分析による副腎白質ジストロフィー患者の血漿中セラミド分子種及び濃度の解析,
第92回日本生化学会, 2019年9月. 道上巧基, 福田達也, 佐藤陽一, 小暮健太朗 :
微弱電流処理による精巣への薬物送達,
遺伝子・デリバリー研究会第19回夏期セミナー, 2019年9月. 森戸克弥, 島田明奈, 宮崎徹, 清水良多, 高橋尚子, 東桃代, 下澤伸行, 西岡安彦, 福田達也, 小暮健太朗, 田中保 :
ヒト血漿中セラミド及びセラミド1-リン酸の分子種組成と動物細胞への取り込みと作用,
第61回日本脂質生化学会, 2019年7月. 道上巧基, 福田達也, 田中保, 佐藤陽一, 小暮健太朗 :
男性不妊症治療を目指した微弱電流処理による精巣への非侵襲的薬物送達技術の開発,
第35回日本DDS学会学術集会, 2019年7月. 真島大, 三橋亮介, 梶本和昭, 福田達也, 田中保, 小暮健太朗 :
トコフェロールコハク酸リポソームによる抗肥満効果の検討,
日本ビタミン学会第71回大会, 2019年6月. 髙橋尚子, 清水良多, 森戸克弥, 東桃代, 下澤伸行, 福田達也, 小暮健太朗, 田中保 :
液体クロマトグラフィー/タンデム質量分析を用いた副腎白質ジストロフィー患者の血中セラミド分析,
第60回日本生化学中国・四国支部例会, 2019年5月. 福田達也, 吉見真太朗, 小暮健太朗 :
炎症血管バリアの突破を目指した白血球模倣リポソームの構築,
日本薬剤学会第34年会, 2019年5月. 福田達也, 小暮健太朗 :
脳梗塞部位の血液脳関門突破を目指した白血球模倣ナノ粒子の開発,
日本膜学会第41年会, 2019年5月. 大島康史, 福田達也, 小暮健太朗 :
微弱電流処理による機能性高分子の皮内デリバリー,
日本薬剤学会第34年会, 2019年5月. Rumana Hasi Yesmin, Makoto Miyagi, Takashi Kida, Tatsuya Fukuta, Kentaro Kogure and Tamotsu Tanaka :
Development of methods for purification of plant sphingolipids, glycosylinositol phosphoceramide and phytoceramide 1-phosphate,
日本農芸化学会2019年度大会, Mar. 2019. 森戸克弥, 島田明奈, 宮﨑徹, 清水良多, 高橋尚子, 東桃代, 小山壱也, 西岡安彦, 福田達也, 小暮健太朗, 田中保 :
ヒト血漿中セラミド及びセラミド1-リン酸の分子種組成と動物細胞へ作用,
日本農芸化学会2019年度大会, 2019年3月. 小暮健太朗, 福田達也 :
循環血流を介さない体内臓器への薬物送達,
日本薬学会第139年会, 2019年3月. 福田達也, 小暮健太朗 :
脳梗塞部位の血液脳関門の能動的突破を目指したDDS開発,
日本薬学会第139年会, 2019年3月. 平田悠真, 福田達也, 田中保, 真島英司, 小暮健太朗 :
Protein Aを用いた新規抗体修飾リポソーム調製法,
日本薬学会第139年会, 2019年3月. 吉見真太朗, 福田達也, 田中保, 小暮健太朗 :
がん親和性付与を目的とした単球膜タンパク質搭載リポソームの構築,
日本薬学会第139年会, 2019年3月. 森戸克弥, 清水良多, 北村苗穂子, 朴時範, 岸野重信, 小川順, 福田達也, 小暮健太朗, 田中保 :
乳酸菌が産生するリノール酸代謝物の動物細胞における代謝と宿主脂質代謝への影響,
第9回学際的脂質創生研究部会, 2019年2月. 濱進, 岡村有里子, 高木玲奈, 福澤健治, 小暮健太朗 :
トコフェロールコハク酸の腫瘍血管抑制メカニズムの解析,
第30回ビタミンE研究会, 2019年1月. 真島大, 三橋亮介, 梶本和昭, 福田達也, 田中保, 小暮健太朗 :
トコフェロールコハク酸リポソームは3T3-L1脂肪細胞の脂肪蓄積を制御する,
第30回ビタミンE研究会, 2019年1月. 小暮健太朗, 石川みすず, 平井将太, 濵進, 細井信造, 吉田達貞, 髙橋侑, 福田達也, 田中保 :
トコトリエノールとアスタキサンチンの相乗的抗酸化効果メカニズム,
第30回ビタミンE研究会, 2019年1月. 小暮健太朗, 三橋亮介, 真島大, 福田達也, 田中保 :
ビタミンEコハク酸による脂肪蓄積抑制作用,
第360回脂溶性ビタミン総合委員会, 2018年12月. 立花洸季, 田中保, 小暮健太朗, 石田竜弘, 奥平桂一郎 :
HDL構成タンパク質分泌に対するスフィンゴシン-1-リン酸及びフィンゴリモドの影響,
第57回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2018年11月. 宮﨑徹, 島田明奈, 高橋尚子, Md. Motiur Rahman, 清水良多, 辻和樹, 森戸克弥, 山下量平, 佐野茂樹, 中尾允泰, 福田達也, 小暮健太朗, 田中保 :
外因的に加えた極長鎖脂肪酸およびこれを含有するセラミドのアポトーシスへの影響,
第11回セラミド研究会, 2018年10月. Mahadi Hasan, susumu Hama and Kentaro Kogure :
Mechanistic study of faint electric treatment mediated cytoplasmic delivery of siRNA,
第40回生体膜と薬物の相互作用シンポジウム, Oct. 2018. 田中保, 宮城諒, 藤原美奈, 辻和樹, 森戸克弥, Rumana Hasi Yesmin, 福田達也, 小暮健太朗, 今井博行, 石川寿樹, 川合真紀 :
植物に見出されたグリコシルイノシトールホスホセラミド特異的ホスホリパーゼD活性の分布と性質,
第11回セラミド研究会学術集会, 2018年10月. 立花洸季, 西辻和親, 田中保, 小暮健太朗, 石田竜弘, 奥平桂一郎 :
スフィンゴシン-1-リン酸(S1P)による高密度リポプロテイン(HDL)構成タンパク質分泌への影響,
第91回日本生化学会大会, 2018年9月. 立花洸季, 田中保, 小暮健太朗, 石田竜弘, 奥平桂一郎 :
HDL構成タンパク質分泌に対するスフィンゴシン-1-リン酸及びフィンゴリモドの影響,
第91回日本生化学会大会, 2018年9月. 田中保, 宮城諒, 辻和樹, 藤原美奈, 森戸克弥, 石川寿樹, 今井博之, 川合真紀, 福田達也, 小暮健太朗 :
植物に見出されたグリコシルイノシトールホスホセラミド特異的ホスホリパーゼDの性質,
日本農芸化学会2018年度中四国支部大会, 2018年9月. 森戸克弥, 清水良多, 高橋尚子, 下澤伸行, 東桃代, 河野弘, 西岡安彦, 福田達也, 小暮健太朗, 田中保 :
ヒト血漿中セラミド及びセラミド1-リン酸の分子種組成と細胞への取り込み,
第91回日本生化学会大会, 2018年9月. 宮城諒, 辻和樹, 藤原美奈, 森戸克弥, 石川寿樹, 今井博之, 川合真紀, 福田達也, 小暮健太朗, 田中保 :
植物に見出されたグリコシルイノシトールホスホセラミド特異的ホスホリパーゼDの性質,
第91回日本生化学会大会, 2018年9月. 田中保, 森戸克弥, 清水良多, 北村苗穂子, 朴時範, 岸野重信, 小川順, 福田達也, 小暮健太朗 :
腸内細菌が産生するヒドロキシ脂肪酸の動物細胞における代謝,
日本脂質栄養学会第27回大会, 2018年8月. 森日向子, 福田達也, 田中保, 小暮健太朗 :
膵臓疾患治療を目指した微弱電流による核酸医薬の膵臓内送達,
第18回遺伝子・デリバリー研究会第18回夏期セミナー, 2018年7月. 大島康史, 福田達也, 田中保, 小暮健太朗 :
微弱電流処理による抗体の細胞内・皮内デリバリー,
第18回遺伝子・デリバリー研究会第18回夏期セミナー, 2018年7月. 福田達也, 虎尾祐, 三村美夕紀, 大島康史, 中谷奈津, 田中保, 小暮健太朗 :
弱電流による特殊なエンドサイトーシスを利用した高分子送達の機構解析,
第18回遺伝子・デリバリー研究会第18回夏期セミナー, 2018年7月. 小暮健太朗, 田中太智, 森日向子, 賀川真夕子, Hasan Mahadi, 福田達也, 田中保 :
微弱電流処理による体内臓器細胞へのsiRNAの送達,
日本核酸医薬学会第4回年会, 2018年7月. 小暮健太朗, 三橋亮介, 福田達也, 田中保 :
脂肪細胞における脂肪蓄積へのトコフェロールコハク酸リポソームの影響,
日本ビタミン学会第70回大会, 2018年6月. 中谷奈津, 田中太智, 平田悠真, 森日向子, 吉見真太朗, 福田達也, 田中保, 小暮健太朗 :
微弱電流処理と活性種(NO)とを組み合わせることによる細胞内取り込みの変化,
第34回日本DDS学会学術集会, 2018年6月. 森戸克弥, 清水良多, 北村苗穂子, 朴時範, 岸野重信, 小川順, 福田達也, 小暮健太朗, 田中保 :
乳酸菌が産生するリノール酸代謝物の動物細胞への取り込みと代謝,
第59回日本生化学会中国・四国支部例会, 2018年5月. 小暮健太朗, 平井将太, 髙橋侑, 田中保, 福田達也, 吉田達貞 :
アスタキサンチンと抗酸化物質の共封入リポソームによる相乗的な抗酸化効果,
71回日本酸化ストレス学会第18回日本NO学会合同学術集会, 2018年5月. 宮﨑徹, 島田明奈, 高橋尚子, Md. Motiur Rahman, 清水良多, 辻和樹, 森戸克弥, 山下量平, 佐野茂樹, 中尾允泰, 福田達也, 小暮健太朗, 田中保 :
外因的に加えた極長鎖脂肪酸および極長鎖脂肪酸含有セラミドのアポトーシスへの影響,
第60回日本脂質生化学会, 2018年5月. 田中太智, Hasan Mahadi, 福田達也, 田中保, 小暮健太朗 :
腎臓疾患治療を目指したイオントフォレシスによる核酸医薬の腎臓内送達,
日本薬剤学会第33年会, 2018年5月. 福田達也, 田中保, 小暮健太朗 :
脂質膜間移行現象を利用したリポソームへの白血球様機能の付与,
日本膜学会40年会, 2018年5月. 虎尾祐, 三村美夕紀, 大島康史, 賀川真夕子, 藤川昂樹, 福田達也, 田中保, 小暮健太朗 :
微弱電流による特殊なエンドサイトーシスを介した体内臓器細胞への高分子送達,
日本膜学会40年会, 2018年5月. Tatsuya Fukuta, T Asai, Kentaro Kogure and N Oku :
Treatment of ischemic stroke by combination therapy with liposomal neuroprotectants and tissue plasminogen activator,
日本薬学会138年会, Mar. 2018. M Hasan, S Hama, Hiroyuki Saito and Kentaro Kogure :
Mechanistic analysis of the intracellular delivery of siRNA mediated by faint electric treatment,
日本薬学会138年会, Mar. 2018. 賀川真夕子, 福田達也, 田中保, 小暮健太朗 :
イオントフォレシスによる肝臓への核酸医薬送達,
日本薬学会138年会, 2018年3月. 平井将太, 髙橋侑, 田中保, 福田達也, 吉田達貞, 小暮健太朗 :
アスタキサンチンと抗酸化物質の組合せによる相乗的な活性酸素消去活性の向上.,
日本薬学会138年会, 2018年3月. 石川みすず, 平井将太, 濵進, 細井信造, 吉田達貞, 髙橋侑, 小暮健太朗 :
アスタキサンチンとα-トコトリエノールの相乗的抗酸化効果における立体構造の影響,
日本薬学会138年会, 2018年3月. 三村美夕紀, 大島康史, 虎尾祐, 藤川昂樹, 福田達也, 田中保, 小暮健太朗 :
微弱電流処理により誘導される細胞取り込み過程の定量的評価,
日本薬学会138年会, 2018年3月. 大島康史, Hasan Mahadi, 田良島典子, 濱進, 福田達也, 田中保, 南川典昭, 小暮健太朗 :
微弱電流処理を利用した機能性核酸の細胞内取り込みの検討,
日本薬学会138年会, 2018年3月. 三橋亮介, 梶本和昭, 福田達也, 田中保, 小暮健太朗 :
トコフェロールコハク酸含有リポソームによる脂肪蓄積の抑制作用,
日本薬学会138年会, 2018年3月. 虎尾祐, 大島康史, 三村美夕紀, 藤川昂樹, 福田達也, 田中保, 小暮健太朗 :
微弱電流処理によるユニークなエンドサイトーシス誘導に関連する因子の検討,
日本薬学会138年会, 2018年3月. 森戸克弥, 清水良多, 北村苗穂子, 朴時範, 岸野重信, 小川順, 福田達也, 小暮健太朗, 田中保 :
乳酸菌が産生する希少脂肪酸のペルオキシソームにおける代謝,
日本農芸化学会 2018年度大会, 2018年3月. 石川みすず, 平井将太, 濵進, 細井信造, 吉田達貞, 髙橋侑, 小暮健太朗 :
トコトリエノールとアスタキサンチンの相乗的抗酸化効果への立体構造の影響,
第29回ビタミンE研究会, 2018年1月. 三橋亮介, 福田達也, 田中保, 小暮健太朗 :
トコフェロールコハク酸含有リポソームによる脂肪細胞の脂肪蓄積抑制効果,
第29回ビタミンE研究会, 2018年1月. 小暮健太朗, 石川みすず, 平井将太, 濵進, 吉田達貞, 髙橋侑, 細井信造, 福田達也, 田中保 :
α-トコトリエノールとアスタキサンチンの相乗的抗酸化効果,
第357回脂溶性ビタミン総合研究委員会, 2017年12月. 清水良多, 山下量平, 伊賀永里奈, Md. Motiur Rahman, 東桃代, 小暮健太朗, 田中保 :
液体クロマトグラフィー/タンデム質量分析によるヒト血漿中のセラミド及びセラミド 1-リン酸の解析,
第40回日本分子生物学会年会，第90回日本生化学会大会プログラム, 439, 2017年12月. Md Motiur Rahman, Erina Iga, Akina Shimada, Tohru Miyazaki, Naoko Takahashi, Mina Fujiwara, Kazuki Tsuji, Kentaro Kogure and Tamotsu Tanaka :
Neuroprotective activity of phytoceramide 1-phosphate on serum deprivation-induced apoptosis of Neuro2a cells,
第40回日本分子生物学会年会，第90回日本生化学会大会プログラム, 439, Dec. 2017. Afroz Sheuli, Katsuya Morito, Kouki Fujikawa, Ayano Yagi, Kazunori Toida, Emi Kiyokage, Kentaro Kogure, Shiro Watanabe, Akira Tokumura and Tamotsu Tanaka :
Antiulcer effect of lysophosphatidic acid-rich medicinal herbs and its mechanism,
第40回日本分子生物学会年会，第90回日本生化学会大会プログラム, 439, Dec. 2017. 辻和樹, 島田明奈, 宮崎徹, 高橋尚子, 伊賀永里奈, Rahman Md Motiur, 中尾允泰, 佐野茂樹, 小暮健太朗, 田中保 :
種々の脂肪酸残基を有するセラミドの化学合成とその生理活性,
第40回日本分子生物学会年会，第90回日本生化学会大会プログラム, 438, 2017年12月. 小暮健太朗, 大島康史, 虎尾祐, 三村美夕紀, 藤川昂樹, Hasan Mahadi, 濱進, 福田達也, 田良島典子, 田中保, 南川典昭 :
微弱電流処理による高分子医薬の細胞質送達と機能発現,
第39回生体膜と薬物の相互作用シンポジウム, 2017年10月. 平井将太, 石川みすず, 高橋侑, 小暮健太朗 :
アスタキサンチンとカプサイシンの組合せによる相乗的な抗酸化活性の向上,
第56回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2017年10月. 石川みすず, 平井将太, 濱進, 細井信造, 吉田達貞, 高橋侑, 小暮健太朗 :
相乗的抗酸化効果を示すアスタキサンチンとα-トコトリエノールのリポソーム膜における至適比率の検討,
第56回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2017年10月. 三橋亮介, 福田達也, 田中保, 小暮健太朗 :
トコフェロールコハク酸含有リポソームによる脂肪蓄積減少効果の検討,
第56回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2017年10月. 虎尾祐, 大島康史, 三村美夕紀, 藤川昂樹, 福田達也, 田中保, 小暮健太朗 :
微弱電流処理によるユニークなエンドサイトーシス誘導機構の検討,
第56回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2017年10月. 三村美夕紀, 大島康史, 虎尾祐, 藤川昂樹, Hasan Mahadi, 濱進, 田中保, 小暮健太朗 :
微弱電流処理により誘起される細胞内取り込みの評価,
第56回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2017年10月. 賀川真夕子, 福田達也, 田中保, 小暮健太朗 :
微弱電流処理によるsiRNAの細胞内送達と肝細胞遺伝子発現制御,
第56回日本薬学会・日本薬剤師会・日本病院薬剤師会, 2017年10月. 大島康史, 虎尾祐, 三村美夕紀, Hasan Mahadi, 田良島典子, 濱進, 福田達也, 田中保, 南川典昭, 小暮健太朗 :
ユニークなエンドサイトーシスを誘起する微弱電流を利用した機能性核酸の細胞質送達,
第56回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2017年10月. 田中保, 山下量平, 清水良多, 森戸克弥, Md. Motiur Rahman, 伊賀永里奈, 島田明奈, 福田達也, 小暮健太朗 :
血液中のセラミド 1-リン酸の分子種組成と生物活性,
セラミド研究会予稿集, 23, 2017年10月. 島田明奈, 宮﨑徹, 高橋尚子, Rahman Motiur Md., 清水良多, 辻和樹, 山下量平, 佐野茂樹, 中尾允泰, 福田達也, 小暮健太朗, 田中保 :
極長鎖脂肪酸およびこれを含有するセラミドのアポトーシス抑制活性,
セラミド研究会, 2017年10月. Md Motiur Rahman, Erina Iga, Tohru Miyazaki, Naoko Takahashi, MIna Fujiwara, Kazuki Tsuji, Kentaro Kogure and Tamotsu Tanaka :
Phytoceramide 1-phosphate in vegetables and its anti-apoptotic effect in animal cells,
日本脂質栄養学会第26回大会予稿集, 187, Sep. 2017. S Afroz, Katsuya Morito, K Fujikawa, A Yagi, Teru Ikoma, E Kiyokage, K Toida, Kentaro Kogure and Tamotsu Tanaka :
Phosphatidic acid-rich cereals as anti-ulcer foods and their mechanisms of action,
日本脂質栄養学会第26回大会, Sep. 2017. 大島康史, 虎尾祐, 三村美夕紀, 藤川昂樹, Hasan Mahadi, 濱進, 福田達也, 田中保, 小暮健太朗 :
微弱電流が誘起するユニークなエンドサイトーシスによる核酸の細胞質送達,
遺伝子・デリバリー研究会第17回夏期セミナー, 2017年9月. 小暮健太朗, 賀川真夕子, 大島康史, 虎尾祐, 三村美夕紀, 福田達也, Mahadi Hasan, 濱進, 田中保 :
微弱電流による核酸医薬の細胞内送達,
第26回DDSカンファランス, 2017年9月. 小暮健太朗, 賀川真夕子, 大島康史, 虎尾祐, 三村美夕紀, 藤川昂樹, 福田達也 :
微弱電流誘導性エンドサイトーシスによるsiRNAの細胞内送達と肝細胞遺伝子発現制御,
日本核酸医薬学会第3回年会, 2017年7月. 虎尾祐, 三村美夕紀, 大島康史, 藤川昂樹, Hasan Mahadi, 濱進, 田中保, 小暮健太朗 :
微弱電流処理によるユニークなエンドサイトーシスの解析,
第33回日本DDS学会学術集会, 2017年7月. 南川典昭, 田良島典子, 高橋知樹, 山本清義, 金城望, 安藤英紀, 石田竜弘, 小暮健太朗 :
化学修飾DNAを利用したRNA創薬,
第33回日本DDS学会学術集会, 2017年7月. 小暮健太朗 :
微弱電流によるナノ粒子の皮内デリバリー,
第35回物性物理化学研究会, 2017年7月. 小暮健太朗, 石川みすず, 平井将太, 濵進, 細井信造, 吉田達貞, 山下栄次, 髙橋侑 :
ビタミンEとの相乗的抗酸化効果におけるアスタキサンチン立体構造の影響,
第70回日本酸化ストレス学会学術集会, 2017年6月. 宮城諒, 喜田孝史, 辻和樹, 小暮健太朗, 田中保 :
グリコシルイノシトールホスホセラミドの抽出と精製,
日本農芸化学会中四国支部第48回公演会要旨集, 37, 2017年6月. 田中保, Md Motiur Rahaman, 伊賀永理奈, 山下量平, 清水良多, 辻和樹, 島田明奈, 中尾允泰, 佐野茂樹, 小暮健太朗 :
血液中に存在する極長鎖セラミド-1-リン酸のアポトーシス抑制作用,
第59回日本脂質生化学会, 講演要旨集, 33-34, 2017年6月. 喜田孝史, 伊藤葵, 木村朱里, 松岡久嗣, 藤原美奈, 辻和樹, 小暮健太朗, 田中保 :
植物におけるグリコシルイノシトールホスホセラミド特異的ホスホリパーゼD活性の分布と性質,
第59回日本脂質生化学会, 2017年6月. 平井将太, 石川みすず, 渋谷菜摘, 濵進, 細井信造, 髙橋侑, 山下栄次, 小暮健太朗 :
トコトリエノールとアスタキサンチンの相乗的な抗酸化活性向上における至適比率の検討,
日本ビタミン学会第69回大会, 2017年6月. 小暮健太朗, 藤川昂樹, Hasan Mahadi, 濱進, 田中保, 田良島典子, 南川典昭 :
微弱電流による新規核酸iRedの細胞内送達と遺伝子発現制御,
遺伝子・デリバリー研究会第17回シンポジウム, 2017年5月. 大島康史, 虎尾祐, 三村美夕紀, 藤川昂樹, Hasan Mahadi, 濱進, 田中保, 小暮健太朗 :
微弱電流により誘起されるユニークなエンドサイトーシスの解析,
遺伝子・デリバリー研究会第17回シンポジウム, 2017年5月. 清水良多, 山下量平, 伊賀永里奈, Rahman Motiur Md., 東桃代, 小暮健太朗, 田中保 :
液体クロマトグラフィー/タンデム質量分析による血漿中のセラミド及びセラミド-1-リン酸の解析,
第58回日本生化学会中国・四国支部例会, 2017年5月. 島田明奈, 伊賀永里奈, Rahman Motiur Md., 山下量平, 清水良多, 小暮健太朗, 田中保 :
セラミド-1-リン酸のアポトーシス抑制活性,
第58回日本生化学会中国・四国支部例会, 2017年5月. 三村美夕紀, 大島康史, 虎尾祐, 藤川昂樹, Hasan Mahadi, 濱進, 田中保, 小暮健太朗 :
微弱電流処理によって誘起されるユニークなエンドサイトーシス,
日本薬剤学会第32年会, 2017年5月. 古曳泰規, 傳田将也, 藤川昴樹, 猪熊翼, 重永章, 小暮健太朗, 大髙章 :
N-Sulfanylethylanilideを用いた細胞内標的タンパク質ラベル化法の開発,
日本薬学会第137年会, 2017年3月. 小暮健太朗 :
微弱電流による高分子物質皮膚透過促進と組織・細胞生理の変化,
日本薬学会第137年会, 2017年3月. 船城凌, 渋谷菜摘, 田中保, 小暮健太朗, 奥平桂一郎 :
HepG2細胞でのスフィンゴシン1リン酸(S1P)によるアポリポタンパク質A-I(apoA-I)発現の抑制,
日本薬学会第137年会, 2017年3月. 小暮健太朗, Mahadi Hasan, 田良島典子, 藤川昂樹, 濱進, 田中保, 樫田啓, 浅沼浩之, 斎藤博幸, 南川典昭 :
微弱電流による機能性核酸の効率的な細胞質送達,
日本核酸医薬学会第2回年会(東京), 2016年12月. 小暮健太朗, 亀崎ちひろ, 渋谷菜摘, 石川みすず, 中島愛美, 石橋博, 濵進, 細井信造, 山下栄次 :
トコトリエノールとの抗酸化併用効果.,
第12回アスタキサンチン研究会(富山), 2016年11月. 藤川昂樹, Hasan Mahadi, 濱進, 田中保, 斎藤博幸, 小暮健太朗 :
微弱電流処理による高分子物質の細胞質送達.,
第38回生体膜と薬物の相互作用シンポジウム(名古屋), 2016年11月. 屋宜亜耶乃, Afroz Sheuli, 生駒照, 德村彰, 小暮健太朗, 田中保 :
食物中のホスファチジン酸の抗胃潰瘍効果とホスホリパーゼA2活性化作用.,
第55回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会(岡山), 2016年10月. 藤川昂樹, Hasan Mahadi, 濱進, 田中保, 小暮健太朗 :
細胞のエンドソーム物性変化を誘導する微弱電流処理.,
第55回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会(岡山), 2016年10月. 小暮健太朗, 亀崎ちひろ, 中島愛美, 石橋博, 濵進, 細井信造, 山下栄次 :
アスタキサンチンとビタミンE共存による抗酸化活性の向上.,
第69回日本酸化ストレス学会学術年会(仙台), 2016年9月. 中島采香, 西貴之, 福澤健治, 小暮健太朗, 斎藤博幸, 濱進 :
多面的な抗癌作用を有するビタミンE誘導体から構成されるナノ粒子による薬剤耐性の克服.,
第14回がんとハイポキシア研究会(岐阜), 2016年8月. 松井諒, 鈴木智子, 板倉祥子, 小暮健太朗, 斎藤博幸, 濱進 :
微小環境応答性ドラッグデリバリーシステムの腫瘍内透過性の改善.,
第14回がんとハイポキシア研究会(岐阜), 2016年8月. 扇田隆司, 林直樹, 上川翼, 籾山京子, 福田昂平, 小暮健太朗, 後藤直正, 斎藤博幸 :
細菌Ⅲ型分泌機構の解明を目指した分泌装置の回転―分泌相関の検討.,
第11回トランスポーター研究会年会(JTRA2016)(京都), 2016年7月. 山下栄次, 小暮健太朗 :
ビタミンE とアスタキサンチンの相乗的抗酸化作用.,
第30回カロテノイド研究談話会(沖縄), 2016年7月. 扇田隆司, 林直樹, 福田昂平, 籾山京子, 小暮健太朗, 後藤直正, 斎藤博幸 :
細菌Ⅲ型分泌装置のエフェクター輸送機構解明のための回転-分泌相関の検討.,
第14回次世代を担う若手のためのフィジカル・ファーマフォーラム (大阪), 2016年7月. 松井諒, 濱進, 鈴木智子, 板倉祥子, 小暮健太朗, 斎藤博幸 :
腫瘍内透過性と微弱低pH応答性を併せ持つ薬物キャリアーの開発.,
第32回日本DDS学会学術集会(静岡), 2016年7月. Hasan Mahadi, Noriko Saito-Tarashima, Kohki Fujikawa, Takashi Ohgita, Susumu Hama, Tamotsu Tanaka, Hiroyuki Saito, Noriaki Minakawa and Kentaro Kogure :
Intracellular delivery of a novel functional nucleic acid iRed by faint electric treatment for effective regulation of target genes,
第32回DDS学術集会, Jun. 2016. 小暮健太朗, 亀崎ちひろ, 中島愛美, 石橋博, 濵進, 細井信造, 山下栄次 :
ビタミンEとアスタキサンチン共存による抗酸化作用の向上効果.,
日本ビタミン学会第68回大会(富山), 2016年6月. 西貴之, 濱進, 西本明功, 鈴木智子, 斎藤博幸, 福澤健治, 小暮健太朗 :
腹腔内貯留型トコフェロールコハク酸含有ナノ粒子の腹膜播種治療への応用.,
日本ビタミン学会第68回大会(富山), 2016年6月. 藤川昂樹, Hasan Mahadi, 濱進, 田中保, 小暮健太朗 :
微弱電流処理によって誘起されるエンドサイトーシスの解析.,
日本薬剤学会第31年会(岐阜), 2016年5月. T Ohgita, K Fukuda, K Momiyama, N Hayashi, 小暮健太朗, N Gotoh, 斎藤博幸 :
Needle-like type III secretion apparatus regulates effector transport by rotational motion.,
第55回日本生物物理学会年会(つくば), 2016年5月. 小暮健太朗, 濵進 :
ビタミンEコハク酸の多彩な生理作用と薬学への展開,
日本薬学会136年会シンポジウム「ビタミンのケミカルバイオロジー研究」, 2016年3月. M Hasan, A Nishimoto, T Ohgita, S Hama, H Kashida, H Asanuma and Kentaro Kogure :
Faint electric treatment enhances cellular uptake and intracellular delivery into cytoplasm.,
日本薬学会第136年会(横浜), Mar. 2016. 扇田隆司, 上川翼, 籾山京子, 林直樹, 小暮健太朗 :
細菌Ⅲ型分泌機構の解明を目指したエフェクター分泌の定量評価.,
日本薬学会第136年会(横浜), 2016年3月. 濱進, 中島采香, 西貴之, 福澤健治, 斎藤博幸, 小暮健太朗 :
薬剤耐性癌の克服を目指したトコフェロールコハク酸ナノベシクルの開発,
第28回ビタミンE研究会(東京), 2016年1月. 石川みすず, 亀崎ちひろ, 中島愛美, 石橋博, 濵進, 細井信造, 山下栄次, 小暮健太朗 :
α-トコトリエノールとアスタキサンチンのリポソーム膜中における相乗効果の検討.,
第28回ビタミンE研究会(東京), 2016年1月. 渋谷菜摘, 亀崎ちひろ, 中島愛美, 石橋博, 濵進, 細井信造, 山下栄次, 小暮健太朗 :
OHラジカル細胞傷害へのアスタキサンチン/トコトリエノールリポソームの抑制効果,
第28回ビタミンE研究会(東京), 2016年1月. 福澤健治, 真鍋幸恵, 小暮健太朗, 德村彰 :
マウスに移植した黒色腫瘍に対するα-トコフェロール誘導体の抗ガン効果,
日本ビタミン学会大会, Vol.57, 2005年5月. 福澤健治, 赤井かおり, 土屋浩一郎, 小暮健太朗, 德村彰, 玉置俊晃 :
配位構造の異なる3つのタイプのFe-NTA錯体による脂質過酸化の誘導,
日本過酸化脂質フリーラジカル学会27回大会, 2003年10月. 赤井かおり, 土屋浩一郎, 小暮健太朗, 德村彰, 玉置俊晃, 福澤健治 :
発癌性鉄錯体Fe³⁺-ニトリロ三酢酸(Fe³⁺-NTA)の光およびphに依存した活性酵素の産出と脂質過酸化の誘導,
第25回日本フリーラジカル学会, 2003年6月. 德村彰, 平尾恵理, 丸山佑史, 小暮健太朗, 福澤健治 :
正常および異常妊娠時のヒト血清リゾホスホリパーゼD活性,
第45回日本脂質生化学会, 2003年6月. 真鍋幸恵, 小暮健太朗, 浜進, 森田健之, 德村彰, 福澤健治 :
ビタミンEコハク酸のガン細胞におけるアポトーシス誘導作用へのH₂O₂の関与,
日本ビタミン学会55回大会, 2003年5月. 蔭山千恵子, 德村彰, 小暮健太朗, 福澤健治, 土肥敏博 :
ヒト唾液に存在するリゾホスホファチジン酸産生酵素リゾホスホリパーゼDの症状,
日本薬学会年会, Vol.123, 2003年3月. 德村彰, 平尾恵理, 丸山佑史, 小暮健太朗, 安田勝彦, 神崎秀陽, 福澤健治 :
異常妊娠婦人の血清リゾホスホリパーゼD活性:正常妊娠婦人との価との比較,
日本薬学会年会, Vol.123, 2003年3月. 小暮健太朗, 濱進, 後藤了, 德村彰, 福澤健治 :
Vitamin Eコハク酸はPKCを直接活性化する,
日本薬学会第123年会, 2003年3月. 齋藤恭章, 赤井かおり, 小暮健太朗, 德村彰, 柴田瑩, 福澤健治 :
血清アルブミンの膜脂質過酸化抑制作用,
第24回生体膜と薬物の相互作用シンポジウム, 2002年11月. 土江明子, 德村彰, 小暮健太朗, 福澤健治 :
ヒト血液中で酸化ストレスを受け生成する短鎖ジカルボン酸含有ホスファチジルコリンの定量,
第41回日本薬学会・日本病院薬剤師会中国四国支部学術大会, 2002年11月. 小暮健太朗, 森田健之, 德村彰, 福澤健治 :
トコフェロールコハク酸のアポトーシス誘導作用と細胞の活性酸素防御能,
日本過酸化脂質フリーラジカル学会26回大会, 2002年10月. 小暮健太朗, 木崎真弓, 鈴木一郎, 德村彰, 渋谷雅之, 福澤健治 :
アポトーシス誘導作用におけるトコフェロールコハク酸類縁体の構造活性相関の検討,
日本過酸化脂質フリーラジカル学会26回大会, 2002年10月. 德村彰, 真島英司, 刈谷優子, 富永恭子, 小暮健太朗, 安田勝彦, 福澤健治 :
生理活性リン脂質LPAを産出する血漿リゾホスホリパーゼDの性状,
日本生化学会大会, Vol.75, 2002年10月. 中島佐和, 小暮健太朗, 土江明子, 德村彰, 福澤健治 :
酸化リン脂質によって誘導される血管平滑筋細胞の障害,
日本生化学会大会, Vol.75, 2002年10月. 蔭山千恵子, 德村彰, 小暮健太朗, 福澤健治, 土肥敏博 :
ヒト唾液中でリゾホスファチジン酸を産出するリゾホスホリパーゼDの性質,
日本生化学会大会, Vol.75, 2002年10月. 小暮健太朗, 浜進, 德村彰, 福澤健治 :
ビタミンEコハク酸の作用発現における細胞内シグナル機構の関与,
日本生化学会大会, Vol.75, 2002年10月. 浜進, 小暮健太朗, 後藤了, 鈴木一郎, 德村彰, 渋谷雅之, 福澤健治 :
トコフェロール-コハク酸によるPKCを介したNO産生促進機構,
第41回日本薬学会·日本病院薬剤師会中国四国支部学術大会, 2002年10月. 德村彰, 富永恭子, 小暮健太朗, 福澤健治, 安田勝彦, 刈谷優子, 真島英司 :
生理活性リン脂質LPAを産出するヒト血漿リゾホスホリパーゼDは多機能性ヌクレオチドホスホジエステラーゼautotaxinである,
日本脂質生化学研究会第44回研究集会, 2002年6月. 真鍋幸恵, 小暮健太朗, 浜進, 中島佐和, 德村彰, 福澤健治 :
黒色腫瘍に対するα-トコフェロールコハク酸の抗ガン効果,
日本ビタミン学会大会, Vol.54, 2002年4月. 浜進, 小暮健太朗, 中島佐和, 真鍋幸恵, 德村彰, 福澤健治 :
トコフェロールコハク酸によるNO産生促進効果の機構解析,
日本ビタミン学会大会, Vol.54, 2002年4月. 土江明子, 德村彰, 小暮健太朗, 福澤健治 :
喫煙者及び非喫煙者血漿に存在する酸化ホスファチジルコリン分子種組成の比較,
日本薬学会年会, Vol.122, 2002年3月. 小暮健太朗, 浜進, 真鍋幸恵, 德村彰, 福澤健治 :
アポトーシス誘導作用を有するトコフェロールコハク酸の構造的因子の検討,
日本薬学会年会, Vol.122, 2002年3月. 德村彰, 平畠宏行, 岡山朋郁, 河上律子, 小暮健太朗, 福澤健治 :
ホスファチジン酸による好中球O2-産出に対するホスホリパーゼA2阻害剤の作用,
日本薬学会年会, Vol.122, 2002年3月. 後藤了, 小暮健太朗, 安部一豊, 堀均, 中馬寛, 赤須通範, 寺田弘 :
Cepharanthineの立体構造と非Phenol型Radical消去活性,
第29回構造活性相関シンポジウム, 2001年11月. 後藤了, 小暮健太朗, 中馬寛, 赤須通範, 寺田弘 :
柔らかいCepharanthineと堅いTetrandrineのラジカル消去活性,
日本薬学会第121年会, 2001年3月. 西村美紀, 小暮健太朗, 後藤了, 寺田弘 :
Capsaicinの特徴的な抗酸化作用機構,
日本薬学会第120年会, 2000年3月. 後藤了, 小暮健太朗, 中馬寛, 赤須通範, 寺田弘 :
セファランチンノラジカル消去活性と化学構造のゆらぎ,
日本薬学会120年会, 2000年3月. 西村美紀, 小暮健太朗, 後藤了, 寺田弘 :
Capsaicinの特徴的な抗酸化作用への膜物性変化の関与,
第38回日本薬学会·日本病院薬剤師会中国四国支部学術大会, 1999年10月. 西村美紀, 小暮健太朗, 後藤了, 寺田弘 :
辛味成分Capsaicinの膜系における抗酸化活性について,
第72回日本生化学会, 1999年9月. 西村美紀, 小暮健太朗, 後藤了, 寺田弘 :
辛味成分Capsaicinの抗酸化作用機構,
日本薬学会119年会, 1999年3月. 後藤了, 小暮健太朗, 中馬寛, 寺田弘, 赤須通範 :
大環状 tetrahydroisoquinoline誘導体の構造とラジカル消去活性の相関,
日本薬学会第119大会, 1999年3月. 後藤了, 小暮健太朗, 安部一豊, 赤須通範, 寺田弘 :
大環状Bis-benzylisoquinoline誘導体の動的構造の解析とラジカル消去活性,
第26回構造活性相関シンポジウム, 1998年11月. 後藤了, 安部一豊, 小暮健太朗, 赤須通範, 寺田弘 :
Cepharanthineおよびその誘導体のラジカル消去活性発現における動的構造の影響,
第24回アルカロイド討論会, 1998年6月.

研究会・報告書: 小暮健太朗 :
抗酸化粒子による活性酸素消去と組織・細胞生理制御による生体内送達.,
第619回新潟薬科大学薬学総合セミナー(新潟), 2016年11月. 小暮健太朗 :
ナノ粒子製剤の構築と微弱電流による非侵襲的投与法の開発,
第53回薬剤学懇談会研究討論会, 2016年6月. 小暮健太朗 :
アスタキサンチンとトコトリエノールの抗酸化併用効果,
アスタリールシンポジウム2016, 2016年2月. 福澤健治, 小暮健太朗, 真鍋幸恵, 德村彰 :
α-トコフェロールジカルボン酸誘導体の抗ガン作用,
第17回ビタミンE研究会, 2006年1月. 福澤健治, 小暮健太朗, 德村彰 :
α-トコフェロール・コハク酸の酸化的アポトーシスと抗ガン作用,
第5回AOB(Antioxidant Biofactor)研究会:食品機能と酸化ストレス, 2005年6月. 福澤健治, 真鍋幸恵, 小暮健太朗, 德村彰 :
α-トコフェロール誘導体のアポトーシス誘導作用:構造-活性相関,
第16回ビタミンE研究会, 2005年1月. 福澤健治, 小暮健太朗, 中島佐和, 土江明子, 德村彰 :
ビタミンEによるリン脂質酸化二次産物誘導血管平滑筋細胞アポトーシスの抑制,
第15回ビタミンE研究会, 2004年1月. 福澤健治, 中島佐和, 土江明子, 小暮健太朗, 德村彰 :
PAF様リン脂質酸化二次産物とビタミンE,
第300回脂溶性ビタミン総合研究委員会, 2003年6月. 真鍋幸恵, 小暮健太朗, 森田健之, 德村彰, 福澤健治 :
抗がん剤として製剤化を指向したビタミンEコハク酸ベクシル,
第14回ビタミンE研究会, 2003年1月. 小暮健太朗, 浜進, 真鍋幸恵, 德村彰, 福澤健治 :
トコフェロールコハク酸のガン細胞に対するアポトーシス誘導作用の検討,
第13回ビタミンE研究会, 2002年1月. 浜進, 小暮健太朗, 森田元喜, 中島佐和, 德村彰, 福澤健治 :
α-トコフェロールコハク酸によるNO産出促進にPKCが関与する,
第13回ビタミンE研究会, 2002年1月.

特許: 小暮健太朗 : 皮膚通電用組成物及びその利用, 特願2023-002384 (2023年1月), .
作品: 研究者総覧に該当データはありませんでした。
補助金・競争的資金: 全身皮膚への非接触型核酸医薬送達システムの開発―SF培養槽への挑戦― (研究課題/領域番号: 23K18592 )
電気とナノ粒子を組み合わせた抗ウイルスケミカル・ワクチンシステムの創製 (研究課題/領域番号: 21K19912 )
化学の力で創造する新しい細胞システム (研究課題/領域番号: 21K19052 )
ゲノム編集ツール臓器内直接送達システムによる生体内ダイレクトゲノム編集技術の開発 (研究課題/領域番号: 21H03797 )
「食べるマイクロRNAを創る」　ー機能性食品としての核酸ー (研究課題/領域番号: 19K22287 )
微弱電流による細胞質薬物送達の分子機構の解明 (研究課題/領域番号: 18F18097 )
iRedによる核酸創薬研究を加速させる外部刺激応答型核酸ナノ構造体の創製 (研究課題/領域番号: 18H02108 )
微弱電流処理による植物の形質制御システムの開発 (研究課題/領域番号: 17K19241 )
微弱電流によるナノ粒子の腫瘍内浸透・細胞取込み亢進による革新的がん治療技術の確立 (研究課題/領域番号: 17H03976 )
腫瘍組織への自走侵入可能なpH感応性べん毛駆動型リポソームの創成 (研究課題/領域番号: 15K14945 )
腫瘍微小環境応答性ペプチド搭載核酸キャリアーの開発と肝転移がん治療への展開 (研究課題/領域番号: 15K07907 )
画像解析による微弱電流依存性の細胞内輸送亢進機構解明と革新的指向性ＤＤＳへの展開 (研究課題/領域番号: 26107718 )
細胞の微弱電流環境下における物質取り込み変化の機構解明と革新的薬物送達への展開 (研究課題/領域番号: 24107523 )
痛くないワクチンによる抗がん治療 (研究課題/領域番号: 24650284 )
腫瘍組織内奥へ積極侵入可能なワームライクＤＤＳの創製 (研究課題/領域番号: 23390014 )
抗原提示バランスとアジュバントの制御に基づいたオーダーメイド癌ワクチン (研究課題/領域番号: 20659020 )
糖尿病遺伝子治療を目指した非侵襲的な皮内遺伝子送達システムの開発 (研究課題/領域番号: 20390016 )
幹細胞標的化miRNAの非侵襲的送達による褐色脂肪細胞の生体内分化誘導法の創製 (研究課題/領域番号: 20200064 )
シャペロンの糖鎖認識を原理とした新規細胞ストレスセンシング法の開発 (研究課題/領域番号: 19350078 )
DNA・mRNAの細胞内高感度可視化情報に基づく高性能人工遺伝子べクターの創製 (研究課題/領域番号: 19021003 )
毛包をターゲットとした多機能性ナノ構造体による遺伝子デリバリー (研究課題/領域番号: 18590134 )
SIRNA搭載多重型ナノ構造体の開発と2型糖尿病関連遺伝子群の機能解析 (研究課題/領域番号: 18200032 )
1分子イメージングに基づく細胞内動態・解離制御型デリバリーシステムの創製 (研究課題/領域番号: 18038001 )
がん選択的多機能性エンベロープ型ナノ構造体の開発とがん遺伝子治療への応用 (研究課題/領域番号: 18015004 )
易分解性を有する脂溶性ジカルボン酸エステルによる抗ガン効果の検討 (研究課題/領域番号: 12771436 )
タンパク質の膜間移行現象を応用した新規癌ワクチンの開発 (研究課題/領域番号: 10771269 )
研究者番号（70262540）による検索

その他: 研究者総覧に該当データはありませんでした。

研究者総覧で最新データを確認する

2024年4月26日更新

専門分野・研究分野: 生物物理化学 (Biophysical Chemistry)
薬物送達学
衛生薬学
所属学会・所属協会: 日本薬剤学会
日本ビタミン学会
日本DDS学会
遺伝子・デリバリー研究会
日本酸化ストレス学会
ビタミンE研究会
物性物理化学研究会
日本膜学会
日本核酸医薬学会
Vitamin E Update Forum
Journal of Clinical Biochemistry and Nutrition
日本薬剤学会第36年会
日本核酸医薬学会第6回大会
膜シンポジウム2022
遺伝子・デリバリー研究会第21回シンポジウム，第20回夏期セミナー
生体膜と薬物の相互作用シンポジウム
日本薬学会
ICOM2023組織委員会
委員歴・役員歴: 日本薬剤学会 (理事,代議員 [2022年4月〜2025年3月])
日本ビタミン学会 (幹事,代議員,編集委員 [2017年6月〜2025年6月])
日本DDS学会 (評議員 [2018年4月〜2025年3月])
遺伝子・デリバリー研究会 (会長 [2022年1月〜2025年3月])
日本酸化ストレス学会 (評議員 [2018年4月〜2025年3月])
ビタミンE研究会 (幹事 [2018年4月〜2025年3月])
物性物理化学研究会 (委員 [2018年4月〜2025年3月])
日本膜学会 (評議員 [2018年4月〜2025年3月])
日本核酸医薬学会 (幹事 [2018年4月〜2025年3月])
Vitamin E Update Forum (組織委員 [2016年1月〜2018年3月])
日本薬剤学会 (第31年会組織委員 [2016年1月〜5月])
日本DDS学会 (第32回学術集会組織委員 [2016年1月〜7月])
日本ビタミン学会 (Journal of Nutritional Science and Vitaminology編集副委員長 [2017年6月〜2025年5月])
Journal of Clinical Biochemistry and Nutrition (編集委員 [2019年4月〜2024年3月])
日本薬剤学会第36年会 (日本薬剤学会第36年会組織委員 [2019年4月〜2021年5月])
日本核酸医薬学会第6回大会 (日本核酸医薬学会第6回大会組織委員 [2019年4月〜2021年6月])
膜シンポジウム2022 (実行委員長 [2021年11月〜2022年11月])
遺伝子・デリバリー研究会第21回シンポジウム，第20回夏期セミナー (実行委員長 [2021年12月〜2022年8月])
日本薬剤学会 (第37年会組織委員 [2021年2月〜2022年5月])
生体膜と薬物の相互作用シンポジウム (運営委員会委員 [2016年1月〜2025年3月])
日本薬学会 (代議員，国際交流委員会委員 [2021年3月〜2025年3月])
ICOM2023(国際膜学会)組織委員会 (委員 [2022年11月〜2023年7月])
受賞: 2021年5月, タケル・アヤ・ヒグチ記念賞 (公益社団法人日本薬剤学会)
活動: 徳島県 (徳島県廃棄物処理施設設置専門委員会委員 [2019年4月〜2025年3月])
岐阜薬科大学 (岐阜薬科大学特別研究費審査委員会委員 [2019年4月〜2025年3月])
薬学共用試験センター (薬学共用試験センター財務委員 [2017年4月〜2025年4月])
6年制薬学教育制度調査検討委員会モデル・コアカリ大項目検討小委員会 (班員 [2021年4月〜2023年3月])
医療教育開発センター副センター長 (2016年4月〜2017年3月)
学務委員会副委員長 (2016年4月〜2017年3月)
大学院医歯薬学研究部薬学系分野研究推進委員会委員長 (2016年4月〜2018年3月)
学務委員会委員長 (2017年4月〜2018年3月)
自己点検·評価委員会委員 (2017年4月〜2019年3月)
薬学部自己点検・評価委員会委員長 (2017年4月〜2019年3月)
副学部長 (2017年4月〜2019年3月)
薬学部自己点検評価委員会委員長 (2017年4月〜2019年3月)
薬学部運営会議メンバー (2017年4月〜2019年3月)
総合薬学研究推進学分野運営委員会委員 (2017年4月〜2019年3月)
薬学部廃棄物等処理委員会委員 (2017年4月〜2019年3月)
薬学教育評価ワーキンググループ (2017年4月〜2019年3月)
教育の成果・効果を検証するためのアンケート調査ワーキンググループ (2018年)
薬学部入試広報委員会委員長 (2018年4月〜2019年3月)
大学開放実践センター運営委員 (2018年4月〜2020年3月)
大学機関別認証評価対応WG (2018年4月〜2020年3月)
薬学部防災環境委員会委員 (2018年4月〜2020年3月)
大学院医歯薬学研究部倫理委員会委員 (2018年4月〜2020年3月)
大学院医歯薬学研究部薬学域研究推進委員会委員長 (2018年4月〜2020年3月)

リサーチマップで最新データを確認するＪグローバルで最新データを確認する

2024年4月21日更新

2024年4月20日更新

Ｊグローバル

Jグローバル最終確認日: 2024/4/20 01:22
氏名（漢字）: 小暮健太朗
氏名（フリガナ）: コグレケンタロウ
氏名（英字）: Kogure Kentaro
所属機関: 徳島大学教授

リサーチマップ

researchmap最終確認日: 2024/4/21 01:34
氏名（漢字）: 小暮健太朗
氏名（フリガナ）: コグレケンタロウ
氏名（英字）: Kogure Kentaro
プロフィール: リサーチマップAPIで取得できませんでした。
登録日時: 2011/1/26 00:00
更新日時: 2024/4/20 06:36
アバター画像URI: https://researchmap.jp/read0187881/avatar.jpg
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所属ID: 0344000000
所属: 徳島大学
部署: 大学院医歯薬学研究部（薬学系）衛生薬学分野
職名: 教授
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経歴
受賞
Misc
論文
講演・口頭発表等
書籍等出版物
研究キーワード
研究分野
所属学協会
担当経験のある科目
その他: リサーチマップAPIで取得できませんでした。
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ＫＡＫＥＮで最新データを確認する

2024年4月20日更新

研究者番号: 70262540

所属（現在）: 2024/4/1 : 徳島大学, 大学院医歯薬学研究部(薬学域), 教授

所属（過去の研究課題 情報に基づく）*注記: 2018/4/1 – 2024/4/1 : 徳島大学, 大学院医歯薬学研究部(薬学域), 教授
2017/4/1 : 徳島大学, 薬学部, 教授
2016/4/1 – 2017/4/1 : 徳島大学, 大学院医歯薬学研究部(薬学系), 教授
2015/4/1 : 徳島大学, 大学院医歯薬学研究部, 教授
2007/4/1 – 2014/4/1 : 京都薬科大学, 薬学部, 教授
2007/4/1 : 京都薬科大学, 教授
2007/4/1 : 北海道大学, 京都薬科大学薬学部, 教授
2006/4/1 : 北海道大学, 大学院薬学研究院, 寄附分野教員(講師)
2006/4/1 : 北海道大学, 大学院薬学研究院, 寄附分野教員(講師)
1998/4/1 – 2001/4/1 : 徳島大学, 薬学部, 助手

審査区分/研究分野

研究代表者

医学 / 薬学 / 物理系薬学
医学 / 薬学 / 医薬分子機能学
生物系 / 医歯薬学 / 薬学 / 物理系薬学
総合・新領域系 / 総合領域 / 人間医工学 / 医用生体工学・生体材料学
生物系 / 医歯薬学 / 薬学 / 医療系薬学
農芸化学およびその関連分野
薬学 / 物理系薬学
理工系
小区分90110:生体医工学関連
中区分90:人間医工学およびその関連分野

研究代表者以外

総合・新領域系 / 総合領域 / 人間医工学 / 医用生体工学・生体材料学
理工系 / 化学 / 複合化学 / 生体関連化学
生物系 / 医歯薬学 / 薬学 / 生物系薬学 / 生物系 / 生物学 / 生物科学 / 発生生物学
生物系 / 医歯薬学 / 薬学 / 医療系薬学
生物系 / 医歯薬学 / 薬学 / 創薬化学
生物系 / 医歯薬学 / 薬学 / 物理系薬学
生物系
理工系
小区分37030:ケミカルバイオロジー関連
中区分38:農芸化学およびその関連分野
中区分37:生体分子化学およびその関連分野

キーワード

研究代表者

リポソーム / タンパク質膜間移行 / 癌ワクチン / アポトーシス / 抗ガン効果 / 活性酸素 / 遺伝子送達 / 糖尿病 / インスリン / 皮膚 / ナノDDS / 癌細胞間隙 / 癌微小環境 / 癌治療 / siRNA / 微弱電流環境 / 細胞内取込み / 細胞内輸送 / エンドソーム脱出 / 送達キャリアー / 薬物送達システム / イオントフォレシス / がんワクチン / ナノ粒子 / 経皮投与 / 微弱電流処理 / 細胞取り込み / エンドソーム漏出 / 微弱電流 / 毛包 / 遺伝子デリバリーシステム / gene delivery / hair follicules / gene delivery system / ドラッグデリバリーシステム / べん毛 / DDSキャリアー / 植物 / siRNA送達 / 遺伝子発現制御 / 形質制御 / ドラッグデリバリー / がん治療 / ゲノム編集 / 脂質ナノ粒子 / 皮内送達 / 抗ウイルス薬 / 細胞シグナル伝達 / 細胞質デリバリー

研究代表者以外

MEND / 遺伝子導入 / MMP / オクタアルギニン / siRNA / がん治療 / がん / 遺伝子治療 / PPD-MEND / 細胞内動態 / 人工ベクター / アデノウイルス / 遺伝子デリバリー / エンドサイトーシス / トランスサイトーシス / 多機能性エンベロープ型ナノ構造体 / 血管透過 / 2型糖尿病 / 網羅的解析 / 遺伝子診断 / 遺伝子デリバリーシステム / GALA / IRO / ハイドロダイナミクス法 / カベオラ / R8-NEND / リアルタイムイメージング / 細胞内動態制御 / mRNA検出 / heterogeneity / 糖鎖 / 量子ドット / 核移行 / 細胞ストレス / シャペロン / 非特異吸着 / 分散性 / イメージング / N-アセチルグルコサミン / 褐色脂肪細胞 / miRNA / 発生・分化 / マイクロアレイ / 白色脂肪細胞 / モノクローナル抗体 / ワクチン / アジュバント / トポロジー / ナノ構造体 / 細胞性免疫 / 細胞透過性ペプチド / MHCクラス-I / 抗原提示 / 抗腫瘍効果 / ナノマシン / マイクロ流路 / 核内動態制御 / ミトコンドリア / ナノパッケージング / pH-感受性カチオニック脂質 / 還元環境応答性 / ミトコンドリア送達 / 自己活性化システム / バイセル / パッケージング / 核送達 / KALA / 機能性核酸 / ドラッグデリバリーシステム / 腫瘍微小環境 / DDS / 腫瘍内透過 / 核酸 / ドラッグデリバリー / がん微小環境 / 核酸創薬 / RNAi医薬 / iRed / 核酸ナノ構造体 / 微弱電流 / RNAi医薬品 / マイクロRNA / 4'-チオRNA / 4'-セレノRNA / 機能性食品 / 核酸化学 / 合成生物学 / 4'-チオ核酸 / 人工細胞 / 人工核酸 / セントラルドグマ / 合成セントラルドグマ

研究課題研究成果共同研究者

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2020年3月27日

次世代型「脳関門創薬」拠点形成：ヒト血液脳関門物流システム解明に基づく脳関門突破型抗体・核酸医薬の開発

立川正憲小迫英尊小暮健太朗石田竜弘山本圭田良島典子鬼塚正義福田達也中島公平藤原敏孝

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小暮 健太朗

Ｊグローバル

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研究代表者

研究代表者以外

研究代表者

研究代表者以外

小暮健太朗