Updated on 2024/11/25

Information

 

写真a

 
HAMAMURA KENGO
 
Organization
Faculty of Pharmaceutical Sciences Department of Pharmaceutical Health Care and Sciences Lecturer
Title
Lecturer
Contact information
メールアドレス
Tel
0926424820
Profile
Among extracellular vesicles, exosomes are lipid bilayer vesicles from 50 to 150 nm in diameter and secreted by cells in vivo and cultured cells. Exosomes are also characterized by their presence in body fluids, such as blood and urine, and are distributed via body fluids to cells throughout the body. We are investigating the impact of exosomes on the pathogenesis and progression of pathological processes.
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Research Areas

  • Life Science / Pharmacology

Degree

  • Ph.D. (Pharmaceutical Sciences)

Research History

  • Kyushu University Department of Clinical Pharmacokinetics, Faculty of Pharmaceutical Sciences Lecturer 

    2023.4 - Present

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  • Daiichi University, College of Pharmaceutical Sciences 薬学部 薬品作用学分野 Lecturer 

    2021.4 - 2023.3

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  • 2013年4月 日本学術振興会特別研究員(DC2) (2015年3月まで) 2015年4月 第一薬科大学 薬学部 助教 (2021年3月まで) 2021年4月 第一薬科大学 薬学部 講師 (2023年3月まで)   

Research Interests・Research Keywords

  • Research theme: 疼痛

    Keyword: 疼痛

    Research period: 2024

  • Research theme: エクソソーム

    Keyword: エクソソーム

    Research period: 2024

  • Research theme: Novel enhancement mechanisms of the nociceptive response by serum exosomes in a mouse model of neuropathic pain

    Keyword: extracellular vesicles, exosomes, neuropathic pain, nociceptive pain

    Research period: 2015.4

  • Research theme: The potential of bergamot essential oil as a medicinal plant

    Keyword: Bergamot Essential Oil

    Research period: 2015.4

  • Research theme: Novel Mechanism of Renal Function Deterioration via Kidney-Liver-Kidney Linkage of Molecular Clock Mechanism in a Mouse Model of Chronic Kidney Disease

    Keyword: Chronic Kidney Disease

    Research period: 2009.4

Awards

  • 優秀発表賞

    2014.11   第8回次世代を担う若手医療薬科学シンポジウム   慢性腎臓病モデルマウスにおける分子時計機構の腎-肝-腎連関を介した新規腎機能悪化機序 の解明

  • 優秀ポスター賞

    2014.11   第21回日本時間生物学会学術大会   慢性腎不全モデルマウスにおける肝代謝酵素発現日内変動変容機構の解明

Papers

  • Clinical and Market Analysis of NanoBEO: A Public-Worth, Innovative Therapy for Behavioral and Psychological Symptoms of Dementia (BPSD)-Emerging Evidence and Its Implications for a Health Technology Assessment (HTA) and Decision-Making in National Health Systems

    Scuteri, D; Pierobon, D; Pagliaro, M; Hamamura, K; Hayashi, T; Pignolo, L; Nicotera, P; Bagetta, G; Corasaniti, MT

    PHARMACEUTICS   16 ( 10 )   2024.10   eISSN:1999-4923

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    Publisher:Pharmaceutics  

    Background: According to scientific literature, some 99% of patients affected by Alzheimer’s disease (AD) suffer from behavioral and psychological symptoms of dementia (BPSD), also known as neuropsychiatric symptoms (NPSs). In particular, agitation is one of the most difficult disorders to treat. States of agitation represent a very serious problem as they make these subjects dangerous for themselves and others and worsen as the disease advances. To date, there are no specific solutions for treating agitation. The only authorized drug is risperidone (as well as brexpiprazole, approved by the FDA on 11 May 2023), which can be used for no longer than 6–12 weeks because it increases the risk of death—owing to cardiocerebrovascular accidents—by 1.6–1.7 times. Methods: In order to address the latter noteworthy unmet medical need, NanoBEO was produced. The aim of the present work is to generate the health technology assessment (HTA) of this nanotechnological device. The latter consists of a controlled release system, based on solid lipid nanoparticles loaded with bergamot essential oil (BEO). Results: The results of the present research assessed the current evidence in the field of non-pharmacological treatments for this condition, including relevant primary preclinical and clinical data studies supporting the use of this device and the production of the operative plan for its launch on the market. The findings offer recommendations for decision-making on its implementation in dementia. Conclusions: NanoBEO represents a public-worth innovation in this neglected area, marking a significant advancement in the history of dementia, moving from academic research to product development.

    DOI: 10.3390/pharmaceutics16101253

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  • Hericenone C attenuates the second phase of formalin-induced nociceptive behavior by suppressing the accumulation of CD11c-positive cells in the paw epidermis via phosphorylated P65 Reviewed

    Junhao Li, Kengo Hamamura, Yuya Yoshida, Shimpei Kawano, Shohei Uchinomiya, Jiahongyi Xie, Damiana Scuteri, Kohei Fukuoka, Orion Zaitsu, Fumiaki Tsurusaki, Yuma Terada, Ryotaro Tsukamoto, Takumi Nishi, Taiki Fukuda, Kosuke Oyama, Giacinto Bagetta, Akio Ojida, Kuniyoshi Shimizu, Shigehiro Ohdo, Naoya Matsunaga

    Biochemical and Biophysical Research Communications   720   150077   2024.8   ISSN:0006291X eISSN:1090-2104

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    Hericenone C is one of the most abundant secondary metabolites derived from Hericium erinaceus, under investigation for medicinal properties. Here, we report that Hericenone C inhibits the second phase of formalin-induced nociceptive behavior in mice. As the second phase is involved in inflammation, in a mechanistic analysis on cultured cells targeting NF-κB response element (NRE): luciferase (Luc)-expressing cells, lipopolysaccharide (LPS)-induced NRE::Luc luciferase activity was found to be significantly inhibited by Hericenone C. Phosphorylation of p65, which is involved in the inflammatory responses of the NF-κB signaling pathway, was also induced by LPS and significantly reduced by Hericenone C. Additionally, in mice, the number of CD11c-positive cells increased in the paw during the peak of the second phase of the formalin test, which decreased upon Hericenone C intake. Our findings confirm the possibility of Hericenone C as a novel therapeutic target for pain-associated inflammation.

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  • Circadian rhythms in CYP2A5 expression underlie the time-dependent effect of tegafur on breast cancer Reviewed

    Yuya Yoshida, Taiki Fukuda, Tomohito Tanihara, Naoki Nishikawa, Serina Iwasa, Satoka Adachi, Orion Zaitsu, Yuma Terada, Ryotaro Tsukamoto, Hideki Shimoshikiryo, Kohei Fukuoka, Fumiaki Tsurusaki, Kengo Hamamura, Kosuke Oyama, Akito Tsuruta, Satoru Koyanagi, Naoya Matsunaga, Shigehiro Ohdo

    Biochemical and Biophysical Research Communications   708   149813 - 149813   2024.5   ISSN:0006-291X eISSN:1090-2104

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    Language:Others   Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    The chemotherapeutic agent tegafur, a prodrug that prolongs the half-life of fluorouracil (5-FU), exerts antitumor effects against various cancers. Since tegafur is metabolized to 5-FU by CYP2A6 in the liver, the expression of CYP2A6 determines the effect of tegafur. Here, we report that the expression rhythm of Cyp2a5, a homolog of human CYP2A6, in female mice causes dosing time-dependent differences in tegafur metabolism. In the livers of female mice, CYP2A5 expression showed a circadian rhythm, peaking during the dark period. This rhythm is regulated by RORA, a core clock component, and abrogation of the CYP2A5 activity abolished the time-dependent difference in the rate of tegafur metabolism in female mice. Furthermore, administration of tegafur to mice transplanted with 4T1 breast cancer cells during the dark period suppressed increases in tumor size compared to female mice treated during the light period. Our findings reveal a novel relationship between 5-FU prodrugs and circadian clock machinery, potentially influencing antitumor effects, and contributing to the development of time-aware chemotherapy regimens for breast cancer.

    DOI: 10.1016/j.bbrc.2024.149813

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  • Prostaglandin F2α Affects the Cycle of Clock Gene Expression and Mouse Behavior Reviewed

    Yuya Tsurudome, Yuya Yoshida, Kengo Hamamura, Takashi Ogino, Sai Yasukochi, Shinobu Yasuo, Ayaka Iwamoto, Tatsuya Yoshihara, Tomoaki Inazumi, Soken Tsuchiya, Toru Takeo, Naomi Nakagata, shigekazu higuchi, Yukihiko Sugimoto, Akito Tsuruta, Satoru Koyanagi, Naoya Matsunaga, Shigehiro Ohdo

    International Journal of Molecular Sciences   25 ( 3 )   2024.2   ISSN:1661-6596 eISSN:1422-0067

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    Prostaglandins are bioactive compounds, and the activation of their receptors affects the expression of clock genes. However, the prostaglandin F receptor (Ptgfr) has no known relationship with biological rhythms. Here, we first measured the locomotor period lengths of Ptgfr-KO (B6.129-Ptgfrtm1Sna) mice and found that they were longer under constant dark conditions (DD) than those of wild-type (C57BL/6J) mice. We then investigated the clock gene patterns within the suprachiasmatic nucleus in Ptgfr-KO mice under DD and observed a decrease in the expression of the clock gene cryptochrome 1 (Cry1), which is related to the circadian cycle. Moreover, the expression of Cry1, Cry2, and Period2 (Per2) mRNA were significantly altered in the mouse liver in Ptgfr-KO mice under DD. In the wild-type mouse, the plasma prostaglandin F2α (PGF2α) levels showed a circadian rhythm under a 12 h cycle of light–dark conditions. In addition, in vitro experiments showed that the addition of PTGFR agonists altered the amplitude of Per2::luc activity, and this alteration differed with the timing of the agonist addition. These results lead us to hypothesize that the plasma rhythm of PGF2α is important for driving clock genes, thus suggesting the involvement of PGF2α- and Ptgfr-targeting drugs in the biological clock cycle.

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  • Inhibition of G protein-coupled receptor 68 using homoharringtonine attenuates chronic kidney disease-associated cardiac impairment. Reviewed International journal

    Yuya Yoshida, Kohei Fukuoka, Miyu Sakugawa, Masayuki Kurogi, Kengo Hamamura, Keika Hamasaki, Fumiaki Tsurusaki, Kurumi Sotono, Takumi Nishi, Taiki Fukuda, Taisei Kumamoto, Kosuke Oyama, Takashi Ogino, Akito Tsuruta, Kouta Mayanagi, Tomohiro Yamashita, Hiroyuki Fuchino, Nobuo Kawahara, Kayo Yoshimatsu, Hitomi Kawakami, Satoru Koyanagi, Naoya Matsunaga, Shigehiro Ohdo

    Translational research : the journal of laboratory and clinical medicine   269   31 - 46   2024.2   ISSN:1931-5244 eISSN:1878-1810

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Translational Research  

    Chronic kidney disease (CKD) induces cardiac inflammation and fibrosis and reduces survival. We previously demonstrated that G protein-coupled receptor 68 (GPR68) promotes cardiac inflammation and fibrosis in mice with 5/6 nephrectomy (5/6Nx) and patients with CKD. However, no method of GPR68 inhibition has been found that has potential for therapeutic application. Here, we report that Cephalotaxus harringtonia var. nana extract and homoharringtonine ameliorate cardiac inflammation and fibrosis under CKD by suppressing GPR68 function. Reagents that inhibit the function of GPR68 were explored by high-throughput screening using a medicinal plant extract library (8,008 species), and we identified an extract from Cephalotaxus harringtonia var. nana as a GPR68 inhibitor that suppresses inflammatory cytokine production in a GPR68 expression-dependent manner. Consumption of the extract inhibited inflammatory cytokine expression and cardiac fibrosis and improved the decreased survival attributable to 5/6Nx. Additionally, homoharringtonine, a cephalotaxane compound characteristic of C. harringtonia, inhibited inflammatory cytokine production. Homoharringtonine administration in drinking water alleviated cardiac fibrosis and improved heart failure and survival in 5/6Nx mice. A previously unknown effect of C. harringtonia extract and homoharringtonine was revealed in which GPR68-dependent inflammation and cardiac dysfunction were suppressed. Utilizing these compounds could represent a new strategy for treating GPR68-associated diseases, including CKD.

    DOI: 10.1016/j.trsl.2024.02.004

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  • Hematopoietic Prostaglandin D Synthase Is Increased in Mast Cells and Pericytes in Autopsy Myocardial Specimens from Patients with Duchenne Muscular Dystrophy Reviewed

    Kengo Hamamura, Yuya Yoshida, Kosuke Oyama, Junhao Li, Shimpei Kawano, Kimiko Inoue, Keiko Toyooka, Misaki Yamadera, Naoya Matsunaga, Tsuyoshi Matsumura, Kosuke Aritake

    International Journal of Molecular Sciences   25 ( 3 )   2024.2   ISSN:1661-6596 eISSN:1422-0067

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    The leading cause of death for patients with Duchenne muscular dystrophy (DMD), a progressive muscle disease, is heart failure. Prostaglandin (PG) D2, a physiologically active fatty acid, is synthesized from the precursor PGH2 by hematopoietic prostaglandin D synthase (HPGDS). Using a DMD animal model (mdx mice), we previously found that HPGDS expression is increased not only in injured muscle but also in the heart. Moreover, HPGDS inhibitors can slow the progression of muscle injury and cardiomyopathy. However, the location of HPGDS in the heart is still unknown. Thus, this study investigated HPGDS expression in autopsy myocardial samples from DMD patients. We confirmed the presence of fibrosis, a characteristic phenotype of DMD, in the autopsy myocardial sections. Additionally, HPGDS was expressed in mast cells, pericytes, and myeloid cells of the myocardial specimens but not in the myocardium. Compared with the non-DMD group, the DMD group showed increased HPGDS expression in mast cells and pericytes. Our findings confirm the possibility of using HPGDS inhibitor therapy to suppress PGD2 production to treat skeletal muscle disorders and cardiomyopathy. It thus provides significant insights for developing therapeutic drugs for DMD.

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  • Time-dependent differences in vancomycin sensitivity of macrophages underlie vancomycin-induced acute kidney injury Reviewed International journal

    Yuya Yoshida, Taiki Fukuda, Kohei Fukuoka, Toshitaka Nagayama, Tomohito Tanihara, Naoki Nishikawa, Kaita Otsuki, Yuma Terada, Kengo Hamamura, Kosuke Oyama, Akito Tsuruta, Kota Mayanagi, Satoru Koyanagi, Naoya Matsunaga, Shigehiro Ohdo

    Journal of Pharmacology and Experimental Therapeutics   388 ( 1 )   JPET - AR   2023.11   ISSN:0022-3565 eISSN:1521-0103

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:American Society for Pharmacology & Experimental Therapeutics (ASPET)  

    Although vancomycin (VCM)-frequently used to treat drug-resistant bacterial infections-often induces acute kidney injury (AKI), discontinuation of the drug is the only effective treatment; therefore, analysis of effective avoidance methods is urgently needed. Here, we report the differences in the induction of AKI by VCM in 1/2-nephrectomized mice depending on the time of administration. Despite the lack of difference in the accumulation of VCM in the kidney between the light (ZT2) and dark (ZT14) phases, the expression of AKI markers due to VCM was observed only in the ZT2 treatment. Genomic analysis of the kidney suggested that the time of administration was involved in VCM-induced changes in monocyte and macrophage activity, and VCM had time-dependent effects on renal macrophage abundance, ATP activity, and interleukin (IL)-1β expression. Furthermore, the depletion of macrophages with clodronate abolished the induction of IL-1β and AKI marker expression by VCM administration at ZT2. This study provides evidence of the need for time-dependent pharmacodynamic considerations in the prevention of VCM-induced AKI as well as the potential for macrophage-targeted AKI therapy. SIGNIFICANCE STATEMENT: There is a time of administration at which vancomycin (VCM)-induced renal injury is more and less likely to occur, and macrophages are involved in this difference. Therefore, there is a need for time-dependent pharmacodynamic considerations in the prevention of VCM-induced acute kidney injury as well as the potential for macrophage-targeted acute kidney injury therapy.

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  • Oral administration of vancomycin alleviates heart failure triggered by chronic kidney disease Reviewed

    Kohei Fukuoka, Yuya Yoshida, Kurumi Sotono, Naoki Nishikawa, Kengo Hamamura, Kosuke Oyama, Akito Tsuruta, Kota Mayanagi, Satoru Koyanagi, Naoya Matsunaga, Shigehiro Ohdo

    Biochemical and Biophysical Research Communications   675   92 - 98   2023.10   ISSN:0006-291X eISSN:1090-2104

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    Chronic kidney disease (CKD) induces an imbalance in the intestinal microbiota, affecting various physiological functions and leading to cardiovascular inflammation and fibrosis. However, the cardiotoxic impact of intestinal microbiota-derived uremic substances in advanced renal dysfunction remains unexplored. Therefore, we developed a 5/6 nephrectomy (5/6Nx) mouse model to investigate the intestinal microbiota and the effects of administering vancomycin (VCM) on the microbiota and the cardiac pathology associated with CKD. Despite VCM administration after the development of irreversible glomerulosclerosis and tubulointerstitial fibrosis, blood indoxyl sulfate and phenyl sulfate levels, which are intestinal bacteria-derived uremic substances, brain natriuretic peptide levels, and the fibrotic area in the heart were decreased. Moreover, VCM administration prevented 5/6Nx-induced weight loss and prolonged survival time. Our findings suggest that VCM-induced changes in the intestinal microbiota composition ameliorate heart failure and improve survival rates by reducing intestinal microbiota-derived cardiotoxic substances despite advanced renal dysfunction. This highlights the potential of using the intestinal microbiota as a target to prevent and treat cardiovascular conditions associated with CKD.

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  • Efficacy of Essential Oils in Relieving Cancer Pain: A Systematic Review and Meta-Analysis Reviewed

    Maria Tiziana Corasaniti, Giacinto Bagetta, Luigi Antonio Morrone, Paolo Tonin, Kengo Hamamura, Takafumi Hayashi, Francesca Guida, Sabatino Maione, Damiana Scuteri

    International Journal of Molecular Sciences   24 ( 8 )   7085 - 7085   2023.4   ISSN:1661-6596 eISSN:1422-0067

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    Over 80% of patients affected by cancer develops cancer-related pain, one of the most feared consequences because of its intractable nature, particularly in the terminal stage of the disease. Recent evidence-based recommendations on integrative medicine for the management of cancer pain underline the role of natural products. The present systematic review and meta-analysis aims at appraising for the first time the efficacy of aromatherapy in cancer pain in clinical studies with different design according to the most updated Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 recommendations. The search retrieves 1002 total records. Twelve studies are included and six are eligible for meta-analysis. The present study demonstrates significant efficacy of the use of essential oils in the reduction of the intensity of pain associated with cancer (p < 0.00001), highlighting the need for earlier, more homogeneous, and appropriately designed clinical trials. Good certainty body of evidence is needed for effective and safe management of cancer-related pain using essential oils by establishment of a step-by-step preclinical-to-clinical pathway to provide a rational basis for clinical use in integrative oncology. PROSPERO registration: CRD42023393182.

    DOI: 10.3390/ijms24087085

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  • Transgenic Mice for the Translational Study of Neuropathic Pain and Dystonia. Reviewed International journal

    Damiana Scuteri, Kengo Hamamura, Chizuko Watanabe, Paolo Tonin, Giacinto Bagetta, Maria Tiziana Corasaniti

    International journal of molecular sciences   23 ( 15 )   2022.8   ISSN:16616596

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    Murine models are fundamental in the study of clinical conditions and the development of new drugs and treatments. Transgenic technology has started to offer advantages in oncology, encompassing all research fields related to the study of painful syndromes. Knockout mice or mice overexpressing genes encoding for proteins linked to pain development and maintenance can be produced and pain models can be applied to transgenic mice to model the most disabling neurological conditions. Due to the association of movement disorders with sensitivity and pain processing, our group focused for the first time on the role of the torsinA gene GAG deletion-responsible for DYT1 dystonia-in baseline sensitivity and neuropathic responses. The aim of the present report are to review the complex network that exists between the chaperonine-like protein torsinA and the baseline sensitivity pattern-which are fundamental in neuropathic pain-and to point at its possible role in neurodegenerative diseases.

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  • Analgesic Characteristics of NanoBEO Released by an Airless Dispenser for the Control of Agitation in Severe Dementia Reviewed International journal

    Damiana Scuteri, Laura Rombolà, Takafumi Hayashi, Chizuko Watanabe, Shinobu Sakurada, Kengo Hamamura, Tsukasa Sakurada, Paolo Tonin, Giacinto Bagetta, Luigi A. Morrone, Maria Tiziana Corasaniti

    Molecules   27 ( 15 )   2022.8

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    Chronic pain is one of the most common causes of the need for clinical evaluation, acquiring more importance in the elderly with cognitive impairment. Reduced self-reporting capabilities cause unrelieved pain contributing to the development of agitation. Safe and effective pain treatment can afford the management of agitation without the serious increase in death risk associated with neuroleptics. To this aim, the essential oil of bergamot (BEO), proven by rigorous evidence to have strong preclinical anti-nociceptive and anti-allodynic properties, has been engineered (NanoBEO, patent EP 4003294) to allow randomized, double-blind, placebo-controlled trials (BRAINAID, NCT04321889). The present study: (1) assesses the analgesic effects of a single therapeutic dose of NanoBEO, as supplied by an airless dispenser for clinical translation, in models of inflammatory, neuropathic, and sensitization types of pain relevant to clinic; (2) provides a dose-response analysis of the efficacy of NanoBEO on scratching behavior, a typical behavioral disturbance occurring in dementia. A single therapeutic dose of NanoBEO confirms efficacy following thirty minutes pre-treatment with capsaicin and on the central sensitization phase induced by formalin. Moreover, it has an ID50 of 0.6312 mg and it is efficacious on static and dynamic mechanical allodynia. Altogether, the gathered results strengthen the potential of NanoBEO for clinical management of pain and agitation.

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  • Pharmacotechnological Advances for Clinical Translation of Essential Oils for the Treatment of Pain and Agitation in Severe Dementia Reviewed

    Damiana Scuteri, Chizuko Watanabe, Shinobu Sakurada, Kengo Hamamura, Tsukasa Sakurada, Paolo Tonin, Giacinto Bagetta, Maria Tiziana Corasaniti

    Processes   10 ( 7 )   2022.7

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    The demand for natural products is steadily increasing, and pharmacotechnological engineering is needed to allow rigorous investigation of their efficacy and safety in clinical conditions representing still unmet needs. Among aged patients affected by dementia, up to 80% of residents in nursing homes suffer from chronic pain and 97% from fluctuant neuropsychiatric symptoms (NPS), of which the most challenging is agitation. It is, at least in part, due to undertreated pain and treated with antipsychotics almost doubling the risk of death. In the frame of a scoping review assessing the existence of essential oils undergoing engineering pharmacotechnological processes using solid lipid nanoparticle delivery systems for clinical translation in pain and/or neuropsychiatric symptoms of dementia following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR), here we identified that the sole essential oil engineered to overcome the criticisms of aromatherapy clinical trials in pain and dementia is the essential oil of bergamot (BEO). Therefore, we present the process leading to the actually ongoing randomized, double-blind, placebo-controlled NCT04321889 clinical trial to assess the efficacy and safety of intervention with bergamot in the management of agitation and pain in severe dementia to be followed also for the proof of concept of efficacy and safety of other essential oils.

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  • Translational Value of the Transdermal Administration of Bergamot Essential Oil and of Its Fractions. Reviewed International journal

    Damiana Scuteri, Laura Rombolà, Michele Crudo, Chizuko Watanabe, Hirokazu Mizoguchi, Shinobu Sakurada, Kengo Hamamura, Tsukasa Sakurada, Luigi Antonio Morrone, Paolo Tonin, Giacinto Bagetta, Maria Tiziana Corasaniti

    Pharmaceutics   14 ( 5 )   2022.5

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    The essential oil of bergamot (BEO) has consistently proven antinociceptive and antiallodynic properties. Accordingly, the analgesic efficacy of the decolored essential oil (DEC), with higher levels of limonene, and the deterpenated (DET) fraction, with higher levels of linalool and linalyl acetate, was investigated using a formalin test after inhalation. The present study was aimed at characterizing the effects of BEO, its components with the highest pharmacological activity (represented by linalool, limonene, and linalyl acetate), and its DEC and DET fractions on the formalin test after transdermal administration relevant to clinical translation through topical application. To this aim, the schedule of intervention involved administration immediately after formalin injection or as a 5 min pretreatment followed by washout in ddY-strain mice. This study demonstrates, for the first time, the significant analgesic effect of all three constituents in the first and second phases, accounting for the efficacy of the essential oil in the formalin test. While all fractions revealed equal activity toward the phytocomplex in the early phase, the reduction in time of licking/biting during the late phase was more markedly induced by DEC. Moreover, pretreatment with BEO and its fractions followed by washout did not produce a significant reduction in licking/biting time in both phases of formalin-induced nociceptive response.

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  • Is there a rational basis for cannabinoids research and development in ocular pain therapy? A systematic review of preclinical evidence Reviewed

    Scuteri D., Rombolà L., Hamamura K., Sakurada T., Watanabe C., Sakurada S., Guida F., Boccella S., Maione S., Gallo Afflitto G., Nucci C., Tonin P., Bagetta G., Corasaniti M.T.

    Biomedicine and Pharmacotherapy   146   2022.2   ISSN:07533322

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    Background: Purpose of the present systematic review is to investigate preclinical evidence in favor of the working hypothesis of efficacy of cannabinoids in ocular pain treatment. Methods: Literature search includes the most relevant repositories for medical scientific literature from inception until November, 24 2021. Data collection and selection of retrieved records adhere to PRISMA criteria. Results: In agreement with a priori established protocol the search retrieved 2471 records leaving 479 results after duplicates removal. Eleven records result from title and abstract screening to meet the inclusion criteria; only 4 results are eligible for inclusion in the qualitative synthesis impeding meta-analysis. The qualitative analysis highlights the antinociceptive and anti-inflammatory efficacy of Δ8-tetrahydrocannabinol, cannabidiol and its derivative HU-308 and of new racemic CB1 allosteric ligand GAT211 and its enantiomers GAT228 and GAT229. Moreover, CB2R agonists RO6871304 and RO6871085 and CB2R ligand HU910 provide evidence of anti-inflammatory efficacy. CB2 agonist HU308 reduces of 241% uveitis-induced leukocyte adhesion and changes lipidome profile. Methodological and design issues raise concern of risk of bias and the amount of studies is too small for generalization. Furthermore, the ocular pain model used can resemble only inflammatory but not neuropathic pain. Conclusions: The role of the endocannabinoid system in ocular pain is underinvestigated, since only two studies assessing the effects of cannabinoid receptors modulators on pain behavior and other two on pain-related inflammatory processes are found. Preclinical studies investigating the efficacy of cannabinoids in ocular inflammatory and neuropathic pain models are needed to pave the way for clinical translation.

    DOI: 10.1016/j.biopha.2021.112505

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  • Preclinical Characterization of Antinociceptive Effect of Bergamot Essential Oil and of Its Fractions for Rational Translation in Complementary Therapy. Reviewed International journal

    Damiana Scuteri, Laura Rombolà, Michele Crudo, Chizuko Watanabe, Hirokazu Mizoguchi, Shinobu Sakurada, Kengo Hamamura, Tsukasa Sakurada, Paolo Tonin, Maria Tiziana Corasaniti, Giacinto Bagetta

    Pharmaceutics   14 ( 2 )   2022.1

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    Bergamot essential oil (BEO) is endowed with consistent and reproducible antinociceptive and anti-allodynic properties when administered via an inhalation route. However, the effects of its main constituents and of its decolored (DEC) and deterpenated (DET) fractions, which are enriched in limonene or in linalool and linalyl acetate, respectively, on spontaneous motor activity related to anxiety and on formalin-induced licking/biting biphasic behavior have never been investigated before. Therefore, the present research aims to characterize the role of BEO components on an experimental pain model that is relevant to clinical translation. Under our present experimental conditions, a paper filter disc soaked with different volumes of the phytocomplex and of its fractions that was applied at the edge of the observation chamber allowed the effects on the spontaneous motor activity and on the formalin-induced nocifensive response in ddY-strain mice to be studied. The present research demonstrated the effects of the DEC fraction of BEO on motor activity and on formalin-induced licking/biting behavior for the first time, proving that limonene is implicated in reduced motor activity and that it is important for the analgesic effect.

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  • Alteration of circadian machinery in monocytes underlies chronic kidney disease-associated cardiac inflammation and fibrosis Reviewed International journal

    Yuya Yoshida, Naoya Matsunaga, Takaharu Nakao, Kengo Hamamura, Hideaki Kondo, Tomomi Ide, Hiroyuki Tsutsui, Akito Tsuruta, Masayuki Kurogi, Michio Nakaya, Hitoshi Kurose, Satoru Koyanagi, Shigehiro Ohdo

    Nature Communications   12 ( 1 )   2783 - 2783   2021.12

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    Dysfunction of the circadian clock has been implicated in the pathogenesis of cardiovascular disease. The CLOCK protein is a core molecular component of the circadian oscillator, so that mice with a mutated Clock gene (Clk/Clk) exhibit abnormal rhythms in numerous physiological processes. However, here we report that chronic kidney disease (CKD)-induced cardiac inflammation and fibrosis are attenuated in Clk/Clk mice even though they have high blood pressure and increased serum angiotensin II levels. A search for the underlying cause of the attenuation of heart disorder in Clk/Clk mice with 5/6 nephrectomy (5/6Nx) led to identification of the monocytic expression of G protein-coupled receptor 68 (GPR68) as a risk factor of CKD-induced inflammation and fibrosis of heart. 5/6Nx induces the expression of GPR68 in circulating monocytes via altered CLOCK activation by increasing serum levels of retinol and its binding protein (RBP4). The high-GPR68-expressing monocytes have increased potential for producing inflammatory cytokines, and their cardiac infiltration under CKD conditions exacerbates inflammation and fibrosis of heart. Serum retinol and RBP4 levels in CKD patients are also sufficient to induce the expression of GPR68 in human monocytes. Our present study reveals an uncovered role of monocytic clock genes in CKD-induced heart failure.

    DOI: 10.1038/s41467-021-23050-x

  • Efficacy of Essential Oils in Pain: A Systematic Review and Meta-Analysis of Preclinical Evidence. Reviewed International journal

    Damiana Scuteri, Kengo Hamamura, Tsukasa Sakurada, Chizuko Watanabe, Shinobu Sakurada, Luigi Antonio Morrone, Laura Rombolà, Paolo Tonin, Giacinto Bagetta, Maria Tiziana Corasaniti

    Frontiers in pharmacology   12   640128 - 640128   2021.12

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    Background: The demand for essential oils (EOs) has been steadily growing over the years. This is mirrored by a substantial increase in research concerned with EOs also in the field of inflammatory and neuropathic pain. The purpose of this present systematic review and meta-analysis is to investigate the preclinical evidence in favor of the working hypothesis of the analgesic properties of EOs, elucidating whether there is a consistent rational basis for translation into clinical settings. Methods: A literature search has been conducted on databases relevant for medical scientific literature, i.e., PubMed/MEDLINE, Scopus, and Web of Science from database inception until November 2, 2020, following the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) criteria for systematic reviews and meta-analyses. Results: The search was conducted in order to answer the following PICOS (participants/population, interventions, comparisons, outcomes, and study design) question: are EOs efficacious in reducing acute nociceptive pain and/or neuropathic pain in mice experimental models? The search retrieved 2,491 records, leaving 954 studies to screen after the removal of duplicates. The title and abstract of all 954 studies were screened, which left 127 records to evaluate in full text. Of these, 30 articles were eligible for inclusion. Conclusion: Most studies (27) assessed the analgesic properties of EOs on acute nociceptive pain models, e.g. the acetic acid writhings test, the formalin test, and the hot plate test. Unfortunately, efficacy in neuropathic pain models, which are a more suitable model for human conditions of chronic pain, had fewer results (only three studies). Moreover, some methodologies raised concerns in terms of the risk of bias. Therefore, EOs with proven efficacy in both types of pain were corroborated by methodologically consistent studies, like the EO of bergamot, which should be studied in clinical trials to enhance the translational impact of preclinical modeling on clinical pain research.

    DOI: 10.3389/fphar.2021.640128

  • Discovery of a Highly Potent and Selective Degrader Targeting Hematopoietic Prostaglandin D Synthase via In Silico Design. Reviewed International journal

    Hidetomo Yokoo, Norihito Shibata, Akinori Endo, Takahito Ito, Yuta Yanase, Yuki Murakami, Kiyonaga Fujii, Kengo Hamamura, Yasushi Saeki, Mikihiko Naito, Kosuke Aritake, Yosuke Demizu

    Journal of medicinal chemistry   64 ( 21 )   15868 - 15882   2021.11

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    Targeted protein degradation by proteolysis-targeting chimera (PROTAC) is one of the exciting modalities for drug discovery and biological discovery. It is important to select an appropriate linker, an E3 ligase ligand, and a target protein ligand in the development; however, it is necessary to synthesize a large number of PROTACs through trial and error. Herein, using a docking simulation of the ternary complex of a hematopoietic prostaglandin D synthase (H-PGDS) degrader, H-PGDS, and cereblon, we have succeeded in developing PROTAC(H-PGDS)-7 (6), which showed potent and selective degradation activity (DC50 = 17.3 pM) and potent suppression of prostaglandin D2 production in KU812 cells. Additionally, in a Duchenne muscular dystrophy model using mdx mice with cardiac hypertrophy, compound 6 showed better inhibition of inflammatory cytokines than a potent H-PGDS inhibitor TFC-007. Thus, our results demonstrated that in silico simulation would be useful for the rational development of PROTACs.

    DOI: 10.1021/acs.jmedchem.1c01206

  • Exploitation of Thermal Sensitivity and Hyperalgesia in a Mouse Model of Dystonia. Reviewed International journal

    Damiana Scuteri, Laura Rombolà, Silvia Natoli, Antonio Pisani, Paola Bonsi, Kengo Hamamura, Giacinto Bagetta, Paolo Tonin, Maria Tiziana Corasaniti

    Life (Basel, Switzerland)   11 ( 9 )   2021.9

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    Neuropathic pain is characterized by mechanical allodynia and thermal hyperalgesia to heat, and it affects some 20% of European population. Patients suffering from several neurologic diseases experience neuropathic pain, often finding no relief in therapy. Transgenic mice expressing the gene encoding the human mutant (hMT) or the human wild-type (hWT) torsin A represent a preclinical model of DYT1 dystonia which is the most common form of early-onset inherited dystonia. Baseline thermal sensitivity and hyperalgesia to heat have never been studied in models of dystonia. Therefore, the aim of this research has been to characterize thermal sensitivity in baseline conditions and hyperalgesia to heat after the induction of neuropathic pain through the spinal nerve ligation (SNL) model in mice overexpressing human wild-type and mutated torsin A in comparison to non-transgenic C57BL/6 mice. According to our results, the paw withdrawal latency time to heat in the Hargreaves' test is significantly lower in the hMT mice (Kruskal-Wallis test = 6.933; p = 0.0312*; hMT vs. hWT p = 0.0317*). On the other hand, no significant differences in SNL-induced thermal hyperalgesia was found among the three strains (Friedman test = 4.933; p = 0.1019). Future studies are needed to better understand the role of torsin A in sensory processing of heat stimuli.

    DOI: 10.3390/life11090985

  • Development and Translation of NanoBEO, a Nanotechnology-Based Delivery System of Bergamot Essential Oil Deprived of Furocumarins, in the Control of Agitation in Severe Dementia. Reviewed International journal

    Damiana Scuteri, Roberta Cassano, Sonia Trombino, Rossella Russo, Hirokazu Mizoguchi, Chizuko Watanabe, Kengo Hamamura, Soh Katsuyama, Takaaki Komatsu, Luigi Antonio Morrone, Laura Rombolà, Annagrazia Adornetto, Annarita S Laganà, Maria Tiziana Corasaniti, Paolo Tonin, Shinobu Sakurada, Tsukasa Sakurada, Pierluigi Nicotera, Giacinto Bagetta

    Pharmaceutics   13 ( 3 )   2021.3

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    Dementia is one of the most common causes of disability worldwide characterized by memory loss, cognitive impairment, and behavioral and psychological symptoms (BPSD), including agitation. Treatment of the latter consists of the off-label use of harmful atypical antipsychotics, though a significant reduction is afforded by pain control. The use of an essential oil endowed with analgesic properties and devoid of toxicity would represent an important option for the management of agitation in dementia. Therefore, the aim of this study was to engineer a nanotechnology delivery system based on solid lipid nanoparticles loaded with bergamot essential oil (BEO) and devised in the pharmaceutical form of an odorless cream (NanoBEO) to confirm its analgesic efficacy for further development and application to control agitation in dementia. BEO has proven strong antinociceptive and anti-allodynic properties and, in its bergapten-free form, it is completely devoid of phototoxicity. NanoBEO has been studied in vivo confirming the previously reported analgesic activity of BEO to which is now added its anti-itching properties. Due to the nanotechnology delivery system, the stability of titrated BEO components is guaranteed. Finally, the latter invention, currently under patent consideration, is smell-devoid allowing efficacy and safety to be established in double-blind clinical trials; until now the latter studies have been impeded in aromatherapy by the strong odor of essential oils. A clinical trial NCT04321889 has been designed to provide information about the efficacy and safety of NanoBEO on agitation and pain in patients suffering from severe dementia.

    DOI: 10.3390/pharmaceutics13030379

  • プレガバリンOD錠「ニプロ」のマウス神経障害性疼痛モデルを用いた鎮痛効果の検討 Reviewed

    濵村賢吾, 瀬頭幸子, 野口由季, 廣瀬雅美, 藤尾信行, 藤川彩香, 柳田百合香, 有竹浩介

    新薬と臨牀   69 ( 12 )   1441 - 1450   2020.12

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    Analgesic Effects of PREGABALIN OD TABLETS “NIPRO” in a Mouse Model of Neuropathic Pain

  • Behavioral Effects of Continuously Administered Bergamot Essential Oil on Mice With Partial Sciatic Nerve Ligation. Reviewed International journal

    Kengo Hamamura, Soh Katsuyama, Takaaki Komatsu, Damiana Scuteri, Giacinto Bagetta, Kosuke Aritake, Tsukasa Sakurada

    Frontiers in pharmacology   11   1310 - 1310   2020.11

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    Neuropathic pain is an intractable chronic pain condition that is mainly caused by allodynia. We had previously reported that intra-plantar administration of bergamot essential oil (BEO) containing an aromatic compound significantly suppressed partial sciatic nerve ligation (PSNL)-induced mechanical allodynia via opioid mu receptors in mice. However, it has also been reported that the inhalation of BEO reduced formalin-induced nociceptive responses. Therefore, we aimed to elucidate whether the analgesic action of BEO is mediated by olfactory stimulation through volatile components. In the current study, BEO was continuously administered with an osmotic pump during PSNL surgery, and the effects on mice behavior were examined pharmacologically using a double activity monitoring system, which can detect two-dimensional planar motion in a cage with an infrared beam sensor as well as active motion with a running wheel. Here, we report that the two-dimensional planar activity significantly increased in mice with PSNL in the light phase (from 8 o'clock to 20 o'clock) but not in the dark phase (from 20 o'clock to 8 o'clock) from the second day after surgery. However, this increase was not observed when BEO was continuously administered. The effect of BEO on the two-dimensional planar counts in mice with PSNL was antagonized by naloxone hydrochloride. Regarding the running wheel activity, the number of rotations decreased by PSNL in the dark phase from the 8th day after surgery. However, this was not apparent with BEO use. The effect of BEO on the number of rotations was also antagonized by naloxone hydrochloride. Furthermore, inhalation of BEO in PSNL mice did not affect mechanical allodynia or the two-dimensional planar motion or running wheel activities. These findings indicate that BEO exhibits an analgesic action, which is mediated by opioid receptors and not by the olfactory system.

    DOI: 10.3389/fphar.2020.01310

  • Role of 5-HT1A Receptor in the Anxiolytic-Relaxant Effects of Bergamot Essential Oil in Rodent. Reviewed International journal

    Laura Rombolà, Damiana Scuteri, Chizuko Watanabe, Shinobu Sakurada, Kengo Hamamura, Tsukasa Sakurada, Paolo Tonin, Maria Tiziana Corasaniti, Giacinto Bagetta, Luigi Antonio Morrone

    International journal of molecular sciences   21 ( 7 )   2020.4

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    The essential oil obtained by the fresh fruit of Citrus bergamia Risso et Poiteau is used worldwide in aromatherapy to reduce pain, facilitate sleep induction, and/or minimize the effects of stress-induced anxiety. Preclinical pharmacological data demonstrate that bergamot essential oil (BEO) modulates specific neurotransmissions and shows an anxiolytic-relaxant effect not superimposable to that of the benzodiazepine diazepam, suggesting that neurotransmissions, other than GABAergic, could be involved. Several studies on essential oils indicate a role for serotonergic (5-HT) neurotransmission in anxiety. Interestingly, among serotonergic receptors, the 5-HT1A subtype seems to play a key role in the control of anxiety. Here, we report that modulation of the 5-HT1A receptor by selective agonist ((±)8-OH-DPAT) or antagonist (WAY-100635) may influence some of the anxiolytic-relaxant effects of BEO in Open Field and Elevated Plus Maze tests.

    DOI: 10.3390/ijms21072597

  • Circadian expression of Glycoprotein 2 (Gp2) gene is controlled by a molecular clock in mouse Peyer's patches. Reviewed International journal

    Naoki Kusunose, Akito Tsuruta, Kengo Hamamura, Yuya Tsurudome, Yuya Yoshida, Takahiro Akamine, Naoya Matsunaga, Satoru Koyanagi, Shigehiro Ohdo

    Genes to cells : devoted to molecular & cellular mechanisms   25 ( 4 )   270 - 278   2020.2

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    The expression levels of many cell-surface proteins vary with the time of day. Glycoprotein 2 (Gp2), specifically expressed on the apical surface of M cells in Peyer's patches, functions as a transcytotic receptor for mucosal antigens. We report that cAMP response element-binding protein (CREB) regulates the transcription of the Gp2 gene, thereby generating the circadian change in its expression in mouse Peyer's patches. The transcytotic receptor activity of Gp2 was increased during the dark phase when the Gp2 protein abundance increased. Rhythmic expression of clock gene mRNA was observed in mouse Peyer's patches, and expression levels of Gp2 mRNA also exhibited circadian oscillation, with peak levels during the early dark phase. The promoter region of the mouse Gp2 gene contains several cAMP response elements (CREs). Chromatin immunoprecipitation assays revealed that CREB bound to the CREs in the Gp2 gene in Peyer's patches. Forskolin, which promotes CREB phosphorylation, increased the transcription of the Gp2 gene in Peyer's patches. As phosphorylation of CREB protein was increased when Gp2 gene transcription was activated, CREB may regulate the rhythmic expression of Gp2 mRNA in Peyer's patches. These findings suggest that intestinal immunity is controlled by the circadian clock system.

    DOI: 10.1111/gtc.12758

  • Possible involvement of the peripheral Mu-opioid system in antinociception induced by bergamot essential oil to allodynia after peripheral nerve injury. Reviewed International journal

    Takaaki Komatsu, Soh Katsuyama, Yasuhito Uezono, Chikai Sakurada, Minoru Tsuzuki, Kengo Hamamura, Giacinto Bagetta, Shinobu Sakurada, Tsukasa Sakurada

    Neuroscience letters   686   127 - 132   2018.11

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    The essential oil of bergamot (BEO) is one of the most common essential oils and is most familiar to the general public. The aims of this study were to investigate the effect of intraplantar (i.pl.) BEO on neuropathic allodynia induced by partial sciatic nerve ligation (PSNL) in mice and the opioid receptor subtypes involved in the antiallodynic effects of BEO. Our findings showed that a single dose of i.pl. administration of BEO significantly inhibited the PSNL-induced neuropathic pain using the von Frey test. The i.pl pretreatment with naloxone methiodide, a peripherally acting μ-opioid receptor preferring antagonist, β-funaltrexamine hydrochloride (β-FNA), a selective μ-opioid receptor antagonist, and β-endorphin antiserum significantly reversed the antiallodynic effect of BEO in the von Frey test, but not by naltrindole, the nonselective δ-opioid receptor antagonist and nor-binaltorphimine, the selective κ-opioid receptor antagonist. Furthermore, in the western blotting analysis, i.pl. administration of BEO resulted in a significant blockage of spinal extracellular signal-regulated protein kinase (ERK) activation induced by PSNL. Naloxone methiodide and β-FNA significantly reversed the blockage of spinal ERK activation induced by BEO. These results suggest that i.pl. injection of BEO-induced antiallodynic effect and blockage of spinal ERK activation may be triggered by activation of peripheral μ-opioid receptors.

    DOI: 10.1016/j.neulet.2018.08.053

  • Angiotensin-II regulates dosing time-dependent intratumoral accumulation of macromolecular drug formulations via 24-h blood pressure rhythm in tumor-bearing mice Reviewed International journal

    Takashi Matsunaga, Naoya Matsunaga, Naoki Kusunose, Eriko Ikeda, Hiroyuki Okazaki, Keisuke Kakimoto, Kengo Hamamura, Satoru Koyanagi, Shigehiro Ohdo

    Biochemical and Biophysical Research Communications   498 ( 1 )   86 - 91   2018.3

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    One approach to increasing pharmacotherapy effects is administering drugs at times of day when they are most effective and/or best tolerated. Circadian variation in expression of pharmacokinetics- and pharmacodynamics-related genes was shown to contribute to dosing time-dependent differences in therapeutic effects of small molecule drugs. However, influence of dosing time of day on effects of high molecular weight formulations, such as drugs encapsulated in liposomes, has not been studied in detail. This study demonstrates that blood pressure rhythm affects dosing time-dependent variation in effects of high molecular weight formulations. Systolic blood pressure in sarcoma 180-bearing mice showed significant 24-h oscillation. Intratumoral accumulation of fluorescein isothiocyanate-labeled bovine serum albumin (FITC-BSA), an indicator of tumor vascular permeability, varied with dosing time of day, matching phases of blood pressure circadian rhythm. Furthermore, intratumoral accumulation of liposome-encapsulated oxaliplatin (Lipo-L-OHP) increased with increases in systolic blood pressure. Our findings suggest that circadian blood pressure oscillations may be an important factor to consider in dosing strategies for macromolecular drugs and liposomes in cancer therapy.

    DOI: 10.1016/j.bbrc.2017.11.162

  • Administering xCT Inhibitors Based on Circadian Clock Improves Antitumor Effects Reviewed International journal

    Fumiyasu Okazaki, Naoya Matsunaga, Kengo Hamamura, Kayoko Suzuki, Takaharu Nakao, Hiroyuki Okazaki, Masahiko Kutsukake, Shiro Fukumori, Yasuhiro Tsuji, Hideto To

    CANCER RESEARCH   77 ( 23 )   6603 - 6613   2017.12

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    Clock genes encoding transcription factors that regulate circadian rhythms may inform chronomodulated chemotherapy, where time-dependent dose alterations might affect drug efficacy and reduce side effects. For example, inhibiting the essential cystine transporter xCT with sulfasalazine induces growth arrest in cancer cells. Although the anticancer effects of sulfasalazine have been studied extensively, its effects on transcriptional control of xCT expression have not been studied. Here, we show that sulfasalazine administration during the period of increased xCT expression improves its anticancer effects and that the Clock gene itself induces xCT expression and regulates its circadian rhythm. Our findings highlight the clinical potential of chronomodulated chemotherapy and the importance of xCT-mediated transcriptional regulation in the utility of such strategies. (C) 2017 AACR.

    DOI: 10.1158/0008-5472.CAN-17-0720

  • The involvement of spinal release of histamine on nociceptive behaviors induced by intrathecally administered spermine Reviewed International journal

    Hirokazu Mizoguchi, Chizuko Watanabe, Takafumi Hayashi, Yoko Iwata, Hiroyuki Watanabe, Soh Katsuyama, Kengo Hamamura, Tsukasa Sakurada, Hiroshi Ohtsu, Kazuhiko Yanai, Shinobu Sakurada

    EUROPEAN JOURNAL OF PHARMACOLOGY   800   9 - 15   2017.4

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    The involvement of spinal release of histamine on nociceptive behaviors induced by spermine was examined in mice. Intrathecal spermine produced dose-dependent nociceptive behaviors, consisting of scratching, biting and licking. The nociceptive behaviors induced by spermine at 0.02 amol and 10 pmol were markedly suppressed by i.t. pretreatment with antiserum against histamine and were abolished in histidine decarboxylase-deficient mice. In histamine H-1 receptor-deficient mice, the nociceptive behaviors induced by spermine were completely abolished after treatment with 0.02 amol of spermine and significantly suppressed after treatment with 10 pmol of spermine. The i.t. pretreatment with takykinin NK1 receptor antagonists eliminated the nociceptive behaviors induced by 0.02 amol of spermine, but did not affect the nociceptive behaviors induced by 10 pmol of spermine. On the other hand, the nociceptive behaviors induced by spermine at both 0.02 amol and 10 pmol were suppressed by i.t. pretreatment with antagonists for the NMDA receptor polyamine-binding site. The present results suggest that the nociceptive behaviors induced by i.t. administration of spermine are mediated through the spinal release of histamine and are elicited via activation of NMDA receptors.

    DOI: 10.1016/j.ejphar.2017.01.031

  • Inhibition of G0/G1 Switch 2 Ameliorates Renal Inflammation in Chronic Kidney Disease Reviewed International journal

    Naoya Matsunaga, Eriko Ikeda, Keisuke Kakimoto, Miyako Watanabe, Naoya Shindo, Akito Tsuruta, Hisako Ikeyama, Kengo Hamamura, Kazuhiro Higashi, Tomohiro Yamashita, Hideaki Kondo, Yuya Yoshida, Masaki Matsuda, Takashi Ogino, Kazutaka Tokushige, Kazufumi Itcho, Yoko Furuichi, Takaharu Nakao, Kaori Yasuda, Atsushi Doi, Toshiaki Amamoto, Hironori Aramaki, Makoto Tsuda, Kazuhide Inoue, Akio Ojida, Satoru Koyanagi, Shigehiro Ohdo

    EBIOMEDICINE   13   262 - 273   2016.11

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    Chronic kidney disease (CKD) is a global health problem, and novel therapies to treat CKD are urgently needed. Here, we showthat inhibition of G(0)/G(1) switch 2 (G0s2) ameliorates renal inflammation in a mouse model of CKD. Renal expression of chemokine (C-C motif) ligand 2 (Ccl2) was increased in response to p65 activation in the kidneys of wild-type 5/6 nephrectomy (5/6Nx) mice. Moreover, 5/6Nx Clk/Clk mice, which carry homozygous mutations in the gene encoding circadian locomotor output cycles kaput (CLOCK), did not exhibit aggravation of apoptosis or induction of F4/80-positive cells. The renal expression of G0s2 in wild-type 5/6Nx mice was important for the transactivation of Ccl2 by p65. These pathologies were ameliorated by G0s2 knockdown. Furthermore, a novel small-molecule inhibitor of G0s2 expression was identified by high-throughput chemical screening, and the inhibitor suppressed renal inflammation in 5/6Nx mice. These findings indicated that G0s2 inhibitors may have applications in the treatment of CKD. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

    DOI: 10.1016/j.ebiom.2016.10.008

  • Alterations of Hepatic Metabolism in Chronic Kidney Disease via D-box-binding Protein Aggravate the Renal Dysfunction Reviewed International journal

    Kengo Hamamura, Naoya Matsunaga, Eriko Ikeda, Hideaki Kondo, Hisako Ikeyama, Kazutaka Tokushige, Kazufumi Itcho, Yoko Furuichi, Yuya Yoshida, Masaki Matsuda, Kaori Yasuda, Atsushi Doi, Yoshifumi Yokota, Toshiaki Amamoto, Hironori Aramaki, Yasuhiro Irino, Satoru Koyanagi, Shigehiro Ohdo

    JOURNAL OF BIOLOGICAL CHEMISTRY   291 ( 10 )   4913 - 4927   2016.3

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    Chronic kidney disease (CKD) is associated with an increase in serum retinol; however, the underlying mechanisms of this disorder are poorly characterized. Here, we found that the alteration of hepatic metabolism induced the accumulation of serum retinol in 5/6 nephrectomy (5/6Nx) mice. The liver is the major organ responsible for retinol metabolism; accordingly, microarray analysis revealed that the hepatic expression of most CYP genes was changed in 5/6Nx mice. In addition, D-box-binding protein (DBP), which controls the expression of several CYP genes, was significantly decreased in these mice. Cyp3a11 and Cyp26a1, encoding key proteins in retinol metabolism, showed the greatest decrease in expression in 5/6Nx mice, a process mediated by the decreased expression of DBP. Furthermore, an increase of plasma transforming growth factor-1 (TGF-1) in 5/6Nx mice led to the decreased expression of the Dbp gene. Consistent with these findings, the alterations of retinol metabolism and renal dysfunction in 5/6Nx mice were ameliorated by administration of an anti-TGF-1 antibody. We also show that the accumulation of serum retinol induced renal apoptosis in 5/6Nx mice fed a normal diet, whereas renal dysfunction was reduced in mice fed a retinol-free diet. These findings indicate that constitutive Dbp expression plays an important role in mediating hepatic dysfunction under CKD. Thus, the aggravation of renal dysfunction in patients with CKD might be prevented by a recovery of hepatic function, potentially through therapies targeting DBP and retinol.

    DOI: 10.1074/jbc.M115.696930

  • Circadian Clock in a Mouse Colon Tumor Regulates Intracellular Iron Levels to Promote Tumor Progression Reviewed International journal

    Fumiyasu Okazaki, Naoya Matsunaga, Hiroyuki Okazaki, Hiroki Azuma, Kengo Hamamura, Akito Tsuruta, Yuya Tsurudome, Takashi Ogino, Yukinori Hara, Takuya Suzuki, Kenji Hyodo, Hiroshi Ishihara, Hiroshi Kikuchi, Hideto To, Hironori Aramaki, Satoru Koyanagi, Shigehiro Ohdo

    JOURNAL OF BIOLOGICAL CHEMISTRY   291 ( 13 )   7017 - 7028   2016.3

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    Iron is an important biological catalyst and is critical for DNA synthesis during cell proliferation. Cellular iron uptake is enhanced in tumor cells to support increased DNA synthesis. Circadian variations in DNA synthesis and proliferation have been identified in tumor cells, but their relationship with intracellular iron levels is unclear. In this study, we identified a 24-h rhythm in iron regulatory protein 2 (IRP2) levels in colon-26 tumors implanted in mice. Our findings suggest that IRP2 regulates the 24-h rhythm of transferrin receptor 1 (Tfr1) mRNA expression post-transcriptionally, by binding to RNA stem-loop structures known as iron-response elements. We also found that Irp2 mRNA transcription is promoted by circadian clock genes, including brain and muscle Arnt-like 1 (BMAL1) and the circadian locomotor output cycles kaput (CLOCK) heterodimer. Moreover, growth in colon-26(19) tumors expressing the clock-mutant protein (CLOCK19) was low compared with that in wild-type colon-26 tumor. The time-dependent variation of cellular iron levels, and the proliferation rate in wild-type colon-26 tumor was decreased by CLOCK19 expression. Our findings suggest that circadian organization contributes to tumor cell proliferation by regulating iron metabolism in the tumor.

    DOI: 10.1074/jbc.M115.713412

  • Mitomycin C modulates the circadian oscillation of clock gene period 2 expression through attenuating the glucocorticoid signaling in mouse fibroblasts Reviewed International journal

    Naoki Kusunose, Naoya Matsunaga, Kenichi Kimoto, Takahiro Akamine, Kengo Hamamura, Satoru Koyanagi, Shigehiro Ohdo, Toshiaki Kubota

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   467 ( 1 )   157 - 163   2015.11

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    Clock gene regulates the circadian rhythm of various physiological functions. The expression of clock gene has been shown to be attenuated by certain drugs, resulting in a rhythm disorder. Mitomycin C (MMC) is often used in combination with ophthalmic surgery, especially in trabeculectomy, a glaucoma surgical procedure. The purpose of this study was to investigate the influence of MMC on clock gene expression in fibroblasts, the target cells of MMC. Following MMC treatment, Bmal1 mRNA levels was significantly decreased, whereas Dbp, Per1, and Rev-erb zeta mRNA levels were significantly increased in the mouse fibroblast cell line NIH3T3 cells. Microarray analysis was performed to explore of the gene(s) responsible for MMC-induced alteration of clock gene expression, and identified Nr3c1 gene encoding glucocorticoid receptor (GR) as a candidate. MMC suppressed the induction of Per1 mRNA by dexamethasone (DEX), ligand of GR, in NIH3T3 cells. MMC also modulated the DEX-driven circadian oscillations of Per2::Luciferase bioluminescence in mouse-derived ocular fibroblasts. Our results demonstrate a previously unknown effect of MMC in GR signaling and the circadian clock system. The present findings suggest that MMC combined with trabeculectomy could increase the risk for a local circadian rhythmdisorder at the ocular surface. (C) 2015 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.bbrc.2015.09.086

  • 24-Hour Rhythm of Aquaporin-3 Function in the Epidermis Is Regulated by Molecular Clocks Reviewed International journal

    Naoya Matsunaga, Kazufumi Itcho, Kengo Hamamura, Eriko Ikeda, Hisako Ikeyama, Yoko Furuichi, Miyako Watanabe, Satoru Koyanagi, Shigehiro Ohdo

    JOURNAL OF INVESTIGATIVE DERMATOLOGY   134 ( 6 )   1636 - 1644   2014.6

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    Language:English   Publishing type:Research paper (scientific journal)  

    Aquaporin 3 (AQP3) is located in the basal layer of the epidermis and regulates biological functions of skin such as water content and trans-epidermal water loss. A recent study showed that the biological function of skin exhibits a 24-hour rhythm, but the molecular mechanism of the variation remains poorly understood. Here we show that mice mutated in the core clock component CLOCK (Clk/Clk) show decreased stratum corneum hydration. An extensive search for the underlying cause led us to identify AQP3 as a new regulator to control the 24-hour variation in biological functions of skin. In mouse epidermis of wild-type mice, mAqp3 exhibits circadian rhythms; however, these are significantly decreased in Clk/Clk. Luciferase reporter gene analysis revealed that transcription of mAqp3 is activated by D-site-binding protein, a clock gene. A human homolog, hAQP3, also exhibited significant oscillation in human keratinocyte (HaCaT) cells synchronized with medium containing 50% serum, and this rhythm was regulated by the endogenous CLOCK/BMAL1 heterodimer. These data indicate that although the molecular mechanisms underlying the rhythmic expression of mAqp3 and hAQP3 are different, clock genes are involved in time-dependent skin hydration. Our current findings provide a molecular link between the circadian clock and AQP3 function in mouse dorsal skin and HaCaT cells.

    DOI: 10.1038/jid.2014.13

  • Molecular Mechanism Regulating 24-Hour Rhythm of Dopamine D3 Receptor Expression in Mouse Ventral Striatums Reviewed International journal

    Eriko Ikeda, Naoya Matsunaga, Keisuke Kakimoto, Kengo Hamamura, Akane Hayashi, Satoru Koyanagi, Shigehiro Ohdo

    MOLECULAR PHARMACOLOGY   83 ( 5 )   959 - 967   2013.5

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    The dopamine D3 receptor (DRD3) in the ventral striatum is thought to influence motivation and motor functions. Although the expression of DRD3 in the ventral striatum has been shown to exhibit 24-hour variations, the mechanisms underlying the variation remain obscure. Here, we demonstrated that molecular components of the circadian clock act as regulators that control the 24-hour variation in the expression of DRD3. The transcription of DRD3 was enhanced by the retinoic acid-related orphan receptor alpha (ROR alpha), and its activation was inhibited by the orphan receptor REV-ERB alpha, an endogenous antagonist of ROR alpha. The serum or dexamethasone-induced oscillation in the expression of DRD3 in cells was abrogated by the downregulation or overexpression of REV-ERB alpha, suggesting that REV-ERB alpha functions as a regulator of DRD3 oscillations in the cellular autonomous clock. Chromatin immunoprecipitation assays of the DRD3 promoter indicated that the binding of the REV-ERB alpha protein to the DRD3 promoter increased in the early dark phase. DRD3 protein expression varied with higher levels during the dark phase. Moreover, the effects of the DRD3 agonist 7-hydroxy-N, N-dipropyl-2-aminotetralin (7-OH-DPAT)-induced locomotor hypoactivity were significantly increased when DRD3 proteins were abundant. These results suggest that ROR alpha and REV-ERB alpha consist of a reciprocating mechanism wherein ROR alpha upregulates the expression of DRD3, whereas REV-ERB alpha periodically suppresses the expression at the time of day when REV-ERB alpha is abundant. Our present findings revealed that a molecular link between the circadian clock and the function of DRD3 in the ventral striatum acts as a modulator of the pharmacological actions of DRD3 agonists/antagonists.

    DOI: 10.1124/mol.112.083535

  • Time-dependent interaction between differentiated embryo chondrocyte-2 and CCAAT/enhancer-binding protein α underlies the circadian expression of CYP2D6 in serum-shocked HepG2 cells. Reviewed International journal

    Matsunaga N, Inoue M, Kusunose N, Kakimoto K, Hamamura K, Hanada Y, Toi A, Yoshiyama Y, Sato F, Fujimoto K, Koyanagi S, Ohdo S

    Molecular pharmacology   81 ( 5 )   739 - 747   2012.5

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    Time-Dependent Interaction between Differentiated Embryo Chondrocyte-2 and CCAAT/Enhancer-Binding Protein alpha Underlies the Circadian Expression of CYP2D6 in Serum-Shocked HepG2 Cells
    Differentiated embryo chondrocyte-2 (DEC2), also known as bHLHE41 or Sharp1, is a pleiotropic transcription repressor that controls the expression of genes involved in cellular differentiation, hypoxia responses, apoptosis, and circadian rhythm regulation. Although a previous study demonstrated that DEC2 participates in the circadian control of hepatic metabolism by regulating the expression of cytochrome P450, the molecular mechanism is not fully understood. We reported previously that brief exposure of HepG2 cells to 50% serum resulted in 24-h oscillation in the expression of CYP3A4 as well as circadian clock genes. In this study, we found that the expression of CYP2D6, a major drug-metabolizing enzyme in humans, also exhibited a significant oscillation in serum-shocked HepG2 cells. DEC2 interacted with CCAAT/enhancer-binding protein (C/EBP alpha), accompanied by formation of a complex with histone deacetylase-1, which suppressed the transcriptional activity of C/EBP alpha to induce the expression of CYP2D6. The oscillation in the protein levels of DEC2 in serum-shocked HepG2 cells was nearly antiphase to that in the mRNA levels of CYP2D6. Transfection of cells with small interfering RNA against DEC2 decreased the amplitude of CYP2D6 mRNA oscillation in serum-shocked cells. These results suggest that DEC2 periodically represses the promoter activity of CYP2D6, resulting in its circadian expression in serum-shocked cells. DEC2 seems to constitute a molecular link through which output components from the circadian clock are associated with the time-dependent expression of hepatic drug-metabolizing enzyme.

    DOI: 10.1124/mol.111.076406

  • Molecular basis for the dosing time-dependency of anti-allodynic effects of gabapentin in a mouse model of neuropathic pain Reviewed International journal

    Naoki Kusunose, Satoru Koyanagi, Kengo Hamamura, Naoya Matsunaga, Miyako Yoshida, Takahiro Uchida, Makoto Tsuda, Kazuhide Inoue, Shigehiro Ohdo

    MOLECULAR PAIN   6   83 - 83   2010.11

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    Background: Neuropathic pain is characterized by hypersensitivity to innocuous stimuli (tactile allodynia) that is nearly always resistant to NSAIDs or even opioids. Gabapentin, a GABA analogue, was originally developed to treat epilepsy. Accumulating clinical evidence supports the effectiveness of this drug for diverse neuropathic pain. In this study, we showed that the anti-allodynic effect of gabapentin was changed by the circadian oscillation in the expression of its target molecule, the calcium channel alpha 2 delta-1 subunit.
    Results: Mice were underwent partial sciatic nerve ligation (PSL) to create a model of neuropathic pain. The paw withdrawal threshold (PWT) in PSL mice significantly decreased and fluctuated with a period length about 24 h. The PWT in PSL mice was dose-dependently increased by intraperitoneal injection of gabapentin, but the antiallodynic effects varied according to its dosing time. The protein levels of alpha 2 delta-1 subunit were up-regulated in the DRG of PSL mice, but the protein levels oscillated in a circadian time-dependent manner. The time-dependent oscillation of alpha 2 delta-1 subunit protein correlated with fluctuations in the maximal binding capacity of gabapentin. The anti-allodynic effect of gabapentin was attenuated at the times of the day when alpha 2 delta-1 subunit protein was abundant.
    Conclusions: These findings suggest that the dosing time-dependent difference in the anti-allodynic effects of gabapentin is attributable to the circadian oscillation of alpha 2 delta-1 subunit expression in the DRG and indicate that the optimizing its dosing schedule helps to achieve rational pharmacotherapy for neuropathic pain.

    DOI: 10.1186/1744-8069-6-83

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Books

  • コンパス薬理学 改訂第3版. 南江堂, 2023.

    編集/櫻田司/木皿重樹. 分担執筆/濵村 賢吾 他 (計16名).(Role:Joint author)

    2023.11 

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    Language:Japanese   Book type:Scholarly book

  • コンパス薬理学 改訂第2版. 南江堂, 2017.

    編集/櫻田 司, 分担執筆/濵村 賢吾 他 (計10名).(Role:Joint author)

    2017.6 

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    Language:Japanese   Book type:Scholarly book

  • 体内時計分子機構と外的要因が耐糖能日周リズムを形成する. 公益社団法人 日本薬学会 学会誌 「ファルマシア」, 2013.

    濵村 賢吾

    2015.12 

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    Language:Japanese  

Presentations

  • Identification of the Tissue Producing Increased Complement C5 on the Extracellular Vesicle Bilayer Membrane in Mice Serum with Partial Sciatic Nerve Ligation International conference

    濵村 賢吾、李 君豪、河野 慎平、吉田 優哉、松永 直哉、櫻田 司、有竹 浩介

    Japan-Italy Joint Meeting 2024  2024.5 

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    Event date: 2024.5

    Language:English  

    Country:Japan  

  • GPR68を標的とした慢性腎臓病誘発性の心炎症・線維化抑制化合物の探索

    吉田 優哉、佐久川 未有、福岡 航平、外野 来海、谷原 智仁、西川 直希、鶴田 朗人、小山 浩舗、濵村 賢吾、小柳 悟、松永 直哉、大戸 茂弘

    第44回日本臨床薬理学会学術総会/第97回日本薬理学会年会  2023.12 

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    Language:Japanese  

    Country:Japan  

  • 微弱電流刺激がマクロファージ貪食能に及ぼす影響の解析

    鶴崎 文彬、吉田 優哉、濵崎 景佳、谷原 智仁、橋本 優希、福田 大輝、鶴田 朗人、小山 浩舗、濵村 賢吾、小柳 悟、松永 直哉、大戸 茂弘

    第44回日本臨床薬理学会学術総会/第97回日本薬理学会年会  2023.12 

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    Event date: 2023.12

    Language:Japanese  

    Country:Japan  

  • GPR68を標的とした慢性腎臓病誘発性の心炎症・線維化抑制化合物の探索

    佐久川 未有、吉田 優哉、福岡 航平、鶴崎 文彬、西 拓海、小山 浩舗、濵村 賢吾、小柳 悟、松永 直哉、大戸 茂弘

    第96回日本生化学会大会  2023.10 

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    Language:Japanese  

    Country:Japan  

  • 抗体医薬品中で最も不安定なCH2ドメインの安定化による凝集の抑制

    小山 浩舗、カアベイロ ホセ、松永 直哉、濵村 賢吾、吉田 優哉、大戸 茂弘、植田 正

    第96回日本生化学会大会  2023.10 

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    Language:Japanese  

    Country:Japan  

  • ヒト膵臓がんのがん幹細胞における時計遺伝子の機能解析

    財津 織音、吉田 優哉、松尾 沙紀、小山 浩舗、濵村 賢吾、松永 直哉

    第96回日本生化学会大会  2023.10 

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    Language:Japanese  

    Country:Japan  

  • 慢性腎臓病による認知機能障害を改善する治療薬の探索

    熊本 大誠、西 拓海、吉田 優哉、北川 陽也、小山 浩舗、濵村 賢吾、大戸 茂弘、松永 直哉

    第96回日本生化学会大会  2023.10 

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    Event date: 2023.10

    Language:Japanese  

    Country:Japan  

  • マクロファージおよび概日時計機構に着目したバンコマイシン性腎障害の発症機構解析

    福田 大輝、吉田 優哉、谷原 智仁、西川 直希、福岡 航平、小山 浩舗、濵村 賢吾、小柳 悟、松永 直哉、大戸 茂弘

    第96回日本生化学会大会  2023.10 

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    Language:Japanese  

    Country:Japan  

  • CKD病態時の小腸リンパ組織におけるCKD関連物質の蓄積がALDH高発現樹状細胞に及ぼす影響の解析

    吉田 優哉、福岡 航平、濵村 賢吾、小柳 悟、松永 直哉、大戸 茂弘

    第96回日本生化学会大会  2023.10 

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    Event date: 2023.10

    Language:Japanese  

    Country:Japan  

  • 微弱電流刺激が時計遺伝子Period1の発現および生理機能の概日リズムに及ぼす影響の解析

    谷原 智仁、橋本 優希、鶴田 朗人、小山 浩舗、濵村 賢吾、小柳 悟、松永 直哉、大戸 茂弘

    第30回 日本時間生物学会学術大会  2023.9 

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    Event date: 2023.9

    Language:Japanese  

    Country:Japan  

  • マクロファージの概日時計機構を標的とした微弱電流刺激によるがん免疫亢進法の開発

    鶴崎 文彬、吉田 優哉、濵崎 景佳、谷原 智仁、橋本 優希、福田 大輝、鶴田 朗人、小山 浩舗、濵村 賢吾、小柳 悟、松永 直哉、大戸 茂弘

    第30回 日本時間生物学会学術大会  2023.9 

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    Event date: 2023.9

    Language:Japanese  

    Country:Japan  

  • デュシェンヌ型筋ジストロフィー患者心臓における造血器型プロスタグランジンD合成酵素の発現解析

    濵村 賢吾、井上 貴美子、豊岡 圭子、山寺 みさき、有竹 浩介、松村 剛

    第9回日本筋学会学術集会/第10回筋ジストロフィー医療研究会  2023.8 

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    Event date: 2023.8

    Language:Japanese  

    Country:Japan  

  • Novel enhancement mechanisms of the nociceptive response by serum exosomes in a mouse model of neuropathic pain International conference

    濵村 賢吾、櫻田 司、有竹 浩介

    Dementia Therapeutics and Cognitive Rehabilitation  2022.11 

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    Event date: 2022.11

    Language:English  

    Country:Italy  

  • Identification of the site of production of complement C5, which is upregulated on exosomal bilayers from serum of mice with partial sciatic nerve ligation

    濵村 賢吾、切通 雅哉、山川 満里奈、有竹 浩介

    第95回日本薬理学会年会  2022.3 

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    Event date: 2022.3

    Language:Japanese  

    Country:Japan  

  • Specific degrader of hematopoietic prostaglandin D synthase prevented the progression of dilated cardiomyopathy in Duchenne muscular dystrophy

    有竹 浩介、前山 優真、細川 由家子、濵村 賢吾、横尾 英知、柴田 識人、出水 庸介、内藤 幹彦

    第95回日本薬理学会年会  2022.3 

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    Event date: 2022.3

    Language:Japanese  

    Country:Japan  

  • 単球に着目した慢性腎臓病時における心臓病態悪化の新規メカニズム解明

    吉田 優哉、松永 直哉、濵村 賢吾、鶴田 朗人、小柳 悟、大戸 茂弘

    医療薬学フォーラム2021/第29回クリニカルファーマシーシンポジウム  2021.7 

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    Event date: 2021.7

    Language:Japanese  

    Country:Japan  

  • 坐骨神経部分結紮マウス血清由来のエクソソームに着目した、低濃度ホルマリン誘発性侵害刺激行動の増強作用機序解明

    池田 康一郎、濵村 賢吾、古賀 真理子、三ヶ尻 幸平、勝山 壮、小松 生明、櫻田 司、有竹 浩介

    第41回日本臨床薬理学会学術総会  2020.12 

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    Event date: 2020.12

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    Country:Japan  

  • 坐骨神経部分結紮マウスにおけるBergamot Essential Oil (BEO) の持続皮下投与による抗アロディニア作用の行動薬理学的解析

    古賀 真理子、濵村 賢吾、池田 康一郎、三ヶ尻 幸平、勝山 壮、小松 生明、櫻田 司、有竹 浩介

    第41回日本臨床薬理学会学術総会  2020.12 

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    Event date: 2020.12

    Language:Japanese  

    Country:Japan  

  • 神経障害性疼痛モデルマウスの血清による低濃度ホルマリン誘発侵害刺激行動の増強に、エクソソームは重要な因子である

    廣瀬 雅美、濵村 賢吾、吉岡 秀哲、勝山 壮、小松 生明、櫻田 司、有竹 浩介

    第72回日本薬理学会西南部会  2019.11 

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    Event date: 2019.11

    Language:Japanese  

    Country:Japan  

  • プロスタグランジン (PG) D2情報伝達抑制によるDuchenne型筋ジストロフィー性心筋症害の進行抑制

    坂口 貴章、進藤 夢加、俣野 祥子、濵村 賢吾、有竹 浩介

    第72回日本薬理学会西南部会  2019.11 

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    Country:Japan  

  • Behavioural effects of continuously administered Bergamot Essential Oil (BEO) in mice with partial sciatic nerve ligation International conference

    濵村 賢吾、勝山 壮、小松 生明、有竹 浩介、Baggeta Giacinto、櫻田 司

    Novel Pain Therapeutics: From Basic Research to Clinical Translation and Rehabilitation  2019.10 

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    Event date: 2019.10

    Language:English  

    Country:Italy  

  • Novel aggravation mechanism of heart failure mediated by monocytes in chronic kidney disease mice

    吉田 優哉、松永 直哉、濵村 賢吾、鶴田 朗人、小柳 悟、大戸 茂弘

    第13回次世代を担う若手医療薬科学シンポジウム  2019.10 

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  • Formalin-induced nociceptive response is enhanced by serum exosomes isolated from partial sciatic nerve ligation (PSL) mice International conference

    濵村 賢吾、勝山 壮、小松 生明、櫻田 司、有竹 浩介

    Neuroscience 2019  2019.10 

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    Event date: 2019.10

    Language:English  

  • 神経障害性疼痛モデルマウスの血清中エクソソームは低濃度ホルマリン誘発侵害刺激行動を増強する

    濵村 賢吾、勝山 壮、小松 生明、櫻田 司、有竹 浩介

    第92回日本薬理学会年会  2019.3 

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    Event date: 2019.3

    Language:Japanese  

    Country:Japan  

  • プロスタグランジンD2情報伝達制御による筋ジストロフィー性心筋障害の進行抑制

    有竹 浩介、濵村 賢吾、俣野 祥子、進藤 夢加、永田 奈々恵、岩田 裕子、裏出 良博

    第92回日本薬理学会年会  2019.3 

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    Country:Japan  

  • マウス血清由来のエクソソームに着目した低濃度ホルマリン誘発性侵害刺激行動の増強作用機序解明

    濵村 賢吾、勝山 壮、小松 生明、櫻田 司、有竹 浩介

    第17回次世代を担う若手ファーマ・バイオフォーラム2018  2018.9 

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    Country:Japan  

  • Novel enhancement mechanisms of the nociceptive response by serum exosomes in a mouse model of neuropathic pain International conference

    濵村 賢吾、勝山 壮、豊福 洋平、渡辺 駿平、西村 友里、居石 奈菜美、田中 大晴、小松 生明、櫻田 司、有竹 浩介

    WCP2018  2018.7 

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    Event date: 2018.7

    Language:English  

    Country:Japan  

  • マウス血清由来のエクソソームに着目した低濃度ホルマリン誘発性侵害刺激行動の増強作用機序解明

    濵村 賢吾、勝山 壮、小松 生明、櫻田 司、有竹 浩介

    第13回トランスポーター研究会年会  2018.7 

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    Language:Japanese  

    Country:Japan  

  • Inhibition of prostaglandin D2 signaling prevents the progression of dilated cardiomyopathy in Duchenne muscular dystrophy International conference

    有竹 浩介、濵村 賢吾、進藤 夢加、俣野 祥子、永田 奈々恵、岩田 裕子、裏出 良博

    WCP2018  2018.7 

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    Event date: 2018.7

    Language:English  

    Country:Japan  

  • 神経障害性疼痛モデルマウスにおけるBergamot Essential Oil (BEO) の持続皮下投与による抗アロディニア作用の行動薬理学的解析

    藤川 彩香、濵村 賢吾、勝山 壮、中野 真由佳、瀬頭 幸子、野口 由季、藤尾 信行、柳田 百合香、小松 生明、有竹 浩介、櫻田 司

    第12回日本緩和医療薬学会  2018.5 

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    Language:Japanese  

    Country:Japan  

  • 香気性化合物を含む精油であるBergamot Essential Oil (BEO) の吸入投与が神経障害性疼痛モデルマウスのアロディニアに与える影響

    藤尾 信行、濵村 賢吾、勝山 壮、中野 真由佳、瀬頭 幸子、野口 由季、藤川 彩香、柳田 百合香、小松 生明、有竹 浩介、櫻田 司

    第12回日本緩和医療薬学会  2018.5 

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    Country:Japan  

  • シノメニンの抗侵害作用メカニズムの解明

    岡村 健正、勝山 壮、櫻田 誓、高野 文秀、田畠 健治、濵村 賢吾、小川 鶴洋、小松 生明、櫻田 司

    第34回日本薬学会九州支部大会  2017.12 

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    Event date: 2017.12

    Language:Japanese  

    Country:Japan  

  • Bergamot Essential Oil (BEO) の持続皮下投与による神経障害性疼痛モデルマウスの行動薬理学的解析

    濵村 賢吾、勝山 壮、有竹 浩介、小松 生明、櫻田 司

    第70回日本薬理学会西南部会  2017.11 

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    Language:Japanese  

    Country:Japan  

  • 慢性腎臓病時の炎症概日リズムに基づく新規治療薬の開発

    松永 直哉、鶴田 朗人、吉田 優哉、中尾 崇治、高露 恵理子、濵村 賢吾、渡邉 美弥子、近藤 英明、小柳 悟、大戸 茂弘

    第11回日本腎臓病薬物療法学会学術集会  2017.10 

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    Event date: 2017.10

    Language:Japanese  

    Country:Japan  

  • 慢性腎臓病モデルマウスにおける分子時計を介した腎‐肝‐腎連関機構の解明

    中尾 崇治、松永 直哉、吉田 優哉、鶴田 朗人、濵村 賢吾、近藤 英明、小柳 悟、大戸 茂弘

    第11回日本腎臓病薬物療法学会学術集会  2017.10 

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    Event date: 2017.10

    Language:Japanese  

    Country:Japan  

  • 防已黄耆湯とその有効成分シノメニンの抗侵害作用メカニズムの解明

    岡村 健正、小松 生明、濵村 賢吾、森永 紀、小川 鶴洋、櫻田 誓、高野 文秀、勝山 壮、林 貴史、櫻田 司

    第34回和漢医薬学会学術大会  2017.8 

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    Event date: 2017.8

    Language:Japanese  

    Country:Japan  

  • 神経障害性疼痛モデルマウス誘発性アロディニアにおけるBergamot Essential Oil (BEO) の持続皮下投与による影響

    田中 あかね、濵村 賢吾、勝山 壮、橋本 和人、下川 杏南、有竹 浩介、小松 生明、櫻田 司

    医療薬学フォーラム2017/第25回クリニカルファーマシーシンポジウム  2017.7 

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    Event date: 2017.7

    Language:Japanese  

    Country:Japan  

  • 防已黄耆湯の末梢性抗侵害刺激作用機構における内因性オピオイドの役割

    岡村 健正、小松 生明、濵村 賢吾、櫻田 誓、高野 文秀、勝山 壮、林 貴史、窪田 篤人、櫻田 司

    第11回日本緩和医療薬学会年会  2017.6 

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    Event date: 2017.6

    Language:Japanese  

    Country:Japan  

  • Serum exosomes in a mouse model of neuropathic pain enhance the formalin-induced nociceptive response International conference

    濵村 賢吾、楠瀬 直喜、 勝山 壮、小松 生明、櫻田 司

    IASP, 16th World congress on pain  2016.9 

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    Event date: 2016.9

    Language:English  

    Country:Japan  

  • 神経障害性モデルマウスの血清中エクソソームは低濃度ホルマリン誘発侵害刺激行動を増強する

    濵村 賢吾、楠瀬 直喜、 勝山 壮、小松 生明、櫻田 司

    第36回鎮痛薬・オピオイドペプチドシンポジウム  2016.8 

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    Event date: 2016.8

    Language:Japanese  

    Country:Japan  

  • 神経障害性モデルマウスの血清中エクソソームは低濃度ホルマリン誘発侵害刺激行動を増強する

    居石 奈菜美、濵村 賢吾、楠瀬 直喜、勝山 壮、西村 友里、古川 翔太、田中 大晴、力久 諒派、荒牧 弘範、小松 生明、櫻田 司

    第24回クリニカルファーマシーシンポジウム/医療薬学フォーラム2016  2016.6 

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    Event date: 2016.6

    Language:Japanese  

    Country:Japan  

  • 慢性腎臓病モデルマウスにおける分子時計機構の腎-肝-腎連関を介した新規腎機能悪化機序の解明

    濵村 賢吾、松永 直哉、池田 恵理子、近藤 英明、池山 久子、徳重 和孝、古市 葉子、吉田 優哉、松田 将希、荒牧 弘範、小柳 悟、大戸 茂弘

    第23回クリニカルファーマシーシンポジウム/医療薬学フォーラム2015  2015.7 

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    Event date: 2015.7

    Language:Japanese  

    Country:Japan  

  • 分子時計機構を基盤とした腎不全進展メカニズム

    松永 直哉、池田 恵理子、濵村 賢吾、近藤 英明、池山 久子、徳重 和孝、古市 葉子、松田 将希、荒牧 弘範、小柳 悟、大戸 茂弘

    日本薬剤学会第30年会  2015.5 

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    Event date: 2015.5

    Language:Japanese  

    Country:Japan  

  • 慢性腎不全モデルマウスにおける肝代謝酵素発現日内変動変容機構の解明

    濵村 賢吾、松永 直哉、池田恵理子、古市 葉子、吉田 優哉、松田 将希、小柳 悟、大戸 茂弘

    第21回日本時間生物学会学術大会  2014.11 

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    Event date: 2014.11

    Language:Japanese  

    Country:Japan  

  • 慢性腎臓病モデルマウスにおける分子時計機構の腎-肝-腎連関を介した新規腎機能悪化機序の解明

    濵村 賢吾、松永 直哉、池田恵理子、古市 葉子、吉田 優哉、松田 将希、小柳 悟、大戸 茂弘

    第8回次世代を担う若手医療薬科学シンポジウム  2014.11 

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    Event date: 2014.11

    Language:Japanese  

    Country:Japan  

  • 分子時計機構を基盤とした慢性腎不全の新規治療標的分子の探索

    松永 直哉、池田 恵理子、濵村 賢吾、近藤 英明、一町 和史、池山 久子、徳重 和孝、古市 葉子、吉田 優哉、小柳 悟、大戸 茂弘

    第24回日本医療薬学会年会  2014.9 

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    Event date: 2014.9

    Language:Japanese  

    Country:Japan  

  • 皮膚の分子時計を基盤としたアクアポリン3 発現の日周リズム制御機構

    松永 直哉、一町 和史、濵村 賢吾、池田 恵理子、小柳 悟、大戸 茂弘

    医療薬学フォーラム2014/第22回クリニカルファーマシーシンポジウム  2014.6 

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    Event date: 2014.6

    Language:Japanese  

    Country:Japan  

  • Molecular basis for rhythmic expression of cytochromes P450 (CYPs) in serum-shocked HepG2 cells

    柿本 啓輔、 松永 直哉、 滝口 貴子、 井上 美季、 楠瀬 直喜、 濵村 賢吾、 小柳 悟、 大戸 茂弘

    第86回日本薬理学会年会  2013.3 

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    Event date: 2013.3

    Language:Japanese  

    Country:Japan  

  • MOLECULAR MECHANISM REGULATING 24-HOUR RHYTHM OF DOPAMINE RECEPTOR D3 EXPRESSION IN MOUSE STRIATUM

    池田 恵理子、 松永 直哉、 柿本 啓輔、 濵村 賢吾、 岡崎 裕之、 小柳 悟、 大戸 茂弘

    第6回次世代を担う若手医療薬科学シンポジウム  2012.11 

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    Event date: 2012.11

    Language:Japanese  

    Country:Japan  

  • MOLECULAR BASIS FOR RHYTHMIC EXPRESSION OF CYTOCHROMES P450 (CYPS) IN SERUM-SHOCKED HEPG2 CELLS

    柿本 啓輔、 松永 直哉、 滝口 貴子、 井上 美季、 楠瀬 直喜、 濵村 賢吾、 小柳 悟、 大戸 茂弘

    第6回次世代を担う若手医療薬科学シンポジウム  2012.11 

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    Event date: 2012.11

    Language:Japanese  

    Country:Japan  

  • ヒト培養肝細胞における薬物動態関連因子の発現リズム制御機構の解析

    松永 直哉、 滝口 貴子、 井上 美季、 楠瀬 直喜、 柿本 啓輔、 濵村 賢吾、 小柳 悟、 大戸 茂弘

    日本薬剤学会第27年会  2012.5 

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    Event date: 2012.5

    Language:Japanese  

    Country:Japan  

  • 慢性腎不全モデルマウスにおける薬物代謝酵素CYP3A11発現リズム変化

    濵村 賢吾、 松永 直哉、 池田 恵理子、 小柳 悟、 大戸 茂弘

    日本薬剤学会第25年会  2010.5 

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    Event date: 2010.5

    Language:Japanese  

    Country:Japan  

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Professional Memberships

  • SOCIETY FOR NEUROSCIENCE

    2019.4 - Present

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  • THE JAPANESE PHARMACOLOGICAL SOCIETY

    2017.10 - Present

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  • JAPANESE SOCIETY FOR CHRONOBIOLOGY

    2014.7 - Present

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  • THE ACADEMY OF PHARMACEUTICAL SCIENCE AND TECHNOLOGY, JAPAN

    2010.4 - Present

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  • JAPANESE SOCIETY FOR CHRONOBIOLOGY

  • THE ACADEMY OF PHARMACEUTICAL SCIENCE AND TECHNOLOGY, JAPAN

  • THE JAPANESE PHARMACOLOGICAL SOCIETY

  • SOCIETY FOR NEUROSCIENCE

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Research Projects

  • エクソソーム二重膜に着目した新たな神経障害性疼痛の治療標的としての可能性

    Grant number:21K11613  2021 - 2023

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

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    Authorship:Principal investigator  Grant type:Scientific research funding

  • プレガバリンOD錠「ニプロ」のマウス神経障害性疼痛モデルを用いた鎮痛効果の検討

    2019.4 - 2020.3

    Research commissions

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    Authorship:Principal investigator  Grant type:Other funds from industry-academia collaboration

  • 神経障害性疼痛の増悪に及ぼすエクソソームの役割

    Grant number:19K16936  2019 - 2020

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Early-Career Scientists

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    Authorship:Principal investigator  Grant type:Scientific research funding

  • 中冨健康科学振興財団研究助成金/神経障害性疼痛の増悪に及ぼすエクソソームの役割

    2018

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    Grant type:Donation

  • エクソソーム二重膜上に存在する疼痛増悪因子の同定と新しい疼痛治療戦略の創出

    Grant number:17K18298  2017 - 2018

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Young Scientists (B)

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    Authorship:Principal investigator  Grant type:Scientific research funding

  • 血清中エクソソームに着目した神経障害性疼痛の増悪機構解明と治療法への応用

    Grant number:15H06795  2015 - 2016

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Research Activity start-up

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    Authorship:Principal investigator  Grant type:Scientific research funding

  • 慢性腎不全モデルマウスにおける肝CYP3A11発現変容機構の解明

    Grant number:13J04175  2013 - 2014

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for JSPS Fellows

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    Authorship:Principal investigator  Grant type:Scientific research funding

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Educational Activities

  • I have been involved in the training of pharmacists by teaching lectures, exercises, and practical training for undergraduate pharmacy students.

Class subject

  • 薬学基礎実習Ⅳ

    2024.6 - 2024.8   Summer quarter

  • 薬物治療学Ⅱ

    2024.6 - 2024.8   Summer quarter

  • 薬剤・動態学

    2024.4 - 2024.6   Spring quarter

  • 薬物動態学ⅠA

    2024.4 - 2024.6   Spring quarter

FD Participation

  • 2024.3   Role:Participation   Title:有体物管理センターの業務および成果有体物収入の配分率の変更について

    Organizer:University-wide

  • 2023.11   Role:Participation   Title:第2回部局FD講演会「機関間連携」

    Organizer:[Undergraduate school/graduate school/graduate faculty]

  • 2023.8   Role:Participation   Title:令和5年度4部局合同男女共同参画FD

    Organizer:[Undergraduate school/graduate school/graduate faculty]

  • 2023.4   Role:Participation   Title:令和5年度 第1回全学FD(新任教員の研修)The 1st All-University FD (training for new faculty members) in FY2023

    Organizer:University-wide

Other educational activity and Special note

  • 2024  Class Teacher  学部

  • 2023  Special Affairs  OSCE評価者

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    OSCE評価者