Updated on 2024/04/08

写真a

 
URUSHIMA Hayato
 
Organization
Graduate School of Medicine Department of Basic Medical Science Associate Professor
School of Medicine Department of Medical Science
Title
Associate Professor
Affiliation
Institute of Medicine
Affiliation campus
Abeno Campus

Position

  • Graduate School of Medicine Department of Basic Medical Science 

    Associate Professor  2024.04 - Now

  • School of Medicine Department of Medical Science 

    Associate Professor  2024.04 - Now

Degree

  • 博士(医学) ( Osaka University )

Research Areas

  • Life Science / Gastroenterology

Research Interests

  • 肝硬変 肝がん 機能性食品

Awards

  • 優秀演題賞

    2023.12   肝類洞壁細胞研究会   増殖様式が異なるHepG2細胞2系統間の遺伝子比較と肝機能改善剤スクリーニングシステムの構築

  • 優秀ポスター報告賞

    2018.07   統合医療機能性食品国際学会  

  • 優秀ポスター報告賞

    2018.07   統合医療機能性食品国際学会  

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    Country:Japan

  • Kansai Liver Club 2018 優秀賞

    2018.04  

  • Kansai Liver Club 2018 優秀賞

    2018.04  

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    Country:Japan

  • Teacher of the Year

    2018.03   大阪市立大学医学部  

  • Teacher of the Year

    2018.03   大阪市立大学医学部  

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    Country:Japan

  • 若手研究奨励賞 

    2013   International Congress on Nutrition and Integrative Medicine  

  • 若手研究奨励賞

    2013   International Congress on Nutrition and Integrative Medicine  

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    Country:Japan

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Job Career (off-campus)

  • 大阪市立大学大学院医学研究科   機能細胞形態学

    2021.07 - Now

  • Osaka City University   Graduate School of Medicine Basic Medicine Course

    2016.10 - 2021.06

  • 国立研究開発法人医薬基盤健康栄養研究所   特任研究員

    2015.04 - 2016.09

  • 国立研究開発法人医薬基盤健康栄養研究所   特任研究員

    2015.04 - 2016.09

Education

  • Osaka University   Doctor's Course  

    2011.04 - 2015.03

  • Tottori University    

Papers

  • Poorly Differentiated Hepatocellular Carcinoma Cells Avoid Apoptosis by Interacting with T Cells via CD40-CD40L Linkage.

    Ngo HV, Thanh Le TT, Vu HN, Hoang H, Ikenaga H, Sato-Matsubara M, Uchida-Kobayashi S, Urushima H, Nguyen KV, Nguyen HT, Shinkawa H, Kubo S, Ohtani N, Enomoto M, Tamori A, Kawada N

    The American journal of pathology   2024.03( ISSN:0002-9440

  • Arteriosclerosis Derived from Cutaneous Inflammation Is Ameliorated by the Deletion of IL-17A and IL-17F.

    Takehisa Nakanishi, Shohei Iida, Junko Maruyama, Hayato Urushima, Masako Ichishi, Yoshiaki Matsushima, Kento Mizutani, Yuichi Nakayama, Kyoko Sugioka, Mai Nishimura, Ai Umaoka, Yoichiro Iwakura, Makoto Kondo, Koji Habe, Daisuke Tsuruta, Osamu Yamamoto, Yasutomo Imai, Keiichi Yamanaka

    International journal of molecular sciences   24 ( 6 )   2023.03( ISSN:16616596

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    The skin is one of the major immune organs producing large amounts of proinflammatory and inflammatory cytokines in response to internal or exogenous stimuli, inducing systemic inflammation in various internal organs. In recent years, organ damage associated with inflammatory skin diseases such as psoriasis and atopic dermatitis has received increasing attention, and vascular disorder such as arteriosclerosis is one of the serious complications of chronic inflammatory skin diseases. However, the detailed mechanism of arteriosclerosis in dermatitis and the role of cytokines have not been clarified so far. In the current study, using a spontaneous dermatitis model, we investigated the pathophysiology of arteriosclerosis and the treatment option for inflammatory skin conditions. We employed spontaneous dermatitis model mice overexpressing human caspase-1 in the epidermal keratinocyte (Kcasp1Tg). The thoracic and abdominal aorta was investigated histologically. GeneChip and RT-PCR analysis were performed to measure the changes in mRNA levels in the aorta. To elucidate the direct effect on the artery by major inflammatory cytokines, endothelial cells, vascular smooth muscle cells, and fibroblast cells were co-cultured with several cytokines, and mRNA expression levels were measured. In order to observe the efficacy of IL-17A/F in arteriosclerosis, cross-mating with IL-17A, IL-17F, and IL-17A/F deficient mice was performed. Finally, we also measured snap tension in the abdominal aorta in WT, Kcasp1Tg, and IL17A/F-deficient mice. Kcasp1Tg showed a decrease in the diameter of the abdominal aorta compared to wild-type mice. mRNA levels for six genes including Apol11b, Camp, Chil3, S100a8, S100a9, and Spta1 were increased in the abdominal aorta of Kcasp1Tg. Some of the above mRNA levels were also increased in the co-culture with major inflammatory cytokines, IL-17A/F, IL-1β, and TNF-α. Dermatitis improved and mRNA levels were partially ameliorated in Kcasp1Tg with IL-17A/F deletion. Arterial fragility was also evidenced in the inflammatory model, but arterial flexibility was revealed in the IL-17A/F deletion model. Severe dermatitis is closely related to secondary arteriosclerosis caused by the persistent release of inflammatory cytokines. The results also proved that treatment against IL-17A and F may ameliorate arteriosclerosis.

    DOI: 10.3390/ijms24065434

    PubMed

  • Hypo-osmolarity induces apoptosis resistance via TRPV2-mediated AKT-Bcl-2 pathway.

    Hayato Urushima, Tsutomu Matsubara, Masaaki Miyakoshi, Shioko Kimura, Hideto Yuasa, Katsutoshi Yoshizato, Kazuo Ikeda

    American journal of physiology. Gastrointestinal and liver physiology   324 ( 3 )   G219 - G230   2023.03( ISSN:0193-1857

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    In cirrhosis, several molecular alterations such as resistance to apoptosis could accelerate carcinogenesis. Recently, mechanotransduction has been attracting attention as one of the causes of these disturbances. In patients with cirrhosis, the serum sodium levels progressively decrease in the later stage of cirrhosis, and hyponatremia leads to serum hypo-osmolality. Since serum sodium levels in patients with cirrhosis with liver cancer are inversely related to cancer's number, size, stage, and cumulative survival, we hypothesized that hypo-osmolality-induced mechanotransduction under cirrhotic conditions might contribute to oncogenesis and/or progression of hepatocellular carcinoma (HCC). In this study, we adjusted osmosis of culture medium by changing the sodium chloride concentration and investigated the influence of hypotonic conditions on the apoptosis resistance of an HCC cell line, HepG2, using a serum-deprivation-induced apoptosis model. By culturing the cells in a serum-free medium, the levels of an antiapoptotic protein Bcl-2 were downregulated. In contrast, the hypotonic conditions caused apoptosis resistance by upregulation of Bcl-2. Next, we examined which pathway was involved in the apoptosis resistance. Hypotonic conditions enhanced AKT signaling, and constitutive activation of AKT in HepG2 cells led to upregulation of Bcl-2. Moreover, we revealed that the enhancement of AKT signaling was caused by intracellular calcium influx via a mechanosensor, TRPV2. Our findings suggested that hyponatremia-induced serum hypotonic in patients with cirrhosis promoted the progression of hepatocellular carcinoma.NEW & NOTEWORTHY Our study first revealed that hypo-osmolarity-induced mechanotransduction enhanced calcium-mediated AKT signaling via TRPV2 activation, resulting in contributing to apoptosis resistance. The finding indicates a possible view that liver cirrhosis-induced hyponatremia promotes hepatocellular carcinogenesis.

    DOI: 10.1152/ajpgi.00138.2022

    PubMed

  • Nitric oxide derived from cytoglobin-deficient hepatic stellate cells causes suppression of cytochrome c oxidase activity in hepatocytes.

    Yoshinori Okina, Misako Sato-Matsubara, Yasutoshi Kido, Hayato Urushima, Atsuko Daikoku, Chiho Kadono, Yu Nakagama, Yuko Nitahara, Truong Huu Hoang, Le Thi Thanh Thuy, Tsutomu Matsubara, Naoko Ohtani, Kazuo Ikeda, Katsutoshi Yoshizato, Norifumi Kawada

    Antioxidants & redox signaling   38 ( 7-9 )   463 - 479   2023.03( ISSN:1523-0864

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    AIMS: Cell-cell interactions between hepatocytes and other liver cells are key to maintaining liver homeostasis. Cytoglobin (CYGB), expressed exclusively by hepatic stellate cells (HSC), is essential in mitigating mitochondrial oxidative stress. CYGB absence causes hepatocyte (Hep) dysfunction and evokes hepatocarcinogenesis through an elusive mechanism. CYGB deficiency is speculated to hinder nitric oxide dioxygenase (NOD) activity, resulting in the elevated formation and release of NO. Hence, we hypothesized that NO accumulation induced by the loss of NOD activity in CYGB-deficient HSC could adversely affect mitochondrial function in Hep, leading to disease progression. RESULTS: NO, a membrane-permeable gas metabolite overproduced by CYGB-deficient HSC, diffuses into neighboring hepatocytes to reversibly inhibit cytochrome c oxidase (CcO), resulting in the suppression of respiratory function in an electron transport chain (ETC). The binding of NO to CcO is proved using purified CcO fractions from Cygb knockout (Cygb-/-) mouse liver mitochondria. It's inhibitory action towards CcO specific activity is fully reversed by the external administration of oxyhemoglobin chasing away the bound NO. Thus, these findings indicate that the attenuation of respiratory function in ETC causes liver damage through formation of excessive reactive oxygen species. Treating Cygb-/- mice with an NO synthase inhibitor successfully relieved NO-induced inhibition of CcO activity in vivo. INNOVATION AND CONCLUSION: Our findings provide a biochemical link between CYGB-absence in HSC and neighboring hepatocyte dysfunction; mechanistically the absence of CYGB in HSC causes mitochondrial dysfunction of Hep via the inhibition of CcO activity by HSC-derived NO.

    DOI: 10.1089/ars.2021.0279

    PubMed

  • Suppression of intrahepatic cholangiocarcinoma cell growth by SKI via upregulation of the CDK inhibitor p21.

    Etsushi Kawamura, Tsutomu Matsubara, Atsuko Daikoku, Sanae Deguchi, Masahiko Kinoshita, Hideto Yuasa, Hayato Urushima, Naoshi Odagiri, Hiroyuki Motoyama, Kohei Kotani, Ritsuzo Kozuka, Atsushi Hagihara, Hideki Fujii, Sawako Uchida-Kobayashi, Shogo Tanaka, Shigekazu Takemura, Keiko Iwaisako, Masaru Enomoto, Y H Taguchi, Akihiro Tamori, Shoji Kubo, Kazuo Ikeda, Norifumi Kawada

    FEBS open bio   12 ( 12 )   2122 - 2135   2022.12

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    Cholangiocarcinoma (CC) has a poor prognosis and different driver genes depending on the site of onset. Intrahepatic CC is the second-most common liver cancer after hepatocellular carcinoma, and novel therapeutic targets are urgently needed. The present study was conducted to identify novel therapeutic targets by exploring differentially regulated genes in human CC. MicroRNA (miRNA) and mRNA microarrays were performed using tissue and serum samples obtained from 24 surgically resected hepatobiliary tumor cases, including 10 CC cases. We conducted principal component analysis to identify differentially expressed miRNA, leading to the identification of miRNA-3648 as a differentially expressed miRNA. We used an in silico screening approach to identify its target mRNA, the tumor suppressor Sloan Kettering Institute (SKI). SKI protein expression was decreased in human CC cells overexpressing miRNA-3648, endogenous SKI protein expression was decreased in human CC tumor tissues, and endogenous SKI mRNA expression was suppressed in human CC cells characterized by rapid growth. SKI-overexpressing OZ cells (human intrahepatic CC cells) showed upregulation of cyclin-dependent kinase inhibitor p21 mRNA and protein expression and suppressed cell proliferation. Nuclear expression of CDT1 (chromatin licensing and DNA replication factor 1), which is required for the G1/S transition, was suppressed in SKI-overexpressing OZ cells. SKI knockdown resulted in the opposite effects. Transgenic p21-luciferase was activated in SKI-overexpressing OZ cells. These data indicate SKI involvement in p21 transcription and that SKI-p21 signaling causes cell cycle arrest in G1, suppressing intrahepatic CC cell growth. Therefore, SKI may be a potential therapeutic target for intrahepatic CC.

    DOI: 10.1002/2211-5463.13489

    PubMed

  • Soluble Immune Checkpoint Protein CD27 Is a Novel Prognostic Biomarker of Hepatocellular Carcinoma Development in Hepatitis C Virus-Sustained Virological Response Patients.

    Minh Phuong Dong, Le Thi Thanh Thuy, Dinh Viet Hoang, Hoang Hai, Truong Huu Hoang, Misako Sato-Matsubara, Vu Ngoc Hieu, Atsuko Daikoku, Ngo Vinh Hanh, Hayato Urushima, Ninh Quoc Dat, Sawako Uchida-Kobayashi, Masaru Enomoto, Naoko Ohtani, Akihiro Tamori, Norifumi Kawada

    The American journal of pathology   192 ( 10 )   1379 - 1396   2022.10( ISSN:0002-9440

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    Factors affecting the probability of hepatocellular carcinoma (HCC) development even after sustained virological response (SVR) following anti-hepatitis C virus (HCV) therapy remain unelucidated. This study characterized the role of 16 soluble (s) immune checkpoint proteins in 168 HCV-SVR patients, with 47 developing HCC at the study end point. At baseline, high concentrations of 10 immune checkpoint proteins were found in the sera of the HCC group. At the study end point, levels of sCD27, sCD28, sCD40, and sCD86 in the HCC group, which were depleted following SVR, returned to higher levels than those in the non-HCC group. More importantly, patients with baseline levels of sCD27 ≥ 4104 pg/mL, sCD28 ≥ 1530 pg/mL, and sCD40 ≥ 688 pg/mL predicted a significantly greater HCC cumulative rate. Although sCD27 was elevated in patient sera, its membrane-bound form, mCD27, accumulated in the tumor and peritumor area, mainly localized in T cells. Interestingly, T-cell activation time dependently induced sCD27. Furthermore, CD70, the ligand of CD27, was robustly expressed in HCC area in which CD70 promoter methylation analysis indicated the hypomethylation compared with the nontumor pairs. Recombinant human CD27 treatment induced the proliferation of CD70-bearing HepG2 cells via the mitogen-activated protein kinase (MEK)-extracellular signal-regulated kinase pathway, but not NF-κB or p38 pathway. In conclusion, these data indicate that baseline sCD27, sCD28, and sCD40 levels could be used as HCC prognostic markers in HCV-SVR patients. sCD27 likely promotes HepG2 cell growth via the CD27-CD70 axis.

    DOI: 10.1016/j.ajpath.2022.07.003

    PubMed

  • Cancer cells produce liver metastasis via gap formation in sinusoidal endothelial cells through proinflammatory paracrine mechanisms.

    Truong Huu Hoang, Misako Sato-Matsubara, Hideto Yuasa, Tsutomu Matsubara, Le Thi Thanh Thuy, Hiroko Ikenaga, Dong Minh Phuong, Ngo Vinh Hanh, Vu Ngoc Hieu, Dinh Viet Hoang, Hoang Hai, Yoshinori Okina, Masaru Enomoto, Akihiro Tamori, Atsuko Daikoku, Hayato Urushima, Kazuo Ikeda, Ninh Quoc Dat, Yutaka Yasui, Hiroji Shinkawa, Shoji Kubo, Ryota Yamagishi, Naoko Ohtani, Katsutoshi Yoshizato, Jordi Gracia-Sancho, Norifumi Kawada

    Science advances   8 ( 39 )   eabo5525   2022.09

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    Intracellular gap (iGap) formation in liver sinusoidal endothelial cells (LSECs) is caused by the destruction of fenestrae and appears under pathological conditions; nevertheless, their role in metastasis of cancer cells to the liver remained unexplored. We elucidated that hepatotoxin-damaged and fibrotic livers gave rise to LSECs-iGap formation, which was positively correlated with increased numbers of metastatic liver foci after intrasplenic injection of Hepa1-6 cells. Hepa1-6 cells induced interleukin-23-dependent tumor necrosis factor-α (TNF-α) secretion by LSECs and triggered LSECs-iGap formation, toward which their processes protruded to transmigrate into the liver parenchyma. TNF-α triggered depolymerization of F-actin and induced matrix metalloproteinase 9 (MMP9), intracellular adhesion molecule 1, and CXCL expression in LSECs. Blocking MMP9 activity by doxycycline or an MMP2/9 inhibitor eliminated LSECs-iGap formation and attenuated liver metastasis of Hepa1-6 cells. Overall, this study revealed that cancer cells induced LSEC-iGap formation via proinflammatory paracrine mechanisms and proposed MMP9 as a favorable target for blocking cancer cell metastasis to the liver.

    DOI: 10.1126/sciadv.abo5525

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  • Activation of Hepatic Stellate Cells Requires Dissociation of E-Cadherin-Containing Adherens Junctions with Hepatocytes. Reviewed

    Urushima H, Yuasa H, Matsubara T, Kuroda N, Hara Y, Inoue K, Wake K, Sato T, Friedman SL, Ikeda K

    The American journal of pathology   191 ( 3 )   438 - 453   2021.03( ISSN:0002-9440

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    DOI: 10.1016/j.ajpath.2020.12.007

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  • Activation of Hepatic Stellate Cells Requires Dissociation of E-Cadherin-Containing Adherens Junctions with Hepatocytes.

    Hayato Urushima, Hideto Yuasa, Tsutomu Matsubara, Noriyuki Kuroda, Yaiko Hara, Kouji Inoue, Kenjiro Wake, Tetsuji Sato, Scott L Friedman, Kazuo Ikeda

    The American journal of pathology   191 ( 3 )   438 - 453   2021.03( ISSN:0002-9440

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    Hepatic stellate cells (HSCs) are resident mesenchymal cells in the space of Disse interposed between liver sinusoidal endothelial cells and hepatocytes. Thorn-like microprojections, or spines, project out from the cell surface of HSCs, crossing the space of Disse, to establish adherens junctions with neighboring hepatocytes. Although HSC activation is initiated largely from stimulation by adjacent cells, isolated HSCs also activate spontaneously in primary culture on plastic. Therefore, other unknown HSC-initiating factors apart from paracrine stimuli may promote activation. The dissociation of adherens junctions between HSCs and hepatocytes as an activating signal for HSCs was explored, establishing epithelial cadherin (E-cadherin) as an adhesion molecule linking hepatocytes and HSCs. In vivo, following carbon tetrachloride-induced liver injury, HSCs lost their spines and dissociated from adherens junctions in the early stages of injury, and were subsequently activated along with an increase in YAP/TAZ expression. After abrogation of liver injury, HSCs reconstructed their spines and adherens junctions. In vitro, reconstitution of E-cadherin-containing adherens junctions by forced E-cadherin expression quiesced HSCs and suppressed TAZ expression. Additionally, increase of TAZ expression leading to the activation of HSCs by autocrine stimulation of transforming growth factor-β, was revealed as a mechanism of spontaneous activation. Thus, we have uncovered a critical event required for HSC activation through enhanced TAZ-mediated mechanotransduction after the loss of adherens junctions between HSCs and hepatocytes.

    DOI: 10.1016/j.ajpath.2020.12.007

    PubMed

  • Involvement of ERK1/2 activation in the gene expression of senescence-associated secretory factors in human hepatic stellate cells. Reviewed

    Odagiri N, Matsubara T, Higuchi M, Takada S, Urushima H, Sato-Matsubara M, Teranishi Y, Yoshizato K, Kawada N, Ikeda K

    Molecular and cellular biochemistry   455 ( 1-2 )   7 - 19   2019.05( ISSN:0300-8177

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    Senescent hepatic stellate cells (senescent HSCs) are found in patients with liver cirrhosis and have been thought to be involved in the development of hepatocellular carcinoma (HCC) in mice via the senescence-associated secretory proteins. However, in humans, which secretory proteins are involved and what regulate their expression remain unclear. In the current study, we characterized senescence-associated β-galactosidase-positive senescent human HSCs (hHSCs) induced by repetitive passaging. They exhibited enhanced expression of 14 genes for secretory protein and persistent phosphorylation of ERK1/2 protein but not JNK or p38 MAPK proteins. Enhanced nuclear ERK1/2 phosphorylation was observed in senescent hHSCs. Treatment of the senescent hHSCs with ERK1/2 inhibitor, SCH772984, significantly decreased the levels of angiopoietin like 4 (ANGPTL4), C-C motif chemokine ligand 7 (CCL7), Interleukin-8 (IL-8), platelet factor 4 variant 1 (PF4V1), and TNF superfamily member 15 (TNFSF15) mRNA levels in a dose-dependent manner. The enhanced phosphorylation of ERK1/2 and expression of ANGPTL4, IL-8 and PF4V1 genes were observed in both of senescent human dermal fibroblasts and X-ray-induced senescent hHSCs. However, transient ERK1/2 activation induced by epidermal growth factor could not mimic the gene profile of the senescent hHSCs. These results revealed involvement of ERK1/2 signaling in the regulation of senescence-associated secretory factors, suggesting that simultaneous induction of ANGPTL4, IL-8, and PF4V1 genes is a marker of hHSC senescence. This study will contribute to understanding roles of senescent hHSCs in liver diseases.

    DOI: 10.1007/s11010-018-3466-x

    PubMed

  • Involvement of ERK1/2 activation in the gene expression of senescence-associated secretory factors in human hepatic stellate cells. Reviewed

    Odagiri N, Matsubara T, Higuchi M, Takada S, Urushima H, Sato-Matsubara M, Teranishi Y, Yoshizato K, Kawada N, Ikeda K

    Molecular and cellular biochemistry   2018.11( ISSN:0300-8177

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/s11010-018-3466-x

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  • Leucine-rich alpha-2 glycoprotein promotes lung fibrosis by modulating TGF-beta signaling in fibroblasts Reviewed

    Honda Hiromi, Fujimoto Minoru, Serada Satoshi, Urushima Hayato, Mishima Takashi, Lee Hyun, Ohkawara Tomoharu, Kohno Nobuoki, Hattori Noboru, Yokoyama Akihito, Naka Tetsuji

    PHYSIOLOGICAL REPORTS   5 ( 24 )   2017.12( ISSN:2051-817X

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.14814/phy2.13556

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  • Leucine-rich alpha-2 glycoprotein promotes lung fibrosis by modulating TGF-beta signaling in fibroblasts Reviewed

    Honda Hiromi, Fujimoto Minoru, Serada Satoshi, Urushima Hayato, Mishima Takashi, Lee Hyun, Ohkawara Tomoharu, Kohno Nobuoki, Hattori Noboru, Yokoyama Akihito, Naka Tetsuji

    PHYSIOLOGICAL REPORTS   5 ( 24 )   2017.12( ISSN:2051-817X

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.14814/phy2.13556

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  • Leucine-rich alpha 2 glycoprotein promotes Th17 differentiation and collagen-induced arthritis in mice through enhancement of TGF-β-Smad2 signaling in naïve helper T cells. Reviewed

    Urushima H, Fujimoto M, Mishima T, Ohkawara T, Honda H, Lee H, Kawahata H, Serada S, Naka T

    Arthritis research & therapy   19 ( 1 )   137   2017.06( ISSN:1478-6354

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1186/s13075-017-1349-2

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  • Leucine-rich alpha 2 glycoprotein promotes Th17 differentiation and collagen-induced arthritis in mice through enhancement of TGF-β-Smad2 signaling in naïve helper T cells. Reviewed

    Urushima H, Fujimoto M, Mishima T, Ohkawara T, Honda H, Lee H, Kawahata H, Serada S, Naka T

    Arthritis research & therapy   19 ( 1 )   137 - 137   2017.06( ISSN:1478-6354

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    BACKGROUND: Leucine-rich alpha 2 glycoprotein (LRG) has been identified as a serum protein elevated in patients with active rheumatoid arthritis (RA). Although the function of LRG is ill-defined, LRG binds with transforming growth factor (TGF)-β and enhances Smad2 phosphorylation. Considering that the imbalance between T helper 17 (Th17) cells and regulatory T cells (Treg) plays important roles in the pathogenesis of RA, LRG may affect arthritic pathology by enhancing the TGF-β-Smad2 pathway that is pivotal for both Treg and Th17 differentiation. The purpose of this study was to explore the contribution of LRG to the pathogenesis of arthritis, with a focus on the role of LRG in T cell differentiation. METHODS: The differentiation of CD4 T cells and the development of collagen-induced arthritis (CIA) were examined in wild-type mice and LRG knockout (KO) mice. To examine the influence of LRG on T cell differentiation, naïve CD4 T cells were isolated from LRG KO mice and cultured under Treg- or Th17-polarization condition in the absence or presence of recombinant LRG. RESULTS: In the CIA model, LRG deficiency led to ameliorated arthritis and reduced Th17 differentiation with no influence on Treg differentiation. By addition of recombinant LRG, the expression of IL-6 receptor (IL-6R) was enhanced through TGF-β-Smad2 signaling. In LRG KO mice, the IL-6R expression and IL-6-STAT3 signaling was attenuated in naïve CD4 T cells, compared to wild-type mice. CONCLUSIONS: Our findings suggest that LRG upregulates IL-6R expression in naïve CD4 T cells by the enhancement of TGF-β-smad2 pathway and promote Th17 differentiation and arthritis development.

    DOI: 10.1186/s13075-017-1349-2

    PubMed

  • Efficacy and interaction of antioxidant supplements as adjuvant therapy in cancer treatment: A systematic review Reviewed

    Asuka Yasueda, Hayato Urushima, Toshinori Ito

    Integrative Cancer Therapies   15 ( 1 )   17 - 39   2016.03( ISSN:1552-695X

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    Oxidative stress is a key component in carcinogenesis. Although radiation produces reactive oxygen species, some anticancer agents such as alkylating agents, platinum and antitumor antibiotics exert cytotoxicity by generating free radicals. Nonenzymatic exogenous antioxidants such as vitamins, minerals, and polyphenols can quench ROS activity. However, whether antioxidants alter antitumor effects during radiotherapy and some types of chemotherapy remains unclear. In the present study, we reviewed antioxidants as an adjuvant therapy for cancer patients during chemotherapy or radiotherapy. Electronic literature searches were performed to select all randomized controlled clinical trials (RCTs) in which antioxidants were administered to cancer patients along with chemotherapy or radiotherapy. Articles or abstracts written in English were included. In total, 399 reports received primary screening. Duplicated articles and those meeting the exclusion criteria (not RCT, not human, and no oral administration) were excluded. Finally, 49 reports matching the inclusion criteria were included. It was difficult to determine whether antioxidants affect treatment outcomes or whether antioxidants ameliorate adverse effects induced by chemotherapy and radiotherapy. It is desirable to use an evidence-based method to select supplements best suited to cancer patients. Although there are many opinions about risks or benefits of antioxidant supplementation, we could mostly conclude that the harm caused by antioxidant supplementation remains unclear for patients during cancer therapy, except for smokers undergoing radiotherapy.

    DOI: 10.1177/1534735415610427

    PubMed

  • Efficacy and Interaction of Antioxidant Supplements as Adjuvant Therapy in Cancer Treatment: A Systematic Review. Reviewed

    Yasueda A, Urushima H, Ito T

    Integrative cancer therapies   15 ( 1 )   17 - 39   2016.03( ISSN:1534-7354

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1177/1534735415610427

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  • Maltitol Prevents the Progression of Fatty Liver Degeneration in Mice Fed High-Fat Diets. Reviewed

    Urushima H, Sanada Y, Sakaue M, Matsuzawa Y, Ito T, Maeda K

    Journal of medicinal food   18 ( 10 )   1081 - 7   2015.10( ISSN:1096-620X

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1089/jmf.2014.3380

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  • Maltitol Prevents the Progression of Fatty Liver Degeneration in Mice Fed High-Fat Diets Reviewed

    Hayato Urushima, Yasuaki Sanada, Miki Sakaue, Yuji Matsuzawa, Toshinori Ito, Kazuhisa Maeda

    JOURNAL OF MEDICINAL FOOD   18 ( 10 )   1081 - 1087   2015.10( ISSN:1096-620X

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    Nonalcoholic fatty liver disease (NAFLD) progresses to nonalcoholic steatohepatitis, ultimately leading to cirrhosis and liver cancer. It is important to prevent this progression during the initial stages of hepatic fatty degeneration. Maltitol is a polyol produced by the hydrogenation of maltose. We investigated the efficacy of maltitol for treating hepatic fatty degeneration in C57BL/6 male mice using a high-fat diet model. Intake of 5.0% maltitol for 8 weeks significantly suppressed weight gain, hepatic fatty degeneration, hyperglycemia, and hypercholesterolemia. With maltitol intake, sterol regulatory element-binding protein 1c (SREBP1c) mRNA expression was significantly decreased, and farnesoid X receptor (FXR), peroxisome proliferator-activated receptor (PPAR), and hydroxymethylglutaryl-Co reductase expressions were significantly higher in the liver. The increase in SREBP1c and suppression of FXR and PPAR expressions are correlated with NAFLD. Our results suggest that maltitol may prevent steatosis of NAFLD with a high-fat diet.

    DOI: 10.1089/jmf.2014.3380

  • The effects of androgen deprivation therapy with weight management on serum aP2 and adiponectin levels in prostate cancer patients. Reviewed

    Urushima H, Inomata-Kurashiki Y, Nishimura K, Sumi R, Shimomura I, Nonomura N, Ito T, Maeda K

    The aging male : the official journal of the International Society for the Study of the Aging Male   18 ( 2 )   72 - 6   2015.06( ISSN:1368-5538

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.3109/13685538.2015.1017809

    PubMed

  • The effects of androgen deprivation therapy with weight management on serum aP2 and adiponectin levels in prostate cancer patients Reviewed

    Hayato Urushima, Yukiko Inomata-Kurashiki, Kazuo Nishimura, Ryoko Sumi, Iichiro Shimomura, Norio Nonomura, Toshinori Ito, Kazuhisa Maeda

    AGING MALE   18 ( 2 )   72 - 76   2015.06( ISSN:1368-5538

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    Androgen deprivation therapy (ADT) for the treatment of prostate cancer (PCa) causes an increase in total body fat, leading to a net gain in body weight. Moreover, the use of the luteinizing hormone-releasing hormone agonists in ADT causes a decrease in serum androgen levels, leading to the development of metabolic syndrome (MetS). Androgen blockade significantly increases plasma adiponectin levels, which has some efficacy against MetS, whereas ADT increases fasting plasma insulin and decreases insulin sensitivity, suggesting that there are other mechanisms involved in the onset of MetS besides adiponectin activation. We investigated the effects of ADT on serum aP2 and adiponectin in PCa patients. Six months post-ADT, serum aP2 and adiponectin levels were significantly increased, although there were no changes in patient body weight and no correlation between the changes in serum aP2 and total adiponectin levels. The serum adiponectin and aP2 levels have independent implications in ADT for PCa; therefore, their combined measurement will clarify the impact on the development of obesity-related diseases during ADT. Contrary to adiponectin, high serum aP2 levels were correlated with the late development of MetS. Further studies are needed to investigate the future occurrence of metabolic diseases post-ADT.

    DOI: 10.3109/13685538.2015.1017809

  • Perilla frutescens extract ameliorates DSS-induced colitis by suppressing proinflammatory cytokines and inducing anti-inflammatory cytokines. Reviewed

    Urushima H, Nishimura J, Mizushima T, Hayashi N, Maeda K, Ito T

    American journal of physiology. Gastrointestinal and liver physiology   308 ( 1 )   G32 - 41   2015.01( ISSN:0193-1857

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    DOI: 10.1152/ajpgi.00294.2014

    PubMed

  • Perilla frutescens extract ameliorates DSS-induced colitis by suppressing proinflammatory cytokines and inducing anti-inflammatory cytokines Reviewed

    Hayato Urushima, Junichi Nishimura, Tsunekazu Mizushima, Noriyuki Hayashi, Kazuhisa Maeda, Toshinori Ito

    AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY   308 ( 1 )   G32 - G41   2015.01( ISSN:0193-1857

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    Anti-inflammatory effects have been reported in Perilla frutescens leaf extract (PE), which is a plant of the genus belonging to the Lamiaceae family. We examined the effect of PE on dextran sulfate sodium (DSS)-induced colitis. Preliminarily, PE was safely administered for 7 wk without any adverse effects. In the preventive protocol, mice were fed 1.5% DSS solution dissolved in distilled water (control group) or 0.54% PE solution (PE group) ad libitum for 7 days. In the therapeutic protocol, distilled water or 0.54% PE solution was given for 10 days just after administration of 1.5% DSS for 5 days. PE intake significantly improved body weight loss. The serum cytokine profile demonstrated that TNF-alpha, IL-17A, and IL-10 were significantly lower in the PE group than in the control group. In the therapeutic protocol, mice in the PE group showed significantly higher body weight and lower histological colitis scores compared with mice in the control group on day 15. The serum cytokine profile demonstrated that TGF-beta was significantly higher in the PE group than in the control group. In distal colon mRNA expression, TNF-alpha, and IL-17A were significantly downregulated. In vitro analyses of biologically active ingredients, such as luteolin, apigenin, and rosmarinic acid, in PE were performed. Luteolin suppressed production of proinflammatory cytokines, such as TNF-alpha, IL-1 beta, IL-6, and IL-17A. Apigenin also suppressed secretion of IL-17A and increased the anti-inflammatory cytokine IL-10. Rosmarinic acid increased the regulatory T cell population. We conclude that PE might be useful in treatment and prevention of DSS-induced colitis.

    DOI: 10.1152/ajpgi.00294.2014

  • Reduction of adverse effects by a mushroom product, active hexose correlated compound (AHCC) in patients with advanced cancer during chemotherapy-the significance of the levels of HHV-6 DNA in saliva as a surrogate biomarker during chemotherapy Reviewed

    Toshinori Ito, Hayato Urushima, Miki Sakaue, Sayoko Yukawa, Hatsumi Honda, Kei Hirai, Takumi Igura, Noriyuki Hayashi, Kazuhisa Maeda, Toru Kitagawa, Kazuhiro Kondo

    Nutrition and Cancer   66 ( 3 )   377 - 382   2014.04( ISSN:1532-7914

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    Chemotherapy improves the outcome of cancer treatment, but patients are sometimes forced to discontinue chemotherapy or drop out of a clinical trial due to adverse effects, such as gastrointestinal disturbances and suppression of bone marrow function. The objective of this study was to evaluate the safety and effectiveness of a mushroom product, active hexose correlated compound (AHCC), on chemotherapy-induced adverse effects and quality of life (QOL) in patients with cancer. Twenty-four patients with cancer received their first cycle of chemotherapy without AHCC and then received their second cycle with AHCC. During chemotherapy, we weekly evaluated adverse effects and QOL via a blood test, EORTC QLQ-C30 questionnaire, and DNA levels of herpes virus type 6 (HHV-6) in saliva. The DNA levels of HHV-6 were significantly increased after chemotherapy. Interestingly, administration of AHCC significantly decreased the levels of HHV-6 in saliva during chemotherapy and improved not only QOL scores in the EORTC QLQ-C30 questionnaire but also hematotoxicity and hepatotoxicity. These findings suggest that salivary HHV-6 levels may be a good biomarker of QOL in patients during chemotherapy, and that AHCC may have a beneficial effect on chemotherapy-associated adverse effects and QOL in patients with cancer undergoing chemotherapy. © 2014 Taylor and Francis Group, LLC.

    DOI: 10.1080/01635581.2014.884232

    PubMed

  • DSS誘導腸炎に対するシソエキスの有効性 Reviewed

    宇留島 隼人, 西村 潤一, 林 紀行, 前田 和久, 伊藤 壽記

    日本消化器免疫学会 消化器と免疫   ( 50 )   74 - 78   2014.03

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    DSS誘導腸炎モデルマウスを用いてシソエキスの有効性を検討した。炎症惹起後にシソエキスを内服させることによって体重の回復が早くなり、腸管におけるTNF-αやIL-17AなどのmRNA発現が有意に抑制されていた。また、炎症を起こした粘膜固有層の抑制性T細胞がシソエキスによって増加していた。シソエキスの代表的な成分であるルテオリン、アピゲニン、ロスマリン酸を用いて単核球からのサイトカイン分泌を調べたところルテオリンには強い炎症性サイトカイン産生抑制効果が確認され、アピゲニンやロスマリン酸にはIL-10産生促進効果があることがわかった。(著者抄録)

  • DSS誘導腸炎に対するシソエキスの有効性

    宇留島 隼人, 西村 潤一, 林 紀行, 前田 和久, 伊藤 壽記

    消化器と免疫   ( 50 )   74 - 78   2014.03

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    DSS誘導腸炎モデルマウスを用いてシソエキスの有効性を検討した。炎症惹起後にシソエキスを内服させることによって体重の回復が早くなり、腸管におけるTNF-αやIL-17AなどのmRNA発現が有意に抑制されていた。また、炎症を起こした粘膜固有層の抑制性T細胞がシソエキスによって増加していた。シソエキスの代表的な成分であるルテオリン、アピゲニン、ロスマリン酸を用いて単核球からのサイトカイン分泌を調べたところルテオリンには強い炎症性サイトカイン産生抑制効果が確認され、アピゲニンやロスマリン酸にはIL-10産生促進効果があることがわかった。(著者抄録)

  • DSS誘導腸炎に対するシソエキスの有効性 Reviewed

    宇留島 隼人, 西村 潤一, 林 紀行, 前田 和久, 伊藤 壽記

    日本消化器免疫学会 消化器と免疫   ( 50 )   74 - 78   2014.03

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    Publishing type:Research paper (scientific journal)  

    DSS誘導腸炎モデルマウスを用いてシソエキスの有効性を検討した。炎症惹起後にシソエキスを内服させることによって体重の回復が早くなり、腸管におけるTNF-αやIL-17AなどのmRNA発現が有意に抑制されていた。また、炎症を起こした粘膜固有層の抑制性T細胞がシソエキスによって増加していた。シソエキスの代表的な成分であるルテオリン、アピゲニン、ロスマリン酸を用いて単核球からのサイトカイン分泌を調べたところルテオリンには強い炎症性サイトカイン産生抑制効果が確認され、アピゲニンやロスマリン酸にはIL-10産生促進効果があることがわかった。(著者抄録)

  • Reduction of adverse effects by a mushroom product, active hexose correlated compound (AHCC) in patients with advanced cancer during chemotherapy--the significance of the levels of HHV-6 DNA in saliva as a surrogate biomarker during chemotherapy. Reviewed

    Ito T, Urushima H, Sakaue M, Yukawa S, Honda H, Hirai K, Igura T, Hayashi N, Maeda K, Kitagawa T, Kondo K

    Nutrition and cancer   66 ( 3 )   377 - 82   2014( ISSN:0163-5581

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    DOI: 10.1080/01635581.2014.884232

    PubMed

  • Inhibition of epithelial cell death by Bcl-2 improved chronic colitis in IL-10 KO mice. Reviewed

    Mizushima T, Arakawa S, Sanada Y, Yoshino I, Miyazaki D, Urushima H, Tsujimoto Y, Ito T, Shimizu S

    The American journal of pathology   183 ( 6 )   1936 - 1944   2013.12( ISSN:0002-9440

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    DOI: 10.1016/j.ajpath.2013.08.012

    PubMed

  • Inhibition of epithelial cell death by Bcl-2 improved chronic colitis in IL-10 KO mice Reviewed

    Tsunekazu Mizushima, Satoko Arakawa, Yasuaki Sanada, Ikuyo Yoshino, Dai Miyazaki, Hayato Urushima, Yoshihide Tsujimoto, Toshinori Ito, Shigeomi Shimizu

    American Journal of Pathology   183 ( 6 )   1936 - 1944   2013.12( ISSN:0002-9440

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    IL-10-deficient mice spontaneously develop intestinal inflammation, which has many similarities to Crohn's disease. Several reports suggest that epithelial cell death may increase the severity of colitis
    however, decisive evidence is lacking. In the present report, we addressed whether and how epithelial cell death plays a role in the development of chronic colitis. We first examined the morphological characteristics of intestines of IL-10-deficient mice and found two forms of epithelial cell death (typical apoptosis and necrosis-like cell death) in colitis. To elucidate the pathological roles of epithelial cell death, we crossbred IL-10-deficient knockout mice with Bcl-2 transgenic mice, in which the anti-apoptosis protein Bcl-2 was overexpressed in intestinal epithelial cells, but not in immune cells. Epithelial cell-specific Bcl-2 protected IL-10 deficiency-induced colitis and markedly reduced their symptoms. Interestingly, morphological analysis revealed that Bcl-2 suppressed apoptosis and necrosis-like cell death, and better maintained mucosal barrier in IL-10-deficient mice. From the immunological aspect, Bcl-2 did not alter the activation of T-helper cell 1 but inhibited the growth of T-helper cell 17, suggesting that mucosal integrity may control the immune responses. These results provide genetic evidence demonstrating that epithelial cell death is crucial for the development of chronic colitis. © 2013 American Society for Investigative Pathology.

    DOI: 10.1016/j.ajpath.2013.08.012

    PubMed

  • 大規模災害の後遺障害に対する統合医療的アプローチ Reviewed

    林 紀行, 前田 和久, 八木 絵香, 平井 啓, 谷向 仁, 伊藤 和憲, 川口 裕子, 渡辺 眞実, 福田 文彦, 石崎 直人, 上島 悦子, 阪上 未紀, 松本 めぐみ, 足立 由香, 谷口 敏淳, 宇留島 隼人, 坂本 淑子, 岩田 昌美, 伊藤 壽記

    (一社)日本統合医療学会 日本統合医療学会誌   6 ( 1 )   65 - 69   2013.05

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    【背景】災害の負傷者、遺族らにおいて、一般保険医療では治療困難な後遺障害に対し、補完代替医療(CAM)に救いを求めることも少なくない。しかしその安全性、効果に対してのエビデンスは乏しい。【方法】この臨床試験は大阪大学医学部附属病院にて災害後遺障害者に対して施行した。そのうちJR福知山線脱線事故の被害者、遺族ら9人に対して解析を行った。一般保険医療が新たに必要な者、もしくは一般保険医療を受診も治療途中で、状態が落ち着いていない者を除外した。主要評価項目は介入完遂率とした。副次評価項目は抑うつ症状、PTSD様症状、介入の満足度、身体的、精神的苦痛などとした。鍼とアロマトリートメントを被検者に選んでもらい(両方も可)、週1回8週間にわたる介入が行われた。【結果】9例全てが鍼とアロマトリートメント両方を選び、完遂した。重篤な有害事象を認めなかった。介入直後は、身体的、精神的苦痛の有意な改善を認めた。介入を通じては、身体的、精神的苦痛の有意な改善は認めなかった。介入を通して、抑うつ尺度の有意な改善を認めた。(著者抄録)

  • 大規模災害の後遺障害に対する統合医療的アプローチ

    林 紀行, 前田 和久, 八木 絵香, 平井 啓, 谷向 仁, 伊藤 和憲, 川口 裕子, 渡辺 眞実, 福田 文彦, 石崎 直人, 上島 悦子, 阪上 未紀, 松本 めぐみ, 足立 由香, 谷口 敏淳, 宇留島 隼人, 坂本 淑子, 岩田 昌美, 伊藤 壽記

    日本統合医療学会誌   6 ( 1 )   65 - 69   2013.05( ISSN:2435-5372

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    【背景】災害の負傷者、遺族らにおいて、一般保険医療では治療困難な後遺障害に対し、補完代替医療(CAM)に救いを求めることも少なくない。しかしその安全性、効果に対してのエビデンスは乏しい。【方法】この臨床試験は大阪大学医学部附属病院にて災害後遺障害者に対して施行した。そのうちJR福知山線脱線事故の被害者、遺族ら9人に対して解析を行った。一般保険医療が新たに必要な者、もしくは一般保険医療を受診も治療途中で、状態が落ち着いていない者を除外した。主要評価項目は介入完遂率とした。副次評価項目は抑うつ症状、PTSD様症状、介入の満足度、身体的、精神的苦痛などとした。鍼とアロマトリートメントを被検者に選んでもらい(両方も可)、週1回8週間にわたる介入が行われた。【結果】9例全てが鍼とアロマトリートメント両方を選び、完遂した。重篤な有害事象を認めなかった。介入直後は、身体的、精神的苦痛の有意な改善を認めた。介入を通じては、身体的、精神的苦痛の有意な改善は認めなかった。介入を通して、抑うつ尺度の有意な改善を認めた。(著者抄録)

  • 大規模災害の後遺障害に対する統合医療的アプローチ Reviewed

    林 紀行, 前田 和久, 八木 絵香, 平井 啓, 谷向 仁, 伊藤 和憲, 川口 裕子, 渡辺 眞実, 福田 文彦, 石崎 直人, 上島 悦子, 阪上 未紀, 松本 めぐみ, 足立 由香, 谷口 敏淳, 宇留島 隼人, 坂本 淑子, 岩田 昌美, 伊藤 壽記

    (一社)日本統合医療学会 日本統合医療学会誌   6 ( 1 )   65 - 69   2013.05( ISSN:2435-5372

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    Publishing type:Research paper (scientific journal)  

    【背景】災害の負傷者、遺族らにおいて、一般保険医療では治療困難な後遺障害に対し、補完代替医療(CAM)に救いを求めることも少なくない。しかしその安全性、効果に対してのエビデンスは乏しい。【方法】この臨床試験は大阪大学医学部附属病院にて災害後遺障害者に対して施行した。そのうちJR福知山線脱線事故の被害者、遺族ら9人に対して解析を行った。一般保険医療が新たに必要な者、もしくは一般保険医療を受診も治療途中で、状態が落ち着いていない者を除外した。主要評価項目は介入完遂率とした。副次評価項目は抑うつ症状、PTSD様症状、介入の満足度、身体的、精神的苦痛などとした。鍼とアロマトリートメントを被検者に選んでもらい(両方も可)、週1回8週間にわたる介入が行われた。【結果】9例全てが鍼とアロマトリートメント両方を選び、完遂した。重篤な有害事象を認めなかった。介入直後は、身体的、精神的苦痛の有意な改善を認めた。介入を通じては、身体的、精神的苦痛の有意な改善は認めなかった。介入を通して、抑うつ尺度の有意な改善を認めた。(著者抄録)

  • 生活習慣病型癌患者を対象とした統合的なライフスタイル介入の試み Reviewed

    須見 遼子, 前田 和久, 宇留島 隼人, 平井 啓, 林 紀行, 蘆原 恵子, 田口 敬太, 松本 めぐみ, 阪上 未紀, 伊藤 和憲, 福田 文彦, 石崎 直人, 伊藤 壽記

    (一社)日本統合医療学会 日本統合医療学会誌   5 ( 2 )   43 - 48   2012.10

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    【背景】肥満は過栄養を介し、多くの癌の発症におけるリスクファクターと考えられている。そこで、生活習慣との関連が示唆される癌患者を対象に、医師、管理栄養士、臨床心理士、鍼灸師、アロマセラピストがチームとなり、統合的な介入を行い、BMI(Body Mass Index)の適正化と血中アディポネクチン濃度の改善を目的として、QOLの改善と合併症の軽減を目指す臨床試験を開始した。【方法】毎月1回介入を実施し、期間は1年とした。心理評価の実施や認知行動療法を取り入れた生活指導、鍼治療とアロマセラピーを含む森林療法を実施した。【結果】1年後のBMI・血中のアディポネクチン濃度は有意に改善した。森林療法の実施前後に測定したPOMS(Profile Mood States)においても有意な改善がみられた。【結語】生活習慣病型癌患者に対し、生活指導に加え、鍼灸治療やアロマセラピー、森林療法などの補完代替医療を集学的に実施する統合的なライフスタイルの介入は有用であると考えられた。(著者抄録)

  • 生活習慣病型癌患者を対象とした統合的なライフスタイル介入の試み Reviewed

    須見 遼子, 前田 和久, 宇留島 隼人, 平井 啓, 林 紀行, 蘆原 恵子, 田口 敬太, 松本 めぐみ, 阪上 未紀, 伊藤 和憲, 福田 文彦, 石崎 直人, 伊藤 壽記

    (一社)日本統合医療学会 日本統合医療学会誌   5 ( 2 )   43 - 48   2012.10

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    【背景】肥満は過栄養を介し、多くの癌の発症におけるリスクファクターと考えられている。そこで、生活習慣との関連が示唆される癌患者を対象に、医師、管理栄養士、臨床心理士、鍼灸師、アロマセラピストがチームとなり、統合的な介入を行い、BMI(Body Mass Index)の適正化と血中アディポネクチン濃度の改善を目的として、QOLの改善と合併症の軽減を目指す臨床試験を開始した。【方法】毎月1回介入を実施し、期間は1年とした。心理評価の実施や認知行動療法を取り入れた生活指導、鍼治療とアロマセラピーを含む森林療法を実施した。【結果】1年後のBMI・血中のアディポネクチン濃度は有意に改善した。森林療法の実施前後に測定したPOMS(Profile Mood States)においても有意な改善がみられた。【結語】生活習慣病型癌患者に対し、生活指導に加え、鍼灸治療やアロマセラピー、森林療法などの補完代替医療を集学的に実施する統合的なライフスタイルの介入は有用であると考えられた。(著者抄録)

    CiNii Article

  • 生活習慣病型癌患者を対象とした統合的なライフスタイル介入の試み

    須見 遼子, 前田 和久, 宇留島 隼人, 平井 啓, 林 紀行, 蘆原 恵子, 田口 敬太, 松本 めぐみ, 阪上 未紀, 伊藤 和憲, 福田 文彦, 石崎 直人, 伊藤 壽記

    日本統合医療学会誌   5 ( 2 )   43 - 48   2012.10( ISSN:2435-5372

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    【背景】肥満は過栄養を介し、多くの癌の発症におけるリスクファクターと考えられている。そこで、生活習慣との関連が示唆される癌患者を対象に、医師、管理栄養士、臨床心理士、鍼灸師、アロマセラピストがチームとなり、統合的な介入を行い、BMI(Body Mass Index)の適正化と血中アディポネクチン濃度の改善を目的として、QOLの改善と合併症の軽減を目指す臨床試験を開始した。【方法】毎月1回介入を実施し、期間は1年とした。心理評価の実施や認知行動療法を取り入れた生活指導、鍼治療とアロマセラピーを含む森林療法を実施した。【結果】1年後のBMI・血中のアディポネクチン濃度は有意に改善した。森林療法の実施前後に測定したPOMS(Profile Mood States)においても有意な改善がみられた。【結語】生活習慣病型癌患者に対し、生活指導に加え、鍼灸治療やアロマセラピー、森林療法などの補完代替医療を集学的に実施する統合的なライフスタイルの介入は有用であると考えられた。(著者抄録)

  • Phylogenetic relationships of rodent pinworms (genus Syphacia) in Japan inferred from 28S rDNA sequences. Reviewed

    Okamoto M, Urushima H, Hasegawa H

    Parasitology international   58 ( 4 )   330 - 3   2009.12( ISSN:1383-5769

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    DOI: 10.1016/j.parint.2009.07.001

    PubMed

  • Phylogenetic relationships of rodent pinworms (genus Syphacia) in Japan inferred from 28S rDNA sequences Reviewed

    Munehiro Okamoto, Hayato Urushima, Hideo Hasegawa

    PARASITOLOGY INTERNATIONAL   58 ( 4 )   330 - 333   2009.12( ISSN:1383-5769

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    The 28S rDNA from nine species of the genus Syphacia collected in Japan was sequenced, and the phylogenetic relationship was inferred from multiple sequence alignment of 28S FDNA by the MAFFT program. Phylogenetic tree indicates that S. petrusewiczi, which was the only species belonging to the subgenus Seuratoxyuris, has diverged earlier than other rodent pinworms examined and was distantly separated from the others genetically. It was revealed that S. agraria and S. vandenbrueli, whose subgeneric status has not been specified, belonged to the subgenus Syphacia together with other 6 species. Syphacia motana from Clethrionomys, Eothenomys and Microtus was very closely related to S. obvelata from Mus, and that S. frederici from Apodemus and S. vandenbrueli from Micromys were comparatively closely related to the former two species. The phylogenetic relationship among the three species of Syphacia found in Japanese Apodemus was inconsistent with the biogeography of host rodents. The co-evolutionary relationship between pinworm species and their host rodents may not be so strict and host switching has probably occurred frequently during the Course of evolution. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.parint.2009.07.001

  • Phylogenetic relationships of rodent pinworms (genus Syphacia) in Japan inferred from mitochondrial CO1 gene sequences. Reviewed

    Okamoto M, Urushima H, Iwasa M, Hasegawa H

    The Journal of veterinary medical science   69 ( 5 )   545 - 7   2007.05( ISSN:0916-7250

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    PubMed

  • Phylogenetic relationships of rodent pinworms (genus Syphacia) in Japan inferred from mitochondrial CO1 gene sequences Reviewed

    Munehiro Okamoto, Hayato Urushima, Masahiro Iwasa, Hideo Hasegawa

    JOURNAL OF VETERINARY MEDICAL SCIENCE   69 ( 5 )   545 - 547   2007.05( ISSN:0916-7250

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    Species of the genus Syphacia are considered to have generally co-evolved with their rodent hosts. This study detennined partial sequences of the CO1 gene from several species in the genus Syphacia and discuss the relationships between pinworms and their hosts. Syphacia montana, which parasitizes Microtinae, was closely related to S. frederici and S. obvelata, which parasitize Murinae. Although both S. obvelata and S. ohtaorum parasitize rodents in the genus Mus, these two species were not found to be closely related to each other. Syphacia frederici, S. emileromani and S. agraria are all pinworms of the Apodemus species, but genetic affiliation between these three species was not indicated. These facts suggest that the co-evolutionary relationship between species of the genus Svphacia and their host rodents may not so strict and host switching has probably occurred during the course of evolution.

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MISC

  • 【肝類洞壁細胞研究における新知見】肝星細胞と肝細胞の「構造-機能相関」 Reviewed

    宇留島 隼人, 池田 一雄

    (株)アークメディア 肝胆膵   82 ( 4 )   593 - 599   2021.04( ISSN:0389-4991

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  • 【肝類洞壁細胞研究における新知見】肝星細胞と肝細胞の「構造-機能相関」

    宇留島 隼人, 池田 一雄

    肝胆膵   82 ( 4 )   593 - 599   2021.04( ISSN:0389-4991

  • Structure-Function correlation between hepatic stellate cells and hepatocytes

    宇留島隼人, 池田一雄

    肝胆膵   82 ( 4 )   2021( ISSN:0389-4991

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  • 【肝星細胞活性化と肝硬変・肝がん】肝星細胞活性化の新規initiation factor Reviewed

    宇留島 隼人, 池田 一雄

    (株)ニュー・サイエンス社 細胞   51 ( 11 )   526 - 529   2019.10( ISSN:1346-7557

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    肝星細胞は肝小葉内で唯一ディッセ腔に存在する間葉系細胞であり、spineと呼ばれる突起を肝細胞へと伸ばし接着結合を形成している。しかしながら各種肝病態下でのサイトカインやケモカインなどの外因性刺激によって肝星細胞は活性化し、筋線維芽細胞へと形質転換することで間質細胞としての機能亢進を引き起こす。活性化肝星細胞は、肝細胞との接着を消失させた後、炎症部位に遊走、増殖し、線維化をもたらすと考えられる。細胞接着結合は単なる接着装置としての機能だけでなく、細胞内シグナル伝達を介して増殖や分化などを制御している。今回我々は肝星細胞における肝細胞との接着結合が肝星細胞の活性化抑制に寄与しており、この接着結合の消失が肝星細胞活性化の新規initiation factorであることを明らかにしたので報告する。(著者抄録)

  • 【肝星細胞活性化と肝硬変・肝がん】肝星細胞活性化の新規initiation factor

    宇留島 隼人, 池田 一雄

    細胞   51 ( 11 )   526 - 529   2019.10( ISSN:1346-7557

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    肝星細胞は肝小葉内で唯一ディッセ腔に存在する間葉系細胞であり、spineと呼ばれる突起を肝細胞へと伸ばし接着結合を形成している。しかしながら各種肝病態下でのサイトカインやケモカインなどの外因性刺激によって肝星細胞は活性化し、筋線維芽細胞へと形質転換することで間質細胞としての機能亢進を引き起こす。活性化肝星細胞は、肝細胞との接着を消失させた後、炎症部位に遊走、増殖し、線維化をもたらすと考えられる。細胞接着結合は単なる接着装置としての機能だけでなく、細胞内シグナル伝達を介して増殖や分化などを制御している。今回我々は肝星細胞における肝細胞との接着結合が肝星細胞の活性化抑制に寄与しており、この接着結合の消失が肝星細胞活性化の新規initiation factorであることを明らかにしたので報告する。(著者抄録)

  • 【肝星細胞活性化と肝硬変・肝がん】肝星細胞活性化の新規initiation factor Reviewed

    宇留島 隼人, 池田 一雄

    (株)ニュー・サイエンス社 細胞   51 ( 11 )   526 - 529   2019.10( ISSN:1346-7557

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    Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

    肝星細胞は肝小葉内で唯一ディッセ腔に存在する間葉系細胞であり、spineと呼ばれる突起を肝細胞へと伸ばし接着結合を形成している。しかしながら各種肝病態下でのサイトカインやケモカインなどの外因性刺激によって肝星細胞は活性化し、筋線維芽細胞へと形質転換することで間質細胞としての機能亢進を引き起こす。活性化肝星細胞は、肝細胞との接着を消失させた後、炎症部位に遊走、増殖し、線維化をもたらすと考えられる。細胞接着結合は単なる接着装置としての機能だけでなく、細胞内シグナル伝達を介して増殖や分化などを制御している。今回我々は肝星細胞における肝細胞との接着結合が肝星細胞の活性化抑制に寄与しており、この接着結合の消失が肝星細胞活性化の新規initiation factorであることを明らかにしたので報告する。(著者抄録)

  • リンパ管拡張症と診断され重度下痢を来したイヌに対し補完的に宮入菌・グルタミンを投与し有効であった1例

    宇留島隼人, 濱谷泰孝, 村雲咲野香, 林紀行, 前田和久, 伊藤壽記

    機能性食品と薬理栄養   8 ( 1 )   108 - 108   2013.12( ISSN:1348-2564

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  • シソエキスのDSS誘導腸炎に対する抑制効果の検討

    宇留島隼人, 西村潤一, 三浦健人, 林紀行, 前田和久, 伊藤壽記

    機能性食品と薬理栄養   7 ( 4 )   353 - 353   2012.12( ISSN:1348-2564

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  • 血管病に関する最新の話題 チアゾリジン誘導体と膀胱がん Reviewed

    宇留島 隼人, 伊藤 壽記, 前田 和久

    (株)先端医学社 Vascular Medicine   8 ( 1 )   85 - 88   2012.04( ISSN:1880-2478

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    チアゾリジン誘導体は、ペルオキシソーム増殖因子活性化受容体γ(PPARγ)のリガンドでインスリン抵抗性改善作用を有し、糖尿病患者の血糖コントロールに寄与している。また、他にも心血管イベントに対するベネフィットも報告されている。一方、大規模疫学調査により膀胱がんの発生リスクを上昇させるという報告もある。膀胱がんの発症には人種差、性差が認められるため、日本人を対象とした疫学研究が必要である。しかし、疫学研究の限界も踏まえ、臨床現場においてはリスク-ベネフィットを考慮した処方が必要である。(著者抄録)

  • 血管病に関する最新の話題 チアゾリジン誘導体と膀胱がん Reviewed

    宇留島 隼人, 伊藤 壽記, 前田 和久

    (株)先端医学社 Vascular Medicine   8 ( 1 )   85 - 88   2012.04( ISSN:1880-2478

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    Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

    チアゾリジン誘導体は、ペルオキシソーム増殖因子活性化受容体γ(PPARγ)のリガンドでインスリン抵抗性改善作用を有し、糖尿病患者の血糖コントロールに寄与している。また、他にも心血管イベントに対するベネフィットも報告されている。一方、大規模疫学調査により膀胱がんの発生リスクを上昇させるという報告もある。膀胱がんの発症には人種差、性差が認められるため、日本人を対象とした疫学研究が必要である。しかし、疫学研究の限界も踏まえ、臨床現場においてはリスク-ベネフィットを考慮した処方が必要である。(著者抄録)

    CiNii Article

  • 血管病に関する最新の話題 チアゾリジン誘導体と膀胱がん

    宇留島 隼人, 伊藤 壽記, 前田 和久

    Vascular Medicine   8 ( 1 )   85 - 88   2012.04( ISSN:1880-2478

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    チアゾリジン誘導体は、ペルオキシソーム増殖因子活性化受容体γ(PPARγ)のリガンドでインスリン抵抗性改善作用を有し、糖尿病患者の血糖コントロールに寄与している。また、他にも心血管イベントに対するベネフィットも報告されている。一方、大規模疫学調査により膀胱がんの発生リスクを上昇させるという報告もある。膀胱がんの発症には人種差、性差が認められるため、日本人を対象とした疫学研究が必要である。しかし、疫学研究の限界も踏まえ、臨床現場においてはリスク-ベネフィットを考慮した処方が必要である。(著者抄録)

  • AHCCによるがん化学療法の有害事象軽減に関する臨床試験

    宇留島隼人, 林紀行, 前田和久, 北川透, 阪上未紀, 須見遼子, 平井啓, 近藤一博, 伊藤壽記

    機能性食品と薬理栄養   7 ( 1 )   131 - 131   2011.12( ISSN:1348-2564

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Presentations

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Grant-in-Aid for Scientific Research

  • メカノトランスダクションを介した肝星細胞活性化メカニズムの解明

    Grant-in-Aid for Young Scientists(B)  2018.04

Contract research

  • 肝線維化を伴う難治疾患と肝星細胞におけるプリオン発現の関連

    大阪難病財団  2019.04

Incentive donations / subsidies

  • 細胞伸展受容体を介する肝がん細胞アポトーシス抑制機序の解明 および新規創薬標的の探索

    大阪市立大学  2018.04

Charge of on-campus class subject

  • 人体を考える

    2019     Undergraduate

Faculty development activities

  • FD活動への貢献  2018

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    FD講演「私の教育への取り組みについて」

Other

  • Job Career

    2021.07 - Now

  • Job Career

    2016.10 - 2021.06