細胞未病エンジニアリング研究グループ

研究課題

老化はALSやアルツハイマー病など様々な神経疾患のリスク因子です。近年、この老化に伴う神経疾患の根本治療や早期診断を目指して、液-液相分離の制御法および可視化法の開発が期待されています。私は寿命の短い線虫C. elegansを用いて液-液相分離・神経機能・老化の制御因子群を明らかにし、その知見を利用したヒト細胞ハイスループット評価系を開発しています。また、これらの評価系を活用した疾患予防・先制に資する機能性物質の探索を進めています。

高齢者が生き生きと暮らせる社会の実現のためには、身体機能のみならず心の健康寿命の延伸が重要です。睡眠障害は、うつ病などの精神疾患や、高血圧や糖尿病といった生活習慣病の発症リスクを高めることが知られています。私たちは、疾患の発症につながるような慢性的な睡眠の乱れを、AI技術も活用しながら、非侵襲的に早期発見するためのバイオマーカーの開発を行っています。同時に、産学官の連携を積極的に推進することにより、時間栄養学を活用した睡眠や体内時計の積極的な制御技術の開発を行っています。

• 生活習慣病の予防や改善を目指した時間栄養学

うつ病は罹患人口の増大化、標的患者層の広範化など大きな焦点をもちます。治療には必ず再発のリスクが伴う医学背景があります。他疾患に罹患している際に、潜在的にうつ病が進行加速する機序や、うつ病が原因で他疾患を誘引する背景の解明を目指しています。うつ病に関連して罹患リスクが増加する疾患、糖尿病や筋疾患など潜在的にうつ病発症増加リスクをもつ疾患などのモデル動物や、抽出し樹立した細胞培養系、誘導培養系らを比較解析します。各疾患のタイムコースに沿う候補遺伝子や作用因子、変化する細胞、臓器内領域を特定します。

骨格筋は運動器として日々の生活活動を支えるのみならず、代謝や神経活動の調節も担っています。私は、健康寿命の延伸を実現するためには、骨格筋の質・量の改善が重要な鍵を握ると考えています。加齢によるサルコペニア発症の新規分子機序の解明と、筋細胞モデルの開発から機能性成分の探索・作用機序の解明を行うことで、食による骨格筋の質・量の改善を目指します。

心理的ストレスは、うつ病などの精神疾患の原因となるだけでなく、肝疾患や心疾患の発症リスクを増大させることが知られています。本課題では主に社会心理的ストレスモデルマウスを用いて、心理的ストレスが肝臓や心臓にもたらす影響の解明を目指すとともに、疾患発症を予測できる未病マーカーの開発に取り組んでいます。 この他、培養細胞や単離ミトコンドリアを用いて、肝疾患や神経疾患の発症メカニズムの解明と、生活習慣による介入方法の開発にも取り組んでいます。

超高齢化社会においては健康寿命の延伸が重要な課題ですが、老化によりがんや認知症など多くの疾患のリスクが高まることが知られています。そこで本研究では、老化のメカニズムを分子レベルで明らかにすることを目的とし、老化促進モデルマウスを用いて老化因子の探索を行っています。さらに、未病の段階から健康維持に寄与するとされる運動にも着目し、実験動物を用いた運動介入実験を実施しています。また、運動の生理的効果を細胞レベルで再現するための模倣技術の開発にも取り組んでいます。これらの研究を通じて、老化や未病の進行に関与する新たな分子メカニズムおよび運動による健康効果の解明を目指しています。

業績リスト

• Ohkura, N; Morimoto-Kamata ,R; Kamikubo, Y; Takahashi, Y; Oishi, K.
  Hypofibrinolytic phenotype in Tsumura Suzuki Obese Diabetes (TSOD) mice unrelated to hyperglycemia.
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• Ohkura, N; Morimoto-Kamata, R; Oishi, K; Higo-Yamamoto, S; Fujinami, A; Inoue, KI; Ohta, M.
  Supplementation with Ashitaba (Angelica keiskei) yellow stem exudate prevents aging-induced thrombotic tendencies and systemic inflammation without affecting body weight gain in mice.
  J Med Food. 2023 Nov;26(11):843-848. doi: 10.1089/jmf.2023.K.0140
• Oishi, K; Yajima, Y; Yoshida, Y; Hagihara, H; Miyakawa, T; Higo-Yamamoto, S; Toyoda, A.
  Metabolic profiles of saliva in male mouse models of chronic sleep disorders induced by psychophysiological stress.
  Sci Rep. 2023;13(1):11156. doi: 10.1038/s41598-023-38289-1
• Hagihara, H; Shoji, H; Hattori, S; Sala, G; Takamiya, Y; Tanaka, M; Ihara, M; Shibutani, M; Hatada, I; Hori, K;... Oishi, K; ... Miyakawa, T.
  Large-scale animal model study uncovers altered brain pH and lactate levels as a transdiagnostic endophenotype of neuropsychiatric disorders involving cognitive impairment.
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• Kanie, S; Wu, C; Kihira, K; Yasuno, R; Mitani, Y; Ohmiya, Y.
  Bioluminescence of (R)-Cypridina Luciferin with Cypridina Luciferase.
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• Sato, T; Oishi, K.
  Time-restricted feeding has a limited effect on hepatic lipid accumulation, inflammation and fibrosis in a choline-deficient high-fat diet-induced murine NASH model.
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• Sato, T; Ochiishi, T; Higo-Yamamoto, S; Oishi, K.
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• Roberts, MD; McCarthy, JJ; Hornberger, TA; Phillips, SM; Mackey, AL; Nader, GA; Boppart, MD; Kavazis, AN; Reidy, PT; Ogasawara, R, Libardi, CA; Ugrinowitsch, C; Booth, FW; Esser, KA.
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• Zhuang, HT; Fujikura, Y, Ohkura, N; Higo-Yamamoto, S; Mishima, T; Oishi, K.
  A ketogenic diet containing medium-chain triglycerides reduces REM sleep duration without significant influence on mouse circadian phenotypes.
  FOOD RESEARCH INTERNATIONAL. 2023 Jul;169:112852. doi: 10.1016/j.foodres.2023.112852
• Abe, T, Sato, T, Murotomi, K.
  Sudachitin and Nobiletin Stimulate Lipolysis via Activation of the cAMP/PKA/HSL Pathway in 3T3-L1 Adipocytes.
  FOODS. 2023 May 10;12(10):1947 doi: 10.3390/foods12101947
• Ato, S; Matsunami, H;Ogasawara, R.
  Aging is associated with impaired postprandial response of skeletal muscle protein synthesis to high-intensity muscle contraction in mice.
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• Yoshida, Y; Yajima, Y; Fujikura, Y; Zhuang, H; Higo-Yamamoto, S; Toyoda, A; Oishi, K.
  Identification of salivary microRNA profiles in male mouse model of chronic sleep disorder.
  Stress. 2022;26(1):21-28. doi: 10.1080/10253890.2022.2156783
• Yoshida, Y; Yajima, Y; Kawakami, K; Nakamura, S; Tsukahara, T; Oishi, K; Toyoda, A.
  Salivary microRNA and metabolic profiles in a mouse model of subchronic and mild social defeat stress.
  Int J Mol Sci. 2022;23:14479. doi: 10.3390/ijms232214479
• Horikawa, K; Hashimoto, C; Kikuchi, Y; Makita, M; Oishi, K.
  Wheat alkylresorcinol increases fecal lipid excretion and suppresses feed efficiency in mice depending on the time of supplementation.
  Nutrition. 2022;103-104:111796. doi: 10.1016/j.nut.2022.111796
• Ohkura, N; Taniguchi, M; Oishi, K; Inoue, K; Ohta, M.
  Angelica keiskei (Ashitaba) has potential as an antithrombotic health food.
  Food Res. 2022;6(2):18-24. doi: 10.26656/fr.2017.6(2).121
• Abe, T.
  Timing of Medium-Chain Triglyceride Consumption Modulates Effects in Mice with Obesity Induced by a High-Fat High-Sucrose Diet.
  NUTRIENTS. 2022 Dec 1;14(23):5096. doi: 10.3390/nu14235096
• Fujikura, Y; Yamanouchi, K; Sugihara, H; Hatakeyama, M; Abe, T; Ato, S; Oishi, K.
  Ketogenic diet containing medium-chain triglyceride ameliorates transcriptome disruption in skeletal muscles of rat models of duchenne muscular dystrophy.
  BIOCHEM BIOPHYS REP. 2022 Nov 11;32:101378. doi: 10.1016/j.bbrep.2022.101378
• Miyazaki, K; Itoh, N; Saiki, P; Kuroki, Y.
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• Yasuno, R; Mitani, Y; Ohmiya, Y.
  Gene Cloning and Functional Analysis of the Luciferase from Luminous Syllids of the Genus Odontosyllis.
  METHODS MOL BIOL. 2022;2524:3-15. doi: 10.1007/978-1-0716-2453-1_1
• Fujikura, Y; Kimura, K; Yamanouchi, K; Sugihara, H; Hatakeyama, M; Zhuang, H; Abe, T; Daimon, M; Morita, H; Komuro, I; Oishi, K.
  A medium-chain triglyceride containing ketogenic diet exacerbates cardiomyopathy in a CRISPR/Cas9 gene-edited rat model with Duchenne muscular dystrophy.
  SCI REP. 2022 Jul 8;12(1):11580. doi: 10.1038/s41598-022-15934-9
• Mitani, Y; Yasuno, R; Kihira, K; Chung, KM; Mitsuda, N; Kanie, S; Tomioka, A; Kaji, H; Ohmiya, Y.
  Host-Dependent Producibility of Recombinant Cypridina noctiluca Luciferase With Glycosylation Defects.
  FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY 10;doi: 10.3389/fbioe.2022.774786 FEB 7
• Saiki, P; Yoshihara, M; Kawano, Y; Miyazaki, H; Miyazaki, K.
  Anti-Inflammatory Effects of Heliangin from Jerusalem Artichoke (Helianthus tuberosus) Leaves Might Prevent Atherosclerosis.
  BIOMOLECULES 12 (1); doi:10.3390/biom12010091 JAN
• Konishi, T; Takahashi, Y; Shiina, Y; Oike, H; Oishi, K.
  Time-of-day effects of consumption of fish oil-enriched sausages on serum lipid parameters and fatty acid composition in normolipidemic adults: A randomized, double-blind, placebo-controlled, and parallel-group pilot study.
  Nutrition. 2021;90:111247. doi: 10.1016/j.nut.2021.111247
• Fujikura, Y; Sugihara, H; Hatakeyama, M; Oishi, K; Yamanouchi, K.
  Ketogenic diet with medium-chain triglycerides restores skeletal muscle function and pathology in a rat model of Duchenne muscular dystrophy.
  FASEB J. 2021 Sep;35(9):e21861. doi: 10.1096/fj.202100629R
• Yamamoto K, Honda T, Yokoyama S, Ma L, Kato A, Ito T, Ishizu Y, Kuzuya T, Nakamura M, Kawashima H, Ishigami M, Tsuji NM, Fujishiro M
  Microbiome, fibrosis and tumor networks in a non-alcoholic steatohepatitis model of a choline-deficient high-fat diet using diethylnitrosamine
  Dig Liver Dis. 2021 Mar 13:S1590-8658(21)00081-5. doi: 10.1016/j.dld.2021.02.013
• Ueoka R, Hashimoto J, Kozone I, Hashimoto T, Kudo K, Kagaya N, Suenaga H, Ikeda H, Shin-Ya K
  A novel methymycin analog, 12-ketomethymycin N-oxide, produced by the heterologous expression of the large pikromycin/methymycin biosynthetic gene cluster of Streptomyces sp. AM4900.
  BIOSCI BIOTECHNOL BIOCHEM. 2020 Dec 22:zbaa111. doi: 10.1093/bbb/zbaa111
• Saito S, Kakizaki N, Okuno A, Maekawa T, Tsuji NM
  Lactococcus lactis subsp. Cremoris C60 restores T Cell Population in Small Intestinal Lamina Propria in Aged Interleukin-18 Deficient Mice
  Nutrients.12(11):E3287. (2020) doi: 10.3390/nu12113287
• Ueoka R, Shinzato N, Kagaya N, Suenaga H, Shin-Ya K
  Pseudoalteropeptide A, a novel lipopeptide from the marine bacterium Pseudoalteromonas piscicida SWA4_PA4 isolated from marine seaweed
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• Saiki P, Kawano Y, Ogi T, Klungsupya P, Muangman T, Phantanaprates W, Kongchinda P, Pinnak N, Miyazaki K
  Purified Gymnemic Acids from Gymnema inodorum Tea Inhibit 3T3-L1 Cell Differentiation into Adipocytes
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• Abe T, Yamamoto S, Konishi T, Takahashi Y, Oishi K
  Maternal fish oil supplementation ameliorates maternal high-fructose diet-induced dyslipidemia in neonatal mice with suppression of lipogenic gene expression in livers of postpartum mice
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• Li X, Wang X, Ito A, Tsuji NM
  A nanoscale metal organic frameworks-based vaccine synergises with PD-1 blockade to potentiate anti-tumour immunity
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• Sakamoto K, Higo-Yamamoto S, Egi Y, Miyazaki K, Oishi K.
  Memory dysfunction and anxiety-like behavior in a mouse model of chronic sleep disorders.
  BIOCHEM BIOPHYS RES COMMUN. 529:175-179. (2020) doi:10.1016/j.bbrc.2020.05.218
• Hishiki H, Kawashima T, Tsuji NM, Ikari N, Takemura R, Kido H, Shimojo N
  A Double-Blind, Randomized, Placebo-Controlled Trial of Heat-Killed Pediococcus acidilactici K15 for Prevention of Respiratory Tract Infections among Preschool Children
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• Kimura Y, Yasuno R, Watanabe M, Kobayashi M, Iwaki T, Fujimura C, Ohmiya Y, Yamakage K, Nakajima Y, Kobayashi M, Mashimo N, Takagi Y, Omori T, Corsini E, Germolec D, Inoue T, Rogen EL, Kojima H, Aiba S
  An international validation study of the IL-2 Luc assay for evaluating the potential immunotoxic effects of chemicals on T cells and a proposal for reference data for immunotoxic chemicals
  Toxicol In Vitro 66: 104832 (2020) doi: 10.1016/j.tiv.2020.104832
• Prapaipat K, Saiki P, Bhusita, W, Supatjaree R, Thanchanok M, Nantana B, Weerasak, T
  Probiotic property and biological activities of Bifidobacterium animalis subsp. lactis TISTR 2591 isolated from Thai population.
  WJARR 5: 149-162 (2020) doi: 10.30574/wjarr.2020.5.3.0072
• Hashimoto T, Kozone I, Hashimoto J, Ueoka R, Kagaya N, Fujie M, Sato N, Ikeda H, Shin-ya K
  Novel macrolactam compound produced by the heterologous expression of a large cryptic biosynthetic gene cluster of Streptomyces rochei IFO12908
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• Okauchi H, Higo-Yamamoto S, Sowa T, Oike H, Yamamoto S, Wada N, Sakamoto K, Oishi K
  Chronically skipping breakfast impairs hippocampal memory-related gene expression and memory function accompanied by reduced wakefulness and body temperature in mice
  Biochem Biophys Res Commun. 524: 129-134 (2020) doi: 10.1016/j.bbrc.2020.01.077
• Oishi K, Okauchi H, Yamamoto S, Higo-Yamamoto S
  Dietary natural cocoa ameliorates disrupted circadian rhythms in locomotor activity and sleep-wake cycles in mice with chronic sleep disorders caused by psychophysiological stress
  Nutrition. 75-76: 110751 (2020) doi: 10.1016/j.nut.2020.110751
• Nakao R, Abe T, Yamamoto S, Oishi K
  Ketogenic diet induces skeletal muscle atrophy via reducing muscle protein synthesis and possibly activating proteolysis in mice
  Sci Rep. 9: 19652 (2019) doi: 10.1038/s41598-019-56166-8
• Abe T, Kazama R, Okauchi H, Oishi K
  Food deprivation during active phase induces skeletal muscle atrophy via IGF-1 reduction in mice
  Arch Biochem Biophys. 677: 1080160 (2019) doi: 10.1016/j.abb.2019.108160
• Oike H, Ogawa Y, Oishi K
  Simple and Quick Visualization of Periodical Data Using Microsoft Excel
  Methods Protoc. 2: 81 (2019) doi: 10.3390/mps2040081
• Saiki P, Kawano Y, Nakajima Y, Van Griensven LJLD, Miyazaki K
  Novel and Stable Dual-Color IL-6 and IL-10 Reporters Derived from RAW 264.7 for Anti-Inflammation Screening of Natural Products
  Int J Mol Sci. 20: 4620 (2019) doi: 10.3390/ijms20184620
• Mitani Y, Yasuno R, Futahashi R, Oakley TH, Ohmiya Y
  Luciferase gene of a Caribbean fireworm (Syllidae) from Puerto Rico
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• Wang XP, Ihara S, Li X, Ito A, Sogo Y, Watanabe Y, Yamazaki A, , Tsuji NM, Ohno T
  Rod-Scale Design Strategies for Immune-Targeted Delivery System toward Cancer Immunotherapy
  Acs Nano 13: 7705-7715 (2019) doi: 10.1021/acsnano.9b01271
• Gabriel GVD, Yasuno R, Mitani Y, Ohmiya Y, Viviani VR
  Novel application of Macrolampis sp2 firefly luciferase for intracellular pH-biosensing in mammalian cells
  Photochemical 18: 1212-1217 (2019) doi: 10.1039/c8pp00573g
• Katsuki R, Sakata S, Nakao R, Oishi K, Nakamura Y
  Lactobacillus curvatus CP2998 Prevents Dexamethasone-Induced Muscle Atrophy in C2C12 Myotubes
  J Nutr Sci Vitaminol 65: 455-458 (2019) doi: 10.3177/jnsv.65.455
• Ohta M, Fujinami A, Oishi K, Kobayashi N, Ohnishi K, Ohkura N
  Ashitaba (Angelica Keiskei) Exudate Prevents Increases in Plasminogen Activator Inhibitor-1 Induced by Obesity in Tsumura Suzuki Obese Diabetic Mice
  J Diet Suppl. 16: 331-344 (2019) doi: 10.1080/19390211.2018.1458366
• Higo-Yamamoto S, Yamamoto S, Miyazaki K, Nakakita Y, Kaneda H, Takata Y, Nakamura T, Oishi K
  Dietary Heat-Killed Lactobacillus brevis SBC8803 Attenuates Chronic Sleep Disorders Induced by Psychophysiological Stress in Mice
  J Nutr Sci Vitaminol 65: 164-170 (2019) doi: 10.3177/jnsv.65.164
• Adachi T, Yoshikawa S, Tezuka H, Tsuji NM, Ohteki T, Karasuyama H, Kumazawa T
  Propolis induces Ca2+ signaling in immune cells
  Biosci Microbiota Food Health 38: 141-149 (2019) doi: 10.12938/bmfh.19-011
• Oishi K, Okauchi H
  Functional CLOCK Is Not Essentially Associated with Metabolic Disruption Caused by Sleep Phase Feeding in Mice
  Biol Pharm Bull. 42: 1038-1043 (2019) doi: 10.1248/bpb.b19-00018
• Akimoto H, Oshima S, Sugiyama T, Negishi A, Nemoto T, Kobayashi D
  Changes in brain metabolites related to stress resilience: Metabolomic analysis of the hippocampus in a rat model of depression
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• Wang X, Ihara S, Li X, Ito A, Sogo Y, Watanabe Y, Tsuji NM, Yamazaki A
  Si-doping increases the adjuvant activity of hydroxyapatite nanorods
  Colloids Surf B Biointerfaces. 174: 300-307 (2019) doi: 10.1016/j.colsurfb.2018.11.026
• Okauchi H, Hashimoto C, Nakao R, Oishi K
  Timing of food intake is more potent than habitual voluntary exercise to prevent diet-induced obesity in mice
  Chronobiol Int. 36: 57-74 (2019) doi: 10.1080/07420528.2018.1516672
• Carreras J, Lopez-Guillermo A, Kikuti YY, Itoh J, Masashi M, Ikoma H, Tomita S, Hiraiwa S, Hamoudi R, Rosenwald A, Leich E, Martinez A, Roncador G, Villamor N, Colomo L, Perez P, Tsuji NM, Campo E, Nakamura N.
  High TNFRSF14 and low BTLA are associated with poor prognosis in Follicular Lymphoma and in Diffuse Large B-cell Lymphoma transformation.
  J Clin Exp Hematop. 59: 1-16 (2019) doi: 10.3960/jslrt.19003
• Shibakami M, Sohma M, Kijima N, Nemoto T
  Melt spinnabilities of thermoplastic paramylon mixed esters
  Heliyon. 5: e02843 (2019) doi: 10.1016/j_heliyon_2019.e02843
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  血液濾過透析が糖尿病性腎臓病 (diabetic kidney disease: DKD) 由来腎不全患者のアミノ酸動態に及ぼす影響 : 予備的検討
  日本透析医学会雑誌 52: 457-462 (2019) doi: 10.4009/jsdt52.457
• Shibakami M, Nemoto T, Sohoma M.
  Dependence of dissolution, dispersion, and aggregation characteristics of cationic polysaccharides made from euglenoid β-1,3-glucan on degree of substitution
  CELLULOSE 25: 2217-2234 (2018) doi: 10.1007/s10570-018-1740-4
• Akimoto H, Oshima S, Michiyama Y, Negishi A, Nemoto T, Kobayashi D
  Metabolic Profiling of the Hippocampus of Rats Experiencing Nicotine-Withdrawal Symptoms
  Biol Pharm Bull. 41: 1879-1884 (2018) doi: 10.1248/bpb.b18-00486
• Saiki P, Nakajima Y, Van Griensven LJLD, Miyazaki K
  Real-time monitoring of IL-6 and IL-10 reporter expression for anti-inflammation activity in live RAW 264.7cells
  Biochem Biophys Res Commun. 505: 885-890 (2018) doi: 10.1016/j.bbrc.2018.09.173
• Oishi K, Hashimoto C
  Short-term time-restricted feeding during the resting phase is sufficient to induce leptin resistance that contributes to development of obesity and metabolic disorders in mice
  Chronobiol Int. 35: 1576-1594 (2018) doi: 10.1080/07420528.2018.1496927
• Lv Y, Cui M, Lv Z, Lu J, Zhang X, Zhao Z, Wang Y, Gao L, Tsuji NM, Yan H
  Expression and significance of peripheral myeloid-derived suppressor cells in chronic hepatitis B patients
  Clin Res Hepatol Gastroenterol. 42: 462-469 (2018) doi: 10.1016/j.clinre.2018.04.002
• Wada T, Ichihashi Y, Suzuki E, Kosuge Y, Ishige K, Uchiyama T, Makishima M, Nakao R, Oishi K, Shimba S
  Deletion of Bmal1 Prevents Diet-Induced Ectopic Fat Accumulation by Controlling Oxidative Capacity in the Skeletal Muscle
  Int J Mol Sci. 19: 2813 (2018) doi: 10.3390/ijms19092813
• Mitani Y, Yasuno R, Isaka M, Mitsuda N, Futahashi R, Kamagata Y, Ohmiya Y
  Novel gene encoding a unique luciferase from the fireworm Odontsyllis undecimdonta
  Sci Rep. 8: 12789 (2018) doi: 10.1038/s41598-018-31086-1
• Yasuno R, Mitani Y, Ohmiya Y
  Effects of N-Glycosylation Deletions on Cypridina Luciferase Activity
  Photochem Photobiol. 94: 338-342 (2018) doi: 10.1111/php.12847
• Kawashima T, Ikari N, Kouchi T, Kowatari Y, Kubota Y, Shimojo N, Tsuji NM
  The molecular mechanism for activating IgA production by Pediococcus acidilactici K15 and the clinical impact in a randomized trial
  Sci Rep. 8: 5065 (2018) doi: 10.1038/s41598-018-23404-4
• Oishi K, Konishi T, Hashimoto C, Yamamoto S, Takahashi Y, Shiina Y
  Dietary fish oil differentially ameliorates high-fructose diet-induced hepatic steatosis and hyperlipidemia in mice depending on time of feeding
  J Nutr Biochem. 42: 462-469 (2018) doi: 10.1016/j.jnutbio.2017.09.024
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  Chronic sleep disorder induced by psychophysiological stress induces glucose intolerance without adipose inflammation in mice
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