財満　信宏 （ザイマ　ノブヒロ）

コミュニケーション情報 byコメンテータガイド

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  血管疾患発症機構の解明と予防・治療法の確立を行っているほか、食品と人間、香りと人間の関係を明らかにする研究を行っています。

• 報道関連出演・掲載一覧

  ＜報道関連出演・掲載一覧＞ ●2023/5/25 　産経新聞 　閉経後の血管を核酸が保護することについて ●2023/2/15 　日刊工業新聞 　中性脂肪「トリカプリン」について ●2020/7/27 夕刊フジ 中性脂肪の役割について

研究者情報

学位

• 博士（農学）（2007年03月 京都大学大学院）

ホームページURL

https://jglobal.jst.go.jp/detail?JGLOBAL_ID=201401009239471795

J-Global ID

• 201401009239471795

プロフィール

• 近畿大学アグリ技術革新研究所　学際生命科学研究室

  
  

  https://www.nara.kindai.ac.jp/laboratory/gakusai-seimei/index.html

研究キーワード

• 脂質代謝異常   質量分析イメージング   質量顕微鏡   脂質蓄積ミオパチー   脂質   ATGL変異症   脂肪肝   動脈硬化   病理解析   粥状動脈硬化   腹部大動脈瘤   自閉症   

現在の研究分野（キーワード）

血管疾患発症機構の解明と予防・治療法の確立を行っているほか、食品と人間、香りと人間の関係を明らかにする研究を行っています。

研究分野

• その他 / その他 / 病態検査学
• ライフサイエンス / 食品科学

経歴

• 2021年04月 - 現在  近畿大学農学部教授
• 2018年 - 現在  近畿大学アグリ技術革新研究所学際生命科学研究室室長（兼任）
• 2015年04月 - 2020年03月  近畿大学農学部准教授
• 2016年09月 - 2017年02月  Imperial College Londonvisiting researcher
• 2011年04月 - 2015年03月  近畿大学農学部講師
• 2008年10月 - 2011年03月  浜松医科大学分子イメージング先端研究センター特任助教
• 2007年04月 - 2008年09月  三菱化学生命科学研究所特別研究員

学歴

• 2004年04月 - 2007年03月   京都大学   農学研究科博士後期課程
• 2002年04月 - 2004年03月   京都大学   大学院農学研究科博士前期課程
• 1997年04月 - 2002年03月   京都大学   農学部

研究活動情報

論文

• Nucleic acids and collagen can attenuate ovariectomy-induced degeneration of fibers in the abdominal aortic wall of female rat

  Mayo Higashihara; Hirona Kugo; Tomomi Nakamura; Tomoko Sumi; Daisuke Shimizu; Keisuke Kiriyama; Mica Fujita; Keita Sutoh; Tatsuya Moriyama; Nobuhiro Zaima

  PharmaNutrition 100360 - 100360 2023年10月 [査読有り]
  
• スギ花粉抗原の経皮感作能の評価と検証

  原田 陽平; 土喰 光希; 嶌田 力也; 棚橋 菜々; 矢野 えりか; 財満 信宏; 森山 達哉

  アレルギーの臨床 43 5 401 - 403 (株)北隆館 2023年05月 

  花粉症では,花粉抗原の吸引感作が発症基盤となるが,近年注目されている経皮感作が成立しうる可能性も想定される。そこで,本研究では,マウスモデルを用いて,スギ花粉抽出液を皮膚に塗布し,血中での抗原特異的Th2型抗体(IgE,IgG1)の産生を検証,評価を試みた。その結果,抗原特異的IgEの産生は認められなかったが,抗原特異的IgG1に関しては,いくつかのマウス個体で確認された。この結果から,条件によっては,花粉抗原も一定の経皮感作能を有する可能性が示唆された。(著者抄録)
• 食品香気成分であるβカリオフィレン吸入後の体内移行と血管に及ぼす影響

  財満 信宏; 東原 真代; 松村 晋一; 吉岡 百合; 森山 達哉

  脂質生化学研究 65 289 - 290 日本脂質生化学会 2023年05月
• ニコチン誘導性血管変性に対するβ-カリオフィレンの保護効果

  東原 真代; 岸 千尋; 竹本 有希; 亀井 萌花; 吉岡 百合; 松村 晋一; 森山 達哉; 財満 信宏

  日本栄養・食糧学会大会講演要旨集 77回 244 - 244 (公社)日本栄養・食糧学会 2023年03月
• 納豆の低アレルゲン性、経皮感作能、及び経口免疫寛容誘導能の検証

  嶌田 力也; 原田 陽平; 米澤 美乃里; 矢野 えりか; 財満 信宏; 森山 達哉

  日本栄養・食糧学会大会講演要旨集 77回 287 - 287 (公社)日本栄養・食糧学会 2023年03月
• Tricaprin can prevent the development of AAA by attenuating aortic degeneration.

  Hirona Kugo; Yuki Sugiura; Rena Fujishima; Shintou Jo; Hirotaka Mishima; Erina Sugamoto; Hiroki Tanaka; Satoshi Yamaguchi; Yoshihiko Ikeda; Ken-Ichi Hirano; Tatsuya Moriyama; Nobuhiro Zaima

  Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 160 114299 - 114299 2023年01月 [査読有り]
   

  Medical therapeutic options to prevent rupture of abdominal aortic aneurysm (AAA), a critical event, must be developed. Moreover, further understanding of the process of AAA development and rupture is crucial. Previous studies have revealed that aortic hypoperfusion can induce the development of AAA, and we successfully developed a hypoperfusion-induced AAA animal model. In this study, we examined the effects of medium-chain triglycerides (MCTs), tricaprylin (C8-TG) and tricaprin (C10-TG), on hypoperfusion-induced AAA rat model. We estimated the effects of MCTs on aortic pathologies, mechanical properties of the aorta, and development of AAA. C10-TG, but not C8-TG, significantly suppressed AAA development and completely prevented the rupture. We observed that C10-TG prevented the development and rupture of AAA, but not C8-TG. Additionally, regression of AAA diameter was observed in the C10-TG group. Pathological analysis revealed C10-TG improved the hypoperfusion-induced increase in hypoxia-inducible factor-1α levels, medial smooth muscle cells (SMCs) loss, degeneration of aortic elastin and collagen fibers, and loss of aortic wall elasticity. In addition, regression of the formed AAA was observed by administration of C10-TG after AAA formation. C10-TG administration after AAA formation improved degeneration of AAA wall including degradation of aortic elastin and collagen fibers, stenosis of vasa vasorum, and loss of medial SMCs. These data suggest C10-TG can prevent AAA by attenuating aortic hypoperfusion and degeneration. Considering the clinical safety of C10-TG, C10-TG can be a promising AAA drug candidate.
• Desorption electrospray ionization-mass spectrometry imaging of carnitine and imidazole dipeptides in pork chop tissues.

  Hirofumi Enomoto; Nobuhiro Zaima

  Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 1216 123601 - 123601 2023年01月 [査読有り]
   

  Carnitine is essential for energy production and lipid metabolism in skeletal muscle. Carnosine and its methylated analogs anserine and balenine are histidine-containing imidazole dipeptides, which are antioxidative compounds. They are major health-related components in meat; however, analytical technique to investigate their distribution among tissues have not fully established. Here, we performed desorption electrospray ionization (DESI)-mass spectrometry imaging (MSI) of pork chop sections containing longissimus thoracis et lumborum muscle (loin), intermuscular fat tissue, transparent tissue, and spinalis muscle to investigate the distributions of carnitine and imidazole dipeptides. Liquid chromatography-MS revealed that the concentrations of carnitine, carnosine, anserine, and balenine were 11.0 ± 0.9, 330.1 ± 15.5, 21.2 ± 1.5, and 9.6 ± 0.5 mg/100 g, respectively. In the mass spectrum obtained by DESI-MSI, peaks corresponding to the chemical formulae of carnitine and imidazole dipeptides were detected. DESI-MSI provided definite identification of carnitine, while DESI-tandem MSI (MS/MSI) was necessary to accurately visualize carnosine, anserine, and balenine. Carnitine and these imidazole dipeptides were mainly distributed in the loin and spinalis muscle, while their distribution was not uniform in both muscle tissues. In addition, the balance between both tissues were different. The concentration of carnitine was higher in the spinalis muscle than that in the loin, while those of imidazole dipeptides were higher in the loin than those in the spinalis muscle. These results were consistent with those obtained by liquid chromatography-MS quantification, suggest that DESI-MSI analysis is useful for the distribution analysis of carnitine and imidazole dipeptides in meat.
• Survey of Food Intake in Patients with Abdominal Aortic Aneurysm.

  Hirona Kugo; Tatsuro Yata; Rie Kanai; Ena Naruse; Kazunori Inuzuka; Hiroki Tanaka; Kenichi Yanagimoto; Tatsuya Moriyama; Naoki Unno; Miho Kogirima; Nobuhiro Zaima

  Journal of oleo science 72 2 211 - 218 2023年01月 [査読有り]
   

  Abdominal aortic aneurysm (AAA) is a vascular disease that involves asymptomatic progressive expansion of the abdominal aorta. Aneurysm rupture is associated with a high mortality rate. Dietary conditions may be associated with the development and rupture of AAA. However, the relationship between nutrition and AAA is not completely understood. In this study, a nutrition survey was conducted using a brief self-administered diet history questionnaire (BDHQ) to evaluate the relationship between AAA and dietary habits. One-hundred and twenty-six Japanese people participated in the nutrition survey. Food intake status was analyzed in four groups: the analyzed group-1 (all men), analyzed group-2 (men with smoking history), analyzed group-3 (all women) and analyzed group-4 (women without smoking history). In group-2 and group-3, the intake of citrus fruits was significantly lower in the AAA group than in the non-AAA group. In group-2, the intake of soybean and soybean products was significantly lower in the AAA group than in the non-AAA group. In analyzed group-3, the intake of other vegetables (vegetables except for green and yellow vegetables and soybeans) and seafood was significantly lower in the AAA group than in the non-AAA group. This study suggests that AAA onset may be associated with low intake of fruits, soybeans, vegetables, and seafood.
• Commercial ELISA kits for soy protein determination: Characterization and compatibility

  Rikiya Shimada; Erika Yano; Nobuhiro Zaima; Tatsuya Moriyama

  Food Science and Technology Research 29 6 553 - 558 2023年
• Effects of inhaled β‑caryophyllene on vascular stiffness in smokers: A randomized, double‑blind, placebo‑controlled trial.

  Kazuya Yamada; Kohei Toyota; Yamato Tsunoda; Yoshiharu Matahira; Shinichi Matsumura; Yuri Yoshioka; Nobuhiro Zaima; Naoki Unno

  Experimental and therapeutic medicine 25 1 57 - 57 2023年01月 [査読有り]
   

  Approximately 1.14 billion smokers worldwide are at risk of developing tumors, cardiovascular diseases and respiratory diseases. Smoking cessation is the first choice of health care; however, the disease should be attenuated in individuals who never stop smoking, which escalates medical costs. Therefore, alternative options are needed to manage the social burden. The present study proposed an alternative method to prevent such diseases by inhalation of β-caryophyllene (BCP). A placebo-targeted, dose-searching, double-blind, parallel-group comparative study was conducted on 19 subjects. The BCP intervention was performed using a flavor capsule inserted in a cigarette filter. The primary endpoint was the reducibility of brachial-ankle pulse wave velocity (baPWV). The secondary endpoints were confirmation of the bioavailability of BCP inhalation with cigarette smoke, confirmation of the effect of BCP inhalation on respiratory function, and association between respiratory function and blood concentration and baPWV reduction. The BCP concentration in the blood reached 4 ng/ml in the BCP 15% group 10 min after inhalation. The baPWV decreased in BCP-inhaling subjects whose initial baPWV was >1,300 cm/sec. The correlation analyses revealed that the higher the forced expiratory volume in 1 sec, the better the transition of baPWV. Inhaled BCP with cigarette smoke could reduce the baPWV and the risk of cardiovascular diseases in smokers. These findings indicated that with the introduction of BCP capsule-cigarettes in the future, smokers will be able to take care of their health, which may help reduce national medical costs. BCP microcapsules placed in cigarette wrapping paper may possibly reduce the risk of sidestream smoke and contribute to improved public health. This clinical research was retrospectively registered in the University Hospital Medical Information Network (UMIN)-Clinical Trials Registry with the following identifications: UMIN000048510 and UMIN000048512 on August 15, 2022.
• Detection of macrophages engulfing cholesterol crystals and docosahexaenoic acid from spontaneous ruptured aortic plaque.

  Hirotaka Noda; Chikao Yutani; Nobuhiro Zaima; Sei Komatsu; Nobuzo Iwa; Satoru Takahashi; Mitsuhiko Takewa; Tomoki Ohara; Kazuhisa Kodama

  Journal of cardiology cases 26 5 364 - 366 2022年11月 [査読有り]
   

  UNLABELLED: We visualized macrophages engulfing cholesterol crystals from spontaneously ruptured aortic plaques sampled by angioscopy. Docosahexaenoic acid cholesterol ester (DHA-CE) was demonstrated by imaging mass spectrometry. DHA-CE is reported to be produced by macrophages against inflammation. Activities of macrophages against atherosclerosis inside plaques was shown from spontaneously ruptured aortic plaques in situ. LEARNING OBJECTIVES: Activities of macrophages such as engulfing cholesterol crystals and producing docosahexaenoic acid cholesterol ester were shown from spontaneously ruptured aortic plaques in situ.
• 臨床的に重要な大豆アレルゲン・コンポーネントである大豆2Sアルブミン(Gly m 8)の検出

  嶌田 力也; 棚橋 菜々; 矢野 えりか; 財満 信宏; 森山 達哉

  アレルギーの臨床 42 11 867 - 870 (株)北隆館 2022年10月 

  近年、種実類や穀類の摂取時におけるアナフィラキシー等の重篤なアレルギー症状の原因となるアレルゲン・コンポーネントとして、2Sアルブミン類が大きな注目を受けている。大豆に関しても、主に小児における重篤な大豆アレルギーの場合は、大豆における2SアルブミンであるGly m 8の重要性が指摘されている。そこで私たちは、この臨床的に重要な大豆2SアルブミンであるGly m 8の検出系の構築を目的として、抗体を作成し、いくつかの大豆加工食品において本アレルゲンの検出を試みた。(著者抄録)
• Inhaled volatile β-caryophyllene is incorporated into the aortic wall and attenuates nicotine-induced aorta degeneration via a CB2 receptor-dependent pathway.

  Chihiro Kishi; Mayo Higashihara; Yuki Takemoto; Moeka Kamei; Yuri Yoshioka; Shinichi Matsumura; Kazuya Yamada; Takanori Kobayashi; Yoshiharu Matahira; Tatsuya Moriyama; Nobuhiro Zaima

  Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 153 113423 - 113423 2022年09月 [査読有り]
   

  β-caryophyllene (BCP) is a volatile bicyclic sesquiterpenoid found in essential oils obtained from several spices such as black pepper, oregano, basil, rosemary, cinnamon, and clove. BCP is a selective agonist of cannabinoid receptor 2 (CB2 receptor), and orally administered BCP exhibits various biological activities, including anti-inflammatory, antioxidant, and neuroprotective effects. However, it is still unclear how volatile BCP affects living organisms. We previously reported that inhaled BCP is transferred to sera and organs in mice; additionally, metabolomic analysis revealed inhaled BCP affect the dynamics of metabolites in the livers of mice. These data suggest that inhaled BCP may affect several biological activities by stimulating biological systems. In this study, we evaluated the effects of BCP inhalation on nicotine-induced degeneration of the aortic wall. In the group of mice which inhaled volatile BCP, nicotine-induced increases in elastic fiber degradation and matrix metalloproteinase-2 (MMP-2)-positive areas were attenuated. In addition, BCP improved the nicotine-induced stiffness of aortae and vulnerability to aortic rupture. In cultured aortae, the suppressive effects of BCP were inhibited by the CB2 receptor inhibitor AM630. These results suggest that inhaled BCP is incorporated into the aortic wall and prevents nicotine-induced degeneration of the aorta via a CB2 receptor-dependent pathway.
• Characterization of extracellular vesicles from Lactiplantibacillus plantarum.

  Atsushi Kurata; Shogo Kiyohara; Tomoya Imai; Shino Yamasaki-Yashiki; Nobuhiro Zaima; Tatsuya Moriyama; Noriaki Kishimoto; Koichi Uegaki

  Scientific reports 12 1 13330 - 13330 2022年08月 [査読有り]
   

  We investigated the characteristics and functionalities of extracellular vesicles (EVs) from Lactiplantibacillus plantarum (previously Lactobacillus plantarum) towards host immune cells. L. plantarum produces EVs that have a cytoplasmic membrane and contain cytoplasmic metabolites, membrane and cytoplasmic proteins, and small RNAs, but not bacterial cell wall components, namely, lipoteichoic acid and peptidoglycan. In the presence of L. plantarum EVs, Raw264 cells inducibly produced the pro-inflammatory cytokines IL-1β and IL-6, the anti-inflammatory cytokine IL-10, and IF-γ and IL-12, which are involved in the differentiation of naive T-helper cells into T-helper type 1 cells. IgA was produced by PP cells following the addition of EVs. Therefore, L. plantarum EVs activated innate and acquired immune responses. L. plantarum EVs are recognized by Toll-like receptor 2 (TLR2), which activates NF-κB, but not by other TLRs or NOD-like receptors. N-acylated peptides from lipoprotein19180 (Lp19180) in L. plantarum EVs were identified as novel TLR2 ligands. Therefore, L. plantarum induces an immunostimulation though the TLR2 recognition of the N-acylated amino acid moiety of Lp19180 in EVs. Additionally, we detected a large amount of EVs in the rat gastrointestinal tract for the first time, suggesting that EVs released by probiotics function as a modulator of intestinal immunity.
• Eicosapentaenoic acid is associated with the attenuation of dysfunctions of mesenchymal stem cells in the abdominal aortic aneurysm wall.

  Hirona Kugo; Hirofumi Enomoto; Kenichi Yanagimoto; Hiroki Tanaka; Tatsuya Moriyama; Nobuhiro Zaima

  Food & function 13 14 7540 - 7547 2022年07月 [査読有り]
   

  Abdominal aortic aneurysm (AAA) is a vascular disease characterized by progressive dilation of the aorta which is reportedly associated with inflammation. Previous studies suggested that eicosapentaenoic acid (EPA) has suppressive effects on AAA development via anti-inflammatory activities. However, relationships between the anti-inflammatory effects and the cells in the AAA wall are poorly understood. In this study, we visualized the distribution of EPA-containing phosphatidylcholine (EPA-PC) in the AAA wall. EPA-PC was not ubiquitously distributed in both animal (hypoperfusion-induced AAA model) and human AAA walls, suggesting the preferential incorporation of EPA into certain cells. In the EPA-PC-high region of both animal and human AAAs, mesenchymal stem cell (MSC) marker positive areas were significantly higher than those in the EPA-PC-low region. Matrix metalloproteinase-positive MSCs were significantly lower in the AAA wall of the animal model which was administered EPA-rich fish oil. These data suggest that EPA is associated with the attenuation of MSC dysfunctions, which result in the suppression of AAA development.
• 高速自動2次元電気泳動を用いたアレルゲン・コンポーネント解析

  嶌田 力也; 棚橋 菜々; 矢野 えりか; 財満 信宏; 森山 達哉

  アレルギーの臨床 42 8 622 - 626 (株)北隆館 2022年07月 

  臨床研究の一環として、アレルギーを惹起する原因物質(食品)の同定や変動解析等のためにイムノブロッティングが汎用されるが、操作性や再現性、分離能に優れた高速自動2次元電気泳動システムを用いたイムノブロッティングを導入することで、これまでカラム操作などによる精製等が必要であった工程が不要となり、非常に簡便に原因分子(抗原)(アレルゲン・コンポーネント)の検出や同定が可能となった。従って、このシステムは、アレルゲン候補分子の検出や同定に大きな威力を発揮し、アレルゲン研究に有用な研究ツールであると考えられた。(著者抄録)
• Inhaled turmerones can be incorporated in the organs via pathways different from oral administration and can affect weight-gain of mice.

  Yuki Takemoto; Chihiro Kishi; Hinano Ehira; Nobutaka Matsui; Taichi Yamaguchi; Yuri Yoshioka; Shinichi Matsumura; Tatsuya Moriyama; Nobuhiro Zaima

  Scientific reports 12 1 11039 - 11039 2022年06月 [査読有り]
   

  Turmerones (α-turmerone, β-turmerone, and ar-turmerone) are the major volatile compounds in turmeric (Curcuma longa), a perennial herb of the ginger family. We previously reported that inhaled volatile turmerones could be transferred in the blood and organs. However, the difference between the two pathways, oral administration and inhalation, and the effect of inhaled turmerones on biological activities remain unknown. In this study, we compared the distribution patterns of turmerones after oral administration and inhalation. The relative levels (concentrations of turmerones in each organ/serum) in the lung, olfactory bulb, brain, heart, kidney, and epididymal fat in the inhalation group tended to be, or are significantly, higher than in the oral administration group. The relative levels of brown adipose tissue in the inhalation group were lower than in the oral administration group. Long-term (50 days) inhalation to volatile turmerones suppressed weight gain and hypertrophy of adipocytes in the epididymal fat of mice fed a high-fat diet. These results suggest that inhaled turmerones can be incorporated into the organs of mice via different pathway from as to those from oral administration and can affect the biological function of the organs under certain conditions.
• Administration of Isoflavone Attenuates Ovariectomy-induced Degeneration of Aortic Wall.

  Kento Miyamoto; Sakura Hasuike; Hirona Kugo; Wanida Sukketsiri; Tatsuya Moriyama; Nobuhiro Zaima

  Journal of oleo science 71 6 889 - 896 2022年06月 [査読有り]
   

  Women are more resistant to vascular diseases; however, the resistance is reduced after menopause. It has been reported that the risk of vascular diseases such as atherosclerosis and abdominal aortic aneurysm is increased in postmenopausal women. Currently, methods to prevent vascular disease in postmenopausal women have not been established. Isoflavones are promising functional food factors that have a chemical structure similar to estrogen. In this study, we investigated the effects of isoflavones on ovariectomized (OVX)-induced degeneration of the aortic wall in mice. Increased destruction of elastic fibers in the thoracic and abdominal aorta was observed in the OVX group, and isoflavones attenuated the destruction of elastic fibers. The positive areas of matrix metalloproteinase (MMP)-2 and MMP-9 in the OVX group were higher than those in the control group. Isoflavones decreased the positive areas of MMP-2 and MMP-9 compared to those in the OVX group. These data suggest that isoflavones have a suppressive effect on OVX-induced degeneration of the aortic wall by inhibiting the increase in MMP-2 and MMP-9.
• 納豆の経口摂取による卵白アレルゲン(OVA)経皮感作抑制効果の検討

  嶌田 力也; 泉 愛理; 衣笠 芹菜; 財満 信宏; 森山 達哉

  日本栄養・食糧学会大会講演要旨集 76回 190 - 190 (公社)日本栄養・食糧学会 2022年05月
• Co-Application with Tannic Acid Prevents Transdermal Sensitization to Ovalbumin in Mice.

  Eri Izumi; Nana Tanahashi; Serina Kinugasa; Shota Hidaka; Nobuhiro Zaima; Tatsuya Moriyama

  International journal of molecular sciences 23 7 2022年04月 

  Transdermal sensitization to allergens is of great concern as a sensitization route for food allergies. This skin-mediated invasion and sensitization to allergens is involved in skin barrier breakdown and inflammation, followed by the production of several kinds of cytokines. Cytokines such as thymic stromal lymphopoietin and thymus and activation-regulated chemokine are also involved. In this study, we investigated the suppressive effect of tannic acid (TA) on transdermal sensitization using ovalbumin (OVA), a major egg-white allergen. We also analyzed the mechanisms associated with the inhibitory effects of TA. The results showed that the co-application with TA prevents transdermal sensitization to OVA. As possible mechanisms, its anti-inflammatory and astringent effect on the skin and binding ability with the protein were considered. These results indicate that TA could be applied to cosmetics and lotions, which could suppress the transdermal sensitization to allergens.
• Characteristic distribution of eicosapentaenoic acid in human abdominal aortic aneurysm wall.

  Hirona Kugo; Hiroki Tanaka; Tatsuya Moriyama; Nobuhiro Zaima

  Journal of lipid research 63 8 100200 - 100200 2022年03月 [査読有り]
  
• Visualization of Functional Food Factors by Matrix-Assisted Laser Desorption/Ionization Imaging Mass Spectrometry.

  Mayo Higashihara; Rena Fujishima; Hirona Kugo; Tatsuya Moriyama; Nobuhiro Zaima

  Journal of nutritional science and vitaminology 68 Supplement S143-S145  2022年 [招待有り]
   

  Dietary habit is closely associated with healthspan. Functional food factors are key to maintaining a health metabolism in our bodies. Because functional food factors are main components to determine the quality of foods, many technologies have been established to analyze functional factors in foods. High-performance liquid chromatography-mass spectrometry or gas chromatography-mass spectrometry is a solid approach to detect functional food factors with high sensitivity and specificity. Findings obtained from these mass spectrometric approaches play essential roles in estimating the quality of foods. However, these technologies are not available for the analysis of the spatial distribution of molecules of interest in foods. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is considered an ideal approach to visualize distribution of molecules in foods. MALDI-MSI is a two-dimensional MALDI-MS technology that can detect compounds in a tissue section without purification, separation, or labeling. MALDI-MSI can be used to visualize the spatial distribution of wide range of food components including protein, peptides, amino acids, lipids, carbohydrate, and vitamins. Although the methodology of MALDI-MSI in food science is not yet fully established, the versatility of MALDI-MSI is expected to open a new frontier in food science. In this mini review, we briefly summarized the applications of MALDI-MSI in the field of food science.
• Different effects of high-fat and high-sucrose diets on the physiology of perivascular adipose tissues of the thoracic and abdominal aorta.

  Tsukasa Sasoh; Hirona Kugo; Yuya Kondo; Kento Miyamoto; Momoka Minami; Mayo Higashihara; Hirokazu Kawamoto; Fumiaki Takeshita; Tatsuya Moriyama; Nobuhiro Zaima

  Adipocyte 10 1 412 - 423 2021年12月 [査読有り]
   

  Vascular diseases such as atherosclerosis and aneurysms are associated with diet. Perivascular adipose tissue (PVAT) was reportedly involved in the regulation of vascular functions. It is suggested that imbalanced diets can cause PVAT inflammation and dysfunction as well as impaired vascular function. However, the association between diets and PVAT are not clearly understood. Here, we showed that a high-fat and a high-sucrose diet affected PVAT at different sites. A high-fat diet induced increased number of large-sized lipid droplets and increased CD (Cluster of differentiation) 68+ macrophage- and monocyte chemotactic protein (MCP)-1-positive areas in the abdominal aortic PVAT (aPVAT). In addition, a high-fat diet caused decreased collagen fibre-positive area and increased CD68+ macrophage- and MCP-1-positive areas in the abdominal aorta. In contrast, a high-sucrose diet induced increased number of large-sized lipid droplets, increased CD68+ macrophage- and MCP-1-positive areas, and decreased UCP-1 positive area in the thoracic aortic PVAT (tPVAT). A high-sucrose diet caused decreased collagen fibre-positive area and increased CD68+ macrophage- and MCP-1-positive areas in the thoracic aorta. These results could be attributed to the different adipocyte populations in the tPVAT and aPVAT. Our results provide pathological evidence to improve our understanding of the relationship between diet and vascular diseases.
• Low glucose and serum levels cause an increased inflammatory factor in 3T3-L1 cell through Akt, MAPKs and NF-кB activation.

  Hirona Kugo; Wanida Sukketsiri; Kazuko Iwamoto; Satoki Suihara; Tatsuya Moriyama; Nobuhiro Zaima

  Adipocyte 10 1 232 - 241 2021年12月 [査読有り]
   

  Abdominal aortic aneurysm (AAA) involves the degradation of vascular fibres, and dilation and rupture of the abdominal aorta. Hypoperfusion in the vascular walls due to stenosis of the vasa vasorum is reportedly a cause of AAA onset and involves the induction of adventitial ectopic adipocytes. Recent studies have reported that ectopic adipocytes are associated with AAA rupture in both human and hypoperfusion-induced animal models, highlighting the pathological importance of hypoperfusion and adipocytes in AAA. However, the relationship between hypoperfusion and AAA remains unknown. In this study, we investigated the changes in inflammation-related factors in adipocytes at low glucose and serum levels. Low glucose and serum levels enhanced the production of AAA-related factors in 3T3-L1 cells. Low glucose and serum levels increased the activation of protein kinase B (also known as Akt), extracellular signal-regulated protein kinase 1/2, p38, c-Jun N-terminal kinase, and nuclear factor (NF) кB at the protein level. The inflammatory factors and related signalling pathways were markedly decreased following the return of the cells to normal culture conditions. These data suggest that low glucose and serum levels increase the levels of inflammatory factors through the activation of Akt, mitogen activated protein kinase, and NF-κB signalling pathways.
• Ovariectomy Causes Degeneration of Perivascular Adipose Tissue.

  Tomomi Nakamura; Kento Miyamoto; Hirona Kugo; Keita Sutoh; Keisuke Kiriyama; Tatsuya Moriyama; Nobuhiro Zaima

  Journal of oleo science 70 11 1651 - 1659 2021年10月 [査読有り]
   

  Women are more resistant than men to the development of vascular diseases. However, menopause is a factor leading to deterioration of female vascular integrity, and it is reported that the risk of vascular diseases such as atherosclerosis and abdominal aortic aneurysm is increased in postmenopausal women. Although it is suggested that perivascular adipose tissue (PVAT) is deeply involved in the increased risk of vascular disease development, the effect of menopause on PVAT integrity is unknown. In this study, we aimed to elucidate the effect of menopause on PVAT in ovariectomized (OVX) rats. PVAT was divided into 4 regions based on characteristics. Hypertrophy and increased inflammation of adipocytes in the PVAT were observed in the OVX group, but the effects of OVX were different for each region. OVX induced matrix metalloproteinase (MMP) -9 which degrade extracellular matrix such as elastin and collagen fibers in PVAT. Degeneration of the arterial fibers of the thoracic and abdominal aorta were observed in the OVX group. These results indicate that OVX can cause dysfunction of PVAT which can cause degradation of arterial fibers. Appropriate management of PVAT may play an important role in the prevention and treatment of diseases originating from ovarian hypofunction.
• Inhibitory Activities of Sulfur Compounds in Garlic Essential Oil against Alzheimer's Disease-Related Enzymes and Their Distribution in the Mouse Brain.

  Yuri Yoshioka; Shinichi Matsumura; Masanori Morimoto; Yuki Takemoto; Chihiro Kishi; Tatsuya Moriyama; Nobuhiro Zaima

  Journal of agricultural and food chemistry 69 35 10163 - 10173 2021年09月 [査読有り]
   

  Alzheimer's disease (AD) is the most common neurodegenerative disease. Garlic reportedly has various physiological effects, including a role in protecting against dementia. However, the action mechanisms of garlic on AD are not entirely clear. In this study, we investigated the inhibitory activity of garlic essential oil (GEO) against AD-related enzymes and evaluated the distribution of active substances in GEO to the brain. We found that several sulfur compounds in GEO significantly inhibited AD-related enzymes. Sulfur compounds were detected in the serum and brain 6 h post administration. The ratios of allyl mercaptan (24.0 ± 3.9%) and allyl methyl sulfide (49.8 ± 15.6%) in the brain were significantly higher than those in GEO, while those of dimethyl trisulfide (0.89 ± 34.8%), allyl methyl trisulfide (0.41 ± 19.0%), and diallyl trisulfide (0.43 ± 72.8%) in the brain were significantly lower than those in GEO. Similar results were observed in the serum, suggesting that the organosulfur compounds were converted to allyl mercaptan or allyl methyl sulfide in the body. Although allyl mercaptan and allyl methyl sulfide are not the main components of GEO, they might be key molecules to understand the bioactivities of GEO in the body.
• Ellagic Acid Suppresses ApoB Secretion and Enhances ApoA-1 Secretion from Human Hepatoma Cells, HepG2.

  Ayana Ieda; Maki Wada; Yuuki Moriyasu; Yuuko Okuno; Nobuhiro Zaima; Tatsuya Moriyama

  Molecules (Basel, Switzerland) 26 13 2021年06月 

  The effect of ellagic acid (EA), a naturally occurring polyphenolic compound, on the secretion of apolipoproteins from human hepatocytes, HepG2, was investigated. The levels of apoB and apoA-1 secreted in the cell culture medium were determined by sandwich ELISA. EA did not affect cell viability at the tested concentrations (up to 50 µM). EA suppressed the secretion of apoB and enhanced that of apoA-1 from HepG2 cells. However, cellular apoB levels were increased, suggesting that EA inhibited the trafficking of apoB during the process of secretion. In contrast, the increase in the cellular levels of apoA-1 was consistent with its secreted levels. These results indicate that EA inhibits the secretion of apoB from hepatocytes and increases the secretion of apoA-1. Both of these effects are beneficial for lipoprotein metabolism in the prevention of lifestyle-related diseases. The detailed mechanism underlying these effects of EA on lipoprotein metabolism should be elucidated in the future, but this naturally occurring polyphenolic compound might be antihyperlipidemic. Based on these results, EA is suggested as a candidate food-derived compound for the prevention of hyperlipidemia.
• Similar distribution of orally administered eicosapentaenoic acid and M2 macrophage marker in the hypoperfusion-induced abdominal aortic aneurysm wall.

  Rena Fujishima; Hirona Kugo; Kenichi Yanagimoto; Hirofumi Enomoto; Tatsuya Moriyama; Nobuhiro Zaima

  Food & function 12 8 3469 - 3475 2021年04月 [査読有り]
   

  Abdominal aortic aneurysm (AAA) is an aortic disease in which the aortic diameter is ≥3.0 cm; if left untreated, the aortic wall continues to weaken, resulting in progressive dilatation. Effective therapeutic drugs for AAA patients have not been discovered. Eicosapentaenoic acid (EPA) reportedly attenuates the development of AAA in experimental AAA animal models. However, the underlying mechanism of action is still not totally clear. To understand the mechanism, we visualized the distribution of EPA-containing phosphatidylcholine (PC) in the AAA wall by matrix-assisted laser desorption ionization-mass spectrometry imaging. EPA-containing PC was characteristically distributed in the AAA wall, and the positive area for the M2 macrophage marker was significantly higher in the region where EPA-containing PC was highly detected (region 2) than in the region where EPA-containing PC was poorly detected (region 1). The M1 macrophage marker levels were not different between regions 1 and 2. A comparative observation showed a similar distribution of the M2 macrophage marker and EPA-containing PC. These data suggest the preferential incorporation of EPA into M2 macrophages. Positive areas for matrix metalloproteinase 2 and malondialdehyde in region 2 were significantly lower than those in region 1. The reported suppressive effect of EPA on the development of AAA may be partly attributed to the increased anti-inflammatory property of M2 macrophages.
• Validation of Antiobesity Effects of Black Soybean Seed Coat Powder Suitable as a Food Material: Comparisons with Conventional Yellow Soybean Seed Coat Powder.

  Yuuki Moriyasu; Chiho Fukumoto; Maki Wada; Erika Yano; Hiroshi Murase; Masatoshi Mizuno; Nobuhiro Zaima; Tatsuya Moriyama

  Foods (Basel, Switzerland) 10 4 2021年04月 

  In this study, we fed obese model mice black soybean seed coat powder (BSCP) and evaluated the antiobesity effects. As a control, normal yellow soybean seed coat powder (YSCP) was used. C57BL/6J, a high-fat diet-induced obesity model mouse, was fed a high-fat diet containing BSCP or YSCP (20% fat) to induce obesity. The results showed that in the BSCP group, it caused significant suppression of body weight gain and suppression of white adipose tissue weight compared with the YSCP group. Moreover, it significantly decreased serum leptin levels, which correlated with visceral fat mass, and increased antidiabetic adipocytokine and adiponectin levels. Therefore, this suggests the pigmented components contained in BSCP have an antiobesity effect in obese model mice. It is suggested that this material, which can be prepared without extraction with an organic solvent and is suitable for use as a food material, could be a functional food material with a practicable antiobesity effect.
• Time-Dependent Pathological Changes in Hypoperfusion-Induced Abdominal Aortic Aneurysm.

  Hirona Kugo; Wanida Sukketsiri; Hiroki Tanaka; Rena Fujishima; Tatsuya Moriyama; Nobuhiro Zaima

  Biology 10 2 2021年02月 [査読有り]
   

  Hypoperfusion due to vasa vasorum stenosis can cause wall hypoxia and abdominal aortic aneurysm (AAA) development. Even though hypoperfusion is an important contributor toward pathological changes in AAA, the correlation between hypoperfusion and AAA is not fully understood. In this study, a time-dependent semi-quantitative pathological analysis of hypoperfusion-induced aortic wall changes was performed to understand the mechanisms underlying the gradual degradation of the aortic wall leading to AAA formation. AAA-related factors evaluated in this study were grouped according to the timing of dynamic change, and five groups were formed as follows: first group: angiotensin II type 1 receptor, endothelin-1 (ET-1), and malondialdehyde (MDA); second group: matrix metalloproteinase (MMP)-2, -9, -12, M1 macrophages (Mac387+ cells), and monocyte chemotactic protein-1; third group: synthetic smooth muscle cells (SMCs); fourth group: neutrophil elastase, contractile SMCs, and angiotensinogen; and the fifth group: M2 macrophages (CD163+ cells). Hypoxia-inducible factor-1α, ET-1, MDA, and MMP-9 were colocalized with alpha-smooth muscle actin cells in 3 h, suggesting that hypoperfusion-induced hypoxia directly affects the activities of contractile SMCs in the initial stage of AAA. Time-dependent pathological analysis clarified the cascade of AAA-related factors. These findings provide clues for understanding complicated multistage pathologies in AAA.
• Distribution of inhaled volatile β-caryophyllene and dynamic changes of liver metabolites in mice.

  Yuki Takemoto; Chihiro Kishi; Yuki Sugiura; Yuri Yoshioka; Shinichi Matsumura; Tatsuya Moriyama; Nobuhiro Zaima

  Scientific reports 11 1 1728 - 1728 2021年01月 [査読有り]
   

  β-caryophyllene (BCP), an essential oil component of many herbs and spices, has various biological activities as a functional food factor. A distinct feature of BCP is its volatile double-ring sesquiterpene structure. Orally administered BCP is reportedly detected in its intact form in mice serum; however, the distribution of inhaled volatile BCP throughout the body remains unknown. This study aimed to estimate the distribution properties of inhaled volatile BCP and to investigate its effects on metabolism. After mice were exposed to volatile BCP, it was detected in the lung, olfactory bulb, brain, serum, heart, liver, kidney, epididymal fat, and brown adipose tissue. BCP was further detected in the brain, liver, and brown adipose tissue 24 h after exposure. Metabolites related to glutathione metabolism were significantly altered in the liver. These results suggest that inhaled volatile BCP is widely distributed in murine tissues and affects the dynamics of metabolites in the liver.
• Thaumatin-Like Protein (Pru av 2) Is a Cherry Allergen That Triggers Percutaneous Sensitization in Mice.

  Eri Izumi; Shota Hidaka; Ayako Hiroi; Serina Kinugasa; Erika Yano; Nobuhiro Zaima; Tatsuya Moriyama

  Foods (Basel, Switzerland) 10 1 2021年01月 [査読有り]
   

  Numerous recent studies have suggested that food allergens enter the skin and predispose individuals to food allergies through the production of IgE antibodies in the body. Cherries are a popular fruit eaten worldwide. However, cherries are an allergenic food and percutaneous sensitization with cherry allergens through the perioral region may occur while ingesting cherries. The identity of the cherry protein that triggers percutaneous sensitization in humans or animal models remains unknown. In this study, the backs of BALB/c mice were shaved and crude cherry extracts containing sodium dodecyl sulfate were applied to the skin. Thereafter, the cherry-specific IgE and IgG1 antibodies generated and secreted in response to the epidermal application were measured using an enzyme-linked immunosorbent assay or immunoblotting. Skin exposure to cherry extracts elevated cherry-specific IgG1 levels. Application of fractionated and purified cherry proteins (antigen candidates for percutaneous sensitization) that bound to the IgG1 antibodies led to the identification of a thaumatin-like protein (Pru av 2). This molecule is known as the major cherry allergen that affects humans. In conclusion, our study identified Pru av 2 as a cherry allergen that triggers percutaneous sensitization in mice for the first time.
• Kiwifruit defense protein, kiwellin (Act d 5) percutaneously sensitizes mouse models through the epidermal application of crude kiwifruit extract.

  Serina Kinugasa; Shota Hidaka; Serina Tanaka; Eri Izumi; Nobuhiro Zaima; Tatsuya Moriyama

  Food & nutrition research 65 2021年 

  Background: Kiwifruit is a popular fruit consumed worldwide and is also used as a cosmetic ingredient. However, it is known to cause allergic reactions in humans. Recent studies have suggested an association between food allergy and food allergens entering the body via the skin. However, percutaneously sensitizing kiwifruit allergens have not been identified in human studies or in animal models. Objective: This study aimed to identify kiwifruit proteins that percutaneously sensitized mice through the epidermal application of crude extracts from green and gold kiwifruit on the dorsal skin, and serum IgE and IgG1 levels were used as sensitization markers. Design: BALB/c mice were back-shaved and their skin was exposed to crude extracts from green and gold kiwifruit that contained sodium dodecyl sulfate. Specific IgE and IgG1 antibodies generated and secreted in response to antigens were measured using enzyme-linked immunosorbent assay or immunoblotting. Results: Skin exposure to kiwifruit extract induced an increase in the levels of kiwifruit-specific IgE and IgG1, which are helper T cell 2-related allergenic antibodies in mice. These antibodies reacted with 18, 23, and 24 kDa proteins found in both green and gold kiwifruits. Thus, three percutaneously sensitizing allergens were identified and purified. Their amino acid sequences partially matched with that of kiwellin (Act d 5). Discussion and conclusion: Kiwellin has been identified as a plant defense-related protein. Interestingly, many plant allergens are biodefense-related proteins belonging to the pathogenesis-related protein family. Kiwellin, which was discovered to be a transdermal sensitizing antigen, might also be categorized as a biodefense-related protein. This study is the first to identify kiwellin (Act d 5) as a percutaneously sensitizing kiwifruit allergen in a mouse model.
• Outside-in signaling by femoral cuff injury induces a distinct vascular lesion in adipose triglyceride lipase knockout mice.

  Hirotsugu Noguchi; Sohsuke Yamada; Ken-Ichi Hirano; Satoshi Yamaguchi; Akira Suzuki; Xin Guo; Nobuhiro Zaima; Ming Li; Kunihisa Kobayashi; Yoshihiko Ikeda; Toshiyuki Nakayama; Yasuyuki Sasaguri

  Histology and histopathology 36 1 91 - 100 2021年01月 [査読有り]
   

  Genetic deficiency of adipose triglyceride lipase (ATGL), a rate-limiting enzyme for intracellular triglyceride (TG) hydrolysis, causes TG-deposit cardiomyovasculopathy (TGCV), a recently identified rare cardiovascular disorder (ORPHA code: 565612) in humans. One of the major characteristics of TGCV is a novel type of diffuse and concentric coronary atherosclerosis with ATGL-deficient smooth muscle cells (SMCs). Patients with TGCV have intractable coronary artery disease. Therefore, it is crucial to investigate the mechanisms underlying vascular lesions in ATGL deficiency using animal models. Cuff injury is an experimental procedure to induce vascular remodeling with neointimal formation with SMCs after placing a cuff around the adventitial side of the artery without direct influence on endothelium. We report the effect of cuff injury on femoral arteries of ATGL-knockout (ATGL⁻/⁻) mice. Cuff-induced concentric neointimal formation with migrating SMCs was exacerbated in ATGL⁻/⁻ mice, mimicking atherosclerotic lesions in patients with TGCV. In the media, cell death of SMCs and loss of elastic fibers increased. Perivascular infiltrating cells expressing tumor necrosis factor-α (TNF-α) were more prominent in ATGL⁻/⁻ mice than in wild-type (WT) mice. In Boyden chamber experiments, a greater number of ATGL⁻/⁻ SMCs migrated in response to TNF-α compared to WT SMCs. These data, for the first time, demonstrated that outside-in signaling by cuff-induced neointimal formation where paracrine stimuli from adventitial infiltrating cells may lead to neointimal formation and mediolysis in ATGL-deficient conditions. Cuff injury might be a valuable model for understanding the mechanisms underlying the development of atherosclerotic lesions in patients with TGCV.
• Neuroprotective effects of aromatic turmerone on activity deprivation-induced apoptosis in cerebellar granule neurons.

  Yuya Saga; Yudai Hatakenaka; Miho Matsumoto; Yuri Yoshioka; Shinichi Matsumura; Nobuhiro Zaima; Yoshiyuki Konishi

  Neuroreport 31 18 1302 - 1307 2020年12月 [査読有り]
   

  Ar-turmerone, which is a major bioactive component found in the essential oil derived from Curcuma longa, has been reported to inhibit proliferation and induce apoptosis in cancer cell lines. Recently, ar-turmerone has been reported to increase the proliferation of neuronal stem cells, in contrast to its actions in cancer cells. These observations raise the possibility that ar-turmerone serves specific functions in neuronal cell lineages. However, the effects of ar-turmerone on postmitotic neurons remain elusive. In the present study, we investigated the neuroprotective functions of ar-turmerone in primary cerebellar granule neuronal cultures. We found that ar-turmerone increased the survival of neurons following activity deprivation. Consistently, the induction of cleaved caspase-3, a hallmark of apoptosis, was prevented by ar-turmerone, although neither the level of reactive oxygen species nor the mitochondrial membrane potential was affected. This study reports a neuroprotective function for ar-turmerone, providing new insights into the potential therapeutic applications of ar-turmerone for neurological disorders.
• Application of Mass Spectrometry Imaging for Visualizing Food Components.

  Yoshimura Yukihiro; Nobuhiro Zaima

  Foods (Basel, Switzerland) 9 5 2020年05月 [査読有り]
   

  Consuming food is essential for survival, maintaining health, and triggering positive emotions like pleasure. One of the factors that drive us toward such behavior is the presence of various compounds in foods. There are many methods to analyze these molecules in foods; however, it is difficult to analyze the spatial distribution of these compounds using conventional techniques, such as mass spectrometry combined with high-performance liquid chromatography or gas chromatography. Mass spectrometry imaging (MSI) is a two-dimensional ionization technology that enables detection of compounds in tissue sections without extraction, purification, separation, or labeling. There are many methods for ionization of analytes, including secondary ion mass spectrometry, matrix-assisted laser desorption/ionization, and desorption electrospray ionization. Such MSI technologies can provide spatial information on the location of a specific analyte in food. The number of studies utilizing MSI technologies in food science has been increasing in the past decade. This review provides an overview of some of the recent applications of MSI in food science and related fields. In the future, MSI will become one of the most promising technologies for visualizing the distribution of food components and for identifying food-related factors by their molecular weights to improve quality, quality assurance, food safety, nutritional analysis, and to locate administered food factors.
• Comparison of Various Soybean Allergen Levels in Genetically and Non-Genetically Modified Soybeans.

  Ayato Matsuo; Kaho Matsushita; Ayano Fukuzumi; Naoki Tokumasu; Erika Yano; Nobuhiro Zaima; Tatsuya Moriyama

  Foods (Basel, Switzerland) 9 4 2020年04月 [査読有り]
   

  Several analyses of allergen levels have been reported as part of the safety assessment of genetically modified (GM) soybean; however, few comprehensive analyses have included new allergens. Thus, in this study the levels of eight major soybean allergens, including Gly m 7 (a newly reported soybean allergen), were semi-quantitatively detected in six GM soybeans and six non-GM soybeans using antigen-immobilized ELISA and immunoblotting. We also analyzed the IgE-reactivity to these soybeans through immunoblotting, using sera from three soybean-allergic patients. The results showed that there were no significant differences in the levels of the major soybean allergens in the GM and non-GM soybeans. Moreover, there were no significant differences in the serum IgE-reactive protein profiles of the patients, as analyzed using immunoblotting. These results indicate that, in general, CP4-EPSPS-transfected GM soybeans are not more allergenic than non-GM soybeans.
• Unique Distribution of Diacyl-, Alkylacyl-, and Alkenylacyl-Phosphatidylcholine Species Visualized in Pork Chop Tissues by Matrix-Assisted Laser Desorption/Ionization-Mass Spectrometry Imaging.

  Hirofumi Enomoto; Tomohiro Furukawa; Shiro Takeda; Hajime Hatta; Nobuhiro Zaima

  Foods (Basel, Switzerland) 9 2 2020年02月 [査読有り]
   

  Phosphatidylcholine (PC) is the major phospholipid in meat and influences meat qualities, such as healthiness. PC is classified into three groups based on the bond at the sn-1 position: Diacyl, alkylacyl, and alkenylacyl. To investigate their composition and distribution in pork tissues, including longissimus thoracis et lumborum (loin) spinalis muscles, intermuscular fat, and transparent tissues, we performed matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI). Eleven diacyl-, seven alkylacyl-, and six alkenylacyl-PCs were identified using liquid chromatography (LC)-tandem MS (MS/MS) analysis. Despite many alkylacyl- and alkenylacyl-PC species sharing identical m/z values, we were able to visualize these PC species using MALDI-MSI. Diacyl- and alkylacyl- and/or alkenylacyl-PC species showed unique distribution patterns in the tissues, suggesting that their distribution patterns were dependent on their fatty acid compositions. PCs are a major dietary source of choline in meat, and the amount was significantly higher in the muscle tissues. Consumption of choline mitigates age-related memory decline and neurodegenerative diseases; therefore, the consumption of pork muscle tissues could help to mitigate these diseases. These results support the use of MALDI-MSI analysis for assessing the association between PC species and the quality parameters of meat.
• The Role of Animal Models in Elucidating the Etiology and Pathology of Abdominal Aortic Aneurysms: Development of a Novel Rupture Mechanism Model.

  Hiroki Tanaka; Nobuhiro Zaima; Hirona Kugo; Tatsuro Yata; Yasunori Iida; Keisuke Hashimoto; Chie Miyamoto; Takeshi Sasaki; Hideto Sano; Yuko Suzuki; Tatsuya Moriyama; Hideyuki Shimizu; Kazunori Inuzuka; Tetsumei Urano; Naoki Unno

  Annals of vascular surgery 63 382 - 390 2020年02月 [査読有り]
   

  Existing animal models do not replicate all aspects of abdominal aortic aneurysms (AAAs), including the rupture mechanisms. From histopathological analyses conducted in humans, it has been found that the vasa vasorum of the AAA wall is the starting point of circulatory failure and that bulging and dilatation of the abdominal aorta occurs through inflammation and tissue degeneration. We created a new animal model (the hypoperfusion-induced model) of AAAs. In this study, we describe the current animal models of AAAs and present the utility of our new model of AAAs.
• The Seed Coat Extract of Black Soybean Decreases Nicotine-Induced Vascular Fiber Degradation by Suppressing Matrix Metalloproteinase 2 Expression.

  Kiyoto Hoshino; Hirona Kugo; Chie Miyamoto; Keisuke Hashimoto; Hiroshi Murase; Masatoshi Mizuno; Tatsuya Moriyama; Nobuhiro Zaima

  Journal of nutritional science and vitaminology 66 1 75 - 81 2020年 [査読有り]
   

  Abdominal aortic aneurysm (AAA) is a vascular disease characterized by weakening of vascular walls and progressive dilation of the abdominal aorta. Nicotine, the main component of tobacco, is reportedly associated with the development and rupture of AAA. It is desirable to attenuate the destructive effect of nicotine on vascular walls, using dietary food components. However, effective methods for preventing AAA progression using dietary food components remain unestablished. This study focuses on proanthocyanidins, well known for their potent antioxidant activity. We speculated that proanthocyanidins can suppress nicotine-induced weakening of vascular walls. To estimate the effect of black soybean seed coat extract (BSSCE), rich in proanthocyanidins, on nicotine-induced weakening of the aortic wall, mice were divided into four groups: the control diet and distilled water group (named C), BSSCE solution diet and distilled water group (named B), control diet and 0.5 mg/mL nicotine solution group (named CN), and BSSCE solution diet and 0.5 mg/mL nicotine solution group (named BN). Nicotine-induced degradation of elastin and collagen fibers were significantly suppressed in BN group. The positive areas for matrix metalloproteinase (MMP)-2 and oxidative stress in BN group were significantly decreased compared to those in CN group. These results suggest that proanthocyanidins-rich BSSCE can prevent the weakening of the aortic wall via inhibiting MMP-2 upregulation.
• Development of Pretreatment Protocols for Determination of Soybean β-Conglycinin in Processed Soybean Foods Using Commercial ELISA Kits.

  Tatsuya Moriyama; Erika Yano; Nobuhiro Zaima; Keiko Miyazaki; Kou Shirotsuki; Aki Sato; Makoto Sawaguchi

  Journal of nutritional science and vitaminology 66 3 270 - 277 2020年 [査読有り]
   

  β-Conglycinin is the major storage protein in soybeans. Pre-clinical animal models and human clinical studies have demonstrated the triglyceride-lowering effect of this protein, suggesting that it could be put into practical use as a functional food material. To date, however, there are no accurate and simple assays for quantification of β-conglycinin. In this study, samples were pretreated by mixing them with rice flour powder prior to extraction of proteins. Then, we used commercially available ELISA kits for detection of allergens that could be present in any contaminating soybean residue. This enabled accurate and highly reproducible quantitation of β-conglycinin content in several processed soybean foods.
• A historical case of primary triglyceride deposit cardiomyovasculopathy.

  Michio Tanaka; Yoshihiko Ikeda; Ming Li; Nobuhiro Zaima; Yutaka Kawahara; Koji Watanabe; Tohru Inaba; Kunihisa Kobayashi; Hirotsugu Noguchi; Sohsuke Yamada; Hiroyuki Hao; Ken-Ichi Hirano

  Pathology international 70 1 58 - 61 2020年01月 [査読有り]
  
• Ovariectomy increases the incidence and diameter of abdominal aortic aneurysm in a hypoperfusion-induced abdominal aortic aneurysm animal model.

  Chie Miyamoto; Hirona Kugo; Keisuke Hashimoto; Tatsuya Moriyama; Nobuhiro Zaima

  Scientific reports 9 1 18330 - 18330 2019年12月 [査読有り]
   

  Abdominal aortic aneurysm (AAA) is a vascular disease characterized by weakening of the vascular walls. Male sex is a risk factor for AAA, and peak AAA incidence occurs in men 10 years earlier than in women. However, the growth rate of AAA is faster in women, and women have a higher mortality due to AAA rupture. The mechanisms underlying sex-related differences in AAA remain unknown. Herein, we evaluated the effects of ovariectomy (OVX) on AAA in rats. Upon evaluation of the effects of OVX and AAA induction, AAA incidence rate and the aneurysm diameter increased in the OVX group. However, the histopathology in the developed AAA wall was not different between groups. When the effects of OVX on the vascular wall without AAA induction were evaluated, elastin and collagen levels were significantly decreased. Furthermore, the level of matrix metalloproteinase-9 significantly increased in the OVX group. According to our results, it is speculated that decreased levels of collagen and elastin fibers induced by OVX might be involved in increased incidence rate and diameter of AAA. Weakening of the vascular wall before the onset of AAA might be one reason for the faster rate of AAA growth in women.
• Isoflavone Ameliorated Oxidative Stress and Vascular Damages in Nicotine-Administrated Mice.

  Wanida Sukketsiri; Kiyoto Hoshino; Hirona Kugo; Tomomi Nakamura; Tsukasa Sasoh; Tatsuya Moriyama; Nobuhiro Zaima

  Journal of oleo science 68 12 1241 - 1249 2019年12月 [査読有り]
   

  Nicotine has been linked to the development of abdominal aortic aneurysms. Isoflavones, a group of polyphenolic compounds, reportedly exhibit antioxidant and anti-inflammatory properties and facilitate cardiovascular protection. However, the effects of isoflavone on nicotine-induced abdominal aortic aneurysms have not yet been elucidated. The objective of the current study was to evaluate the inhibitory effect of isoflavone on nicotine-induced weakening of the aortic wall in mouse models. Nicotine reportedly increases the occurrence of abdominal aortic aneurysms by activating endothelin-1 (ET-1), angiotensinogen and the angiotensin II type 1 (AT1) receptor, leading to an increase in neutrophil elastase, oxidative stress, and matrix metalloproteinase (MMP)-2 expression, which causes vascular wall weakness and damage. Immunohistological analyses have indicated that isoflavone significantly inhibits the activation of ET-1, angiotensinogen and the AT1 receptor in nicotine-administered mice. Additionally, isoflavone suppressed elastic fiber destruction and decreased areas positive for MMP-2, neutrophil elastase, and malondialdehyde in the vascular wall of nicotine-administered mice. Considered together, these findings suggest that isoflavone shows potential for preventing vascular wall injury induced by nicotine administration, and that food containing isoflavone may protect against abdominal aortic aneurysms.
• The role of perivascular adipose tissue in the appearance of ectopic adipocytes in the abdominal aortic aneurysmal wall.

  Hirona Kugo; Tatsuya Moriyama; Nobuhiro Zaima

  Adipocyte 8 1 229 - 239 2019年12月 [査読有り]
   

  Abdominal aortic aneurysm (AAA) is a vascular disease characterized by the dilation of the abdominal aorta, resulting in a high mortality rate caused by vascular rupture. Previous studies have suggested that the abnormal appearance of adipocytes in the vascular wall is associated with the development of AAA. However, the mechanisms underlying the appearance of the ectopic adipocytes remain unknown. In this study, we showed that CD44+CD90+ MSCs express adipogenic transcription factors in the AAA wall of a hypoperfusion-induced AAA model. The number of CD44+CD90+ cells and adipocytes in the AAA wall significantly decreased in the perivascular adipose tissue (PVAT)-removed vascular wall. The AAA diameter significantly decreased in the PVAT-removed vascular wall compared with that in the vascular wall with PVAT. These data suggested that PVAT plays important roles in the differentiation of MSCs into adipocytes in response to vascular hypoperfusion. The decreased number of adipocytes in the PVAT-removed vascular wall might be associated with the decreased AAA diameter.
• Mixing Ginkgo biloba Extract with Sesame Extract and Turmeric Oil Increases Bioavailability of Ginkgolide A in Mice Brain.

  Kazuko Iwamoto; Hirokazu Kawamoto; Fumiaki Takeshita; Shinichi Matsumura; Ikuto Ayaki; Tatsuya Moriyama; Nobuhiro Zaima

  Journal of oleo science 68 9 923 - 930 2019年09月 [査読有り]
   

  Ginkgo biloba extract (GBE) is widely used as herbal medicine. Preventive effect of GBE against dementia, including Alzheimer's disease, has been reported. The bioactive compounds in GBE that impart these beneficial effects, flavonoids and terpene lactones, have poor bioavailability. Our previous study found distribution of bioactive compounds of sesame extract in mice brain after mixing it with turmeric oil. Here, we evaluate the distribution of bioactive compounds of GBE by combining it with the mixture of sesame extract and turmeric oil (MST). The content of terpene lactones in mice serum was significantly increased in a dose-dependent manner after administration of GBE. However, the contents of terpene lactones in mice brain were not significantly changed. Concentration of ginkgolide A in mice brain increased significantly when GBE was co-administrated with MST than when GBE was administered alone. These results suggest that MST may be effective in enhancing the bioavailability of ginkgolide A in GBE.
• Tissue-Specific Distribution of Sphingomyelin Species in Pork Chop Revealed by Matrix-Assisted Laser Desorption/Ionization-Imaging Mass Spectrometry.

  Hirofumi Enomoto; Shiro Takeda; Hajime Hatta; Nobuhiro Zaima

  Journal of food science 84 7 1758 - 1763 2019年07月 [査読有り]
   

  Sphingomyelin (SM) species are major sphingolipids in pork meat that affect quality parameters, such as health benefits due to their protective properties against chronic diseases; however, their spatial distribution remains unclear. We used matrix-assisted laser desorption/ionization (MALDI)-imaging mass spectrometry (IMS) to investigate the distribution and composition of SM species in pork chop consisting of longissimus thoracis et lumborum muscle (loin), intermuscular fat tissue, transparent tissue, and spinalis muscle. Four SM species were identified by liquid chromatography-electrospray ionization-tandem MS (MS/MS) and MALDI-MS/MS and visualized using MALDI-IMS. SM species containing stearic acid were predominantly distributed in the loin and spinalis muscle, whereas SM species containing palmitic, lignoceric, and nervonic acids were predominantly distributed in transparent tissue. These results indicated that the distribution of SM species differed among the pork tissues, depending on the tissue-specific fatty acid composition. The total amount including all identified SM species was higher in the loin than in spinalis muscle. Pork is reportedly associated with increased risk for chronic diseases due to the high amount of heme iron. From the observation of color, the amount of heme iron was lower in loin than in spinalis muscle. Thus, the degree of risk for chronic diseases might be lower in the loin than in spinalis muscle. This is the first report on the tissue-specific distribution of SM species in meat at a microscopic resolution using IMS. MALDI-IMS analysis may be useful in assessing the association between SM species and quality parameters of pork meat. PRACTICAL APPLICATION: Sphingomyelin (SM) species are major sphingolipids in pork meat. SM species affect quality parameters such as health benefits due to their protective properties against colon cancer and atherosclerosis. Matrix-assisted laser desorption/ionization-imaging mass spectrometry analysis combined with liquid chromatography-electrospray ionization-tandem mass spectrometry is a suitable method to directly investigate the distribution and composition of SM species at microscopic level among different tissues of pork meat. Therefore, this method is useful to assess the SM species-induced health effect of different tissues of pork meat.
• Triglyceride deposit cardiomyovasculopathy: a rare cardiovascular disorder.

  Ming Li; Ken-Ichi Hirano; Yoshihiko Ikeda; Masahiro Higashi; Chikako Hashimoto; Bo Zhang; Junji Kozawa; Koichiro Sugimura; Hideyuki Miyauchi; Akira Suzuki; Yasuhiro Hara; Atsuko Takagi; Yasuyuki Ikeda; Kazuhiro Kobayashi; Yoshiaki Futsukaichi; Nobuhiro Zaima; Satoshi Yamaguchi; Rojeet Shrestha; Hiroshi Nakamura; Katsuhiro Kawaguchi; Eiryu Sai; Shu-Ping Hui; Yusuke Nakano; Akinori Sawamura; Tohru Inaba; Yasuhiko Sakata; Yoko Yasui; Yasuyuki Nagasawa; Shintaro Kinugawa; Kazunori Shimada; Sohsuke Yamada; Hiroyuki Hao; Daisaku Nakatani; Tomomi Ide; Tetsuya Amano; Hiroaki Naito; Hironori Nagasaka; Kunihisa Kobayashi

  Orphanet journal of rare diseases 14 1 134 - 134 2019年06月 [査読有り]
   

  Triglyceride deposit cardiomyovasculopathy (TGCV) is a phenotype primarily reported in patients carrying genetic mutations in PNPLA2 encoding adipose triglyceride lipase (ATGL) which releases long chain fatty acid (LCFA) as a major energy source by the intracellular TG hydrolysis. These patients suffered from intractable heart failure requiring cardiac transplantation. Moreover, we identified TGCV patients without PNPLA2 mutations based on pathological and clinical studies. We provided the diagnostic criteria, in which TGCV with and without PNPLA2 mutations were designated as primary TGCV (P-TGCV) and idiopathic TGCV (I-TGCV), respectively. We hereby report clinical profiles of TGCV patients. Between 2014 and 2018, 7 P-TGCV and 18 I-TGCV Japanese patients have been registered in the International Registry. Patients with I-TGCV, of which etiologies and causes are not known yet, suffered from adult-onset severe heart disease, including heart failure and coronary artery disease, associated with a marked reduction in ATGL activity and myocardial washout rate of LCFA tracer, as similar to those with P-TGCV. The present first registry-based study showed that TGCV is an intractable, at least at the moment, and heterogeneous cardiovascular disorder.
• Using Turmeric Oil as a Solvent Improves the Distribution of Sesamin-Sesamolin in the Serum and Brain of Mice.

  Kazuko Iwamoto; Shinichi Matsumura; Yuri Yoshioka; Ayami Yamamoto; Shohei Makino; Tatsuya Moriyama; Nobuhiro Zaima

  Lipids 54 5 311 - 320 2019年05月 [査読有り]
   

  Accumulation of amyloid-β peptide is associated with Alzheimer's dementia. Previously, we reported that sesamin and sesamolin inhibited β-secretase activity in vitro, and each was transported to the serum and brain in mice after oral administration. However, the bioavailability of sesamin and sesamolin was poor in mice. In this study, we aimed to improve the bioavailability of sesamin and sesamolin. We found that the levels of sesamin and sesamolin in mouse serum and brain were higher after the administration of a mixture of sesame extract and turmeric oil (MST) than those after administering sesame extract alone. Serum sesamin and sesamolin contents in the MST-treated group were 23-fold and 15-fold higher, respectively, than those in the sesame extract-treated group. Brain sesamin and sesamolin contents in the MST-treated group were 14-fold and 11-fold higher, respectively, than those in the sesame extract-treated group. These results suggest that turmeric oil is an effective solvent to enhance the bioavailability of sesamin and sesamolin.
• Sesame Extract Attenuates the Degradation of Collagen and Elastin Fibers in the Vascular Walls of Nicotine-administered Mice.

  Hirona Kugo; Chie Miyamoto; Ayaka Sawaragi; Kiyoto Hoshino; Yuka Hamatani; Shinichi Matsumura; Yuri Yoshioka; Tatsuya Moriyama; Nobuhiro Zaima

  Journal of oleo science 68 1 79 - 85 2019年 [査読有り]
   

  Abdominal aortic aneurysm (AAA) is a vascular disease characterized by the weakening of the vascular walls and the progressive dilation of the abdominal aorta. Nicotine, a primary component of cigarette smoke, is associated with AAA development and rupture. Nicotine induces AAA development by weakening vascular walls. However, little is known about preventive methods using functional food factors for nicotine-induced vascular destruction. Sesamin and sesamolin are functional food factors that are fat-soluble lignans found in Sesamum indicum seeds. Previous reports indicated that sesamin and sesamolin have anti-oxidative and anti-inflammatory effects. In this study, we evaluated the effects of sesamin and sesamolin-rich sesame extract on the weakening of vascular walls in nicotine-administered mice. Sesame extract attenuated the degradation of collagen and elastin fibers caused by nicotine. In addition, sesame extract decreased the area positive for matrix metalloproteinase 12 (MMP-12) and oxidative stress in the vascular walls. These results suggest that sesame extract may decrease the weakening of vascular walls by suppressing the nicotine-induced degradation of collagen and elastin fibers. Sesame extract may be effective in preventing AAA development by decreasing both, MMP-12 expression and oxidative stress in vascular walls.
• Soyasapogenols reduce cellular triglyceride levels in 3T3-L1 mouse adipocyte cells by accelerating triglyceride lipolysis.

  Kazuko Iwamoto; Shuichi Kamo; Yuichi Takada; Ayana Ieda; Takatoshi Yamashita; Toshiro Sato; Nobuhiro Zaima; Tatsuya Moriyama

  Biochemistry and biophysics reports 16 44 - 49 2018年12月 [査読有り]
   

  Soyasapogenol is a soyasaponin aglycone, which has been suggested to exert a more potent function than the glycoside form. In this study, the effect of soyasapogenol A and B on cultured adipocyte cell function was investigated using mouse 3T3-L1 adipocyte cells. 3T3-L1 cells were treated with insulin, dexamethasone, and 3-isobutyl-1-methylxanthine for differentiation to adipocytes, and the cells were then cultured in the presence of soyasapogenol A or B (6.25 or 12.5 µM). The media were harvested and refreshed every 2 d. After a 10 d culture, the cells were harvested and the triglyceride content of the cells was determined. The triglyceride content of soyasapogenol B-treated cells was significantly lower than those of vehicle-treated cells. Glycerol and free fatty acid levels in the soyasapogenol-treated cell media were higher than those in vehicle cells. However, there was no difference in the level of adipose triglyceride lipase among soyasapogenol A-, soyasapogenol B-, and vehicle-treated cells. The secreted adiponectin and resistin levels of soyasapogenol-treated cell media were also different compared with those of vehicle-treated cells. Especially, the secreted resistin level in soyasapogenol B-treated cell media was obviously reduced compared with that of vehicle-treated cells. Taken together, these results suggest that soyasapogenol B exerted an anti-obesity and anti-diabetic effect on adipocytes by lowering the cellular triglyceride level by accelerating triglyceride lipolysis with reduced resistin secretion.
• Identification of the 7S and 11S globulins as percutaneously sensitizing soybean allergens as demonstrated through epidermal application of crude soybean extract.

  Murakami H; Ogawa T; Takafuta A; Yano E; Zaima N; Moriyama T

  Bioscience, biotechnology, and biochemistry 82 8 1408 - 1416 2018年08月 [査読有り]
   

  Cutaneous exposure to food allergens can predispose individuals to food allergies. Soybean, a major allergenic food, is an ingredient in various cosmetic products. However, the types of soybean proteins that are percutaneously sensitizing in humans or animal models remain unknown. In this study, BALB/c mice were dorsally shaved and epicutaneously exposed to a crude soybean extract including sodium dodecyl sulfate or distilled water alone. Specific IgEs secreted in response to 7S globulin (Gly m 5), 11S globulin (Gly m 6), Gly m 3, and Gly m 4 were measured using enzyme-linked immunosorbent assays or immunoblots. Exposure to soybean extract elicited the secretion of soybean-specific IgEs. Of the soybean proteins, 7S and 11S globulins acted as percutaneous sensitizers in 6/9 mice (67%). Additionally, IgE bound specifically and preferentially to the 7S globulin β subunit. In conclusion, this is the first report to identify percutaneously sensitizing soybean allergens in a mouse model.
• Worm wounding increases levels of pollen-related food allergens in soybean (Glycine max).

  Hanafusa K; Murakami H; Ueda T; Yano E; Zaima N; Moriyama T

  Bioscience, biotechnology, and biochemistry 82 7 1207 - 1215 2018年07月 [査読有り]
   

  The levels of food allergens in worm-wounded or non-wounded green soybeans (edamame) and mature soybeans were investigated by immunoblotting and enzyme-linked immunosorbent assay (ELISA), using allergen-specific antibodies. Non-wounded and worm-wounded soybeans showed similar total protein profiles after Coomassie brilliant blue staining, but some protein bands were observed to have been changed by worm wounding. Immunoblotting with specific antibodies for major soybean allergens (Gly m 5, Gly m 6, Gly m Bd 30 K, and Kunitz soybean trypsin inhibitor) revealed that protein band profiles and intensities were not significantly changed by worm wounding. In contrast, levels of the pollen-related soybean allergens Gly m 4 and Gly m 3 were strongly increased by worm wounding in both green and mature soybeans, as detected by immunoblotting and ELISA. These results suggested that the pollen-related food allergen risk (i.e., oral allergy syndrome; OAS) from soybeans might be enhanced by worm wounding of soybeans.
• Pathological Implication of Adipocytes in AAA Development and the Rupture.

  Hirona Kugo; Hiroki Tanaka; Tatsuya Moriyama; Nobuhiro Zaima

  Annals of vascular diseases 11 2 159 - 168 2018年06月 [査読有り]
   

  Abdominal aortic aneurysm (AAA) is a vascular disease that involves the gradual dilation of the abdominal aorta followed by its rupture. AAA is closely associated with weakening of the vascular wall due to oxidative stress, chronic inflammation, and degradation of the extracellular matrix. No effective drug therapy is currently available for preventing aneurysm progression or rupture. Adipocytes in the vascular wall are reportedly closely associated with AAA development and rupture. Fiber degradation in the aneurysm wall is enhanced by increased numbers of adipocytes, and rupture risk may increase as well. Recent studies suggested that appropriate control of adipocytes in the vascular wall may be an important strategy to prevent AAA rupture, and further studies may aid in the establishment of a method for preventing AAA rupture by therapeutic drugs or functional foods. In this review, we summarize adipocyte function and the correlation between AAA and adipocytes.
• Effect of a High-sucrose Diet on Abdominal Aortic Aneurysm Development in a Hypoperfusion-induced Animal Model.

  Miyamoto C; Kugo H; Hashimoto K; Sawaragi A; Zaima N; Moriyama T

  Journal of oleo science 67 5 589 - 597 2018年05月 [査読有り]
   

  Abdominal aortic aneurysm (AAA) is a vascular disease that results in rupture of the abdominal aorta. The risk factors for the development of AAA include smoking, male sex, hypertension, and age. AAA has a high mortality rate, but therapy for AAA is restricted to surgery in cases of large aneurysms. Clarifying the effect of dietary food on the development of AAA would be helpful for patients with AAAs. However, the relationship between dietary habits and the development of AAA is largely unknown. In our previous study, we demonstrated that adipocytes in vascular wall can induce the rupture of AAA. Therefore, we focused on the diet-induced abnormal triglyceride metabolism, which has the potential to drive AAA development. In this study, we have evaluated the effects of a high-sucrose diet on the development of AAA in a vascular hypoperfusion-induced animal model. A high sucrose diet induced high serum TG level and fatty liver. However, the AAA rupture risk and the AAA diameter were not significantly different between the control and high-sucrose groups. The intergroup differences in the elastin degradation score and collagen-positive area were insignificant. Moreover, matrix metalloproteinases, macrophages, and monocyte chemoattractant protein-1-positive areas did not differ significantly between groups. These results suggest that a high-sucrose diet does not affect the appearance of vascular adipocyte and AAA development under the vascular hypoperfusion condition.
• Elevated Plasma Levels of LDL Cholesterol Promote Dissecting Thoracic Aortic Aneurysms in Angiotensin II-Induced Mice.

  Hiroki Tanaka; Yasunori Iida; Takayuki Iwaki; Yuko Suzuki; Hideto Sano; Chiharu Miyajima; Nobuhiro Zaima; Takeshi Sasaki; Ayato Sumioka; Shogo Hakamata; Hideyuki Shimizu; Kazuo Umemura; Tetsumei Urano

  Annals of vascular surgery 48 204 - 213 2018年04月 [査読有り]
   

  BACKGROUND: Plasma low-density lipoprotein (LDL) cholesterol is implicated in abdominal aorta (AA) and aortic dissection (AD); however, its role in the pathogenesis of AA and AD, a disease with a high mortality rate, is unknown. The existing animal models such as apolipoprotein E-deficient (Apoe-/-) mice cannot reproduce all the conditions of AA/AD, including elevated LDL-cholesterol levels and spontaneous atheroma formation; therefore, a more reliable in vivo model is required. Here, we analyzed angiotensin II (Ang II)-induced mice with combined deficiency of the LDL receptor and the catalytic component of the apolipoprotein B-edisome complex (Ldlr-/-/Apobec1-/- [WKO]) to understand AA formation and AD occurrence in relation to plasma lipid composition. METHODS: AAs and ADs were created in 18- to 22- week-old male Apoe-/- and Ldlr-/-/Apobec1-/- mice by Ang II infusion. Immunostaining allowed assessment of smooth muscle cells and mural monocytes/macrophages. RESULTS: Ldlr-/-/Apobec1-/- mice had elevated LDL-cholesterol levels characteristic for human type IIa hyperlipidemia, resulting in atherogenesis, which promoted mortality, AA formation, and AD development. Interestingly, variations in the distribution of atheromas and inflammatory sites between Apoe-/- and Ldlr-/-/Apobec1-/- mice depending on lipid profiles resulted in differences in AA formation and AD occurrence in the thoracic aorta. CONCLUSIONS: Our results indicate the presence of a pathogenic pathway involving serum lipid composition that plays a key role in AA formation and AD occurrence in Ang II-induced mice.
• Visualization of the distribution of anthocyanin species in mice eyeball by matrix-assisted laser desorption/ionization mass spectrometry imaging

  Shuhei Yamada; Nobuhiro Zaima; Yukihiro Yoshimura; Shiori Inaba; Takamichi Fujimori; Tetsuya Sogon; Tatsuya Moriyama

  Rapid Communications in Mass Spectrometry 32 5 380 - 384 2018年03月 [査読有り]
   

  Rationale: Anthocyanins, which belong to a class of molecules called flavonoids, are known to have beneficial effects for both humans and animals. Many physiological functions have been attributed to anthocyanins since ancient times. The most important function is the relief of eyestrain, but the biodistribution of anthocyanins remains unknown. In this study, we analyzed the kinetics of anthocyanin species in mice eyeballs and surrounding tissues. Methods: We used mice that were administered bilberry extract solution intraperitoneally. After harvesting eyeballs, cross-sections were prepared using a cryostat and analyzed using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). Results: Various ions of anthocyanin species, m/z 419, 449, 463, 465, 479, and 493, were observed in MALDI-MSI spectra. Most of these peaks corresponded to places considered to be extraocular muscles with the outer layer of the retina. Conclusions: Through MALDI-MSI and MALDI-MS/MS analyses, we demonstrated that anthocyanin species are distributed at muscle tissues with the outer layer of the retina. It is speculated that anthocyanin species directly improve eyestrain at the extraocular muscles.
• Group B Soyasaponin Aglycone Suppresses Body Weight Gain and Fat Levels in High Fat-Fed Mice.

  Kamo S; Takada Y; Yamashita T; Sato T; Yano E; Zaima N; Moriyama T

  Journal of nutritional science and vitaminology 64 3 222 - 228 2018年 [査読有り]
   

  Group B soyasaponins, found in soy, have various health-promoting properties, but it is unclear whether they have an anti-obesity effect. The aim of this study was to evaluate the anti-obesity effect of group B soyasaponin glycosides and aglycone in mice fed a high-fat diet. Six-week-old C57/BL6 mice were divided into three groups (each n=10) and orally administered a high-fat diet for 35 d; two of the groups also received group B soyasaponin glycosides or aglycone. Although there was no significant difference among the three groups in consumption, the weight of fat adipose tissue at autopsy was more than 30% lower in the group B soyasaponin aglycone group than in the control group, but X-ray computed tomography showed no significant difference in muscle weight between these two groups. The ratio of muscle to whole body weight was higher in the group B soyasaponin aglycone group than in the control group. These results suggest that group B soyasaponin aglycone has a stronger anti-obesity effect than group B soyasaponin glycosides, without a loss in muscle weight, and that it increases the ratio of muscle to whole body weight. To our knowledge, this is the first report showing the anti-obesity effect of soyasaponin aglycone in vivo using animal models.
• Adipocytes and abdominal aortic aneurysm: Putative potential role of adipocytes in the process of AAA development.

  Kugo H; Moriyama T; Zaima N

  Current drug targets 19 11 1228 - 1232 2018年01月 [査読有り]
  
• The Effect of a High-Fat Diet on the Development of Abdominal Aortic Aneurysm in a Vascular Hypoperfusion-Induced Animal Model.

  Keisuke Hashimoto; Hirona Kugo; Hiroki Tanaka; Kazuko Iwamoto; Chie Miyamoto; Tetsumei Urano; Naoki Unno; Kohsuke Hayamizu; Nobuhiro Zaima; Tatsuya Moriyama

  Journal of vascular research 55 2 63 - 74 2018年 [査読有り]
   

  Abdominal aortic aneurysm (AAA) is a vascular disease characterized by chronic inflammation in the infrarenal aorta. Most cases of AAA remain asymptomatic until rupture, and the mortality rate of patients with AAA rupture is very high. Currently, the relation between dietary habits and AAA development remains unknown. In this study, we evaluated the effects of a high-fat diet on the development of AAA in a vascular hypoperfusion-induced animal model. The risk of AAA rupture and AAA diameter in the high-fat group significantly increased compared with those in the control group. The number and size of adipocytes in the vascular wall in the high-fat group significantly increased as compared with those in the control group. Additionally, the collagen-positive sections in the areas with adipocytes significantly decreased as compared with those without adipocytes. The protein levels of matrix metalloproteinase (MMP)-2, MMP-9, and MMP-12, and macrophage-positive areas in the parts with adipocytes also significantly increased as compared with those without adipocytes. These data suggested that AAA rupture risk increased through accelerating chronic inflammation due to the accumulation of adipocytes in the vascular wall in the high-fat group.
• Appearance of Adipocytes in Thoracic Aortic Aneurysm.

  Hirona Kugo; Yoshihiko Ikeda; Tatsuya Moriyama; Nobuhiro Zaima

  Journal of oleo science 67 12 1543 - 1549 2018年 [査読有り]
   

  Thoracic aortic aneurysm (TAA) is a lethal vascular disease that involves localized dilation of the thoracic aorta. The detailed mechanisms of TAA development and rupture are not fully understood. Recent reports have shown that the abnormal appearance of adipocytes in the vascular wall is associated with abdominal aortic aneurysm (AAA) progression or rupture. However, the presence of adipocytes in the TAA wall remains unknown. In this study, we observed the pathology of thoracic aortae to investigate whether adipocytes abnormally appear in the TAA wall. Abnormal appearance of adipocytes was mainly observed in the adventitia in the TAA vascular walls. The adipocyte area in the vascular wall was significantly increased in the TAA wall compared to the control wall. Destruction of collagen fibers, and increase in areas positive for matrix metalloproteinase (MMP) -2, MMP-9, and Mac387+ macrophages were observed in the area around adipocytes in the vascular wall. This study demonstrated the appearance of adipocytes in the TAA wall. The accumulation of adipocytes in AAA wall reportedly facilitates the destruction of fibers surrounding adipocytes, and thereby, leads to vascular wall weakness. Therefore, adipocytes in the TAA wall can be associated with the weakening of the vascular wall as well as the AAA wall. The appropriate control of adipocytes in the vascular wall may prevent weakening of the vascular wall in TAA.
• Percutaneous Sensitization to Soybean Proteins Is Attenuated by Oral Tolerance.

  Hiroki Murakami; Takashi Ogawa; Akiho Takafuta; Erika Yano; Nobuhiro Zaima; Tatsuya Moriyama

  Journal of nutritional science and vitaminology 64 6 483 - 486 2018年 [査読有り]
   

  Oral tolerance prevents allergic responses, but cutaneous exposure to food allergens predisposes individuals to food allergies. Soybean, a major allergenic food, is also an ingredient in various cosmetic products. However, it remains to be determined whether oral tolerance prevents percutaneous sensitization to soybean proteins in humans or animal models. In this study, BALB/c mice were divided into three groups; the SS group fed a soybean-containing diet, and the CS and control (C) groups fed a soybean-free diet. After being dorsally shaved, the CS and SS groups were epicutaneously exposed to a soybean extract while the control group was exposed to only the carrier. Specific IgE and IgG1 immunoglobulins secreted in response to the soybean proteins were measured using enzyme-linked immunosorbent assays. Exposure to the soybean extract elicited the secretion of IgE and IgG1 specific for Gly m 5 and Gly m 6, and trypsin inhibitor. Oral soybean consumption attenuated the secretion of all the soybean-specific IgEs and IgG1s, suggesting that percutaneous sensitization to soybean proteins is attenuated by oral tolerance.
• Dietary DNA Attenuates the Degradation of Elastin Fibers in the Aortic Wall in Nicotine-Administrated Mice.

  Keisuke Hashimoto; Nobuhiro Zaima; Hirotaka Sekiguchi; Hirona Kugo; Chie Miyamoto; Kiyoto Hoshino; Natsumi Kawasaki; Keita Sutoh; Koji Usumi; Tatsuya Moriyama

  Journal of nutritional science and vitaminology 64 4 271 - 276 2018年 [査読有り]
   

  Abdominal aortic aneurysm (AAA) is a vascular disease characterized by chronic inflammation in the infrarenal aorta. Epidemiologic data have clearly linked tobacco smoking to aneurysm formation and a faster rate of expansion. It suggested that nicotine, one of the main ingredients of tobacco, has been suggested to be associated with AAA development and rupture. In the condition where no established drugs are available; therefore, an effective approach to prevent the vascular damage from nicotine consumption may be the use of dietary functional food factors. However, little is known about the relationship between dietary components and AAA. In this study, we estimated the effect of dietary deoxyribonucleic acid (DNA) on the vascular wall. After habituation for 5 d, the mice were divided into four groups: control diet and distilled water group (C), DNA-Na diet and distilled water group (DNA), control diet and 0.5 mg/mL nicotine solution group (C-Nic), DNA-Na diet, and 0.5 mg/mL nicotine solution group (DNA-Nic). The dietary DNA attenuated the degradation of elastin fibers induced by nicotine administration. The areas stained positive for MMP-2 in the DNA-Nic group were significantly suppressed compared to C-Nic mice. These data suggest that the dietary DNA may prevent the weakening of the aortic wall via inhibition of the MMP-2-dependent pathway. In conclusion, we have revealed the protective effect of dietary DNA on the vascular pathology of nicotine-administrated mice. A nucleic acid-rich diet might be useful for people who consume nicotine via smoking, chewing tobacco, or nicotine patches.
• Creation of a Rodent Model of Abdominal Aortic Aneurysm by Blocking Adventitial Vasa Vasorum Perfusion

  Hiroki Tanaka; Naoki Unno; Tatsuro Yata; Hirona Kugo; Nobuhiro Zaima; Takeshi Sasaki; Tetsumei Urano

  JOVE-JOURNAL OF VISUALIZED EXPERIMENTS 129 2017年11月 [査読有り]
   

  The adventitial vasa vasorum (VV) provides oxygen and nourishment to the aortic wall. Hypoxia in the aortic wall can cause enlarged abdominal aortic aneurysms (AAAs). This article introduces and describes a standard protocol used to induce AAAs through adventitial VV hypoperfusion created with a combination of polyurethane catheter insertion into the aortic lumen and suture ligation of the infrarenal abdominal aorta. The protocol involves the use of male rats weighing 300-400 g, which are provided food and water ad libitum. After laparotomy with a ventral midline abdominal incision, exfoliation of the aorta is performed, which blocks blood flow from the perivascular tissue. Aortotomy involving a small incision adjacent to the renal artery branches is performed, and a polyurethane catheter is inserted using an 18-gauge indwelling needle. After repairing the incision, tight ligation of the aorta over the catheter blocks VV blood flow from the proximal direction through the aortic wall without disturbing the aortic blood flow. This technique can induce an AAA with progressive aortic dilatation. The greatest benefit of this model is that VV hypoperfusion causes tissue hypoxia and the development of an infrarenal AAA, which has morphological and pathological characteristics similar to those of a human AAA.
• Antiosteoporotic activity of a syringic acid diet in ovariectomized mice

  Teruyoshi Tanaka; Nobuhisa Kawaguchi; Nobuhiro Zaima; Tatsuya Moriyama; Yasuhisa Fukuta; Norifumi Shirasaka

  JOURNAL OF NATURAL MEDICINES 71 4 632 - 641 2017年10月 [査読有り]
   

  In recent years, the number of patients with osteoporosis has risen with the increase in average longevity. Therefore, the chemoprevention of osteoporosis using food materials or food components has become an increasingly important target. Syringic acid (SA) is a phenolic compound present in the fruit of the a double dagger ai palm Euterpe oleracea and the mycelium of the shiitake mushroom Lentinula edodes. This compound has no affinity for estrogen receptors and is potentially useful for disease prevention. However, little is known about the effects of a SA diet on bone metabolism, particularly bone resorption in vivo. Here, we demonstrated the effects of a SA diet on bone loss and uterine weight loss in ovariectomized (OVX) mice. Ten-week-old OVX mice were fed SA-containing diets (100 mg/kg body weight/day) for 10 weeks. After 10 weeks of dietary SA, the body weight, food intake, and uterine weight of the OVX mice were unaffected; however, femoral bone mineral density (cortical bone density, cancellous bone density, and total bone density) was higher in the SA-fed groups than in the OVX-control group. Furthermore, histomorphometric analysis revealed that the number of osteoclasts and osteoblasts was decreased and increased, respectively, in the SA-fed groups. These results suggest that a SA diet suppresses bone loss by downregulating bone resorption and upregulating bone formation without affecting the uterus in OVX mice. Although further studies are needed, SA may be a compound that can be used to prevent or retard osteoporosis.
• 「成人食物アレルギーUpdate」に寄せる 新規大豆アレルゲンGly m7の検出と特性解析

  徳舛直樹; 花房佳世; 野地和音; 矢野えりか; 財満信宏; 森山達哉

  月刊アレルギーの臨床 503 856‐859  2017年08月
• Imaging Modalities for Triglyceride deposit cardiomyovasculopathy

  Higashi M; Ikeda Y; Miyauchi H; Zaima N; Suzuki A; Li M; Kobayashi K; Naito H; Hirano K

  Annals of Nuclear Cardiology 3 1 94 - 102 日本心臓核医学会 2017年08月 [査読有り]
   

  Triglyceride deposit cardiomyovasculopathy (TGCV) is a novel clinical entity we found in patients with severe heart failure waiting for cardiac transplantation. The probands carried genetic mutations in adipose triglyceride lipase (ATGL), which is an essential molecule for the intracellular hydrolysis of TG. Patients with TGCV showed ectopic accumulation of TG in cardiomyocytes and smooth muscle cells resulting from the abnormal intracellular metabolism of TG and its substrates, long chain fatty acids (LCFAs). Our postmortem analyses demonstrated substantial numbers of autopsied individuals with TGCV phenotype, whose expression of ATGL was conserved. These results suggest that TGCV might be difficult to diagnose in daily clinics, however be more prevalent than expected, and a possible important cause of cardiac death. This review article focuses on imaging modalities to evaluate cardiomyovascular TG accumulation of this novel disease. Data and images are shown from pathological analyses, imaging mass spectrometry, myocardial scintigraphy with a radioactive analogue for LCFA, iodine-123-β-methyl iodophenyl-pentadecanoic acid, MR spectroscopy, and CT-based TG imagings in primary TGCV patients with genetic ATGL deficiency, which is ultra-rare, but the monogenic model.
• Suppressive effects of dietary EPA-rich fish oil on the degradation of elastin fibers in the aortic wall in nicotine-administered mice

  Hirona Kugo; Nobuhiro Zaima; Megumi Onozato; Chie Miyamoto; Keisuke Hashimoto; Kenichi Yanagimoto; Tatsuya Moriyama

  FOOD & FUNCTION 8 8 2829 - 2835 2017年08月 [査読有り]
   

  Abdominal aortic aneurysm (AAA) is a vascular disease involving gradual dilation of the abdominal aorta. Recent studies suggest that nicotine, which is a primary component in cigarette smoke, is closely associated with the development and rupture of an AAA. Nicotine accelerates AAA development through the weakening of the vascular wall by increasing oxidative stress and matrix metalloproteinase (MMP)-2 expression. However, little is known about preventing the AAA induced by nicotine. A non-surgical means of preventing the weakening of the vascular wall before the onset of AAA by functional food factors would be a valuable option over surgery. Fish oil is a functional food that is rich in n-3 polyunsaturated fatty acids that have an anti-inflammatory effect. In this study, we evaluated the effect of dietary fish oil on the weakening of the aortic wall due to nicotine administration in a mouse model. Histological analysis showed that the dietary fish oil suppressed the degradation of elastin fibers in the nicotine-administered mice. Additionally, the dietary fish oil suppressed the protein level of MMP-12, macrophage infiltration, and the oxidative stress in the vascular wall. These results suggest that fish oil could suppress the weakening of the vascular wall by suppressing the elastin fiber degradation caused by nicotine. By suppressing the nicotine induced weakening of the vascular wall, fish oil might help prevent the development of AAA.
• Pathological Analysis of the Ruptured Vascular Wall of Hypoperfusion-induced Abdominal Aortic Aneurysm Animal Model

  Hirona Kugo; Nobuhiro Zaima; Hiroki Tanaka; Keisuke Hashimoto; Chie Miyamoto; Ayaka Sawaragi; Tetsumei Urano; Naoki Unno; Tatsuya Moriyama

  JOURNAL OF OLEO SCIENCE 66 5 499 - 506 2017年05月 [査読有り]
   

  Abdominal aortic aneurysm (AAA) is a vascular disease that results in the gradual dilation of the abdominal aorta and has a high rupture-related mortality rate. However, the mechanism of AAA rupture remains unknown. In our previous study, we established a novel AAA animal model (hypoperfusion-induced AAA rat model) with spontaneous AAA rupture. Using the hypoperfusion-induced AAA rat model, we demonstrated that the abnormal appearance of adipocytes in the vascular wall is associated with AAA rupture. However, pathological analysis of the rupture area has not been performed because it is particularly difficult to identify the rupture point. In this study, we succeeded in obtaining samples from the rupture point and performed a histological analysis of the ruptured area in the vascular wall in the hypoperfusion-induced AAA rat model. Adipocytes were observed along the AAA-ruptured area of the vascular wall. In the areas around the adipocytes, macrophage infiltration and protein levels of matrix metalloproteinases 2 and 9 were significantly increased and collagen-positive areas were significantly decreased, as compared with areas without adipocytes. The AAA diameter was correlated with the number of adipocytes in the vascular wall of the hypoperfusion-induced AAA rat model. On the other hand, serum triglyceride levels and serum total cholesterol levels were not correlated with the number of adipocytes in the vascular wall. These results suggest that local adipocyte accumulation in the vascular wall, not serum lipids, has an important role in AAA rupture.
• 「自然免疫とアレルギー疾患―最新の病態―」に寄せる 野菜・果実飲料のOASリスク評価

  村上浩規; 植田啄也; 矢野えりか; 岩本和子; 財満信宏; 森山達哉

  月刊アレルギーの臨床 37 497 265‐268 - 268 (株)北隆館 2017年03月 

  花粉症に関連するクラス2食物アレルギーにおいては、主な症例として豆乳や野菜・果物などの摂取時のOASが一般的である。この原因抗原として、汎アレルゲンであるPR-10やプロフィリンがよく知られている。そこで、本稿では、プロフィリン(Profilin)に注目し、各種野菜・果実飲料の可溶性画分における本アレルゲンを検出することで、プロフィリンによるOAS発症リスクを評価した。市販のこれら飲料では、加熱等による殺菌過程で、本アレルゲンは変性・不溶化しており、OASリスクは低いことが示唆された。(著者抄録)
• Hyperglycemia Suppresses RANKL-Induced Osteoclast Differentiation through LXRβ Expression in RAW264.7 Cells.

  Tanaka T; Takei Y; Zaima N; Moriyama T; Yamanouchi D

  Journal of nutritional science and vitaminology 63 1 28 - 34 2017年02月 [査読有り]
   

  There have been reports that hyperglycemia suppresses osteoclast (OCL) differentiation, although the underlying mechanism is poorly understood. Here we demonstrated that high glucose suppresses OCL differentiation through activation of liver X receptor (LXR) beta, a recently reported glucose-sensing nuclear receptor. The effect of hyperglycemia on osteoclastogenesis was tested in RAW264.7 cells, a murine macrophage cell line. Cells were treated with receptor activator of NF-kappa B ligand (RANKL) under normoglycemic (5.5 mM glucose), normoglycemic with high osmotic pressure (5.5 mM glucose + 10.0 mM mannitol), and hyperglycemic (15.5 mM glucose) conditions. RANKL-induced osteoclastogenesis was significantly suppressed by high-glucose treatment. Mannitol treatment also significantly suppressed osteoclastogenesis, but the inhibitory effect was lower than for high-glucose treatment. The suppression of mRNA expression of Lxr beta by RANKL was significantly restored by high glucose, but not mannitol. Additionally, the deactivation of Lxr beta by siRNA attenuated high-glucose-induced suppression of osteoclastogenesis. Although further validation of the underlying pathway is necessary, targeting LXR beta is a potential therapeutic approach to treating osteoporosis.
• 「蕁麻疹の原因と最新治療」に寄せる 各種大豆加工食品における花粉症関連大豆アレルゲンGly m3(プロフィリン)の検出

  植田啄也; 花房佳世; 矢野えりか; 岩本和子; 財満信宏; 森山達哉

  月刊アレルギーの臨床 37 495 58‐61 - 61 (株)北隆館 2017年01月 

  花粉症に関連する大豆アレルギー(大豆によるクラス2食物アレルギー)の主な症例としては、豆乳などの摂取時のOASが一般的である。大豆には、様々な加工食品が存在するが、それらのOASリスクは多様である。クラス2大豆アレルギーの主要抗原としてGly m 4とGly m 3が同定されている。そこで、各種大豆加工食品の抽出後の上清画分から可溶性のGly m 3を検出することで、Gly m 3によるOAS発症リスクを評価した。得られた結果はGly m 4の場合と類似していた。これら2つの花粉症関連抗原の上清中での検出量を評価することで、各種大豆加工食品のOASリスクの指標となることが示唆された。(著者抄録)
• Insufficient Lymph Drainage Causes Abnormal Lipid Accumulation and Vein Wall Degeneration (vol 9, pg 277, 2016)

  Tanaka Hiroki; Zaima Nobuhiro; Sasaki Takeshi; Konno Hiroyuki; Setou Mitsutoshi; Unno Naoki

  ANNALS OF VASCULAR DISEASES 10 1 78  2017年 [査読有り]
  
• The effects of nicotine administration on the pathophysiology of rat aortic wall

  H. Kugo; N. Zaima; H. Tanaka; T. Urano; N. Unno; T. Moriyama

  BIOTECHNIC & HISTOCHEMISTRY 92 2 141 - 148 2017年 [査読有り]
   

  Abdominal aortic aneurysm (AAA) is the progressive dilation of the abdominal aorta. Nicotine is reported to be associated with the development and rupture of AAA, but the pathological effects of nicotine on normal rat aorta have not been determined. We investigated pathological changes in the aortic wall of rats caused by the administration of nicotine. Nicotine administration weakened the vascular wall, increased gelatinolytic activity and promoted the destruction of elastin and collagen in the rat abdominal aorta. There were no differences in the areas positive for matrix metalloproteinase (MMP)-2 and MMP-9 between the control and nicotine treated groups. The areas positive for MMP-12 in the nicotine group were significantly greater than for the control group. Gelatinolytic activity in the aortic wall was increased significantly in the nicotine group. Our findings suggest that MMP-12 is sensitive to nicotine exposure in rats.
• The effect of n-3 PUFA on the development of abdominal aortic aneurysm

  Nobuhiro Zaima

  Journal of Atherosclerosis and Thrombosis 24 9 908 - 909 2017年 [査読有り]
  
• Lysophosphatidylcholine Acyltransferase-3 Expression Is Associated with Atherosclerosis Progression

  Hiroki Tanaka; Nobuhiro Zaima; Takeshi Sasaki; Naoto Yamamoto; Kazunori Inuzuka; Tatsuro Yata; Takayuki Iwaki; Kazuo Umemura; Hideto Sano; Yuko Suzuki; Tetsumei Urano; Mitsutoshi Setou; Naoki Unno

  JOURNAL OF VASCULAR RESEARCH 54 4 200 - 208 2017年 [査読有り]
   

  Free arachidonic acid (AA) is an important precursor of lipid mediators such as leukotrienes and prostaglandins that induces inflammation and is associated with atherosclerosis progression. Recent studies have shown that lysophosphatidylcholine acyltransferase-3 (LPCAT3) converts lysophosphatidylcholine (LPC) and free AA into phosphatidylcholine (PC)-containing AA (arachidonyl-PC) and thereby can regulate intracellular free-AA levels. However, the association between LPCAT3 and atherosclerosis remains to be established. In this study, we analyzed human and mouse atherosclerotic tissues to gain insight into the arachidonyl-PC metabolism involving LPCAT3 using imaging mass spectrometry. The data revealed a complementary distribution of arachidonyl-PC and LPC in human atherosclerotic tissues with arachidonyl-PC decreasing and LPC increasing as atherosclerosis progressed. Furthermore, we found a homologous distribution of LPCAT3 expression and arachidonyl-PC based on atherosclerotic progression. In contrast, in ApoE-deficient mice, atherosclerosis increased both arachidonyl-PC accumulation and LPCAT3 expression. Taken together, these findings suggest that the regulation of LPCAT3 expression might be associated with atherosclerotic progression in humans. (C) 2017 S. Karger AG, Basel
• Significant advancement of mass spectrometry imaging for food chemistry

  Yukihiro Yoshimura; Naoko Goto-Inoue; Tatsuya Moriyama; Nobuhiro Zaima

  FOOD CHEMISTRY 210 200 - 211 2016年11月 [査読有り]
   

  Food contains various compounds that have an impact on our daily lives. Many technologies have been established to analyze these molecules of interest in foods. However, the analysis of the spatial distribution of these compounds in foods using conventional technology, such as high-performance liquid chromatography-mass spectrometry or gas chromatography-mass spectrometry is difficult. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is considered an ideal complementary approach. MALDI-MSI is a two-dimensional MALDI-MS technology that can detect compounds in a tissue section without extraction, purification, separation, or labeling. MALDI-MSI can be used to visualize the spatial distribution of chemical compounds or biomolecules in foods. Although the methodology of MALDI-MSI in food science is not yet fully established, the versatility of MALDI-MSI is expected to open a new frontier in food science. Herein, we describe the principles and applications of MALDI-MSI in food science and related fields. (C) 2016 Elsevier Ltd. All rights reserved.
• Inhibitory Activities of Sesame Seed Extract and its Constituents against beta-Secretase

  Shinichi Matsumura; Kazuya Murata; Nobuhiro Zaima; Yuri Yoshioka; Masanori Morimoto; Hideaki Matsuda; Masahiro Iwaki

  NATURAL PRODUCT COMMUNICATIONS 11 11 1671 - 1674 2016年11月 [査読有り]
   

  The need for a preventive agent against dementia led us to screen natural plant resources. Among the herbs and spices tested, sesame seed prepared from Sesamum indicum seeds showed potent beta-secretase inhibitory activity. The active principles were determined to be sesamin and sesamolin, typical lignans in S. indicum. The IC50 values of sesamin and sesamolin were 257 and 140 mu M, respectively. These compounds were investigated in a preliminary absorption experiment. After oral administration, these compounds were detected in an intact form in the brain and serum. These results suggest that consumption of sesame seeds may prevent dementia by sesamin and sesamolin, the constituents in sesame seeds.
• Anti-Hyperglycemic Effect of a Kudzu (Pueraria lobata) Vine Extract in Ovariectomized Mice

  Teruyoshi Tanaka; Yukihiro Yokota; Hanjun Tang; Nobuhiro Zaima; Tatsuya Moriyama; Yukio Kawamura

  JOURNAL OF NUTRITIONAL SCIENCE AND VITAMINOLOGY 62 5 341 - 349 2016年10月 [査読有り]
   

  Postmenopausal diabetes is exacerbated by estrogen deficiency. Ovariectomized (OVX) animal models can be used to develop strategies for preventing or treating postmenopausal symptoms. We previously found that a diet containing kudzu (Pueraria lobata) vine ethanol extract (PVEE) suppressed weight gain in OVX mice. Therefore, this study further elucidated how PVEE affected OVX mice. Ten-week-old OVX or sham-operated mice were fed diets containing either no PVEE (control) or 20 mg.kg(-1).d(-1) PVEE for 8 wk, 5 mg.kg(-1).d(-1) PVEE for 24 wk, or 20 mg.kg(-1).d(-1) puerarin (daidzein-8-C-glucoside), a major isoflavone present in PVEE, for 10 wk. The effects of puerarin on glucose tolerance were also tested in OVX mice. The experimental diets were not associated with any abnormalities in any mice tested in the present study. Weight gain and serum glucose levels were increased in OVX mice and these effects were significantly attenuated in OVX mice that consumed PVEE (5 or 20 mg.kg(-1).d(-1)) or puerarin. Puerarin-treated OVX mice also showed reduced serum glucose levels following administration of 1,000 mg.kg(-1) glucose. These results suggested that puerarin contributed to PVEE-mediated improvements in glucose metabolism in OVX mice. Although further studies are needed to clarify the molecular mechanism underlying these observations, PVEE and puerarin could provide effective approaches to the amelioration of postmenopausal diabetes.
• Effect of dietary fish oil on mouse testosterone level and the distribution of eicosapentaenoic acid-containing phosphatidylcholine in testicular interstitium

  Nobuhiro Zaima; Saori Kinoshita; Nao Hieda; Hirona Kugo; Kaori Narisawa; Ayami Yamamoto; Kenichi Yanagimoto; Tatsuya Moriyama

  Biochemistry and Biophysics Reports 7 259 - 265 2016年09月 [査読有り]
   

  Low levels of serum testosterone are characteristically associated with diabetes, coronary atherosclerosis, obstructive sleep apnea, rheumatoid arthritis, and chronic obstructive pulmonary disease. Testosterone replacement therapy is effective against many of these disorders, indicating the importance of maintaining a healthy testosterone level. In this study, we investigated the effects of fish oil on murine testosterone metabolism and analyzed the dynamics of relevant lipids in testes by matrix-assisted laser desorption ionization mass spectrometry imaging. Testosterone was upregulated in mice that received fish oil. In the testicular interstitium, eicosapentaenoic acid-containing phosphatidylcholine was distributed characteristically. These data suggest that eicosapentaenoic acid is involved in testosterone metabolism.
• The anti-obesity effect of Taheebo (Tabebuia avellanedae Lorentz ex Griseb) extract in ovariectomized mice and the identification of a potential anti-obesity compound

  Kazuko Iwamoto; Youichi Fukuda; Chisato Tokikura; Mayuko Noda; Ayami Yamamoto; Misato Yamamoto; Mitsuaki Yamashita; Nobuhiro Zaima; Akira Iida; Tatsuya Moriyama

  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 478 3 1136 - 1140 2016年09月 [査読有り]
   

  Estrogen deficiency-induced obesity has a high risk of visceral fat accumulation and body weight gain. It is also associated with many adverse health conditions. Taheebo extract from Tabebuia avellanedae has been recognized as playing several biological and pharmacological roles. Therefore, we investigated whether the intake of n-BuOH extract of Taheebo shows anti-obesity effect in ovariectomized (OVX) mice. After 16 weeks of feeding, the mice administrated with 0.5% n-BuOH extract of Taheebo showed significantly decreased body weight compared with that of the control mice, and the fat mass also showed a significant decrease. In 3T3-L1 cells, supplementation with n-BuOH extract of Taheebo significantly reduced the triglyceride ( TG) levels. Furthermore, bioassay-guided purification of the nBuOH extract based on the TG levels in 3T3-L1 cells led to the isolation of compound 2 ( 1-dehydroxy-3,4-dihydroaucubigenin). These results suggested that the anti obesity effect of Taheebo extract is due to its capability in preventing the accumulation of adipocyte in mice. Taheebo extract might be a promising functional food resources capable of protecting against OVX-induced obesity. (C) 2016 Elsevier Inc. All rights reserved.
• 「アレルギー疾患の発症・増悪の予防-最新のアプローチ-」に寄せる 競合ELISA法による大豆アレルゲンGly m4の定量の試み

  花房 佳世; 植田 啄也; 矢野 えりか; 財満 信宏; 森山 達哉

  アレルギーの臨床 36 9 874 - 878 (株)北隆館 2016年08月 

  花粉症と関連する大豆食品による口腔アレルギー症候群の主要原因抗原としてGly m4が知られている。今回、このGly m4の競合ELISA定量系を構築し、各種豆乳や豆腐におけるGly m4を定量した。その結果、タンパク質濃度の高い豆乳ではGly m4濃度が高く、タンパク質濃度の低いものではGly m4濃度も低いという結果が得られ、豆乳においてはタンパク質濃度とGly m4濃度は相関することが明らかとなった。よって、豆乳類のOASリスクは、概ねタンパク質濃度を参考にすることで推測できる可能性が示唆された。(著者抄録)
• Adipocyte in vascular wall can induce the rupture of abdominal aortic aneurysm

  Hirona Kugo; Nobuhiro Zaima; Hiroki Tanaka; Youhei Mouri; Kenichi Yanagimoto; Kohsuke Hayamizu; Keisuke Hashimoto; Takeshi Sasaki; Masaki Sano; Tatsuro Yata; Tetsumei Urano; Mitsutoshi Setou; Naoki Unno; Tatsuya Moriyama

  Scientific Reports 6 31268  2016年08月 [査読有り]
   

  Abdominal aortic aneurysm (AAA) is a vascular disease involving the gradual dilation of the abdominal aorta. It has been reported that development of AAA is associated with inflammation of the vascular wall; however, the mechanism of AAA rupture is not fully understood. In this study, we investigated the mechanism underlying AAA rupture using a hypoperfusion-induced animal model. We found that the administration of triolein increased the AAA rupture rate in the animal model and that the number of adipocytes was increased in ruptured vascular walls compared to non-ruptured walls. In the ruptured group, macrophage infiltration and the protein levels of matrix metalloproteinases 2 and 9 were increased in the areas around adipocytes, while collagen-positive areas were decreased in the areas with adipocytes compared to those without adipocytes. The administration of fish oil, which suppresses adipocyte hypertrophy, decreased the number and size of adipocytes, as well as decreased the risk of AAA rupture ratio by 0.23 compared to the triolein administered group. In human AAA samples, the amount of triglyceride in the adventitia was correlated with the diameter of the AAA. These results suggest that AAA rupture is related to the abnormal appearance of adipocytes in the vascular wall.
• Inhibitory activities of sesame seed extract and its constituents against β-secretase

  Shinichi Matsumura; Kazuya Murata; Nobuhiro Zaima; Yuri Yoshioka; Masanori Morimoto; Hideaki Matsuda; Masahiro Iwaki; Masahiro Iwaki

  Natural Product Communications 11 1671 - 1674 2016年01月 

  The need for a preventive agent against dementia led us to screen natural plant resources. Among the herbs and spices tested, sesame seed prepared from Sesamum indicum seeds showed potent β-secretase inhibitory activity. The active principles were determined to be sesamin and sesamolin, typical lignans in S. indicum. The IC 50 values of sesamin and sesamolin were 257 and 140 μM, respectively. These compounds were investigated in a preliminary absorption experiment. After oral administration, these compounds were detected in an intact form in the brain and serum. These results suggest that consumption of sesame seeds may prevent dementia by sesamin and sesamolin, the constituents in sesame seeds.
• Inhibitory activities of essential oil obtained from turmeric and its constituents against β-secretase

  Shinichi Matsumura; Kazuya Murata; Nobuhiro Zaima; Yuri Yoshioka; Masanori Morimoto; Hirona Kugo; Ayami Yamamoto; Tatsuya Moriyama; Hideaki Matsuda

  Natural Product Communications 11 1785 - 1788 2016年01月 

  The need for a preventive agent against dementia led us to screen natural plant resources. Among the herbs and spices tested, turmeric, from rhizomes of Curcuma longa, showed high potency against β-secretase. The active principles were determined as α-turmerone, β-turmerone and ar-turmerone, with IC 50 values of 39, 62 and 92 μM respectively. In this study, the efficiency of collecting the essential oil using steam distillation of the volatile substance was disclosed. The active principles were explored, and four sesquiterpenoids and five monoterpenoids were revealed as active principles against β-secretase. On the other hand, α-turmerone, β-turmerone and ar-turmerone were also investigated in a pharmacokinetic absorption experiment. After oral administration, these compounds were detected in an intact form in the brain and serum. These results suggest that consumption of turmeric constituents may prevent dementia.
• Mass spectrometry based chemical imaging of foods

  Shekhar U. Kadam; N. N. Misra; Nobuhiro Zaima

  RSC ADVANCES 6 40 33537 - 33546 2016年 [査読有り]
   

  Chemical imaging based on mass spectrometry is an emerging technology which has opened opportunities for fundamental research in food science. The ability to quantitatively determine the spatial distribution of several chemical entities simultaneously makes it a method of choice for chemical characterization of plant materials and foods. In this review, an overview of the ionization methods is presented, followed by a discussion of the current state of the art in mass spectrometry imaging (MSI) of relevance to practices in food research. The known applications, analytical challenges, and future research potential are highlighted. MSI has been successfully utilized to a variable degree for obtaining information about spatial distribution of a variety of molecules and metabolites in foods. It allows visualizing the spatial molecular maps without extraction, purification, separation, or labelling of foods. The method is likely to find wider adoption with developments in ionization sources and inter-laboratory collaborations.
• Insufficient Lymph Drainage Causes Abnormal Lipid Accumulation and Vein Wall Degeneration.

  Tanaka H; Yamamoto N; Suzuki M; Mano Y; Sano M; Zaima N; Sasaki T; Setou M; Unno N

  Annals of vascular diseases 9 4 277 - 284 2016年 [査読有り]
  
• Characteristic Distribution Pattern of Lysophosphatidylcholine in Fibromuscular Dysplasia-Associated Visceral Artery Aneurysms Compared with Atherosclerotic Visceral Artery Aneurysms

  Hiroki Tanaka; Nobuhiro Zaima; Takeshi Sasaki; Naoto Yamamoto; Kazunori Inuzuka; Masaki Sano; Hiroyuki Konno; Tetsumei Urano; Mitsutoshi Setou; Naoki Unno

  JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS 23 6 673 - 680 2016年 [査読有り]
   

  Aim: Asymptomatic visceral artery aneurysms (VAAs) have increasingly been found, with most being either atherosclerotic VAAs or fibromuscular dysplasia (FMD)-associated VAAs. However, little is known about the pathogenesis of both diseases. We aimed to identify the differences in the distribution pattern of lipid molecules between atherosclerotic VAAs and FMD-associated VAAs. Methods: We conducted a histological study of VAAs using imaging mass spectrometry (IMS) to assess the accumulation of lipid molecules in both the aneurysmal sac and the adjacent arteries without aneurysmal changes in 17 VAA samples, which were resected during the surgery. Results: IMS revealed characteristic distributions of cholesterol ester in intima and media in the atherosclerotic VAAs, which was hardly detected in FMD-associated VAAs. However, lysophosphatidylcholine (lysoPC), a proinflammatory and proapoptotic lipid mediator, was accumulated in the medial ridge of the adventitia of FMD-associated in the aneurysmal sac, and it was also diffusely accumulated in the adjacent arteries. In contrast, lysoPC was accumulated in the area of intimal hyperplasia in atherosclerotic VAAs and the adjacent arteries. Conclusion: The distribution patterns of lipid molecules were different between the FMD-associated and atherosclerotic VAAs. The diffuse accumulation of lysoPCs in the visceral arteries may be a predisposition for the formation of FMD-associated VAAs.
• The preventive effect of fish oil on abdominal aortic aneurysm development

  Hirona Kugo; Nobuhiro Zaima; Youhei Mouri; Hiroki Tanaka; Kenichi Yanagimoto; Tetsumei Urano; Naoki Unno; Tatsuya Moriyama

  BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 80 6 1186 - 1191 2016年 [査読有り]
   

  Abdominal aortic aneurysm (AAA) is a vascular disease involving gradual dilation of the abdominal aorta and high rupture-related mortality rates. AAA is histologically characterized by oxidative stress, chronic inflammation, and extracellular matrix degradation in the vascular wall. We previously demonstrated that aortic hypoperfusion could cause the vascular inflammation and AAA formation. However, the preventive method for hypoperfusion-induced AAA remains unknown. In this study, we evaluated the effect of fish oil on AAA development using a hypoperfusion-induced AAA animal model. Dilation of the abdominal aorta in the fish oil administration group was smaller than in the control group. Collagen destruction and oxidative stress were suppressed in the fish oil administration group than in the control group. These results suggested that fish oil could prevent the development of AAA induced by hypoperfusion.
• カビ被害による農作物汎アレルゲン（PR-10,PR-5,プロフィリン）の変動解析

  三口志穂; 矢野えりか; 末森祐輔; 財満信宏; 森山達哉

  アレルギーの臨床 35 9 876 - 879 2015年09月 [査読有り][招待有り]
  
• MALDI Mass Spectrometry Imaging of Biological Structures

  Zaima N; Goto-Inoue N; Hayasaka T

  Encyclopedia of Analytical Chemistry 2015年09月 [査読有り]
  
• Distinct cardiac phenotype between two homozygotes born in a village with accumulation of a genetic deficiency of adipose triglyceride lipase

  Masahiro Higashi; Ken-ichi Hirano; Kazuhiro Kobayashi; Yoshihiko Ikeda; Ami Issiki; Tetsuo Otsuka; Akira Suzuki; Satoshi Yamaguchi; Nobuhiro Zaima; Seiki Hamada; Hironori Hanada; Chieko Suzuki; Hiroshi Nakamura; Hironori Nagasaka; Toshiyuki Miyata; Yoshihiro Miyamoto; Kunihisa Kobayashi; Hiroaki Naito; Tatsushi Toda

  INTERNATIONAL JOURNAL OF CARDIOLOGY 192 30 - 32 2015年08月 [査読有り]
  
• Hypoperfusion of the Adventitial Vasa Vasorum Develops an Abdominal Aortic Aneurysm

  Hiroki Tanaka; Nobuhiro Zaima; Takeshi Sasaki; Masaki Sano; Naoto Yamamoto; Takaaki Saito; Kazunori Inuzuka; Takahiro Hayasaka; Naoko Goto-Inoue; Yuki Sugiura; Kohji Sato; Hirona Kugo; Tatsuya Moriyama; Hiroyuki Konno; Mitsutoshi Setou; Naoki Unno

  PLOS ONE 10 8 e0134386  2015年08月 [査読有り]
   

  The aortic wall is perfused by the adventitial vasa vasorum (VV). Tissue hypoxia has previously been observed as a manifestation of enlarged abdominal aortic aneurysms (AAAs). We sought to determine whether hypoperfusion of the adventitial VV could develop AAAs. We created a novel animal model of adventitial VV hypoperfusion with a combination of a polyurethane catheter insertion and a suture ligation of the infrarenal abdominal aorta in rats. VV hypoperfusion caused tissue hypoxia and developed infrarenal AAA, which had similar morphological and pathological characteristics to human AAA. In human AAA tissue, the adventitial VV were stenotic in both small AAAs (30-49 mm in diameter) and in large AAAs (>50 mm in diameter), with the sac tissue in these AAAs being ischemic and hypoxic. These results indicate that hypoperfusion of adventitial VV has critical effects on the development of infrarenal AAA.
• 炎症・アレルギーに関わるレジスチンの変動解析

  山本美里; 何 陽; 財満信宏; 森山達哉

  アレルギーの臨床 35 14 58 - 61 2015年 [査読有り]
  
• Incompetent Lymph Drainage Causes Lipid Accumulation in Perivascular Tissue and Changes Vein Wall Structure.

  Tanaka H; Zaima N; Sasaki T; Konno H; Setou M; Unno N

  Jap J Phlebol 26 227 - 235 2015年 [査読有り]
  
• Imaging Mass Spectrometry Reveals a Unique Distribution of Triglycerides in the Abdominal Aortic Aneurysmal Wall

  Hiroki Tanaka; Nobuhiro Zaima; Takeshi Sasaki; Naoto Yamamoto; Kazunori Inuzuka; Masaki Sano; Takaaki Saito; Takahiro Hayasaka; Naoko Goto-Inoue; Kohji Sato; Hirona Kugo; Tatsuya Moriyama; Hiroyuki Konno; Mitsutoshi Setou; Naoki Unno

  JOURNAL OF VASCULAR RESEARCH 52 2 127 - 135 2015年 [査読有り]
   

  The pathophysiology underlying abdominal aortic aneurysms (AAAs) remains unknown. In this study, we applied imaging mass spectrometry (IMS) to analyze the pathophysiology of the aneurysmal wall. Comparisons were performed between the tissue samples from the neck and the sac of the AAA, at a single time point, in 30 patients who underwent elective surgery of their AAAs. The localization of each lipid molecule in the aortic wall was assessed by IMS. Histopathological examination and IMS revealed a characteristic distribution of triglycerides (TGs) specifically in the aneurismal adventitia of the sac. This characteristic TG distribution was derived from an ectopic appearance of adipocytes in the adventitia. Furthermore, ectopic adipocyte accumulation in the aortic wall leads to the loss of the collagen fiber network subsequent to the wall rupture. The underlying mechanism of adipocyte accumulation involves the presence of adipose-derived stem cells (ADSCs) in the aneurismal adventitia and the expression of peroxisome proliferator-activated receptor gamma 2, a master regulator of adipocyte differentiation by some ADSCs. This study reveals new, previously overlooked aspects of AAA pathology. (C) 2015 S. Karger AG, Basel
• DHA-PC and PSD-95 decrease after loss of synaptophysin and before neuronal loss in patients with Alzheimer's disease

  Dai Yuki; Yuki Sugiura; Nobuhiro Zaima; Hiroyasu Akatsu; Shiro Takei; Ikuko Yao; Masato Maesako; Ayae Kinoshita; Takayuki Yamamoto; Ryo Kon; Keikichi Sugiyama; Mitsutoshi Setou

  SCIENTIFIC REPORTS 4 7130  2014年11月 [査読有り]
   

  Alzheimer's disease (AD) is a progressive neurodegenerative disease that is characterized by senile plaques, neurofibrillary tangles, synaptic disruption, and neuronal loss. Several studies have demonstrated decreases of docosahexaenoic acid-containing phosphatidylcholines (DHA-PCs) in the AD brain. In this study, we used matrix-assisted laser desorption/ionization imaging mass spectrometry in postmortem AD brain to show that PC molecular species containing stearate and DHA, namely PC(18:0/22:6), was selectively depleted in the gray matter of patients with AD. Moreover, in the brain regions with marked amyloid beta (A beta) deposition, the magnitude of the PC(18:0/22:6) reduction significantly correlated with disease duration. Furthermore, at the molecular level, this depletion was associated with reduced levels of the postsynaptic protein PSD-95 but not the presynaptic protein synaptophysin. Interestingly, this reduction in PC(18:0/22:6) levels did not correlate with the degrees of A beta deposition and neuronal loss in AD. The analysis of the correlations of key factors and disease duration showed that their effects on the disease time course were arranged in order as Ab deposition, presynaptic disruption, postsynaptic disruption coupled with PC(18:0/22:6) reduction, and neuronal loss.
• Enhanced specificity for phosphatidylcholine analysis by positive ion mode matrix-assisted laser desorption/ionization imaging mass spectrometry

  Nobuhiro Zaima; Sayaka Yoshioka; Yayoi Sato; Saki Shinano; Yoshihiko Ikeda; Tatsuya Moriyama

  RAPID COMMUNICATIONS IN MASS SPECTROMETRY 28 13 1453 - 1458 2014年07月 [査読有り]
   

  RATIONALEVisualization of the spatial distribution of phosphatidylcholine (PC) in tissues by matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) provides insights into key physiological and pathophysiological processes. In MALDI-IMS analysis, the heterogeneity of adduct ions formed from PC lowers the specificity of detection of PC molecular species and poses a challenge in the identification of these species. To solve this problem, modified matrix solution and desalting with ammonium acetate (NH4Ac) buffer have been employed. However, the utility of these methods is limited to the analysis of brain sections. METHODSThe MALDI signal intensities of [PC+H], [PC+Na] and [PC+K] were compared after three different pretreatments (modified matrix solution, desalting with 150mM ammonium acetate, treatment with 150mM potassium acetate). RESULTSPretreatment of tissue sections with 150mM potassium acetate resulted in an increase in the signal intensity of [PC+K] ions produced from cryosections of the pancreas, brain, and liver tissues. CONCLUSIONSPretreatment with potassium acetate can be a simple, improved, and highly useful method for the reliable analysis of PC in tissues. Copyright (c) 2014 John Wiley & Sons, Ltd.
• Distribution of lysophosphatidylcholine in the endosperm of Oryza sativa rice

  Nobuhiro Zaima; Yukihiro Yoshimura; Yukio Kawamura; Tatsuya Moriyama

  RAPID COMMUNICATIONS IN MASS SPECTROMETRY 28 13 1515 - 1520 2014年07月 [査読有り]
   

  RATIONALESake is made from fermented rice and has been drunk in Japan for more than 1000 years. The rice must be polished prior to fermentation to obtain high-quality sake. It is traditionally recognized that the quality of sake is improved as the rice polishing ratio (percentage removed in the polishing process) increases. However, the underlying chemistry of the rice polishing process is incompletely understood. Herein, we analyzed the distribution of lysophosphatidylcholine (LPC) molecular species with unsaturated fatty acids in rice, as their presence is thought to exert a negative effect on the flavor of sake. METHODSThe distribution of LPC molecular species in rice was visualized via matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). RESULTSLPC (16:0) is ubiquitously present in the endosperm of rice while LPC (18:0) is localized in the core of the endosperm. In contrast, LPC (18:2) and LPC (18:1) are present in the outer region of the endosperm. CONCLUSIONSThe enhancement of the quality of sake as the polishing ratio of the rice increases might be explained in terms of the distribution of LPC with unsaturated fatty acids in the rice. Copyright (c) 2014 John Wiley & Sons, Ltd.
• Coronary triglyceride deposition in contemporary advanced diabetics

  Yoshihiko Ikeda; Nobuhiro Zaima; Ken-ichi Hirano; Masayuki Mano; Kunihisa Kobayashi; Sohsuke Yamada; Satoshi Yamaguchi; Akira Suzuki; Hideaki Kanzaki; Toshimitsu Hamasaki; Jun-ichi Kotani; Seiya Kato; Hironori Nagasaka; Mitsutoshi Setou; Hatsue Ishibashi-Ueda

  PATHOLOGY INTERNATIONAL 64 7 325 - 335 2014年07月 [査読有り]
   

  It is of importance to clarify pathophysiology of diabetic heart diseases such as heart failure and coronary artery disease. We reported a novel clinical phenotype called triglyceride deposit cardiomyovasculopathy (TGCV), showing aberrant TG accumulation in both coronary arteries and myocardium, in a cardiac transplant recipient. Here, we examined autopsied diabetics for TG deposition in cardiovasculature. Consecutive series of hearts from advanced diabetes mellitus (DM) subjects (DM group: DMG, n = 20) and those from age- and sex-matched non-diabetic controls (non DM group: NDMG, n = 20) were examined. The diagnostic criteria of advanced DM' was made based on 2014 Clinical Practice Recommendations proposed by the American Diabetes Association. The mean duration of DM was 15.8 years. All DMG suffered from heart diseases including coronary artery diseases and 14 subjects had multi-vessel disease. Tissue TG contents were measured biochemically. Coronary arterial TG contents was significantly higher in DMG compared with NDMG. Spatial distribution of TG in transverse sections of coronary arteries showed TG deposition mainly in smooth muscle cells by Imaging Mass Spectrometry. Abundant TG deposition in coronary artery might be associated with advanced DM.
• Molecular cloning and expression profiling of procollagen alpha 1 (I) of cultured Pacific bluefin tuna

  Teruyoshi Tanaka; Kenji Takahashi; Kohsuke Adachi; Haruki Ohta; Yukihiro Yoshimura; Yasuo Agawa; Yoshifumi Sawada; Osamu Takaoka; Amal Kumar Biswas; Kenji Takii; Nobuhiro Zaima; Tatsuya Moriyama; Yukio Kawamura

  FISHERIES SCIENCE 80 3 603 - 612 2014年05月 [査読有り]
   

  Type I collagen is widely distributed in most organs in teleosts. It plays a role not only in intercellular adhesion, but also in molecular signaling. In this study, Pacific bluefin tuna (PBT) procollagen alpha 1 (I) cDNA was cloned and characterized. The nine fragments of a procollagen alpha 1 (I) chain cDNA clone were prepared and spliced together to create the complete coding region. The resulting amino acid sequence was homologous with that of other teleosts. The mRNA expression profile of PBT procollagen alpha 1 (I) in various tissues and the phylogenetic analysis with other vertebrate procollagen alpha 1 (I) chains suggest that PBT procollagen alpha 1 (I) could be a precursor form of the PBT type I collagen alpha 1 chain. In addition, its level of expression in PBT larvae and early juveniles gradually increased with somatic growth. This increase was related to the standard length, wet body weight, and protein content of each individual fish. Therefore, the expression profile of procollagen alpha 1 (I) may be a useful indicator for somatic growth in fish larvae and juveniles.
• Lymphangiogenesis and Angiogenesis in Abdominal Aortic Aneurysm

  Masaki Sano; Takeshi Sasaki; Satoshi Hirakawa; Junichi Sakabe; Mikako Ogawa; Satoshi Baba; Nobuhiro Zaima; Hiroki Tanaka; Kazunori Inuzuka; Naoto Yamamoto; Mitsutoshi Setou; Kohji Sato; Hiroyuki Konno; Naoki Unno

  PLOS ONE 9 3 2014年03月 

  The pathogenesis of abdominal aortic aneurysm (AAA) is characterized to be inflammation-associated degeneration of vascular wall. Neovascularization is regularly found in human AAA and considered to play critical roles in the development and rupture of AAA. However, little is known about lymphangiogenesis in AAA. The purpose of this study was to demonstrate both angiogenesis and lymphangiogenesis in AAA. Abdominal aortic tissue was harvested either from autopsy (control group) and during open-repair surgery for AAA (AAA group). Adventitial lymphatic vasa vasorum was observed in both groups, but seemed to be no significant morphological changes in AAA. Immunohistochemical studies identified infiltration of lymphatic vessel endothelial hyaluronan receptor (LYVE) -1, vascular endothelial growth factor (VEGF)-C, and matrix metalloproteinase (MMP)-9-positive macrophages and podoplanin and Prox-1-positive microvessels in the intima/media in AAA wall, where hypoxia-inducible factors (HIF)-1 alpha was expressed. VEGF-C and MMP-9 were not expressed in macrophages infiltrating in the adventitia. Intraoperative indocyanine green fluorescence lymphography revealed lymph stasis in intima/medial in AAA. Fluorescence microscopy of the collected samples also confirmed the accumulation of lymph in the intima/media but not in adventitia. These results demonstrate that infiltration of macrophages in intima/media is associated with lymphangiogenesis and angiogenesis in AAA. Lymph-drainage appeared to be insufficient in the AAA wall.
• Genetic mutations in adipose triglyceride lipase and myocardial up-regulation of peroxisome proliferated activated receptor-γ in patients with triglyceride deposit cardiomyovasculopathy

  Ken Ichi Hirano; Ken Ichi Hirano; Tatsuya Tanaka; Yoshihiko Ikeda; Satoshi Yamaguchi; Satoshi Yamaguchi; Nobuhiro Zaima; Kazuhiro Kobayashi; Akira Suzuki; Akira Suzuki; Yasuhiko Sakata; Yasuhiko Sakata; Yasushi Sakata; Kunihisa Kobayashi; Tatsushi Toda; Norihide Fukushima; Hatsue Ishibashi-Ueda; Daniela Tavian; Hironori Nagasaka; Shu Ping Hui; Hitoshi Chiba; Yoshiki Sawa; Masatsugu Hori

  Biochemical and Biophysical Research Communications 443 2 574 - 579 2014年01月 

  Adipose triglyceride lipase (ATGL, also known as PNPLA2) is an essential molecule for hydrolysis of intracellular triglyceride (TG). Genetic ATGL deficiency is a rare multi-systemic neutral lipid storage disease. Information regarding its clinical profile and pathophysiology, particularly for cardiac involvement, is still very limited. A previous middle-aged ATGL-deficient patient in our institute (Case 1) with severe heart failure required cardiac transplantation (CTx) and exhibited a novel phenotype, "Triglyceride deposit cardiomyovasculopathy (TGCV)". Here, we tried to elucidate molecular mechanism underlying TGCV. The subjects were two cases with TGCV, including our second case who was a 33-year-old male patient (Case 2) with congestive heart failure requiring CTx. Case 2 was homozygous for a point mutation in the 5′ splice donor site of intron 5 in the ATGL, which results in at least two types of mRNAs due to splicing defects. The myocardium of both patients (Cases 1 and 2) showed up-regulation of peroxisome proliferated activated receptors (PPARs), key transcription factors for metabolism of long chain fatty acids (LCFAs), which was in contrast to these molecules' lower expression in ATGL-targeted mice. We investigated the intracellular metabolism of LCFAs under human ATGL-deficient conditions using patients' passaged skin fibroblasts as a model. ATGL-deficient cells showed higher uptake and abnormal intracellular transport of LCFA, resulting in massive TG accumulation. We used these findings from cardiac specimens and cell-biological experiments to construct a hypothetical model to clarify the pathophysiology of the human disorder. In patients with TGCV, even when hydrolysis of intracellular TG is defective, the marked up-regulation of PPARγ and related genes may lead to increased uptake of LCFAs, the substrates for TG synthesis. This potentially vicious cycle of LCFAs could explain the massive accumulation of TG and severe clinical course for this rare disease. © 2013 Elsevier Inc. All rights reserved.
• Matrix-Assisted Laser Desorption/Iionization Imaging Mass Spectrometry: New Technology for Vascular Pathology

  Nobuhiro Zairna; Naoko Goto-Inoue; Tatsuya Moriyama

  JOURNAL OF VASCULAR RESEARCH 51 2 144 - 148 2014年 [査読有り]
   

  The use of matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) for the assessment of vascular pathology is attracting attention as a new valuable tool for diagnosing disease and finding new markers. MALDI-IMS is a molecular imaging technique whereby the simultaneous measurement of multiple samples directly from clinical tissue sections is possible. The versatility of MALDI-IMS has opened a new frontier in vascular pathology. In this review, we describe the principle and applications of MALDI-IMS. (C) 2014 S. Karger AG, Basel
• Cilostazol inhibits accumulation of triglycerides in a rat model of carotid artery ligation

  Hiroki Tanaka; Nobuhiro Zaima; Hideki Ito; Katsuji Hattori; Naoto Yamamoto; Hiroyuki Konno; Mitsutoshi Setou; Naoki Unno

  JOURNAL OF VASCULAR SURGERY 58 5 1366 - 1374 2013年11月 

  Objective: Triglyceride (TG) accumulation in arterial tissue is associated with the development of cardiovascular disease; however, the underlying mechanism remains unclear. Cilostazol (CLZ), a selective inhibitor of phosphodiesterase 3, has antiplatelet and vasodilating effects and may decrease serum TG levels. We examined the effect of CLZ on TG accumulation in the arterial tissue of a rat model of carotid artery ligation. Methods: Rats were fed normal chow with 0.1% CLZ (CLZ group) or without CLZ (control group) for 4 weeks after unilateral carotid artery ligation near the carotid bifurcation. Results: At the end of this period, the control group showed 3.3-fold higher TG levels in the ligated carotid artery than in the contralateral artery; however, compared with the contralateral artery, the ligated artery in the CLZ group showed significantly lower levels of TG accumulation but similar serum levels of TG, total cholesterol, and high-density lipoprotein cholesterol. Furthermore, matrix-assisted laser desorption/ionization imaging mass spectrometry revealed that the ligated carotid artery in both groups had ubiquitous accumulation of TG in the intima, media, and adventitia, along with decreased heme B signals, which was indicative of ischemia. However, heme B signals were less reduced in the CLZ group than in the control group. Conclusions: Our results indicate that CLZ can inhibit the ubiquitous accumulation of TG in arterial tissues, possibly by ameliorating tissue ischemia. CLZ may be useful in improving arterial tissue hemodynamics and lipid metabolism.
• Ellagic acid improves hepatic steatosis and serum lipid composition through reduction of serum resistin levels and transcriptional activation of hepatic ppara in obese, diabetic KK-A(y) mice

  Yukihiro Yoshimura; Saori Nishii; Nobuhiro Zaima; Tatsuya Moriyarha; Yukio Kawamura

  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 434 3 486 - 491 2013年05月 [査読有り]
   

  Ellagic acid (EA) is a polyphenol found in a wide variety of plant foods that not only exhibits free radicalscavenging activity, but also confers protective effects against liver injury. Previously, we reported that pomegranate fruit extract (PFE) had an inhibitory effect on resistin secretion from differentiated murine 3T3-L1 adipocytes and identified EA contained in PFE as a potent suppressor of resistin secretion. Resistin, an adipocytokine, is considered the link between obesity and type 2 diabetes. In this study, we explored whether EA supplementation reduces serum resistin and improves hepatic steatosis and serum lipid profile by using KK-A(y) mice fed high-fat diet as a model for obese type 2 diabetes. We found that EA supplementation improved serum lipid profile and hepatic steatosis, and reduced serum resistin levels without altering mRNA expression levels in adipose tissue. Moreover, EA supplementation' upregulated mRNA expression of apoa1, ldlr, cpt1a, and ppara genes in the liver. In conclusion, our findings indicate that EA is a potent suppressor of resistin secretion in vivo and a transcriptional activator of ppara in the liver, suggesting a possibility for improving obesity-induced dyslipidemia and hepatic steatosis in KK-A(y) mice. (C) 2013 Elsevier Inc. All rights reserved.
• Adventitial Vasa Vasorum Arteriosclerosis in Abdominal Aortic Aneurysm

  Hiroki Tanaka; Nobuhiro Zaima; Takeshi Sasaki; Takahiro Hayasaka; Naoko Goto-Inoue; Kenji Onoue; Koji Ikegami; Yoshifumi Morita; Naoto Yamamoto; Yuuki Mano; Masaki Sano; Takaaki Saito; Kohji Sato; Hiroyuki Konno; Mitsutoshi Setou; Naoki Unno

  PLoS ONE 8 2 2013年02月 [査読有り]
   

  Abdominal aortic aneurysm (AAA) is a common disease among elderly individuals. However, the precise pathophysiology of AAA remains unknown. In AAA, an intraluminal thrombus prevents luminal perfusion of oxygen, allowing only the adventitial vaso vasorum (VV) to deliver oxygen and nutrients to the aortic wall. In this study, we examined changes in the adventitial VV wall in AAA to clarify the histopathological mechanisms underlying AAA. We found marked intimal hyperplasia of the adventitial VV in the AAA sac further, immunohistological studies revealed proliferation of smooth muscle cells, which caused luminal stenosis of the VV. We also found decreased HemeB signals in the aortic wall of the sac as compared with those in the aortic wall of the neck region in AAA. The stenosis of adventitial VV in the AAA sac and the malperfusion of the aortic wall observed in the present study are new aspects of AAA pathology that are expected to enhance our understanding of this disease. © 2013 Tanaka et al.
• Hypoallergenicity of various miso pastes manufactured in Japan

  Tatsuya Moriyama; Erika Yano; Yuusuke Suemori; Kyoko Nakano; Nobuhiro Zaima; Yukio Kawamura

  Journal of Nutritional Science and Vitaminology 59 5 462 - 469 2013年 

  Miso paste (miso), a fermented soybean food, is popular in Japan and other Asian countries. However, the soybean is known to induce an allergenic response in some individuals. In the present study, we evaluated the allergenicity of various kinds of miso available in Japan. Total proteins were extracted from Amakuti-kome miso, Karakuti-kome miso, Mugi-miso and Mame-miso, and the protein profiles were analyzed. The major protein bands detected in the intact soybean extract were not present in any of the miso samples, which instead showed various low molecular weight protein bands of approximately 10-25 kDa. The existence levels of six major soybean allergens were determined by Western blotting using specific antibodies. We found that the allergen levels varied among miso and allergen types however, allergen levels were consistently lower in miso than in the soybean extract. We obtained similar results for IgE-ELISA experiments using serum IgE from soybean allergy patients. Taken together, these results indicate that compared to soybean extract, various types of miso contain small quantities of intact soybean allergens. Additionally, several lines of evidence indicated that the allergen levels were exceptionally low in the dark-colored Karakuti-kome miso and Mame-miso, which are produced with relatively long fermentation periods, suggesting that the duration of fermentation might be a key factor in the hypoallergenicity of miso.
• Visualization of alpha-tocopherol in biological samples using imaging mass spectrometry

  Nobuhiro Zaima; Itsuko Ishizaki

  Tocopherol: Sources, Uses and Health Benefits 35 - 43 2012年12月 

  Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and secondary ion mass spectrometry (SIMS) are powerful tools for visualization of alpha-tocopherol in biological samples. In this review, we describe the methodology and applications of imaging mass spectrometry based on MALDI-MS (MALDI-IMS) and time-of-flight SIMS (TOF-SIMS) for visualization of alpha-tocopherol in biological samples. © 2012 by Nova Science Publishers, Inc. All rights reserved.
• Application of matrix-assisted laser desorption/ionization imaging mass spectrometry for the analysis of Oryza sativa rice

  Nobuhiro Zaima

  Rice: Production, Consumption and Health Benefits 175 - 182 2012年12月 

  Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) is a two-dimensional MALDI-mass spectrometric technique used to visualize the spatial distribution of biomolecules without the need for extraction, purification, separation, or labeling of biological samples. MALDI-IMS has revealed the characteristic distribution of several biomolecules, including proteins, peptides, amino acids, lipids, carbohydrates, and nucleotides, in various tissues. The versatility of MALDI-IMS has opened a new frontier in several fields. In this review, the methodology and applications of MALDI-IMS for analysis of rice samples are described. © 2012 by Nova Science Publishers, Inc. All rights reserved.
• Imaging Mass Spectrometry Visualizes Ceramides and the Pathogenesis of Dorfman-Chanarin Syndrome Due to Ceramide Metabolic Abnormality in the Skin

  Naoko Goto-Inoue; Takahiro Hayasaka; Nobuhiro Zaima; Kimiko Nakajima; Walter M. Holleran; Shigetoshi Sano; Yoshikazu Uchida; Mitsutoshi Setou

  PLOS ONE 7 11 2012年11月 

  Imaging mass spectrometry (IMS) is a useful cutting edge technology used to investigate the distribution of biomolecules such as drugs and metabolites, as well as to identify molecular species in tissues and cells without labeling. To protect against excess water loss that is essential for survival in a terrestrial environment, mammalian skin possesses a competent permeability barrier in the stratum corneum (SC), the outermost layer of the epidermis. The key lipids constituting this barrier in the SC are the ceramides (Cers) comprising of a heterogeneous molecular species. Alterations in Cer composition have been reported in several skin diseases that display abnormalities in the epidermal permeability barrier function. Not only the amounts of different Cers, but also their localizations are critical for the barrier function. We have employed our new imaging system, capable of high-lateral-resolution IMS with an atmospheric-pressure ionization source, to directly visualize the distribution of Cers. Moreover, we show an ichthyotic disease pathogenesis due to abnormal Cer metabolism in Dorfman-Chanarin syndrome, a neutral lipid storage disorder with ichthyosis in human skin, demonstrating that IMS is a novel diagnostic approach for assessing lipid abnormalities in clinical setting, as well as for investigating physiological roles of lipids in cells/tissues.
• Hepatoprotective action of dietary bluefin tuna skin proteins on CCl4-intoxicated mice

  Teruyoshi Tanaka; Kenji Takahashi; Naoki Iwamoto; Yasuo Agawa; Yoshifumi Sawada; Yukihiro Yoshimura; Nobuhiro Zaima; Tatsuya Moriyama; Yukio Kawamura

  FISHERIES SCIENCE 78 4 911 - 921 2012年07月 

  We have shown that dietary bluefin tuna skin (TUS) protects against carbon tetrachloride (CCl4)-induced hepatic damage in mice. The CCl4-induced necrotic area was decreased in mice fed a TUS-containing diet. Consistent with the decreased necrotic area, dietary TUS markedly lowered the elevated serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and the thiobarbituric acid-reactive substance (TBARS) formation induced by CCl4 injection. TUS diets also decreased phosphorylation of inhibitory kappa B-alpha and blocked the translocation of nuclear factor-kappa B to the nucleus. TUS is composed mainly (80.7 %) of type I collagen, and our results revealed that dietary tuna collagen peptides (TUCP) attenuated the increased hepatic necrotic area, serum AST and ALT activities, and liver TBARS levels induced by CCl4, similar to TUS, thus enabling us to attribute the hepatoprotective action of TUS in CCl4-intoxicated mice to tuna collagen. Therefore, TUS and TUCP may be potential food resources that are capable of alleviating hepatitis symptoms.
• Visualization of acetylcholine distribution in central nervous system tissue sections by tandem imaging mass spectrometry

  Yuki Sugiura; Nobuhiro Zaima; Mitsutoshi Setou; Seiji Ito; Ikuko Yao

  ANALYTICAL AND BIOANALYTICAL CHEMISTRY 403 7 1851 - 1861 2012年06月 

  Metabolite distribution imaging via imaging mass spectrometry (IMS) is an increasingly utilized tool in the field of neurochemistry. As most previous IMS studies analyzed the relative abundances of larger metabolite species, it is important to expand its application to smaller molecules, such as neurotransmitters. This study aimed to develop an IMS application to visualize neurotransmitter distribution in central nervous system tissue sections. Here, we raise two technical problems that must be resolved to achieve neurotransmitter imaging: (1) the lower concentrations of bioactive molecules, compared with those of membrane lipids, require higher sensitivity and/or signal-to-noise (S/N) ratios in signal detection, and (2) the molecular turnover of the neurotransmitters is rapid; thus, tissue preparation procedures should be performed carefully to minimize postmortem changes. We first evaluated intrinsic sensitivity and matrix interference using Matrix Assisted Laser Desorption/Ionization (MALDI) mass spectrometry (MS) to detect six neurotransmitters and chose acetylcholine (ACh) as a model for study. Next, we examined both single MS imaging and MS/MS imaging for ACh and found that via an ion transition from m/z 146 to m/z 87 in MS/MS imaging, ACh could be visualized with a high S/N ratio. Furthermore, we found that in situ freezing method of brain samples improved IMS data quality in terms of the number of effective pixels and the image contrast (i.e., the sensitivity and dynamic range). Therefore, by addressing the aforementioned problems, we demonstrated the tissue distribution of ACh, the most suitable molecular specimen for positive ion detection by IMS, to reveal its localization in central nervous system tissues.
• Visualization of anthocyanin species in rabbiteye blueberry Vaccinium ashei by matrix-assisted laser desorption/ionization imaging mass spectrometry

  Yukihiro Yoshimura; Hirofumi Enomoto; Tatsuya Moriyama; Yukio Kawamura; Mitsutoshi Setou; Nobuhiro Zaima

  ANALYTICAL AND BIOANALYTICAL CHEMISTRY 403 7 1885 - 1895 2012年06月 [査読有り]
   

  Anthocyanins are naturally occurring compounds that impart color to fruits, vegetables, and plants, and are believed to have a number of beneficial health effects in both humans and animals. Because of these properties, pharmacokinetic analysis of anthocyanins in tissue has been performed to quantify and identify anthocyanin species although, currently, no methods exist for investigating tissue localization of anthocyanin species or for elucidating the mechanisms of anthocyanin activity. Imaging mass spectrometry (IMS) is powerful tool for determining and visualizing the distribution of a wide range of biomolecules. To investigate whether anthocyanin species could be identified and visualized by IMS, we performed matrix-assisted laser desorption/ionization (MALDI)-IMS analysis, by tandem mass spectrometry (MALDI-IMS-MS), of ten anthocyanin molecular species in rabbiteye blueberry (Vaccinium ashei). The distribution patterns of each anthocyanin species were different in the exocarp and endocarp of blueberry sections. Anthocyanin species composed of delphinidin and petunidin were localized mainly in the exocarp. In contrast, those species composed of cyanidin, peonidin, and malvidin were localized in both the exocarp and the endocarp. Moreover, MALDI-IMS analysis of anthocyanidins in a blueberry section indicated that the distribution patterns of each anthocyanidin species were nearly identical with those of the corresponding anthocyanins. These results suggested that the different distribution patterns of anthocyanin species in the exocarp and endocarp depended on the aglycone rather than on the sugar moieties. This study is the first to visualize anthocyanin molecular species in fruits.
• Imaging mass spectrometry reveals changes of metabolites distribution in mouse testis during testicular maturation

  Naoko Goto-Inoue; Takahiro Hayasaka; Nobuhiro Zaima; Mitsutoshi Setou

  SURFACE AND INTERFACE ANALYSIS 44 6 749 - 754 2012年06月 

  Although lipid metabolism is thought to be important for proper testicular maturation, the molecular mechanisms underlying this dynamic process remain incompletely understood. Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) can generate molecular ion images of tissue surfaces with high sensitivities and minimal chemical damage. With a wide range of detectable targets, we visualized various kinds of metabolites, such as glutathione, UDP-HexNAc, phosphatidylcholine, sphingomyelin, phosphatidylinositol, seminolipid, and sulfatide. Here, we demonstrate the use of MALDI-IMS with frozen sections of mouse testis at different developmental stages and clearly reveal that some molecular species of phosphatidylcholines and seminolipids show stage-specific expression in testis. The result suggested that these molecular species serve different cellular functions during maturation. Copyright (c) 2011 John Wiley & Sons, Ltd.
• Transcriptome Analysis of the Duodenum, Pancreas, Liver, and Muscle from Diabetic Goto-Kakizaki Rats Fed a Trypsin Inhibitors Derived from Squid Viscera

  Kohsuke Adachi; Kana Fukumorita; Michihiro Araki; Nobuhiro Zaima; Zhi-Hong Yang; Satoru Chiba; Hideki Kishimura; Hiroki Saeki

  JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 60 22 5540 - 5546 2012年06月 

  Trypsin inhibitors (TIs) have various nutritional effects. However, a detailed mechanism for their effects, especially on the gene expression patterns in various tissues, remains unknown. Here, we used transcriptome techniques and gene ontology (GO) analysis to examine the effects of squid TI (sqTI), a biochemically stable peptide, on diabetic Goto-Kakizaki rats after feeding for 10 weeks. We demonstrated that downregulation of SREBP1c in the liver via duodenal/pancreatic hormones suppresses the blood cholesterol level. Consistently, in GO analysis, the term "cholesterol biosynthetic process" was enriched among downregulated genes. No hypoglycemic or insulinotropic effects were observed, in contrast to the results from our previous studies (single stimulation with the same dose of TI), which can be partly ascribed to the inactive responses of the duodenum and pancreas in this condition.
• Loss of lymphatic vessels and regional lipid accumulation is associated with great saphenous vein incompetence

  Hiroki Tanaka; Nobuhiro Zaima; Takeshi Sasaki; Naoto Yamamoto; Masaki Sano; Hiroyuki Konno; Mitsutoshi Setou; Naoki Unno

  JOURNAL OF VASCULAR SURGERY 55 5 1440 - 1448 2012年05月 

  Objective: Recent studies suggest that biologic changes in the vein wall associated with varicose veins (VVs) occur not only in valvular tissue but also in nonvalvular regions. We previously used imaging mass spectrometry (IMS) to determine the distribution of lipid molecules in incompetent valve tissue. In this study, we used IMS to analyze incompetent great saphenous veins (GSVs) in patients with varicose vein (VV) to assess the distribution of lipid molecules. Methods: We obtained GSV tissue from 38 VV patients (50 limbs) who underwent GSV stripping. For the control veins (CV), we obtained GSV samples from 10 patients undergoing infrainguinal bypass with reversed GSV grafting for peripheral artery occlusive disease (10 limbs). Conventional and immunofluorescence staining were performed for histopathologic examination. The total lipid content in the homogenized vein tissue was determined. The localization of each lipid molecule in the vein wall was assessed by IMS. Results: The histologic examination showed the VV walls were significantly thicker than the CV walls, and only the VV adventitia was positive for lipid staining. The VV wall had higher concentrations of phospholipids and triglycerides than the CV wall. IMS revealed an abnormal accumulation of lysophosphatidylcholine (LPC; 1-acyl 16:0) and phosphatidylcholine (diacyl 16:0/20:4) in the VV intima and media. Triglyceride was found only in VV adventitia. The number of lymphatic vessels, as measured by staining with D2-40, a lymphatic vessel-specific marker, was significantly lower in the VV adventitia than in the CV adventitia. Lymphatic vessel reduction may be associated with insufficient lymphatic drainage in the VV adventitia causing histologic changes in VV tissue. Conclusions: The accumulation of LPC(1-acyl 16: 0) and PC(diacyl 16:0/20: 4) in the VV intima and media may be associated with chronic inflammation, leading to VV tissue degeneration. Furthermore, insufficient lipid drainage by lymphatic vessel may be responsible for accumulation of lipid molecules and subsequent vein wall degeneration. (J Vasc Surg 2012;55:1440-8.)
• 2型糖尿病関連中性脂肪蓄積心筋血管症

  平野 賢一; 池田 善彦; 財満 信宏; 眞能 正幸; 小林 邦久; 神崎 秀明; 加藤 誠也; 笹栗 靖之; 友池 仁暢; 瀬藤 光利; 植田 初江

  日本病理学会会誌 101 1 283 - 283 (一社)日本病理学会 2012年03月
• ヒト頸動脈と動脈硬化性プラークのメタボロミクス

  武藤 清佳; 植田 初江; 飯原 弘二; 山本 卓志; 財満 信宏; 松山 高明; 池田 善彦; 池川 雅哉

  日本病理学会会誌 101 1 399 - 399 (一社)日本病理学会 2012年03月
• Visualization of neuropeptides in paraffin-embedded tissue sections of the central nervous system in the decapod crustacean, Penaeus monodon, by imaging mass spectrometry

  Piyachat Chansela; Naoko Goto-Inoue; Nobuhiro Zaima; Morakot Sroyraya; Prasert Sobhon; Mitsutoshi Setou

  PEPTIDES 34 1 10 - 18 2012年03月 

  The distributions of neuropeptides in paraffin-embedded tissue sections (PETS) of the eyestalk, brain, and thoracic ganglia of the shrimp Penaeus monodon were visualized by imaging mass spectrometry (IMS). Peptide signals were obtained from PETS without affecting morphological features. Twenty-nine neuropeptides comprising members of FMRFamide, SIFamides, crustacean hyperglycaemic hormone, orcokinin-related peptides, tachykinin-related peptides, and allatostatin A were detected and visualized. Among these findings we first identified tachykinin-related peptide as a novel neuropeptide in this shrimp species. We found that these neuropeptides were distributed at specific areas in the three neural organs. In addition, 28 peptide sequences derived from 4 types of constitutive proteins, including actin, histones, arginine kinase, and cyclophilin A were also detected. All peptide sequences were verified by liquid chromatography-tandem mass spectrometry. The use of IMS on acetic acid-treated PETS enabled us to identify peptides and obtain their specific localizations in correlation with the undisturbed histological structure of the tissue samples. (C) 2011 Elsevier Inc. All rights reserved.
• Composition and Localization of Lipids in Penaeus merguiensis Ovaries during the Ovarian Maturation Cycle as Revealed by Imaging Mass Spectrometry

  Piyachat Chansela; Naoko Goto-Inoue; Nobuhiro Zaima; Takahiro Hayasaka; Morakot Sroyraya; Napamanee Kornthong; Attakorn Engsusophon; Montakan Tamtin; Chatchawalee Chaisri; Prasert Sobhon; Mitsutoshi Setou

  PLOS ONE 7 3 2012年03月 

  Ovary maturation, oocyte differentiation, and embryonic development in shrimp are highly dependent on nutritional lipids taken up by female broodstocks. These lipids are important as energy sources as well as for cell signaling. In this study, we report on the compositions of major lipids, i.e. phosphatidylcholines (PCs), triacylglycerols (TAGs), and fatty acids (FAs), in the ovaries of the banana shrimp, Penaeus merguiensis, during ovarian maturation. Thin-layer chromatography analysis showed that the total PC and TAG signal intensities increased during ovarian maturation. Further, by using gas chromatography, we found that (1) FAs 14:0, 16:1, 18:1, 18:2, 20:1, and 22:6 proportionally increased as ovarian development progressed to more mature stages; (2) FAs 16:0, 18:0, 20:4, and 20:5 proportionally decreased; and (3) FAs 15:0, 17:0, and 20:2 remained unchanged. By using imaging mass spectrometry, we found that PC 16:0/16:1 and TAG 18:1/18:2/22:6 were detected in oocytes stages 1 and 2. PCs 16:1/20:4, 16:0/22:6, 18:3/22:6, 18:1/22:6, 20:5/22:6, and 22:6/22:6 and TAGs 16:0/16:1/18:3, 16:0/18:1/18:3, 16:0/18:1/18:1, and 16:0/18:2/22:6 were present in all stages of oocytes. In contrast, the PC-and TAG-associated FAs 20:4, 20:5, and 22:6 showed high signal intensities in stage 3 and 4 oocytes. These FAs may act as nutrition sources as well as signaling molecules for developing embryos and the hatching process. Knowledge of lipid compositions and localization could be helpful for formulating the diet for female broodstocks to promote fecundity and larval production.
• 我が国で見いだされた新規疾患単位、中性脂肪蓄積心筋血管症 希少難病からcommon diseaseへの展開

  平野 賢一; 財満 信宏; 池田 善彦; 眞能 正幸; 小林 邦久; 神崎 秀明; 北風 政史; 小室 一成; 瀬藤 光利; 友池 仁暢

  日本内科学会雑誌 101 Suppl. 229 - 229 (一社)日本内科学会 2012年02月
• Different Localization Patterns of Anthocyanin Species in the Pericarp of Black Rice Revealed by Imaging Mass Spectrometry

  Yukihiro Yoshimura; Nobuhiro Zaima; Tatsuya Moriyama; Yukio Kawamura

  PLOS ONE 7 2 2012年02月 

  Black rice (Oryza sativa L. Japonica) contains high levels of anthocyanins in the pericarp and is considered an effective health-promoting food. Several studies have identified the molecular species of anthocyanins in black rice, but information about the localization of each anthocyanin species is limited because methodologies for investigating the localization such as determining specific antibodies to anthocyanin, have not yet been developed Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) is a suitable tool for investigating the localization of metabolites. In this study, we identified 7 species of anthocyanin monoglycosides and 2 species of anthocyanin diglycosides in crude extracts from black rice by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) analysis. We also analyzed black rice sections by MALDI-IMS and found 2 additional species of anthocyanin pentosides and revealed different localization patterns of anthocyanin species composed of different sugar moieties. Anthocyanin species composed of a pentose moiety (cyanidin-3-O-pentoside and petunidin-3-O-pentoside) were localized in the entire pericarp, whereas anthocyanin species composed of a hexose moiety (cyanidin-3-O-hexoside and peonidin-3-O-hexoside) were focally localized in the dorsal pericarp. These results indicate that anthocyanin species composed of different sugar moieties exhibit different localization patterns in the pericarp of black rice. This is the first detailed investigation into the localization of molecular species of anthocyanins by MALDI-IMS.
• Ellagic acid in pomegranate suppresses resistin secretion by a novel regulatory mechanism involving the degradation of intracellular resistin protein in adipocytes

  Yasuko Makino-Wakagi; Yukihiro Yoshimura; Yuki Uzawa; Nobuhiro Zaima; Tatsuya Moriyama; Yukio Kawamura

  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 417 2 880 - 885 2012年01月 [査読有り]
   

  Resistin, an adipocytokine, is considered the link between obesity and type 2 diabetes. Pomegranate is a rich source of compounds used to treat metabolic diseases including type 2 diabetes. In this study, we found that consumption of pomegranate fruit extract (PFE) predominantly reduced the serum resistin levels in ovariectomized mice, an animal model with elevated resistin levels in serum and upregulated resistin mRNA expression in white adipose tissue. Moreover, the PFE significantly reduced the secretion and intracellular protein levels of resistin in differentiated murine 3T3-L1 adipocytes, but it did not alter resistin mRNA expression. When de novo protein synthesis was inhibited by the protein synthesis inhibitor cycloheximide, the intracellular resistin protein levels were drastically reduced by the PFE, suggesting that the PFE promoted the degradation of resistin at the protein level. We also found that ellagic acid (EA), a main component of pomegranate, had the same effects on the secretion and intracellular protein level of resistin. These results suggest that EA in pomegranate suppresses resistin secretion by a novel mechanism involving the degradation of intracellular resistin protein in adipocytes. (C) 2011 Elsevier Inc. All rights reserved.
• Kudzu (Pueraria lobata) Vine Ethanol Extracts Improve Ovariectomy-Induced Bone Loss in Female Mice

  Teruyoshi Tanaka; Hanjun Tang; Fengnian Yu; Seiwa Michihara; Yuki Uzawa; Nobuhiro Zaima; Tatsuya Moriyama; Yukio Kawamura

  JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 59 24 13230 - 13237 2011年12月 

  Bone-loss-improving action of kudzu vine ethanol extracts (PVEE) was clarified. PVEE was composed roughly of 80% fiber, 10% puerarin, 3.6% daidzin, 2.5% 6 ''-O-malonyldaidzin, and the other minor isoflavones. Ten-week-old ovariectomized (OVX) mice were fed diets containing PVEE (20 mg/kg body weight/day) for 8 weeks. The bone resorption markers (urinary deoxypyridinoline and tartrate-resistant acid phosphatase activity) was elevated in OVX mice and was significantly decreased in OVX mice that consumed PVEE for 8 weeks. Consistent with the decrease in the markers, the number of matured osteoclasts in the distal femur was diminished in OVX mice fed PVEE diets. PVEE diets also suppressed the decrease in femoral bone mineral density (BMD) by OVX. PVEE showed the affinity for estrogen receptor alpha and beta 3 nearly 1/10000 weaker than 17 beta-estradiol. No hypertrophy in the uterus by the PVEE diet was observed. These results suggest that PVEE could be a promising resource for a functional food that improves osteoporosis.
• Imaging mass spectrometry for lipidomics.

  Goto-Inoue N; Hayasaka T; Zaima N; Setou M

  Biochimica et biophysica acta 1811 11 961 - 969 11 2011年11月 [査読有り]
  
• Imaging mass spectrometry for lipidomics

  Naoko Goto-Inoue; Takahiro Hayasaka; Nobuhiro Zaima; Mitsutoshi Setou

  Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids 1811 11 961 - 969 2011年11月 

  Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is a powerful tool that enables the simultaneous detection and identification of biomolecules in analytes. MALDI-imaging mass spectrometry (MALDI-IMS) is a two-dimensional MALDI-MS technique used to visualize the spatial distribution of biomolecules without extraction, purification, separation, or labeling of biological samples. This technique can reveal the distribution of hundreds of ion signals in a single measurement and also helps in understanding the cellular profile of the biological system. MALDI-IMS has already revealed the characteristic distribution of several kinds of lipids in various tissues. The versatility of MALDI-IMS has opened a new frontier in several fields, especially in lipidomics. In this review, we describe the methodology and applications of MALDI-IMS to biological samples. This article is part of a Special Issue entitled: Lipodomics and Imaging Mass Spectrometry. © 2011 Elsevier B.V.
• HYDROXYLATED AND NON-HYDROXYLATED SULFATIDE ARE DISTINCTLY DISTRIBUTED IN THE HUMAN CEREBRAL CORTEX

  D. Yuki; Y. Sugiura; N. Zaima; H. Akatsu; Y. Hashizume; T. Yamamoto; M. Fujiwara; K. Sugiyama; M. Setou

  NEUROSCIENCE 193 44 - 53 2011年10月 

  Sulfatide (ST) is a sphingolipid with an important role in the central nervous system as a major component of the myelin sheath. ST contains a structurally variable ceramide moiety, with a fatty acid substituent of varying carbon-chain length and double-bond number. Hydroxylation at the alpha-2 carbon position of the fatty acid is found in half the population of ST molecules. Recent genetic studies of fatty acid 2-hydroxylase (FA2H) indicate that these hydroxylated sphingolipids influence myelin sheath stability. However, their distribution is unknown. Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) enables the analysis of distinct distributions of individual ST molecular species in tissue section. We examined human cerebral cortex tissue sections with MALDI-IMS, identifying and characterizing the distributions of 14 ST species. The distribution analysis reveals that the composition ratios of non-hydroxylated/hydroxylated STs are clearly reversed at the border between white and gray matter; the hydroxylated group is the dominant ST species in the gray matter. These results suggest that hydroxylated STs are highly expressed in oligodendrocytes in gray matter and might form stable myelin sheaths. As a clinical application, we analyzed a brain with Alzheimer's disease (AD) as a representative neurodegenerative disease. Although previous studies of AD pathology have reported that the amount of total ST is decreased in the cerebral cortex, as far as the compositional distributions of STs are concerned, AD brains were similar to those in control brains. In conclusion, we suggest that MALDI-IMS is a useful tool for analysis of the distributions of various STs and this application might provide novel insight in the clinical study of demyelinating diseases. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.
• Investigation by Imaging Mass Spectrometry of Biomarker Candidates for Aging in the Hair Cortex

  Michihiko Luca Waki; Kenji Onoue; Tsukasa Takahashi; Kensuke Goto; Yusuke Saito; Katsuaki Inami; Ippei Makita; Yurika Angata; Tomomi Suzuki; Mihi Yamashita; Narumi Sato; Saki Nakamura; Dai Yuki; Yuki Sugiura; Nobuhiro Zaima; Naoko Goto-Inoue; Takahiro Hayasaka; Yutaka Shimomura; Mitsutoshi Setou

  PLOS ONE 6 10 2011年10月 [査読有り]
   

  Background: Human hair is one of the essential components that define appearance and is a useful source of samples for non-invasive biomonitoring. We describe a novel application of imaging mass spectrometry (IMS) of hair biomolecules for advanced molecular characterization and a better understanding of hair aging. As a cosmetic and biomedical application, molecules whose levels in hair altered with aging were comprehensively investigated. Methods: Human hair was collected from 15 young (20 +/- 65 years old) and 15 older (50 +/- 65 years old) volunteers. Matrix-free laser desorption/ionization IMS was used to visualize molecular distribution in the hair sections. Hair-specific ions displaying a significant difference in the intensities between the 2 age groups were extracted as candidate markers for aging. Tissue localization of the molecules and alterations in their levels in the cortex and medulla in the young and old groups were determined. Results: Among the 31 molecules detected specifically in hair sections, 2-one at m/z 153.00, tentatively assigned to be dihydrouracil, and the other at m/z 207.04, identified to be 3,4-dihydroxymandelic acid (DHMA)-exhibited a higher signal intensity in the young group than in the old, and 1 molecule at m/z 164.00, presumed to be O-phosphoethanolamine, displayed a higher intensity in the old group. Among the 3, putative O-phosphoethanolamine showed a cortex-specific distribution. The 3 molecules in cortex presented the same pattern of alteration in signal intensity with aging, whereas those in medulla did not exhibit significant alteration. Conclusion: Three molecules whose levels in hair altered with age were extracted. While they are all possible markers for aging, putative dihydrouracil and DHMA, are also suspected to play a role in maintaining hair properties and could be targets for cosmetic supplementation. Mapping of ion localization in hair by IMS is a powerful method to extract biomolecules in specified regions and determine their tissue distribution.
• Imaging mass spectrometry-based histopathologic examination of atherosclerotic lesions

  Nobuhiro Zaima; Takeshi Sasaki; Hiroki Tanaka; Xian Wu Cheng; Kenji Onoue; Takahiro Hayasaka; Naoko Goto-Inoue; Hirofumi Enomoto; Naoki Unno; Masafumi Kuzuya; Mitsutoshi Setou

  ATHEROSCLEROSIS 217 2 427 - 432 2011年08月 [査読有り]
   

  Aims: Imaging mass spectrometry (IMS) enables the visualization of individual molecules present on tissue sections. We attempted to identify and visualize specific markers for aortic atherosclerotic lesions. Methods and results: Atherosclerotic lesions were obtained from aortic roots of apolipoprotein E (ApoE)deficient mice at 60 weeks of age and from femoral arteries of humans with peripheral artery occlusive disease. IMS was performed with a matrix-assisted laser desorption/ionization mass spectrometry time-of-flight (TOF)/TOF-type instrument. The molecular ions at m/z 671.6 and 673.6 were found to be specific molecules in the mouse and human lipid-rich regions. These molecules were assigned as cholesterol linoleate (CE 18:2) and cholesterol oleate (CE 18:1). In the case of the human samples, triacylglycerol was also localized in the lipid-rich regions. The distributions of the molecular ions at m/z 804.5 and 832.5 were the same as the distribution of both the mouse and the human SMCs. These molecules were assigned as phosphatidylcholine (PC) (diacyl 16: 0/20:4) and PC (diacyl 18: 0/20:4). The molecular ion at m/z 566.9 was localized in the mouse calcified regions, and the molecular ions at m/z 539.0 were localized in the human calcified regions. Conclusions: The IMS-based histopathologic examination (IbHE) revealed the characteristic peaks of lipid-rich regions, SMCs, and calcified regions in the atherosclerotic lesions. In addition, IbHE revealed the characteristic distribution of lipids in human atherosclerotic lesions. These data indicate that an IMS-based pathologic approach is of considerable value as a new histopathologic examination. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
• Transcriptome Analysis of the Duodenum in Wistar Rats Fed a Trypsin Inhibitor Derived from Squid Viscera

  Kohsuke Adachi; Kana Fukumorita; Michihiro Araki; Nobuhiro Zaima; Satoru Chiba; Hideki Kishimura; Hiroki Saeki

  JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 59 16 9001 - 9010 2011年08月 

  To investigate the effects of oral administration of a trypsin inhibitor (TI), normal Wistar rats were fed a TI derived from squid (Todarodes pacificus) for 10 weeks and gene expression profiles in the duodenum, pancreas, liver, and muscle were then analyzed using DNA microarrays. Although no significant changes could be observed in growth, food intake, tissue weight, or blood tests among the tissues tested, the duodenum showed the most remarkable changes in the global gene expression profile. Significant up-regulation of mRNAs encoding gastrin, gastrokine, cholecystokinin and somatostatin in the duodenum was validated by qPCR analysis. In gene ontology (GO) analysis of the up-regulated differentially expressed genes (DEGs), GO terms related to keratinization and innate mucosal defense were enriched (p < 0.001) in the category of biological processes in addition to assumable terms such as regulation of secretion and response to nutrients, vesicle-mediated transport, and so forth. In the same analysis, calcium ion binding was listed at the deepest hierarchy in the category of molecular function. These results indicate that the duodenum responds to TI treatment by a wider range of physiological processes than previously assumed such as keratinocyte differentiation and innate mucosal defense, in which calcium plays a crucial role.
• Distribution of phospholipid molecular species in autogenous access grafts for hemodialysis analyzed using imaging mass spectrometry

  Hiroki Tanaka; Nobuhiro Zaima; Naoto Yamamoto; Minoru Suzuki; Yuuki Mano; Hiroyuki Konno; Naoki Unno; Mitsutoshi Setou

  ANALYTICAL AND BIOANALYTICAL CHEMISTRY 400 7 1873 - 1880 2011年06月 

  Arteriovenous fistulae (AVF) using vein grafts are frequently used for vascular access in hemodialysis. When superficial veins are used as autogenous access grafts for hemodialysis, atherosclerotic-like tissue degeneration often causes stenosis and obstruction. Although the differences between the pathology of degeneration in AVF and atherosclerosis (i.e., peripheral artery occlusive disease (PAD)) are known, their underlying molecular mechanisms are not. We determined the characteristic abnormal lipid metabolism of AVF. Oil red O staining clearly showed the accumulation of lipid molecules in AVF and PAD tissues. We found that the staining pattern was different between AVF and PAD tissues. The media and adventitia of AVF and the intima and media of PAD were intensely stained. Quantitative lipid analysis revealed that the amount of PL was significantly increased in AVF and PAD. Next, we performed matrix-assisted laser desorption/ionization imaging mass spectroscopy and determined the characteristic distribution of lysophosphatidylcholine (LPC) and phosphatidylcholine (PC) in AVF. The distribution patterns of LPC (1-acyl 16:0) and PC (diacyl 16:0/20:4) were consistent with the Oil red O staining images, suggesting that metabolisms related to LPC (1-acyl 16:0) and PC (diacyl 16:0/20:4) are altered in AVF.
• Visualization of phosphatidylcholine, lysophosphatidylcholine and sphingomyelin in mouse tongue body by matrix-assisted laser desorption/ionization imaging mass spectrometry

  Hirofumi Enomoto; Yuki Sugiura; Mitsutoshi Setou; Nobuhiro Zaima

  ANALYTICAL AND BIOANALYTICAL CHEMISTRY 400 7 1913 - 1921 2011年06月 [査読有り]
   

  The mammalian tongue is one of the most important organs during food uptake because it is helpful for mastication and swallowing. In addition, taste receptors are present on the surface of the tongue. Lipids are the second most abundant biomolecules after water in the tongue. Lipids such as phosphatidylcholine (PC), lysophosphatidylcholine (LPC) and sphingomyelin (SM) are considered to play fundamental roles in the mediation of cell signaling. Imaging mass spectrometry (IMS) is powerful tool for determining and visualizing the distribution of lipids across sections of dissected tissue. In this study, we identified and visualized the PC, LPC, and SM species in a mouse tongue body section with matrix-assisted laser desorption/ionization (MALDI)-IMS. The ion image constructed from the peaks revealed that docosahexaenoic acid (DHA)-containing PC, LPC, linoleic acid-containing PC and SM (d18:1/16:0), and oleic acid-containing PC were mainly distributed in muscle, connective tissue, stratified epithelium, and the peripheral nerve, respectively. Furthermore, the distribution of SM (d18:1/16:0) corresponded to the distribution of nerve tissue relating to taste in the stratified epithelium. This study represents the first visualization of PC, LPC and SM localization in the mouse tongue body.
• Abnormal phospholipids distribution in the prefrontal cortex from a patient with schizophrenia revealed by matrix-assisted laser desorption/ionization imaging mass spectrometry

  Junya Matsumoto; Yuki Sugiura; Dai Yuki; Takahiro Hayasaka; Naoko Goto-Inoue; Nobuhiro Zaima; Yasuto Kunii; Akira Wada; Qiaohui Yang; Keisuke Nishiura; Hiroyasu Akatsu; Akira Hori; Yoshio Hashizume; Takayuki Yamamoto; Keiko Ikemoto; Mitsutoshi Setou; Shin-ichi Niwa

  ANALYTICAL AND BIOANALYTICAL CHEMISTRY 400 7 1933 - 1943 2011年06月 

  Schizophrenia is one of the major psychiatric disorders, and lipids have focused on the important roles in this disorder. In fact, lipids related to various functions in the brain. Previous studies have indicated that phospholipids, particularly ones containing polyunsaturated fatty acyl residues, are deficient in postmortem brains from patients with schizophrenia. However, due to the difficulties in handling human postmortem brains, particularly the large size and complex structures of the human brain, there is little agreement regarding the qualitative and quantitative abnormalities of phospholipids in brains from patients with schizophrenia, particularly if corresponding brain regions are not used. In this study, to overcome these problems, we employed matrix-assisted laser desorption/ionization imaging mass spectrometry (IMS), enabling direct microregion analysis of phospholipids in the postmortem brain of a patient with schizophrenia via brain sections prepared on glass slides. With integration of traditional histochemical examination, we could analyze regions of interest in the brain at the micrometric level. We found abnormal phospholipid distributions within internal brain structures, namely, the frontal cortex and occipital cortex. IMS revealed abnormal distributions of phosphatidylcholine molecular species particularly in the cortical layer of frontal cortex region. In addition, the combined use of liquid chromatography/electrospray ionization tandem mass spectrometry strengthened the capability for identification of numerous lipid molecular species. Our results are expected to further elucidate various metabolic processes in the neural system.
• Authenticity assessment of beef origin by principal component analysis of matrix-assisted laser desorption/ionization mass spectrometric data

  Nobuhiro Zaima; Naoko Goto-Inoue; Takahiro Hayasaka; Hirofumi Enomoto; Mitsutoshi Setou

  ANALYTICAL AND BIOANALYTICAL CHEMISTRY 400 7 1865 - 1871 2011年06月 [査読有り]
   

  It has become necessary to assess the authenticity of beef origin because of concerns regarding human health hazards. In this study, we used a metabolomic approach involving matrix-assisted laser desorption/ionization imaging mass spectrometry to assess the authenticity of beef origin. Highly accurate data were obtained for samples of extracted lipids from beef of different origin; the samples were grouped according to their origin. The analysis of extracted lipids in this study ended within 10 min, suggesting this approach can be used as a simple authenticity assessment before a definitive identification by isotope analysis.
• Imaging mass spectrometry reveals characteristic changes in triglyceride and phospholipid species in regenerating mouse liver

  Norio Miyamura; Takashi Nakamura; Naoko Goto-Inoue; Nobuhiro Zaima; Takahiro Hayasaka; Tokiwa Yamasaki; Shuji Terai; Isao Sakaida; Mitsutoshi Setou; Hiroshi Nishina

  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 408 1 120 - 125 2011年04月 [査読有り]
   

  After partial hepatectomy (PH), regenerating liver accumulates unknown lipid species. Here, we analyzed lipids in murine liver and adipose tissues following PH by thin-layer chromatography (TLC), imaging mass spectrometry (IMS), and real-time RT-PCR. In liver, IMS revealed that a single TLC band comprised major 19 TG species. Similarly, IMS showed a single phospholipid TLC band to be major 13 species. In adipose tissues, PH induced changes to expression of genes regulating lipid metabolism. Finally, IMS of phosphatidylcholine species demonstrated distribution gradients in lobules that resembled hepatic zonation. IMS is thus a novel and power tool for analyzing lipid species with high resolution. (C) 2011 Elsevier Inc. All rights reserved.
• 水産物が脳機能に及ぼす影響 : 質量顕微鏡法を用いた脳の解析

  財満 信宏

  日本水産學會誌 = Bulletin of the Japanese Society of Scientific Fisheries 77 2 260 - 260 The Japanese Society of Fisheries Science 2011年03月
• Selective Analysis of Lipids by Thin-Layer Chromatography Blot Matrix-Assisted Laser Desorption/Ionization Imaging Mass Spectrometry

  Nobuhiro Zaima; Naoko Goto-Inoue; Kohsuke Adachi; Mitsutoshi Setou

  JOURNAL OF OLEO SCIENCE 60 2 93 - 98 2011年02月 [査読有り]
   

  Thin-layer chromatography (TLC) is an essential method for food composition analyses such as lipid nutrition analysis. TLC can be used to obtain information about the lipid composition of foods; however, it cannot be used for analyses at the molecular level. Recently we developed a new method that combines matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) with TLC-blotting (TLC-Blot-MALDI-IMS). The combination of MALDI-IMS and TLC blotting enabled detailed and sensitive analyses of lipids. In this study, we applied TLC-Blot-MALDI-IMS for analysis of major phospholipids extracted from bluefin tuna. We showed that TLC-Blot-MALDI-IMS analysis could visualize and identify major phospholipids such as phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, phosphatidylcholine, and sphingomyelin.
• Using Imaging Mass Spectrometry to Accurately Diagnose Fabry's Disease

  Kenji Onoue; Zaima Nobuhiro; Sugiura Yuki; Isojima Takuya; Okayama Satoshi; Horii Manabu; Akai Yasuhiro; Uemura Shiro; Takemura Genzou; Sakuraba Hitoshi; Sakaguchi Yasuhiro; Setou Mitsutoshi; Saito Yoshihiko

  THE JAPANESE CIRCULATION SOCIETY 2011年01月
• Using Imaging Mass Spectrometry to Accurately Diagnose Fabry's Disease

  Kenji Onoue; Nobuhiro Zaima; Yuki Sugiura; Takuya Isojima; Satoshi Okayama; Manabu Horii; Yasuhiro Akai; Shiro Uemura; Genzou Takemura; Hitoshi Sakuraba; Yasuhiro Sakaguchi; Mitsutoshi Setou; Yoshihiko Saito

  CIRCULATION JOURNAL 75 1 221 - 223 2011年01月
• I-3. the effect of dietary seafood on the brain function: Analysis of brain by imaging mass spectrometry

  Nobuhiro Zaima

  Nippon Suisan Gakkaishi (Japanese Edition) 77 2 260  2011年
• Matrix-Assisted Laser Desorption/Ionization Imaging Mass Spectrometry

  Nobuhiro Zaima; Takahiro Hayasaka; Naoko Goto-Inoue; Mitsutoshi Setou

  INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 11 12 5041 - 5056 2010年12月 [査読有り]
   

  Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is a powerful tool that enables the simultaneous detection and identification of biomolecules in analytes. MALDI-imaging mass spectrometry (MALDI-IMS) is a two-dimensional MALDI-mass spectrometric technique used to visualize the spatial distribution of biomolecules without extraction, purification, separation, or labeling of biological samples. MALDI-IMS has revealed the characteristic distribution of several biomolecules, including proteins, peptides, amino acids, lipids, carbohydrates, and nucleotides, in various tissues. The versatility of MALDI-IMS has opened a new frontier in several fields such as medicine, agriculture, biology, pharmacology, and pathology. MALDI-IMS has a great potential for discovery of unknown biomarkers. In this review, we describe the methodology and applications of MALDI-IMS for biological samples.
• Ionic Matrix for Enhanced MALDI Imaging Mass Spectrometry for Identification of Phospholipids in Mouse Liver and Cerebellum Tissue Sections

  Kamlesh Shrivas; Takahiro Hayasaka; Naoko Goto-Inoue; Yuki Sugiura; Nobuhiro Zaima; Mitsutoshi Setou

  ANALYTICAL CHEMISTRY 82 21 8800 - 8806 2010年11月 

  The ionic matrix (IM) is considered to be versatile for matrix-assisted laser desorption/ionization mass spectrometry (MAL)I-MS) for the identification of a wide range of biomolecules due to its good solubility for a variety of analytes, formation of homogeneous crystals with analytes, and high vacuum stability. When these advantages are exploited, the performance of IM of alpha-cyano-4-hydroxycinnamic acid butylamine (CHCAB) and 2,5-dihydroxybenzoic acid butylamine (DHBB) was compared with other matrixes for the identification of phospholipids in standard mixtures and mouse liver tissue sections. The results showed that the IM of CHCAB caused higher signal intensity and allowed the detection of a number phospholipids such as phosphatidylethanolamine (PE) and phosphatidylserine (PS) in addition to detection of phosphatidylcholine (PC) on the surface of the liver tissue sample. The IM of CHCAB was also used to identify the species of lipids present in different layers of cerebellum where the greater numbers of biomolecules were detected as compared to DHB matrix. Further, the feasibility of the proposed method was extended for the analysis of tryptic digested cytochrome c for increased signal intensity and number of peptide sequences in MALDI-MS. Thus, the application of IM to MALDI-MS could be a promising tool for imaging biomolecules in tissue sections in high throughput analyses with high sensitivity.
• Imaging Mass Spectrometry Reveals Unique Lipid Distribution in Primary Varicose Veins

  H. Tanaka; N. Zaima; N. Yamamoto; D. Sagara; M. Suzuki; M. Nishiyama; Y. Mano; M. Sano; T. Hayasaka; N. Goto-Inoue; T. Sasaki; H. Konno; N. Unno; M. Setou

  EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY 40 5 657 - 663 2010年11月 

  Background: The lipid metabolism of varicose veins (VVs) remains unknown. To elucidate the pathogenesis of VV, we utilized the novel technique of imaging mass spectrometry (IMS). Materials and methods: We obtained W tissues from 10 limbs of 10 W patients who underwent great saphenous vein stripping. As control vein samples, we harvested segmental vein tissues from 6 limbs of 6 patients with peripheral artery occlusive disease who underwent infra-inguinal bypass with reversed saphenous vein grafting. To identify the localisation of lipid molecules in the W tissues, we performed matrix-assisted laser desorption/ionization IMS (MALDI-IMS). We also performed MS/MS analyses to identify the structure of each molecule. Results: We obtained mass spectra directly from control vein tissues and VV tissues and found a unique localisation of lipid molecules in the VV tissues. We localised lysophosphatidylcholine (LPC) (1-acyl 16:0), phosphatidylcholine (PC) (1-acyl 36:4) and sphingomyelin (SM) (d18:1/16:0) at the site of the VV valve. Conclusion: MALDI-IMS revealed the distribution of various lipid molecules in normal veins and VVs both. Accumulation of LPC (1-acyl 16:0), PC (1-acyl 36:4) and SM (d18:1/16:0) in the VV tissues suggested that inflammation associated with abnormal lipid metabolism may contribute to the development of VV. (C) 2010 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
• The Detection of Glycosphingolipids in Brain Tissue Sections by Imaging Mass Spectrometry Using Gold Nanoparticles

  Naoko Goto-Inoue; Takahiro Hayasaka; Nobuhiro Zaima; Yukiyasu Kashiwagi; Mari Yamamoto; Masami Nakamoto; Mitsutoshi Setou

  JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY 21 11 1940 - 1943 2010年11月 

  Glycosphingolipids (GSLs) are amphiphilic molecules consisting of a hydrophilic carbohydrate chain and a hydrophobic ceramide moiety. They appear to be involved primarily in biological processes such as cell proliferation, differentiation, and signaling. To investigate the mechanism of brain function in more detail, a more highly sensitive method that would reveal the GSL distribution in the brain is required. In this report, we describe a simple and efficient method for mapping the distribution and localization of GSLs present in mouse brain sections using nanoparticle-assisted laser desorption/ionization imaging mass spectrometry (IMS). We have developed and tested gold nanoparticles (AuNPs) as a new matrix to maximize the detection of GSLs. A matrix of AuNPs modified with alkylamine was used to detect various GSLs, such as minor molecular species of sulfatides and gangliosides, in mouse brain sections; these GSLs were hardly detected using 2,5-dihydroxybenzoic acid (DHB), which is the conventional matrix for GSLs. We achieved approximately 20 times more sensitive detection of GSLs using AuNPs compared to a DHB matrix. We believe that our new approach using AuNPs in IMS could lead to a new strategy for analyzing basic biological mechanisms and several diseases through the distribution of minor GSLs. (J Am Soc Mass Spectrom 2010, 21, 1940-1943) (C) 2010 American Society for Mass Spectrometry
• Imaging of lipids in cultured mammalian neurons by matrix assisted laser/desorption ionization and secondary ion mass spectrometry

  Hyun-Jeong Yang; Yuki Sugiura; Itsuko Ishizaki; Noriaki Sanada; Koji Ikegami; Nobuhiro Zaima; Kamlesh Shrivas; Mitsutoshi Setou

  SURFACE AND INTERFACE ANALYSIS 42 10-11 1606 - 1611 2010年10月 

  Imaging mass spectrometry (IMS) provides a novel opportunity for visualization of molecular ion distribution. Currently, there are two major ionization techniques, matrix-assisted laser desorption/ionization (MALDI) and secondary ion mass spectrometry (SIMS) are widely used for imaging of biomolecules in tissue samples. MALDI and SIMS-based IMS have the following features; measurable mass ranges are wide and small, and the spatial resolutions are low and high, respectively. To the best of our knowledge, this is a first report to identify the lipids in cultured mammalian neurons by MALDI-IMS. Further, those neurons were analyzed with SIMS-IMS in order to compare the distribution pattern of lipids and other derived fragments. The parameters which influence the identification of lipids in cultured neurons were optimized in order to get an optimum detection of lipid molecules. The combined spatial data of MALDI and SIMS supported the idea that the signals of small molecules such as phosphatidylcholine head groups and fatty acids (detected in SIMS) are derived from the intact lipids (detected in MALDI-IMS). Copyright (C) 2010 John Wiley & Sons, Ltd.
• Visualization of biomolecules in the eyestalk of the blue swimming crab, Portunus pelagicus, by imaging mass spectrometry using the atmospheric-pressure mass microscope

  Morakot Sroyraya; Naoko Goto-Inoue; Nobuhiro Zaima; Takahiro Hayasaka; Piyachat Chansela; Supita Tanasawet; Kamlesh Shrivas; Prasert Sobhon; Mitsutoshi Setou

  SURFACE AND INTERFACE ANALYSIS 42 10-11 1589 - 1592 2010年10月 [査読有り]
   

  We have developed an imaging mass spectrometer - the atmospheric-pressure mass microscope - with high spatial resolution, which is composed of an atmospheric pressure ion-source chamber for matrix-assisted laser desorption/ionization (AP-MALDI) and a quadrupole ion trap time-of-flight (QIT-TOF) mass spectrometer. The production of 2-dimensional mass spectrum intensity by the atmospheric-pressure mass microscope with a very fine scan pitch enables us to visualize the distribution of lipids and their metabolites in frozen sections without any specific probes or labels. In this study, we applied AP-MALDI-QIT-TOF imaging mass spectrometry to investigate the distribution of lipids in the compound eye-associated eyestalk of the blue swimming crab, Portunus pelagicus. The eyestalk of crustaceans responds to many signaling substances, and most of these substances are involved in lipid metabolism. The merged ion image of five significant biomolecules clearly showed seven separate zones in the eye and eyestalk. The results indicate that the lipid components of each cell layer of the compound eye are different. This study provides information regarding lipid compositions and locations on real tissue that correlate with function. Imaging mass spectrometry (IMS) with high spatial resolution could thus be a powerful tool for imaging and measurement of various samples for a first molecular screening. Copyright (C) 2010 John Wiley & Sons, Ltd.
• Detection of characteristic distributions of phospholipid head groups and fatty acids on neurite surface by time-of-flight secondary ion mass spectrometry

  Hyun-Jeong Yang; Itsuko Ishizaki; Noriaki Sanada; Nobuhiro Zaima; Yuki Sugiura; Ikuko Yao; Koji Ikegami; Mitsutoshi Setou

  MEDICAL MOLECULAR MORPHOLOGY 43 3 158 - 164 2010年09月 

  Neurons have a large surface because of their long and thin neurites. This surface is composed of a lipid bilayer. Lipids have not been actively investigated so far because of some technical difficulties, although evidence from cell biology is emerging that lipids contain valuable information about their roles in the central nervous system. Recent progress in techniques, e.g., mass spectrometry, opens a new epoch of lipid research. We show herein the characteristic localization of phospholipid components in neurites by means of time-of-flight secondary ion mass spectrometry. We used explant cultures of mouse superior cervical ganglia, which are widely used by neurite investigation research. In a positive-ion detection mode, phospholipid head group molecules were predominantly detected. The ions of m/z 206.1 [phosphocholine, a common component of phosphatidylcholine (PC) and sphingomyelin (SM)] were evenly distributed throughout the neurites, whereas the ions of m/z 224.1, 246.1 (glycerophosphocholine, a part of PC, but not SM) showed relatively strong intensity on neurites adjacent to soma. In a negative-ion detection mode, fatty acids such as oleic and palmitic acids were mainly detected, showing high intensity on neurites adjacent to soma. Our results suggest that lipid components on the neuritic surface show characteristic distributions depending on neurite region.
• Application of imaging mass spectrometry for the analysis of Oryza sativa rice

  Nobuhiro Zaima; Naoko Goto-Inoue; Takahiro Hayasaka; Mitsutoshi Setou

  RAPID COMMUNICATIONS IN MASS SPECTROMETRY 24 18 2723 - 2729 2010年09月 [査読有り]
   

  Rice is one of the most important food crops in the world and new varieties have been bred for specific purposes, such as the development of drought-resistance, or the enrichment of functional food factors. The localization and composition of metabolites in such new varieties must be investigated because all artificial interventions are expected to change the metabolites of rice. Imaging mass spectrometry using matrix-assisted laser desorption/ionization (MALDI-IMS) is a suitable tool for investigating the localization and composition of metabolites; however, suitable methodologies for the MALDI-IMS analysis of rice have not yet been established. In this study, we optimized the methods for analyzing rice grains by MALDI-IMS using adhesive film and found the characteristic distribution of metabolites in rice. Lysophosphatidylcholine (LPC) was localized in the endosperm. Phosphatidylcholine (PC), gamma-oryzanol and phytic acid were localized in the bran (germ and seed coat), and alpha-tocopherol was distributed in the germ (especially in the scutellum). In addition, MALDI-IMS revealed the LPC and PC composition of the rice samples. The LPC composition, LPC (1-acyl 16:0), LPC (1-acyl 18:2), LPC (1-acyl 18:1) and LPC (1-acyl 18:0), was 59.4 +/- 4.5%, 19.6 +/- 2.5%, 14.2 +/- 4.5% and 6.8 +/- 1.4%. The PC composition, PC (diacyl 16:0/18:2), PC (diacyl 16:0/18;1), PC (diacyl 18:1/18:3), PC (diacyl 18:1/18:2) and PC (diacyl 18:1/18:2), was 19.6 +/- 1.0%, 21.0 +/- 1.0%, 15.0 +/- 1.4%, 26.7 +/- 0.7% and 17.8 +/- 1.9%. This approach can be applied to the assessment of metabolites not only in rice, but also in other foods for which the preparation of sections is a challenging task. Copyright (c) 2010 John Wiley & Sons, Ltd.
• Imaging Mass Spectrometry with Silver Nanoparticles Reveals the Distribution of Fatty Acids in Mouse Retinal Sections

  Takahiro Hayasaka; Naoko Goto-Inoue; Nobuhiro Zaima; Kamlesh Shrivas; Yukiyasu Kashiwagi; Mari Yamamoto; Masami Nakamoto; Mitsutoshi Setou

  JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY 21 8 1446 - 1454 2010年08月 

  A new approach to the visualization of fatty acids in mouse liver and retinal samples has been developed using silver nanoparticles (AgNPs) in nanoparticle-assisted laser desorption/ionization imaging mass spectrometry (nano-PALDI-IMS) in negative ion mode. So far, IMS analysis has concentrated on main cell components, such as cell membrane phospholipids and cytoskeletal peptides. AgNPs modified with alkylcarboxylate and alkylamine were used for nano-PALDI-IMS to identify fatty acids, such as stearic, oleic, linoleic, arachidonic, and eicosapentaenoic acids, as well as palmitic acid, in mouse liver sections; these fatty acids are not detected using 2,5-dihydroxybenzoic acid (DHB) as a matrix. The limit of detection for the determination of palmitic acid was 50 pmol using nano-PALDI-IMS. The nano-PALDI-IMS method is successfully applied to the reconstruction of the ion images of fatty acids in mouse liver sections. We verified the detection of fatty acids in liver tissue sections of mice by analyzing standard lipid samples, which showed that fatty acids were from free fatty acids and dissociated fatty acids from lipids when irradiated with a laser. Additionally, we applied the proposed method to the identification of fatty acids in mouse retinal tissue sections, which enabled us to learn the six-zonal distribution of fatty acids in different layers of the retina. We believe that the current approach using AgNPs in nano-PALDI-IMS could lead to a new strategy to analyze basic biological mechanisms and several diseases through the distribution of fatty acids. (J Am Soc Mass Spectrom 2010, 21, 1446-1454) (C) 2010 American Society for Mass Spectrometry
• Dominant-negative effects of a novel mutation in the filamin myopathy (Retracted article. See vol. 75, pg. 2138, 2010)

  S. Kono; T. Nishio; Y. Takahashi; N. Goto-Inoue; M. Kinoshita; N. Zaima; H. Suzuki; A. Fukutoku-Otsuji; M. Setou; H. Miyajima

  NEUROLOGY 75 6 547 - 554 2010年08月 

  Background: Filamin myopathy is associated with mutations in the filamin C gene ( FLNC) and is a myofibrillar myopathy characterized by focal myofibrillar destruction and cytoplasmic aggregates containing several Z-disk-related proteins. Methods: This study investigated 6 Japanese patients with dominantly inherited myofibrillar myopathy manifested by adult-onset, slow and progressive muscle weakness and atrophy in the distal extremities. Results: The abundantly expressed proteins in the affected muscles were identified as filamin C by nano liquid chromatography-tandem mass spectrometry. A genetic analysis of FLNC identified a heterozygous c.8107delG mutation that was localized to the dimerization domain of filamin C. A biochemical crosslinking analysis of bacterially expressed recombinant wild-type and mutant filamin C fragments demonstrated that the mutant monomer disturbed the proper dimerization of the wild-type filamin dimer, resulting in formation of a heterotrimer with the wild-type filamin dimer. The expression study in C2C12 myoblasts showed that the mutant filamin fragments formed cytoplasmic aggregates with endogenous wild-type filamin C. Conclusions: This study provides evidence for the dominant-negative effects of the FLNC mutation. These effects may be mutation-specific and likely result in the variation in the clinical phenotypes seen in patients with filamin myopathy. Neurology (R) 2010; 75: 547-554
• Visualization of spatial distribution of γ-aminobutyric acid in eggplant (Solanum melongena) by matrix-assisted laser desorption/ionization imaging mass spectrometry

  Naoko Goto-Inoue; Mitsutoshi Setou; Nobuhiro Zaima

  Analytical Sciences 26 7 821 - 825 2010年07月 [査読有り]
   

  We applied imaging mass spectrometry (IMS) to determine the spatial distribution of γ-aminobutyric acid (GABA). We found that GABA had a specific localization in seeds. We also visualized various biomolecules as well as GABA with higher spatial resolution than in the previous report. Our work suggests that IMS might be a powerful tool for exploring functional food factors, investigating the specific distribution of nutrients in unused natural resources, and evaluating the quality of functional foods. 2010 © The Japan Society for Analytical Chemistry.
• SIRT1 regulates thyroid-stimulating hormone release by enhancing PIP5Kγ activity through deacetylation of specific lysine residues in mammals

  Sayaka Akieda-Asai; Sayaka Akieda-Asai; Nobuhiro Zaima; Nobuhiro Zaima; Koji Ikegami; Koji Ikegami; Tomoaki Kahyo; Tomoaki Kahyo; Ikuko Yao; Ikuko Yao; Takahiro Hatanaka; Shun ichiro Iemura; Rika Sugiyama; Takeaki Yokozeki; Yoshinobu Eishi; Morio Koike; Kyoji Ikeda; Takuya Chiba; Haruyoshi Yamaza; Haruyoshi Yamaza; Isao Shimokawa; Si Young Song; Akira Matsuno; Akiko Mizutani; Motoji Sawabe; Moses V. Chao; Masashi Tanaka; Yasunori Kanaho; Tohru Natsume; Haruhiko Sugimura; Yukari Date; Michael W. Mcburney; Leonard Guarente; Mitsutoshi Setou; Mitsutoshi Setou

  PLoS ONE 5 7 2010年07月 

  Background: SIRT1, a NAD-dependent deacetylase, has diverse roles in a variety of organs such as regulation of endocrine function and metabolism. However, it remains to be addressed how it regulates hormone release there. Methodology/Principal Findings: Here, we report that SIRT1 is abundantly expressed in pituitary thyrotropes and regulates thyroid hormone secretion. Manipulation of SIRT1 level revealed that SIRT1 positively regulated the exocytosis of TSH-containing granules. Using LC/MS-based interactomics, phosphatidylinositol-4-phosphate 5-kinase (PIP5K)y was identified as a SIRT1 binding partner and deacetylation substrate. SIRT1 deacetylated two specific lysine residues (K265/K268) in PIP5Ky and enhanced PIP5Ky enzyme activity. SIRT1-mediated TSH secretion was abolished by PIP5Ky knockdown. SIRT1 knockdown decreased the levels of deacetylated PIP5Ky, PI(4,5)P 2 , and reduced the secretion of TSH from pituitary cells. These results were also observed in SIRT1-knockout mice. Conclusions/Significance: Our findings indicated that the control of TSH release by the SIRT1-PIP5Kγ pathway is important for regulating the metabolism of the whole body. © 2010 Akieda-Asai et al.
• 質量顕微鏡法の開発と応用

  尾上 健児; 財満 信宏; 斎藤 能彦

  内分泌・糖尿病・代謝内科 30 4 359 - 367 科学評論社 2010年04月
• Developments and applications of mass microscopy

  Mitsutoshi Setou; Kamlesh Shrivas; Morakot Sroyraya; Hyunjeong Yang; Yuki Sugiura; Junji Moribe; Akira Kondo; Koji Tsutsumi; Yoshishige Kimura; Nobuya Kurabe; Takahiro Hayasaka; Naoko Goto-Inoue; Nobuhiro Zaima; Koji Ikegami; Prasert Sobhon; Yoshiyuki Konishi

  MEDICAL MOLECULAR MORPHOLOGY 43 1 1 - 5 2010年03月 

  We have developed a mass microscopy technique, i.e., a microscope combined with high-resolution matrixassisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS), which is a powerful tool for investigating the spatial distribution of biomolecules without any time-consuming extraction, purification, and separation procedures for biological tissue sections. Mass microscopy provides clear images about the distribution of hundreds of biomolecules in a single measurement and also helps in understanding the cellular profile of the biological system. The sample preparation and the spatial resolution and speed of the technique are all important steps that affect the identification of biomolecules in mass microscopy. In this Award Lecture Review, we focus on some of the recent developments in clinical applications to show how mass microscopy can be employed to assess medical molecular morphology.
• OP-241 腎癌の脂質プロファイリング(腎腫瘍/基礎2,一般演題口演,第98回日本泌尿器科学会総会)

  高山 達也; 財満 信宏; 宮崎 美紀; 高岡 直央; 京野 陽子; 伊藤 寿樹; 杉山 貴之; 永田 仁夫; 古瀬 洋; 栗田 豊; 麦谷 荘一; 瀬藤 光利; 大園 誠一郎

  日本泌尿器科学会雑誌 101 2 293 - 293 一般社団法人 日本泌尿器科学会 2010年
• 農作物中の代謝物の質量顕微鏡法による解析

  榎元廣文; 井上菜穂子; 瀬藤光利; 財満信宏

  食品加工技術 30 4 153 - 159 日本食品機械研究会 2010年 [招待有り]
  
• Imaging mass spectrometry of gastric carcinoma in formalin-fixed paraffin-embedded tissue microarray

  Yoshifumi Morita; Koji Ikegami; Naoko Goto-Inoue; Takahiro Hayasaka; Nobuhiro Zaima; Hiroki Tanaka; Takashi Uehara; Tomohiko Setoguchi; Takanori Sakaguchi; Hisashi Igarashi; Haruhiko Sugimura; Mitsutoshi Setou; Hiroyuki Konno

  CANCER SCIENCE 101 1 267 - 273 2010年01月 

  The popularity of imaging mass spectrometry (IMS) of tissue samples, which enables the direct scanning of tissue sections within a short time-period, has been considerably increasing in cancer proteomics. Most pathological specimens stored in medical institutes are formalin-fixed; thus, they had been regarded to be unsuitable for proteomic analyses, including IMS, until recently. Here, we report an easy-to-use screening method that enables the analysis of multiple samples in one experiment without extractions and purifications of proteins. We scanned, with an IMS technique, a tissue microarray (TMA) of formalin-fixed paraffin-embedded (FFPE) specimens. We detected a large amount of signals from trypsin-treated FFPE-TMA samples of gastric carcinoma tissues of different histological types. Of the signals detected, 54 were classified as signals specific to cancer with statistically significant differences between adenocarcinomas and normal tissues. We detected a total of 14 of the 54 signals as histological type-specific with the support of statistical analyses. Tandem MS revealed that a signal specific to poorly differentiated cancer tissue corresponded to histone H4. Finally, we verified the IMS-based finding by immunohistochemical analysis of more than 300 specimens spotted on TMAs; the immunoreactivity of histone H4 was remarkably strong in poorly differentiated cancer tissues. Thus, the application of IMS to FFPE-TMA can enable high-throughput analysis in cancer proteomics to aid in the understanding of molecular mechanisms underlying carcinogenesis, invasiveness, metastasis, and prognosis. Further, results obtained from the IMS of FFPE-TMA can be readily confirmed by commonly used immunohistochemical analyses. (Cancer Sci 2009).
• Visualization of volatile substances in different organelles with an atmospheric-pressure mass microscope

  T. Harada; A. Yuba-Kubo; Y. Sugiura; N. Zaima; T. Hayasaka; N. Goto-Inoue; M. Wakui; M. Suematsu; K. Takeshita; K. Ogawa; Y. Yoshida; M. Setou

  Anal Chem 81 21 9153 - 7 2009年11月 

  We have developed a mass microscope (mass spectrometry imager with spatial resolution higher than the naked eye) equipped with an atmospheric pressure ion-source chamber for laser desorption/ionization (AP-LDI) and a quadrupole ion trap time-of-flight (QIT-TOF) analyzer. The optical microscope combined with the mass spectrometer permitted us to precisely determine the relevant tissue region prior to performing imaging mass spectrometry (IMS). An ultraviolet laser tightly focused with a triplet lens was used to achieve high spatial resolution. An atmospheric pressure ion-source chamber enables us to analyze fresh samples with minimal loss of intrinsic water or volatile compounds. Mass-microscopic AP-LDI imaging of freshly cut ginger rhizome sections revealed that 6-gingerol ([M + K](+)at m/z 333.15, positive mode; [M - H](-) at m/z 293.17, negative mode) and the monoterpene ([M + K](+) at m/z 191.09), which are the compounds related to pungency and flavor, respectively, were localized in oil drop-containing organelles. AP-LDI-tandem MS/MS analyses were applied to compare authentic signals from freshly cut ginger directly with the standard reagent. Thus, our atmosphere-imaging mass s
• Visualization of Volatile Substances in Different Organelles with an Atmospheric-Pressure Mass Microscope

  Takahiro Harada; Akiko Yuba-Kubo; Yuki Sugiura; Nobuhiro Zaima; Takahiro Hayasaka; Naoko Goto-Inoue; Masatoshi Wakui; Makoto Suematsu; Kengo Takeshita; Kiyoshi Ogawa; Yoshikazu Yoshida; Mitsutoshi Setou

  ANALYTICAL CHEMISTRY 81 21 9153 - 9157 2009年11月 

  We have developed a mass microscope (mass spectrometry imager with spatial resolution higher than the naked eye) equipped with an atmospheric pressure ion-source chamber for laser desorption/ionization (AP-LDI) and a quadrupole ion trap time-of-flight (QIT-TOF) analyzer. The optical microscope combined with the mass spectrometer permitted us to precisely determine the relevant tissue region prior to performing imaging mass spectrometry (IMS). An ultraviolet laser tightly focused with a triplet lens was used to achieve high spatial resolution. An atmospheric pressure ion-source chamber enables us to analyze fresh samples with minimal loss of intrinsic water or volatile compounds. Mass-microscopic AP-LDI imaging of freshly cut ginger rhizome sections revealed that 6-gingerol ([M + K](+) at m/z 333.15, positive mode; [M - H](-) at m/z 293.17, negative mode) and the monoterpene ([M + Kr](-) at m/z 191.09), which are the compounds related to pungency and flavor, respectively, were localized in oil drop-containing organelles. AP-LDI-tandem MS/MS analyses were applied to compare authentic signals from freshly cut ginger directly with the standard reagent. Thus, our atmosphere-imaging mass spectrometer enabled us to monitor a quality of plants at the organelle level.
• Analysis of lipid profile of renal cell carcinoma by imaging mass spectrometry

  T. Takayama; N. Zaima; Y. Kyono; M. Miyazaki; N. Takaoka; M. Nagata; F. Kai; T. Sugiyama; M. Setou; S. Ozono

  EJC SUPPLEMENTS 7 2 435 - 435 2009年09月
• The specific localization of seminolipid molecular species on mouse testis during testicular maturation revealed by imaging mass spectrometry

  Naoko Goto-Inoue; Takahiro Hayasaka; Nobuhiro Zaima; Mitsutoshi Setou

  GLYCOBIOLOGY 19 9 950 - 957 2009年09月 

  More than 90% of the glycolipid in mammalian testis consists of a unique sulfated glyceroglycolipid called seminolipid. The galactosylation of the molecule is catalyzed by UDP-galactose:ceramide galactosyltransferase (CGT). Disruption of the CGT gene in mice results in male infertility due to the arrest of spermatogenesis, indicating that seminolipid plays an important role in reproductive function. Seminolipid molecules can be assigned to different molecular species based on the fatty acid composition. In this report, we investigated the localizations of the molecular species of seminolipid by imaging mass spectrometry and demonstrated that major molecule (C16:0-alkyl-C16:0-acyl) was expressed throughout the tubules: some (C16:0-alkyl-C14:0-acyl and C14:0-alkyl-C16:0-acyl) were predominantly expressed in spermatocytes and the other (C17:0-alkyl-C16:0-acyl) was specifically expressed in spermatids and spermatozoa. This is the first report to show the cell-specific localization of each molecular species of seminolipid during testicular maturation.
• Organ-Specific Distributions of Lysophosphatidylcholine and Triacylglycerol in Mouse Embryo

  Takahiro Hayasaka; Naoko Goto-Inoue; Nobuhiro Zaima; Yoshishige Kimura; Mitsutoshi Setou

  LIPIDS 44 9 837 - 848 2009年09月 

  Imaging mass spectrometry (IMS) has been developed as a method for determining and visualizing the distribution of proteins and lipids across sections of dissected tissue. Although lipids play an important role in mammal development, their detailed distributions have not been analyzed by conventional methods. In this study, we tried to determine and visualize lysophosphatidylcholine (LysoPtdCho) and triacylglycerol (TAG) in a mouse embryo by matrix-assisted laser desorption/ionization (MALDI) hybrid quadrupole time-of-flight (TOF) mass spectrometer. Many peaks were detected from a raster scan of the whole embryonic sections. The peaks at m/z 496.33, 524.36, 879.72, 881.74, and 921.74 were identified by MS/MS analyses as [LysoPtdCho (16:0) + H](+), [LysoPtdCho (18:0) + H](+), [TAG (16:0/18:2/18:1) + Na](+), [TAG (16:0/18:1/18:1) + Na](+), and [TAG (16:0/20:3/18:1) + K](+), respectively. The ion images constructed from the peaks revealed that LysoPtdCho were distributed throughout the body and TAGs were distributed around the brown adipose tissue and in the liver at embryo day 17.5. Thus, IMS system based on MALDI hybrid quadrupole TOF MS revealed the distribution of LysoPtdCho and, more importantly, the organ-specific distribution of TAGs in the embryonic stages of mammals for the first time. We can conclude that this technique enables us to analyze the roles of various lipids during embryogenesis and gives insight for lipid research.
• Visualization of the cell-selective distribution of PUFA-containing phosphatidylcholines in mouse brain by imaging mass spectrometry

  Yuki Sugiura; Yoshiyuki Konishi; Nobuhiro Zaima; Shigeki Kajihara; Hiroki Nakanishi; Ryo Taguchi; Mitsutoshi Setou

  JOURNAL OF LIPID RESEARCH 50 9 1776 - 1788 2009年09月 

  Previous studies have shown that MALDI-imaging mass spectrometry (IMS) can be used to visualize the distribution of various biomolecules, especially lipids, in the cells and tissues. In this study, we report the cell-selective distribution of PUFA-containing glycerophospholipids (GPLs) in the mouse brain. We established a practical experimental procedure for the IMS of GPLs. We demonstrated that optimization of the composition of the matrix solution and spectrum normalization to the total ion current (TIC) is critical. Using our procedure, we simultaneously differentiated and visualized the localizations of specific molecular species of GPLs in mouse brain sections. The results showed that PUFA-containing phosphatidylcholines (PCs) were distributed in a cell-selective manner: arachidonic acid-and docosahexaenoic acid-containing PCs were seen in the hippocampal neurons and cerebellar Purkinje cells, respectively. Furthermore, these characteristic localizations of PUFA-PCs were formed during neuronal maturation. The phenomenon of brain cell-selective production of specific PUFA-GPLs will help elucidate the potential physiological functions of PUFAs in specific brain regions.-Sugiura, Y., Y. Konishi, N. Zaima, S. Kajihara, H. Nakanishi, R. Taguchi, and M. Setou. Visualization of the cell-selective distribution of PUFA-containing phosphatidylcholines in mouse brain by imaging mass spectrometry. J. Lipid Res. 2009. 50: 1776-1788.
• Imaging of Metabolites by MALDI Mass Spectrometry

  Nobuhiro Zaima; Takahiro Hayasaka; Naoko Goto-Inoue; Mitsutoshi Setou

  JOURNAL OF OLEO SCIENCE 58 8 415 - 419 2009年08月 [査読有り]
   

  Visualization of endogenous molecules in small experimental animals is very important in order to investigate the localization of specific molecules. Conventional imaging techniques are not suitable for simultaneous visualization of endogenous molecules. We recently developed a new imaging method-imaging mass spectrometry (IMS) using matrix-assisted laser desorption/ionization quadrupole ion trap time-of-flight (MALDI-QIT-TOF). In this study, we applied IMS using MALDI-QIT-TOF to visualize the metabolites in medaka (Oryzias latipes) sections and determined the spatial distribution of metabolites including lipids.
• Principal Component Analysis of Direct Matrix-Assisted Laser Desorption/Ionization Mass Spectrometric Data Related to Metabolites of Fatty Liver

  Nobuhiro Zaima; Yumiko Matsuyama; Mitsutoshi Setou

  JOURNAL OF OLEO SCIENCE 58 5 267 - 273 2009年05月 [査読有り]
   

  Non-alcoholic steatohepatitis (NASH) is a common liver disease. NASH is characterized by fatty liver, along with inflammation. Most people with NASH are not aware of their condition, even though NASH can lead to hepatic cirrhosis. Several approaches have been tested to clarify the pathology of NASH. However, the mechanism of onset of NASH was not well-defined. In this study, a supervised multivariate analysis (principal component analysis) approach using direct matrix-assisted laser desorption/ionization mass spectrometry (dMALDI-MS) was applied to the analysis of metabolites in starvation-induced fatty liver tissue sections. This approach does not require complex pretreatments. We investigated the characteristic dynamics of metabolites in fatty liver. This approach can be applied to the analysis of human biopsy specimens of fatty liver in future studies.
• Layer-specific sulfatide localization in rat hippocampus middle molecular layer is revealed by nanoparticle-assisted laser desorption/ionization imaging mass spectrometry

  Hiroshi Ageta; Sayaka Asai; Yuki Sugiura; Naoko Goto-Inoue; Nobuhiro Zaima; Mitsutoshi Setou

  MEDICAL MOLECULAR MORPHOLOGY 42 1 16 - 23 2009年03月 

  Lipids are major structural component of the brain and play key roles in signaling functions in the central nervous system (CNS), such as the hippocampus. In particular, sulfatide is an abundant glycosphingolipid component of both the central and the peripheral nervous system and is an essential lipid component of myelin membranes. Lack of sulfatide is observed in myelin deformation and neurological deficits. Previous studies with antisulfatide antibody have investigated distribution of sulfatide expression in neurons; however, this method cannot distinguish the differences of sulfatide lipid species raised by difference of carbon-chain length in the ceramide portion in addition to the differences of sulfatide and seminolipid. In this study, we solved the problem by our recently developed nanoparticle-assisted laser desorption/ionization (nano-PALDI)-based imaging mass spectrometry (IMS). We revealed that the level of sulfatide in the middle molecular layer was significantly higher than that in granule cell layers and the inner molecular layer in the dentate gyrus of rat hippocampus.
• Triglyceride Deposit Cardiomyovasculopathy

  Ken-ichi Hirano; Yoshihiko Ikeda; Nobuhiro Zaima; Yasuhiko Sakata; Goro Matsumiya

  NEW ENGLAND JOURNAL OF MEDICINE 359 22 2396 - 2398 2008年11月 [査読有り]
  
• Matrix-assisted laser desorption/ionization quadrupole ion trap time-of-flight (MALDI-QIT-TOF)-based imaging mass spectrometry reveals a layered distribution of phospholipid molecular species in the mouse retina

  Takahiro Hayasaka; Naoko Goto-Inoue; Yuki Sugiura; Nobuhiro Zaima; Hiroki Nakanish; Kentaro Ohishi; Setsuko Nakanish; Takayuki Naito; Ryo Taguchi; Mitsutoshi Setou

  RAPID COMMUNICATIONS IN MASS SPECTROMETRY 22 21 3415 - 3426 2008年11月 [査読有り]
   

  We recently developed a matrix-assisted laser desorption/ionization quadrupole ion trap time-of-flight (MALDI-QIT-TOF)-based imaging mass spectrometry (IMS) system. This system enables us to perform structural analyses using tandem mass spectrometry (MS/MS), as well as to visualize phospholipids and peptides in frozen sections. In the retina, phototransduction is regulated by the light-sensitive interaction between visual pigment-coupled receptor proteins, such as rhodopsin, and G proteins, such as transducin. There are some reports that the conformation of rhodopsin is influenced by the composition of phospholipids in the lipid bilayer membrane. However, these results were based on in vitro experiments and have not been analyzed in vivo. In this study, we visualized and identified phospholipids in mouse retinal sections with the MALDI-QIT-TOF-based IMS system. From a spectrum obtained by raster-scanned analysis of the sections, ions with high signal intensities were selected and analyzed by MS/MS. As a result, sixteen ions were identified as being from four diacyl-phosphatidylcholine (PC) species, i.e., PC (16:0/16:0), PC (16:0/18:1), PC (16:0/22:6), and PC (18:0/22:6), with different ion forms. The ion images revealed different distributions on the retinal sections: PC (16:0/18:1) was distributed in the inner nuclear layer and outer plexiform layer, PC (16:0/16:0) in the outer nuclear layer and inner segment, and both PC (16:0/22:6) and PC (18:0/22:6) in the outer segment and pigment epithelium. In conclusion, our in vivo IMS analyses demonstrated a three-zone distribution of PC species on the retinal sections. This approach may be useful for analyzing lipid changes and their contribution to phototransduction in the retina. Copyright (C) 2008 John Wiley & Sons, Ltd.
• Effects of Trans and Conjugated LC N-3 Polyunsaturated Fatty Acids on Lipid Composition and Abdominal Fat Weight in Rats

  T. Okada; R. Noguchi; M. Hosokawa; K. Fukunaga; T. Nishiyama; N. Zaima; T. Hirata; K. Miyashita

  JOURNAL OF FOOD SCIENCE 73 8 H201 - H206 2008年10月 

  Trans and conjugated fatty acids may exhibit either beneficial or detrimental bioactive effects depending on their metabolic properties. This study was conducted to elucidate if isomerization and conjugation of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) demonstrate more favorable bioactivity on lipid metabolism compared to unmodified EPA and DHA. The effects of dietary intake of trans and conjugated forms of EPA and DHA on lipid metabolism were evaluated in animal trials and compared to a control group fed soybean oil. None of the experimental diets showed significant differences from the control in terms of body weight; however, the white adipose tissue weight of rodents fed trans DHA, conjugated EPA (CEPA), and conjugated DHA (CDHA) was significantly lower than the control. Triacylglycerol levels in plasma were significantly decreased in groups fed trans DHA (17.2 mg/dL) and CDHA (31.9 mg/dL) relative to the control (51.3 mg/dL). The total cholesterol concentrations were significantly lower than the control (68.0 mg/dL) in all experimental groups (47.3 to 53.7 mg/dL) except CEPA (58.3 mg/dL). Fatty acid compositions of lipids extracted from rodent livers were influenced by the dietary fatty acid profiles, with all groups showing higher concentrations of stearic acid and lower levels of linoleic acid compared to the control. Rodents fed trans DHA did not have detectable levels of these fatty acid isomers in their livers, suggesting either quick metabolism or a difficulty with bio-absorption.
• Mass imaging and identification of biomolecules with MALDI-QIT-TOF-based system

  Shuichi Shimma; Yuki Sugiura; Takahiro Hayasaka; Nobuhiro Zaima; Mineo Matsumoto; Mitsutoshi Setou

  ANALYTICAL CHEMISTRY 80 3 878 - 885 2008年02月 [査読有り]
   

  Imaging mass spectrometry is becoming a popular visualization technique in the medical and biological sciences. For its continued development, the ability to both visualize and identify molecules directly on the tissue surface using tandem mass spectrometry (MSn) is essential. We established an imaging system based on a matrix-assisted laser/desorption ionization quadrupole ion trap time-of-flight type instrument (AXIMA-QIT, Shimadzu, Kyoto, Japan), which was compatible with both imaging and highly sensitive MSn. In this paper, we present the operating conditions of the AXIMA-QIT as an imaging instrument and introduce the data converter we developed that is available free of charge. The converted data can be applied to Biomap, the commonly used visualization software. For the feasibility experiments, we demonstrated the visualization of phospholipids, glycolipid, and tryptic-digested proteins in the mouse cerebellum. The visualized lipids were successfully identified by MSn directly on the tissue surface, with a strong ability to isolate precursor ions. In the analysis of tryptic-digested proteins, we compared the product ion spectra between AXIMA-QIT and a tandem TOF-type instrument. The results confirmed that AXIMA-QIT can provide a high quality of product ion spectra even on the tissue surface.
• Effects of reactive radicals and heat on trans-isomerization of eicosapentaenoic acid

  Nobuhiro Zaima; Tatsuya Sugawara; Yuki Otsubo; Takashi Hirata

  FISHERIES SCIENCE 73 4 897 - 901 2007年08月 [査読有り]
   

  Trans geometric isomers of eicosapentaenoic acid (TEPA) have been found as minor components in human platelets. However, there is little information on the mechanism of trans-isomerization of eicosapentaenoic acid (EPA) in vitro and in vivo. The effects of reactive radicals and heat on trans-isomerization of EPA were examined. Trans-isomerization occurred when EPA ethyl ester reacted with nitrogen dioxide radical (NO2) but not with 2,2'-azobis(2,4-dimethylvaleronitrile). TEPA was also produced from EPA ethyl ester heated at 200 degrees C for 60 h. No TEPA, however, was detected in sardines Sardinops melanostictus after boiling, roasting, or microwave heating. These results suggest that EPA is trans-isomerized by NO2 in vivo while trans-isomerization of EPA does not occur during conventional cooking.
• Isolation of sphingoid bases of sea cucumber cerebrosides and their cytotoxicity against human colon cancer cells

  Tatsuya Sugawara; Nobuhiro Zaima; Akiyo Yamamoto; Shota Sakai; Ryoko Noguchi; Takashi Hirata

  BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 70 12 2906 - 2912 2006年12月 [査読有り]
   

  Sea cucumber is a health-beneficial food, and contains a variety of physiologically active substances including glycosphingolipids. We show here the sphingoid base composition of cerebrosides prepared from sea cucumber and the cytotoxicity against human colon cancer cell lines. The composition of sphingoid bases prepared from sea cucumber was different from that of mammals, and the major constituents estimated from mass spectra had a branched C17-19 alkyl chain with 1-3 double bonds. The viability of DLD-1, WiDr and Caco-2 cells treated with sea cucumber sphingoid bases was reduced in a dose-dependent manner and was similar to that of cells treated with sphingosine. The sphingoid bases induced such a morphological change as condensed chromatin fragments and increased the caspase-3 activity, indicating that the sphingoid bases reduced the cell viability by causing apoptosis in these cells. Sphingolipids of sea cucumber might therefore serve as bioactive dietary components to suppress colon cancer.
• Trans geometric isomers of EPA decrease LXRα-induced cellular triacylglycerol via suppression of SREBP-1c and PGC-1β

  Nobuhiro Zaima; Tatsuya Sugawara; Dai Goto; Takashi Hirata

  Journal of Lipid Research 47 12 2712 - 2717 2006年12月 [査読有り]
   

  Dietary mono- or di-trans fatty acids with chain lengths of 18-22 increase the risk of cardiovascular diseases because they increase LDL cholesterol and decrease HDL cholesterol in the plasma. However, the effects of trans isomers of PUFAs on lipid metabolism remain unknown. Dietary PUFAs, especially eicosapentaenoic acid (EPA) in marine oils, improve serum lipid profiles by suppressing liver X receptor a (LXRα) activity in the liver. In this study, we compared the effects of trans geometric isomers of eicosapentaenoic acid (TEPA) on triacylglycerol synthesis induced by a synthetic LXRα agonist (T0901317) with the effects of EPA in HepG2 cells. TEPA significantly decreased the amount of cellular triacylglycerol and the expression of mRNAs encoding fatty acid synthase, stearoyl-CoA desaturase-1, and glycerol-3-phosphate acyltransferase induced by T0901317 compared with EPA. However, there was no significant difference between the suppressive effect of TEPA or EPA on the expression of sterol-regulatory element binding protein-1c (SREBP-1c) induced by T0901317. We found that TEPA, but not EPA, decreased the mRNA expression of peroxisome proliferator-activated receptor g coactivator 1β (PGC-1β), which is a coactivator of both LXRα and SREBP-1. These results suggest that the hypolipidemic effect of TEPA can be attributed to a decrease not only in SREBP-1 but also in PGC-1β expression. Copyright ©2006 by the American Society for Biochemistry and Molecular Biology, Inc.
• Hydrotropic pulping and biobleaching of kenaf

  Daisuke Tatsumi; Nobuhiro Zaima; Takayoshi Matsumoto; Hidehiko Sugiyama; Haruo Takahashi

  Zairyo/Journal of the Society of Materials Science, Japan 55 4 363 - 366 2006年04月 

  Kenaf is a fast-growing plant and is noticed as a nonwood fiber resource. There will be significance in the kenaf utilization when the unique characteristics of kenaf will be effective for certain purposes. In this study, pulping and bleaching of kenaf were carried out to examine the usability of kenaf as a fibrous material. We examined a hydrotropic pulping and an enzymatic bleaching, considering the environmental feasibility. Sodium m-xylene sulfonate solution (NaXS) and sodium p-toluene sulfonate solution (NaTS) were used as the hydrotropic regents. The characteristic peaks for lignin were detected by means of UV, 13C-NMR, and FT-IR measurements of the solution after the hydrotropic cooking. The solution after the NaTS cooking produced precipitation when it was stand at room temperature, although the NaXS was stable. This shows that NaXS has higher power of dissolution of lignin. The molecular orbital calculation implied that this difference was originated from the micelle forming ability of the regents. The enzymatic bleaching by manganese peroxidase (MnP) was applied for the obtained pulp. The brightness was increased in 17.4% and the Kappa number was lowered in 9.0 for the bast fibers by the biobleaching.
• ケナフのハイドロトロピックパルプ化と酵素漂白(<特集>木質材料)

  巽 大輔; 財満 信宏; 松本 孝芳; 杉山 英彦; 高橋 治雄

  材料 55 4 363 - 366 社団法人日本材料学会 2006年04月 

  Kenaf is a fast-growing plant and is noticed as a nonwood fiber resource. There will be significance in the kenaf utilization when the unique characteristics of kenaf will be effective for certain purposes. In this study, pulping and bleaching of kenaf were carried out to examine the usability of kenaf as a fibrous material. We examined a hydrotropic pulping and an enzymatic bleaching, considering the environmental feasibility. Sodium m-xylene sulfonate solution (NaXS) and sodium p-toluene sulfonate solution (NaTS) were used as the hydrotropic regents. The characteristic peaks for lignin were detected by means of UV, ^<13>C-NMR, and FT IR measurements of the solution after the hydrotropic cooking. The solution after the NaTS cooking produced precipitation when it was stand at room temperature, although the NaXS was stable. This shows that NaXS has higher power of dissolution of lignin. The molecular orbital calculation implied that this difference was originated from the micelle forming ability of the regents. The enzymatic bleaching by manganese peroxidase (MnP) was applied for the obtained pulp. The brightness was increased in 17.4% and the Kappa number was lowered in 9.0 for the bast fibers by the biobleaching.
• Characterization of Trans Eicosapentaenoic Acid Isomers: Oxidative Stability and Anti-Inflammatory Activity

  Nobuhiro Zaima; Tatsuya Sugawara; Hirofumi Arai; Kazuyuki Nakamura; Mikako Takasugi; Kenji Fukunaga; Ryoko Noguchi; Takashi Hirata

  Journal of Oleo Science 54 9 505 - 512 2005年 [査読有り]
   

  Although trans geometric isomers of unsaturated fatty acids are formed during heat treatment, little is known about the physicochemical properties and the bioactivities of trans eicosapentaenoic acid (TEPA). We examined the oxidative stability and the anti-inflammatory activity of TEPA prepared using p-toluenesulfinic acid. TEPA was more stable to oxidation induced by radical generators than eicosapentaenoic acid (EPA) in organic and in aqueous solutions, and was less suitable as a substrate for 15-lipoxygenase oxidation than was EPA. These results suggest that the trans conformation may be a more stable structure to oxidation. In addition, the release of leukotriene B4 (LTB4) from Ca-ionophore-stimulated rat peritoneal exudate cells (PEC) was not affected by treatment with TEPA, and TEPA was taken up into PEC at lower levels compared to EPA. These results suggest that dietary TEPA has different physiological effects than EPA. © 2005, Japan Oil Chemists' Society. All rights reserved.

書籍

• 栄養素でわかる食品と健康＝WEB連動テキスト

  財満信宏 (担当:分担執筆範囲:)培風館 2016年04月
• Encyclopedia of Analytical Chemistry.

  財満信宏 (担当:共著範囲:)John Wiley & Sons, Ltd 2015年09月
• アンチエイジングをめざした水産物の利用 (水産学シリーズ)

  平田 孝; 菅原 達也; 又平 芳春; 酒井 祥太; 都築 毅; 宮澤 陽夫; 橋本 道男; 財満 信宏; 齋藤 洋昭; 眞岡 孝至; 水田 尚志; 日本水産学会; 平田 孝; 菅原 達也 恒星社厚生閣 2011年10月 ISBN: 4769912595 130
• Imaging Mass Spectrometry

  財満信宏 (担当:共著範囲:)Springer 2010年01月
• 質量顕微鏡法

  財満信宏 (担当:共著範囲:)シュプリンガージャパン株式会社 2008年11月
• Pharmacology

  財満信宏 (担当:共著範囲:)

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  小川昂志; 高葢秋穂; 村上浩規; 岩本和子; 矢野えりか; 財満信宏; 森山達哉

  日本農芸化学会大会講演要旨集(Web) 2017年03月
• キノコに含まれるシリンガ酸はエストロゲンレセプター非依存的に骨粗鬆症モデルマウスの骨密度減少を抑制する  [通常講演]

  田中照佳; 川口信久; 財満信宏; 森山達哉; 福田泰久; 白坂憲章

  日本農芸化学会大会講演要旨集(Web) 2017年03月
• 腹部大動脈瘤の進展・破裂に及ぼす高脂肪食の影響評価  [通常講演]

  橋本佳祐; 久後裕菜; 財満信宏; 森山達哉

  日本農芸化学会大会講演要旨集(Web) 2017年03月
• セサミン・セサモリンの脳内移行におよぼすウコン由来ターメロン高含有画分の影響  [通常講演]

  松村 晋一; 吉岡 百合; 財満 信宏; 森本 正則; 村田 和也; 松田 秀秋

  日本薬学会年会要旨集 2017年03月
• アレルギー性鼻炎の免疫療法―最新知見―」に寄せる 汎アレルゲンであるチェリーのソーマチンライクプロテイン(Pru av2)の特性解析  [通常講演]

  高葢秋穂; 村上浩規; 三口志穂; 矢野えりか; 岩本和子; 財満信宏; 森山達哉

  月刊アレルギーの臨床 2017年02月 

  保存性が高く植物界に広く分布する汎アレルゲンは、全身症状や花粉症に関連したOASなどを引き起こす。汎アレルゲンの1つであるソーマチンライクプロテイン(PR-5)は、花粉にも含まれるが、OASを中心とした症状を惹起するのか、あるいは経腸的に吸収されて全身症状を惹起するのかいまだ十分に解明されていない。そこで、本研究ではサクランボやチェリーに含まれるソーマチンライクプロテイン(Pru av2)の特性を多様な観点から評価した。さらに、近年問題となっている新たな感作経路である経皮感作を起こしうるのかをマウスを用いて検討した。(著者抄録)
• Adipocyte in vascular wall can induce the rupture of abdominal aortic aneurysm  [通常講演]

  Hirona Kugo; Nobuhiro Zaima; Hiroki Tanaka; Youhei Mouri; Kenichi Yanagimoto; Kohsuke Hayamizu; Keisuke Hashimoto; Takeshi Sasaki; Masaki Sano; Tatsuro Yata; Tetsumei Urano; Mitsutoshi Setou; Naoki Unno; Tatsuya Moriyama

  第24回日本血管生物医学会学術集会 2016年12月
• 経口免疫寛容によって大豆タンパク質の経皮感作が抑制される  [通常講演]

  村上浩規; 高葢秋穂; 小川昂志; 矢野えりか; 財満信宏; 森山達哉

  2016年10月
• 腹部大動脈瘤の進展・破裂に及ぼす高脂肪食の影響評価  [通常講演]

  橋本佳祐; 久後裕菜; 財満信宏; 森山達哉

  2016年10月
• 腹部大動脈瘤の新規モデル動物の作出とその病理解析  [通常講演]

  宮本智絵; 橋本佳祐; 久後裕菜; 田中 宏樹; 海野直樹; 財満信宏; 森山達哉

  2016年10月
• 植物汎アレルゲンであるソーマチンライクプロテイン(PR-5)の特性解析  [通常講演]

  高葢秋穂; 三口志穂; 小川昂志; 村上浩規; 矢野えりか; 財満信宏; 森山達哉

  日本栄養・食糧学会 第55回近畿支部大会 2016年10月
• 経皮感作される卵白タンパク質の解析  [通常講演]

  小川昂志; 高葢秋穂; 村上浩規; 矢野えりか; 財満信宏; 森山達哉

  日本栄養・食糧学会 第55回近畿支部大会 2016年10月
• マウス眼球及び周囲組織におけるアントシアニン分子種の動態解析  [通常講演]

  山田周平; 荘厳哲哉; 財満信宏; 森山達哉

  日本栄養・食糧学会 第55回近畿支部大会 2016年10月
• The effect of high fat diet on development of abdominal aortic aneurysm  [通常講演]

  Keisuke Hashimoto; Hirona Kugo; Nobuhiro Zaima; Tatsuya Moriyama

  2016年10月
• The effect of dietary food on the development of abdominal aortic aneurysm  [通常講演]

  Hirona Kugo; Nobuhiro Zaima; Youhei Mouri; Hiroki Tanaka; Kenichi Yanagimoto; Tetsumei Urano; Naoki Unno; Tatsuya Moriyama

  The 1st Joint Meeting of ISFP and PA Workshop 2016年10月
• ウコン精油のβ-セクレターゼ阻害作用  [通常講演]

  松村 晋一; 村田 和也; 吉岡 百合; 財満 信宏; 森本 正則; 岩城 正宏; 松田 秀秋

  日本生薬学会年会講演要旨集 2016年08月
• 食品による疾患の予防  [招待講演]

  財満信宏

  近畿大学農学部 公開講座 2016年05月
• 腹部大動脈瘤発症に対する魚油の予防効果の検討  [通常講演]

  久後裕菜; 財満信宏; 毛利陽平; 田中宏樹; 柳本賢一; 浦野哲盟; 海野直樹; 森山達哉

  第70回 日本栄養・食糧学会 2016年05月
• ヒト腹部大動脈瘤の病理解析と新規モデル動物の作出  [通常講演]

  財満信宏; 久後裕菜; 田中宏樹; 海野直樹; 森山達哉

  第70回 日本栄養・食糧学会 2016年05月
• 低アレルゲン性新規食品素材としての大豆ホエイの特性解析  [通常講演]

  植田啄也; 和田宏章; 矢野えりか; 石黒貴寛; 村澤久司; 小川正; 財満信宏; 森山達哉

  第70回 日本栄養・食糧学会 2016年05月
• 経皮感作し得る大豆タンパク質の検出及び同定  [通常講演]

  村上浩規; 小川祥平; 矢野えりか; 財満信宏; 森山達哉

  第70回 日本栄養・食糧学会 2016年05月
• 虫害被害を受けた大豆(枝豆)のプロテオノーム・アレルゲノーム解析  [通常講演]

  花房佳世; 矢野えりか; 末森祐輔; 財満信宏; 森山達哉

  第70回 日本栄養・食糧学会 2016年05月
• 低アレルゲン性新規食品素材としての大豆ホエイの特性解析  [通常講演]

  植田 啄也; 和田 宏章; 矢野 えりか; 石黒 貴寛; 村澤 久司; 小川 正; 財満 信宏; 森山 達哉

  日本栄養・食糧学会大会講演要旨集 2016年04月
• 経皮感作し得る大豆タンパク質の検出及び同定  [通常講演]

  村上 浩規; 小川 祥平; 矢野 えりか; 財満 信宏; 森山 達哉

  日本栄養・食糧学会大会講演要旨集 2016年04月
• 虫害被害を受けた大豆(枝豆)のプロテオーム・アレルゲノーム解析  [通常講演]

  花房 佳世; 矢野 えりか; 末森 佑輔; 財満 信宏; 森山 達哉

  日本栄養・食糧学会大会講演要旨集 2016年04月
• お米の栄養はどこにある？目に見えない分子を可視化する技術ー質量分析イメージングの原理と実際－  [招待講演]

  財満信宏

  機能性健康米協会シンポジウム 2016年02月
• 食品による疾患の予防  [招待講演]

  財満信宏

  近畿大学農学部 公開講座 2015年10月
• アントシアニンの体内動態解析  [通常講演]

  財満信宏; 稲葉栞里; 藤森隆道; 荘厳哲哉; 小林沙織; 森山達哉

  第40回日本医用マススペクトル学会年会 2015年09月
• 経皮感作し得る大豆タンパク質の特性解析  [通常講演]

  村上浩規; 小川祥平; 和田宏章; 末森祐輔; 矢野えりか; 財満信宏; 森山達哉

  日本食品科学工学会 第62回大会 2015年08月
• The preventive effect of fish oil on the development of abdominal aortic aneurysm  [通常講演]

  Hirona Kugo; Youhei Mouri; Ken-ichi Yanagimoto; Nobuhiro Zaima; Tatsuya Moriyama

  12th Asian Congress of Nutrition 2015年05月
• Characteristic Distribution of Metabolites in Oryza sativa Rice  [通常講演]

  Nobuhiro Zaima; Yukihiro Yoshimura; Yukio Kawamura; Tatsuya Moriyama

  106th AOCS Annual Meeting 2015年05月
• 新精米法による新たな機能性米の創出とその機能成分の可視化  [通常講演]

  財満信宏; 郡俊之; 森山達哉; 川西孝彦; 寺下隆夫; 白坂憲章

  日本農芸化学会2015年度大会 2015年03月
• イメージングマススペクトロメトリーの原理と分析事例  [招待講演]

  財満信宏

  第45回中部化学関連学協会連合秋季大会 2014年11月
• 悪玉アディポサイトカインであるレジスチンの変動解析の再検討  [通常講演]

  山本美里; 田前 諒; 山中大輔; 矢野えりか; 末森祐輔; 鵜澤有希; 財満信宏; 森山達哉

  日本栄養・食糧学会 第53回近畿支部大会 2014年10月
• Nicotine投与がラット腹部大動脈血管壁に及ぼす影響の評価  [通常講演]

  久後裕菜; 財満信宏; 森山達哉

  日本栄養・食糧学会 第53回近畿支部大会 2014年10月
• 農作物の収穫後処理による汎アレルゲンの変動解析  [通常講演]

  三口志穂; 矢野喜裕; 矢野えりか; 末森祐輔; 鵜澤有希; 財満信宏; 小川 正; 森山達哉

  日本栄養・食糧学会 第53回近畿支部大会 2014年10月
• イメージングマススペクトロメトリー(IMS)による卵黄脂質層構造の解析  [通常講演]

  東埜恭明; 財満信宏; 森山達哉

  日本栄養・食糧学会 第53回近畿支部大会 2014年10月
• イメージングマススペクトロメトリーによる食品機能研究  [通常講演]

  財満 信宏; 森山達哉

  第59回食品新素材研究会 2014年09月
• 中性脂肪蓄積心筋血管症患者由来繊維芽細胞のTG代謝に及ぼすカルニチンの影響  [通常講演]

  須見友子; 鵜澤有希; 平野賢一; 財満信宏; 森山達哉

  日本油化学会 2014年09月
• イメージング質量分析の食品科学への応用  [招待講演]

  財満信宏

  第41回BMSコンファレンス 2014年07月
• イメージングマススペクトロメトリーによるスフィンゴ脂質の可視化  [招待講演]

  財満信宏

  日本農芸化学会2014年度大会シンポジウム 2014年03月
• 腹部大動脈瘤発症に及ぼすn-3系高度不飽和脂肪酸の影響評価  [通常講演]

  久後裕菜; 毛利陽平; 柳本賢一; 韓力; 財満信宏; 森山達哉

  日本農芸化学会 2014年03月
• イメージングマススペクトロメトリーによる脂質の可視化  [招待講演]

  財満信宏

  健康・長寿談話会 2013年11月
• イメージングマススペクトロメトリーによる機能性食品成分の可視化  [通常講演]

  財満信宏

  メタボロームシンポジウム 2013年10月
• 凍り豆腐の大豆クラス2アレルギーリスク低減化 の実証  [通常講演]

  和田宏章; 末森祐輔; 矢野えりか; 財満信宏; 石黒貴寛; 村澤久司; 小川正; 森山達哉; 河村幸雄

  日本栄食・食糧学会 第52回近畿支部大会 2013年10月
• 豆味噌抽出物による破骨細胞分化抑制効果  [通常講演]

  土岐倉千智; 木村裕; 田中照佳; 鵜澤有希; 財満信宏; 森山達哉; 河村幸雄

  日本栄食・食糧学会 第52回近畿支部大会 2013年10月
• 中性脂肪蓄積心筋血管症患者由来繊維芽細胞の脂質代謝に及ぼすカルニチンの影響  [通常講演]

  須見友子; 鵜澤有希; 平野賢一; 財満信宏; 森山達哉; 河村幸雄

  日本栄食・食糧学会 第52回近畿支部大会 2013年10月
• 大豆サポニンアグリコン（ソヤサポゲノール）の脂肪細胞分化抑制効果  [通常講演]

  小林知世; 境野眞善; 山下貴稔; 加茂修一; 佐藤俊郎; 財満信宏; 森山達哉; 河村幸雄

  日本栄食・食糧学会 第52回近畿支部大会 2013年10月
• イメージングマススペクトロメトリー－質量分析で脂質を見る－  [招待講演]

  財満信宏

  日本油化学会 2013年09月
• 肥満・糖尿病モデルマウスに対する大豆サポニンの抗肥満効果  [通常講演]

  小林知世; 境野眞善; 山下貴稔; 加茂修一; 佐藤俊郎; 財満信宏; 森山達哉; 河村幸雄

  第60回日本食品科学工学会大会 2013年08月
• 新規大豆食品素材(大豆ペースト)の低アレルゲン性及び消化性の解析  [通常講演]

  森山達哉; 山田陽子; 矢野えりか; 崎川貴文; 末森祐輔; 財満信宏; 片岡雅人; 長瀬二郎; 河村幸雄

  第60回日本食品科学工学会大会 2013年08月
• Ba-8 wx/ae二重変異体米の澱粉吸着型リゾホスファチヂルコリンの定量と胚乳部における局在解析(澱粉の構造・物性・利用,一般講演,日本応用糖質科学会平成25年度大会(第62回))  [通常講演]

  庄野 陽祐; 小谷口 美也子; 藤原 美乃里; 中屋 慎; 財満 信宏; 北村 進一

  応用糖質科学 : 日本応用糖質科学会誌 2013年08月
• IMSによる組織内代謝変動の可視化－食品成分動態解析と病理解析への応用－  [招待講演]

  財満信宏

  日本農芸化学会2013年度大会シンポジウム 2013年03月
• メタボローム可視化の生命科学への応用  [招待講演]

  財満信宏

  生命医薬情報学連合大会 2012年10月
• ヒト腹部大動脈瘤の病理解析とモデル動物の新規作出  [通常講演]

  毛利陽平; 財満信宏; 田中宏樹; 森山達哉; 河村幸雄; 海野直樹; 瀬藤光利

  日本食品科学工学会2012年度大会 2012年08月
• 脂肪細胞からのレジスチン分泌を抑制する食品成分の探索  [通常講演]

  若木泰子; 吉村征浩; 鵜澤有希; 財満信宏; 森山達哉; 河村幸雄

  第29回日本微量栄養素学会学術集会 2012年06月
• クロマグロ皮たんぱく質経口摂取によるマウスの肝機能保護作用  [通常講演]

  髙橋賢次; 田中照佳; 岩本直樹; 阿川泰夫; 澤田好史; 吉村征浩; 財満信宏; 森山達哉; 河村幸雄

  日本農芸化学大会 2012年03月
• ザクロ抽出物およびエラグ酸によるタンパク質分解亢進を介したレジスチン分泌抑制効果  [通常講演]

  若木泰子; 吉村征浩; 鵜澤有希; 財満信宏; 森山達哉; 河村幸雄

  日本農芸化学会大会 2012年03月
• 新規の腹部大動脈瘤モデルラットの作出と病理解析  [通常講演]

  毛利陽平; 財満信宏; 田中宏樹; 森山達哉; 河村幸雄; 海野直樹; 瀬藤光利

  日本農芸化学会2012年度大会 2012年03月
• 経口摂取プエラリンのマウス骨吸収抑制作用と大腿骨への移行  [通常講演]

  田中照佳; 吉村征浩; 道原成和; 山本彩実; 財満信宏; 森山達哉; 河村幸雄

  日本農芸化学大会 2012年03月
• IMSによるプエラリンの体内動態解析  [通常講演]

  山本彩実; 財満信宏; 吉村征浩; 田中照佳; 森山達哉; 河村幸雄

  日本農芸化学大会 2012年03月
• IMS解析が明らかにするアントシアニンの分子種による組織内局在の違い  [通常講演]

  吉村征浩; 財満信宏; 森山達哉; 河村幸雄

  日本農芸化学大会 2012年03月
• イメージングマススペクトロメトリーによる農作物の機能性食品成分の局在解析  [通常講演]

  財満信宏; 吉村征浩; 森山達哉; 河村幸雄

  日本農芸化学大会 2012年03月
• SF-051-2 一次性下肢静脈瘤の弁不全機序に関与する脂質分子の同定(血管-2,サージカルフォーラム,第110回日本外科学会定期学術集会)  [通常講演]

  田中 宏樹; 海野 直樹; 山本 尚人; 相良 大輔; 鈴木 実; 西山 元啓; 眞野 勇記; 佐野 真規; 財満 信宏; 佐々木 健; 瀬藤 光利

  日本外科学会雑誌 2010年03月
• OP-241 腎癌の脂質プロファイリング(腎腫瘍/基礎2,一般演題口演,第98回日本泌尿器科学会総会)  [通常講演]

  高山 達也; 財満 信宏; 宮崎 美紀; 高岡 直央; 京野 陽子; 伊藤 寿樹; 杉山 貴之; 永田 仁夫; 古瀬 洋; 栗田 豊; 麦谷 荘一; 瀬藤 光利; 大園 誠一郎

  日本泌尿器科学会雑誌 2010年

MISC

• 〈総説〉穀物や果物等の農作物に含まれる食物アレルゲン

  衣笠, 芹菜; 泉, 愛理; 福住, 綾乃; 矢野, えりか; 財満, 信宏; 森山, 達哉 近畿大学農学部紀要 = MEMOIRS OF THE FACULTY OF AGRICULTURE OF KINDAI UNIVERSITY 55 1 -14 2022年03月
• 食物アレルゲンとしての植物由来生体防御タンパク質

  泉 愛理; 衣笠 芹菜; 福住 綾乃; 矢野 えりか; 財満 信宏; 森山 達哉 アレルギーの臨床 41 (14) 1319 -1322 2021年12月
• 経皮感作しうる果物由来アレルゲン・コンポーネント

  衣笠 芹菜; 泉 愛理; 棚橋 菜々; 財満 信宏; 森山 達哉 アレルギーの臨床 41 (12) 1096 -1100 2021年11月
• シリンガ酸による閉経後肥満予防効果の作用機構の検討

  和田 真希; 田中 照佳; 鈴木 俊幸; 川口 信久; 白坂 憲章; 財満 信宏; 森山 達哉; 本間 好 日本栄養・食糧学会大会講演要旨集 75回 69 -69 2021年07月
• チェリータンパク質の経皮感作能の検討と経皮感作抗原の同定及び特性解析

  泉 愛理; 日高 翔太; 廣井 彩子; 衣笠 芹菜; 矢野 えりか; 財満 信宏; 森山 達哉 日本栄養・食糧学会大会講演要旨集 75回 125 -125 2021年07月
• きのこの機能性に対する消費者の期待-共分散構造分析によるアプローチ-

  大石卓史; 大石卓史; 財満信宏; 財満信宏; 福田泰久; 白坂憲章 日本きのこ学会誌 28 (4) 2021年
• キウイタンパク質の経皮感作能の評価および経皮感作抗原の同定

  衣笠芹菜; 泉愛理; 日高翔太; 田中芹奈; 丸本浩平; 矢野えりか; 矢野えりか; 財満信宏; 財満信宏; 財満信宏; 森山達哉; 森山達哉; 森山達哉 日本栄養・食糧学会大会講演要旨集 75th 2021年
• 大豆アレルゲンの網羅的検出による納豆類の低アレルゲン性の検証

  嶌田力也; 福住綾乃; 矢野えりか; 財満信宏; 財満信宏; 財満信宏; 森山達哉; 森山達哉; 森山達哉 日本食品科学工学会関西支部大会市民フォーラム講演要旨集 4th 2021年
• タンニン酸による経皮感作抑制効果とそのメカニズムの検討

  棚橋菜々; 日高翔太; 泉愛理; 衣笠芹菜; 財満信宏; 財満信宏; 財満信宏; 森山達哉; 森山達哉; 森山達哉 日本食品科学工学会関西支部大会市民フォーラム講演要旨集 4th 2021年
• 食用昆虫(コオロギ)タンパク質の経皮感作能の検討と経皮感作アレルゲンの検出

  徳永涼香; 筒泉清香; 棚橋菜々; 泉愛理; 衣笠芹菜; 財満信宏; 財満信宏; 財満信宏; 森山達哉; 森山達哉; 森山達哉 日本食品科学工学会関西支部大会市民フォーラム講演要旨集 4th 2021年
• ダニ等の環境アレルゲンの経皮感作能の検討と経皮感作アレルゲンの検出

  筒泉清香; 土喰光希; 日高翔太; 泉愛理; 衣笠芹菜; 財満信宏; 財満信宏; 財満信宏; 森山達哉; 森山達哉; 森山達哉 日本食品科学工学会関西支部大会市民フォーラム講演要旨集 4th 2021年
• 植物性食品に含まれるアレルゲンのリスク変動解析

  福住綾乃; 泉愛理; 衣笠芹菜; 日高翔太; 矢野えりか; 財満信宏; 財満信宏; 森山達哉; 森山達哉 月刊アレルギーの臨床 (557) 2021年
• Clinical Academic Topics 大豆アレルゲン研究の最近の話題

  福住 綾乃; 松尾 綾人; 矢野 えりか; 財満 信宏; 森山 達哉 アレルギーの臨床 40 (5) 403 -406 2020年05月
• Clinical Academic Topics 大豆アレルゲン研究の最近の話題

  福住 綾乃; 松尾 綾人; 矢野 えりか; 財満 信宏; 森山 達哉 アレルギーの臨床 40 (5) 403 -406 2020年05月
• 気化したウコン精油のマウス体内移行と各種臓器への分布の検討

  松村 晋一; 須見 友子; 吉岡 百合; 牧野 祥平; 竹本 有希; 森山 達哉; 財満 信宏 日本薬学会年会要旨集 140年会 26P -pm240 2020年03月
• 経皮感作しうる大豆アレルゲンに関する研究

  日高翔太; 福住綾乃; 矢野えりか; 財満信宏; 財満信宏; 森山達哉; 森山達哉 アグリバイオ 4 (12) 2020年
• 経皮感作しうる食物アレルゲンに関する最近の知見

  日高翔太; 衣笠芹菜; 泉愛理; 福住綾乃; 財満信宏; 財満信宏; 森山達哉; 森山達哉 月刊アレルギーの臨床 (544) 2020年
• 植物性食物アレルゲンのリスク変動解析に関する研究

  日高翔太; 福住綾乃; 泉愛理; 衣笠芹菜; 矢野えりか; 財満信宏; 財満信宏; 森山達哉; 森山達哉 月刊アレルギーの臨床 (550) 2020年
• キウイタンパク質の経皮感作能の評価および経皮感作抗原の同定

  衣笠芹菜; 日高翔太; 泉愛理; 田中芹奈; 矢野えりか; 矢野えりか; 財満信宏; 財満信宏; 財満信宏; 森山達哉; 森山達哉; 森山達哉 日本食品科学工学会関西支部大会市民フォーラム講演要旨集 3rd 2020年
• チェリーの経皮感作能の検討と経皮感作抗原の同定及び特性解析

  泉愛理; 日高翔太; 衣笠芹菜; 廣井彩子; 矢野えりか; 矢野えりか; 財満信宏; 財満信宏; 財満信宏; 森山達哉; 森山達哉; 森山達哉 日本食品科学工学会関西支部大会市民フォーラム講演要旨集 3rd 2020年
• 花粉症関連リンゴアレルゲンMal d1の品種間差異について

  泉愛理; 澤田絵理奈; 矢野えりか; 財満信宏; 財満信宏; 森山達哉; 森山達哉 月刊アレルギーの臨床 40 (538) 154 -157 2020年
• 気化したウコン精油のマウス体内移行と各種臓器への分布の検討

  松村晋一; 須見友子; 吉岡百合; 牧野祥平; 竹本有希; 森山達哉; 森山達哉; 財満信宏; 財満信宏 日本薬学会年会要旨集(CD-ROM) 140th (Web) 26P -pm240 2020年
• 大動脈瘤・大動脈解離の成因 大動脈壁の循環不全によって誘導される脂肪細胞異常出現機構とその病理学的意義

  財満 信宏; 久後 裕菜; 森山 達哉 脈管学 59 (Suppl.) S149 -S149 2019年10月
• 腹部大動脈瘤の進展と破裂に及ぼす魚油の影響評価と血管組織中におけるEPA分布の可視化

  藤嶋 玲奈; 星野 健斗; 久後 裕菜; 毛利 陽平; 柳本 賢一; 財満 信宏; 森山 達哉 日本病態生理学会雑誌 28 (2) 44 -44 2019年07月
• 異所性脂肪細胞が関与する腹部大動脈瘤進展の新規病態

  久後 裕菜; 藤嶋 玲奈; 森山 達哉; 財満 信宏 日本病態生理学会雑誌 28 (2) 56 -56 2019年07月
• 大豆アレルゲンに関する最近の知見

  福住 綾乃; 松尾 綾人; 矢野 えりか; 財満 信宏; 森山 達哉 アレルギーの臨床 39 (7) 586 -589 2019年07月
• 食品素材として好適な黒大豆種皮由来素材の抗肥満効果

  森安 祐輝; 福本 知歩; 杢谷 奈々子; 高田 祐一; 矢野 えりか; 村瀬 浩; 水野 雅敏; 財満 信宏; 森山 達哉 日本栄養・食糧学会大会講演要旨集 73回 191 -191 2019年04月
• 福祉の現場から 成人における食物アレルギーの多様性 花粉症と経皮感作の関与

  日高 翔太; 高葢 秋穂; 小川 昂志; 矢野 えりか; 財満 信宏; 森山 達哉 地域ケアリング 21 (4) 89 -92 2019年04月
• 低栄養状態がマウス由来前駆脂肪細胞の脂肪蓄積とMMPs発現に及ぼす影響

  岩本和子; 吸原慧紀; 財満信宏; 財満信宏; 森山達哉; 森山達哉 日本農芸化学会大会講演要旨集(Web) 2019 ROMBUNNO.4B1a08 (WEB ONLY) 2019年03月
• イチョウ葉エキス、ピペリン含有ヒハツエキスおよびゴマリグナン溶解ウコン精油の単体および混合物での経口投与による血清および脳内移行に及ぼす影響 食べ合わせについて

  松村 晋一; 岩本 和子; 吉岡 百合; 竹下 文章; 川本 宏和; 財満 信宏 日本薬学会年会要旨集 139年会 (2) 173 -173 2019年03月
• Tabebuia avellanedaeから単離された脂肪蓄積予防活性を有するイリドイドの合成

  山下 光明; 畑 柊平; 早川 眞矢; 村上 穂乃佳; 福田 陽一; 家田 彩菜; 岩本 和子; 財満 信宏; 森山 達哉; 飯田 彰 2019年03月
• 脂肪細胞機能を調節しうる農作物由来食品成分に関する研究

  家田彩菜; 高田祐一; 岩本和子; 財満信宏; 財満信宏; 森山達哉; 森山達哉 アグリバイオ 3 (1) 47‐51 2019年01月
• 大動脈壁の循環不全によって誘導される脂肪細胞異常出現機構とその病理学的意義

  財満信宏; 財満信宏; 久後裕菜; 森山達哉; 森山達哉 脈管学(Web) 59 (supplement) 2019年
• チェリータンパク質の経皮感作の検討

  廣井彩子; 日高翔太; 財満信宏; 森山達哉; 財満信宏; 森山達哉; 財満信宏; 森山達哉 日本食品科学工学会関西支部大会市民フォーラム講演要旨集 2nd 2019年
• キウイタンパク質の経皮感作能の評価及び感作抗原の同定

  田中芹奈; 日高翔太; 衣笠芹菜; 泉愛理; 矢野えりか; 矢野えりか; 財満信宏; 財満信宏; 財満信宏; 森山達哉; 森山達哉; 森山達哉 日本栄養・食糧学会近畿支部大会および公開シンポジウム講演抄録集 58th 2019年
• 米ぬかタンパク質の経皮感作能の検討

  衣笠芹菜; 石川穂香; 日高翔太; 田中芹奈; 泉愛理; 矢野えりか; 矢野えりか; 財満信宏; 財満信宏; 財満信宏; 森山達哉; 森山達哉; 森山達哉 日本栄養・食糧学会近畿支部大会および公開シンポジウム講演抄録集 58th 2019年
• キウイタンパク質の経皮感作能の評価及び感作抗原の同定

  日高翔太; 田中芹奈; 泉愛理; 衣笠芹菜; 矢野えりか; 矢野えりか; 財満信宏; 森山達哉; 財満信宏; 森山達哉; 財満信宏; 森山達哉 日本食品科学工学会関西支部大会市民フォーラム講演要旨集 2nd 2019年
• アディポサイトカインやリポタンパク質の分泌に及ぼすエラグ酸代謝物の影響

  家田彩菜; 森安祐輝; 奥谷百々香; 財満信宏; 森山達哉; 財満信宏; 森山達哉; 財満信宏; 森山達哉 日本食品科学工学会関西支部大会市民フォーラム講演要旨集 2nd 2019年
• 経皮感作しうるアレルゲン・コンポーネント

  衣笠芹菜; 泉愛理; 日高翔太; 福住綾乃; 財満信宏; 財満信宏; 森山達哉; 森山達哉 月刊アレルギーの臨床 39 (534) 1029 -1032 2019年
• 遺伝子組換え大豆のアレルゲンレベルの解析

  松尾綾人; 松下佳穂; 矢野えりか; 矢野えりか; 財満信宏; 財満信宏; 財満信宏; 森山達哉; 森山達哉; 森山達哉 日本栄養・食糧学会大会講演要旨集 73rd 264 -264 2019年
• イチョウ薬エキス,ゴマ抽出物,ターメリックオイルの混合投与がマウス血清および脳内への機能性成分の移行に及ぼす影響の評価

  岩本和子; 松村晋一; 吉岡百合; 竹下文章; 川本宏和; 綾木郁人; 財満信宏; 財満信宏; 森山達哉; 森山達哉 日本栄養・食糧学会大会講演要旨集 73rd 309 -309 2019年
• 黒ゴマ中に含まれるタンニンは食品タンパク質の経皮感作を抑制する

  日高翔太; 高葢秋穂; 小川昂志; 村上浩規; 渡辺瑞生; 角木綾花; 岩本和子; 岩本和子; 矢野えりか; 矢野えりか; 財満信宏; 財満信宏; 財満信宏; 森山達哉; 森山達哉; 森山達哉 日本栄養・食糧学会大会講演要旨集 73rd 312 -312 2019年
• マウスモデル系による牛乳タンパク質の経皮感作抗原の探索

  日高翔太; 高宮隆樹; 小川昂志; 高蓋秋穂; 矢野えりか; 財満信宏; 財満信宏; 森山達哉; 森山達哉 月刊アレルギーの臨床 39 (527) 401 -404 2019年
• 循環不全が生じた腹部大動脈瘤壁に観察される脂肪細胞の異常出現とその出現機構

  財満信宏; 財満信宏; 久後裕菜; 森山達哉; 森山達哉 脂質生化学研究 61 214 -214 2019年
• 研究者の最新動向 生活習慣病を予防改善しうる食品成分に関する研究

  家田 彩菜; 高田 祐一; 岩本 和子; 財満 信宏; 森山 達哉 Precision Medicine 1 (2) 215 -218 2018年11月
• 血管壁に異常出現する脂肪細胞が腹部大動脈瘤破裂に及ぼす影響の評価

  財満 信宏; 久後 裕菜; 田中 宏樹; 佐々木 健; 浦野 哲盟; 海野 直樹; 森山 達哉 脈管学 58 (Suppl.) S255 -S255 2018年09月
• EPA高含有魚油投与が腹部大動脈瘤の進展と破裂に及ぼす影響の評価

  久後 裕菜; 財満 信宏; 田中 宏樹; 柳本 賢一; 佐々木 健; 浦野 哲盟; 海野 直樹; 森山 達哉 脈管学 58 (Suppl.) S255 -S255 2018年09月
• イメージングと質量分析 質量分析イメージングによって発見した、動脈硬化・腹部大動脈瘤における新規病態とそれらを標的とした予防・治療の可能性

  財満 信宏 JSBMS Letters 43 (Suppl.) 38 -38 2018年08月
• 「アレルギーの臨床」に寄せる 経皮感作とアレルゲン

  小川 昂志; 高葢 秋穂; 村上 浩規; 岩本 和子; 矢野 えりか; 財満 信宏; 森山 達哉 アレルギーの臨床 38 (5) 472 -475 2018年05月
• 中性脂肪蓄積心筋血管症の冠動脈における中膜嚢胞状融解性変化についての検討

  池田 善彦; 平野 賢一; 財満 信宏; 松本 学; 大郷 恵子; 植田 初江 日本病理学会会誌 107 (1) 331 -331 2018年04月
• 「花粉‐食物アレルギー症候群の病態と治療」に寄せる 各種食用豆類における花粉症関連食物アレルゲンの検出

  松尾綾人; 徳舛直樹; 矢野えりか; 財満信宏; 森山達哉 月刊アレルギーの臨床 38 (511) 264‐267 -267 2018年03月
• ゴマ由来セサミン・セサモリンの水中油型乳剤の粒子径が脳内移行に及ぼす影響

  松村 晋一; 岩本 和子; 久後 裕菜; 橋本 佳祐; 宮本 智絵; 財満 信宏; 森山 達哉; 吉岡 百合 日本薬学会年会要旨集 138年会 (2) 211 -211 2018年03月
• ゴマ由来セサミン・セサモリンの水中油型乳剤の粒子径が脳内移行に及ぼす影響

  松村 晋一; 岩本 和子; 久後 裕菜; 橋本 佳祐; 宮本 智絵; 財満 信宏; 森山 達哉; 吉岡 百合 日本薬学会年会要旨集 138年会 (2) 211 -211 2018年03月
• EPA高含有魚油投与が腹部大動脈瘤の進展と破裂に及ぼす影響の評価

  久後裕菜; 財満信宏; 財満信宏; 田中宏樹; 柳本賢一; 佐々木健; 浦野哲盟; 海野直樹; 海野直樹; 森山達哉; 森山達哉 脈管学(Web) 58 (supplement) 2018年
• 血管壁に異常出現する脂肪細胞が腹部大動脈瘤破裂に及ぼす影響の評価

  財満信宏; 財満信宏; 久後裕菜; 田中宏樹; 佐々木健; 浦野哲盟; 海野直樹; 海野直樹; 森山達哉; 森山達哉 脈管学(Web) 58 (supplement) 2018年
• アポリポタンパク質及びアディポサイトカインの分泌に及ぼすエラグ酸の影響

  家田彩菜; 高田祐一; 奥野悠子; 岩本和子; 財満信宏; 財満信宏; 財満信宏; 森山達哉; 森山達哉; 森山達哉 日本栄養・食糧学会近畿支部大会および公開シンポジウム講演抄録集 57th 2018年
• アポリポタンパク質及びアディポサイトカインの分泌に及ぼすエラグ酸の影響

  家田彩菜; 高田祐一; 奥野悠子; 岩本和子; 財満信宏; 財満信宏; 財満信宏; 森山達哉; 森山達哉; 森山達哉 日本食品科学工学会関西支部大会市民フォーラム講演要旨集 1st 2018年
• 「アレルギーの臨床」に寄せる―905―マウスモデル系を用いた卵白の経皮感作

  小川昂志; 高葢秋穂; 村上浩規; 岩本和子; 矢野えりか; 財満信宏; 森山達哉 月刊アレルギーの臨床 (508) 1389‐1393 2017年12月
• 【食物アレルギー】 食物アレルギーの現状と多様性

  村上 浩規; 財満 信宏; 森山 達哉 栄養 2 (4) 203 -213 2017年12月
• 【食物アレルギー】 食物アレルギーの現状と多様性

  村上 浩規; 財満 信宏; 森山 達哉 栄養 2 (4) 203 -213 2017年12月
• 魚油摂取がニコチン投与マウスの血管壁に及ぼす影響の評価

  星野健斗; 久後裕菜; 小野里恵; 宮本智絵; 橋本佳祐; 柳本賢一; 財満信宏; 森山達哉 日本栄養・食糧学会近畿支部大会および公開シンポジウム講演抄録集 56th 42 2017年11月
• 高シュークロース食の摂取が腹部大動脈瘤の進展・破裂に及ぼす影響の病理学的評価

  宮本智絵; 橋本佳祐; 久後裕菜; 財満信宏; 森山達哉 日本栄養・食糧学会近畿支部大会および公開シンポジウム講演抄録集 56th 49 2017年11月
• マウスモデル系を用いた卵白中の経皮感作抗原の同定と反応性比較

  小川昂志; 高葢秋穂; 村上浩規; 岩本和子; 矢野えりか; 財満信宏; 森山達哉 日本栄養・食糧学会近畿支部大会および公開シンポジウム講演抄録集 56th 50 2017年11月
• 花粉症関連大豆アレルゲンGly m4のELISA定量系の構築と検証

  花房佳世; 村上浩規; 岩本和子; 矢野えりか; 財満信宏; 森山達哉 日本栄養・食糧学会近畿支部大会および公開シンポジウム講演抄録集 56th 29 2017年11月
• 乳酸発酵と酵素消化によるアレルゲン低減化大豆食品の開発と評価

  植田啄也; 矢野えりか; 立垣愛郎; 財満信宏; 森山達哉 日本栄養・食糧学会近畿支部大会および公開シンポジウム講演抄録集 56th 29 2017年11月
• 腹部大動脈瘤の破裂機構の解明と破裂予防法の検討

  財満 信宏; 久後 裕菜; 田中 宏樹; 柳本 賢一; 佐々木 健; 浦野 哲盟; 海野 直樹; 森山 達哉 脂質生化学研究 59 43 -43 2017年06月
• 腹部大動脈瘤の破裂機構の解明と破裂予防法の検討

  財満 信宏; 久後 裕菜; 田中 宏樹; 柳本 賢一; 佐々木 健; 浦野 哲盟; 海野 直樹; 森山 達哉 脂質生化学研究 59 43 -43 2017年06月
• 血管壁に異常出現した脂肪細胞が腹部大動脈瘤破裂を誘導する

  久後 裕菜; 財満 信宏; 田中 宏樹; 毛利 陽平; 柳本 賢一; 佐々木 健; 浦野 哲盟; 海野 直樹; 森山 達哉 日本栄養・食糧学会大会講演要旨集 71回 340 -340 2017年04月
• 質量分析イメージング法による脂質の可視化 (特集 脂質分析の新展開)

  久後 裕菜; 山本 彩実; 森山 達哉; 財満 信宏 オレオサイエンス 16 (5) 225 -231 2016年05月
• ヒト腹部大動脈瘤の病理解析と新規モデル動物の作出

  財満 信宏; 久後 裕菜; 田中 宏樹; 海野 直樹; 森山 達哉 日本栄養・食糧学会大会講演要旨集 70回 295 -295 2016年04月
• 腹部大動脈瘤発症に対する魚油の予防効果の検討

  久後 裕菜; 財満 信宏; 毛利 陽平; 田中 宏樹; 柳本 賢一; 浦野 哲盟; 海野 直樹; 森山 達哉 日本栄養・食糧学会大会講演要旨集 70回 296 -296 2016年04月
• イメージング質量分析の食品科学への応用

  久後 裕菜; 山本 彩実; 森山 達哉; 財満 信宏 質量分析 64 (1) 11 -15 2016年
• 新しい腹部大動脈瘤動物モデルの開発 大動脈壁の虚血が瘤化を惹起する

  田中 宏樹; 財満 信宏; 佐々木 健; 山本 尚人; 犬塚 和徳; 佐野 真規; 斎藤 貴明; 杉澤 良太; 片橋 一人; 矢田 達朗; 今野 弘之; 浦野 哲盟; 瀬藤 光利; 海野 直樹 脈管学 55 (Suppl.) S122 -S122 2015年10月
• アントシアニンの体内動態解析

  財満 信宏; 稲葉 栞里; 藤森 隆道; 荘厳 哲哉; 小林 沙織; 森山 達哉 JSBMS Letters 40 (Suppl.) 98 -98 2015年08月
• アントシアニンの体内動態解析

  財満 信宏; 稲葉 栞里; 藤森 隆道; 荘厳 哲哉; 小林 沙織; 森山 達哉 JSBMS Letters 40 (Suppl.) 98 -98 2015年08月
• リンパ還流不全による静脈壁ならびに静脈周囲組織変性についての実験的検討

  田中 宏樹; 財満 信宏; 佐々木 健; 今野 弘之; 瀬藤 光利; 海野 直樹 静脈学 26 (3) 227 -235 2015年08月
• 新精米法による新たな機能性米の創出とその機能成分の可視化

  財満信宏; 郡俊之; 森山達哉; 川西孝彦; 寺下隆夫; 白坂憲章 日本農芸化学会大会講演要旨集(Web) 2015 4F26P08 (WEB ONLY) 2015年03月
• 新しい腹部大動脈瘤動物モデルの開発-大動脈壁の虚血が瘤化を惹起する-

  田中宏樹; 田中宏樹; 財満信宏; 佐々木健; 山本尚人; 犬塚和徳; 佐野真規; 斎藤貴明; 杉澤良太; 片橋一人; 矢田達朗; 今野弘之; 浦野哲盟; 瀬藤光利; 海野直樹 脈管学(Web) 55 (supplement) 2015年
• Tubulin tyrosine ligase-like 4 is important for maintaining the structural integrity of erythrocyte plasma membrane.

  F. Ijaz; K. Tsutsumi; Y. Hatanaka; T. Hatanaka; S. Asai-Akeida; N. Zaima; K. Ikegami; M. Setou MOLECULAR BIOLOGY OF THE CELL 25 2014年12月
• Tabebuia avellanedaeの抗酸化および骨吸収阻害活性

  上田和典; 上田和典; 笠井彩加; 土岐倉千智; 福田陽一; 福田陽一; 山下光明; 財満信宏; 森山達哉; 飯田彰 機能性食品と薬理栄養 8 (5) 461 2014年12月
• ドコサヘキサエン酸は腎がんの進展を抑制する(Docosahexaenoic acid inhibits the progression of renal cancer)

  高山 達也; 高岡 直久; 財満 信宏; 潭 成; 宮崎 美紀; 杉山 貴之; 森田 辰男; 瀬藤 光利; おおぞの せいいちろう 日本癌学会総会記事 73回 P -3212 2014年09月
• フトモモ科ペドラ・ウメ・カーの血糖降下作用成分

  飯田彰; 上田和典; 大川貴弘; 岩竹さゆり; 山本美里; 福田陽一; 山下光明; 財満信宏; 森山達哉 日本補完代替医療学会学術集会プログラム・抄録集 17th 86 2014年
• 伝統薬物タヒボの抗酸化および骨吸収阻害活性成分

  上田和典; 笠井彩加; 土岐倉千智; 福田陽一; 山下光明; 財満信宏; 森山達哉; 飯田彰 日本補完代替医療学会学術集会プログラム・抄録集 17th 88 2014年
• Ba-8 wx/ae二重変異体米の澱粉吸着型リゾホスファチヂルコリンの定量と胚乳部における局在解析(澱粉の構造・物性・利用,一般講演,日本応用糖質科学会平成25年度大会(第62回))

  庄野 陽祐; 小谷口 美也子; 藤原 美乃里; 中屋 慎; 財満 信宏; 北村 進一 応用糖質科学 : 日本応用糖質科学会誌 3 (3) B34 2013年08月
• Docosahexaenoic Acid Inhibits Cell Growth of Renal Cell Carcinoma

  T. Takayama; N. Zaima; N. Takaoka; M. Miyazaki; C. Tan; T. Sugiyama; H. Furuse; S. Mugiya; M. Setou; S. Ozono UROLOGY 80 (3) S247 -S248 2012年09月
• 動脈硬化の臨床と病理 腹部大動脈瘤壁外膜vaso vasorumの動脈硬化と瘤壁組織の低酸素についての病理学的研究

  海野 直樹; 田中 宏樹; 財満 信宏; 佐々木 健; 山本 尚人; 鈴木 実; 眞野 勇記; 佐野 真規; 斉藤 貴明; 杉澤 良太; 今野 弘之; 瀬藤 光利 脈管学 52 (Suppl.) S78 -S79 2012年09月
• Imaging mass spectrometry visualizes epidermal barrier ceramides and their immediate precursors

  N. Goto-Inoue; T. Hayasaka; N. Zaima; K. Nakajima; W. M. Holleran; S. Sano; M. Setou; Y. Uchida JOURNAL OF INVESTIGATIVE DERMATOLOGY 132 S54 -S54 2012年05月
• 腹部大動脈瘤壁外膜vaso vasorumの動脈硬化と瘤壁組織の低酸素についての病理学的研究

  海野直樹; 田中宏樹; 田中宏樹; 財満信宏; 財満信宏; 佐々木健; 山本尚人; 鈴木実; 眞野勇記; 佐野真規; 斉藤貴明; 杉澤良太; 今野弘之; 瀬藤光利 脈管学(Web) 52 (supplement) 2012年
• 除虫菊におけるピレトリンの局在

  武田健吾; 植田浩一; 財満信宏; 森山達哉; 河村幸雄; 畑中顯和; 松田一彦 日本農芸化学会大会講演要旨集(Web) 2012 2012年
• リンパ還流不全による静脈壁並びに静脈周囲組織変性についての実験的検討

  田中 宏樹; 海野 直樹; 山本 尚人; 鈴木 実; 眞野 勇記; 佐野 真規; 斉藤 貴明; 財満 信宏; 佐々木 健; 今野 弘之; 瀬藤 光利 脈管学 51 (Suppl.) S100 -S100 2011年09月
• 循環器疾患の制圧に向けて 心血管病理病態研究の新展開 腹部大動脈瘤と外膜の脂肪細胞化

  瀬藤 光利; 田中 宏樹; 財満 信宏; 海野 直樹; 今野 弘之 日本病理学会会誌 100 (1) 223 -223 2011年03月
• Dominant-negative effects of a novel mutation in the filamin myopathy (Retraction of vol 75, pg 547, 2010)

  S. Kono; T. Nishio; Y. Takahashi; N. Goto-Inoue; M. Kinoshita; N. Zaima; H. Suzuki; A. Fukutoku-Otsuji; M. Setou; H. Miyajima NEUROLOGY 75 (23) 2138 -2138 2010年12月
• Dominant-negative effects of a novel mutation in the filamin myopathy

  S. Kono; T. Nishio; Y. Takahashi; N. Goto-Inoue; M. Kinoshita; N. Zaima; H. Suzuki; A. Fukutoku-Otsuji; M. Setou; H. Miyajima EUROPEAN JOURNAL OF NEUROLOGY 17 527 -527 2010年09月
• 静脈逆流の影響を受けた大伏在静脈壁脂質分子の挙動

  田中 宏樹; 海野 直樹; 山本 尚人; 相良 大輔; 鈴木 実; 西山 元啓; 眞野 勇記; 佐野 真規; 斉藤 貴明; 井田 艶子; 岡田 晴子; 兼子 由美; 波多野 絹江; 財満 信宏; 瀬藤 光利 脈管学 50 (Suppl.) S275 -S275 2010年09月
• 質量顕微鏡法によるヒト脳脂質の分子イメージング(Molecular imaging of lipids in the human brain by mass spectrometry)

  由木 大; 財満 信宏; 杉浦 悠毅; 赤津 裕康; 橋詰 良夫; 山本 孝之; 藤原 正美; 杉山 圭吉; 瀬藤 光利 神経化学 49 (2-3) 689 -689 2010年08月
• MSの新展開 質量顕微鏡による血管壁構造の観察

  田中 宏樹; 財満 信宏; 海野 直樹; 瀬藤 光利 JSBMS Letters 35 (Suppl.) 37 -37 2010年08月
• 銀ナノ微粒子を用いたマウス網膜の質量分析イメージング

  早坂孝宏; 井上菜穂子; 財満信宏; SHRIVAS Kamlesh; 柏木行康; 山本真理; 中許昌美; 瀬藤光利 質量分析総合討論会講演要旨集 58th 246 2010年06月
• 一次性下肢静脈瘤における大伏在静脈の質量顕微鏡法による観察

  田中 宏樹; 海野 直樹; 山本 尚人; 相良 大輔; 鈴木 実; 西山 元啓; 眞野 勇記; 佐野 真規; 財満 信宏; 瀬藤 光利 静脈学 21 (2) 179 -179 2010年05月
• Autogenous Arteriovenous Graftの質量顕微鏡法による観察

  田中 宏樹; 海野 直樹; 山本 尚人; 相良 大輔; 鈴木 実; 西山 元啓; 眞野 勇記; 佐野 真規; 財満 信宏; 瀬藤 光利 日本血管外科学会雑誌 19 (2) 407 -407 2010年04月
• 一次性下肢静脈瘤の弁不全機序に関与する脂質分子の同定

  田中 宏樹; 海野 直樹; 山本 尚人; 相良 大輔; 鈴木 実; 西山 元啓; 眞野 勇記; 佐野 真規; 財満 信宏; 佐々木 健; 瀬藤 光利 日本外科学会雑誌 111 (臨増2) 247 -247 2010年03月
• Molecular imaging of lipids in the human brain by mass spectrometry

  Dai Yuki; Nobuhiro Zaima; Yuki Sugiura; Hiroyasu Akatsu; Yosio Hashizume; Takayuki Yamamoto; Masami Fujiwara; Keikichi Sugiyama; Mitsutoshi Setou NEUROSCIENCE RESEARCH 68 E333 -E333 2010年
• ミオパチー生検筋の質量分析顕微鏡を用いた多変量解析

  衣斐 達; 小澤 史子; 佐橋 功; 財満 信宏; 杉浦 悠毅; 瀬藤 光利; 西野 一三 臨床神経学 48 (12) 1118 -1118 2008年12月 [査読有り]
  
• 直接質量分析装置の疾患組織解析への応用

  財満 信宏; 杉浦 悠毅; 大熊 彩; 岡橋 里美; 野口 悟; 西野 一三; 衣斐 達; 小澤 史子; 佐橋 功; 瀬藤 光利 JSBMS Letters 33 (Suppl.) 85 -85 2008年08月 [査読有り]
  

産業財産権

• 特許第7244024号:ニコチン摂取の影響による血管壁のコラーゲン分解防止剤  

  財満 信宏, 松村 晋一, 吉岡 百合  学校法人近畿大学, 稲畑香料株式会社  202303014378758897
• 特許第7236119号:大動脈瘤の予防用医薬組成物および加工食品  

  財満 信宏, 久後 裕菜, 北野 幹浩, 廣田 益教, 平野 賢一  学校法人近畿大学, 株式会社八代, 国立大学法人大阪大学  202303011314199810
• 特開2023-001102:植物性色素を含有する組成物  2023年01月04日

  財満 信宏, 松村 晋一, 吉岡 百合, 須見 友子, 山田 和哉, 望月 雄斗, 野津 昌史, 小林 崇典  学校法人近畿大学, 稲畑香料株式会社, 三生医薬株式会社  202303007070948230
• 特開2022-056264:血管保護のためのターメリックオイルを含有する組成物、ならびにこのような組成物を含む飲食品および香料  2022年04月08日

  財満 信宏, 松村 晋一, 吉岡 百合, 牧野 祥平  学校法人近畿大学, 稲畑香料株式会社  202203006745231850
• 特開2021-159086:リグナン類化合物と精油と油脂とを含有する組成物  2021年10月11日

  財満 信宏, 松村 晋一, 吉岡 百合, 小林 崇典, 山田 和哉  学校法人近畿大学, 稲畑香料株式会社, 三生医薬株式会社  202103019521735477
• 特開2021-127338:リグナン類化合物を精油に溶解して含有する組成物  2021年09月02日

  財満 信宏, 松村 晋一, 岩本 好平, 牧野 祥平, 吉岡 百合, 南 久美子, 小林 崇典, 山田 和哉  学校法人近畿大学, 稲畑香料株式会社, 三生医薬株式会社  202103020743928905
• WO2020-003363:ニコチン摂取の影響による血管の劣化を防止するための健康食品または医薬組成物  2020年01月02日

  財満 信宏, 松村 晋一, 吉岡 百合  学校法人近畿大学, 稲畑香料株式会社  202103015177302587
• 特許第5810166号:糖尿病性心血管合併症の予防・治療剤  2015年09月18日

  平野 賢一, 安井 洋子, 池田 善彦, 瀬藤 光利, 財満 信宏  国立大学法人大阪大学, 国立研究開発法人国立循環器病研究センター, 国立大学法人浜松医科大学, 興和株式会社  201503018297550357
• WO2015-005393:大動脈瘤の予防または治療剤および容器詰飲食品  2015年01月15日

  財満 信宏, 毛利 陽平, 柳本 賢一, 韓 力  日本水産株式会社, 学校法人近畿大学  201703008544697195
• WO2013-031729:糖尿病性心血管合併症の予防・治療剤  2013年03月07日

  平野 賢一, 安井 洋子, 池田 善彦, 瀬藤 光利, 財満 信宏  国立大学法人大阪大学, 独立行政法人国立循環器病研究センター, 国立大学法人浜松医科大学, 興和株式会社  201503092442322982
• 特開2012-235715:大動脈瘤モデル動物  2012年12月06日

  海野 直樹, 田中 宏樹, 眞野 勇記, 佐野 真規, 財満 信宏, 瀬藤 光利, 佐々木 健  国立大学法人浜松医科大学  201203061928354202
• WO2011-007565:PPARγ阻害剤を用いる動脈瘤の予防および治療  2011年01月20日

  瀬藤 光利, 財満 信宏, 海野 直樹, 田中 宏樹  国立大学法人浜松医科大学  201303020895501645

受賞

• 2020年 15th J. Oleo Sci. Impact Award
  
• 2018年 日本栄養・食糧学会 奨励賞
   

  受賞者: 財満信宏
• 2017年 日本油化学会 第16回日本油化学会オレオサイエンス賞
   

  受賞者: 財満信宏
• 2012年 日本農芸化学会 日本農芸化学会2012年度大会トピックス賞
   

  受賞者: 財満信宏
• 2011年 日本農芸化学会 日本農芸化学会2011年度大会トピックス賞
   

  受賞者: 財満信宏
• 2011年 6th J.Oleo Sci. Impact Award
   

  受賞者: 財満信宏
• 2010年 J.Oleo Sci. Editors’ Award
   

  受賞者: 財満信宏
• 2009年 JOCS-ILSI JOCS-ILSI Japan Joint Symposium優秀ポスター賞
   

  受賞者: 財満信宏
• 2009年 日本油化学会 ヤングフェロー賞
   

  受賞者: 財満信宏

共同研究・競争的資金等の研究課題

• 腹部大動脈瘤予防法確立にむけた栄養学的基盤研究

  日本学術振興会：科学研究費助成事業 基盤研究(B)

  研究期間 : 2021年04月 -2025年03月 

  代表者 : 財満 信宏
• 食品香気成分と生体の未知なる関係を理解するための萌芽的研究

  日本学術振興会：科学研究費助成事業 挑戦的研究(萌芽)

  研究期間 : 2021年07月 -2024年03月 

  代表者 : 財満 信宏
• 血管周囲脂肪細胞による血管壁炎症に着目した腹部大動脈瘤形成の機序解明と治療戦略

  日本学術振興会：科学研究費助成事業 基盤研究(C)

  研究期間 : 2020年04月 -2023年03月 

  代表者 : 佐々木 健; 財満 信宏; 佐野 真規
• 腹部大動脈瘤の進展・破裂予防法の確立

  日本学術振興会：科学研究費助成事業 基盤研究(B)

  研究期間 : 2017年04月 -2021年03月 

  代表者 : 財満 信宏; 佐々木 健; 田中 宏樹

   

  腹部大動脈瘤は腹部大動脈の進行的な拡張を特徴とする疾患であり、大動脈の拡張につれて破裂のリスクが増加する。破裂した腹部大動脈瘤の救命リスクは著しく低く、破裂を予防することが重要であるが、これを実現するためには「破裂機構が完全には解明されていない」、「腹部大動脈瘤の治療薬が存在しない」、「腹部大動脈瘤の進展と食生活の関連に関する知見が少ない」などの課題が存在する。これまでに腹部大動脈瘤の進展・破裂予防法を確立することを目的として、①腹部大動脈瘤を予防しうる食品成分の探索とその作用機序の解明、②胸部大動脈瘤の病理解析、に関して本年度も引き続き研究を行った。以下にその概要を記す。 腹部大動脈瘤の進展を予防しうる機能性成分の探索を行い、大豆由来イソフラボンと黒大豆由来プロアントシアニジンに血管壁の脆弱化を予防する効果があることを見出し、その推定作用機序を報告した。また、我々はこれまでに腹部大動脈瘤壁に異常出現する脂肪細胞が破裂に関与している可能性があることを報告した。本年の解析では、動脈壁における間葉系幹細胞の分化異常が脂肪細胞の異常出現に関与する可能性を見出し、これを報告した。また、腹部大動脈瘤は男性に多い疾患であるが、破裂率は女性の方が高い。この原因は完全には明らかになっていない。本年度はこの原因を明らかにするための研究を行い、卵巣機能の低下が女性に形成される腹部大動脈瘤の進展促進に影響している可能性があることを見出し、これを報告した。
• 腹部大動脈瘤の進展・破裂予防法の確立

  文部省科学研究費 (基盤研究B)

  研究期間 : 2017年 -2020年 

  代表者 : 財満信宏
• 分光イメージング法による脂質分子の選択的可視化

  日本学術振興会：科学研究費助成事業 挑戦的萌芽研究

  研究期間 : 2016年04月 -2019年03月 

  代表者 : 財満 信宏

   

  日本人の死因の上位を占める疾患の原因となる動脈硬化症は、動脈壁内にコレステロールが蓄積することを特徴とする。我々は新たなタイプの動脈硬化病巣として、コレステロールエステルではなく、中性脂肪が蓄積するタイプの動脈硬化巣（中性脂肪蓄積心筋血管症）を発見した。中性脂肪蓄積心筋血管症は不明な点の多い病態であり、多くの知見の収集を必要とする段階であるが、現時点では、一般的な病態検査機関で中性脂肪蓄積心筋血管症と通常の動脈硬化病巣を区別するのは極めて困難である。本研究は、両者を区別するための手法の確立のために重要な技術基盤となる脂質の選択的な可視化に取り組み、これが可能な可能性をしめした。
• 分光イメージング法による脂質の選択的可視化

  文部省科学研究費 (挑戦的萌芽）

  研究期間 : 2016年04月 -2019年03月 

  代表者 : 財満信宏
• 質量顕微鏡を用いた病態検査法の開発

  日本学術振興会：科学研究費助成事業 若手研究(A)

  研究期間 : 2013年04月 -2017年03月 

  代表者 : 財満 信宏

   

  質量顕微鏡法は組織切片中に存在する物質の分布を可視化することができる質量分析手法を応用した手法である。これまでの病理染色では観察できなかった分子の可視化観察を可能にする手法であり、病態検査への応用が期待されているが、検出感度や特異性が十分ではない、得られたデータの病理学的な裏付けが不足している、などの問題点があった。本研究では、これまでの研究で基礎的な知見を多く有していた血管疾患をモデルにして、これらの問題解決に取り組み、検出感度と特異性の向上させる手法を明らかにしたほか、検出されたデータの病理学的意味の解明などに成功した。
• In situメタボロミクスによる機能性食品成分の新しい評価

  日本学術振興会：科学研究費助成事業 挑戦的萌芽研究

  研究期間 : 2013年04月 -2016年03月 

  代表者 : 財満 信宏

   

  食品に含まれる機能性成分には疾患を予防する効果があることが報告されている。機能性成分の作用機序に関する研究は多く行われているが、摂取した機能性成分が体内の「どこ」に「どのような形」で存在しているのかを評価する手法は十分には確立されていない。機能性成分が体内のどこにどのような形で存在しているのかを明らかにすることは、食品が私たちの体に与える影響のメカニズムを理解するための重要な手がかりとなる。本研究では、質量分析イメージングという技術を利用して、摂取した食品中の機能性成分が体の「どこ」に「どのような形で」分布し、その場で「どのような影響を与えるのか」を明らかにした。
• 質量顕微鏡を用いた新規疾患解析手法の実用性の検討

  文部省科学研究費 (基盤研究C)

  研究期間 : 2010年04月 -2013年03月 

  代表者 : 財満信宏
• 高品質な農林水産物・食品創出のための質量顕微鏡技術基盤の構築

  生物系特定産業技術研究支援センター：イノベーション創出基礎的研究推進事業

  研究期間 : 2009年04月 -2012年03月 

  代表者 : 財満信宏
• 質量顕微鏡を用いた新規疾患解析手法の実用性の検討

  日本学術振興会：科学研究費助成事業 基盤研究(C)

  研究期間 : 2010年 -2012年 

  代表者 : 財満 信宏

   

  本研究は新たな疾患組織検査手法として、質量顕微鏡法の実用性を向上させることを目的とするものである。質量顕微鏡法は組織切片を二次元に質量分析することによって、組織切片に存在する生体分子の局在を可視化する手法である。疾患検査法として質量顕微鏡法の実用性を判断するためには、多くの疾患に適用が可能であることを示すことが重要である。本研究期間にATGL変異症、粥状動脈硬化病巣、腹部大動脈瘤(AAA)の解析法を検討し、疾患発症時の代謝変動などを可視化した。
• 脂肪酸代謝疾患として捉える自閉症の生物学的基盤の解明

  日本学術振興会：科学研究費助成事業 新学術領域研究(研究課題提案型)

  研究期間 : 2009年 -2011年 

  代表者 : 松崎 秀夫; 財満 信宏; 岩田 圭子; 小川 美香子; 辻井 正次; 瀬藤 光利; 土屋 賢治; 伊東 宏晃; 間賀田 泰寛

   

  自閉症者血清中の脂質VLDL分画の低下から(1)自閉症者血清中の脂肪酸解析、(2)脂肪酸所見に基づく自閉症動物モデルの確立とその解析、(3)動物モデルを用いた新規自閉症治療法を検討した。その結果、VLDL分画の低下に関連の深い脂肪酸としてω６脂肪酸を含む6種類の脂肪酸を見出した。ついでCD38KOマウスに自閉症者同様の血清中脂質VLDL分画・ω６脂肪酸の低下を認め、血中ω６脂肪酸の低下を出生直後に補うと社会認識行動の修復につながることを見出した。VLDLR-Tgラットにも多動と組織中のアラキドン酸の欠乏が示された。
• 質量顕微分析を用いた疾患組織検査方法の確立

  文部科学省科研費 (若手研究B)

  研究期間 : 2008年04月 -2010年03月 

  代表者 : 財満信宏
• 質量顕微分析を用いた疾患組織検査方法の確立

  日本学術振興会：科学研究費助成事業 若手研究(B)

  研究期間 : 2008年 -2009年 

  代表者 : 財満 信宏

   

  現在の生検組織検査は染色などの生化学的手法によるものが一般的である。この生化学的手法は疾患の診断や病理解析には不可欠の技術であるが、ターゲット不明の疾患には不向きであるという欠点がある。原因不明疾患の解析ではノンターゲティングな病理解析の方法が必須である。本研究は、近年開発された質量顕微鏡を用いて簡便で多くの情報を得ることができる病態検査方法を検討し、ノンターゲティングで病理サンプル上の異常代謝物を同定する方法を確立した。

委員歴

• 2023年10月 - 現在   国立研究開発法人科学技術振興機構   創発的研究支援事業 アドバイザー
• 2023年09月 - 現在   日本食品分析学会   評議員
• 2022年03月 - 現在   国立研究開発法人科学技術振興機構   ERATO運営・評価委員会分化会委員
• 2021年04月 - 現在   日本栄養・食糧学会   参与
• 2020年04月 - 現在   Prince of Songkla University   Visiting instructor in Master of Science Program in Pharmacology
• 2020年01月 - 現在   Journal of Nutritional Science and Vitaminology   Editor
• - 現在   中性脂肪蓄積心筋症研究会   世話人
• - 現在   機能性健康米協会   理事
• - 現在   日本動脈硬化学会   評議員
• - 現在   中性脂肪学会   副理事長
• 2022年03月 - 2024年02月   日本食品科学工学会   関西支部運営委員
• 2019年 - 2019年   The National Science Centre（ポーランド）   Reviewer of scientific grant proposal
• 国立研究開発法人農業・食品産業技術総合研究機構   イノベーション創出強化研究推進事業評議委員

その他

• 2020年04月 - 現在  "オール近大"新型コロナウイルス感染症対策支援プロジェクト 研究提案代表 

  "オール近大"新型コロナウイルス感染症対策支援プロジェクト 実学教育の新しい在り方の模索と提示

その他のリンク

researchmap

https://researchmap.jp/zaima