基本情報

所属

• 保健科学研究院　保健科学部門　病態解析学分野

職名

• 准教授

学位

• 博士（保健科学）（北海道大学）

科研費研究者番号

• 60707602

J-Global ID

• 201701019279144833

プロフィール

• 2006年取得 臨床検査技師（登録番号：160066）
  2007年取得 第2種ME技術者（登録番号：2070623）
  2018年取得 健康食品管理士 認定資格（登録番号：11656）
  2018年修了 厚生労働省大臣の指定する「検体採取並びに味覚検査及び嗅覚検査の実施に必要な知識及び技能取得講習会」（登録番号：49000）

  
  

  2021年取得 認定臨床化学者 一般社団法人日本臨床化学会認定資格（登録番号：21-004）

  
  

   

研究キーワード

• LDL−TG   HDL   LDL   肝臓   分析   臨床検査   食品   酸化ストレス   リポタンパク質   脂質   

研究分野

• ライフサイエンス / 食品科学
• ライフサイエンス / 代謝、内分泌学
• ライフサイエンス / 栄養学、健康科学
• ライフサイエンス / 消化器内科学
• その他 / その他 / 病態検査学

担当教育組織

•  学士課程　医学部（保健学科）
•  修士課程　保健科学院
•  博士課程　保健科学院

職歴

• 2022年04月 - 現在 北海道大学大学院保健科学研究院 病態解析学分野 准教授
• 2016年11月 - 2022年03月 北海道大学大学院保健科学研究院 病態解析学分野 講師
• 2016年06月 - 2016年10月 北海道大学大学院保健科学研究院 健康科学分野 助教
• 2013年06月 - 2016年05月 National Institutes of Health Dr. Alan Remaley’s laboratory Postdoctoral fellow
• 2013年04月 - 2013年05月 北海道大学保健科学研究院 惠 淑萍研究室 博士研究員
• 2011年04月 - 2013年03月 日本学術振興会特別研究員 DC

学歴

• 2010年04月 - 2013年03月   北海道大学   大学院保健科学院   博士後期課程
• 2008年04月 - 2010年03月   北海道大学   大学院保健科学院   博士前期課程
• 2006年04月 - 2008年03月   北海道大学   医学部   保健学科検査技術科学専攻（三年次編入）
• 2003年04月 - 2006年03月   北海道大学   医療技術短期大学部   衛生技術学科

所属学協会

• 日本食品安全協会   日本医用マススペクトル学会   日本臨床検査医学会   日本臨床化学会   American Association for Clinical Chemistry   

研究活動情報

論文

• Kaempferol Improves Cardiolipin and ATP in Hepatic Cells: A Cellular Model Perspective in the Context of Metabolic Dysfunction-Associated Steatotic Liver Disease.

  Akiko Sakurai, Toshihiro Sakurai, Hsin-Jung Ho, Hitoshi Chiba, Shu-Ping Hui

  Nutrients 16 4 2024年02月11日 

  Targeting mitochondrial function is a promising approach to prevent metabolic dysfunction-associated steatotic liver disease (MASLD). Cardiolipin (CL) is a unique lipid comprising four fatty acyl chains localized in the mitochondrial inner membrane. CL is a crucial phospholipid in mitochondrial function, and MASLD exhibits CL-related anomalies. Kaempferol (KMP), a natural flavonoid, has hepatoprotective and mitochondrial function-improving effects; however, its influence on CL metabolism in fatty liver conditions is unknown. In this study, we investigated the effects of KMP on mitochondrial function, focusing on CL metabolism in a fatty liver cell model (linoleic-acid-loaded C3A cell). KMP promoted mitochondrial respiratory functions such as ATP production, basal respiration, and proton leak. KMP also increased the gene expression levels of CPT1A and PPARGC1A, which are involved in mitochondrial β-oxidation. Comprehensive quantification of CL species and related molecules via liquid chromatography/mass spectrometry showed that KMP increased not only total CL content but also CL72:8, which strongly favors ATP production. Furthermore, KMP improved the monolysocardiolipin (MLCL)/CL ratio, an indicator of mitochondrial function. Our results suggest that KMP promotes energy production in a fatty liver cell model, associated with improvement in mitochondrial CL profile, and can serve as a potential nutrition factor in preventing MASLD.
• Identification of a β-Carboline Alkaloid from Chemoselectively Derived Vanilla Bean Extract and Its Prevention of Lipid Droplet Accumulation in Human Hepatocytes (HepG2)

  Dya Fita Dibwe, Nire Takeishi, Saki Oba, Akiko Sakurai, Toshihiro Sakurai, Takayuki Tsukui, Hitoshi Chiba, Shu-Ping Hui

  Molecules 28 24 8024 - 8024 2023年12月09日 

  Targeting bioactive compounds to prevent lipid droplet accumulation in the liver, we explored an antioxidative extract from vanilla bean (Vainilla planifolia) after chemo-selective derivatization through heating and acid modification. The chemical analysis of vanilla bean extract through chemoselective derivatization resulted in the identification of sixteen compounds (34–50) using LC-MS/MS analysis. A β-carboline alkaloid with a piperidine C-ring and a vanillin moiety at C-1 (34) was identified by molecular networking and diagnostic fragmentation filtering approaches. β-carboline alkaloid 34 exhibited significant inhibitory activity of lipid droplet accumulation (LDAI) in oleic acid-loaded hepatocellular carcinoma HepG2 cells. The LDAI activity was associated with both activation of lipolysis and suppression of lipogenesis in the cells. The study indicates that crude plant extracts, following chemoselective derivatization, may contain bioactive compounds that could be beneficial in preventing hepatosteatosis and could serve as a source of lead compounds for drug development. This approach may be useful to investigate other mixtures of natural products and food resources.
• A Pacific Oyster-Derived Antioxidant, DHMBA, Protects Renal Tubular HK-2 Cells against Oxidative Stress via Reduction of Mitochondrial ROS Production and Fragmentation.

  Hsin-Jung Ho, Natsumi Aoki, Yi-Jou Wu, Ming-Chen Gao, Karin Sekine, Toshihiro Sakurai, Hitoshi Chiba, Hideaki Watanabe, Mitsugu Watanabe, Shu-Ping Hui

  International journal of molecular sciences 24 12 2023年06月13日 [査読有り]
   

  The kidney contains numerous mitochondria in proximal tubular cells that provide energy for tubular secretion and reabsorption. Mitochondrial injury and consequent excessive reactive oxygen species (ROS) production can cause tubular damage and play a major role in the pathogenesis of kidney diseases, including diabetic nephropathy. Accordingly, bioactive compounds that protect the renal tubular mitochondria from ROS are desirable. Here, we aimed to report 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA), isolated from the Pacific oyster (Crassostrea gigas) as a potentially useful compound. In human renal tubular HK-2 cells, DHMBA significantly mitigated the cytotoxicity induced by the ROS inducer L-buthionine-(S, R)-sulfoximine (BSO). DHMBA reduced the mitochondrial ROS production and subsequently regulated mitochondrial homeostasis, including mitochondrial biogenesis, fusion/fission balance, and mitophagy; DHMBA also enhanced mitochondrial respiration in BSO-treated cells. These findings highlight the potential of DHMBA to protect renal tubular mitochondrial function against oxidative stress.
• Oxidized Low-Density Lipoproteins Trigger Hepatocellular Oxidative Stress with the Formation of Cholesteryl Ester Hydroperoxide-Enriched Lipid Droplets

  Iku Sazaki, Toshihiro Sakurai, Arisa Yamahata, Sumire Mogi, Nao Inoue, Koutaro Ishida, Ami Kikkai, Hana Takeshita, Akiko Sakurai, Yuji Takahashi, Hitoshi Chiba, Shu-Ping Hui

  International Journal of Molecular Sciences 24 5 4281 - 4281 2023年02月21日 [査読有り]
   

  Oxidized low-density lipoproteins (oxLDLs) induce oxidative stress in the liver tissue, leading to hepatic steatosis, inflammation, and fibrosis. Precise information on the role of oxLDL in this process is needed to establish strategies for the prevention and management of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Here, we report the effects of native LDL (nLDL) and oxLDL on lipid metabolism, lipid droplet formation, and gene expression in a human liver-derived C3A cell line. The results showed that nLDL induced lipid droplets enriched with cholesteryl ester (CE) and promoted triglyceride hydrolysis and inhibited oxidative degeneration of CE in association with the altered expression of LIPE, FASN, SCD1, ATGL, and CAT genes. In contrast, oxLDL showed a striking increase in lipid droplets enriched with CE hydroperoxides (CE-OOH) in association with the altered expression of SREBP1, FASN, and DGAT1. Phosphatidylcholine (PC)-OOH/PC was increased in oxLDL-supplemented cells as compared with other groups, suggesting that oxidative stress increased hepatocellular damage. Thus, intracellular lipid droplets enriched with CE-OOH appear to play a crucial role in NAFLD and NASH, triggered by oxLDL. We propose oxLDL as a novel therapeutic target and candidate biomarker for NAFLD and NASH.
• リゾホスファチジルエタノールアミンと肝疾患

  櫻井俊宏, 惠淑萍

  臨床化学51巻3号 2022年08月
• Profiling of lysophosphatidylethanolamine molecular species in human serum and in silico prediction of the binding site on albumin.

  Nao Inoue, Toshihiro Sakurai, Yusuke Yamamoto, Hitoshi Chiba, Shu-Ping Hui

  BioFactors (Oxford, England) 48 5 1076 - 1088 2022年06月10日 [査読有り]
   

  Lysophosphatidylethanolamine (LPE) is a major lysophospholipid produced by phospholipids and binds to human serum albumin (HSA). LPEs may play various roles in vivo depending on the differences in their acyl chains. However, only few reports have been published on the biological functions of LPEs. Hence, we determined the exact relative abundance of the major LPEs in the serum of healthy participants (n = 8) using liquid chromatography-tandem mass spectrometry. Consequently, LPE 18:2 (24.1 ± 5.2%) was found to be the most abundant in serum. To understand the distribution of LPEs, the serum separated via gel-filtration high-performance liquid chromatography was subjected to quantitative measurement. LPEs were more observed in the albumin fraction than the lipoprotein fraction. We also performed a fluorescence displacement assay and an in silico molecular docking experiment using AutoDock to confirm the affinity and binding sites of the LPEs on HSA. The binding affinities of the LPEs for drug sites 1 and 2 on HSA were relatively low, with Ki values of approximately 11 and 3.8 μM, respectively. AutoDock analysis revealed the conformation of the LPEs bound to drug sites and the possibility of LPEs binding to other HSA sites. These findings could help to elucidate the biological and pathological functions of LPEs.
• Food-Derived β-Carboline Alkaloids Ameliorate Lipid Droplet Accumulation in Human Hepatocytes.

  Dya Fita Dibwe, Saki Oba, Nire Takeishi, Toshihiro Sakurai, Takayuki Tsukui, Hitoshi Chiba, Shu-Ping Hui

  Pharmaceuticals (Basel, Switzerland) 15 5 2022年05月05日 [査読有り]
   

  Lipid droplet accumulation (LDA) in hepatocytes is the initial stage of nonalcoholic fatty liver disease (NAFLD). In the search for natural compounds for the prevention of NAFLD, a series of β-carboline alkaloid derivatives, inspired by flazin and its derivative, newly identified in Crassostrea gigas Thunberg. extracts, were examined for LDA inhibition (LDAI) activity in oleic acid-loaded hepatocytes (HepG2). Eight compounds with a piperidine or pyridine C-ring were chemically synthesized (1-8). Among them, compounds 2 and 4 (flazin) with a carboxy group at C-3 and furfuryl alcohol moiety at C-1 showed low cytotoxicity and they exhibited significant LDAI activity. Compound 2 with piperidine C-ring was identified for the first time in C. gigas extract, and ameliorated the lipid accumulation with the LDAI value of 25.4%. Active compounds 2 and 4 significantly inhibited triacylglycerol species accumulation in cells. These compounds upregulated ATGL and downregulated SREBP1, FASN, and SCD1 genes, suggesting that they activated lipolysis and suppressed lipogenesis, respectively. These results suggest that β-carboline alkaloids, especially compounds 2 and 4, might be potentially useful for preventing NAFLD.
• Simple and Sensitive Method for the Quantitative Determination of Lipid Hydroperoxides by Liquid Chromatography/Mass Spectrometry

  Chongsheng Liang, Siddabasave Gowda B. Gowda, Divyavani Gowda, Toshihiro Sakurai, Iku Sazaki, Hitoshi Chiba, Shu Ping Hui

  Antioxidants 11 2 2022年02月 [査読有り]
   

  Lipid hydroperoxides (LOOH) are the initial products of the peroxidation of unsaturated lipids and play a crucial role in lipid oxidation due to their ability to decompose into free radicals and cause adverse effects on human health. Thus, LOOHs are commonly considered biomarkers of oxidative stress-associated pathological conditions. Despite their importance, the sensitive and selective analytical method for determination is limited, due to their low abundance, poor stability, and low ionizing efficiency. To overcome these limitations, in this study, we chemically synthesized eight fatty acid hydroperoxides (FAOOH), including FA 18:1-OOH, FA 18:2-OOH, FA 18:3-OOH, FA 20:4-OOH, FA 20:5-OOH, FA 22:1-OOH, FA 22:6-OOH as analytes, and FA 19:1-OOH as internal standard. Then, they were chemically labeled with 2-methoxypropene (2-MxP) to obtain FAOOMxP by one-step derivatization (for 10 min). A selected reaction monitoring assisted targeted analytical method was developed using liquid chromatography/tandem mass spectrometry (LC-MS/MS). The MxP-labelling improved the stability and enhanced the ionization efficiency in positive mode. Application of reverse-phase chromatography allowed coelution of analytes and internal standards with a short analysis time of 6 min. The limit of detection and quantification for FAOOH ranged from 0.1–1 pmol/µL and 1–2.5 pmol/µL, respectively. The method was applied to profile total FAOOHs in chemically oxidized human serum samples (n = 5) and their fractions of low and high-density lipoproteins (n = 4). The linoleic acid hydroperoxide (FA 18:2-OOH) and oleic acid hydroperoxide (FA 18:1-OOH) were the most abundant FAOOHs in human serum and lipoproteins. Overall, our validated LC-MS/MS methodology features enhanced detection and rapid separation that enables facile quantitation of multiple FAOOHs, therefore providing a valuable tool for determining the level of lipid peroxidation with potential diagnostic applications.
• Lysophosphatidylethanolamine Affects Lipid Accumulation and Metabolism in a Human Liver-Derived Cell Line

  Yusuke Yamamoto, Toshihiro Sakurai, Zhen Chen, Nao Inoue, Hitoshi Chiba, Shu Ping Hui

  Nutrients 14 3 2022年02月01日 [査読有り]
   

  The physiological functions of lysophosphatidylethanolamine (lysoPE) have not been fully elucidated. In this study, the effects of lysoPE on lipogenesis and lipolysis were investigated in a cultured human liver-derived cell line. The intracellular lipid profile was investigated in detail using liquid chromatography–tandem mass spectrometry (LC-MS/MS) to better understand the underlying mechanism. The expression of genes related to lipid metabolism and catabolism was analyzed using real-time PCR. LysoPE supplementation induced cellular lipid droplet formation and altered triacylglycerol (TAG) profiles. Furthermore, lysoPE downregulated expression of the TAG hydrolyzation regulation factor ATGL, and reduced the expression of fatty acid biosynthesis-related genes SREBP1 and SCD1. LC-MS/MS-based lipidomic profiling revealed that the addition of lysoPE 18:2 increased the PE species containing linoleic acyl, as well as the CE 18:2 species, likely due to the incorporation of linoleic acyl from lysoPE 18:2. Collectively, these findings suggest that lysoPE 18:2 is involved in lipid droplet formation by suppressing lipolysis and fatty acid biosynthesis. Thus, lysoPE might play a pathological role in the induction of fatty liver disease.
• Adverse Effects of Chrysene on Human Hepatocytes via Inducement of Oxidative Stress and Dysregulation of Xenobiotic Metabolism

  Zijian Zhu, Zhen Chen, Toshihiro Sakurai, Hitoshi Chiba, Shu-Ping Hui

  POLYCYCLIC AROMATIC COMPOUNDS 2021年12月 [査読有り]
   

  Chrysene is a four-ring polycyclic aromatic hydrocarbon, which has been demonstrated to induce adverse effects through the inducement of oxidative stress. However, the possible mechanisms and potential pathways of chrysene-induced oxidative damages are scarcely investigated. In the present study, oxidative stress and xenobiotic metabolism disorder were investigated in human hepatocytes. Chrysene could cause cell viability reduction and cellular reactive oxygen species accumulation in a dose-dependent manner from 10 to 400 ng/mL. Moreover, the mRNA expression detoxification phases, including phase I and phase II as xenobiotic metabolizing enzymes, along with phase III, were investigated by real-time PCR. The results showed that chrysene upregulated the phase I enzymes cytochrome P-450 1A1, 1A2, and epoxide hydrolase 1, while at the same time downregulated the phase II enzymes glutathione S-transferase alpha 1, NAD(P)H: quinone oxidoreductase 1, and the phase III transporters multiple drug resistant 1 and multidrug resistance-associated protein 2. Furthermore, the inflammatory markers tumor necrosis factor alpha, interleukin-6, interleukin-8, and cyclooxygenase-2 were increased, whereas the antioxidant transcription factor nuclear factor erythroid 2-related factor 2 and its regulated enzymes glutathione peroxidase1, heme oxygenase-1, and superoxide dismutase 2 were decreased. These data suggested that chrysene expressed oxidative stress to hepatocytes, resulting in cytotoxicity and inflammation, which might be due to the damage of the antioxidant system and xenobiotic metabolism.
• Comparison of dimension reduction methods on fatty acids food source study.

  Yifan Chen, Yusuke Miura, Toshihiro Sakurai, Zhen Chen, Rojeet Shrestha, Sota Kato, Emiko Okada, Shigekazu Ukawa, Takafumi Nakagawa, Koshi Nakamura, Akiko Tamakoshi, Hitoshi Chiba, Hideyuki Imai, Hiroyuki Minami, Masahiro Mizuta, Shu-Ping Hui

  Scientific reports 11 1 18748 - 18748 2021年09月21日 [査読有り]
   

  Serum fatty acids (FAs) exist in the four lipid fractions of triglycerides (TGs), phospholipids (PLs), cholesteryl esters (CEs) and free fatty acids (FFAs). Total fatty acids (TFAs) indicate the sum of FAs in them. In this study, four statistical analysis methods, which are independent component analysis (ICA), factor analysis, common principal component analysis (CPCA) and principal component analysis (PCA), were conducted to uncover food sources of FAs among the four lipid fractions (CE, FFA, and TG + PL). Among the methods, ICA provided the most suggestive results. To distinguish the animal fat intake from endogenous fatty acids, FFA variables in ICA and factor analysis were studied. ICA provided more distinct suggestions of FA food sources (endogenous, plant oil intake, animal fat intake, and fish oil intake) than factor analysis. Moreover, ICA was discovered as a new approach to distinguish animal FAs from endogenous FAs, which will have an impact on epidemiological studies. In addition, the correlation coefficients between a published dataset of food FA compositions and the loading values obtained in the present ICA study suggested specific foods as serum FA sources. In conclusion, we found that ICA is a useful tool to uncover food sources of serum FAs.
• A mouse model of short-term, diet-induced fatty liver with abnormal cardiolipin remodeling via downregulated Tafazzin gene expression.

  Toshihiro Sakurai, Zhen Chen, Arisa Yamahata, Takahiro Hayasaka, Hiroshi Satoh, Hirotaka Sekiguchi, Hitoshi Chiba, Shu-Ping Hui

  Journal of the science of food and agriculture 101 12 4995 - 5001 2021年02月05日 [査読有り]
   

  BACKGROUND: Cardiolipin (CL) helps maintain mitochondrial structure and function. Here we investigated whether a high carbohydrate diet (HCD) fed to mice for a short term (5 days) can modulate the CL level including that of monolysoCL (MLCL) in the liver. RESULTS: Total CL in the HCD group was 22% lower than that in the normal chow diet (NCD) group (P <0.05). CL72:8 level strikingly decreased by 93% (P <0.0001), whereas total nascent CL (CLs other than CL72:8) increased (P <0.01) in the HCD group. Moreover, total MLCL in the HCD group increased by 2.4-fold compared with that in the NCD group (P <0.05). Tafazzin expression in the HCD group was significantly downregulated compared with that in the NCD group (P <0.05). A strong positive correlation between nascent CL and total MLCL (r = 0.955, P <0.0001), and a negative correlation between MLCL and Tafazzin expression (r = -0.593, P = 0.0883) were observed. CONCLUSION: HCD modulated fatty acid compositions of CL and MLCL via Tafazzin in the liver, which could lead to mitochondrial dysfunction. This model may be useful for elucidating the relationship between fatty liver and mitochondrial dysfunction. This article is protected by copyright. All rights reserved.
• Analysis of serum lysophosphatidylethanolamine levels in patients with non-alcoholic fatty liver disease by liquid chromatography-tandem mass spectrometry.

  Yusuke Yamamoto, Toshihiro Sakurai, Zhen Chen, Takayuki Furukawa, Siddabasave Gowda B Gowda, Yue Wu, Kazuhiro Nouso, Yuki Fujii, Yuki Yoshikawa, Hitoshi Chiba, Shu-Ping Hui

  Analytical and bioanalytical chemistry 413 1 245 - 254 2020年10月22日 [査読有り]
   

  Lysophosphatidylethanolamines (LysoPEs) are the partial hydrolysis products of phosphatidylethanolamine. Despite the unique in vitro bioactivities of LysoPEs, there are limited reports on the pathophysiological role of LysoPEs in the serum, due to the lack of sensitive analytical methods for determination of each molecular species in clinical samples. Herein, we developed a highly sensitive quantitative method to profile the serum LysoPE species by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with selected reaction monitoring (SRM). The internal standard (IS), chemically synthesized in-house, and the lineup of seven major LysoPE species were used in this study. The limits of detection and quantification for each LysoPE species ranged within 0.5-3.3 pmol/mL and 1.0-5.0 pmol/mL, respectively. The combined concentrations of LysoPEs in the serum from healthy subjects (n = 8) and the patients with non-alcoholic fatty liver diseases (NAFLD) including simple steatosis (SS, n = 9) and non-alcoholic steatohepatitis (NASH, n = 27) were 18.030 ± 3.832, 4.867 ± 1.852, and 5.497 ± 2.495 nmol/mL, respectively. The combined and individual concentrations of LysoPEs, except for LysoPE 18:0, significantly decreased in the patients with NAFLD compared with those for the healthy subjects. However, no significant difference was observed between the SS and NASH groups. Our proposed LC-MS/MS method is valid and has advantages of small sample volume, high sensitivity, and simultaneous absolute quantitation for multiple molecular species. This method may enable diagnostic evaluation and elucidation of the as-yet uncovered pathophysiological role of LysoPEs.
• Low-Density Lipoprotein (LDL)-Triglyceride and Its Ratio to LDL-Cholesterol as Diagnostic Biomarkers for Nonalcoholic Steatohepatitis.

  Yuki Fujii, Kazuhiro Nouso, Hiroshi Matsushita, Kazuya Kariyama, Toshihiro Sakurai, Yuji Takahashi, Hitoshi Chiba, Shu-Ping Hui, Yasuki Ito, Motoko Ohta, Hiroyuki Okada

  The journal of applied laboratory medicine 5 6 1206 - 1215 2020年05月01日 [査読有り][通常論文]
   

  BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common type of liver disease, but it is difficult to distinguish its pathogenic phenotype, nonalcoholic steatohepatitis (NASH), from nonalcoholic fatty liver (NAFL) without a liver biopsy. We analyzed serum lipids, including low-density lipoprotein triglyceride (LDL-TG), to elucidate their usefulness for diagnosing NASH. PATIENTS AND METHODS: Serum samples obtained from 35 NASH and 9 NAFL biopsy-confirmed patients and 6 healthy volunteers (HLT) were studied for 13 lipid-related markers and compared between HLT, NAFL, and NASH groups. The relationship between histological findings and the lipid markers was also analyzed. RESULTS: There were significant differences in triglyceride, LDL-TG, the ratio of LDL-TG to the LDL-cholesterol (LDL-TG/LDL-C), small dense LDL-C, and apolipoprotein E between the three groups. Among the 5 lipid components, serum LDL-TG level and the ratio of LDL-TG to the LDL-cholesterol (LDL-TG/LDL-C) were significantly elevated in NASH. The median concentrations of LDL-TG in HLT, NAFL, and NASH were 9, 15, and 20 mg/dL (P < 0.001), and those of LDL-TG/LDL-C were 0.097, 0.102, and 0.173 (P < 0.001), respectively. Although the degree of steatosis was not correlated with the LDL-TG/LDL-C, the ratio was significantly higher in patients with lobular inflammation (P = 0.071), ballooning (P = 0.031), and fibrosis (P < 0.001). The area under the receiver operating characteristic curve of the ratio for distinguishing NASH from NAFL was 0.857. The rest of studied markers showed no significant utility. CONCLUSION: Serum LDL-TG levels and the LDL-TG/LDL-C ratio might serve as simple and noninvasive diagnostic biomarkers for NASH.
• Multivariate Analysis for Molecular Species of Cholesteryl Ester in the Human Serum.

  Yifan Chen, Shu-Ping Hui, Yusuke Miura, Sota Kato, Toshihiro Sakurai, Zhen Chen, Emiko Okada, Shigekazu Ukawa, Takafumi Nakagawa, Koshi Nakamura, Akiko Tamakoshi, Hitoshi Chiba, Hiroyuki Minami, Masahiro Mizuta

  Analytical sciences : the international journal of the Japan Society for Analytical Chemistry 36 3 373 - 378 2020年03月10日 [査読有り][通常論文]
   

  Cholesteryl ester (CE) is an ester of cholesterol and fatty acid (FA). Plasma CE reflects complicated metabolisms of cholesterol, phospholipids, lipoproteins, and dietary FAs. An informatics approach could be useful for analysis of the CE species. In this study, two basic dimension reduction methods, principal component analysis (PCA) and factor analysis, were applied to serum CE species determined by LC-MS/MS in a Japanese population (n = 545). PCA and factor analysis both reflected the size (concentration), food source, fat solubility, and biological aspect of the CE species. In a comparison between PCA (PC4) and factor analysis (factor 4), the latter was found to be more suggestive from a biological aspect of n-6 FAs. Cholesteryl docosahexaenoate (DHA) was found to be unique by a factor analysis, possibly relevant to the unique accumulation of DHA in the brain. An informatics approach, especially factor analysis, might be useful for the analysis of complicated metabolism of CE species in the serum.
• Identification of molecular species of phosphatidylcholine hydroperoxides in native and copper-oxidized triglyceride-rich lipoproteins in humans.

  Shrestha R, Chen Z, Miura Y, Yamamoto Y, Sakurai T, Chiba H, Hui SP

  Annals of clinical biochemistry 57 1 95 - 98 2020年01月 [査読有り][通常論文]
  
• Author Correction: Circulating Apolipoprotein L1 is associated with insulin resistance-induced abnormal lipid metabolism.

  Kenji Nishimura, Taichi Murakami, Toshihiro Sakurai, Masashi Miyoshi, Kiyoe Kurahashi, Seiji Kishi, Masanori Tamaki, Tatsuya Tominaga, Sumiko Yoshida, Kojiro Nagai, Hideharu Abe, Shu-Ping Hui, Kazuhiko Kotani, Toshio Doi

  Scientific reports 9 1 20270 - 20270 2019年12月27日 [査読有り]
   

  An amendment to this paper has been published and can be accessed via a link at the top of the paper.
• Novel Fluorescence-Based Method To Characterize the Antioxidative Effects of Food Metabolites on Lipid Droplets in Cultured Hepatocytes.

  Tsukui T, Chen Z, Fuda H, Furukawa T, Oura K, Sakurai T, Hui SP, Chiba H

  Journal of agricultural and food chemistry 67 35 9934 - 9941 2019年09月 [査読有り][通常論文]
   

  A fluorescence microscopic method for characterizing size, quantity, and oxidation of lipid droplets (LDs) in HepG2 cells was developed. LDs were induced by palmitic (PA), oleic (OA), or linoleic acids (LA) and stained with two fluorescent probes for neutral lipids and lipid peroxides. Each fatty acid increased the number of LDs and oxidized LDs (oxLDs) and the degree of LD oxidation time dependently, as well as increased intracellular triglyceride hydroperoxides. LDs induced by LA without 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH) showed the most significant oxidation degree over PA and OA, especially in large LDs (area ≥ 3 μm2, oxLD/LD = 52.3 ± 21.7%). Under this condition, two food-derived antioxidants were evaluated, and both of them significantly improved the LD characteristics. Moreover, chlorogenic acid reduced the quantity of large LDs by 74.0-87.6% in a dose-dependent manner. The proposed method provides a new approach to evaluate the effect of dietary antioxidants on LD characteristics.
• 糖化がLDLの物性に与える影響について(Effect of glycation on the physical properties of low density-lipoprotein)

  Takeda Seiji, Sakurai Toshihiro, Hui Shu-Ping, Chiba Hitoshi

  生物物理 59 Suppl.1-2 S310 - S310 2019年08月
• Analysis of molecular species of phosphatidylcholine hydroperoxide in human native and copper-oxidized triglyceride-rich lipoproteins

  シュレスタ ロジート

  Clinica Chimica Acta 439 S82 - S83 2019年06月 [査読有り][通常論文]
  
• Cover Image, Volume 99, Issue 4

  Journal of the Science of Food and Agriculture 2019年03月 [査読有り][通常論文]
  
• Composition of plasmalogens in serum lipoproteins from patients with non-alcoholic steatohepatitis and their susceptibility to oxidation.

  Ikuta A, Sakurai T, Nishimukai M, Takahashi Y, Nagasaka A, Hui SP, Hara H, Chiba H

  Clinica chimica acta; international journal of clinical chemistry 2019年02月 [査読有り][通常論文]
  
• Apolipoprotein C-II Mimetic Peptide Promotes the Plasma Clearance of Triglyceride Rich Lipid Emulsion and the Incorporation of Fatty Acids into Peripheral Tissues of Mice.

  Komatsu T, Sakurai T, Wolska A, Amar M, Sakurai A, Vaisman B, Sviridov D, Demosky S, Pryor M, Ikewaki K, Remaley AT

  Journal of Nutrition and Metabolism 2019 7078241  2019年01月 [査読有り][通常論文]
  
• Dietary salmon milt extracts attenuate hepatosteatosis and liver dysfunction in diet-induced fatty liver model.

  Sakurai T, Hayasaka T, Sekiguchi H, Satoh H, Chen Z, Chiba H, Hui SP

  Journal of the science of food and agriculture Wiley 2018年09月 [査読有り][通常論文]
  
• A two-step homogeneous assay for apolipoprotein E-containing high-density lipoprotein-cholesterol.

  Takahashi Y, Ito Y, Sakurai T, Wada N, Nagasaka A, Fujikawa M, Chiba H, Hui SP

  Annals of clinical biochemistry 4563218795212  2018年08月 [査読有り][通常論文]
  
• Development of a novel fluorescent activity assay for lecithin:cholesterol acyltransferase

  Toshihiro Sakurai, Akiko Sakurai, Boris L Vaisman, Takafumi Nishida, Edward B Neufeld, Stephen J Demosky, Maureen L Sampson, Robert D Shamburek, Lita A Freeman, Alan T Remaley

  Annals of Clinical Biochemistry 55 4 414 - 421 2018年07月01日 [査読有り][通常論文]
   

  Background: Lecithin:cholesterol acyltransferase (LCAT) is a plasma enzyme that esterifies cholesterol. Recombinant human LCAT (rhLCAT) is now being developed as an enzyme replacement therapy for familial LCAT deficiency and as a possible treatment for acute coronary syndrome. The current ‘gold standard’ assay for LCAT activity involves the use of radioisotopes, thus making it difficult for routine clinical use. Methods: We have developed a novel and more convenient LCAT activity assay using fluorescence-labelled cholesterol (BODIPY-cholesterol), which is incorporated into proteoliposomes as a substrate instead of radiolabelled cholesterol. Results: The apparent Km and Vmax were 31.5 µmol/L and 55.8 nmol/h/nmoL, rhLCAT, respectively, for the 3H-cholesterol method and 103.1 µmol/L and 13.4 nmol/h/nmol rhLCAT, respectively, for the BODIPY-cholesterol method. Although the two assays differed in their absolute units of LCAT activity, there was a good correlation between the two test assays (r = 0.849, P < 1.6 × 10−7, y = 0.1378x + 1.106). The BODIPY-cholesterol assay had an intra-assay CV of 13.7%, which was superior to the intra-assay CV of 20.8% for the radioisotopic assay. The proteoliposome substrate made with BODIPY-cholesterol was stable to storage for at least 10 months. The reference range (n = 20) for the fluorescent LCAT activity assay was 4.6–24.1 U/mL/h in healthy subjects. Conclusions: In summary, a novel fluorescent LCAT activity assay that utilizes BODIPY-cholesterol as a substrate is described that yields comparable results to the radioisotopic method.
• Effects of enzymes on elastic modulus of low-density lipoproteins were investigated using atomic force microscopy

  Seiji Takeda, Toshihiro Sakurai, Shu-Ping Hui, Hirotoshi Fuda, Hitoshi Chiba

  Biochemical and Biophysical Research Communications 501 3 607 - 611 2018年06月27日 [査読有り][通常論文]
   

  Oxidation of low-density lipoproteins (LDLs) induces development of cardiovascular disease. Recently, reports of studies using atomic force microscopy (AFM) have described that the elastic modulus of metal-induced oxidized LDLs is lower than the modulus before oxidation. However, the mechanisms of change of the elastic modulus have not been well investigated. We postulated that disorder of the LDL structure might decrease the elastic modulus. This study measured the elastic modulus of LDLs before and after enzyme treatment with V8 protease, α-chymotrypsin, and phospholipase A2. After LDLs were obtained from serum by ultracentrifugation, LDLs or enzyme-treated LDLs were physically absorbed. They were crowded on a mica surface. Although V8 protease and α-chymotrypsin did not induce the elastic modulus change, treatment with PLA2 decreased the elastic modulus. The LDL particle size did not change during the enzyme treatment. Results suggest that disordering of the lipid structure of the LDL might contribute to the elastic modulus change. Results show that AFM might be a useful tool to evaluate disorders of complex nanoscale particle structures from lipids and proteins such as lipoproteins.
• Dietary α-cyclodextrin reduces atherosclerosis and modifies gut flora in apolipoprotein E-deficient mice.

  Sakurai T, Sakurai A, Chen Y, Vaisman BL, Amar MJ, Pryor M, Thacker SG, Zhang X, Wang X, Zhang Y, Zhu J, Yang ZH, Freeman LA, Remaley AT

  Molecular nutrition & food research 61 8 2017年08月 [査読有り][通常論文]
   

  Scope: alpha-Cyclodextrin (alpha-CD), a cyclic polymer of glucose, has been shown to lower plasma cholesterol in animals and humans; however, its effect on atherosclerosis has not been previously described. Methods and results: apoE-knockout mice were fed either low-fat diet (LFD; 5.2% fat, w/w), or Western high fat diet (21.2% fat) containing either no additions (WD), 1.5% alpha-CD (WDA); 1.5% beta-CD (WDB); or 1.5% oligofructose-enriched inulin (WDI). Although plasma lipids were similar after 11 weeks on theWDvs. WDA diets, aortic atherosclerotic lesions were 65% less in mice on WDA compared toWD (P < 0.05), and similar tomice fed the LFD. No effect on atherosclerosis was observed for the other WD supplemented diets. By RNA-seq analysis of 16S rRNA, addition of alpha-CD to the WD resulted in significantly decreased cecal bacterial counts in genera Clostridium and Turicibacterium, and significantly increased Dehalobacteriaceae. At family level, Comamonadaceae significantly increased and Peptostreptococcaceae showed a negative trend. Several of these bacterial count changes correlated negatively with % atherosclerotic lesion and were associated with increased cecum weight and decreased plasma cholesterol levels. Conclusion: Addition of alpha-CD to the diet of apoE-knockoutmice decreases atherosclerosis and is associated with changes in the gut flora.
• Long-chain monounsaturated fatty acid-rich fish oil attenuates the development of atherosclerosis in mouse models

  Zhi-Hong Yang, Masahiro Bando, Toshihiro Sakurai, Ye Chen, Beatrice Emma-Okon, Bree Wilhite, Daiju Fukuda, Boris Vaisman, Milton Pryor, Yoshiyuki Wakabayashi, Maureen Sampson, Zu-Xi Yu, Akiko Sakurai, Abdalrahman Zarzour, Hiroko Miyahara, Jiro Takeo, Hiroshi Sakaue, Masataka Sata, Alan T. Remaley

  MOLECULAR NUTRITION & FOOD RESEARCH 60 10 2208 - 2218 2016年10月 [査読有り][通常論文]
   

  Scope: Fish oil-derived long-chain monounsaturated fatty acids (LCMUFA) containing chain lengths longer than 18 were previously shown to improve cardiovascular disease risk factors in mice. However, it is not known if LCMUFA also exerts anti-atherogenic effects. The main objective of the present study was to investigate the effect of LCMUFA on the development of atherosclerosis in mouse models. Methods and results: LDLR-KO mice were fed Western diet supplemented with 2% (w/w) of either LCMUFA concentrate, olive oil, or not (control) for 12 wk. LCMUFA, but not olive oil, significantly suppressed the development of atherosclerotic lesions and several plasma inflammatory cytokine levels, although there were no major differences in plasma lipids between the three groups. At higher doses 5% (w/w) LCMUFA supplementation was observed to reduce pro-atherogenic plasma lipoproteins and to also reduce atherosclerosis in ApoE-KO mice fed a Western diet. RNA sequencing and subsequent qPCR analyses revealed that LCMUFA upregulated PPAR signaling pathways in liver. In cell culture studies, apoB-depleted plasma from LDLR-K mice fed LCMUFA showed greater cholesterol efflux from macrophage-like THP-1 cells and ABCA1-overexpressing BHK cells. Conclusion: Our research showed for the first time that LCMUFA consumption protects against diet-induced atherosclerosis, possibly by upregulating the PPAR signaling pathway.
• Creation of Apolipoprotein C-II (ApoC-II) Mutant Mice and Correction of Their Hypertriglyceridemia with an ApoC-II Mimetic Peptides

  Toshihiro Sakurai, Akiko Sakurai, Boris L. Vaisman, Marcelo J. Amar, Chengyu Liu, Scott M. Gordon, Steven K. Drake, Milton Pryor, Maureen L. Sampson, Ling Yang, Lita A. Freeman, Alan T. Remaley

  JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 356 2 341 - 353 2016年02月 [査読有り][通常論文]
   

  Apolipoprotein C-II (apoC-II) is a cofactor for lipoprotein lipase, a plasma enzyme that hydrolyzes triglycerides (TGs). ApoC-II deficiency in humans results in hypertriglyceridemia. We used zinc finger nucleases to create Apoc2 mutant mice to investigate the use of C-II-a, a short apoC-II mimetic peptide, as a therapy for apoC-II deficiency. Mutant mice produced a form of apoC-II with an uncleaved signal peptide that preferentially binds high-density lipoproteins (HDLs) due to a 3-amino acid deletion at the signal peptide cleavage site. Homozygous Apoc2 mutant mice had increased plasma TG (757.5 +/- 281.2 mg/dl) and low HDL cholesterol (31.4 +/- 14.7 mg/dl) compared with wild-type mice (TG, 55.9 +/- 13.3 mg/dl; HDL cholesterol, 55.9 +/- 14.3 mg/dl). TGs were found in light (density < 1.063 g/ml) lipoproteins in the size range of very-low-density lipoprotein and chylomicron remnants (40-200 nm). Intravenous injection of C-II-a (0.2, 1, and 5 mu mol/kg) reduced plasma TG in a dose-dependent manner, with a maximum decrease of 90% occurring 30 minutes after the high dose. Plasma TG did not return to baseline until 48 hours later. Similar results were found with subcutaneous or intramuscular injections. Plasma half-life of C-II-a is 1.33 +/- 0.72 hours, indicating that C-II-a only acutely activates lipolysis, and the sustained TG reduction is due to the relatively slow rate of new TG-rich lipoprotein synthesis. In summary, we describe a novel mouse model of apoC-II deficiency and show that an apoC-II mimetic peptide can reverse the hypertriglyceridemia in these mice, and thus could be a potential new therapy for apoC-II deficiency.
• Development of homogeneous assay for simultaneous measurement of apoE-deficient, apoE-containing, and total HDL-cholesterol

  Yuji Takahashi, Yasuki Ito, Norio Wada, Atsushi Nagasaka, Masato Fujikawa, Toshihiro Sakurai, Rojeet Shrestha, Shu-Ping Hui, Hitoshi Chiba

  CLINICA CHIMICA ACTA 454 135 - 142 2016年02月 [査読有り][通常論文]
   

  Background: Pathophysiological role for high-density lipoprotein (HDL) subclasses remains to be elucidated. Homogeneous assay for simultaneous measurements of apoE-deficient HDL-cholesterol (HDL-C), apoE-containing HDL-.C, and total HDL-C is desired, because apoE plays important roles in lipid metabolism. Methods: The proposed assay consists of a primary reaction to remove non-HDL-C, a secondary reaction to measure apoE-deficient HDL-C, and a tertiary reaction to measure apoE-containing HDL-C. The assay is completed within 10 min. For control study, 13% polyethylene glycol precipitation assay and phosphotungstate-dextran sulfate -magnesium precipitation assay were carried out. Results: Good correlations between the control assays and the proposed assay was obtained in serum samples from patients without liver disease (n = 33): r = 0.987, 0.957, and 0.991 for apoE-deficient, apoE-containing, and total HDL-C, respectively. ApoE-containing HDL-C by the proposed method in healthy individuals (n = 12) and patients with hyper-HDL-cholesterolemia (n = 5) were 0.11 +/- 0.03 and 0.26 +/- 0.05 mmol/l (4.1 +/- 1.3 and 10.1 +/- 2.0 mg/dl), respectively. ApoE-containing HDL-C increased rapidly at >2.59 mmol/l (100 mg/dl) of total HDL-C, suggesting a unique regulating mechanism of apoE-containing HDL-C. Conclusions: The established homogeneous assay might be useful for clinical and epidemiological studies on apoE-deficient and apoE-containing HDL subclasses. (C) 2016 Elsevier B.V. All rights reserved.
• Practical technique to quantify small, dense low-density lipoprotein cholesterol using dynamic light scattering

  Trirongjitmoah S, Iinaga K, Sakurai T, Chiba H, Sriyudthsak M, Shimizu K

  Optical Review 23 2 265 - 272 2016年 [査読有り][通常論文]
  
• A Novel Apolipoprotein C-II Mimetic Peptide That Activates Lipoprotein Lipase and Decreases Serum Triglycerides in Apolipoprotein E-Knockout Mice

  Marcelo J. A. Amar, Toshihiro Sakurai, Akiko Sakurai-Ikuta, Denis Sviridov, Lita Freeman, Lusana Ahsan, Alan T. Remaley

  JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 352 2 227 - 235 2015年02月 [査読有り][通常論文]
   

  Apolipoprotein A-I (apoA-I) mimetic peptides are currently being developed as possible new agents for the treatment of cardiovascular disease based on their ability to promote cholesterol efflux and their other beneficial antiatherogenic properties. Many of these peptides, however, have been reported to cause transient hypertriglyceridemia due to inhibition of lipolysis by lipoprotein lipase (LPL). We describe a novel bihelical amphipathic peptide (C-II-a) that contains an amphipathic helix (18A) for binding to lipoproteins and stimulating cholesterol efflux as well as a motif based on the last helix of apolipoprotein C-II (apoC-II) that activates lipolysis by LPL. The C-II-a peptide promoted cholesterol efflux from ATP-binding cassette transporter ABCA1-transfected BHK cells similar to apoA-I mimetic peptides. Furthermore, it was shown in vitro to be comparable to the full-length apoC-II protein in activating lipolysis by LPL. When added to serum from a patient with apoC-II deficiency, it restored normal levels of LPL-induced lipolysis and also enhanced lipolysis in serum from patients with type IV and V hypertriglyceridemia. Intravenous injection of C-II-a (30 mg/kg) in apolipoprotein E-knockout mice resulted in a significant reduction of plasma cholesterol and triglycerides of 38 +/- 6% and 85 +/- 7%, respectively, at 4 hours. When coinjected with the 5A peptide (60 mg/kg), the C-II-a (30 mg/kg) peptide was found to completely block the hypertriglyceridemic effect of the 5A peptide in C57Bl/6 mice. In summary, C-II-a is a novel peptide based on apoC-II, which promotes cholesterol efflux and lipolysis and may therefore be useful for the treatment of apoC-II deficiency and other forms of hypertriglyceridemia.
• Identification of molecular species of cholesteryl ester hydroperoxides in very low-density and intermediate-density lipoproteins

  Rojeet Shrestha, Shu-Ping Hui, Toshihiro Sakurai, Akiko Yagi, Yuji Takahashi, Seiji Takeda, Shigeki Jin, Hirotoshi Fuda, Hitoshi Chiba

  ANNALS OF CLINICAL BIOCHEMISTRY 51 6 662 - 671 2014年11月 [査読有り][通常論文]
   

  Background Oxidation of lipoproteins is thought to play a crucial role in atherogenesis. Role for triglyceride-rich lipoproteins in atherogenesis is unclear. Thus, we aimed to investigate whether cholesteryl ester hydroperoxides (CEOOH) are present in very low-density lipoproteins (VLDL) and intermediate-density lipoproteins (IDL) by using highly sensitive liquid chromatography/mass spectrometry. Methods Total lipids were extracted from the plasma of healthy donors (n=6) and their fractions of VLDL and IDL. Additional three plasma samples were analysed freshly for CEOOH. Detection and identification of CEOOH was conducted by liquid chromatography/LTQ ion trap mass spectrometry/Orbitrap high mass accuracy mass spectrometry. Authentic standards of CEOOH were used for unequivocal identification on the basis of their mass spectra. Results We identified six molecular CEOOH species overall, namely, Ch18:1-OOH, Ch18:2-OOH, Ch18:3-OOH, Ch20:4-OOH, Ch20:5-OOH and Ch22:6-OOH. Of them, Ch18:2-OOH, Ch20:5-OOH, Ch20:4-OOH and Ch22:6-OOH were detected in all IDL samples, while only Ch20:4-OOH was detected in all VLDL samples. All of CEOOH species except for Ch18:3-OOH were detected in plasma, with constant detection of Ch20:5-OOH, and Ch22:6-OOH in all plasma samples. Conclusion The presence of CEOOH species in VLDL and IDL was confirmed with the analytical sensitivity of 0.1pmol, showing the constant appearance of more CEOOH species in IDL than VLDL. This finding might add biochemical evidences of atherogenicity of these lipoproteins. Clinical utility of measuring CEOOH level in these lipoproteins need to be investigated for the risk assessment of the cardiovascular disease.
• Serum choline plasmalogens-those with oleic acid in sn-2-are biomarkers for coronary artery disease

  Megumi Nishimukai, Ryouta Maeba, Akiko Ikuta, Naoya Asakawa, Kiwamu Kamiya, Shiro Yamada, Takashi Yokota, Mamoru Sakakibara, Hiroyuki Tsutsui, Toshihiro Sakurai, Yuji Takahashi, Shu-Ping Hui, Hitoshi Chiba, Tomoki Okazaki, Hiroshi Hara

  CLINICA CHIMICA ACTA 437 147 - 154 2014年11月 [査読有り][通常論文]
   

  Background: Identifying risk factors is crucial for preventing cardiovascular events, but there are no widely accepted predictive biomarkers. In our previous study of Japanese asymptomatic cohorts, we performed global analysis of serum ether glycerophospholipids (Egp) molecular profiles, and found that choline plasmalogens (PlsCho; 1-O-alk-1'-enyl-2-acyl-sn-glycero-3-phosphocholine), particularly those containing oleic acid (18:1) in the sn-2 position, were strongly associated with a wide range of risk factors for metabolic syndrome/atherosclerosis. Methods: We determined serum concentrations of Egp molecular species of coronary artery disease patients (n = 50; 31 males and 19 females) by LC/MS/MS, and plasmalogen (Pls; 1-O-alk-1'-enyl-2-acyl-sn-glycerophospholipids) contents in lipoprotein fractions by HPLC using radioactive iodine. Results: We found that the serum concentrations of ether choline glycerophospholipids (EgpCho), particularly PlsCho, were not only significantly lower in males with significant coronary stenosis but also associated with atherosclerosis-related parameters, and their association was stronger than either high-density lipoprotein cholesterol or adiponectin. In addition, serum PlsCho containing 18:1 or linoleic acid (18:2) in sn-2 showed the highest correlations with a wide range of atherogenic parameters among PlsCho molecular species. Conclusion: These results verify our previous findings that serum PlsCho, particularly those containing 18:1 in sn-2, may serve as reliable biomarkers for atherosclerosis. (C) 2014 Elsevier B.V. All rights reserved.
• Changes of lipoproteins in phenylalanine hydroxylase-deficient children during the first year of life

  Hironori Nagasaka, Hirokazu Tsukahara, Yoshiyuki Okano, Ken-ichi Hirano, Toshihiro Sakurai, Shu-Ping Hui, Toshihiro Ohura, Hiromi Usui, Tohru Yorifuji, Satoshi Hirayama, Akira Ohtake, Takashi Miida

  CLINICA CHIMICA ACTA 433 1 - 4 2014年06月 [査読有り][通常論文]
   

  Background: Influence of hyperphenylalaninemia on lipoproteins in early life remains unclear. Methods: We enrolled 24 phenylalanine hydroxylase (PAH)-deficient children who were classified into a phenylketonuria (PKU) group (n = 12) lacking PAH activity and a benign hyperphenylalaninemia (HPA) group (n = 12) having partial PAH activity, and their 11 non-affected siblings. We measured serum total-cholesterol, low-density lipoprotein (LDL)-cholesterol, and high-density lipoprotein (HDL)-cholesterol levels together with apolipoproteins for the first year of life, and compared them with those of 30 age-matched healthy controls. Results: The affected groups invariably had lower cholesterol levels than non-affected groups. At birth, HDL-cholesterol decrease was greatest and predominated over the LDL-cholesterol decrease: total cholesterol, 28/36% decrease to the control level in HPA/PKU; HDL-cholesterol, 33/51%; LDL-cholesterol, 20/28%. At 3 months, the opposite changes were observed: total cholesterol, 16/28%; HDL-cholesterol, 13/23%; LDL-cholesterol, 16/33%. At 12 months, LDL were still significantly lower in both groups (8/18%, p < .05 and .001), although HDL was significantly decreased only in the PKU group (15%, p < .05). Apolipoprotein A-I/A-II and B changed respectively in accordance with HDL-cholesterol and LDL-cholesterol changes. Despite similar phenylalanine levels, the PKU group invariably had lower cholesterol concentrations than the HPA group had. Conclusion: Irrespective of phenylalanine concentrations, lipoprotein synthesis in PAH-deficient children, particularly in PKU children, was suppressed in early life. (C) 2014 Elsevier B.V. All rights reserved.
• Serum choline plasmalogens, particularly those with oleic acid in sn-2, are associated with proatherogenic state

  Megumi Nishimukai, Ryouta Maeba, Yuya Yamazaki, Toru Nezu, Toshihiro Sakurai, Yuji Takahashi, Shu-Ping Hui, Hitoshi Chiba, Tomoki Okazaki, Hiroshi Hara

  JOURNAL OF LIPID RESEARCH 55 5 956 - 965 2014年05月 [査読有り][通常論文]
   

  Serum plasmalogens (Pls) (1-O-alk-1'-enyl-2-acyl glycerophospholipids) are of particular interest for studies on metabolic disorders associated with oxidative stress and chronic inflammation. Serum levels of Pls are known to correlate positively with HDL-cholesterol (HDL-C); however, few studies have examined serum Pls molecular species in association with pathophysiological conditions and their clinical significance. To clarify these, we determined serum levels of individual ether glycerophospholipids in Japanese asymptomatic cohorts (n = 428; 362 male and 66 female subjects) by LC/MS/MS, and examined their correlations with clinical parameters. We found that the proportion of choline Pls (PlsCho) among total serum phospholipids was significantly lower in the male group over 40 years old and was associated with multiple risk parameters more strongly than HDL-C. The abundance of serum PlsCho with oleic acid (18:1) in sn-2 exhibited the strongest positive correlation with serum concentrations of adiponectin and HDL-C, while being inversely associated with waist circumference and the serum levels of TG and small dense LDL-cholesterol. The characterization of serum ether glycerophospholipids verified the specificity of PlsCho, particularly the ones with 18:1 in sn-2, as a sensitive biomarker for the atherogenic state.
• Evaluation of Antioxidant Activity of Natural and Synthetic Compounds Against LDL Oxidation Using CNT Electrode

  Futaba Ohkawa, Seiji Takeda, Shu-Ping Hui, Toshihiro Sakurai, Shigeki Jin, Hirotoshi Fuda, Kazuhisa Sueoka, Hitoshi Chiba

  IEEE SENSORS JOURNAL 14 2 532 - 537 2014年02月 [査読有り][通常論文]
   

  In this paper, a novel method for evaluating antioxidant activity against low density lipoprotein (LDL) oxidation (anti-LDLox) using a carbon nanotube (CNT) based electrode was investigated. Although ORAC and DPPH are known methods to evaluate antioxidant activity, they do not directly reflect the capacities of anti-LDLox. A method has been reported for measuring oxidized LDL using a CNT electrode. We evaluated anti-LDLox by measuring the amount of oxidized LDL using the electrode after incubation of LDL with antioxidants during copper-mediated oxidation. Thiobarbituric acid reactive substances (TBARS) were also determined for comparison with the CNT electrode. There was a correlation of the CNT electrode with the TBARS and the ORAC, whereas no correlation was found between the CNT electrode and the DPPH. We demonstrate here that a CNT electrode method has a potential for the determination of the antioxidant activity of various natural and synthetic compounds by detecting oxidized LDL.
• Measurement of single low-density lipoprotein particles by atomic force microscopy

  Toshihiro Sakurai, Seiji Takeda, Jun-ya Takahashi, Yuji Takahashi, Norio Wada, Suchin Trirongjitmoah, Takeshi Namita, Shigeki Jin, Akiko Ikuta, Hiroaki Furumaki, Shu-Ping Hui, Hirotoshi Fuda, Masato Fujikawa, Koichi Shimizu, Hitoshi Chiba

  ANNALS OF CLINICAL BIOCHEMISTRY 50 6 564 - 570 2013年11月 [査読有り][通常論文]
   

  Background The size of lipoprotein particles is relevant to the risk of coronary artery disease (CAD). Methods We investigated the feasibility of atomic force microscopy (AFM) for evaluating the size of large low-density lipoprotein (LDL) and small dense LDL (sd-LDL) separated by ultracentrifugation. The measurements by AFM in tapping mode were compared to those by electron microscopy (EM). Results There was a significant difference in particle sizes determined by AFM between large LDL (20.61.9nm, mean +/- SD) and sd-LDL (16.2 +/- 1.4nm) obtained from six healthy volunteers (P<0.05). The particle sizes determined by EM for the same samples were 23.2 +/- 1.4nm for large LDL and 20.4 +/- 1.4nm for sd-LDL. The difference between large LDL and sd-LDL detected by EM was also statistically significant (P<0.05). In addition, the particle sizes of each lipoprotein fraction were significantly different between AFM and EM: P<0.05 for large LDL and P<0.05 for sd-LDL. Conclusions AFM can differentiate between sd-LDL and large LDL particles by their size, and might be useful for evaluating risk for CAD.
• Evaluation of Oxidized-Low-Density Lipoproteins Using Kelvin Force Microscopy

  Seiji Takeda, Futaba Ohkawa, Shu-Ping Hui, Toshihiro Sakurai, Shigeki Jin, Hirotoshi Fuda, Kazuhisa Sueoka, Hitoshi Chiba

  IEEE SENSORS JOURNAL 13 9 3449 - 3453 2013年09月 [査読有り][通常論文]
   

  Oxidized-low-density lipoprotein (ox-LDL), which is generated by LDL oxidation, is a risk factor of cardiovascular disease development. LDL has positive charges on the surface attributable to amino groups of lysine moieties on Apo B-100. Its positive charge is decreased by oxidation. For this paper, the topography and surface potential of LDL and ox-LDL are measured using atomic force microscopy and Kelvin probe force microscopy (KPFM). Although it is difficult to ascertain a difference between topographic images of LDL and ox-LDL, the KPFM images of ox-LDL differ from those obtained using LDL. The averaged potential of the surface decreases concomitantly with increasing oxidation time of the LDL. We demonstrate a method to evaluate the oxidation level of LDL using KPFM.
• Quantification of urinary 18-hydroxycortisol using LC-MS/MS

  Shigeki Jin, Norio Wada, Yuji Takahashi, Shu-Ping Hui, Toshihiro Sakurai, Hirotoshi Fuda, Seiji Takeda, Masato Fujikawa, Katsuyuki Yanagisawa, Shigeo Ikegawa, Takao Kurosawa, Hitoshi Chiba

  ANNALS OF CLINICAL BIOCHEMISTRY 50 5 450 - 456 2013年09月 [査読有り][通常論文]
   

  Background: Urinary 18-hydroxycortisol has been investigated as a marker of aldosterone-producing adenoma (APA). The aim of this study was to develop and validate a method for the measurement of 18-hydroxycortisol using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Methods: Urine was collected over a 24-hour period in patients with APA (n=11), idiopathic hyperaldosteronism (IHA, n=9), and essential hypertension (EH, n=6). 18-Hydroxycortisol was extracted in solid-phase, and measured by LC-MS/MS based on selected reaction monitoring. Results: The method allowed quantification of 18-hydroxycortisol with a lower quantification limit of 0.26nmol/L, intra- and inter-assay coefficients of variation of <3.4% and a range of analytical recovery of 98.0-103.7%. Urinary 18-hydroxycortisol excretion for APA, IHA and EH were determined as 725 (SD 451), 102 (SD 68) and 88 (SD 76) nmol/day, respectively. Conclusions: The proposed method met the basic analytical requirements and was considered to be useful in the screening and differential diagnosis of APA.
• Immunological detection of large oxidized lipoproteins in hypertriglyceridemic serum

  Toshihiro Sakurai, Norio Wada, Yuji Takahashi, Ayako Ichikawa, Akiko Ikuta, Hiroaki Furumaki, Shu-Ping Hui, Shigeki Jin, Seiji Takeda, Hirotoshi Fuda, Masato Fujikawa, Chikara Shimizu, Hironori Nagasaka, Hiroyuki Furukawa, Seiichi Kobayashi, Hitoshi Chiba

  ANNALS OF CLINICAL BIOCHEMISTRY 50 5 465 - 472 2013年09月 [査読有り][通常論文]
   

  Background: Triglyceride-rich, low-density lipoproteins (TG-rich LDL) have been reported as an oxidized lipoprotein species in patients with severe liver disease. Using TG-rich LDL as an immunogen, we obtained a monoclonal antibody (G11-6) that reacted with TG-rich LDL from patients with liver disease and with metal-oxidized LDL only in the early process of the oxidation reaction. This study determined the G11-6-reactive lipoproteins in hypertriglyceridemic serum. Methods: Serum samples from healthy volunteers (n=12) and hypertriglyceridemic patients (n=9) were fractionated by gel filtration and subjected to a sandwich enzyme-linked immunosorbent assay (ELISA) using G11-6 and polyclonal anti-apolipoprotein B antibodies. Results: Small LDL and larger lipoproteins reacted with G11-6. G11-6-reactive small LDL was identified in both the healthy subjects and hypertriglyceridemic patients, whereas G11-6-reactive larger lipoproteins were found only in the hypertriglyceridemic patients. Conclusions: G11-6 is a useful tool for detecting increased large oxidized lipoproteins in hypertriglyceridemic patients.
• Evaluation of various electrode materials for detection of oxidized low-density lipoproteins

  Seiji Takeda, Shu-Ping Hui, Hirotoshi Fuda, Shigeki Jin, Toshihiro Sakurai, Atsushi Ishii, Koichi Mukasa, Kazuhisa Sueoka, Hitoshi Chiba

  Journal of Biomedical Nanotechnology 9 2 303 - 306 2013年02月 [査読有り][通常論文]
   

  Measurement of oxidized low-density lipoprotein (LDL) generated by oxidative stress of various kinds might be useful for evaluating the risk of cardiovascular disease. We evaluated some electrode materials to detect oxidized LDL electrochemically. Some carbon nanotube dispersions were studied as electrode materials. Native LDL was isolated from normal human serum using ultracentrifugation. Oxidized LDL was prepared by treating the native LDL with CuSO4. Electrodes were fabricated by depositing the nanotube dispersion on a gold electrode, with subsequent drying. The potential change of the electrode against a reference electrode was monitored before and after adding native LDL or oxidized LDL. Only acid-treated carbon nanotubes were able to discriminate both LDL preparations, perhaps because of the carboxylic acid groups introduced on the nanotube by acid treatment. Copyright © 2013 American Scientific Publishers All rights reserved.
• Analysis of triacylglycerol hydroperoxides in human lipoproteins by Orbitrap mass spectrometer

  Shu-Ping Hui, Toshihiro Sakurai, Seiji Takeda, Shigeki Jin, Hirotoshi Fuda, Takao Kurosawa, Hitoshi Chiba

  Analytical and Bioanalytical Chemistry 405 14 4981 - 4987 2013年 [査読有り][通常論文]
   

  Herein, we represent a simple method for the detection and characterization of molecular species of triacylglycerol monohydroperoxides (TGOOH) in biological samples by use of reversed-phase liquid chromatography with a LTQ Orbitrap XL mass spectrometer (LC/LTQ Orbitrap) via an electrospray ionization source. Data were acquired using high-resolution, high-mass accuracy in Fourier-transform mode. Platform performance, related to the identification of TGOOH in human lipoproteins and plasma, was estimated using extracted ion chromatograms with mass tolerance windows of 5 ppm. Native low-density lipoproteins (nLDL) and native high-density lipoproteins (nHDL) from a healthy donor were oxidized by CuSO4 to generate oxidized LDL (oxLDL) and oxidized HDL (oxHDL). No TGOOH molecular species were detected in the nLDL and nHDL, whereas 11 species of TGOOH molecules were detected in the oxLDL and oxHDL. In positiveion mode, TGOOH was found as [M + NH4]+. In negativeion mode, TGOOH was observed as [M + CH3COO]-. TGOOH was more easily ionized in positive-ion mode than in negative-ion mode. The LC/LTQ Orbitrap method was applied to human plasma and three molecular species of TGOOH were detected. The limit of detection is 0.1 pmol (S/N=10:1) for each synthesized TGOOH. © Springer-Verlag Berlin Heidelberg 2013.
• Estimation of Scattering Coefficient in CW Reflectance Measurement for Noninvasive Triglyceride Evaluation

  Kazuya Iinaga, Takeshi Namita, Toshihiro Sakurai, Hitoshi Chiba, Koichi Shimizu

  2013 CONFERENCE ON LASERS AND ELECTRO-OPTICS PACIFIC RIM (CLEO-PR) 2013年 [査読有り][通常論文]
   

  For noninvasive measurement of the triglyceride in the blood, a technique was developed to estimate the scattering coefficient of a turbid medium from the backscattered intensity at two different points on the human body surface.
• Effects of acid oxidation on carbon nanotube based electrodes for detection of oxidized LDL

  Seiji Takeda, Toshihiro Sakurai, Futaba Ohkawa, Shigeki Jin, Shu-Ping Hui, Hirotoshi Fuda, Koichi Mukasa, Hitoshi Chiba, Kazuhisa Sueoka

  2013 IEEE SENSORS 1038 - 1041 2013年 [査読有り][通常論文]
   

  Carbon nanotubes are sometimes treated with an acid or mixture of acids to increase their solubility. From results of our study of single-walled carbon nanotubes, we reported that a CNT-based electrode can detect oxidation of low density-lipoproteins. As described herein, we investigated the effects of acid treatment time on electrode sensitivity for detection of oxidized low-density lipoproteins. Response capabilities of CNT-based electrodes for detecting ox-LDL were improved by acid treatment. However, further increased treatment time degraded their sensitivity. Although detailed mechanisms related to the response are under investigation, results show that an optimum condition exists for acid treatment condition to detect ox-LDL using an electrode.
• A phenolic antioxidant from the Pacific oyster (Crassostrea gigas) inhibits oxidation of cultured human hepatocytes mediated by diphenyl-1-pyrenylphosphine

  Mitsugu Watanabe, Hirotoshi Fuda, Shigeki Jin, Toshihiro Sakurai, Shu-Ping Hui, Seiji Takeda, Takayuki Watanabe, Takao Koike, Hitoshi Chiba

  FOOD CHEMISTRY 134 4 2086 - 2089 2012年10月 [査読有り][通常論文]
   

  3,5-Dihydroxy-4-methoxybenzyl alcohol (DHMBA), an antioxidant isolated from the Pacific oyster (Crassostrea gigas), was studied in a cell-based fluorometric antioxidant assay using human hepatocyte-derived cells (C3A) and diphenyl-1-pyrenylphosphine (DPPP) as a fluorescent probe. In comparison with two hydrophilic antioxidants. DHMBA showed the stronger inhibition of DPPP-mediated fluorescence than chlorogenic acid and L-ascorbic acid: at a concentration of 320 mu M of DPPP, the inhibition was 26.4 +/- 2.6%, 11.1 +/- 1.2%, and 0 +/- 2.0% for DHMBA, chlorogenic acid, and L-ascorbic acid, respectively (mean +/- SD, n = 4). Their relative oxygen radical absorbance capacities (ORAC) were dissociated with their cell-based antioxidant activities: 1.47 +/- 0.40, 4.57 +/- 0.30, and 0.53 +/- 0.13 mu mol TE/mu mol for DHMBA, chlorogenic acid, and L-ascorbic acid, respectively (mean +/- SD, n = 4). The amphiphilicity of DHMBA was better than chlorogenic acid and L-ascorbic acid might underlie this dissociation. Since the C3A cells are human hepatoma-derived cells, DHMBA might be useful in the prevention and treatment of liver diseases by involving an oxidation process. (C) 2012 Elsevier Ltd. All rights reserved.
• Novel monoclonal antibody recognizing triglyceride-rich oxidized LDLs associated with severe liver disease and small oxidized LDLs in normal subjects

  Toshihiro Sakurai, Ayako Ichikawa, Hiroyuki Furukawa, Norio Wada, Atsushi Nagasaka, Yuji Takahashi, Masato Fujikawa, Akiko Ikuta, Hiroaki Furumaki, Maiko Shiga, Chikara Shimizu, Shu-Ping Hui, Shigeki Jin, Seiji Takeda, Hirotoshi Fuda, Hironori Nagasaka, Seiichi Kobayashi, Hitoshi Chiba

  ANNALS OF CLINICAL BIOCHEMISTRY 49 Pt 5 456 - 462 2012年09月 [査読有り][通常論文]
   

  Background: Triglyceride-rich low-density lipoproteins (TG-rich LDLs) in the plasma of patients with severe liver disease are reported to change macrophages into foam cells in vitro. Methods: Male BALB/c mice were immunized with TG-rich LDLs isolated from the plasma of a patient with severe liver disease. The resulting monoclonal antibody (G11-6) was used in a sandwich enzyme-linked immunosorbent assay (ELISA) in combination with polyclonal anti-apolipoprotein B antibodies. The time course of copper-mediated LDL oxidation was monitored using this ELISA. The results were compared with those of the two commercial ELISAs for oxidized LDLs using DLH or ML25, thiobarbituric acid reactive substances and the optical absorbance for the conjugated dienes generated in lipid peroxides. Furthermore, the lipoprotein fractions separated by gel filtration were tested with this ELISA in healthy volunteers (n = 11) and patients (n = 3) with liver disease. Results: G11-6 reacted with oxidized LDLs during only the early phase of copper oxidation, being distinct from the other monoclonal antibodies and methods. G11-6 was confirmed to react with TG-rich LDLs in patients, while it reacted with small LDL particles in normal controls. Conclusions: The monoclonal antibody G11-6 is useful for detecting oxidized small LDLs in normal controls and oxidized TG-rich LDLs in patients with severe liver disease.
• Detection and characterization of cholesteryl ester hydroperoxides in oxidized LDL and oxidized HDL by use of an Orbitrap mass spectrometer

  Shu-Ping Hui, Toshihiro Sakurai, Futaba Ohkawa, Hiroaki Furumaki, Shigeki Jin, Hirotoshi Fuda, Seiji Takeda, Takao Kurosawa, Hitoshi Chiba

  ANALYTICAL AND BIOANALYTICAL CHEMISTRY 404 1 101 - 112 2012年07月 [査読有り][通常論文]
   

  Oxidation of cholesteryl esters in lipoproteins by reactive oxygen species yields cholesteryl ester hydroperoxides (CEOOH). In this study, we developed a novel method for identification and characterization of CEOOH molecules in human lipoproteins by use of reversed-phase liquid chromatography with an hybrid linear ion trap-Orbitrap mass spectrometer (LC-LTQ Orbitrap). Electrospray ionization tandem mass spectrometric analysis was performed in both positive-ion and negative-ion modes. Identification of CEOOH molecules was completed by use of high-mass-accuracy (MA) mass spectrometric data obtained by using the spectrometer in Fourier-transform (FT) mode. Native low-density lipoproteins (nLDL) and native high-density lipoproteins (nHDL) from a healthy donor were oxidized by CuSO4, furnishing oxidized LDL (oxLDL) and oxidized HDL (oxHDL). No CEOOH molecules were detected in the nLDL and the nHDL, whereas six CEOOH molecules were detected in the oxLDL and the oxHDL. In positive-ion mode, CEOOH was detected as [M + NH4](+) and [M + Na](+) ions. In negative-ion mode, CEOOH was detected as [M + CH3COO](-) ions. CEOOH were more easily ionized in positive-ion mode than in negative-ion mode. The LC-LTQ Orbitrap method was applied to human plasma and six species of CEOOH were detected. The limit of detection was 0.1 pmol (S/N = 5:1) for synthesized CEOOH.
• Quantitative determination of phosphatidylcholine hydroperoxides during copper oxidation of LDL and HDL by liquid chromatography/mass spectrometry

  Shu-Ping Hui, Yudai Taguchi, Seiji Takeda, Futaba Ohkawa, Toshihiro Sakurai, Shinobu Yamaki, Shigeki Jin, Hirotoshi Fuda, Takao Kurosawa, Hitoshi Chiba

  ANALYTICAL AND BIOANALYTICAL CHEMISTRY 403 7 1831 - 1840 2012年06月 [査読有り][通常論文]
   

  1-Palmitoyl-2-linoleoylphosphatidylcholine monohydroperoxide (PC 16:0/18:2-OOH) and 1-stearoyl-2-linoleoylphosphatidylcholine monohydroperoxide (PC 18:0/18:2-OOH) were measured by liquid chromatography/mass spectrometry (LC/MS) using nonendogenous 1-palmitoyl-2-heptadecenoylphosphatidylcholine monohydroperoxide as an internal standard. The calibration curves for synthetic PC 16:0/18:2-OOH and PC 18:0/18:2-OOH, which were obtained by direct injection of the internal standard into the LC/MS system, were linear throughout the calibration range (0.8-12.8 pmol). Within-day and between-day coefficients of variation were less than 10%, and the recoveries were between 86% and 105%. The limit of detection (LOD) and the limit of quantification (LOQ) were determined using synthetic standards. The LOD (signal-to-noise ratio 3:1) was 0.01 pmol, and the LOQ (signal-to-noise ratio 6:1) was 0.08 pmol for both PC 16:0/18:2-OOH and PC 18:0/18:2-OOH. With use of this method, the concentrations of PC 16:0/18:2-OOH and PC 18:0/18:2-OOH in the lipoprotein fractions during copper-mediated oxidation were determined. We prepared oxLDL and oxHDL by incubating native LDL and native HDL from human plasma (n = 10) with CuSO4 for up to 4 h. The time course of the PC 16:0/18:2-OOH and PC 18:0/18:2-OOH levels during oxidation consisted of three phases. For oxidized LDL, both compounds exhibited a slow lag phase and a subsequent rapidly increasing propagation phase, followed by a gradually decreasing degradation phase. In contrast, for oxidized HDL, both compounds initially exhibited a prompt propagation phase with a subsequent plateau phase, followed by a rapid degradation phase. The analytical LC/MS method for phosphatidylcholine hydroperoxides might be useful for the analysis of biological samples.
• Detection of oxidized LDL using a carbon nanotube electrode

  Seiji Takeda, Shu-Ping Hui, Keisuke Fukuda, Hirotoshi Fuda, Shigeki Jin, Toshihiro Sakurai, Atsushi Ishii, Koichi Mukasa, Kazuhisa Sueoka, Hitoshi Chiba

  SENSORS AND ACTUATORS B-CHEMICAL 166 833 - 836 2012年05月 [査読有り][通常論文]
   

  Oxidized low-density lipoproteins (LDLs) play a key role in cardiovascular disease development, but no convenient measurement method is available for them. Using a carbon nanotube (CNT) electrode, we measured oxidized LDL using amperometric detection. Treating SWCNT with a mixture of acids produced a CNT dispersion that yielded nanotube-based electrodes after deposition on a gold electrode and drying. Current was monitored in the nanotube electrode before and after adding LDL or oxidization of LDL Oxidized LDL changed the current more than 10 nA, although LDL addition induced no significant change. Our CNT electrode enables simple detection of oxidized LDL. (C) 2012 Elsevier B.V. All rights reserved.
• A novel murine model for non-alcoholic steatohepatitis developed by combination of a high-fat diet and oxidized low-density lipoprotein

  Yin Lin, Hiroaki Furumaki, Shiho Matsuoka, Toshihiro Sakurai, Masashi Kohanawa, Songji Zhao, Yuji Kuge, Nagara Tamaki, Hitoshi Chiba

  LABORATORY INVESTIGATION 92 2 265 - 281 2012年02月 [査読有り][通常論文]
   

  Not-alcoholic steatohepatitis (NASH) is the hepatic manifestation of metabolic syndrome that is characterized by steritosis, inflammation, and fibrosis, and may progress to cirrhosis and carcinoma. To investigate its pathogenic processes, we established a novel murine model for NASH by combination of a high-fat diet (HFD) and oxidized low-density lipoprotein (oxLDL). Mice that received HFD for 23 weeks showed hepatic steatosis, slight fibrosis, and a high level of lipid peroxidation compared with a regular diet (RD)-fed mice. Hepatic injury and elevated tumor necrosis factoor (TNF)-alpha mRNA expression were also detected in these mice. Moreover, oxLDL administration to HFD-fed mice during weeks 21-23 not only aggravated hepatic steatosis, fibrosis, and lipid metabolism, but also resulted in intense inflammation, including severe hepatic injury and inflammatory cell infiltration, which are the typical histological features of NASH. Inflammation was accompanied by increased gene expression of TNF-alpha and interleukin (IL)-6. Additionally, the livers of RD-fed animals treated with oxLDL during weeks 21-23 were characterized by foamy macrophages and inflammatory cell infiltration along with an elevated IL-6 mRNA level. These results suggest that an increased oxidative state, including HFD-induced intracellular lipid peroxidation and its extracellular source from oxLDL, is the actual trigger for hepatic inflammation in which liver injury is mediated by TNF-alpha: and inflammatory cell accumulation is dependent on HFD and oxLDL also induced insulin resistance in mice; additionally, oxLDL downregulated insulin secretion. In his model, CD36 overexpression was observed in the hepatocytes of HFD-fed mice and those treated with HFD and oxl DL, and in the hepatic macrophages of RD-fed mice immediately after oxLDL treatment. In vitro experiments indicated a rapid and transient elevation of CD36 on macrophage plasma membrane in response to oxLDL. Our findings demonstrate that CD36 expressed on hepatocytes and hepatic macrophages mediates the pathophysiology of NASH. Laboratory Investigation (2012) 92, 265-281; doi:10.1038/labinvest.2011.159; published online 7 November 2011
• Isolation and Characterization of a Phenolic Antioxidant from the Pacific Oyster (Crassostrea gigas)

  Mitsugu Watanabe, Hirotoshi Fuda, Shigeki Jin, Toshihiro Sakurai, Futaba Ohkawa, Shu-Ping Hui, Seiji Takeda, Takayuki Watanabe, Takao Koike, Hitoshi Chiba

  JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 60 3 830 - 835 2012年01月 [査読有り][通常論文]
   

  Using an oxygen radical absorbance capacity (ORAC) assay, antioxidant activity was detected in the ethanol extract of the Pacific oyster, which was purified by sequential extraction with organic solvents. The ethyl acetate fraction showed the strongest antioxidant activity and was further purified, yielding a single compound [as assessed by thin-layer chromatography (TLC) reverse-phase high-performance liquid chromatography (HPLC)]. This compound was identified as 3,5-dihydroxy4-metboxybenzyl alcohol on the basis of H-1 and C-13 nuclear magnetic resonance (NMR), heteronuclear multiple-bond correlz.tion (HMBC), and electrospray ionization-mass spectrometry (ESI-MS) spectral analyses, a conclusion that was confirmed bycheinical synthesis. The concentration of the compound was 6.7 mg/100 g of whole oyster meat wet weight. This azaphi'philic gritiosidant retarded the copper mediated oxidation of low density lipoproteins (LDLs) and the generation of,tr.ickarbitonc acid.teactive substances. Furthermore, the compound showed substantial antioxidant activity using the ORAC and 2,2-diphenyl-1-picrythy'drazyl (DPPH) assays compared to natural antioxidants. Although the same compound was previously found in brown algae, its presence in other organisms and antioxidant activity are reported here for the first time.
• Application of Kelvin force microscopy for evaluation of oxidized low-density lipoprotein

  Seiji Takeda, Futaba Ohkawa, Toshihiro Sakurai, Shigeki Jin, Hirotoshi Fuda, Shu-Ping Hui, Hitoshi Chiba, Kazuhisa Sueoka

  2012 IEEE SENSORS PROCEEDINGS 1751 - 1754 2012年 [査読有り][通常論文]
   

  Investigation of the properties of oxidized low-density lipoprotein is important because it is a risk factor of cardiovascular disease development. Low-density lipoprotein is known to have a positive charge on the surface attributable to amino groups of lysine moieties. Its positive charge can be decreased by oxidation. For this study, the topography and surface potential of LDL and ox-LDL were measured using atomic force microscopy and Kelvin probe force microscopy. The Kelvin probe force microscopy images of ox-LDL differ from those obtained using n-LDL. We demonstrated a method to evaluate the oxidation level of LDL using AFM and KPFM.
• Measurement of lipoprotein particle sizes using dynamic light scattering

  Toshihiro Sakurai, Suchin Trirongjitmoah, Yuka Nishibata, Takeshi Namita, Masahiro Tsuji, Shu-Ping Hui, Shigeki Jin, Koichi Shimizu, Hitoshi Chiba

  ANNALS OF CLINICAL BIOCHEMISTRY 47 Pt 5 476 - 481 2010年09月 [査読有り][通常論文]
   

  Background: A simple method for the measurement of LDL particle sizes is needed in clinical laboratories because a predominance of small, dense LDL (sd LDL) has been associated with coronary heart disease. We applied dynamic light scattering (DLS) to measure lipoprotein particle sizes, with special reference to sd LDL. Methods: Human serum lipoproteins isolated by a combination of ultracentrifugation and gel chromatography, or by sequential ultracentrifugation, were measured for particle size using DLS. Results: The sizes of polystyrene beads, with diameters of 21 and 28 nm according to the manufacturer, were determined by DLS as 19.3 +/- 1.0 nm (mean +/- SD, n = 11) and 25.5 +/- 1.0 nm, respectively. The coefficients of variation for the 21 and 28 nm beads were 5.1% and 3.8% (within-run, n = 11), and 2.9% and 6.2% (between-run, n = 3), respectively. The lipoprotein sizes determined by DLS for lipoprotein fractions isolated by chromatography were consistent with the elution profile. Whole serum, four isolated lipoprotein fractions (CM + VLDL + IDL, large LDL, sd LDL and HDL) and a non-lipoprotein fraction isolated by sequential ultracentrifugation were determined by DLS to be 13.1 +/- 7.5, 37.0 +/- 5.2, 21.5 +/- 0.8, 20.3 +/- 1.1, 8.6 +/- 1.5 and 8.8 +/- 2.0 nm, respectively. Conclusions: The proposed DLS method can differentiate the sizes of isolated lipoprotein particles, including large LDL and sd LDL, and might be used in clinical laboratories in combination with convenient lipoprotein separation.
• Fraction estimation of small, dense LDL using autocorrelation function of dynamic light scattering

  Suchin Trirongjitmoah, Toshihiro Sakurai, Kazuya Iinaga, Hitoshi Chiba, Koichi Shimizu

  OPTICS EXPRESS 18 6 6315 - 6326 2010年03月 [査読有り][通常論文]
   

  Small, dense low-density lipoprotein (sdLDL) in total LDL is strongly related with the cardiovascular risk level. An optical technique using dynamic light scattering (DLS) measurement is useful for point-of-care testing of sdLDL. However, the sdLDL fraction estimated from the particle size distribution in DLS data is sensitive to noise and artifacts. Therefore, we derived analytical solutions in a closed form to estimate the fraction of scatterers using the autocorrelation function of scattered light from a polydisperse solution. The effect of the undesired large particles can be eliminated by the pre-processing of the autocorrelation function. The proposed technique was verified using latex standard particles and LDL solutions. Results suggest the feasibility of this technique to estimate the sdLDL fraction using optical scattering measurements. (C) 2010 Optical Society of America
• An improved HPLC assay for phosphatidylcholine hydroperoxides (PCOOH) in human plasma with synthetic PCOOH as internal standard

  Shu-Ping Hui, Hitoshi Chiba, Toshihiro Sakurai, Chitose Asakawa, Hironori Nagasaka, Tsuyoshi Murai, Hajime Ide, Takao Kurosawa

  JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES 857 1 158 - 163 2007年09月 [査読有り][通常論文]
   

  Quantitative and qualitative analyses of 1-palmitoyl-2-linoleoyl-phosphatidylcholne monohydroperoxide [PC 16:0/18:2-OOH] and 1-stearoyl-2-linoleoyl-phosphatidylcholine monohydroperoxide [PC 18:0/18:2-OOH] in human plasma were improved by chemiluminescence HPLC using synthetic 1-stearoyl-2-erucoyl-phosphatidylcholine monohydroperoxide (PC 18:0/22:1-OOH) as internal standard. The calibration curves of synthetic PC 16:0/18:2-OOH and PC 18:0/18:2-OOH, obtained by their direct injections with the IS into the HPLC system, were linear throughout the calibration range (10-1000 pmol). Within-day and between-day coefficients of variation were below 8%, and the recoveries were between 84% and 101%. Plasma concentrations of PC 16:0/18:2-OOH and PC 18:0/18:2-OOH were 102 +/- 59 nM (mean +/- SD) and 36 +/- 120 nM. respectively, in the 33 healthy volunteers. The present method might help understanding incompletely understood pathway of plasma phosphatidylcholine hydroperoxides. (c) 2007 Elsevier B.V. All rights reserved.

書籍

• 知っておきたい臨床検査値 第2版

  櫻井 俊宏, 高橋 祐司, 分担執筆, 範囲, 章, 梅毒血清 (範囲:櫻井 俊宏, 高橋 祐司 (担当: 分担執筆, 範囲: 第12章 梅毒血清反応))
  東京化学同人 2019年03月
• Medical Technology

  櫻井 俊宏 (担当:共著範囲:Small dense LDL)
  医歯薬出版 2010年12月

講演・口頭発表等

• 道産食材の機能性の探索  [招待講演]

  櫻井俊宏

  健康食品管理士会北海道支部秋季研修会/市民公開講座 2023年09月
• 尿中コレステリルエステルと腎障害の関連  [招待講演]

  櫻井俊宏, 三浦佑介, 高田康徳, Divyavani Gowda, 陳 震, 関島将人, 千葉仁志, 惠淑萍

  第7回日本医用マススペクトル学会東部会 2022年08月
• NASH鑑別マーカーとしての血中LDL-TG値の有用性

  櫻井俊宏

  第60回日本臨床化学会年次学術集会, YIAシンポジウム 2020年10月
• LDL-TG測定試薬の臨床検体への応用  [通常講演]

  櫻井俊宏

  第58回日本臨床化学会年次学術集会 若手育成シンポジウム 2018年08月 シンポジウム・ワークショップパネル（指名）
• 研究留学を振り返って  [通常講演]

  櫻井 俊宏

  北海道大学大学院保健科学研究院 保健科学セミナー 2016年06月 公開講演，セミナー，チュートリアル，講習，講義等
• Efficacy of apoC-II mimetic peptide in novel Apoc2 mutant mice with hypertriglyceridemia and impaired insulin sensitivity  [通常講演]

  Toshihiro Sakurai

  Arteriosclerosis, Thrombosis and Vascular Biology/Peripheral Vascular Disease Annual Conference 2016年05月
• Injection of apoC-II mimetic peptide normalizes triglycerides in apoC-II knockout mice, a new model of hypertriglyceridemia  [通常講演]

  Toshihiro Sakurai

  NHLBI DIR Research Festival 2015 2015年06月 口頭発表（一般）
• Increase of oxidized lipoproteins in liver disease, detected by monoclonal antibody recognizing early lipoprotein change during copper-oxidation  [通常講演]

  Toshihiro Sakurai

  European atherosclerosis society congress annual conference 2012 2012年05月 ポスター発表
• 原子間力顕微鏡によるリポ蛋白の1粒子計測  [通常講演]

  櫻井 俊宏

  第44回日本臨床検査医学会北海道支部総会 シンポジウム、パネルディスカッション 2010年10月 シンポジウム・ワークショップパネル（指名）
• Evaluation of Lipoprotein Particle Sizes Using Dynamic Light Scattering  [通常講演]

  Toshihiro Sakurai

  American Association for Clinical Chemistry annual conference 2010 2010年07月 ポスター発表

その他活動・業績

• Enhancement of mitochondrial function with kaempferol, contained as glycoside in Aojiru

  Sakurai A, Sakurai T, Ho HJ, Chiba H, Hui SP The Indian Scientists Association in Japan 2023年11月
• Determination of plasma lysophosphatidylethanolamine levels in preadolescent children

  Inoue N, Gowda SGB, Gowda D, Sakurai T, Ketema RM, Ikeda A, Chiba H, Hui SP The 6th FHS International Conference 2023年10月
• Sasa M, Sakurai T, Ishida K, Chiba H, Hui SP

  Search for, Oxidized High-Density Lipoprotein Receptor in, Human Liver-Derived Cell Line The 6th FHS International Conference 2023年10月
• Lipidomic Analysis of Very-Low Density Lipoprotein Released from Human Liver-Derived Cell Line

  Masuko N, Sakurai T, Yamahata A, Sazaki I, Mogi S, Chiba H, Hui SP The 6th FHS International Conference 2023年10月
• The effect of 12-EPAHSA on mitochondrial morphology in fatty liver model cells

  Takeshita H, Sakurai T, Gowda SGB, Chiba H, Hui SP The 6th FHS International Conference 2023年10月
• Kaempferol Improves Mitochondrial Respiratory Function in Human Liver-Derived Cell Line

  Sakurai A, Sakurai T, Ho HJ, Chiba H, Hui SP The 6th FHS International Conference 2023年10月
• 学童の血中リゾホスファチジルエタノールアミン濃度と肥満との関連

  井上夏緒, Siddabasave Gowda, B. Gowda, Divyavani Gowda, 櫻井俊宏, Rahel Mesfin Ketema, 池田 敦子, 千葉仁志, 惠 淑萍 第63回日本臨床化学会年次学術集会 2023年10月
• 脂肪肝モデル細胞における12-EPAHSAのミトコンドリア形態への影響

  竹下 花, 櫻井俊宏, Siddabasave Gowda, B. Gowda, 千葉仁志, 惠 淑萍 第63回日本臨床化学会年次学術集会, 学生シンポジウム 2023年10月
• 脂肪肝モデル細胞におけるミトコンドリア膜脂質への酸化HDLの影響

  石田航太郎, 櫻井俊宏, 茂木すみれ, 井上夏緒, 千葉仁志, 惠 淑萍 第63回日本臨床化学会年次学術集会 2023年10月
• ケンペロールによるミトコンドリアへの作用

  櫻井知子, 櫻井俊宏, 何 欣蓉, 千葉仁志, 惠 淑萍 第63回日本臨床化学会年次学術集会 2023年10月
• LDL添加による肝ミトコンドリア呼吸機能の変化は酸化により悪化する

  佐﨑 生, 櫻井俊宏, 千葉仁志, 惠 淑萍 第63回日本臨床化学会年次学術集会, YIAシンポジウム 2023年10月
• 培養肝細胞から放出されるLDLの脂質プロフィール解析

  櫻井俊宏, 陳 震, 茂木すみれ, 千葉仁志, 惠 淑萍 第63回日本臨床化学会年次学術集会 2023年10月
• 培養ヒト肝細胞から放出されるVLDL中のTG及びTG-OOHの解析

  益子真明, 櫻井俊宏, 山端ありさ, 佐﨑 生, 茂木 すみれ, 千葉仁志, 惠 淑萍 第48回日本医用マススペクトル学会年会 2023年09月
• 肝細胞における酸化HDLの受容体の探索

  笹 真穂, 櫻井俊宏, 石田航太郎, 千葉仁志, 惠 淑萍 第57回日本臨床検査医学会北海道支部総会・第33回日本臨床化学会北海道支部例会（合同開催） 2023年09月
• Protection of 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA), a component of the Pacific Oyster Crassostrea gigas, on mitochondrial function under oxidative stress

  Eguchi M, Ho HJ, Sekine K, Aoki N, Sakurai T, Chiba H, Watanabe H, Watanabe M, Hui SP The 31st International Congress on Nutrition and Integrative Medicine (ICNIM2023) 2023年07月
• マガキ由来抗酸化物質DHMBAの腎臓尿細管細胞における抗酸化作用

  何 欣蓉, 関根かりん, 青木菜摘, 櫻井俊宏, 千葉仁志, 渡辺秀明, 渡辺 貢, 惠 淑萍 第29回日本未病学会年次学術集会 2022年11月
• サケ白子抽出物のカルジオリピン代謝に関する機能性

  吉貝あみ, 櫻井俊宏, 茂木すみれ, 山端ありさ, 佐藤浩志, 千葉仁志, 惠 淑萍 第62回日本臨床化学会年次学術集会, 学生シンポジウム 2022年09月
• Food-Derived β-Carboline Alkaloids Ameliorate Lipid Droplet Accumulation in Human Hepatocytes

  Dya Fita Dibwe, 住友徹平, 櫻井俊宏, 津久井隆行, 千葉仁志, 惠 淑萍 第62回日本臨床化学会年次学術集会 2022年09月
• 主要なリゾホスファチジルエタノールアミンのアルブミン薬物結合サイトに対する結合親和性の比較

  井上夏緒, 櫻井俊宏, 千葉仁志, 惠 淑萍 第62回日本臨床化学会年次学術集会 2022年09月
• カルジオリピン代謝に対するβ-カルボリンアルカロイドの効果

  櫻井知子, 櫻井俊宏, Dya Fita Dibwe, 住友徹平, 千葉仁志, 惠 淑萍 第62回日本臨床化学会年次学術集会 2022年09月
• 酸化HDLによる肝細胞のミトコンドリア機能低下作用

  櫻井俊宏, 山端ありさ, 関島将人, 井上夏緒, 上野朱音, 茂木すみれ, 何 欣蓉, 陳 震, 千葉仁志, 惠 淑萍 第62回日本臨床化学会年次学術集会 2022年09月
• LDLの肝ミトコンドリア呼吸機能への影響

  佐﨑 生, 櫻井俊宏, 吉貝あみ, 千葉仁志, 惠 淑萍 第56回日本臨床検査医学会北海道支部総会・第32回日本臨床化会北海道支部例会 2022年09月
• 脂肪肝モデル細胞を用いたサケ白子抽出物によるカルジオリピン代謝の変動機序の解明

  佐藤美涼, 櫻井俊宏, 吉貝あみ, 関島将人, 茂木すみれ, 山端ありさ, 佐藤浩志, 千葉仁志, 惠 淑萍 第56回日本臨床検査医学会北海道支部総会・第32回日本臨床化会北海道支部例会 2022年09月
• 酸化LDLの肝カルジオリピン生合成への影響

  佐﨑 生, 櫻井俊宏, 茂木すみれ, 千葉仁志, 惠 淑萍 第47回日本医用マススペクトル学会年会 2022年09月
• 脂肪肝モデル細胞におけるサケ白子抽出物のカルジオリピン代謝改善作用

  櫻井俊宏, 吉貝あみ, 茂木すみれ, 山端ありさ, 関島将人, 佐藤美涼, 佐藤浩志, 千葉仁志, 惠 淑萍 第47回日本医用マススペクトル学会年会 2022年09月
• Comparison of four informatica methods for discovering dietary sources by human serum fatty acids

  Yifan Chen, Yusuke Miura, Toshihiro Sakurai, Zhen Chen, Rojeet Shrestha, Sota Kato, Emiko Okada, Shigekazu Ukawa, Takafumi Nakagawa, Akiko Tamakoshi, Hideyuki Imai, Hiroyuki Minami, Masahiro Mizuta, Shu-Ping Hui 第28回日本未病学会学術総会 2021年11月
• Development of analytical method for sensitive determination of fatty acid hydroperoxides in human plasma by LC/MS

  Chongsheng Liang, Siddabasavegowda, B. Gowda, 櫻井俊宏, 千葉仁志, 惠 淑萍 第61回日本臨床化学会年次学術集会 2021年11月
• C3Aを用いる脂肪肝モデルにおけるサケ白子抽出物のミトコンドリア機能改善作用

  櫻井俊宏, 佐藤 浩志, 何 欣蓉, 千葉仁志, 惠 淑萍 第61回日本臨床化学会年次学術集会 2021年11月
• ヒト血中リゾホスファチジルエタノールアミンのプロファイルとアルブミンとの結合予測

  井上夏緒, 櫻井俊宏, 千葉仁志, 惠 淑萍 第61回日本臨床化学会年次学術集会 2021年11月
• One-step derivatization assisted targeted analysis of fatty acid hydroperoxides by LC/MS

  Chongsheng Liang, Siddabasavegowda, B. Gowda, 櫻井俊宏, 千葉仁志, 惠 淑萍 第46回日本医用マススペクトル学会年会 46 (Supplement) 2021年09月
• Lipid fingerprinting for lipid biomarker discovery of drug-resistance in leukemia

  松久知優, Siddabasavegowda, B. Gowda, 臼杵靖剛, 櫻井俊宏, 千葉仁志, 惠 淑萍 第46回日本医用マススペクトル学会年会 46 (Supplement) 2021年09月
• リゾホスファチジルエタノールアミンが肝脂質代謝とミトコンドリア代謝に及ぼす影響

  櫻井俊宏, 井上夏緒, 山本祐輔, 陳 震, 千葉仁志, 惠 淑萍 第46回日本医用マススペクトル学会年会 46 (Supplement) 2021年09月
• 酸化LDLの肝脂質代謝への影響

  佐﨑 生, 櫻井俊宏, 山端ありさ, 千葉 仁志, 惠 淑萍 第55回日本臨床検査医学会北海道支部総会・第31回日本臨床化会北海道支部例会 2021年09月
• Chemical constituents from vanilla beans and their hepatic lipid accumulation activity

  武石にれ, ディブエ ディアフィタ, 大場早紀, 櫻井俊宏, 津久井隆行, 千葉仁志, 惠 淑萍 第55回日本臨床検査医学会北海道支部総会・第31回日本臨床化会北海道支部例会 2021年09月
• Food extracts as a potential source of a new generation of lipid droplet accumulation inhibitors

  ディブエ ディアフィタ, 津久井隆行, 櫻井俊宏, 千葉仁志, 惠 淑萍 第55回日本臨床検査医学会北海道支部総会・第31回日本臨床化会北海道支部例会 2021年09月
• Selected Allium vegetable extracts targeting lipid droplet accumulation in HepG2 cells loaded with free fatty acids

  大場早紀, ディブエ ディアフィタ, 武石にれ, 櫻井俊宏, 津久井隆行, 千葉仁志, 惠 淑萍 第55回日本臨床検査医学会北海道支部総会・第31回日本臨床化会北海道支部例会 2021年09月
• AutoDockによるリゾホスファチジルエタノールアミンとアルブミンとの結合予測

  井上夏緒, 櫻井俊宏, 千葉 仁志, 惠 淑萍 第55回日本臨床検査医学会北海道支部総会・第31回日本臨床化会北海道支部例会 2021年09月
• Study on the combination of correlation coefficients and factor analysis for discovering fatty acids dietary sources

  陳 一凡, 三浦佑介, 櫻井俊宏, 陳 震, シュレスタ ロジート, 岡田恵美子, 鵜川重和, 中川貴史, 中村幸志, 玉腰暁子, 千葉仁志, 今井英幸, 南 弘征, 水田正弘, 惠 淑萍 第55回日本臨床検査医学会北海道支部総会・第31回日本臨床化会北海道支部例会 2021年09月
• サケ白子抽出物のミトコンドリア形態への影響

  竹下 花, 櫻井俊宏, 山端ありさ, 佐藤浩志, 千葉仁志, 惠 淑萍 第55回日本臨床検査医学会北海道支部総会・第31回日本臨床化会北海道支部例会 2021年09月
• NASH鑑別マーカーとしての血中LDL-TG値の有用性

  櫻井 俊宏, 高橋 祐司, 藤井 佑樹, 能祖 一裕, 太田 素子, 伊藤 康樹, 千葉 仁志, 惠 淑萍 臨床化学 49 (Suppl.1) 141 -141 2020年10月
• 酸化HDLの肝脂質代謝及びミトコンドリアへの影響

  山端 ありさ, 櫻井 俊宏, 関島 将人, 上野 朱音, 千葉 仁志, 惠 淑萍 臨床化学 49 (Suppl.1) 150 -150 2020年10月
• 酸化HDLにより誘導された肝細胞過酸化脂質プロフィールの変動

  上野 朱音, 櫻井 俊宏, 関島 将人, 山端 ありさ, 陳 震, 千葉 仁志, 惠 淑萍 臨床化学 49 (Suppl.1) 151 -151 2020年10月
• サケ白子抽出物の培養ヒト肝細胞におけるミトコンドリア活性化作用

  関島 将人, 櫻井 俊宏, 佐藤 浩志, 何 欣蓉, 千葉 仁志, 惠 淑萍 臨床化学 49 (Suppl.1) 152 -152 2020年10月
• 健常者及び非アルコール性脂肪性肝疾患患者の血清中LysoPEプロファイル

  山本 祐輔, 櫻井 俊宏, 陳 震, Wu Yue, 藤井 佑樹, 能祖 一裕, 千葉 仁志, 惠 淑萍 臨床化学 49 (Suppl.1) 213 -213 2020年10月
• NASHモデルマウスを用いた肝・腎内の脂質に関する網羅的解析(Comprehensive analysis of lipids in the liver and kidney from NASH model mice)

  惠 淑萍, 齋藤 捺希, 陳 震, 櫻井 俊宏, Wu Yue, 津久井 隆行, 布田 博敏, 千葉 仁志 日本未病学会学術総会抄録集 27回 100 -100 2020年10月
• NASHモデルマウスの肝及び腎における脂質の網羅的解析

  齋藤捺希, 陳 震, 櫻井俊宏, Wu Yue, 津久井隆行, 布田博敏, 千葉仁志, 惠 淑萍 第54回日本臨床検査医学会北海道支部総会・第30回日本臨床化会北海道支部例会 2020年09月
• 酸化HDL刺激による肝細胞中のリン脂質過酸化物の変動

  茂木すみれ, 櫻井俊宏, 上野朱音, 山端ありさ, 陳 震, 千葉 仁志, 惠 淑萍 第54回日本臨床検査医学会北海道支部総会・第30回日本臨床化会北海道支部例会 2020年09月
• 高炭水化物食由来脂肪肝マウスの肝cardiolipinプロフィールの変化とその機序の解明

  櫻井俊宏, 山端ありさ, 陳 震, 千葉仁志, 惠 淑萍 第54回日本臨床検査医学会北海道支部総会・第30回日本臨床化会北海道支部例会 2020年09月
• Compositional analysis of lipid droplets in HepG2 cells after treatment with oxidized lipoproteins

  Rojeet Shrestha, Zhen Chen, 櫻井俊宏, 千葉 仁志, 惠 淑萍 第53回日本臨床検査医学会北海道支部総会・第29回日本臨床化会北海道支部例会 2019年10月
• リゾホスファチジルエタノールアミンのLC/MS定量法の検討

  山本祐輔, 櫻井俊宏, 陳 震, 三浦佑介, 千葉仁志, 惠 淑萍 第53回日本臨床検査医学会北海道支部総会・第29回日本臨床化会北海道支部例会 2019年10月
• 肝細胞の脂質代謝とミトコンドリア代謝への酸化HDLの影響

  山端ありさ, 櫻井俊宏, 関島将人, 上野朱音, 布田博敏, 千葉仁志, 惠 淑萍 第53回日本臨床検査医学会北海道支部総会・第29回日本臨床化会北海道支部例会 2019年10月
• NASH鑑別のための血中LDL-TG値の有用性

  櫻井俊宏, 高橋祐司, 藤井佑樹, 能祖一裕, 太田素子, 伊藤康樹, 千葉仁志, 惠 淑萍 第53回日本臨床検査医学会北海道支部総会・第29回日本臨床化会北海道支部例会 2019年10月
• ヒト近位尿細管上皮細胞の脂肪滴形成がミトコンドリア固有リン脂質への影響に関する検討

  惠 淑萍, 三浦 佑介, 櫻井 俊宏, 陳 震, 千葉 仁志 日本未病システム学会学術総会抄録集 26回 108 -108 2019年10月 [査読無し][通常論文]
  
• LC/MSによる糖尿病性腎症患者の尿中コレステリルエステル定量分析

  惠 淑萍, 三浦 祐介, 辻川 諒哉, 櫻井 俊宏, 高田 康徳, 千葉 仁志 臨床病理 67 (補冊) 260 -260 2019年10月 [査読無し][通常論文]
  
• ヒト肝培養細胞における酸化HDLの線維化促進作用

  関島 将人, 櫻井 俊宏, 千葉 仁志, 惠 淑萍 臨床化学 48 (Suppl.1) 205 -205 2019年08月 [査読無し][通常論文]
  
• 酸化リポタンパク質はHepG2細胞の脂質滴中の脂質過酸化水素の蓄積を誘発する(Oxidized lipoproteins induce accumulation of lipid hydroperoxides in lipid droplets of HepG2 cells)

  Shrestha Rojeet, 陳 震, 桜井 俊宏, 千葉 仁志, 惠 淑萍 臨床化学 48 (Suppl.1) 258 -258 2019年08月 [査読無し][通常論文]
  
• 高炭水化物食由来脂肪肝マウスの肝臓中cardiolipin及びmonolysocardiolipinの組成解析

  櫻井 俊宏, 陳 震, 早坂 孝宏, 千葉 仁志, 惠 淑萍 JSBMS Letters 44 (Suppl.) 99 -99 2019年08月 [査読無し][通常論文]
  
• HK-2細胞における脂肪滴とカルジオリピンの関連性についての検討

  三浦 佑介, 櫻井 俊宏, 陳 震, 千葉 仁志, 惠 淑萍 臨床化学 48 (Suppl.1) 256 -256 2019年08月 [査読無し][通常論文]
  
• 非アルコール性脂肪性肝炎発症に対する酸化HDLの関与

  櫻井 俊宏, 関島 将人, 田村 宥人, 仲門 菜月, 津久井 隆行, 布田 博敏, 千葉 仁志, 惠 淑萍 臨床化学 48 (Suppl.1) 256 -256 2019年08月 [査読無し][通常論文]
  
• リゾホスファチジルエタノールアミンの定量系開発のための標準品および内部標準物質の合成

  山本 祐輔, 櫻井 俊宏, 三浦 佑介, 陳 震, 千葉 仁志, 惠 淑萍 臨床化学 48 (Suppl.1) 259 -259 2019年08月 [査読無し][通常論文]
  
• 非アルコール性脂肪性肝炎患者の血中酸化LDLの解析

  櫻井俊宏, 永坂 敦, 和田典夫, 千葉仁志, 惠 淑萍 第52回日本臨床検査医学会北海道支部総会・第28回日本臨床化会北海道支部例会 2018年09月
• LC/MSによるヒト血清中における分子種別コレステリルエステルの定量分析

  三浦佑介, 加藤颯太, 櫻井俊宏, CHEN Zhen, WU Yue, GAO Zijun, SHRESTHA Rojeet, 中村幸志, 鵜川重和, 鵜川重和, 中川貴史, 玉腰暁子, 千葉仁志, 千葉仁志, HUI Shu‐Ping JSBMS Letters 43 (Supplement) 82 -82 2018年08月25日 [査読無し][通常論文]
  
• 食餌由来脂肪肝モデルマウスにおいて鮭白子抽出物の摂取は肝機能障害の改善とミトコンドリアを活性化させる

  櫻井俊宏, 早坂孝宏, 関口博太, 佐藤浩志, CHEN Zhen, 千葉仁志, HUI Shu‐Ping JSBMS Letters 43 (Supplement) 147 2018年08月 [査読無し][通常論文]
  
• LDL‐TG測定試薬の臨床検体への応用

  櫻井俊宏, 高橋祐司, 藤井佑樹, 能祖一裕, 太田素子, 伊藤康樹, 永坂敦, 和田典男, 千葉仁志, 惠淑萍 臨床化学 47 383 2018年07月24日 [査読無し][通常論文]
  
• LDL‐TG測定試薬の臨床検体への応用

  櫻井俊宏, 高橋祐司, 藤井佑樹, 能祖一裕, 太田素子, 伊藤康樹, 永坂敦, 和田典男, 千葉仁志, 惠淑萍 臨床化学 47 244 2018年07月24日 [査読無し][通常論文]
  
• LDLの硬さと加齢について

  武田晴治, 櫻井俊宏, 惠淑萍, 千葉仁志, 千葉仁志 臨床化学 47 382 2018年07月24日 [査読無し][通常論文]
  
• 近位尿細管上皮細胞の脂肪酸負荷による脂質変化

  三浦佑介, 櫻井俊宏, 陳震, 布田博敏, 千葉仁志, 惠淑萍 臨床化学 47 378 2018年07月24日 [査読無し][通常論文]
  
• LC/MSによる腎疾患患者の血清・尿中の脂質分析

  惠淑萍, 三浦佑介, 寺田航, 櫻井俊宏, 陳震, 古川貴之, 小林美穂, 清水力, 千葉仁志 腎と脂質研究会プログラム・抄録集 30th 43 2018年 [査読無し][通常論文]
  
• ヒトリポ蛋白中の過酸化コレステリルエステル及びトリグリセリドの同定

  惠 淑萍, 三浦 佑介, 櫻井 俊宏, 武田 晴治, 布田 博敏, 千葉 仁志 日本未病システム学会学術総会抄録集 24回 99 -99 2017年10月 [査読無し][通常論文]
  
• ヒト血中酸化トリグリセリドに関する研究

  惠 淑萍, 三浦佑介, Rojeet Shrestha, 櫻井俊宏, 千葉仁志 中性脂肪学会第1 回学術集会 2017年09月
• apoC2‐knockout mouseは耐糖能異常を引き起こす

  櫻井俊宏, REMALEY Alan T 臨床化学 46 334 2017年09月 [査読無し][通常論文]
  
• Bodipy‐cholesterolを用いるLCAT活性測定法の開発

  櫻井俊宏, REMALEY Alan T 臨床化学 46 334 2017年09月 [査読無し][通常論文]
  
• apoC2mimetic peptideは食後のTG上昇を抑制する

  櫻井俊宏, REMALEY Alan T 臨床化学 46 335 2017年09月 [査読無し][通常論文]
  
• ヒト近位尿細管上皮細胞における蓄積脂質の分析

  三浦佑介, 櫻井俊宏, 津久井隆行, 陳震, 布田博敏, 千葉仁志, 惠淑萍 臨床化学 46 (Suppl.1) 315 -203 2017年09月01日 [査読無し][通常論文]
  
• 酸化HDLが肝由来株化細胞C3Aに及ぼす影響

  仲門菜月, 櫻井俊宏, 岸田佳倫, 布田博敏, 津久井隆行, 千葉仁志, 惠淑萍 臨床化学 46 (Suppl.1) 333 -333 2017年09月01日 [査読無し][通常論文]
  
• 質量分析による血清コレステリルエステルの分析

  加藤颯太, 三浦佑介, 櫻井俊宏, SHRESTHA Rojeet, 陳震, 玉腰暁子, 千葉仁志, 惠淑萍 臨床化学 46 287 2017年09月01日 [査読無し][通常論文]
  
• 冷保存肝の脂質の網羅的解析

  白澤憲典, 早坂孝宏, 早坂孝宏, 深井原, 梅本浩平, 石川隆壽, 櫻井俊宏, 布田博敏, 橋本咲月, 大谷晋太郎, 中藪拓哉, 島田慎吾, 嶋村剛, 武冨紹信, 千葉仁志, 惠淑萍 臨床化学 46 198 2017年09月01日 [査読無し][通常論文]
  
• プロテオミクスを用いる抗酸化酵素群の発現量解析

  岸田佳倫, 櫻井俊宏, 仲門菜月, 布田博敏, 古川貴之, 千葉仁志, 惠淑萍 臨床化学 46 347 2017年09月01日 [査読無し][通常論文]
  
• 冷保存肝の脂質の網羅的解析

  白澤憲典, 早坂孝宏, 早坂孝宏, 深井原, 梅本浩平, 石川隆壽, 櫻井俊宏, 布田博敏, 橋本咲月, 大谷晋太郎, 中藪拓哉, 島田慎吾, 嶋村剛, 武冨紹信, 千葉仁志, 惠淑萍 臨床化学 46 313 2017年09月01日 [査読無し][通常論文]
  
• ヒトリポタンパク質における非極性脂質の酸化に関する分析

  惠 淑萍, 三浦 佑介, Shrestha Rojeet, 櫻井 俊宏, 武田 晴治, 布田 博敏, 千葉 仁志 臨床化学 46 (Suppl.1) 330 -330 2017年09月 [査読無し][通常論文]
  
• ヒト近位尿細管上皮細胞における蓄積脂質の分析

  三浦佑介, 櫻井俊宏, 津久井隆行, 陳震, 布田博敏, 千葉仁志, 惠淑萍 臨床化学 46 203 2017年09月01日 [査読無し][通常論文]
  
• LC‐MS/MSによる近位尿細管上皮細胞の脂質分析

  三浦佑介, 櫻井俊宏, 津久井隆行, ZHEN Chen, 布田博敏, 千葉仁志, HUI Shu‐Ping JSBMS Letters 42 (Supplement) 110 -110 2017年08月25日 [査読無し][通常論文]
  
• ApoC-II Mimetic Peptide Blunts Post-Prandial Hypertriglyceridemia in Mice

  Anna Wolska, Toshihiro Sakurai, Denis Sviridov, Milton Pryor, Larry Lo, Soumitra Ghosh, Madhav Devalaraja, Alan T. Remaley ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY 37 2017年05月 [査読無し][通常論文]
  
• 血中リポタンパク質の粒子径及び硬さの評価系開発

  櫻井俊宏, 武田晴治, Suchin Trirongjitmoah, 清水孝一, 惠 淑萍, 千葉仁志 第11回遺伝子栄養学研究会 2016年09月
• DEVELOPMENT OF AN AUTOMATED ASSAY FOR APOE-CONTAINING HDL-CHOLESTEROL

  Y. Takahashi, T. Sakurai, M. Fujikawa, A. Nagasaka, S. Hui, S. Jin, S. Takeda, H. Fuda, Y. Ito, H. Chiba ATHEROSCLEROSIS 235 (2) E102 -E102 2014年08月 [査読無し][通常論文]
  
• マガキ由来の抗酸化物質における培養肝細胞保護作用

  布田博敏, 渡邉貢, 上甲紗愛, 神繁樹, 川西範明, 吉田繁, HUI Shu‐Ping, 武田晴治, 櫻井俊宏, SHRESTHA Rojeet, 池川繁男, 三木恵美子, 渡邉孝之, 千葉仁志 日本農芸化学会大会講演要旨集(Web) 2014 2B04A04 (WEB ONLY) 2014年03月05日 [査読無し][通常論文]
  
• マガキ由来の新規抗酸化物質における肝保護作用

  布田博敏, 渡邉貢, 神繁樹, 上甲紗愛, 惠淑萍, 武田晴治, 櫻井俊宏, 渡邉孝之, 千葉仁志 日本未病システム学会学術総会抄録集 20th 173 2013年10月15日 [査読無し][通常論文]
  
• マガキ(Crassostrea gigas)から単離されたフェノール系抗酸化物はヒト肝臓の培養細胞における酸化を抑制する

  渡邉 貢, 布田 博敏, 神 繁樹, 櫻井 俊宏, 惠 淑萍, 武田 晴治, 渡邉 孝之, 小池 隆夫, 千葉 仁志 北海道醫學雜誌 = Acta medica Hokkaidonensia 88 (4) 141 -142 2013年09月01日 [査読無し][通常論文]
  
• カーボンナノチューブ電極による酸化LDLの検出

  武田 晴治, 惠 淑萍, 福田 慶介, 布田 博敏, 神 繁樹, 櫻井 俊宏, 石井 睦, 武笠 幸一, 末岡 和久, 千葉 仁志 北海道醫學雜誌 = Acta medica Hokkaidonensia 88 (4) 151 -151 2013年09月01日 [査読無し][通常論文]
  
• 血漿、VLDL、およびIDL中のコレステロールエステル過酸化水素のLC/MSによる定性分析(Qualitative analysis of cholesteryl ester hydroperoxides in plasma, VLDL and IDL by LC/MS)

  Shrestha Rojeet, 惠 淑萍, 櫻井 俊宏, 八木 亜希子, 高橋 祐司, 武田 晴治, 神 繁樹, 布田 博敏, 千葉 仁志 臨床病理 61 (補冊) 126 -126 2013年09月 [査読無し][通常論文]
  
• Triglyceride-rich lipoproteinsの過酸化脂質の分析(Analyses of lipid hydroperoxides in triglyceride-rich lipoproteins)

  Shrestha Rojeet, 惠 淑萍, 八木 亜希子, 櫻井 俊宏, 高橋 祐司, 武田 晴治, 神 繁樹, 布田 博敏, 池川 繁男, 千葉 仁志 JSBMS Letters 38 (Suppl.) 68 -68 2013年08月 [査読無し][通常論文]
  
• マガキ由来の新規抗酸化物質における肝保護作用

  上甲紗愛, 布田博敏, 渡邉貢, 神繁樹, 惠淑萍, 武田晴治, 櫻井俊宏, 渡邉孝之, 千葉仁志 臨床化学 42 229 2013年07月31日 [査読無し][通常論文]
  
• 金属酸化LDLに由来する粒子の電気化学的検討

  寺嶋駿, 武田晴治, 山田理絵, 大川芙多葉, 恵淑萍, 布田博敏, 櫻井俊宏, 神繁樹, 千葉仁志 臨床化学 42 184 2013年07月31日 [査読無し][通常論文]
  
• apoE‐containing HDL‐cholesterol直接法の開発

  高橋祐司, 櫻井俊宏, 惠淑萍, 神繁樹, 武田晴治, 布田博敏, 伊藤康樹, 千葉仁志 臨床化学 42 219 2013年07月31日 [査読無し][通常論文]
  
• 原子間力顕微鏡によるLDL酸化状態評価

  武田晴治, 櫻井俊宏, 大川芙多葉, 惠淑萍, 神繁樹, 布田博敏, 千葉仁志 臨床化学 42 216 2013年07月31日 [査読無し][通常論文]
  
• LC/MSによるVLDLとIDL中のトリアシルグリセロール過酸化水素の定性分析(Qualitative analysis of triacylglycerol hydroperoxide in VLDL and IDL by LC/MS)

  Shrestha Rojeet, 惠 淑萍, 櫻井 俊宏, 高橋 祐司, 武田 晴治, 神 繁樹, 布田 博敏, 千葉 仁志 臨床化学 42 (Suppl.1) 185 -185 2013年07月 [査読無し][通常論文]
  
• Qualitative Determination of Triacylglycerol Hydroperoxide in VLDL, Intermediate Density Lipoprotein and Human Plasma using Orbitrap Mass Spectrometer.

  Shrestha R, Hui SP, Sakurai T, Takahashi Y, Ohkawa F, Miyazaki R, Xiao N, Takeda S, Jin S, Fuda H, Chiba H American Association for Clinical Chemistry 2013年07月 [査読無し][通常論文]
  
• Detection and characterization of lipid hydroperoxides in human lipoproteins by LC/MS.

  Hui SP, Shrestha R, Sakurai T, Takahashi Y, Xiao N, Takeda S, Jin S, Fuda H, Chiba H American Association for Clinical Chemistry, Houston 2013年07月 [査読無し][通常論文]
  
• LDLに対する抗酸化能のCNT電極センサーによる測定法

  大川芙多葉, 武田晴治, HUI S.P, 武笠幸一, 櫻井俊宏, 神繁樹, 布田博敏, 末岡和久, 千葉仁志 電気化学会大会講演要旨集 80th 327 2013年03月29日 [査読無し][通常論文]
  
• ケルビン測定を利用した低比重リポ蛋白質の酸化状態の評価

  武田晴治, HUI S‐P, 武笠幸一, 櫻井俊宏, 神繁樹, 布田博敏, 末岡和久, 千葉仁志 電気化学会大会講演要旨集 80th 332 2013年03月29日 [査読無し][通常論文]
  
• マガキ由来の新規抗酸化物質における肝保護作用

  布田博敏, 渡邉貢, 神繁樹, HUI Shu‐Ping, 武田晴治, 櫻井俊宏, 渡邉孝之, 千葉仁志 日本農芸化学会大会講演要旨集(Web) 2013 2A16A15 (WEB ONLY) 2013年03月05日 [査読無し][通常論文]
  
• LC/MSを用いたVLDL,中密度リポ蛋白質とヒト血漿におけるトリアシルグリセロールヒドロペルオキシドの解析

  SHRESTHA Rojeet, HUI Shu-Ping, SAKURAI Toshihiro, TAKAHASHI Yuji, YAGI Akiko, TAKEDA Seiji, JIN Shigeki, FUDA Hirotoshi, CHIBA Hitoshi バイオメディカル分析科学シンポジウム講演要旨集 26th 2013年
• リポタンパク質の金属酸化時のphosphatidyl choline hydroperoxides及びTBARSの経時変化

  惠淑萍, 櫻井俊宏, 神繁樹, 布田博敏, 武田晴治, 千葉仁志 臨床病理 60 113 2012年10月20日 [査読無し][通常論文]
  
• 原子間力顕微鏡によるリポタンパク質の粒径分布の解析

  櫻井俊宏, 高橋順也, 武田晴治, SUCHIN Trirongjitmoah, 浪田健, 神繁樹, 清水孝一, 千葉仁志 臨床病理 60 117 2012年10月20日 [査読無し][通常論文]
  
• マガキ由来の新規抗酸化物質の抗酸化能とその生化学的性状

  布田博敏, 渡邉貢, 神繁樹, 櫻井俊宏, 千葉仁志 日本未病システム学会学術総会抄録集 19th 97 2012年10月01日 [査読無し][通常論文]
  
• TBARSは酸化リポタンパク質中のphosphatidylcholine hydroperoxidesのレベルを反映していない

  HUI Shu‐Ping, 櫻井俊宏, 神繁樹, 布田博敏, 武田晴治, 黒澤隆夫, 千葉仁志 JSBMS Lett 37 (Supplement) 58 2012年09月10日 [査読無し][通常論文]
  
• 原子間力顕微鏡を用いた酸化LDLの電位変化測定

  武田晴治, 大川芙多葉, 櫻井俊宏, 神繁樹, 布田博敏, 惠淑萍, 末岡和久, 千葉仁志 臨床化学 41 226 2012年07月31日 [査読無し][通常論文]
  
• 直接法によるHDL亜分画中のコレステロール同時測定法の開発

  高橋祐司, 櫻井俊宏, 永坂敦, 藤川正人, 惠淑萍, 神繁樹, 武田晴治, 布田博敏, 伊藤康樹, 千葉仁志 臨床化学 41 227 2012年07月31日 [査読無し][通常論文]
  
• 酸化リポタンパク質における過酸化脂質とプラズマローゲンの濃度変化

  惠淑萍, 櫻井俊宏, 武田晴治, 神繁樹, 布田博敏, 黒澤隆夫, 千葉仁志 臨床化学 41 239 2012年07月31日 [査読無し][通常論文]
  
• 過酸化脂質測定CNT電極センサーを用いた抗酸化能測定法

  大川芙多葉, 武田晴治, 櫻井俊宏, 惠淑萍, 布田博敏, 神繁樹, 千葉仁志 臨床化学 41 200 2012年07月31日 [査読無し][通常論文]
  
• 脂質異常症患者および健常者における粒子サイズ別の酸化LDLの解析

  櫻井俊宏, 高橋祐司, 和田典男, 古川博之, 永坂敦, 惠淑萍, 神繁樹, 武田晴治, 布田博敏, 小林清一, 千葉仁志 臨床化学 41 226 2012年07月31日 [査読無し][通常論文]
  
• 新しい臨床検査技術の開発 カーボンナノチューブセンサーの臨床検査化学への応用

  武田 晴治, 惠 淑萍, 櫻井 俊宏, 石井 睦, 武笠 幸一, 神 繁樹, 布田 博敏, 末岡 和久, 千葉 仁志 臨床病理 60 (7) 630 -630 2012年07月 [査読無し][通常論文]
  
• LC‐MS/MSによる酸化リポタンパク質における過酸化リン脂質の定量分析

  惠淑萍, 櫻井俊宏, 武田晴治, 神繁樹, 布田博敏, 千葉仁志 日本酸化ストレス学会学術集会プログラム・抄録集 65th 72 2012年06月05日 [査読無し][通常論文]
  
• Increase of oxidized lipoproteins in liver disease, detected by monoclonal antibody recognizing early lipoprotein change during copper-oxidation.

  Sakurai T, Ichikawa A, Furukawa F, Wada N, Nagasaka A, Takahashi Y, Fujikawa M, Ikuta A, Furumaki H, Shiga M, Shimizu C, Hui SP, Jin S, Takeda S, Fuda H, Nagasaka S, Kobayashi S, Chiba H European Atherosclerosis Society, Milan 2012年05月 [査読無し][通常論文]
  
• 冠動脈硬化性疾患の病態の把握及び早期診断のための血漿プラスマローゲンの有用性に関しての検討

  西向めぐみ, 榊原守, 横田卓, 山田史郎, 櫻井俊宏, 高橋祐司, 生田知子, 古牧宏啓, 山木志展, 前場良太, 千葉仁志, 筒井裕之, 原博 日本栄養・食糧学会大会講演要旨集 66th 154 2012年04月27日 [査読無し][通常論文]
  
• 酸化低比重リポ蛋白質検出におけるCNT電極の特異性

  武田晴治, 惠淑萍, 櫻井俊宏, 石井睦, 武笠幸一, 神繁樹, 布田博敏, 末岡和久, 千葉仁志 電気化学会大会講演要旨集 79th 38 2012年03月29日 [査読無し][通常論文]
  
• LC/MSによる酸化リポタンパク質におけるcholesterylester hydroperoxidesの分析

  惠淑萍, 田口裕大, 櫻井俊宏, 神繁樹, 布田博敏, 武田晴治, 黒澤隆夫, 千葉仁志 日本薬学会年会要旨集 132nd (4) 135 2012年03月05日 [査読無し][通常論文]
  
• カーボンナノチューブセンサーの臨床検査化学への応用

  武田晴治, 惠淑萍, 櫻井俊宏, 石井睦, 武笠幸一, 神繁樹, 布田博敏, 末岡和久, 千葉仁志 臨床病理 59 19 2011年10月15日 [査読無し][通常論文]
  
• 自製ELISAによる酸化リポ蛋白の測定とその有用性の検討

  櫻井俊宏, 生田知子, 古牧宏啓, 高橋祐司, 西端友香, 石川明彦, 古川博之, 和田典男, 永坂敦, 惠淑萍, 神繁樹, 武田晴治, 布田博敏, 小林清一, 千葉仁志 臨床病理 59 (補冊) 204 -204 2011年10月15日 [査読無し][通常論文]
  
• LC/MSによるLDL及びHDLにおける過酸化トリグリセリドの分析

  惠淑萍, 田口裕大, 櫻井俊宏, 山木志展, 古牧宏啓, 神繁樹, 布田博敏, 武田晴治, 千葉仁志 臨床病理 59 206 2011年10月15日 [査読無し][通常論文]
  
• 食品由来の新規抗酸化物の同定

  布田博敏, 渡邉貢, 神繁樹, 櫻井俊宏, 惠淑萍, 武田晴治, 千葉仁志 臨床病理 59 123 2011年10月15日 [査読無し][通常論文]
  
• 原発性アルドステロン症鑑別診断における血清18‐ヒドロキシコルチゾール定量の有用性の検討

  神繁樹, 和田典男, HUI Shu‐Ping, 櫻井俊宏, 高橋祐司, 柳澤克之, 黒澤隆夫, 千葉仁志 JSBMS Lett 36 (Supplement) 69 2011年08月10日 [査読無し][通常論文]
  
• LC‐MS/MSを用いた血清18‐ヒドロキシコルチゾール定量法の開発

  神繁樹, HUI Shu‐Ping, 和田典男, 櫻井俊宏, 高橋祐司, 柳澤克之, 黒澤隆夫, 千葉仁志 JSBMS Lett 36 (Supplement) 68 2011年08月10日 [査読無し][通常論文]
  
• LC/MSによるLDL及びHDLにおけるtriglyceride hydroperoxidesの分析

  HUI Shu‐Ping, 田口裕大, 櫻井俊宏, 山木志展, 古牧宏啓, 神繁樹, 布田博敏, 武田晴治, 黒澤隆夫, 千葉仁志 JSBMS Lett 36 (Supplement) 67 2011年08月10日 [査読無し][通常論文]
  
• マガキ由来の新規抗酸化物質の単離

  神繁樹, 渡邉貢, 布田博敏, 櫻井俊宏, 千葉仁志 臨床化学 40 245 2011年07月31日 [査読無し][通常論文]
  
• LC‐MS/MSによる血清中18‐ヒドロキシコルチゾールの測定法の開発

  神繁樹, 惠淑萍, 和田典男, 櫻井俊宏, 柳澤克之, 黒澤隆夫, 千葉仁志 臨床化学 40 229 2011年07月31日 [査読無し][通常論文]
  
• 2種類のHDL‐C直接法を用いたapoE‐containing HDL定量法

  高橋祐司, 櫻井俊宏, 永坂敦, 藤川正人, 惠淑萍, 神繁樹, 武田晴治, 布田博敏, 千葉仁志 臨床化学 40 209 2011年07月31日 [査読無し][通常論文]
  
• 原子間力顕微鏡によるリポ蛋白の1粒子計測の試み

  櫻井俊宏, 高橋順也, 武田晴治, TRIRONGJITMOAH Suchin, 浪田健, 神繁樹, 清水孝一, 千葉仁志 臨床化学 40 207 2011年07月31日 [査読無し][通常論文]
  
• マガキ由来の新規抗酸化物質の抗酸化能

  布田博敏, 渡邉貢, 神繁樹, 櫻井俊宏, 千葉仁志 臨床化学 40 246 2011年07月31日 [査読無し][通常論文]
  
• Oxidized LDL and HDLにおけるコレステリルエステル過酸化脂質のLC/MSによる分析

  惠淑萍, 櫻井俊宏, 古牧宏啓, 黒澤隆夫, 千葉仁志 臨床化学 40 202 2011年07月31日 [査読無し][通常論文]
  
• マガキ由来の新規抗酸化物質の抗酸化能

  布田博敏, 渡邉貢, 神繁樹, 櫻井俊宏, 惠淑萍, 武田晴治, 千葉仁志 日本酸化ストレス学会学術集会プログラム・抄録集 64th 97 2011年06月27日 [査読無し][通常論文]
  
• 金属酸化により得られた酸化LDLと酸化HDLにおける過酸化トリグリセリドのLC/MS定性分析

  惠淑萍, 櫻井俊宏, 古牧宏啓, 山木志展, 田口裕大, 神繁樹, 布田博俊, 武田晴治, 黒澤隆夫, 千葉仁志 日本酸化ストレス学会学術集会プログラム・抄録集 64th 87 2011年06月27日 [査読無し][通常論文]
  
• 新規測定法による酸化リポ蛋白の解析

  櫻井俊宏, 生田知子, 古牧宏啓, 高橋祐司, 西端友香, 石川明彦, 古川博之, 和田典男, 永坂敦, 惠淑萍, 神繁樹, 武田晴治, 布田博敏, 小林清一, 千葉仁志 日本酸化ストレス学会学術集会プログラム・抄録集 64th 72 2011年06月27日 [査読無し][通常論文]
  
• CD36欠損者の長期フルクトース摂取による代謝変化

  鈴木純子, 千葉仁志, 櫻井俊宏, 高橋祐司, 神繁樹, 惠淑萍, 小池隆夫 糖尿病 54 (Supplement 1) S.359 -359 2011年04月25日 [査読無し][通常論文]
  
• Chlamydomonas reinhardtiiのgranule‐bound starch synthase欠損がピレノイドデンプンの形態及び構造に及ぼす影響

  櫻井俊宏, 出雲旦子, 藤原祥子, BALL Steven G, 小野光, 藤田直子, 中村保典, 都筑幹夫 日本植物生理学会年会要旨集 52nd 287 2011年03月11日 [査読無し][通常論文]
  
• 動脈硬化を診る―リスク評価と病態の検査―1 脂質・リポ蛋白の検査 a)脂質・リポ蛋白分画の測定法 4)small dense LDL

  櫻井俊宏, 千葉仁志 Med Technol 38 (13) 1333 -1336 2010年12月20日 [査読無し][通常論文]
  
• リポ蛋白中プラズマローゲンの分布に関する研究

  生田知子, 西向めぐみ, 惠淑萍, 櫻井俊宏, 神繁樹, 原博, 千葉仁志 臨床化学 39 117 2010年07月31日 [査読無し][通常論文]
  
• apoCIIIとapoEの両者を持つリポ蛋白粒子(Lp‐CIII‐E)の分布の検討

  古牧宏啓, 櫻井俊宏, 高橋祐司, 生田知子, 西端友香, 惠淑萍, 神繁樹, 布田博敏, 武田晴治, 千葉仁志 臨床化学 39 (Suppl.1) 123 -123 2010年07月31日 [査読無し][通常論文]
  
• HDL‐C直接法における界面活性剤種による反応性変化について

  高橋祐司, 古牧宏啓, 櫻井俊宏, 永坂敦, 藤川正人, 惠淑萍, 神繁樹, 武田晴治, 布田博敏, 千葉仁志 臨床化学 39 121 2010年07月31日 [査読無し][通常論文]
  
• LC‐MS/MSによる健常人と肝不全患者血中過酸化リン脂質の分析

  惠淑萍, 千葉仁志, 櫻井俊宏, 神繁樹, 黒澤隆夫 臨床化学 39 119 2010年07月31日 [査読無し][通常論文]
  
• 酸化リポ蛋白の新規測定法の開発

  櫻井俊宏, 生田知子, 古牧宏啓, 高橋祐司, 西端友香, 古川博之, 和田典男, 永坂敦, 惠淑萍, 神繁樹, 武田晴治, 布田博敏, 小林清一, 千葉仁志 臨床化学 39 (Suppl.1) 121 -121 2010年07月31日 [査読無し][通常論文]
  
• 抗apoE抗体と抗apoCIII抗体のsandwich‐ELISAによるレムナントリポ蛋白の検出について

  古牧宏啓, 櫻井俊宏, 高橋祐司, 生田知子, 西端友香, 惠淑萍, 神繁樹, 布田博敏, 千葉仁志 臨床病理 58 (補冊) 96 -96 2010年07月30日 [査読無し][通常論文]
  
• 酸化リポ蛋白自己抗体の研究:臨床的検討

  櫻井俊宏, 西端友香, 高橋祐司, 古川博之, 和田典夫, 永坂敦, 惠淑萍, 生田知子, 古牧宏啓, 神繁樹, 武田晴治, 布田博敏, 小林清一, 千葉仁志 臨床病理 58 (補冊) 94 -94 2010年07月30日 [査読無し][通常論文]
  
• 酸化リポ蛋白自己抗体の研究:モノクローナル抗体の作製

  西端友香, 櫻井俊宏, 高橋祐司, 古川博之, 和田典男, 永坂敦, 惠淑萍, 生田知子, 古牧宏啓, 神繁樹, 武田晴治, 布田博敏, 小林清一, 千葉仁志 臨床病理 58 (補冊) 173 -173 2010年07月30日 [査読無し][通常論文]
  
• LC‐MS/MSによるヒト血中過酸化リン脂質の分析

  惠淑萍, 千葉仁志, 櫻井俊宏, 神繁樹, 黒澤隆夫 臨床病理 58 162 2010年07月30日 [査読無し][通常論文]
  
• LC‐MS/MSによるプラズマローゲンのリポ蛋白分布の検討

  生田知子, 西向めぐみ, 惠淑萍, 櫻井俊宏, 神繁樹, 原博, 千葉仁志 臨床病理 58 92 2010年07月30日 [査読無し][通常論文]
  
• LC‐MS/MSによる健常者血中過酸化リン脂質の分析

  惠淑萍, 千葉仁志, 櫻井俊宏, 黒澤隆夫 日本酸化ストレス学会学術集会プログラム・抄録集 63rd 83 2010年06月24日 [査読無し][通常論文]
  
• 酸化リポ蛋白に対する自己抗体の新規測定法の開発

  櫻井俊宏, 西端友香, 高橋祐司, 古川博之, 和田典男, 永坂敦, 惠淑萍, 生田知子, 古牧宏啓, 神繁樹, 武田晴治, 布田博敏, 小林清一, 千葉仁志 日本酸化ストレス学会学術集会プログラム・抄録集 63rd 89 2010年06月24日 [査読無し][通常論文]
  
• Development of technique to estimate small dense LDL fraction by dynamic light scattering: II

  TRIRONGJITMOAH Suchin, SAKURAI Toshihiro, NISHIBATA Yuka, NAMITA Takeshi, KATO Yuji, IINAGA Kazuya, CHIBA Hitoshi, SHIMIZU Koichi Optics & Photonics Japan講演予稿集 2009 64 -65 2009年11月 [査読無し][通常論文]
  
• LC‐MS/MSを用いた尿中の18‐ヒドロキシコルチゾールの定量

  神繁樹, 和田典男, 岩渕亜美, 佐藤祐輔, 櫻井俊宏, 高橋祐司, 柳澤克之, HUI Shu‐Ping, 黒澤隆夫, 千葉仁志 JSBMS Lett 34 (Supplement) 56 2009年08月15日 [査読無し][通常論文]
  
• 18‐ヒドロキシコルチゾール定量分析におけるLC‐MSの有用性の検討

  神繁樹, 岩渕亜美, 櫻井俊宏, 佐藤祐輔, 高橋祐司, 和田典男, 柳澤克之, 惠淑萍, 黒澤隆夫, 千葉仁志 臨床化学 38 115 2009年07月31日 [査読無し][通常論文]
  
• apoE‐richHDLの分離とHDL測定試薬の反応性

  高橋祐司, 古牧宏啓, 櫻井俊宏, 神繁樹, 惠淑萍, 伊敏, 千葉仁志 臨床化学 38 147 2009年07月31日 [査読無し][通常論文]
  
• 原発性アルドステロン症の鑑別診断における種々の採尿条件での尿中18‐hydroxycortisol測定の評価

  和田典男, 神繁樹, 岩渕亜美, 佐藤祐輔, 櫻井俊宏, 高橋祐司, 柳澤克之, 惠淑萍, 黒澤隆夫, 千葉仁志 臨床化学 38 114 2009年07月31日 [査読無し][通常論文]
  
• 原子間力顕微鏡を用いたリポ蛋白粒径計測法

  櫻井俊宏, SUCHIN Trirongjitmoah, 西端友香, 神繁樹, 清水孝一, 千葉仁志 臨床化学 38 (Suppl.1) 150 -150 2009年07月31日 [査読無し][通常論文]
  
• apoE‐rich HDLと各種沈殿試薬の反応性について

  古牧宏啓, 高橋祐司, 櫻井俊宏, 伊敏, 惠淑萍, 神繁樹, 千葉仁志 臨床化学 38 146 2009年07月31日 [査読無し][通常論文]
  
• 動脈硬化惹起性リポ蛋白測定系の若年健常者における検討

  鈴木純子, 櫻井俊宏, 高橋祐司, 惠淑萍, 神繁樹, 伊敏, 千葉仁志 臨床化学 38 151 2009年07月31日 [査読無し][通常論文]
  
• 動的光散乱法を用いたリポ蛋白粒径計測法

  西端友香, 櫻井俊宏, SUCHIN Trirongjitmoah, 浪田健, 神繁樹, 清水孝一, 千葉仁志 臨床化学 38 (Suppl.1) 149 -149 2009年07月31日 [査読無し][通常論文]
  
• 尿中18‐hydroxycortisolを測定した副腎癌の1例

  和田典男, 神繁樹, 岩渕亜美, 佐藤祐輔, 櫻井俊宏, 高橋祐司, 柳澤克之, 惠淑萍, 黒沢隆夫, 千葉仁志 臨床病理 57 273 2009年07月28日 [査読無し][通常論文]
  
• 動的光散乱法を用いた各種リポ蛋白粒径の計測

  西端友香, 櫻井俊宏, SUCHIN Trirongjitmoah, 浪田健, 神繁樹, 清水孝一, 千葉仁志 臨床病理 57 (補冊) 241 -241 2009年07月28日 [査読無し][通常論文]
  
• 18‐ヒドロキシコルチゾールのLC‐MS/MS定量法の検討

  神繁樹, 岩渕亜美, 櫻井俊宏, 佐藤祐輔, 高橋祐司, 和田典男, 柳澤克之, 惠淑萍, 黒澤隆夫, 千葉仁志 臨床病理 57 206 2009年07月28日 [査読無し][通常論文]
  
• 酸化LDLによるCD36の発現変化

  伊敏, 櫻井俊宏, 松岡志保, 須藤祐, 古牧宏啓, 神繁樹, 恵淑萍, 千葉仁志 臨床病理 57 175 2009年07月28日 [査読無し][通常論文]
  
• CD36欠損者の長期フルクトース摂取による代謝変化―脂肪負荷試験による検討―

  高橋祐司, 鈴木純子, 櫻井俊宏, 神繁樹, 惠淑萍, 伊敏, 千葉仁志 臨床病理 57 176 2009年07月28日 [査読無し][通常論文]
  
• CD36欠損者の長期フルクトース摂取による代謝変化―糖負荷試験による検討―

  櫻井俊宏, 鈴木純子, 高橋祐司, 神繁樹, 惠淑萍, 伊敏, 千葉仁志 臨床病理 57 175 2009年07月28日 [査読無し][通常論文]
  
• CD36欠損者の長期フルクトース摂取が,H‐MRS測定法による骨格筋細胞内脂質量に及ぼす影響

  鈴木純子, 山本徹, 辻真太郎, 櫻井俊宏, 高橋祐司, 神繁樹, 惠淑萍, 伊敏, 千葉仁志 臨床病理 57 176 2009年07月28日 [査読無し][通常論文]
  
• 動的光散乱によるsmall dense LDLの割合推定の試み

  トライロンジットモア スチン, 浪田健, 西端友香, 櫻井俊宏, 加藤祐次, 飯永一也, 千葉仁志, 清水孝一 生体医工学 47 (3) 321 -321 2009年06月10日 [査読無し][通常論文]
  
• 血中クルクミノイドのUV検出高速液体クロマトグラフィーによる分離定量法の開発

  HUI Shuping, 林千登勢, 櫻井俊宏, 神繁樹, 石井智美, 村井毅, 上馬塲和夫, 小川弘子, 千葉仁志, 黒澤隆夫 臨床化学 38 (1) 59 -68 2009年01月31日 [査読無し][通常論文]
   

  ウコン（ターメリック）に含まれるポリフェノールであるクルクミノイドのヒトにおける吸収・代謝・動態は不明である。我々は，血中クルクミノイドのUV検出高速液体クロマトグラフィー（HPLC）による定量法を開発し，ターメリック粉3g（クルクミノイド60～90mg含有）を服用した健常成人7名（m：f＝－5：2，24±1歳）と市販ウコン錠（90％精製クルクミノイド480mg含有）を服用した健常成人7名（m：f＝4：3，22±2歳）の血中抱合型並びに非抱合型のクルクミノイド（非還元型）を本法により測定した。ターメリック粉群では服用1時間後に最大血中濃度が142.9±63.7nmol／lに達した。一方，ウコン錠群では服用8時間に最大血中濃度が26.9±17.7nmol／lとなり，クルクミノイドの精製度が消化管吸収速度に影響する可能性が示唆された。酵素水解反応の結果から，非還元型クルクミノイドは大部分がグルクロン酸抱合体あるいはグルクロン酸と硫酸の二重抱合型として存在し，一部が遊離型として存在することが推測された。今回開発したHPLC法は，ウコン食品の薬理学的研究に有用なツールとなることが期待される。 Curcuminoids are the polyphenols contained in turmeric. They are getting more popular in Japan as an ingredient of health foods. However, little is known about the intestinal absorption, metabolites and pharmacokinetic profiles of orally administered curcuminoids in human. In this report, quantitative analyses of curcuminoids in human plasma after oral administration were done by using HPLC with the aid of synthetic curcuminoid derivatives as an internal standard. For non-reduced forms of curcuminoids, the average recoveries from plasma were 93.1%～114.8%, and the coefficients of variation were less than 16.2%. The enzymatic hydrolysis demonstrated that the non-reduced curcuminoids were glucuronides (50.0%) , glucuronide/ sulfate double conjugates (45.4%) and free (4.6%) at 1 hour after oral ingestion of 4 g turmeric powder. The maximum plasma concentrations of curcuminoids (non-reduced form) in the turmeric powder group (60～90 mg curcuminoids included, n=7) and the turmeric tablet group (90% purified curcuminoids 480 mg included, n=7) were 142.9 + 63.7 nmol/l (mean ± SD) at 1 hour and 26.9 ± 17.7 nmol/l (mean ± SD) at 8 hour, respectively, indicating the different intestinal absorption rates. The present method will serve as a useful analytical tool for pharmacological studies of curcuminoids.
• 動的光散乱を用いた各種リポ蛋白粒径の簡易計測法の開発

  櫻井俊宏, 西端友香, TRIRONGJITMOAH Suchin, 浪田健, 清水孝一, 千葉仁志 臨床化学 37 (Suppl.1) 105 -105 2008年08月29日 [査読無し][通常論文]
  
• ダイナミック光散乱による小型高密度LDL分画の評価

  TRIRONGJITMOAH Suchin, NAMITA Takeshi, SAKURAI Toshihiro, KATO Yuji, IINAGA Kazuya, CHIBA Hitoshi, SHIMIZU Koichi 日本生体医工学会大会プログラム・論文集(CD-ROM) 47th 2008年
• ターメリック摂取後のクルクミノイドの血中動態と存在様式

  浅川千登勢, 惠淑萍, 山田小百合, 櫻井俊宏, 小川弘子, 許鳳浩, 上馬場和夫, 黒澤隆夫, 千葉仁志 臨床病理 55 209 2007年10月31日 [査読無し][通常論文]
  
• 酸化ストレスに対する単球CD36のtranslocationの検討

  竹内淳, 三好秀明, 櫻井俊宏, 惠淑萍, 浅川千登勢, 清水力, 小池隆夫, 千葉仁志 臨床病理 55 141 2007年10月31日 [査読無し][通常論文]
  
• 健常者の血中過酸化リン脂質濃度と他の脂質項目との関係

  惠淑萍, 千葉仁志, 桜井俊宏, 浅川千登勢, 村井毅, 黒澤隆夫 臨床病理 55 (Suppl.2) 142 -142 2007年10月31日 [査読無し][通常論文]
  

受賞

• 2020年10月 日本臨床化学会 日本臨床化学会 学会賞 Young Investigator Award
  
• 2019年10月 第29回日本臨床化学会北海道支部例会 若手優秀演題賞
   

  受賞者: 櫻井 俊宏
• 2018年09月 第43回日本医用マススペクトル学会年会 若手優秀ポスター賞
   

  受賞者: 櫻井 俊宏
• 2018年05月 北海道大学大学院保健科学研究院 優秀論文賞
   

  受賞者: 櫻井 俊宏
• 2016年05月 ATVB Young Investigator Travel Award 2016
   

  受賞者: 櫻井 俊宏
• 2014年09月 日本臨床化学会 論文賞
   

  受賞者: 櫻井 俊宏
• 2013年10月 日本臨床検査医学会 若手研究者奨励賞
   

  受賞者: 櫻井 俊宏
• 2013年03月 北海道大学 保健科学院長賞
   

  受賞者: 櫻井 俊宏
• 2010年09月 日本臨床化学会学会賞 奨励賞
   

  受賞者: 櫻井 俊宏

共同研究・競争的資金等の研究課題

• ミトコンドリア機能評価に関する新規技術の構築および応用

  日本学術振興会：科学研究費助成事業

  研究期間 : 2023年04月 -2026年03月 

  代表者 : 千葉 仁志, 櫻井 俊宏, 惠 淑萍
• ミトコンドリア機能障害に着目した酸化HDLとNASH発症機序の関連解明

  日本学術振興会科研費基盤研究(C)：

  研究期間 : 2022年04月 -2025年03月 

  代表者 : 櫻井 俊宏
• -

  ノーステック財団：「研究開発助成事業」イノベーション創出研究支援事業（産学連携創出補助金）

  研究期間 : 2023年04月 -2024年03月 

  代表者 : -
• 酸化HDLに焦点を当てたNASHの発症機序の解明と診断マーカーの探索

  日本学術振興会：科研費 若手研究

  研究期間 : 2019年04月 -2022年03月 

  代表者 : 櫻井 俊宏
• ミトコンドリア代謝の包括的評価系の開発

  北海道大学：令和元年度若手研究加速事業

  研究期間 : 2019年07月 -2020年03月 

  代表者 : 櫻井 俊宏
• 血中低比重リポ蛋白の性質と生活習慣・代謝異常・動脈硬化に関する地域疫学研究

  日本学術振興会：科研費 基盤研究(B)

  研究期間 : 2017年04月 -2020年03月 

  代表者 : 中村 幸志
• 酸化リポ蛋白代謝に関連する心疾患診断マーカーの開発

  公益財団法人アステラス病態代謝研究会：平成24年度海外留学助成

  研究期間 : 2013年04月 -2014年03月 

  代表者 : 櫻井 俊宏
• トリグリセリド代謝に適した新しい酸化ストレスマーカーの開発

  日本学術振興会：特別研究員DC

  研究期間 : 2011年04月 -2013年03月 

  代表者 : 櫻井 俊宏

教育活動情報

主要な担当授業

大学運営

委員歴

• 2023年04月 - 現在   健康食品管理士会北海道支部, 副支部長
• 2019年09月 - 現在   日本臨床化学会 [JSCC]   リポ蛋白検査専門委員会
• 2019年04月 - 現在   健康食品管理士会北海道支部   幹事役員
• 2019年04月 - 現在   日本医用マススペクトル学会 [JSBMS]   評議員
• 2017年04月 - 現在   日本臨床化学会 [JSCC]   評議員
• 2016年10月 - 現在   日本臨床化学会 [JSCC] 北海道支部   幹事役員

社会貢献活動

• 監事（日本臨床化学会北海道支部、2022年〜）

  期間 : 2022年

  役割 : 運営参加・支援
• 事務局長（日本医用マススペクトル学会東日本支部 2022年度東部会）

  期間 : 2022年

  役割 : 運営参加・支援
• 事務局長（第29回日本臨床化学会北海道支部例会、2020年）

  期間 : 2020年

  役割 : 運営参加・支援
• 事務局長（第43回日本医用マススペクトル学会年会、2018年）

  期間 : 2018年

  役割 : 運営参加・支援
• 事務局長（日本臨床化学会 北海道支部、2018年度〜2021年度）

  期間 : 2018年

  役割 : 運営参加・支援
• 事務局長（第57回日本臨床化学会年会、2017年）

  期間 : 2017年

  役割 : 運営参加・支援

その他

• 2023年09月  ミトコンドリア機能向上用剤（特願2023- 165920） 

  特許出願
• 2022年08月  ミトコンドリア成分であるカルジオリピン分子種の増加剤（特願2022-126781） 

  特許出願
• 2021年08月  細胞保護用剤（特願2021-127042） 

  特許出願
• 2021年06月  非アルコール性脂肪性肝炎の診断方法（PCT/JP2021/022648） 

  PCT特許出願
• 2021年02月  Method for aiding detection of nonalcoholic steatohepatitis（PCT/JP2021/004008）
• 2021年02月  Method for aiding detection of nonalcoholic steatohepatitis (PCT/JP2019/032738) 

  米国特許出願番号：17/270, 190. 欧州特許出願番号：19851821.9.
• 2020年09月  非アルコール性脂肪性肝炎の診断方法（特願2020-149798） 

  特許出願
• 2020年07月  ミトコンドリア機能活性化剤（特願2020-120617） 

  特許出願
• 2020年02月  非アルコール性脂肪性肝炎の検出を補助する方法（特願2020-16820） 

  特許出願
• 2018年08月 - 2018年08月  非アルコール性脂肪性肝炎の検出を補助する方法（特願2018-156797） 

  特許出願
• 2018年08月 - 2018年08月  原発性胆汁性胆管炎の検出を補助する方法（特願2018-156744） 

  特許出願
• 2014年05月 - 2014年05月  軽度に酸化された酸化低密度リポタンパク質に対するモノクローナル抗体およびこれを産生するハイブリドーマ（出願番号 PCT/JP2011/060376） 

  特許出願・取得に貢献 米国出願番号13/695,043 米国特許番号US8729240B2
• 2014年04月 - 2014年04月  軽度に酸化された酸化低密度リポタンパク質に対するモノクローナル抗体およびこれを産生するハイブリドーマ（特願2012－512908） 

  特許出願・取得に貢献
• 2010年02月 - 2010年02月  トリグリセリド高含有低密度リポタンパク質を認識する自己抗体に対するモノクローナル抗体およびこれを産生するハイブリドーマ（特願2010-022076） 

  特許出願・取得に貢献