188 results on '"Nishiumi S"'
Search Results
2. Vitamin K3 attenuates lipopolysaccharide-induced acute lung injury through inhibition of nuclear factor-κB activation
- Author
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Tanaka, S., Nishiumi, S., Nishida, M., Mizushina, Y., Kobayashi, K., Masuda, A., Fujita, T., Morita, Y., Mizuno, S., Kutsumi, H., Azuma, T., and Yoshida, M.
- Published
- 2010
- Full Text
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3. Usefulness of the first screening using apolipoprotein A2 isoforms as the enrichment strategy for pancreatic cancer and its risk diseases
- Author
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Sato, Y., primary, Kobayashi, T., additional, Nishiumi, S., additional, Okaya, S., additional, Yoshida, M., additional, Kodama, Y., additional, Nagashima, K., additional, and Honda, K., additional
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- 2018
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4. Interaction Between Blood Components and Hydrogels With Poly(Oxyethylene) Chains
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Nagaoka, S., Mori, Y., Takiuchi, H., Yokota, K., Tanzawa, H., Nishiumi, S., Shalaby, Shalaby W., editor, Hoffman, Allan S., editor, Ratner, Buddy D., editor, and Horbett, Thomas A., editor
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- 1984
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5. 133 A novel serum metabolomics-based approach for skin cancers
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Fukumoto, T., primary, Nishiumi, S., additional, Yoshida, M., additional, Fujiwara, S., additional, and Nishigori, C., additional
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- 2017
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6. 746P - Usefulness of the first screening using apolipoprotein A2 isoforms as the enrichment strategy for pancreatic cancer and its risk diseases
- Author
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Sato, Y., Kobayashi, T., Nishiumi, S., Okaya, S., Yoshida, M., Kodama, Y., Nagashima, K., and Honda, K.
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- 2018
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7. Interferon-γ-producing B cells induce the formation of gastric lymphoid follicles after Helicobacter suis infection
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Yang, L., primary, Yamamoto, K., additional, Nishiumi, S., additional, Nakamura, M., additional, Matsui, H., additional, Takahashi, S., additional, Dohi, T., additional, Okada, T., additional, Kakimoto, K., additional, Hoshi, N., additional, Yoshida, M., additional, and Azuma, T., additional
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- 2015
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8. Anti-CXCL13 antibody can inhibit the formation of gastric lymphoid follicles induced by Helicobacter infection
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Yamamoto, K, primary, Nishiumi, S, additional, Yang, L, additional, Klimatcheva, E, additional, Pandina, T, additional, Takahashi, S, additional, Matsui, H, additional, Nakamura, M, additional, Zauderer, M, additional, Yoshida, M, additional, and Azuma, T, additional
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- 2014
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9. Neonatal Fc receptor for IgG (FcRn) expressed in the gastric epithelium regulates bacterial infection in mice
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Ben Suleiman, Y, primary, Yoshida, M, additional, Nishiumi, S, additional, Tanaka, H, additional, Mimura, T, additional, Nobutani, K, additional, Yamamoto, K, additional, Takenaka, M, additional, Aoganghua, A, additional, Miki, I, additional, Ota, H, additional, Takahashi, S, additional, Matsui, H, additional, Nakamura, M, additional, Blumberg, R S, additional, and Azuma, T, additional
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- 2012
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10. PLASMA COLLECTION BY ON–LINE MEMBRANE PLASMAPHERESIS WITH PLASMAX
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Komoriyama, H., Idezuki, Y., Hamabe, S., Kiyotoh, K., Tanaka, F., Yonaha, T., Watanabe, H., Sonoda, T., Nishiumi, S., and Tanzawa, H.
- Published
- 1983
11. EFFICACY AND BIOCOMPATIBILITY OF A NOVEL ANTI-CANCER FIBER IN HEMOPERFUSION ON CANCER-BEARING RABBITS
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Tani, T., Kodama, M., Oka, T., Hanasawa, K., Teramoto, K., and Nishiumi, S.
- Published
- 1984
12. Vitamin K3 attenuates lipopolysaccharide-induced acute lung injury through inhibition of nuclear factor-κB activation
- Author
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Tanaka, S, primary, Nishiumi, S, additional, Nishida, M, additional, Mizushina, Y, additional, Kobayashi, K, additional, Masuda, A, additional, Fujita, T, additional, Morita, Y, additional, Mizuno, S, additional, Kutsumi, H, additional, Azuma, T, additional, and Yoshida, M, additional
- Published
- 2009
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13. Involvement of SREBPs in 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced disruption of lipid metabolism in male guinea pig
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NISHIUMI, S, primary, YABUSHITA, Y, additional, FURUYASHIKI, T, additional, FUKUDA, I, additional, and ASHIDA, H, additional
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- 2008
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14. Efficacy and Biocompatibility of a Novel Anti‐Cancer Fiber in Hemoperfusion on Cancer‐Bearing Rabbits
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Tani, T., primary, Kodama, M., additional, Oka, T., additional, Hanasawa, K., additional, Teramoto, K., additional, and Nishiumi, S., additional
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- 2000
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15. Vitamin K3 attenuates lipopolysaccharide-induced acute lung injury through inhibition of nuclear factor-κB activation.
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Tanaka, S., Nishiumi, S., Nishida, M., Mizushina, Y., Kobayashi, K., Masuda, A., Fujita, T., Morita, Y., Mizuno, S., Kutsumi, H., Azuma, T., and Yoshida, M.
- Subjects
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VITAMIN K , *ISOPENTENOIDS , *VITAMIN deficiency , *RESPIRATORY distress syndrome , *CYTOKINES - Abstract
Vitamin K is a family of fat-soluble compounds including phylloquinone (vitamin K1), menaquinone (vitamin K2) and menadione (vitamin K3). Recently, it was reported that vitamin K, especially vitamins K1 and K2, exerts a variety of biological effects, and these compounds are expected to be candidates for therapeutic agents against various diseases. In this study, we investigated the anti-inflammatory effects of vitamin K3 in in vitro cultured cell experiments and in vivo animal experiments. In human embryonic kidney (HEK)293 cells, vitamin K3 inhibited the tumour necrosis factor (TNF)-α-evoked translocation of nuclear factor (NF)-κB into the nucleus, although vitamins K1 and K2 did not. Vitamin K3 also suppressed the lipopolysaccharide (LPS)-induced nuclear translocation of NF-κB and production of TNF-α in mouse macrophage RAW264·7 cells. Moreover, the addition of vitamin K3 before and after LPS administration attenuated the severity of lung injury in an animal model of acute lung injury/acute respiratory distress syndrome (ARDS), which occurs in the setting of acute severe illness complicated by systemic inflammation. In the ARDS model, vitamin K3 also suppressed the LPS-induced increase in the serum TNF-α level and inhibited the LPS-evoked nuclear translocation of NF-κB in lung tissue. Despite marked efforts, little therapeutic progress has been made, and the mortality rate of ARDS remains high. Vitamin K3 may be an effective therapeutic strategy against acute lung injury including ARDS. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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16. A New Treatment for Endotoxemia with Direct Hemoperfusion by Polymyxin Immobilized Fiber
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Hanasawa, K., Tani, T., Oka, T., Yoshioka, T., Endo, Y., Horisawa, M., Nakane, Y., Kodama, M., Teramoto, K., and Nishiumi, S.
- Abstract
Guest Editor's Introduction: Endotoxins, which consist of lipopolysaccharides (LPS), are known to be a pathogenic substance in patients with septic shock. Since Nolan reported endotoxin adsorption by ion exchange resin and activated charcoal, the search for more effective adsorbents were continued and have lead to the development of polymyxin B immobilized fibers. Polymyxin B is a cationic antibiotic agent which interacts with acidic phospholipids and LPL by electrostatic force. This paper was the first report written in English regarding polymixin B immobilized fibers. The adsorbent is now known as Toraymyxin PMX-20R and manufactured by Toray Co. This paper was published in Therapeutic Apheresis: A Critical Look, Y. Nosé, P.S. Malchesky, and J,W. Smith eds., ISAO Press, page 167-170 (1984).A new method of preparing polymyxin B fixed to insoluble fiber (PMX-F) was developed. PMX-F (1 g) was detoxified with 0.5-4.8 mg of lipopolysaccharides (LPS) as endotoxin (ET) in a batch system. Fixed polymyxin B(PX) was found to be firmly attached to fiber even after washing with isotonic saline or endotoxin solution. Toxicological study of the mortality of mice after injection of PMX-F-treated ET indicated that 24% (5 of 21) of the treated group survived, whereas 100% (21 of 21) of the untreated group died. In ex vivo experiments, direct hemoperfusion (DHP) by PMX-F was performed for ET-injected canine. Only 12.5% (1 of 8) survived in the control group, but 83% (10 of 12) survived in the group receiving DHP with PMX-F. Mortality in the treated group decreased remarkably. The results thus indicate the efficacy of PMX-F in neutralizing ET.
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- 2000
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17. EFFICACY AND BIOCOMPATIBILITY OF A NOVEL ANTICANCER FIBER IN HEMOPERFUSION ON CANCERBEARING RABBITS
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Tani, T., Kodama, M., Oka, T., Hanasawa, K., Teramoto, K., and Nishiumi, S.
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- 1984
18. Evaluation of Outer Structure and Form of Fibers, Yarns and Fabrics
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Nishiumi, S., primary
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- 1972
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19. Hitzehäartung von Polyäthylenterephthalat I. Unterschied in der Kristallinität von Proben, die durch trockenes Erhitzen bzw. mit Dampf gehärtet wurden
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von Ueda, N., primary and Nishiumi, S., additional
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- 1964
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20. Composition of Structure in the Melt Spinning Process
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Nishiumi, S., primary
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- 1965
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21. User-friendly relative quantification procedure for gas chromatography/mass spectrometry-based plasma metabolome analysis.
- Author
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Nishiumi S, Yokoyama T, and Ojima N
- Subjects
- Gas Chromatography-Mass Spectrometry methods, Quality Control, Metabolomics methods, Metabolome, Plasma
- Abstract
Rationale: Recently, metabolome analysis has been applied to a variety of research fields, but differences between batches or facilities can cause discrepancies in the results of such analyses. To resolve these issues using comprehensive metabolome analysis, in which it is difficult to perform quantitative analyses of all detected metabolites, internal standard compounds are used to obtain relative metabolite levels. This study investigated gas chromatography/mass spectrometry-based plasma metabolome analysis methods that are superior to relative quantification using internal standard compounds., Methods: In experiment I, four analyses were performed under different analytical conditions at one facility, and then the data from the four analyses were compared. In experiment II, the same samples were analyzed at three facilities, and then the data from the three facilities were compared., Results: Regarding the relative values obtained through comparisons with the internal standard compound, differences in the analytical results were observed among the four analytical conditions in experiment I and among the three facilities in experiment II, and the differences observed among the three facilities (experiment II) were larger. When correction was performed using plasma as a quality control, which is the procedure suggested in this study, these differences were markedly ameliorated., Conclusion: The suggested procedure involves the analysis of a plasma standard as a quality control for each batch and the calculation of relative target plasma to quality-control plasma values for each metabolite. This is an easy and low-cost method and could be readily employed by researchers during comprehensive plasma metabolome analysis., (© 2023 John Wiley & Sons Ltd.)
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- 2024
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22. Exploration of Metabolite Biomarkers to Predict the Efficacy of Dupilumab Treatment for Atopic Dermatitis.
- Author
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Miyamoto S, Imai Y, Matsutani M, Nagai M, Yamanishi K, Kanazawa N, and Nishiumi S
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- Humans, Retrospective Studies, Ribose therapeutic use, Treatment Outcome, Severity of Illness Index, Biomarkers, Dermatitis, Atopic drug therapy
- Abstract
Dupilumab (DUP) is the first biological agent used treating atopic dermatitis (AD). Notwithstanding its high cost, the type of patient group for which the drug is effective remains unclear. In this retrospective study, we aimed to identify novel and reliable biomarkers which can be measured before DUP administration and to predict the efficacy of DUP. Serum samples from 19 patients with AD treated with DUP were analysed by metabolome analysis using gas chromatography-mass spectrometry. Total 148 metabolites were detected, and the relative values of the metabolites were compared between the patient group that achieved 75% improvement in Eczema Area and Severity Index 16 weeks after administration of DUP (high responders: HR; n = 11) and that did not (low responders: LR; n = 8). The HR and LR groups had significant differences in the relative values of the eight metabolites (lactic acid, alanine, glyceric acid, fumaric acid, nonanoic acid, ribose, sorbitol, and ornithine), with ribose emerging as the best. Furthermore, we evaluated the serum concentrations of ribose and found that ribose may be a useful metabolite biomarker for predicting the efficacy of DUP in AD., Competing Interests: YI has received honoraria for lectures from Sanofi and Maruho. SN belongs to the Department of Omics Medicine, Hyogo Medical University, which is funded by Shimadzu Co. The remaining authors declare no conflict of interest regarding the publication of this article., (Copyright © 2023 Shoko Miyamoto et al.)
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- 2023
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23. Corrigendum: 'Genome-wide association study of gastric cancer- and duodenal ulcer-derived Helicobacter pylori strains reveals discriminatory genetic variations and novel oncoprotein candidates'.
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Tuan VP, Yahara K, Dung HDQ, Binh TT, Tung PH, Tri TD, Thuan NPM, Khien VV, Trang TTH, Phuc BH, Tshibangu-Kabamba E, Matsumoto T, Akada J, Suzuki R, Okimoto T, Kodama M, Murakami K, Yano H, Fukuyo M, Takahashi N, Kato M, Nishiumi S, Azuma T, Ogura Y, Hayashi T, Toyoda A, Kobayashi I, and Yamaoka Y
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- 2023
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24. Itraconazole Modulates Phospholipid Levels in Tumor-associated Macrophages.
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Takimoto Y, Tsubamoto H, Isono-Taniguchi R, Ueda T, Sakata K, Nakagawa K, Narita S, Wakimoto YU, Shibahara H, and Nishiumi S
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- Humans, Phospholipids metabolism, Phospholipids pharmacology, Cell Differentiation, Macrophages metabolism, Cell Line, Tumor, Tumor Microenvironment, Tumor-Associated Macrophages, Itraconazole pharmacology
- Abstract
Background/aim: Itraconazole, an antifungal drug, repolarizes pro-tumorigenic M2 tumor-associated macrophages to anti-tumorigenic M1-like phenotypes, thereby inhibiting the proliferation of cancer cells; however, the underlying mechanism remains unclear. Therefore, we investigated the effect of itraconazole on membrane-associated lipids in tumor-associated macrophages (TAM)., Materials and Methods: M1 and M2 macrophages were derived from the human monocyte leukemia cell line (THP-1) and cultured with or without 10 μM itraconazole. Cells were homogenized and subjected to liquid chromatography/mass spectrometry (LC/MS) analysis to estimate the glycerophospholipid levels in the cells., Results: Lipidomic analysis results, displayed on a volcano plot, revealed that itraconazole-induced altered phospholipid composition, with more pronounced changes in M2 macrophages than in M1. Notably, itraconazole significantly increased intracellular phosphatidylinositol and lysophosphatidylcholine levels in M2 macrophages., Conclusion: Itraconazole modulates the lipid metabolism of TAMs, which could have implications for the development of novel cancer therapies., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
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- 2023
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25. Exosome-derived small non-coding RNAs reveal immune response upon grafting transplantation in Pinctada fucata (Mollusca).
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Huang S, Nishiumi S, Asaduzzaman M, Pan Y, Liu G, Yoshitake K, Maeyama K, Kinoshita S, Nagai K, Watabe S, Yoshida T, and Asakawa S
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- Animals, Immunity, RNA, Small Interfering genetics, RNA, Small Interfering metabolism, Exosomes genetics, Exosomes metabolism, MicroRNAs genetics, Pinctada genetics, Pinctada metabolism, RNA, Small Untranslated
- Abstract
Exosomes, a subset of small extracellular vesicles, carry various nucleic acids, proteins, lipids, amino acids and metabolites. They function as a mode of intercellular communication and molecular transfer. Exosome cargo molecules, including small non-coding RNAs (sncRNAs), are involved in the immune response in various organisms. However, the role of exosome-derived sncRNAs in immune responses in molluscs remains unclear. Here, we aimed to reveal the sncRNAs involved in the immune response during grafting transplantation by the pearl oyster Pinctada fucata . Exosomes were successfully extracted from the P. fucata haemolymph during graft transplantation. Abundant microRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs) were simultaneously discovered in P. fucata exosomes by small RNA sequencing. The expression patterns of the miRNAs and piRNAs at the grafting and initial stages were not substantially different, but varied significantly between the initial and later stages. Target prediction and functional analysis indicate that these miRNAs and piRNAs are related to immune response upon grafting transplantation, whereas piRNAs may also be associated with transposon silencing by targeting with genome transposon elements. This work provides the basis for a functional understanding of exosome-derived sncRNAs and helps to gain further insight into the PIWI/piRNA pathway function outside of germline cells in molluscs.
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- 2022
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26. Comparative Evaluation of Plasma Metabolomic Data from Multiple Laboratories.
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Nishiumi S, Izumi Y, Hirayama A, Takahashi M, Nakao M, Hata K, Saigusa D, Hishinuma E, Matsukawa N, Tokuoka SM, Kita Y, Hamano F, Okahashi N, Ikeda K, Nakanishi H, Saito K, Hirai MY, Yoshida M, Oda Y, Matsuda F, and Bamba T
- Abstract
In mass spectrometry-based metabolomics, the differences in the analytical results from different laboratories/machines are an issue to be considered because various types of machines are used in each laboratory. Moreover, the analytical methods are unique to each laboratory. It is important to understand the reality of inter-laboratory differences in metabolomics. Therefore, we have evaluated whether the differences in analytical methods, with the exception sample pretreatment and including metabolite extraction, are involved in the inter-laboratory differences or not. In this study, nine facilities are evaluated for inter-laboratory comparisons of metabolomic analysis. Identical dried samples prepared from human and mouse plasma are distributed to each laboratory, and the metabolites are measured without the pretreatment that is unique to each laboratory. In these measurements, hydrophilic and hydrophobic metabolites are analyzed using 11 and 7 analytical methods, respectively. The metabolomic data acquired at each laboratory are integrated, and the differences in the metabolomic data from the laboratories are evaluated. No substantial difference in the relative quantitative data (human/mouse) for a little less than 50% of the detected metabolites is observed, and the hydrophilic metabolites have fewer differences between the laboratories compared with hydrophobic metabolites. From evaluating selected quantitatively guaranteed metabolites, the proportion of metabolites without the inter-laboratory differences is observed to be slightly high. It is difficult to resolve the inter-laboratory differences in metabolomics because all laboratories cannot prepare the same analytical environments. However, the results from this study indicate that the inter-laboratory differences in metabolomic data are due to measurement and data analysis rather than sample preparation, which will facilitate the understanding of the problems in metabolomics studies involving multiple laboratories.
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- 2022
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27. Effect of a High-Fat Diet on the Small-Intestinal Environment and Mucosal Integrity in the Gut-Liver Axis.
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Nakanishi T, Fukui H, Wang X, Nishiumi S, Yokota H, Makizaki Y, Tanaka Y, Ohno H, Tomita T, Oshima T, and Miwa H
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- Animals, Antimicrobial Cationic Peptides metabolism, Body Weight, Cytokines genetics, Cytokines metabolism, Gastrointestinal Microbiome, Lipopolysaccharides metabolism, Male, Mice, Inbred C57BL, RNA, Messenger genetics, RNA, Messenger metabolism, Tight Junction Proteins metabolism, Mice, Diet, High-Fat, Intestinal Mucosa pathology, Intestine, Small pathology, Liver pathology
- Abstract
Although high-fat diet (HFD)-related dysbiosis is involved in the development of steatohepatitis, its pathophysiology especially in the small intestine remains unclear. We comprehensively investigated not only the liver pathology but also the microbiome profile, mucosal integrity and luminal environment in the small intestine of mice with HFD-induced obesity. C57BL/6J mice were fed either a normal diet or an HFD, and their small-intestinal contents were subjected to microbial 16S rDNA analysis. Intestinal mucosal permeability was evaluated by FITC-dextran assay. The levels of bile acids in the small-intestinal contents were measured by liquid chromatography/mass spectrometry. The expression of tight junction molecules, antimicrobial peptides, lipopolysaccharide and macrophage marker F4/80 in the small intestine and/or liver was examined by real-time RT-PCR and immunohistochemistry. The abundance of Lactobacillus was markedly increased and that of Clostridium was drastically decreased in the small intestine of mice fed the HFD. The level of conjugated taurocholic acid was significantly increased and those of deconjugated cholic acid/secondary bile acids were conversely decreased in the small-intestinal contents. The expression of occludin, antimicrobial Reg IIIβ/γ and IL-22 was significantly decreased in the small intestine of HFD-fed mice, and the intestinal permeability was significantly accelerated. Infiltration of lipopolysaccharide was significantly increased in not only the small-intestinal mucosa but also the liver of HFD-fed mice, and fat drops were apparently accumulated in the liver. Pathophysiological alteration of the luminal environment in the small intestine resulting from a HFD is closely associated with minimal inflammation involving the gut-liver axis through disturbance of small-intestinal mucosal integrity.
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- 2021
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28. Genome-wide association study of gastric cancer- and duodenal ulcer-derived Helicobacter pylori strains reveals discriminatory genetic variations and novel oncoprotein candidates.
- Author
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Tuan VP, Yahara K, Dung HDQ, Binh TT, Huu Tung P, Tri TD, Thuan NPM, Khien VV, Trang TTH, Phuc BH, Tshibangu-Kabamba E, Matsumoto T, Akada J, Suzuki R, Okimoto T, Kodama M, Murakami K, Yano H, Fukuyo M, Takahashi N, Kato M, Nishiumi S, Azuma T, Ogura Y, Hayashi T, Toyoda A, Kobayashi I, and Yamaoka Y
- Subjects
- Genome-Wide Association Study, Humans, Oncogene Proteins genetics, Polymorphism, Single Nucleotide, Duodenal Ulcer complications, Duodenal Ulcer genetics, Duodenal Ulcer microbiology, Helicobacter Infections genetics, Helicobacter Infections microbiology, Helicobacter pylori genetics, Stomach Neoplasms complications, Stomach Neoplasms genetics, Stomach Neoplasms microbiology
- Abstract
Genome-wide association studies (GWASs) can reveal genetic variations associated with a phenotype in the absence of any hypothesis of candidate genes. The problem of false-positive sites linked with the responsible site might be bypassed in bacteria with a high homologous recombination rate, such as Helicobacter pylori , which causes gastric cancer. We conducted a small-sample GWAS (125 gastric cancer cases and 115 controls) followed by prediction of gastric cancer and control (duodenal ulcer) H. pylori strains. We identified 11 single nucleotide polymorphisms (eight amino acid changes) and three DNA motifs that, combined, allowed effective disease discrimination. They were often informative of the underlying molecular mechanisms, such as electric charge alteration at the ligand-binding pocket, alteration in subunit interaction, and mode-switching of DNA methylation. We also identified three novel virulence factors/oncoprotein candidates. These results provide both defined targets for further informatic and experimental analyses to gain insights into gastric cancer pathogenesis and a basis for identifying a set of biomarkers for distinguishing these H. pylori -related diseases.
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- 2021
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29. Itraconazole Inhibits Intracellular Cholesterol Trafficking and Decreases Phosphatidylserine Level in Cervical Cancer Cells.
- Author
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Isono R, Tsubamoto H, Ueda T, Takimoto Y, Inoue K, Sakata K, Shibahara H, and Nishiumi S
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- Biological Transport, Cell Line, Tumor, Female, Humans, Lysophosphatidylcholines metabolism, Uterine Cervical Neoplasms metabolism, Uterine Cervical Neoplasms pathology, Antineoplastic Agents pharmacology, Cholesterol metabolism, Itraconazole pharmacology, Phosphatidylserines metabolism, Uterine Cervical Neoplasms drug therapy
- Abstract
Background/aim: Itraconazole shows anticancer activity in various types of cancer but its underlying mechanism is unclear. We investigated the effect of itraconazole on membrane-associated lipids., Materials and Methods: To investigate the influences of itraconazole on cholesterol trafficking, cervical cancer CaSki cells were cultured with itraconazole and analyzed by Filipin staining followed by confocal microscopy. Effect on the glycerophospholipid profiles was analyzed by liquid chromatography/mass spectrometry (LC/MS)., Results: After itraconazole treatment, Filipin staining revealed cholesterol accumulation in the intracellular compartments, which was similar to the distribution after treatment of U18666A (cholesterol transport inhibitor). LC/MS analysis showed a significant decrease in phosphatidylserine levels and an increase in lysophosphatidylcholine levels in CaSki cells., Conclusion: Itraconazole inhibited cholesterol trafficking and altered the phospholipid composition. Alterations in the cell membrane can potentiate the anticancer activity of itraconazole., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
- Published
- 2021
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30. Tumor resistance to ferroptosis driven by Stearoyl-CoA Desaturase-1 (SCD1) in cancer cells and Fatty Acid Biding Protein-4 (FABP4) in tumor microenvironment promote tumor recurrence.
- Author
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Luis G, Godfroid A, Nishiumi S, Cimino J, Blacher S, Maquoi E, Wery C, Collignon A, Longuespée R, Montero-Ruiz L, Dassoul I, Maloujahmoum N, Pottier C, Mazzucchelli G, Depauw E, Bellahcène A, Yoshida M, Noel A, and Sounni NE
- Subjects
- Endothelial Cells metabolism, Fatty Acid-Binding Proteins, Fatty Acids, Humans, Neoplasm Recurrence, Local, Stearoyl-CoA Desaturase metabolism, Tumor Microenvironment, Ferroptosis
- Abstract
Problem: Tumor recurrence is a major clinical issue that represents the principal cause of cancer-related deaths, with few targetable common pathways. Mechanisms by which residual tumors persist and progress under a continuous shift between hypoxia-reoxygenation after neoadjuvent-therapy are unknown. In this study, we investigated the role of lipid metabolism and tumor redox balance in tumor recurrence., Methods: Lipidomics, proteomics and mass spectrometry imaging approaches where applied to mouse tumor models of recurrence. Genetic and pharmacological inhibitions of lipid mediators in tumors were used in vivo and in functional assays in vitro., Results: We found that stearoyl-CoA desaturase-1 (SCD1) expressed by cancer cells and fatty acid binding protein-4 (FABP4) produced by tumor endothelial cells (TECs) and adipocytes in the tumor microenvironment (TME) are essential for tumor relapse in response to tyrosine kinase inhibitors (TKI) and chemotherapy. SCD1 and FABP4 were also found upregulated in recurrent human breast cancer samples and correlated with worse prognosis of cancer patients with different types of tumors. Mechanistically, SCD1 leads to fatty acid (FA) desaturation and FABP4 derived from TEM enhances lipid droplet (LD) in cancer cells, which cooperatively protect from oxidative stress-induced ferroptosis. We revealed that lipid mobilization and desaturation elicit tumor intrinsic antioxidant and anti-ferroptotic resources for survival and regrowth in a harsh TME. Inhibition of lipid transport from TME by FABP4 inhibitor reduced tumor regrowth and by genetic - or by pharmacological - targeting SCD1 in vivo, tumor regrowth was abolished completely., Conclusion: This finding unveils that it is worth taking advantage of tumor lipid addiction, as a tumor vulnerability to design novel treatment strategy to prevent cancer recurrence., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2021
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31. Adrenic acid induces oxidative stress in hepatocytes.
- Author
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Zhao J, Nishiumi S, Tagawa R, Yano Y, Inoue J, Hoshi N, Yoshida M, and Kodama Y
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- Antioxidants metabolism, Arachidonic Acid pharmacology, Cell Survival drug effects, Fatty Acid Elongases metabolism, Fatty Acids, Unsaturated metabolism, Hep G2 Cells, Hepatocytes enzymology, Hepatocytes metabolism, Humans, Kelch-Like ECH-Associated Protein 1 metabolism, NF-E2-Related Factor 2 metabolism, Reactive Oxygen Species metabolism, Fatty Acids, Unsaturated pharmacology, Hepatocytes drug effects, Oxidative Stress
- Abstract
Adrenic acid (ADA), which is an endogenously synthesized polyunsaturated free fatty acid, was significantly increased in nonalcoholic fatty liver disease (NAFLD) patients and NAFLD-model mice compared with the corresponding controls in our previous study. To elucidate the involvement of ADA in NAFLD and nonalcoholic steatohepatitis (NASH), we examined ADA-induced lipotoxicity in human hepatocarcinoma HepG2 cells. The ROS production in HepG2 cells was increased by exposure to ADA. It was also shown that the treatment with ADA decreased cell viability in a dose-dependent manner. The N-Acetyl-L-Cysteine pretreatment counteracted this ADA-induced ROS production and cell death. Furthermore, ADA modulated the expressions of SOD2, HO-1 and Gpx1 as antioxidant enzymes. These findings suggest that ADA could induce oxidative stress accompanied by cell death, providing new insights into lipotoxicity that is involved in the pathogenesis of NAFLD and NASH., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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32. Prospective Study Using Plasma Apolipoprotein A2-Isoforms to Screen for High-Risk Status of Pancreatic Cancer.
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Sato Y, Kobayashi T, Nishiumi S, Okada A, Fujita T, Sanuki T, Kobayashi M, Asahara M, Adachi M, Sakai A, Shiomi H, Masuda A, Yoshida M, Takeuchi K, Kodama Y, Kutsumi H, Nagashima K, and Honda K
- Abstract
Apolipoprotein A2-ATQ/AT (apoA2-ATQ/AT) has been identified as a minimally invasive biomarker for detecting pancreatic cancer (PC) and high-risk (HR) individuals for PC. To establish an efficient enrichment strategy for HR, we carried out a plasma apoA2-ATQ/AT level-based prospective screening study among the general population. The subjects for the screening study were recruited at six medical check-up facilities in Japan between October 2015 and January 2017. We evaluated the positive predictive value (PPV) of the plasma apoA2-ATQ/AT level of ≤35 μg/mL for detecting PC and HR. Furthermore, we prospectively confirmed its diagnostic accuracy with another post-diagnosis population in a cross-sectional study. We enrolled 5120 subjects in experimental screening, with 84 subjects (1.3%) showing positive results for apoA2-ATQ/AT. Pancreatic abnormalities were recognized in 26 of the 84 subjects from imaging examinations. Pancreatic abnormalities detected included 1 PC and 15 HR abnormalities, such as cystic lesions including intraductal papillary mucinous neoplasm. The PPV of apoA2-ATQ/AT for detecting PC and HR was 33.3%. Moreover, a combination study with another cross-sectional study revealed that the area under the curve for apoA2-ATQ/AT to distinguish PC from healthy controls was 0.903. ApoA2-ATQ/AT has the potential to enrich PC and HR by increasing the diagnostic probability before imaging examinations.
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- 2020
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33. Effects of differences in pre-analytical processing on blood protein profiles determined with SWATH-MS.
- Author
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Nambu M, Nishiumi S, Kobayashi T, Masuda T, Ito S, Yoshida M, and Ohtsuki S
- Subjects
- Blood Specimen Collection, Humans, Metabolomics, Proteome, Blood Proteins, Proteomics
- Abstract
The purpose of the present study was to assess the differences between the human serum and plasma proteomes, and the stability of human plasma proteins under different storage conditions following blood collection, by means of SWATH-MS analysis. When we compared plasma and serum prepared immediately after blood sampling, 95.5% of 176 quantified proteins differed by less than 1.5-fold. When we compared plasma samples prepared by centrifugation after storage of blood at room temperature for 0, 15 or 30 min, or under refrigeration at 0-5 °C for 1, 4 or 8 h, no protein showed a significant change (q < 0.05) that amounted to 1.5-fold or more, except hemoglobins. Those proteins were greatly increased in a single sample at 8 h, probably due to hemolysis. Comparison of data from the same samples indicates that the blood proteome is more stable than the blood metabolome. The present results suggest that most components of the proteome are essentially the same in plasma and serum, and are stable under the storage conditions examined in the present study. However, it may be important to pay attention to the extent of coagulation, and levels of platelet and hemolysis-related proteins. SIGNIFICANCE: Pre-analytical processing and storage conditions after blood collection are expected to influence the blood proteome. Therefore, we investigated differences in the proteome between human serum and plasma, as well as the stability of human plasma proteins under different storage conditions: at room temperature for 0-30 min, or at 0-5 °C for 1-8 h, which may reflect the clinical situation of blood collection. Proteomics analysis with SWATH-MS identified 342 proteins, and 176 proteins quantified with two or more unique peptides were compared. The levels of most components of the proteome were similar in plasma and serum, and were stable under the storage conditions examined. However, it is necessary to consider the possibility of coagulation, as this affects the levels of platelet and hemolysis-related proteins. Interestingly, the blood proteome appears to be more stable than the blood metabolome, based on previously reported metabolomics data with same samples. These data will be helpful in designing protocols for blood sampling and for blood biomarker discovery and validation., Competing Interests: Declaration of Competing Interest S.O. is a full professor at Kumamoto University and is also a director of Proteomedix Frontiers. This study was not supported by the company, and its position at the company did not influence the design of the study, the collection of the data, the analysis or interpretation of the data, the decision to submit the manuscript for publication, or the writing of the manuscript and did not present any financial conflicts. The other authors declare no competing interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)
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- 2020
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34. Possibility of detecting intraductal papillary mucinous neoplasms using metabolite biomarkers for pancreatic cancer.
- Author
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Nakano R, Nishiumi S, Kobayashi T, Ikegawa T, Kodama Y, and Yoshida M
- Abstract
Aim: The aim of this study was to identify whether metabolite biomarker candidates for pancreatic cancer (PC) could aid detection of intraductal papillary mucinous neoplasms (IPMN), recognized as high-risk factors for PC. Materials & methods: The 12 metabolite biomarker candidates, which were found to be useful to detect PC in our previous study, were evaluated for plasma samples from patients with PC (n = 44) or IPMN (n = 24) or healthy volunteers (n = 46). Results: Regarding the performance of individual biomarkers of PC and PC high-risk IPMN, lysine exhibited the best performance (sensitivity: 67.8%; specificity: 86.9%). The multiple logistic regression analysis-based detection model displayed high sensitivity and specificity values of 92.5 and 90.6%, respectively. Conclusion: Metabolite biomarker candidates for PC are useful for detecting high-risk IPMN, which can progress to PC.
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- 2020
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35. Effects of Helicobacter pylori on the glutathione-related pathway in gastric epithelial cells.
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Matsuoka K, Nishiumi S, Yoshida M, and Kodama Y
- Subjects
- Cell Line, Tumor, Down-Regulation genetics, Glutathione Disulfide metabolism, Glutathione Synthase metabolism, Helicobacter Infections metabolism, Helicobacter Infections microbiology, Humans, Interleukin-8 genetics, Interleukin-8 metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Virulence Factors, Epithelial Cells metabolism, Epithelial Cells microbiology, Glutathione metabolism, Helicobacter pylori physiology, Metabolic Networks and Pathways, Stomach pathology
- Abstract
Virulence factors of Helicobacter pylori (H. pylori) are diverse, so various biological responses happen in a host infected with H. pylori. The aim of this study is to conduct the metabolomics-based evaluation on H. pylori infection. AGS human gastric carcinoma cells were infected with H. pylori strain 26695, and then the altered metabolite pathways in the infected AGS cells were analyzed by metabolomics. Metabolites related to the glutathione (GSH) cycle were downregulated by H. pylori infection. Next, we evaluated the effects of H. pylori on the GSH-related pathway in AGS cells infected with H. pylori isolated from patients with atrophic gastritis (AG), duodenal ulcer (DU) and gastric cancer (GC). We found that the declined degree of GSH levels and oxidative stress were greater in AGS cells infected with GC strains than DU and AG-derived strains. There were no significant differences in almost mRNA expressions of GSH-related factors among different clinical strains, but the protein expression of glutathione synthetase was lower in AGS cells infected with GC-derived strains than DU and AG-derived strains. Our data demonstrates that GC-derived H. pylori-induced oxidative stress in a host is stronger and GC-derived strains may have suppressive influences on the host's GSH-related defense systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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36. Detection of Novel Amino Acid Polymorphisms in the East Asian CagA of Helicobacter Pylori with Full Sequencing Data.
- Author
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Hayashi H, Inoue J, Oyama K, Matsuoka K, Nishiumi S, Yoshida M, Yano Y, and Kodama Y
- Subjects
- Antigens, Bacterial chemistry, Bacterial Proteins chemistry, Databases, Genetic, Asia, Eastern, Japan, Virulence Factors chemistry, Whole Genome Sequencing, Antigens, Bacterial genetics, Bacterial Proteins genetics, Helicobacter pylori genetics, Helicobacter pylori pathogenicity, Polymorphism, Single Nucleotide, Virulence Factors genetics
- Abstract
Cytotoxin-associated gene A (CagA) is generally accepted to be the most important virulence factor of Helicobacter pylori and increases the risk of developing gastric cancer. East Asian CagA, which includes the EPIYA-D segment at the C-terminal region, has a significantly higher gastric carcinogenic rate than Western CagA including the EPIYA-C segment. Although the amino acid polymorphism surrounding the EPIYA motif in the C-terminal region has been examined in detail, limited information is currently available on the amino acid polymorphism of the N-terminal region of East Asian CagA. In the present study, we analyzed the sequencing data of East Asian CagA that we obtained previously to detect amino acid changes (AACs) in the N-terminal region of East Asian CagA. Four highly frequent AACs in the N-terminal region of East Asian CagA were detected in our datasets, two of which (V356A, Y677F) exhibited reproducible specificity using a validation dataset from the NCBI database, which are candidate AACs related to the pathogenic function of CagA. We examined whether these AACs affect the functions of CagA in silico model. The computational docking simulation model showed that binding affinity between CagA and phosphatidylserine remained unchanged in the model of mutant CagA reflecting both AAC, whereas that between CagA and α5β1 integrin significantly increased. Based on whole genome sequencing data we herein identified novel specific AACs in the N-terminal regions of EPIYA-D that have the potential to change the function of CagA.
- Published
- 2020
37. Possible Involvement of Lipids in the Effectiveness of Kombu in Individuals with Abnormally High Serum Triglyceride Levels.
- Author
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Nishiumi S, Izumi Y, Kobayashi T, and Yoshida M
- Subjects
- Adult, Aged, Aged, 80 and over, Biological Products therapeutic use, Fatty Acids, Nonesterified blood, Female, Humans, Hypertriglyceridemia drug therapy, Japan, Lysophosphatidylcholines blood, Male, Middle Aged, Phosphatidylcholines blood, Phosphatidylethanolamines blood, Triglycerides blood, Biological Products pharmacology, Diet, Hypertriglyceridemia blood, Laminaria, Lipids blood, Seaweed
- Abstract
In Japan, Kombu (Laminaria japonica), which is a type of seaweed, is considered to be a foodstuff with health-promoting benefits, and Japanese people actively incorporate Kombu into their diets. Previously, we reported that the frequent intake of Kombu reduced the serum triglyceride levels of subjects with abnormally high serum triglyceride levels. In the current human study, we performed metabolomic analysis of serum lipids, and then the molecular species profiles of phosphatidylcholines (PC), phosphatidylethanolamines (PE), lysophosphatidylcholines (LPC), lysophosphatidylethanolamines (LPE), and free fatty acids (FFA) were evaluated. As a result, it was found that there were no marked differences between the lipid profiles obtained before and after the intake of Kombu for 4 wk in all subjects. In the subjects with abnormal serum triglyceride levels, the intake of Kombu improved the subjects' molecular species profiles in terms of their serum levels of the diacyl and acyl forms of PC, PE, LPC, and LPE, and FFA. Furthermore, the intake of Kombu also tended to increase the serum levels of both the plasmanyl and plasmenyl forms of PC and PE in these subjects. The lipid alterations observed in our study might be related to the functionality of Kombu. Furthermore, it is important to evaluate the quality of lipids as well as the quantity of lipids in various types of research, including food functionality studies.
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- 2020
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38. GC/MS and LC/MS-based Tissue Metabolomic Analysis Detected Increased Levels of Antioxidant Metabolites in Colorectal Cancer.
- Author
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Kibi M, Nishiumi S, Kobayashi T, Kodama Y, and Yoshida M
- Subjects
- Chromatography, Liquid methods, Female, Humans, Male, Mass Spectrometry methods, Middle Aged, NAD biosynthesis, Tryptophan metabolism, Antioxidants metabolism, Colorectal Neoplasms metabolism, Gas Chromatography-Mass Spectrometry methods, Metabolomics methods
- Abstract
Late-stage colorectal cancer is resistant to current treatments. Understanding the biological processes responsible for the development and progression of colorectal cancer could aid the development of new diagnostic and treatment approaches. We used gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry-based metabolomic analysis to measure metabolite levels in pairs of colorectal cancer tissue samples and samples of the adjacent macroscopically normal mucosal tissue from 10 colon cancer patients. Regarding nucleotide metabolomic intermediates, the colorectal cancer tissue contained lower levels of ribulose 5-phosphate and higher levels of xanthine, adenine, and hypoxanthine than the normal tissue. The levels of antioxidant metabolites, such as sulfur-containing amino acids, were also significantly higher in the colorectal cancer tissue. The level of tryptophan was decreased, and the levels of molecules downstream of the tryptophan pathway, such as kynurenine and quinolinic acid, which protect colorectal cancer against the host's immune system and function in de novo nicotinamide adenine dinucleotide synthesis, were increased in the colorectal cancer tissue. The colorectal cancer tissue samples also contained higher levels of lysophospholipids and fatty acids, especially stearic acid and polyunsaturated fatty acids, including arachidonic acid and docosahexaenoic acid. Thus, understanding these cancer-specific alterations could make it possible to detect colorectal cancer early and aid the development of additional treatments for the disease, leading to improvements in colorectal cancer patients' quality of life.
- Published
- 2019
39. β-hydroxybutyrate protects hepatocytes against endoplasmic reticulum stress in a sirtuin 1-independent manner.
- Author
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Tagawa R, Kawano Y, Minami A, Nishiumi S, Yano Y, Yoshida M, and Kodama Y
- Subjects
- AMP-Activated Protein Kinases metabolism, Animals, Cell Line, Tumor, Hep G2 Cells, Hepatocytes metabolism, Humans, Mice, Phosphorylation, Tunicamycin pharmacology, 3-Hydroxybutyric Acid pharmacology, Endoplasmic Reticulum Stress drug effects, Hepatocytes drug effects, Sirtuin 1 metabolism
- Abstract
β-hydroxybutyrate (BHB), a major ketone body in mammals, is produced from fatty acids through mitochondrial fatty acid oxidation in hepatocytes. To elucidate the role of BHB in the hepatic endoplasmic reticulum (ER), we examined the effects of BHB on hepatic ER stress induced by tunicamycin. In mouse hepatoma Hepa1c1c7 cells, BHB treatment suppressed the protein expression of ER stress responsive genes and increased cell viability, while reducing the protein expression of apoptosis inducible genes, without causing any alterations in the protein expression of sirtuin 1 (SIRT1) or the phosphorylation of AMP-activated protein kinase. The intraperitoneal administration of BHB also reduced the protein expression of ER stress responsive genes in mouse livers. In human hepatoma HepG2 cells, the protein expression levels of ER stress responsive genes were increased by the partial inhibition of BHB production with siRNA targeting endogenous 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) lyase, whereas they were decreased by promoting BHB production with fenofibrate. These findings revealed that BHB helps to suppress hepatic ER stress via a SIRT1-independent pathway, and it might be possible to manipulate ER stress by regulating BHB production genetically or pharmacologically., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
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40. Comparative proteomics of Helicobacter pylori strains reveals geographical features rather than genomic variations.
- Author
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Sugiyama N, Miyake S, Lin MH, Wakabayashi M, Marusawa H, Nishiumi S, Yoshida M, and Ishihama Y
- Subjects
- Bacterial Proteins genetics, Gene Expression Profiling, Genome, Bacterial, Geography, Helicobacter Infections genetics, Helicobacter Infections metabolism, Helicobacter pylori classification, Helicobacter pylori genetics, Humans, Phosphoproteins genetics, Phylogeny, Proteome metabolism, Bacterial Proteins metabolism, Genetic Variation, Helicobacter Infections microbiology, Helicobacter pylori metabolism, Phosphoproteins metabolism, Proteome analysis
- Abstract
Helicobacter pylori, a pathogen of various gastric diseases, has many genome sequence variants. Thus, the pathogenesis and infection mechanisms of the H. pylori-driven gastric diseases have not been elucidated. Here, we carried out a large-scale proteome analysis to profile the heterogeneity of the proteome expression of 7 H. pylori strains by using an LC/MS/MS-based proteomics approach combined with a customized database consisting of nonredundant tryptic peptide sequences derived from full genome sequences of 52 H. pylori strains. The nonredundant peptide database enabled us to identify more peptides in the database search of MS/MS data compared with a simply merged protein database. Using this approach, we carried out proteome analysis of genome-unknown strains of H. pylori at as large a scale as genome-known ones. Clustering of the H. pylori strains using proteome profiling slightly differed from the genome profiling and more clearly divided the strains into two groups based on the isolated area. Furthermore, we identified phosphorylated proteins and sites of the H. pylori strains and obtained the phosphorylation motifs located in the N-terminus that are commonly observed in bacteria., (© 2018 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)
- Published
- 2019
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41. Comparison of venous and fingertip plasma using non-targeted proteomics and metabolomics.
- Author
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Nishiumi S, Kohata T, Kobayashi T, Kodama Y, Ohtsuki S, and Yoshida M
- Subjects
- Fingers, Humans, Blood Chemical Analysis, Blood Proteins analysis, Blood Proteins metabolism, Blood Specimen Collection, Metabolomics, Proteomics
- Abstract
Blood tests, which are used to evaluate health status, are relatively non-invasive and provide a great deal of health-related information. Blood is usually collected using a standard venous blood sampling protocol, but it is possible to collect blood from a subject's fingertip, and previous studies have investigated whether fingertip-derived blood can be used for various blood tests. In this study, the proteomes and metabolomes of venous and fingertip plasma were analyzed using non-targeted proteomics and metabolomics, respectively. In proteomics, the levels of 523 proteins were compared between venous and fingertip plasma. The correlation coefficient (r) for the relationship between protein levels of venous and fingertip plasma was 0.9999. Some proteins had high fingertip to venous plasma level ratios (finger:venous ratios), whereas others had low finger:venous ratios, and the mean±standard deviation (SD) finger:venous ratio was 0.994 ± 0.304. In metabolomics, 40, 33, and 216 cationic metabolites, anionic metabolites, and lipids, respectively, were detected in venous plasma, and the equivalent figures for fingertip plasma were 40, 35, and 216, respectively. Regarding the correlations between metabolite levels in venous and fingertip plasma, the correlation coefficients (r) for cationic metabolites, anionic metabolites, and lipids were 0.9952, 0.9699, and 0.9980, respectively. The mean±SD finger:venous ratio was 1.19 ± 0.584 for cationic metabolites, 1.23 ± 0.548 for anionic metabolites, and 1.00 ± 0.245 for lipids. Our study suggests that it might be possible to use fingertip plasma to measure plasma protein and metabolite levels, and will contribute to development of a fingertip blood sampling procedure for measuring blood biomarker levels., (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Published
- 2019
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42. Serum level of octanoic acid predicts the efficacy of chemotherapy for colorectal cancer.
- Author
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Iemoto T, Nishiumi S, Kobayashi T, Fujigaki S, Hamaguchi T, Kato K, Shoji H, Matsumura Y, Honda K, and Yoshida M
- Abstract
The survival times of patients with advanced colorectal cancer (CRC) have increased due to the introduction of chemotherapy involving irinotecan and cetuximab. However, further studies are required on the effective pretreatment methods for identifying patients with CRC who would respond to particular treatments. The aim of the present study was to identify biomarkers for predicting the efficacy of chemotherapy for CRC. A total of 123 serum samples were collected from 31 patients with CRC just prior to each of the first four rounds of chemotherapy. Serum metabolome analysis was performed using a multiplatform metabolomics system, and univariate Cox regression hazards analysis of the time to disease progression was conducted. Octanoic acid and 1,5-anhydro-D-glucitol were identified as biomarker candidates. In addition, the serum level of octanoic acid was indicated to be significantly associated with the time to disease progression (hazard ratio, 3.3; 95% confidence interval, 1.099-11.840; P=0.033). The serum levels of fatty acids, in particular polyunsaturated fatty acids, tended to be downregulated in the partial response group. The findings of the present study suggest that the serum level of octanoic acid may serve as a useful predictor for the prognosis of CRC.
- Published
- 2019
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43. Metabolomics-based Discovery of Serum Biomarkers to Predict the Side-effects of Neoadjuvant Chemoradiotherapy for Esophageal Squamous Cell Carcinoma.
- Author
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Nishiumi S, Fujigaki S, Kobayashi T, Kojima T, Ito Y, Daiko H, Kato K, Shoji H, Kodama Y, Honda K, and Yoshida M
- Subjects
- Adult, Aged, Cisplatin adverse effects, Combined Modality Therapy adverse effects, Esophageal Squamous Cell Carcinoma drug therapy, Esophageal Squamous Cell Carcinoma pathology, Esophageal Squamous Cell Carcinoma radiotherapy, Female, Humans, Male, Metabolomics, Middle Aged, Neoadjuvant Therapy adverse effects, Quality of Life, Biomarkers, Pharmacological blood, Biomarkers, Tumor blood, Chemoradiotherapy adverse effects, Esophageal Squamous Cell Carcinoma blood
- Abstract
Background/aim: Neoadjuvant chemoradiotherapy has side-effects that adversely affect patients' quality of life. The aim of this study was to identify serum metabolite biomarkers that might be used to predict the side-effects of neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma (ESCC)., Patients and Methods: Metabolomic analysis of serum samples from 26 patients with ESCC that were collected before neoadjuvant chemoradiotherapy was performed. The metabolites associated with hematological toxicity or nephrotoxicity were evaluated., Results: Serum levels of glutaric acid, glucuronic acid, and cystine were significantly higher in hematological toxicity, and phosphatidylcholines and phosphatidylethanolamines exhibited a tendency to be higher in those with hematological toxicity. The serum level of pyruvic acid was significantly lower in nephrotoxicity, and lysophosphatidylcholines and lysophosphatidylethanolamines tended to be lower in those with nephrotoxicity., Conclusion: Our study found that serum levels of some metabolites differed significantly between patients with and without hematological or renal side-effects. These metabolites may be useful biomarkers for predicting hematological toxicity or nephrotoxicity after neoadjuvant chemoradiotherapy for ESCC., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
- Published
- 2019
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44. Increased Levels of Branched-Chain Amino Acid Associated With Increased Risk of Pancreatic Cancer in a Prospective Case-Control Study of a Large Cohort.
- Author
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Katagiri R, Goto A, Nakagawa T, Nishiumi S, Kobayashi T, Hidaka A, Budhathoki S, Yamaji T, Sawada N, Shimazu T, Inoue M, Iwasaki M, Yoshida M, and Tsugane S
- Subjects
- Adult, Aged, Female, Humans, Male, Middle Aged, Pancreatic Neoplasms blood, Prospective Studies, Risk Factors, Amino Acids, Branched-Chain blood, Pancreatic Neoplasms etiology
- Abstract
Background & Aims: A marker is needed to identify individuals at risk for pancreatic cancer. Increases in branched-chain amino acids (BCAAs) have been associated with pancreatic cancer. We performed a prospective case-control study to study the association between plasma BCAA levels and risk of pancreatic cancer in a large cohort., Methods: We conducted a nested case-control study selected from 30,239 eligible participants 40-69 years old within the Japan Public Health Center-based prospective study. Over 16.4 years, 170 newly diagnosed pancreatic cancer cases were identified. Each case was matched to 2 controls by age, gender, geographic area, and fasting time at blood collection. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for pancreatic cancer were calculated using conditional logistic regression models with adjustment for potential confounding factors., Results: Increased plasma BCAA levels at baseline were associated with an increased risk of pancreatic cancer. Compared with the lowest quartile of BCAA levels, the OR in the highest quartile was 2.43 (95% CI 1.21-4.90), and the OR per 1 SD increase in BCAA levels was 1.32 (95% CI 1.05-1.67). The association was especially strong for cases with blood samples collected at least 10 years before cancer diagnosis (OR per SD 1.60, 95% CI 1.10-2.32) compared with those detected less than 10 years before diagnosis (OR per SD 1.16, 95% CI 0.86-1.57)., Conclusions: In an analysis of data from the Japan Public Health Center-based prospective study, we found an association between increased plasma BCAA level and increased risk of pancreatic cancer-particularly when the increase in BCAAs was observed at least 10 years before diagnosis. These findings add to the growing body of evidence for the association between BCAA levels and pancreatic cancer risk., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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45. Alterations in metabolic pathways in gastric epithelial cells infected with Helicobacter pylori.
- Author
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Matsunaga S, Nishiumi S, Tagawa R, and Yoshida M
- Subjects
- Cell Line, Tumor, Gas Chromatography-Mass Spectrometry, Humans, Metabolomics, Models, Biological, Time Factors, Epithelial Cells metabolism, Epithelial Cells microbiology, Helicobacter Infections microbiology, Helicobacter Infections pathology, Helicobacter pylori growth & development, Metabolic Networks and Pathways, Metabolome
- Abstract
Helicobacter pylori (H. pylori), which is a spiral-shaped Gram-negative microaerobic bacterium, is a causative pathogen. The entry of H. pylori into gastric epithelial cells involves various host signal transduction events, and its virulence factors can also cause a variety of biological responses. In this study, AGS human gastric carcinoma cells were infected with CagA-positive H. pylori strain ATCC43504, and then the metabolites in the AGS cells after the 2-, 6- and 12-h infections were analyzed by GC/MS-based metabolomic analysis. Among 67 metabolites detected, 11 metabolites were significantly altered by the H. pylori infection. The metabolite profiles of H. pylori-infected AGS cells were evaluated on the basis of metabolite pathways, and it was found that glycolysis, tricarboxylic acid (TCA) cycle, and amino acid metabolism displayed characteristic changes in the H. pylori-infected AGS cells. At 2 h post-infection, the levels of many metabolites related to TCA cycle and amino acid metabolism were lower in H. pylori-infected AGS cells than in the corresponding uninfected AGS cells. On the contrary, after 6-h and 12-h infections the levels of most of these metabolites were higher in the H. pylori-infected AGS cells than in the corresponding uninfected AGS cells. In addition, it was shown that the H. pylori infection might regulate the pathways related to isocitrate dehydrogenase and asparagine synthetase. These metabolite alterations in gastric epithelial cells might be involved in H. pylori-induced biological responses; thus, our findings are important for understanding H. pylori-related gastric diseases., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Published
- 2018
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46. Exploring a Novel Screening Method for Patients with Oral Squamous Cell Carcinoma: A plasma Metabolomics Analysis.
- Author
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Enomoto Y, Kimoto A, Suzuki H, Nishiumi S, Yoshida M, and Komori T
- Subjects
- Aged, Blood Glucose metabolism, Carcinoma, Squamous Cell diagnosis, Cysteine blood, Cystine blood, Early Detection of Cancer methods, Fatty Acids blood, Female, Galactose blood, Gas Chromatography-Mass Spectrometry, Humans, Male, Middle Aged, Mouth Neoplasms diagnosis, Biomarkers, Tumor blood, Carcinoma, Squamous Cell blood, Metabolomics methods, Mouth Neoplasms blood
- Abstract
Aim: This study aimed to explore novel metabolite biomarker candidates for screening oral squamous cell carcinoma (OSCC)., Patients & Methods: We collected plasma samples from 48 patients with OSCC and 29 with an oral disease and conducted a plasma metabolomics analysis of patients with OSCC using gas chromatography mass spectrometry. Then, we used the cross-validation procedure to ensure the accuracy of biomarker candidates., Results: We selected four biomarker candidates against OSCC. Their sensitivity was more than 90%, and the AUC was over 0.9 according to the receiver operating characteristic curve analysis., Conclusions: The findings of this study suggest four potential metabolites as biomarkers for OSCC screening.
- Published
- 2018
47. Identification of serum biomarkers of chemoradiosensitivity in esophageal cancer via the targeted metabolomics approach.
- Author
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Fujigaki S, Nishiumi S, Kobayashi T, Suzuki M, Iemoto T, Kojima T, Ito Y, Daiko H, Kato K, Shouji H, Honda K, Azuma T, and Yoshida M
- Subjects
- Aged, Esophageal Neoplasms therapy, Esophageal Squamous Cell Carcinoma therapy, Female, Humans, Male, Middle Aged, Biomarkers, Tumor metabolism, Chemoradiotherapy, Esophageal Neoplasms metabolism, Esophageal Squamous Cell Carcinoma metabolism, Metabolomics, Neoadjuvant Therapy
- Abstract
Aim: To identify the serum metabolomics signature that is correlated with the chemoradiosensitivity of esophageal squamous cell carcinoma (ESCC)., Materials & Methods: Untargeted and targeted metabolomics analysis of serum samples from 26 ESCC patients, which were collected before the neoadjuvant chemoradiotherapy, was performed., Results: On receiving the results of untargeted metabolomics analysis, we performed the targeted metabolomics analysis of the six metabolites (arabitol, betaine, glycine, L-serine, L-arginine and L-aspartate). The serum levels of the four metabolites (arabitol, glycine, L-serine and L-arginine) were significantly lower in the patients who achieved pathological complete response with neoadjuvant chemoradiotherapy compared with the patients who did not achieve pathological complete response (p = 0.0086, 0.0345, 0.0106 and 0.0373, respectively)., Conclusion: The serum levels of metabolites might be useful for predicting the chemoradiosensitivity of ESCC patients.
- Published
- 2018
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48. [Possibility of Metabolite Biomarkers for Early Detection of Cancer].
- Author
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Nishiumi S and Yoshida M
- Subjects
- Humans, Biomarkers, Tumor metabolism, Early Detection of Cancer methods, Metabolome, Neoplasms diagnosis, Neoplasms metabolism
- Abstract
Recently, the omics analysis, which comprehensively analyzed the biological molecules such as DNA, RNA, protein and low molecular weight metabolites, has been developed. The metabolome analysis that comprehensively analyzes low molecular weight metabolites is one of the most recent omics analysis, and attracts rising attention. Evaluating the metabolite alterations and clarifying the metabolite profiles in the body will lead to understandings of biological information, and the metabolome analysis has the potential of elucidation of novel pathological conditions and discovery of metabolite biomarkers. In this article, we explain the characteristics of the omics analysis. Regarding the metabolome analysis, its detailed explanations are carried out, and we also introduce our metabolite biomarker research about pancreatic cancer using the metabolome analysis.
- Published
- 2018
49. Alterations in Docosahexaenoic Acid-Related Lipid Cascades in Inflammatory Bowel Disease Model Mice.
- Author
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Nishiumi S, Izumi Y, and Yoshida M
- Subjects
- Animals, Ascitic Fluid metabolism, Chromatography, Liquid, Disease Models, Animal, Gas Chromatography-Mass Spectrometry, Genetic Predisposition to Disease, Inflammatory Bowel Diseases genetics, Inflammatory Bowel Diseases pathology, Interleukin-10 deficiency, Interleukin-10 genetics, Intestine, Large pathology, Metabolomics methods, Mice, Inbred C57BL, Mice, Knockout, Phenotype, Signal Transduction, Tandem Mass Spectrometry, Docosahexaenoic Acids blood, Inflammation Mediators blood, Inflammatory Bowel Diseases blood, Intestine, Large metabolism
- Abstract
Background: Inflammatory bowel disease (IBD) is an intestinal disorder, involving chronic and relapsing inflammation of the digestive tract. Dysregulation of the immune system based on genetic, environmental, and other factors seems to be involved in the onset of IBD, but its exact pathogenesis remains unclear. Therefore, radical treatments for ulcerative colitis and Crohn's disease remain to be found, and IBD is considered to be a refractory disease., Aims: The aim of this study is to obtain novel insights into IBD via metabolite profiling of interleukin (IL)-10 knockout mice (an IBD animal model that exhibits a dysregulated immune system)., Methods: In this study, the metabolites in the large intestine and plasma of IL-10 knockout mice were analyzed. In our analytical system, two kinds of analysis (gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry) were used to detect a broader range of metabolites, including both hydrophilic and hydrophobic metabolites. In addition, an analysis of lipid mediators in the large intestine and ascites of IL-10 knockout mice was carried out., Results: The levels of a variety of metabolites, including lipid mediators, were altered in IL-10 knockout mice. For example, high large intestinal and plasma levels of docosahexaenoic acid (DHA) were observed. In addition, arachidonic acid- and DHA-related lipid cascades were upregulated in the ascites of the IL-10 knockout mice., Conclusions: Our findings based on metabolite profiles including lipid mediators must contribute to development of researches about IBD.
- Published
- 2018
- Full Text
- View/download PDF
50. Differences in metabolite profiles caused by pre-analytical blood processing procedures.
- Author
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Nishiumi S, Suzuki M, Kobayashi T, and Yoshida M
- Subjects
- Blood Specimen Collection adverse effects, Chromatography, Liquid methods, Gas Chromatography-Mass Spectrometry methods, Healthy Volunteers, Humans, Mass Spectrometry methods, Plasma chemistry, Plasma metabolism, Serum chemistry, Serum metabolism, Specimen Handling adverse effects, Specimen Handling methods, Biomarkers analysis, Biomarkers blood, Blood Specimen Collection methods, Metabolome, Metabolomics methods
- Abstract
Recently, the use of metabolomic analysis of human serum and plasma for biomarker discovery and disease diagnosis in clinical studies has been increasing. The feasibility of using a metabolite biomarker for disease diagnosis is strongly dependent on the metabolite's stability during pre-analytical blood processing procedures, such as serum or plasma sampling and sample storage prior to centrifugation. However, the influence of blood processing procedures on the stability of metabolites has not been fully characterized. In the present study, we compared the levels of metabolites in matched human serum and plasma samples using gas chromatography coupled with mass spectrometry and liquid chromatography coupled with mass spectrometry. In addition, we evaluated the changes in plasma metabolite levels induced by storage at room temperature or at a cold temperature prior to centrifugation. As a result, it was found that 76 metabolites exhibited significant differences between their serum and plasma levels. Furthermore, the pre-centrifugation storage conditions significantly affected the plasma levels of 45 metabolites. These results highlight the importance of blood processing procedures during metabolome analysis, which should be considered during biomarker discovery and the subsequent use of biomarkers for disease diagnosis., (Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
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