• Title/Summary/Keyword: metabolic biomarker

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Application of metabolic profiling for biomarker discovery

  • Hwang, Geum-Sook
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2007.11a
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    • pp.19-27
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    • 2007
  • An important potential of metabolomics-based approach is the possibility to develop fingerprints of diseases or cellular responses to classes of compounds with known common biological effect. Such fingerprints have the potential to allow classification of disease states or compounds, to provide mechanistic information on cellular perturbations and pathways and to identify biomarkers specific for disease severity and drug efficacy. Metabolic profiles of biological fluids contain a vast array of endogenous metabolites. Changes in those profiles resulting from perturbations of the system can be observed using analytical techniques, such as NMR and MS. $^1H$ NMR was used to generate a molecular fingerprint of serum or urinary sample, and then pattern recognition technique was applied to identity molecular signatures associated with the specific diseases or drug efficiency. Several metabolites that differentiate disease samples from the control were thoroughly characterized by NMR spectroscopy. We investigated the metabolic changes in human normal and clinical samples using $^1H$ NMR. Spectral data were applied to targeted profiling and spectral binning method, and then multivariate statistical data analysis (MVDA) was used to examine in detail the modulation of small molecule candidate biomarkers. We show that targeted profiling produces robust models, generates accurate metabolite concentration data, and provides data that can be used to help understand metabolic differences between healthy and disease population. Such metabolic signatures could provide diagnostic markers for a disease state or biomarkers for drug response phenotypes.

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Glutathione (GSH) Response as a Metabolic Biomarker to Benzo(α)pyrene and Aroclor 1254 Exposure in the Pacific Oyster Crassostrea gigas

  • Jo, Qtae;Choy, Eun-Jung;Lee, Yong-Hwa;Ko, Sung-Jung;Song, Young-Chae;Kim, Myoung-Jin;Hwang, Eung-Ju
    • Fisheries and Aquatic Sciences
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    • v.9 no.4
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    • pp.140-145
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    • 2006
  • We measured activities of the ubiquitous tripeptide non-protein thiol (L-${\gamma}$-glutamyl-L-cysteinyl-glycine), glutathione (GSH), which is believed to playa fundamental role in detoxifying xenobiotics in biological systems, as a metabolic biomarker for benzo(${\alpha}$)pyrene and Aroclor 1254 exposure in the Pacific oyster Crassostrea gigas. Reproductive oysters were exposed to the pollutants for 50 days by the algal vectoring method in which the oysters were fed with concentrated standard algal foods grown in culture media containing Aroclor 1254 (0, 5, 50, 500 ng/g) or benzo(${\alpha}$)pyrene (0, 10, 100, 1,000 ng/g). Both pollutants induced maternal GSH activities in 10 days in a dosage-dependent manner (p<0.05), although Aroclor 1254 was stronger. The pollutant-driven GSH elevation persisted for 20 to 30 days depending on the pollutants and concentrations. Thereafter, a drastic decline in the GSH activity was observed due to metabolic failure, after which the oyster GSH remained at low levels throughout the remainder of the experiment. The pollutant exposures influenced maternal reproductive output in terms of fertilization, hatching, and morphology. These results imply that changes in activity of the GST-catalyzing molecule can be used as an oyster biomarker for Aroclor 1254 and benzo(${\alpha}$)pyrene exposure.

Mass Spectrometry-based Hair Metabolomics for Biomarker Discovery

  • Lee, Yu Ra;Hong, Jongki;Chung, Bong Chul
    • Mass Spectrometry Letters
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    • v.13 no.1
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    • pp.2-10
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    • 2022
  • Metabolomics makes it possible to analyze the interrelationships between various signaling molecules based on the metabolic pathways involved by using high-resolution devices. This approach can also be used to obtain large-scale metabolic information to identify the relevant pathways for disease diagnosis and prognosis and search for potential biomarkers. In the fields of medicine and forensics, hair analysis is used to detect various metabolites in the body. Hair can be harvested readily in a noninvasive manner and is easier to transport and store than blood and urine. Another advantage from a forensic viewpoint is that hair reflects all the components of body fluids. In addition, because of the unique coating structure of hair, it can be used for measurements without changing or destroying its adsorbed components. In this review, the pretreatments for hair analysis, instrumental conditions and clinical applications are discussed. Especially, the clinical use of hair metabolomics in the diagnosis of various diseases and the limitations of the technique are described.

Association Between Metabolic Syndrome and Adiponectin according to Sasang Constitution (사상체질에 따른 대사증후군과 Adiponectin의 상관성)

  • Yu, Jun-Sang;Koh, Sang-Baek;Park, Jong-Ku
    • Journal of Sasang Constitutional Medicine
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    • v.21 no.3
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    • pp.122-130
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    • 2009
  • 1. Objectives: The objective of this study is to investigate the relationship between adiponectin and metabolic syndrome according to Sasang Constitution. 2. Methods: Six hundred sixty six participants were included in this cohort study. Sex, age, BMI(Body Mass Index), smoking, drinking, adiponectin level and Metabolic syndrome components were considerd. Sasang constitutional diagnosis was carried out by a sasang constitutional specialist using photos, questionnaires and PSSC(Phonetic System for Sasang Classification). 3. Results: In binary logistic analysis after adjustment of age, sex, BMI, smoking, drinking, adiponectin level and sasang constitution were related with Metabolic syndrome. 4. Conclusions: We suggest that adiponectin and sasang constitution are the important biomarker in Metabolic syndorme.

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Simultaneous Quantification of Urinary L-, and D-Lactate by Reversed-Phase Liquid Chromatography Tandem Mass Spectrometry (액체크로마토그래프-탠덤질량분석기(LC-MS/MS)를 이용한 소변 내 D-, L- Lactate 분리 및 정량)

  • Moon, Chul Jin;Yang, Song Hyun
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.15 no.2
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    • pp.59-64
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    • 2015
  • Purpose: Lactate has two optical isomers, L-lactate and D-lactate. In human L-lactate is the most abundant enantiomer of lactate. As plasma and urinary levels of L-lactate is associated with inherited metabolic disorders in general, D-lactate have been linked to the presence of diabetes and inflammatory bowel disease. Previously developed techniques have shown several limitations to further evaluate D-lactate as a biomarker for this condition. In this paper, we describe a highly sensitive, specific and fast liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the analysis of D-, L-lactate in urine. Methods: D- and L-lactate were quantified using high performance liquid chromatography tandem mass spectrometry (LC-MS/MS) with labelled internal standard. Samples were derivatized with (+)-O,O'-diacety-L-tartaric anhydride (DATAN) and seperated on a Poroshell 120 EC-C18 column. Results: Quantitative analysis of D-, and L-lactate was achieved successfully. Calibration curves were linear (r>0.999) over $0.5-100{\mu}g/mL$. Stabilities for samples were within the 10% varation. Inter- and Intra-day assay variations were below 10%. Conclusion: The presented method proved to be suitable for the quantitation of D- and L-lactate and opens the possibility to explore the use of D-lactate as a biomarker.

The Analysis of the Archaeological Soils excavated at Wanggung-ri (토양분석을 통한 고고학적 해석-익산 왕궁리 수혈유구 토양을 대상으로)

  • Kim, Min-Hee;Seo, Min-Seok;Chung, Yong-Jea;Jeon, Yong-Ho
    • 보존과학연구
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    • s.26
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    • pp.103-126
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    • 2005
  • Coprostanol is a metabolic product of cholesterol, formed by microbial action in the mammalian gut. This chemical compound is the major sterol in human and has been routinely studied as a biomarker of sewage pollution in marine and lacustrinesediments. This has led to the search for coprostanol as a biomarker in archaeologicalsoils, in order to detect the presence of fecal material. In this study, five samples of archaeological soils excavated at Wanggung ri, Iksancity, were used to assess the possibility of using coprostanol as indicators of ancient human activity in archaeological areas. The sampled soils were analyzed MXRD,EDXRF for their physical and chemical properties. And coprostanol was analysed byGC/MSD, using SIM method to detect and quantify specific compound. The results showed the soils were composed of quartz and feldspars, inorganicelement such as $SiO_2$, $Al_2O_3$, $Fe_2O_3$ etc. Moreover, the result from the analysis wasindicated that the specific compound is coprostanol. The coprostanol was determined at $0.16~1.01\mug$/g in the range of concentrations. This finding indicate that clear promise exists for the exploitation of coprostanol as biomarker of ancient human activity inarchaeological survey. Therefore such studies can serve to increase the confidence we place on biomarker-based methodologies for assessing fecal pollution. The application of this methodology has proved a simple and effective way of searching for that pattern in successively more aged deposits either known or suspected to contain fecal material. And the more scientific analysis of the soils will be showed to utility of the area ancient dietary life style, ancient environment.

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Responses of Various Biomarkers in Common Carp (Cyprinus carpio) Exposed to Benzo[k]fluoranthene

  • Kim, Woo-Keun;Kim, Ja-Hyun;Yeom, Dong-Hyuk;Lee, Sung-Kyu
    • Korean Journal of Ecology and Environment
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    • v.41 no.3
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    • pp.331-337
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    • 2008
  • Polycyclic aromatic hydrocarbons (PAHs) derived from leakage of fossil fuels and incomplete combustion of organic materials have been considered as harmful contaminants in environments. This study evaluated the effect of benzo[k]fluoranthene (BkF), one of the PAHs, using the multiple biomarkers and applied the integration model with those biomarker responses. After 10 days of the exposure at the measured concentrations of BkF (6, 25, and 45 ${\mu}g\;L^{-1}$), the changes of the four biomarkers, that is, 7-ethoxyresorufin-O-deethylase (EROD), DNA single-strand breaks (Comet), acetylcholinesterase (AChE) and vitellogenin (VTG) in the common carp (Cyprinus carpio) were observed. The standardized values of four biomarker responses were computed and integrated as star plots, representing Integrated Biomarker Respnse (IBR) values. DNA damage was induced in a dose-dependent manner, and increased significantly compared with that in the control. EROD and VTG levels were significantly elevated at low concentrations of BkF. On the other hand, AChE activities were not altered by BkF. IBR values increased as the exposure concentrations increased. Thus, the metabolic, endocrine and genetic changes of the biomarker responses in the common carp exposed to BkF should be considered in the case of the ecological risk assessment of the BkF in fish and it can be used as a biomonitoring tool in aquatic ecosystems. In addition, star plots can be used as a useful analysis tool in multibiomarker integration approach.

Mass Spectrometry for Metabolome Analysis

  • Wang, Xiaohang;Li, Liang
    • Mass Spectrometry Letters
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    • v.11 no.2
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    • pp.17-24
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    • 2020
  • Metabolomics has become an important research field with many areas of applications ranging from disease biomarker discovery to global biology systems study. A key step in metabolomics is to perform metabolome analysis to obtain quantitative information on metabolic changes among comparative samples. Mass spectrometry (MS) is widely used for highly sensitive detection of many different types of metabolites. In this review, we highlight some of the more commonly used MS techniques for metabolome analysis.

DNA methylation: a cause and consequence of type 2 diabetes

  • Kim, Mirang
    • Genomics & Informatics
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    • v.17 no.4
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    • pp.38.1-38.6
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    • 2019
  • DNA methylation is a relatively stable epigenetic modification that can regulate and stabilize gene expression patterns and hence establish cell identity. Because metabolic intermediates are key factors of DNA methylation and demethylation, perturbations in metabolic homeostasis can trigger alterations in cell-specific patterns of DNA methylation and contribute to disease development, including type 2 diabetes (T2D). During the past decade, genome-wide DNA methylation studies of T2D have expanded our knowledge of the molecular mechanisms underlying T2D. This review summarizes case-control studies of the DNA methylome of T2D and discusses DNA methylation as both a cause and consequence of T2D. Therefore, DNA methylation has potential as a promising T2D biomarker that can be applied to the development of therapeutic strategies for T2D.

Diagnostic Evaluation of Enzyme Activity Related to Steroid Metabolism by Mass Spectrometry-Based Steroid Profiling

  • Choi, Man Ho;Chung, Bong Chul
    • Mass Spectrometry Letters
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    • v.5 no.2
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    • pp.35-41
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    • 2014
  • Gas chromatography-mass spectrometry (GC-MS) methods have been used extensively in clinical steroid analyses. Evaluating the metabolic ratios of precursors to products by accurate quantification of individual steroid levels in biological samples can reveal the activities of enzymes associated with steroid metabolism. This review article discusses the impact of GC-MS-based steroid profiling on our understanding of the biochemical role of steroids and their metabolic enzymes in hormone-dependent diseases, such as congenital adrenal hyperplasia (CAH), cortisol-mediated hypertension, apparent mineralocorticoid excess (AME), male-pattern baldness, and breast and thyroid cancers. Steroid profiling is a comprehensive analytical technique that can be applied whenever the highest specificity is required and may be a reasonable initial diagnostic approach.