• 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.

• Journal of Microbiology and Biotechnology
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• v.33 no.1
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• pp.114-122
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• 2023

A family of signal transduction pathways known as wingless type (Wnt) signaling pathways is essential to developmental processes like cell division and proliferation. Mutation in Wnt signaling results in a variety of diseases, including cancers of the breast, colon, and skin, metabolic disease, and neurodegenerative disease; thus, the Wnt signaling pathways have been attractive targets for disease treatment. However, the complicatedness and large involveness of the pathway often hampers pinpointing the specific targets of the metabolic process. In our current study, we investigated the differential metabolic regulation by the overexpression of the Wnt signaling pathway in a timely-resolved manner by applying high-throughput and un-targeted metabolite profiling. We have detected and annotated 321 metabolite peaks from a total of 36 human embryonic kidney (HEK) 293 cells using GC-TOF MS and LC-Orbitrap MS. The un-targeted metabolomic analysis identified the radical reprogramming of a range of central carbon/nitrogen metabolism pathways, including glycolysis, TCA cycle, and glutaminolysis, and fatty acid pathways. The investigation, combined with targeted mRNA profiles, elucidated an explicit understanding of activated fatty acid metabolism (β-oxidation and biosynthesis). The findings proposed detailed mechanistic biochemical dynamics in response to Wnt-driven metabolic changes, which may help design precise therapeutic targets for Wnt-related diseases.

• Mass Spectrometry Letters
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• v.3 no.1
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• pp.4-9
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• 2012

• Proceedings of the Korean Society of Crop Science Conference
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• 2021.10a
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• pp.252-252
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• 2021

• Journal of the Korean Magnetic Resonance Society
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• v.15 no.1
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• pp.54-68
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• 2011

$^1H$ nuclear magnetic resonance (NMR) spectroscopy of biological samples has been proven to be an effective and nondestructive approach to probe drug toxicity within an organism. In this study, ketoprofen toxicity was investigated using $^1H$-NMR spectroscopy coupled with multivariate statistical analysis. Histopathologic test of ketoprofen-induced acute gastrointestinal damage in rats demonstrated a significant dose-dependent effect. Furthermore, principal component analysis (PCA) derived from $^1H$-NMR spectra of urinary samples showed clear separation between the vehicle-treated control and ketoprofen-treated groups. Moreover, PCA derived from endogenous metabolite concentrations through targeted profiling revealed a dose-dependent metabolic shift between the vehicle-treated control, low-dose ketoprofen-treated (10 mg/kg body weight), and high-dose ketoprofen-treated (50 mg/kg) groups coinciding with their gastric damage scores after ketoprofen administration. The resultant metabolic profiles demonstrated that the ketoprofen-induced gastric damage exhibited energy metabolism perturbations that increased urinary levels of citrate, cis-aconitate, succinate, and phosphocreatine. In addition, ketoprofen administration induced an enhancement of xenobiotic activity in fatty oxidation, which caused increase levels of N-isovalerylglycine, adipate, phenylacetylglycine, dimethylamine, betaine, hippurate, 3-indoxylsulfate, N,N-dimethylglycine, trimethyl-N-oxide, and glycine. These findings demonstrate that $^1H$-NMR-based urinary metabolic profiling can be used for noninvasive and rapid way to diagnose adverse drug effects and is suitable for explaining the possible biological pathways perturbed by nonsteroidal anti-inflammatory drug toxicity.

• Journal of Microbiology and Biotechnology
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• v.27 no.6
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• pp.1150-1156
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• 2017

Understanding phosphorus metabolism in photosynthetic organisms is important as it is closely associated with enhanced crop productivity and pollution management for natural ecosystems (e.g., algal blooming). Accordingly, we exploited highly time-resolved metabolic responses to different levels of phosphate deprivation in Chlamydomonas reinhardtii, a photosynthetic model organism. We conducted non-targeted primary metabolite profiling using gas-chromatography time-of-flight mass spectrometric analysis. Primarily, we systematically identified main contributors to degree-wise responses corresponding to the levels of phosphate deprivation. Additionally, we systematically characterized the metabolite sets specific to different phosphate conditions and their interactions with culture time. Among them were various types of fatty acids that were most dynamically modulated by the phosphate availability and culture time in addition to phosphorylated compounds.