• Environmental Analysis Health and Toxicology
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• 제25권4호
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• pp.295-306
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• 2010

Objectives : This study was undertaken to examine the metabolomic changes due to gender and diurnal variation at sampling time and to identify an appropriate time point for urine sampling in epidemiologic studies using metabolomic profiles. Methods : Urine samples were collected twice a day (morning and afternoon) from 20 healthy Korean adults after fasting for 8 hours. The metabolomic assay was investigated using $^1H$ NMR spectroscopy coupled with the principal components analysis (PCA) and partial least squares discriminant analysis (PLS-DA). The metabolites responsible for differentiation between groups were identified through the loading plot of PLS-DA and quantified using Chenomx NMR Suite with a 600 MHz library. Results : Metabolites responsible for differentiation in gender and sampling time were creatinine, trimethyl anine oxide (TMAO), hippurate, mannitol, citrate and acetoacetate. Dimethylamine showed difference only as a factor of diurnal time. The level of creatinine was higher in men compared to women, and the levels of citrate, TMAO, hippurate, mannitol, and acetoacetate were higher in women compared to men. The levels of creatinine, TMAO, hippurate, dimethylamine and mannitol were higher in the morning rather than the afternoon while those of citrate and acetoacetate were higher in the afternoon rather than the morning. Conclusions : Since urinary metabolomic profiles varied by gender and diurnal cycle, urine sampling should be performed at the same time point for all participants in epidemiologic studies using metabolomic profiles.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2007년도 Proceedings of The Convention
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• pp.11-15
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• 2007

Metabolomics is an emerging technology which makes it possible to evaluate change of biological system in response to the physiological, environmental alterations. It has advantages in the simplicity and sensitivity to analyze metabolites since the researcher can use cutting edge instrument, such as mass spectrometry and simple sample preparation method compared to genomics or proteomics. Nowadays this technology has been tried in pharmaceutical area to investigate toxicity and efficacy of drug candidates and drugs in preclinical test. The metabolomic applications on the pharmaceutics for early prediction on toxicity and efficacy are described in this presentation. The multivariate analysis to get metabolic fingerprinting and its relations with the physiological changes are investigated with several drugs. Feasibility of metabolomic application for pharmaceutical area would be suggested from those researches.

• Translational and Clinical Pharmacology
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• 제25권2호
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• pp.67-73
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• 2017

Glimepiride, a third generation sulfonylurea, is an antihyperglycemic agent widely used to treat type 2 diabetes mellitus. In this study, an untargeted urinary metabolomic analysis was performed to identify endogenous metabolites affected by glimepiride administration. Urine samples of twelve healthy male volunteers were collected before and after administration of 2 mg glimepiride. These samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and then subjected to multivariate data analysis including principal component analysis and orthogonal partial least squares discriminant analysis. Through this metabolomic profiling, we identified several endogenous metabolites such as adenosine 3', 5'-cyclic monophosphate (cAMP), quercetin, tyramine, and urocanic acid, which exhibit significant metabolomic changes between pre- and posturine samples. Among these, cAMP, which is known to be related to insulin secretion, was the most significantly altered metabolite following glimepiride administration. In addition, the pathway analysis showed that purine, tyrosine, and histidine metabolism was affected by pharmacological responses to glimepiride. Together, the results suggest that the pharmacometabolomic approach, based on LC-MS/MS, is useful in understanding the alterations in biochemical pathways associated with glimepiride action.

• 농업과학연구
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• 제45권3호
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• pp.447-454
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• 2018

Zearalenone (ZEN), a mycotoxin produced by Fusarium in food and feed, causes serious damage to the health of humans and livestock. Therefore, we compared the metabolomic profiles in the liver, serum, and urine of piglets fed a ZEN-contaminated diet using proton nuclear magnetic resonance ($^1H-NMR$) spectroscopy. The spectra from the three different samples, treated with ZEN concentrations of 0.8 mg/kg for 4 weeks, were aligned and identified using MATLAB. The aligned data were subjected to discriminating analysis using multivariate statistical analysis and a web server for metabolite set enrichment analysis. The ZEN-exposed groups were almost separated in the three different samples. Metabolic analysis showed that 28, 29, and 20 metabolites were profiled in the liver, serum, and urine, respectively. The discriminating analysis showed that the alanine, arginine, choline, and glucose concentrations were increased in the liver. Phenylalanine and tyrosine metabolites showed high concentrations in serum, whereas valine showed a low concentration. In addition, the formate levels were increased in the ZEN-treated urine. For the integrated analysis, glucose, lactate, taurine, glycine, alanine, glutamate, glutamine, and creatine from orthogonal partial least squares discriminant analysis (OPLS-DA) were potential compounds for the discriminating analysis. In conclusion, our findings suggest that potential biomarker compounds can provide a better understanding on how ZEN contaminated feed in swine affects the liver, serum, and urine.

• Journal of Microbiology and Biotechnology
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• 제23권7호
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• pp.923-931
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• 2013

Rapamycin, known as an inhibitor of Target of Rapamycin (TOR), is an immunosuppressant drug used to prevent rejection in organ transplantation. Despite the close association of the TOR signaling cascade with various scopes of metabolism, it has not yet been thoroughly investigated at the metabolome level. In our current study, we applied mass spectrometric analysis for profiling primary metabolism in order to capture the responsive dynamics of the Chlamydomonas metabolome to the inhibition of TOR by rapamycin. Accordingly, we identified the impact of the rapamycin treatment at the level of metabolomic phenotypes that were clearly distinguished by multivariate statistical analysis. Pathway analysis pinpointed that inactivation of the TCA cycle was accompanied by the inhibition of cellular growth. Relative to the constant suppression of the TCA cycle, most amino acids were significantly increased in a time-dependent manner by longer exposure to rapamycin treatment, after an initial down-regulation at the early stage of exposure. Finally, we explored the isolation of the responsive metabolic factors into the rapamycin treatment and the culture duration, respectively.

• Toxicological Research
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• 제34권3호
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• pp.199-210
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• 2018

Skeletal muscle can be ultrastructurally damaged by eccentric exercise, and the damage causes metabolic disruption in muscle. This study aimed to determine changes in the metabolomic patterns in urine and metabolomic markers in muscle damage after eccentric exercise. Five men and 6 women aged 19~23 years performed 30 min of the bench step exercise at 70 steps per min at a determined step height of 110% of the lower leg length, and stepping frequency at 15 cycles per min. $^1H$ NMR spectral analysis was performed in urine collected from all participants before and after eccentric exercise-induced muscle damage conventionally determined using a visual analogue scale (VAS) and maximal voluntary contraction (MVC). Urinary metabolic profiles were built by multivariate analysis of principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA) using SIMCA-P. From the OPLS-DA, men and women were separated 2 hr after the eccentric exercise and the separated patterns were maintained or clarified until 96 hr after the eccentric exercise. Subsequently, urinary metabolic profiles showed distinct trajectory patterns between men and women. Finally, we found increased urinary metabolites (men: alanine, asparagine, citrate, creatine phosphate, ethanol, formate, glucose, glycine, histidine, and lactate; women: adenine) after the eccentric exercise. These results could contribute to understanding metabolic responses following eccentric exercise-induced muscle damage in humans.

• 한국식품영양과학회지
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• 제43권3호
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• pp.419-424
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• 2014

본 연구에서는 LC-MS/MS를 이용한 블루베리의 methanol과 ethyl acetate 추출 분획에 존재하는 대사체의 분석을 통해 효율적인 대사체 profiling의 가능성을 탐색하였다. LC-MS/MS에서 검출되는 대사체를 통계 처리한 결과, methanol 추출 분획에서는 5-O-feruloylquinic acid, malvidin hexoside, malvidin-3-arabinoside, petunidin-3-arabinoside, delphinidin hexoside, delphinidin, petunidin hexoside와 같은 안토시아닌 계열의 화합물들이 존재하였고, ethyl acetate 분획에서는 chlorogenic acid, chlorogenic acid dimer, 6,8-di-C-arabinopyranosylluteolin, luteolin과 같은 플라보노이드 계열의 화합물이 검출되었다. 본 연구는 기존 연구와 달리 대사체학 기법을 이용한 블루베리 추출물 전체 대사물질의 profiling을 시도한 최초의 연구로서 블루베리에 함유된 유용 성분의 스크리닝 등 향후 응용 연구에 유용한 기반으로 이용될 수 있을 것으로 기대된다.

• 한국축산식품학회지
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• 제42권5호
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• pp.744-761
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• 2022

The liquid chromatography mass spectrometry (LC-MS)-based metabolomic and lipidomic methodology has great sensitivity and can describe the fingerprint of metabolites and lipids in pork and beef. This approach is commonly used to identify and characterize small molecules such as metabolites and lipids, in meat products with high accuracy. Since the metabolites and lipids can be used as markers for many properties of a food, they can provide further evidence of the foods authenticity claim. Chromatography coupled to mass spectrometry is used to separate lipids and metabolites from meat samples. The research data usually is compared to lipid and metabolite databases and evaluated using multivariate statistics. LC-MS instruments directly connected to the metabolite and lipid databases software can be used to assess the authenticity of meat products. LC-MS has good selectivity and sensitivity for metabolomic and lipidomic analysis. This review highlighted the combination of metabolomics and lipidomics can be used as a reference for analyzing authentication meat products.

• Journal of Ginseng Research
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• 제38권1호
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• pp.59-65
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• 2014

Discriminating between two herbal medicines (Panax ginseng and Panax quinquefolius), with similar chemical and physical properties but different therapeutic effects, is a very serious and difficult problem. Differentiation between two processed ginseng genera is even more difficult because the characteristics of their appearance are very similar. An ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF MS)-based metabolomic technique was applied for the metabolite profiling of 40 processed P. ginseng and processed P. quinquefolius. Currently known biomarkers such as ginsenoside Rf and F11 have been used for the analysis using the UPLC-photodiode array detector. However, this method was not able to fully discriminate between the two processed ginseng genera. Thus, an optimized UPLC-QTOF-based metabolic profiling method was adapted for the analysis and evaluation of two processed ginseng genera. As a result, all known biomarkers were identified by the proposed metabolomics, and additional potential biomarkers were extracted from the huge amounts of global analysis data. Therefore, it is expected that such metabolomics techniques would be widely applied to the ginseng research field.

• 한국가금학회지
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• 제48권4호
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• pp.239-253
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• 2021

본 연구는 Cobb종 및 Ross 308종 육계가 동물복지 사육환경에 따라 나타내는 대사체학적 변화를 연구하기 위하여 수행되었다. 일반농장과 동물복지농장(사육면적, 사육밀도, 암모니아 농도, 볏짚 등 제공)에 1일령의 Cobb종 및 Ross종 육계를 35일간 사육하고, 도계 후 가슴육과 다리육을 채취하여 분석에 이용하였다. 대사체 분석은 one-dimensional ¹H 핵자기공명분광법을 이용하였고, 직교부분최소자승판별분석(OPLS-DA)과 대사경로 분석을 함께 수행하였다. OPLS-DA 결과 육계 가슴육은 Ross종에 한하여 사육농장간 뚜렷한 구분이 가능하였다. 동물복지농장 유래 Ross종 육계 가슴육은 acetate, anserine, creatine, inosine monophosphate 함량이 일반농장 닭가슴육에 비해 유의적으로 높았다(P<0.05). 반면 육계 다리육은 OPLS-DA 결과 Cobb종 육계에서만 사육농장에 따른 구분이 뚜렷하게 나타났는데, glucose와 lactate를 포함한 5종의 대사체 함량은 동물복지농장에서 사육된 경우에 높았으나 7종의 유리아미노산을 포함한 9종의 대사체 함량은 낮았다(P<0.05). 대사경로 분석 결과 Ross종 육계 가슴육에서는 4종, Cobb종 육계 다리육에서는 glycolysis/gluconeogenesis를 포함한 20종의 대사경로에서 사육농장 간 유의적인 차이(P<0.05)가 나타났다. 동물복지농장에서 사육된 Ross종 육계 가슴육과 Cobb종 육계 다리육은 일반농장에서 사육된 경우와는 다른 대사체학적 특성을 나타냈으며, 특히 풍미 물질에의 뚜렷한 차이를 보여 관능적 특성에 영향을 미칠 수 있으리라 사료된다.