• Journal of Animal Science and Technology
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• 제64권4호
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• pp.800-811
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• 2022

The integration of metabolomics and transcriptomics may elucidate the correlation between the genotypic and phenotypic patterns in organisms. In equine physiology, various metabolite levels vary during exercise, which may be correlated with a modified gene expression pattern of related genes. Integrated metabolomic and transcriptomic studies in horses have not been conducted to date. The objective of this study was to detect the effect of moderate exercise on the metabolomic and transcriptomic levels in horses. In this study, using nuclear magnetic resonance (NMR) spectroscopy, we analyzed the concentrations of metabolites in muscle and plasma; we also determined the gene expression patterns of branched chain (alpha) keto acid dehydrogenase kinase complex (BCKDK), which encodes the key regulatory enzymes in branched-chain amino acid (BCAA) catabolism, in two breeds of horses, Thoroughbred and Jeju, at different time intervals. The concentrations of metabolites in muscle and plasma were measured by ¹H NMR (nuclear magnetic resonance) spectroscopy, and the relative metabolite levels before and after exercise in the two samples were compared. Subsequently, multivariate data analysis based on the metabolic profiles was performed using orthogonal partial least square discriminant analysis (OPLS-DA), and variable important plots and t-test were used for basic statistical analysis. The stress-induced expression patterns of BCKDK genes in horse muscle-derived cells were examined using quantitative reverse transcription polymerase chain reaction (qPCR) to gain insight into the role of transcript in response to exercise stress. In this study, we found higher concentrations of aspartate, leucine, isoleucine, and lysine in the skeletal muscle of Jeju horses than in Thoroughbred horses. In plasma, compared with Jeju horses, Thoroughbred horses had higher levels of alanine and methionine before exercise; whereas post-exercise, lysine levels were increased. Gene expression analysis revealed a decreased expression level of BCKDK in the post-exercise period in Thoroughbred horses.

• Archives of Pharmacal Research
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• 제27권4호
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• pp.402-406
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• 2004

This research team found in previous studies, that the ginseng saponin metabolite IH901 induces apoptosis in HepG2 cells via a mitochondrial-mediated pathway, which resulted in the activation of caspase-9 and subsequently of caspase-3 and -8. Based on these results, the involvement of the Fas/Fas ligand (FasL) death-receptor pathway, in IH901-induced apoptosis in HepG2 cells, was investigated. Levels of Fas and the Fas ligand (FasL) mRNA or protein were not increased by IH901, rather they were decreased significantly at 18 h post treatment. Soluble FasL (sFasL) was detectable by immunoprecipitation analysis En the medium of HepG2 cells treated with IH901. Increased levels of sFasL were inversely correlated with the levels of FasL. Preincubation of HepG2 cells with antagonistic anti-Fas antibody showed little protective effect, if any, on IH901-induced cell death. At a $30{\mu}M$ (24 and 48 h) and $40{\mu}M$ (24 h) concentration of IH901, the cytotoxic effect of IH901 was less then $50\%$, anti-Fas antibody prevented IH901-induced cell death. However, at a $60{\mu}M$ (24 and 48 h) and $40{\mu}M$ (48 h) concentration of IH901, cell death rates were about $80\%$ or more and most of the chemopreventive and chemotherapeutic effects of IH901 were manifested. Blocking the Fas receptor did not influence IH901-induced cell death. These results indicate that the Fas/FasL system is engaged, but not required for IH901-induced cell death, at pharmacologically significant concentrations.

• The Korean Journal of Physiology and Pharmacology
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• 제5권2호
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• pp.165-175
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• 2001

Background: Recent in vivo experimental evidence suggests that isoflurane-induced cardioprotection may involve $K_{ATP}$ channel activation. However, it was demonstrated that isoflurane inhibited $K_{ATP}$ channel activities in the inside-out patch mode. To explain this discrepancy, the present investigation tested the hypothesis that a metabolite of isoflurane, trifluoroacetic acid (TFA), contributes to isoflurnae-induced cardioprotection via $K_{ATP}$ channel activation during myocardial ischemia and reperfusion. Methods: Single ventricular myocytes were isolated from rabbit hearts by an enzymatic dissociation procedure. Patch-clamp techniques were used to record single-channel currents. $K_{ATP}$ channel activities were assessed before and after the application of TFA with the inside-out patch mode. Results: TFA enhanced channel activity in a concentration-dependent fashion. The concentration of TFA for half-maximal activation and the Hill coefficient were 0.03 mM and 1.2, respectively. TFA did not affect the single channel conductance of $K_{ATP}$ channels. Analysis of open and closed time distributions showed that TFA increased burst duration and decreased the interburst interval without changes in open and closed time distributions shorter than 5 ms. TFA diminished ATP sensitivity of $K_{ATP}$ channels in a concentration-response relationship for ATP. Conclusions: TFA, a metabolite of isoflurane, enhanced $K_{ATP}$ channel activity in a concentration-dependent fashion. These results imply that TFA could mediate isoflurane-induced cardioprotection via $K_{ATP}$ channel activation during myocardial ischemia and reperfusion.

• Journal of Microbiology and Biotechnology
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• 제22권11호
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• pp.1523-1531
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• 2012

The metabolite profile of meju during fermentation was analyzed using mass spectrometry techniques, including GC-MS and LC-MS, and the bacterial diversity was characterized. The relative proportions of bacterial strains indicated that lactic acid bacteria, such as Enterococcus faecium and Leuconostoc lactis, were the dominant species. In partial least-squares discriminate analysis (PLS-DA), the componential changes, which depended on fermentation, proceeded gradually in both the GC-MS and LC-MS data sets. During fermentation, lactic acid, amino acids, monosaccharides, sugar alcohols, and isoflavonoid aglycones (daidzein and genistein) increased, whereas citric acid, glucosides, and disaccharides decreased. MS-based metabolite profiling and bacterial diversity characterization of meju demonstrated the changes in metabolites according to the fermentation period and provided a better understanding of the correlation between metabolites and bacterial diversity.

• 한국식품영양과학회지
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• 제43권2호
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• pp.179-186
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• 2014

대사체학이 질병, 약물, 스트레스, 식이, 생활습관, 유전적 차이, 장내 미생물 등에 의해서 발생하는 비정상적인 대사 메커니즘을 규명하고 관련 바이오 마커 발굴에 중요한 역할이 증명됨에 따라, 식품 영양학과 대사체학이 융합된 영양 대사체학의 역할이 더욱 중요해지고 있다. 특히 잘못된 식생활에 따른 미래의 질병 예측이 가능해지고 있어 향후 적절한 질병 예방이나 치료를 위한 적절한 식생활이나 식이에 대한 정보를 제공함으로써 건강 증진은 물론 개인별 맞춤식이나 맞춤약물 처방을 통한 개인 맞춤형 건강관리(personalized health care) 시대가 멀지 않았다. 또한 복잡한 식생활 패턴, 대사 반응에 대한 개인 간 차이 그리고 방대한 대사체 데이터와의 관계들을 효과적으로 밝혀낼 수 있는 기술에 대한 지속적인 개발과 영양 대사체학(nutritional metabolomics)이 유전체학(genomics or transcriptomics)과 단백체학(proteomics) 기술과 융합적으로 연구가 이루어질 때 질병과 식사 섭취 사이의 관계가 더욱 투명하게 규명될 것이다.

• Journal of Pharmaceutical Investigation
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• 제28권2호
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• pp.73-80
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• 1998

In order to elucidate the effect of N-demethylation on the in vivo metabolite kinetics, especially hepatic first-pass effect of trimebutine(TMB), the N-demethylation of TMB to N-monodesmethyl trimebutine(N-TMB) was studied in rats. TMB(10 mg/kg) and N-TMB(10 mg/kg) were injected into the femoral and the portal vein, respectively. And the pharmacokinetic parameters were obtained from the plasma concentration-time profiles of TMB and N-TMB determined by the simultaneous analysis using high-performance liquid chromatography. It was supposed that these drugs were almost metabolized in vivo because the urinary and biliary excreated amounts of TMB and N-TMB were lower than 0.1% of the administered dose. According to the hepatic biotransformation model and metabolic pathways of TMB proposed, it was found that the fraction of systemic clearance of TMB which formed N-TMB in liver$(G_{mi})$ was 0.826, that of TMB which furnishes the available N-TMB to the systemic circulation$(F_{mi})$ was 0.083, and the absolute hepatic bioavailability of N-TMB formed trom TMB$(F_{mi.p})$ was 0.1. These results showed that TMB was suspected of the sequential hepatic first-pass metabolism and N-demethylated by 82.6%. Therefore, the residue would be hydrolyzed by the esterase in the liver. That is, the ability of N-demethylation of TMB was 4.75-fold larger than that of hydrolysis by the esterase in rats.

• Food Science and Biotechnology
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• 제16권4호
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• pp.636-640
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• 2007

In order to investigate the major metabolite patterns of aged Panax ginseng C.A. Meyer roots, the ginsenoside contents for white ginseng roots of various ages were compared. The 1-year to 6-year old roots were extracted with methanol, and then the methanol-soluble metabolites were analyzed by high performance liquid chromatography (HPLC). The metabolite contents of the 1-year and 2-year roots, including the ginsenosides and minor components, were not different, but the $Rg_1$, Re, and Rc ginsenoside contents between the 2-year and 3-year roots showed significant differences. $Rg_1$ and Rc increased significantly in the 1-year to 2-year roots, and Re increased significantly from the 3-year root age. Rd increased slightly until the 2-year age and decreased from the 3-year age. Based on the ginsenoside distributions and contents at various root ages, we have suggested 2 biogenesis schemes using the ginsenosides that have been isolated from the roots of P. ginseng so far.

• Journal of Microbiology and Biotechnology
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• 제10권4호
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• pp.518-521
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• 2000

Aspergillus niger is capable of metabolizing dimethyphthalate. The maximum weight of mycelium wa observed afterabout 6-8 dys of incubation. A TLC analysis revealed the accumulation of metabolites in the resting cell culture. Monomethylphthalate, phthalate, and protocatechuate were shown to be the intermediates by thin layer chromatographic and spectrophotometric analyses. The fungus metabolized dimethylphthalate through monomethylphthalate, phthalate, and protocatechuate as evidenced by the oxygen uptake and an enzymatic analysis. The terminal aromatic metabolite, protocatechuate, is metabolized via the ortho-cleavage pathway.

• 제어로봇시스템학회:학술대회논문집
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• 제어로봇시스템학회 2002년도 ICCAS
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• pp.57.3-57
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• 2002

1. Introduction 2. General flux balance model 3. MetaFluxNet 3.1 Overview of MetaFluxNet 3.2 Project file format 3.3 Construction of metabolite reaction model 3.4 Metabolic flux analysis using linear programming 3.5 Visualization of MFA results 4. Conclusion and plan 5. Acknowledgement. References.

• 대한방사선기술학회지:방사선기술과학
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• 제39권2호
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• pp.143-148
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• 2016

본 연구에서는 MRS 정량적 분석 중 jMRUI AMARES방법의 관찰자의 의존적 원인 요소를 숙련자와 비숙련자의 측정을 통하여 파악하고 하였다. 실험용 10주령 수컷 쥐의 간 부분을 3T MRI 장치를 활용하여 point resolved spectroscopy 펄스시퀀스를 이용하여 자기공명분광 데이터를 획득하였다. 획득된 데이터는 기준 값으로 사용하기 위해서 LCModel software 이용하여 1.3 ppm의 메틸렌 양성자와 4.7 ppm의 물 분자 양성자의 정량 비를 계산하였다. 7명의 비숙련 관찰자는 jMRUI AMARES 방법으로 총 지질을 1, 2주 간격으로 측정한 후 측정된 값을 SPSS를 이용하여 interclass correlation coefficient를 시행하였다. 관찰자 사이 간 측정치의 일관성의 신뢰도 분석을 표현한 크논바 알파 계수는 0.1 미만으로 나타났다. 1주차 데이터 값과 2주차 데이터 값의 평균값은 $0.096{\pm}0.038$로 LCModel의 분석 값보다 0.048로 50% 높게 관찰되었다. jMRUI AMARES분석 방법이 LCModel과 동일한 결과를 얻기 위해서는 정확한 대사물질의 개요를 숙지하고 획득된 그래프의 형태를 잘 파악하여 잔존 대사물질를 최소화 하여야 한다.