• 한국전자통신학회논문지
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• 제11권10호
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• pp.969-982
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• 2016

최근 천연물로부터 신약 후보물질을 개발하려는 연구가 활발히 이루어지고 있다. 인체 내에서 천연물은 주로 효소에 의해 대사된다. 본 연구는 화합물의 인체내 대사반응과 주로 관련된 효소에 의한 대사반응의 특징을 연관규칙마이닝을 활용하여 분석한다. 화합물이 인체 내에서 효소 대사반응과 관련된 데이터를 BRENDA(: BRaunschweig ENzyme DAtabase)로부터 수집하였다. 수집된 데이터를 효소대사반응의 기본 틀에 근거하여, 대사물들을 기질대사물, 생성대사물, 억제대사물, 그리고 활성대사물들로 구분한다. 이러한 대사물들로 이루어진 기질대사물 트랜잭션, 생성대사물 트랜잭션, 그리고 모든 대사물들을 포함한 효소반응트랜잭션들을 구성하였다. 또한 종 정보를 반영한 6개의 트랜잭션들로 구성하였다. 연관규칙 마이닝을 활용하여 6개의 트랜잭션에서 빈발대사물 및 패턴을 분석하였다. 또한 대사물들 사이의 관련성을 분석하였다. 그 결과 효소대사반응에 참여하는 대사물들의 분포와 패턴을 식별할 수 있었다. 더욱이 기질에만 속하는 순수 기질대사물들을 식별하였고 이들 대부분이 아주 낮은 지지도임을 확인할 수 있었다. 연구결과는 순수 기질대사물은 효과적인 대사변환 예측 모델 개발에 활용될 수 있다.

• Journal of Microbiology and Biotechnology
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• 제22권1호
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• pp.100-106
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• 2012

In this study, the metabolite profiles of three Aspergillus strains during rice koji fermentation were compared. In the partial least squares discriminant analysis-based gas chromatography-mass spectrometry data sets, the metabolite patterns of A. oryzae (KCCM 60345) were clearly distinguished from A. kawachii (KCCM 60552) and only marginal differences were observed for A. oryzae (KCCM 60551) fermentation. In the 2 days fermentation samples, the overall metabolite levels of A. oryzae (KCCM 60345) were similar to the A. oryzae (KCCM 60551) levels and lower than the A. kawachii (KCCM 60552) levels. In addition, we identified discriminators that were mainly contributing tyrosinase inhibition (kojic acid) and antioxidant activities (pyranonigrin A) in A. oryzae (KCCM 60345) and A. kawachii (KCCM 60552) inoculated rice koji, respectively. In this study, we demonstrated that the optimal inoculant Aspergillus strains and fermentation time for functional rice koji could be determined through a metabolomics approach with bioactivity correlations.

• Biomolecules & Therapeutics
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• 제6권3호
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• pp.283-288
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• 1998

YH 1885 (5,6-dimethyl -2-(4-fluorophenylamino)-4-(1-methyl -1,2,3,4-tetrahydroisoquinolin -2- yl) pyrimidine hydrochloride) was developed as an antiulcer drug. The objective of this study was to examine a comparative metabolism of YH1885 in rat, dog, monkey and human liver tissues and to determine the metabolite profiles produced by the four species. YH1885 was metabolized by liver 59 fractions from all four species. Control incubations containing 59 fraction but no cofactors, contained essentially no metabolites. Metabolism of YH1885 apparently became saturated in the concentration range studied because the % of YH 1885 metabolized decreased with increasing drug concentration for all four species. Six to nine metabolite peaks were detected in the incubations and the particular profile of metabolites varied with species. The total amount of metabolites formed by liver microsomes from human and monkey were less than microsomes from rat or dog. The major metabolite peak formed by rat liver 597actions fluted near the solvent front on the HPLC or remained at the origin in TLC, indicating that it contained one or more polar metabolites. Dog liver 59 fractions incubations contained four major metabolites that each accounted for about 15 to 20 % of the total radioactivity at the low concentration of YH1885. The metabolite profiles of YH1885 appeared to be similar in incubations with rhesus monkey and human liver 59 fraction. The amount of metabolites formed by rhesus monkey liver preparations was greater than that of human liver that contained prominent metabolite peaks with approximate relative retention time of 0.14 and 0.43.

• 한국미생물·생명공학회지
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• 제38권4호
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• pp.475-480
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• 2010

Actinomycetes are Gram-positive soil bacteria and one of the most important industrial microorganisms due to superior biosynthetic capabilities of many valuable secondary metabolites as well as production of various valuable bioconversion enzymes. Among them are cytochrome P450 hydroxylase (CYP), which are hemoproteins encoded by a super family of genes, are universally distributed in most of the organisms from all biological kingdoms. Actinomycetes are a rich source of soluble CYP enzymes, which play critical roles in the bioactivation and detoxification of a wide variety of metabolite biosynthesis and xenobiotic transformation. Cyclosporin A (CyA), one of the most commonly-prescribed immunosuppressive drugs, was previously reported to be hydroxylated at the position of 4th N-methyl leucine by a rare actinomycetes called Sebekia benihana, leading to display different biological activity spectrum such as loss of immunosuppressive activities yet retaining hair growth-stimulating side effect. In order to improve this regio-selective CyA hydroxylation in S. benihana, previously-identified several secondary metabolite up-regulatory genes from Streptomyces coelicolor and S. avermitilis were heterologously overexpressed in S. benihana using an $ermE^*$ promoter-containing Streptomyces integrative expression vector. Among tested, SCO4967 encoding a conserved hypothetical protein significantly stimulated region-specific CyA hydroxylation in S. benihana, implying that some common regulatory systems functioning in both biosynthesis and bioconversion of secondary metabolite might be present in different actinomycetes species.

• Journal of Microbiology and Biotechnology
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• 제32권3호
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• pp.387-395
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• 2022

Deciphering the metabolites of human diseases is an important objective of biomedical research. Here, we aimed to capture the core metabolites of Fanconi anemia (FA) using the bioinformatics method of a multi-omics composite network. Based on the assumption that metabolite levels can directly mirror the physiological state of the human body, we used a multi-omics composite network that integrates six types of interactions in humans (gene-gene, disease phenotype-phenotype, disease-related metabolite-metabolite, gene-phenotype, gene-metabolite, and metabolite-phenotype) to procure the core metabolites of FA. This method is applicable in predicting and prioritizing disease candidate metabolites and is effective in a network without known disease metabolites. In this report, we first singled out the differentially expressed genes upon different groups that were related with FA and then constructed the multi-omics composite network of FA by integrating the aforementioned six networks. Ultimately, we utilized random walk with restart (RWR) to screen the prioritized candidate metabolites of FA, and meanwhile the co-expression gene network of FA was also obtained. As a result, the top 5 metabolites of FA were tenormin (TN), guanosine 5'-triphosphate, guanosine 5'-diphosphate, triphosadenine (DCF) and adenosine 5'-diphosphate, all of which were reported to have a direct or indirect relationship with FA. Furthermore, the top 5 co-expressed genes were CASP3, BCL2, HSPD1, RAF1 and MMP9. By prioritizing the metabolites, the multi-omics composite network may provide us with additional indicators closely linked to FA.

• 한국산업보건학회지
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• 제33권4호
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• pp.385-394
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• 2023

Objectives: Firefighters could be exposed to a range of toxic chemicals during firefighting. When tyre burns, various toxic chemicals including volatile organic compounds(VOCs) could be emitted. In this study, the researchers assessed the VOC exposure of firefighters during tyre fire suppression through biomonitoring. Methods: There was a big tyre fire on 12 March 2023. Of the responding firefighters, we recruited 14 participants to collect their urine after firefighting. One week later, researchers collected firefighters' urine again right after their off-duty period. We analyzed each metabolite of benzene, toluene, xylene, and styrene in urine and compared their exposure level based on sampling time. Results: The detection rate for metabolite of benzene, toluene, styrene, and xylene in urine sampled at each time was 43%-64%, 100%, 86%-100%, and 100%, respectively. Except for the benzene, metabolite levels measured in urine after firefighting were similar to that from off-duty period. However, the median concentration of benzene metabolite in urine sampled after firefighting was three times higher compared to that from off-duty period(34.2 ㎍/g crea. and 10.9 ㎍/g crea., respectively.) The estimated airborne concentration of benzene calculated from metabolite level in urine was 0.16 ppm, which exceeded the recommended exposure level set by the National Institute for Occupational Safety and Health. Conclusions: This study shows that firefighters could be exposed to the high level of VOCs including benzene during their firefighting especially at tyre fire. These results could be used as a valuable data to prove firefighters' exposure to hazardous chemicals during their duty.

• 한국의학물리학회지:의학물리
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• 제18권3호
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• pp.179-185
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• 2007

본 연구는 자기공명분광법(Magnetic Resonance Spectroscopy: MRS)에 있어서 기존 개발된 Multi-Voxel Spectroscopy (MVS)을 위한 MR 원뿔형 팬톰을 Single voxel spectroscopy (SVS)용으로 개선하여 선정된 Voxel내의 대사물질의 양과 TE 변화에 따른 스펙트럼의 변화를 관찰하였다. 원뿔형 팬톰은 Voxel를 선정하는 위치에 따라서 그 안에 포함되는 대사물질의 양을 변화시킬 수 있다는 점에 착안하여 Voxel안에 포함되는 뇌대사물질의 양과 TE시간에 따른 각 대사물질(NAA, Cr, Cho, Lac 등)의 Peak에 대한 정량적인 분석을 시도하였다. 실험은 3T MRI/MRS 장비에서 이루어졌고, 데이터를 분석하는데 $jMRUI^{(R)}$라는 프로그램이 사용되었다. 실험 및 분석 결과 대체로 Echo Time (TE)가 커질수록 잡음이 감소하는 경향을 확인할 수 있었고 또한 TE가 커질수록, Voxel 안의 뇌대사물질의 양이 적을수록 각 대사물질의 peak intensity가 감소하는 것을 관찰할 수 있었다. 특히 Lactate의 경우, 정위선정된 Voxel안에 가장 많은 양의 대사물질이 포함되었을 때만 스펙트럼 분석이 가능한 정도의 Peak intensity를 얻을 수 있었고 대부분의 TE에서 분석 가능한 것으로 보아 각 대사물질의 intensity는 TE보다는 Voxel내의 대사물질의 양에 더욱 민감하다는 결론을 도출 할 수 있었고, 이러한 Lac에 대한 in vitro 데이터는 정량분석 시에 있어서 in vivo상에서 대사물질의 정량화를 하는 데 있어서 중요한 가이드라인을 제시할 것으로 예상된다. 그러나, 원뿔의 모서리 부분에 표면장력에 의하여 수많은 공기방울이 MR image상에서 관찰되고 또한 MRS상에서 그 스펙트럼을 얻을 수 없었는데 이는 앞으로 원뿔형 MRS 팬톰을 구조적, 기술적으로 더욱 개선해야 할 여지를 남겨두고 있다.

• Asian-Australasian Journal of Animal Sciences
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• 제6권4호
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• pp.607-617
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• 1993

Three experiments were carried out in which lactating Hereford ${\times}$ Friesian cattle walked up to ten kilometers a day for three periods of five days with two non-walking days between each walking period and in which the animals were fed different diets. Measurements were made of milk yield, milk constituent yields and concentrations and blood metabolite concentrations. Exercise caused significant reductions in milk yield and in the yields of lactose and milk protein. Milk fat yield was not reduced when animals were exercised. During exercise the concentrations of ${\beta}-OH$ butyrate and free fatty acids increased, whereas the concentrations of glucose, magnesium and inorganic phosphorus decreased. Diet influenced the effect of exercise on some blood metabolite concentrations.

• Journal of Microbiology and Biotechnology
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• 제12권6호
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• pp.1017-1021
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• 2002

A novel antibacterial metabolite, ARK42, was elated from a xerophilic fungal strain K42, and Identified as Aspergillus repens based on its morphological characteristics. The metabolite exhibited antibacterial activities towards Staphylococcus aureus, Bacillus cereus, and Pseudomonas aeruginosa, with MICs of 25, 12.5, and $3.125{\mu}g/ml$, respectively, and killed Pseudomonas aeruginosa with minimal bactericidal concentration (MBC) of $12.5{\mu}g/ml$. Furthermore, anticancer activities were demonstrated against human colon cancer DLD- 1 and lung cancer LXFL529 cells with an $IC_50$ of 10 and $1{\mu}g/ml$, respectively.

• 한국자기공명학회논문지
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• 제13권1호
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• pp.7-14
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• 2009

The spectral data were collected from the two 600 MHz spectrometers from the two major manufacturers, Broker and Varian. The samples were prepared to create standard curves for quantitative measurements of metabolite concentrations. Instead of employing one-dimensional $^1H$ experiments, the two-dimensional $^1H-^{13}C$ HSQC experiments were performed for better separation of resonances. For some resonances, the high salt condition hindered the linear correlation between the intensity and actual metabolite concentration. Excluding overlapped ones, most resonances showed good linearity. Although the Varian spectrometer showed better linearity, both spectrometers were able to generate acceptable standard curves. From this data, we could identify resonances that could be used to better quantify the concentrations of the particular metabolites. With these standard curves, the quantitative measurements of the metabolites from the real samples will be facilitated.