• 제목/요약/키워드: Metabolites

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Determination of Phthalate Metabolites in Human Serum and Urine as Biomarkers for Phthalate Exposure Using Column-Switching LC-MS/MS

  • Jeong, Jee-Yeon;Lee, Ji-Hyun;Kim, Eun-Young;Kim, Pan-Gyi;Kho, Young-Lim
    • Safety and Health at Work
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    • 제2권1호
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    • pp.57-64
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    • 2011
  • Objectives: Although phthalates like dibutyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) are commonly used as plasticizers and their metabolites are especially suspected of reproductive toxicity, little is known about occupational exposure to those phthalates. The aim of this study was to assess the utility of measuring the metabolite concentrations of DBP and DEHP in serum and urine samples as an indicator of occupational exposure to those phthalates. Methods: Phthalate metabolites were analyzed by using column-switching high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS). Results: We detected phthalate metabolites in serum and urine matrices at approximately 10-fold lower than the limit of detection of those metabolites in the same matrix by LC-MS/MS without column switching, which was sufficient to evaluate concentrations of phthalate metabolites for industrial workers and the general population. Conclusion: The accuracy and precision of the analytical method indicate that urinary metabolite determination can be a more acceptable biomarker for studying phthalate exposure and adverse health outcomes.

Optimal Conditions for Antimicrobial Metabolites Production from a New Streptomyces sp. RUPA-08PR Isolated from Bangladeshi Soil

  • Ripa, F.A.;Nikkon, F.;Zaman, S.;Khondkar, P.
    • Mycobiology
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    • 제37권3호
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    • pp.211-214
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    • 2009
  • An actinomycete strain was isolated from northern part of Bangladesh and identified as a new Streptomyces species on the basis of its morphological, biochemical, cultural characteristics and 16S rRNA data. Attempts were made to optimize the culture conditions for the production of antimicrobial metabolites by this strain. Antimicrobial metabolites production was started after 7 days of incubation of culture broth and reached its maximum levels after 10 days and thereafter gradually decreased. The maximum production of antimicrobial metabolites was obtained when the culture medium pH was adjusted to 8. The optimum temperature for antimicrobial metabolites production was $39^{\circ}C$, indicated the new strain as mesophilic organism. Basel medium supplemented with glucose and yeast extract as carbon and nitrogen sources, respectively, was proved to be the best for the production of bioactive metabolites. Maximum production of bioactive metabolites was when NaCl concentration was 1% and among different minerals tested, $K_2HPO_4$ and NaCl showed positive influence on antibiotic production by the strain.

Probiotics-Mediated Bioconversion and Periodontitis

  • Lee, Yewon;Yoon, Yohan;Choi, Kyoung-hee
    • 한국축산식품학회지
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    • 제41권6호
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    • pp.905-922
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    • 2021
  • Novel bioactive metabolites have been developed through a bioconversion of dairy products or other foods using probiotics isolated from dairy products or other fermented foods. These probiotics-mediated bioconversion (PMB) metabolites show antioxidant, anti-inflammatory, antimicrobial, epithelial barrier, and anticancer activities. In addition, the effect of PMB metabolites in periodontitis is recently reported in several studies. Periodontitis is a chronic inflammatory disease caused by infections, and the tooth support tissue is destroyed. Common treatments for periodontitis include scaling and root planning with systemic antibiotics. However, the overuse of antibiotics has led to the emergence of drug-resistant microorganisms and disturbs the beneficial bacteria, including lactobacilli in the oral cavity. For this reason, PMB metabolites, such as fermented milk, have been suggested as substitutes for antibiotics to reduce periodontitis. This paper reviews the recent studies on the correlation between periodontitis and PMB metabolites and classifies the efficacy of major PMB metabolites for periodontitis. The review suggests that PMB is effective for periodontitis, and further studies are needed to confirm the therapeutic effect of PMB metabolites on periodontitis.

Global Regulators to Activate Silent Biosynthetic Gene Clusters

  • Shim, Sang Hee
    • Natural Product Sciences
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    • 제26권3호
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    • pp.183-190
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    • 2020
  • Genome mining has recently emerged as a powerful strategy to discover novel microbial secondary metabolites. However, more than 50% of biosynthetic gene clusters are not transcribed under standardized laboratory culture condition. Several methods have been applied to activate silent biosynthetic gene clusters in the microbes so far. Among the regulatory systems for production of secondary metabolites, global regulators, which affect transcription of genes through regulatory cascades, typically govern the production of small molecules. In this review, global regulators to affect production of microbial secondary metabolites were discussed.

The Serum or Urinary Levels of Cyclohexane Metabolites in Liver Damaged Rats

  • 조현성
    • 대한의생명과학회지
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    • 제12권3호
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    • pp.241-247
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    • 2006
  • To evaluate an effect of pathological liver damage on the cyclohexane (CH) metabolism, rats were pretreated with 50% carbon tetrachloride $(CCl_4)$ dissolved in olive oil (0.1ml/100g body weight) 10 or 17 times intraperitoneally at intervals of every other day. To these liver damaged animals, CH (a single dose of 1.56g/kg body weight, i.p.) was administered at 48hr after the last injection of $CCl_4$. The CH metabolites; cyclohexanol (CH-ol), cyclohexane-l,2-diol (CH-l,2-diol) and cyclohexane-l,4-diol (CH-l,4-diol) and cyclohexanone (CH-one) were detected in the urine of CH treated rats. After CH treatment, the serum levels of CH-ol and CH-one were remarkably increased at 4 hr and then decreased at 8hr in normal group. Whereas in liver damaged rats, these CH metabolites were higher at 8hr than at 4hr. The excretion rate of CH metabolites trom serum into urine was more decreased in liver damaged animals than normal group, with the levels of excretion rate being lower in $CCl_4$ 17 times injected animals than 10 times injected ones. It was interesting that the urinary concentration of CH metabolites was generally more increased in liver damaged animals than normal ones, and the increasing rate was higher in $CCl_4$ 17 times injected rats than 10 times injected ones. Taken all together, it is assumed that reduced urinary excretion rate of CH metabolites in liver damaged rats might be resulted from deteriorated hepatic and renal blood flow, and an increased urinary excretion amount of CH metabolites in liver damaged rats might be caused by reduced expiration amount of the metabolites due to lung damage.

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Analysis of polyphenolic metabolites from Artemisia gmelinii Weber ex Stechm. and regional comparison in Korea

  • Park, Mi Hyeon;Kim, Doo-Young;Jang, Hyun-Jae;Jo, Yang Hee;Jeong, Jin Tae;Lee, Dae Young;Baek, Nam-In;Ryu, Hyung Won;Oh, Sei-Ryang
    • Journal of Applied Biological Chemistry
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    • 제62권4호
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    • pp.433-439
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    • 2019
  • Artemisia species are widely used as food ingredients and raw material in traditional medicine. However, to date, the secondary metabolites of Artemisia gmelinii Weber ex Stechm. have not been sufficiently investigated. The secondary metabolites of A. gmelinii, which was collected from representative regions in Chungbuk, Gangwon, and Gyeongbuk, were analyzed using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTof MS) combined with an unsupervised principal component analysis (PCA) multivariate analysis. In the loading scatter plot of PCA, significant changes in metabolites were observed between the regions, ten metabolites (3: 5-O-caffeoylquinic acid, 4: 4-O-caffeoylquinic acid, 8: trans-melilotoside, 12: quercetin 3-O-hexoside, 15: 3,4-O-dicaffeoylquinic acid, 17: 3,5-O-dicaffeoylquinic acid, 18: 4,5-O-dicaffeoylquinic acid, 19: syringaldehyde, 20: caffeoylquinic acid derivative, and 23: icariside II) were evaluated as key markers among twenty-five identified metabolites. Interestingly, the contents of the identified marker significantly differed between the three groups. This is the first study to report the presence of marker metabolites and their correlating geographical cultivation in A. gmelinii.

Mitogenic Estrogen Metabolites Alter the Expression of β-estradiol-regulated Proteins Including Heat Shock Proteins in Human MCF-7 Breast Cancer Cells

  • Kim, Seong Hwan;Lee, Su-Ui;Kim, Myung Hee;Kim, Bum Tae;Min, Yong Ki
    • Molecules and Cells
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    • 제20권3호
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    • pp.378-384
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    • 2005
  • Estrogen metabolites are carcinogenic. The comparative mitogenic activities of $17{\beta}$-estradiol (E2) and four metabolites, 2-hydroxyestradiol (2-OHE2), 4-hydroxyestradiol (4-OHE2), $16{\alpha}$-hydroxyestrone ($16{\alpha}$-OHE1) and 2-methoxyestradiol (2-ME), were determined in estrogen receptor(ER)-positive MCF-7 human breast cancer cells. Each of the E2 metabolites caused proliferation of the MCF-7 cells, but only E2 and $16{\alpha}$-OHE1 induced a greater than 20-fold increases in transcripts of the progesterone receptor (PR) gene, a classical ER-mediated gene. This suggests that the mitogenic action of E2 and $16{\alpha}$-OHE1 could result from their effects on gene expression via the ER. E2 metabolites altered the expression of E2-regulated proteins including heat shock proteins (Hsps). $16{\alpha}$-OHE1 and 2-ME as well as E2 increased levels of Hsp56, Hsp60, $Hsp90{\alpha}$ and Hsp110 transcripts, and the patterns of these inductions resembled that of PR. Hsp56 and Hsp60 protein levels were increased by all the E2 metabolites. Levels of the transcripts of 3 E2-upregulated proteins (XTP3-transactivated protein A, protein disulfide isomerase-associated 4 protein and stathmin 1) and an E2-downregulated protein (aminoacylase 1) were also affected by the E2 metabolites. These results suggest that the altered expression of Hsps (especially Hsp56 and Hsp60) by E2 metabolites such as E2, $16{\alpha}$-OHE1 and 2-ME could be closely linked to their mitogenic action.

Clues to Understand the Regulatory Metabolisms Governing the Biosynthesis of Fungal Secondary Metabolites

  • Choi, Yoon-E
    • 한국균학회소식:학술대회논문집
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    • 한국균학회 2015년도 춘계학술대회 및 임시총회
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    • pp.14-14
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    • 2015
  • Fungi are of particular interest due to their capacity to produce an extensive array of secondary metabolites. While many secondary metabolites have no known functions to the producing fungal organisms, these metabolites have tremendous importance to humans with beneficial (e.g., antibiotics) or detrimental (e.g., mycotoxins) properties. In this study, two important filamentous fungi, Fusarium verticillioides and Mycosphaerella graminicola were selected as target species and the genes regulatory functions on the biosynthesis of secondary metabolisms were studied. Functional genomics including forward and reverse genetics, and proteomics were utilized to better understand the complex secondary metabolism regulations in both F. verticillioides and M. graminicola. Identified genes in either F. verticillioides or M. graminicola background were CPP1 (a putative protein phosphatase gene), GAC1 (encoding a GTPase activating protein), MCC1(encoding c-type cyclin), and the velvet gene, MVE1. Our data suggest that there are diverse regulatory genes on fungal secondary metabolites with distinct or overlapping functional roles.

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Biotransformation of Valdecoxib by Microbial Cultures

  • Srisailam, K.;Veeresham, C.
    • Journal of Microbiology and Biotechnology
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    • 제20권4호
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    • pp.809-816
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    • 2010
  • Microbial biotransformations can be used to predict mammalian drug metabolism. The present investigation deals with microbial biotransformation of valdecoxib using microbial cultures. Thirty-nine bacterial, fungal, and yeast cultures were used to elucidate the biotransformation pathway of valdecoxib. A number of microorganisms metabolized valdecoxib to various levels to yield nine metabolites, which were identified by HPLC-DAD and LC-MS-MS analyses. HPLC analysis of biotransformed products indicated that a majority of the metabolites are more polar than the substrate valdecoxib. Basing on LC-MS-MS analysis, the major metabolite was identified as a hydroxymethyl metabolite of valdecoxib, whereas the remaining metabolites were produced by carboxylation, demethylation, ring hydroxylation, N-acetylation, or a combination of these reactions. The hydroxymethyl and carboxylic acid metabolites were known to be produced in metabolism by mammals. From the results, it can be concluded that microbial cultures, particularly fungi, can be used to predict mammalian drug metabolism.

흡연자와 비흡연자의 소변 중 다환방향족탄화수소(PAHs) 대사체 농도 비교 (Comparison of Concentration of Urinary Metabolites of PAHs from Smokers and Nonsmokers)

  • 고영림;이은희
    • 한국환경보건학회지
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    • 제37권6호
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    • pp.474-481
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    • 2011
  • This study investigated urinary metabolites of polycyclic aromatic hydrocarbons (PAHs) in the urine of smokers and non-smokers by liquid chromatography triple quordrupole tandem mass spectroscopy (LC/MS/MS). Compounds analyzed for urinary biomarkers of PAHs were five mono-hydroxylated PAHs metabolites; 1-naphthol, 2-naphthol, 1-hydroxypyrene(1-OHP), 3-phenanthrol, 2-fluorenol. Urine samples were pretreated by enzymatic hydrolysis and solid phase extraction method. Smokers were composed of 17 men and five women; non-smokers 17 men and 16 women. Smoking increased urinary concentrations of five PAHs metabolites significantly higher than those of nonsmokers. Statistically significant correlations among the five PAHs metabolites were shown. The results suggest that LC/MS/MS technology should be useful in the environmental health discipline.