• 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.

• Journal of Microbiology and Biotechnology
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• 제16권6호
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• pp.870-879
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• 2006

The present study describes the formation of succinic acid by a nonvirulent, highly osmotolerant Klebsiella pneumoniae strain SAP (succinic acid producer), its profile of metabolites, and enzymes of the succinate production pathway. The strain produced succinate along with other metabolites such as lactate, acetate, and ethanol under aerobic as well as anaerobic growth conditions. The yield of succinate was higher in the presence of $MgCO_3$ under $N_2$ atmosphere as compared with that under $CO_2$ atmosphere. Analysis of intracellular metabolites showed the presence of a smaller PEP pool than that of pyruvate. Oxaloacetate, citrate, and $\alpha$-ketoglutarate pools were considerably larger than those of isocitrate and fumarate. In order to understand the synthesis of succinate, the enzymes involved in end-product formation were studied. Levels of phosphoenolpyruvate carboxykinase, fumarate reductase, pyruvate kinase, and acetate kinase were higher under anaerobic growth conditions. Based on the profiles of the metabolites and enzymes, it was concluded that the synthesis of succinate took place via oxaloacetate, malate, and fumarate in the strain under anaerobic growth conditions. The strain SAP showed potential for the bioconversion of fumarate to succinate under $N_2$ atmosphere in the presence of $MgCO_3$. At an initial fumarate concentration of 10 g/l, 7.1 g/l fumarate was converted to 7 g/l succinate with a molar conversion efficiency of 97.3%. The conversion efficiency and succinate yield were increased in the presence of glucose. Cells grown on fumarate contained an 18-fold higher fumarate reductase activity as compared with the activity obtained when grown on glucose.

• Korean Circulation Journal
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• 제53권8호
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• pp.499-518
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• 2023

Cardiovascular diseases (CVDs), including coronary artery disease, stroke, heart failure, and hypertension, are the global leading causes of death, accounting for more than 30% of deaths worldwide. Although the risk factors of CVDs have been well understood and various treatment and preventive measures have been established, the mortality rate and the financial burden of CVDs are expected to grow exponentially over time due to the changes in lifestyles and increasing life expectancies of the present generation. Recent advancements in metagenomics and metabolomics analysis have identified gut microbiome and its associated metabolites as potential risk factors for CVDs, suggesting the possibility of developing more effective novel therapeutic strategies against CVD. In addition, increasing evidence has demonstrated the alterations in the ratio of Firmicutes to Bacteroidetes and the imbalance of microbial-dependent metabolites, including short-chain fatty acids and trimethylamine N-oxide, play a crucial role in the pathogenesis of CVD. However, the exact mechanism of action remains undefined to this day. In this review, we focus on the compositional changes in the gut microbiome and its related metabolites in various CVDs. Moreover, the potential treatment and preventive strategies targeting the gut microbiome and its metabolites are discussed.

• Asian-Australasian Journal of Animal Sciences
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• 제18권1호
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• pp.38-41
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• 2005

An experiment was conducted on 3 male rumen fistulated adult buffaloes fed on wheaten straw and concentrate mixture in a Latin square design to study the impact of niacin supplementation on rumen metabolites. Three animals were fed wheaten straw+concentrate mixture (group I, control), wheaten straw+concentrate mixture+100 ppm niacin (group II), and wheaten straw +concentrate mixture+200 ppm niacin (group III). After 21 days feeding, rumen liquor was drawn for 3 consecutive days at different time intervals (0, 2, 4, 6 and 8 h) to study the various rumen metabolites i.e., rumen pH, ammonia-N, total-N, trichloroacetic acid precipitable-N, non-protein nitrogen, total volatile fatty acids, their fractions and number of protozoa. Mean pH values in strained rumen liquor (SRL) of animals in 3 groups were 6.64, 6.71 and 6.67, indicating no statistically significant difference. Results revealed a significant (p<0.01) increase in TVFA concentration among the supplemented groups (group II and III) in comparison to control group. Mean TVFA concentration (meq/dl) was 9.75, 10.97 and 11.44 in 3 groups respectively. The highest concentration of TVFA was observed at 4 h and minimum at 0 h in all the 3 groups. The percentage of acetic, propionic, butyric and isobutyric acid was statistically similar among the three groups. The mean ammonia-N concentration (mg/dl SRL) was significantly (p<0.01) lower in group II (16.38) and group III (15.42) than group I (18.14). Ammonia-N concentration was higher (p<0.01) at 4 h as compared to all the time intervals. The mean total-N concentration (mg/dl SRL) was higher (p<0.01) in group II (74.16) and group III (75.47) as compared to group I (62.04). Total-N concentration was higher (p<0.01) at 4 h as compared to other time intervals and lowest value was recorded at 0 h.Concentration of TCA-ppt-N (mg/dl SRL) was significantly (p<0.01) lower in control group as compared to niacin supplemented groups. Mean value of NPN (mg/dl SRL) was significantly (p<0.01) lower in group III (23.21) as compared to group I (25.71), whereas groups I and II, and groups II and III were similar to each other. Total protozoa number (${\times}10^4$/ml SRL) ranged from 18.06 to 27.41 in group I, 20.89 to 38.44 in group II and 27.61 to 39.45 in group III. The mean protozoa number was significantly (p<0.01) higher in SRL of group II (27.60) and III (30.59) as compared to group I (22.48). It can be concluded from the study that supplementation of niacin in the diet of buffaloes had improved the rumen fermentation by decreasing the concentration of ammonia-N and increasing protein synthesis.

• 한국산학기술학회논문지
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• 제21권2호
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• pp.432-439
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• 2020

이 연구는 급여하는 조사료와 농후사료 비율을 달리하였을 때, 우분 내 대사체 비교를 핵자기공명장치로 확인하기 위해 실시되었다. 착유중인 젖소 6마리를 두 그룹으로 나누어 조사료와 농후사료 급여 비율(HR 그룹=8:2, HC 그룹=2:8)을 달리 하였다. 우분은 직장을 통해 마리별 1회 채취 하였으며 대사체 분석은 SPE-800 MHz NMR-MS system을 이용하였다. 대사체의 정성 및 정량은 Chenomx NMR suite 8.4을 이용하였으며, 확인된 대사체들을 Metaboanalyst 4.0을 이용하여 다변량 분석, 대사경로 분석을 진행하였다. 통계분석은 SAS program을 이용하여 Dunnett's test로 그룹 간 대사체 평균값을 비교 하였다. 분석 결과, 다변량 분석에서는 그룹간의 분리가 확인 되었으며 확인된 대사체 중 통계분석에는 77개의 대사체가 이용되었다. HC 그룹에서 유의적으로 높았던 대사체는 succinate를 포함한 dimethylamine, histamine, homovanillate, thymol, acetate, propionate, butyrate, isovalerate, valerate, imidazole, N-Nitrosodimethylamine 그리고 O-Acetylcholine 이다. HC 그룹에서 분석된 대사체들의 평균 농도가 HR 그룹에 비해 높았으며, 분석된 대사경로 또한 HR 그룹에 비해 다양했다. 연구결과, 핵자기공명분광장치를 통해 분석한 우분 내 대사체는 장내 미생물 뿐 만 아니라 체내 대사 그리고 향후 축산 관련 다양한 연구에 유용하게 사용될 것으로 사료된다.

• 한국자기공명학회논문지
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• 제12권1호
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• pp.14-25
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• 2008

To investigate the 3-bond connectivity of human brain metabolites by scalar coupling interaction through 2D-correlation spectroscopy (COSY) techniques using high field NMR spectroscopy. All NMR experiments were performed at 298K on Unity Inova 500 or 600 (Varian Inc.) equipped with a triple resonance probe head with z-shield gradient. Human brain metabolites were prepared with 10% $D_2O$. Two dimensional 2D COSY spectra were acquired with 4096 complex data points in $t_2$ and 128 or 256 increments in $t_1$ dimension. The spectral width was 9615.4 Hz and solvent suppression was achieved using presaturation using low power irradiation of the water resonance during 2s of relaxation delay. NMR data were processed using VNMRJ (Varian Instrument) software and all the chemical shifts were referenced to the methyl resonance of N-acetyl aspartate (NAA) peak at 2.0 ppm. Total 10 metabolites such as N-acetyl aspartate (NAA), creatine (Cr), choline (Cho), glutamine (Gln), glutamate (Glu), myo-inositol (Ins), lactate (Lac), taurine (Tau), ${\gamma}$-aminobutyricacid (GABA), alanine (Ala) were included for major target metabolites. Symmetrical 2D-COSY spectra were successfully acquired. Total 14 COSY cross peaks were observed even though there were parallel/orthogonal noisy peaks induced by water suppression. Except for Cr, all of human brain metabolites produced COSY cross peaks. The spectra of NAA methyl proton at 2.02 ppm and Glu methylene proton ($CH_2(3)$) at 2.11 ppm and Gln methylene proton ($CH_2(3)$) at 2.14 ppm were overlapped in the similar resonance frequency between 2.00 ppm and 2.15 ppm. The present study demonstrated that in vitro 2D-COSY represented the 3-bond connectivity of human brain metabolites by scalar coupling interaction. This study could aid in better understanding the interactions between human brain metabolites in vivo 2D-COSY study. Also it would be helpful to determine the molecular stereochemistry in vivo by using two-dimensional MR spectroscopy.

• Nutrition Research and Practice
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• 제14권2호
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• pp.102-108
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• 2020

BACKGROUND/OBJECTIVES: In Oriental medicine, certain foods may be beneficial or detrimental based on an individual's constitution; however, the scientific basis for this theory is insufficient. The purpose of this study was to investigate the effect of body constitution, based on the Sasang type of Korean traditional medical classification system, on the bioavailability of soy isoflavones of Cheonggukjang, a quick-fermented soybean paste. SUBJECTS/METHODS: A pilot study was conducted on 48 healthy Korean men to evaluate the bioavailability of isoflavone after ingestion of food based on constitution types classified by the Sasang typology. The participants were classified into the Taeeumin (TE; n = 15), Soyangin (SY; n = 15), and Soeumin (SE; n = 18) groups. Each participant ingested 50 g of Cheonggukjang per 60 kg body weight. Thereafter, blood was collected, and the soy isoflavone metabolites were analyzed by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. Ntrikinetic analysis of individual isoflavone-derived metabolites was performed. RESULTS: Our nutrikinetic analysis identified 21 metabolites derived from isoflavones in the blood samples from 48 healthy Korean men (age range, 21-29 years). Significant differences were observed in the time to maximum concentration (T_max) and elimination half-life (t_1/2) for nine metabolites among the three groups. The T_max and t_1/2 of the nine metabolites were higher in the SE group than in the other groups. Moreover, the absorption rates, as determined by the area under the plasma-level curve (AUC) values of intact isoflavone, were 5.3 and 9.4 times higher in the TE group than in the SY and SE groups, respectively. Additionally, the highest AUC values for phase I and II metabolites were observed in the TE group. CONCLUSIONS: These findings indicate that isoflavone bioavailability, following Cheonggukjang insgestion, is high in individuals with the TE constitution, and relatively lower in those with the SE and SY constitutions.

• Journal of Microbiology and Biotechnology
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• 제19권10호
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• pp.1142-1149
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• 2009

Several bioactive metabolites, including pyrrolnitrin, N-acylhomoserine lactones, and polyhydroxyalkanoates were isolated from Burkholderia sp. O33. Effects of various nutrients, including sugars, gluconolactone, glycerol, tryptophan, chloride, and zinc were investigated in relation to the production of these metabolites. Logarithmic increase of pyrrolnitrin was observed between 2-5 days and reached a maximum at 7-10 days. Tryptophan concentration reached the maximum at 3 days, whereas 7-chlorotryptophan was gradually increased throughout the studies. Among various carbon sources, gluconolactone, trehalose, and glycerol enhanced pyrrolnitrin production, whereas strong inhibitory effects were found with glucose. Relative concentrations of pyrrolnitrin and its precursors were in the order of pyrrolnitrin$\gg$dechloroaminopyrrolnitrin or aminopyrrolnitrin throughout the experiments. Among three N-acylhomoserine lactones, the N-octanoyl analog was the most abundant quorum sensing signal, of which the concentrations reached the maximum in 2-3 days, followed by a rapid dissipation to trace level. No significant changes in pyrrolnitrin biosynthesis were observed by external addition of N-acylhomoserine lactones. Polyhydroxyalkanoates accumulated up to 3-4 days and decreased slowly thereafter. According to the kinetic analyses, no strong correlations were found between the levels of pyrrolnitrin, N-acylhomoserine lactones, and polyhydroxyalkanoates.

• Journal of Microbiology and Biotechnology
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• 제25권5호
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• pp.672-680
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• 2015

As a global regulatory gene in Streptomyces, afsR can activate the biosynthesis of many secondary metabolites. The effect of afsR on the biosynthesis of a phenazine metabolite, lomofungin, was studied in Streptomyces lomondensis S015. There was a 2.5-fold increase of lomofungin production in the afsR-overexpressing strain of S. lomondensis S015 N1 compared with the wild-type strain. Meanwhile, the transcription levels of afsR and two important genes involved in the biosynthesis of lomofungin (i.e., phzC and phzE) were significantly upregulated in S. lomondensis S015 N1. The optimization of metal chlorides was investigated to further increase the production of lomofungin in the afsR-overexpressing strain. The addition of different metal chlorides to S. lomondensis S015 N1 cultivations showed that CaCl₂, FeCl₂, and MnCl₂ led to an increase in lomofungin biosynthesis. The optimum concentrations of these metal chlorides were obtained using response surface methodology. CaCl₂ (0.04 mM), FeCl₂ (0.33 mM), and MnCl₂ (0.38 mM) gave a maximum lomofungin production titer of 318.0 ± 10.7 mg/l, which was a 4.1-fold increase compared with that of S. lomondensis S015 N1 without the addition of a metal chloride. This work demonstrates that the biosynthesis of phenazine metabolites can be induced by afsR. The results also indicate that metal chlorides addition might be a simple and useful strategy for improving the production of other phenazine metabolites in Streptomyces.

• Journal of Nutrition and Health
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• 제40권1호
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• pp.5-13
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• 2007

This study was designed to examine the effects of Salicornia herbacea L. (glasswort: GW) on the plasma blood glucose and lipid metabolites in diabetic rats. Diabetes mellitus was induced in male Sprague-Dawley rats weighing 200-220g by an injection of streptozotocin (STZ) dissolved in a citrate buffer into the tail vein at a dose of 45 mg/kg of body weight. Sprague-Dawley rats were fed an AIN-93 recommended diet and the experimental groups were fed a modified diet containing 10% and 20% of glasswort powder for 4 weeks. The experimental groups were divided into 6 groups which consisted of normal (N)-control group, N-GW 10% and N-GW 20% treated groups, STZ-control, STZ-GW 10% and STZ-GW 20% treated groups. The rats' body weights, aminotransferase activities and hematocrit (Hct) values were measured, along with plasma levels of glucose, protein, cholesterol, HDL-cholesterol, triglyceride (TG) and free fatty acids (FFA). The non-diabetic rats gained weight, while the diabetic rats lost weight. There were significant differences between the control group and the diabetic groups in the weight of the kidney, liver and pancreas. Asparate aminotransferase activity was lower in the non-diabetic control group compared to diabetic experimental groups, even though the difference was not significant. The plasma protein of N-GW 20% group was lower among all experimental groups but it was not significantly different. The blood glucose levels of the STZ-GW 10% group and STZ-GW 20% group were significantly lower than for the diabetic-control group. There were no significant difference of cholesterol levels among diabetic groups. The normal rats of 20% glasswort group in FFA and TG levels showed significant changes among all groups. These results exhibited dose related effect of glasswort and it may contain antihypoglycemic compounds.