• Proceedings of the Korean Society of Medical Physics Conference
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• 2002.09a
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• pp.345-351
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• 2002

The purpose of this study was to assess clinical proton MR spectroscopy (MRS) as a noninvasive method for evaluating brain tumor malignancy at 3T high field system. Using 3T MRI/MRS system, localized water-suppressed single-voxe1 technique in patients with brain tumors was employed to evaluate spectra with peaks of N-acetyl aspartate (NAA), choline-containing compounds (Cho), creatine/phosphocreatine (Cr) and lactate. On the basis of Cr, these peak areas were quantificated as a relative ratio. The variation of metabolites measurements of the designated region in 10 normal volunteers was less than 10%. Normal ranges of NAA/Cr and Cho/Cr ratios were 1.67${\pm}$018 and 1.16${\pm}$0.15, respectively. NAA/Cr ratio of all tumor tissues was significantly lower than that of the normal tissues (p=0.005), but Cho/Cr ratio of all tumor tissue was significantly higher (p=0.001). Cho/Cr ratio of high-grade gliomas was significantly higher than that of low-grade gliomas (P=0.001). Except 4 menigiomas, lactate signal was observed in all tumor cases. The present study demonstrated that the neuronal degradation or loss was observed in all tumor tissues. Higher grade of brain tumors was correlated with higher Cho/Cr ratio, indicating a significant dependence of Cho levels on malignancy of gliomas. Our results suggest that clinical proton MR spectroscopy could be useful to predict tumor malignancy.

• Mass Spectrometry Letters
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• v.7 no.4
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• pp.106-110
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• 2016

Ginseng, a traditional herbal drug, has been used in Eastern Asia for more than 2000 years. Various ginsenosides, which are the major bioactive components of ginseng products, have been shown to exert numerous beneficial effects on the human body when co-administered with drugs. However, this may give rise to ginsenoside-drug interactions, which is an important research consideration. In this study, acassette assay was performed the inhibitory effects of 12 ginsenosides on seven cytochrome P450 (CYP) isoforms in human liver microsomes (HLMs) using LC-MS/MS to predict the herb-drug interaction. After incubation of the 12 ginsenosides with seven cocktail CYP probes, the generated specific metabolites were quantified by LC-MS/MS to determine their activities. Ginsenoside Rb1 and F2 showed strong selective inhibitory effect on CYP2C9-catalyzed diclofenac 4'-hydroxylation and CYP2B6-catalyzed bupropion hydroxylation, respectively. Ginsenosides Rd showed weak inhibitory effect on the activities of CYP2B6, 2C9, 2C19, 2D6, 3A4, and compound K, while ginsenoside Rg3 showed weak inhibitory effects on CYP2B6. Other ginsenosides, Rc, Rf, Rg1, Rh1, Rf, and Re did not show significant inhibitory effects on the activities of the seven CYPs in HLM. Owing to the poor absorption of ginsenosides after oral administration in vivo, ginsenosides may not have significant side effects caused by interaction with other drugs.

• Mycobiology
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• v.47 no.4
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• pp.441-448
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• 2019

Two new SAM-dependent methyltransferase encoding genes (fvsmt1 and fvsmt2) were identified from the genome of Flammulina velutipes. In order to make a comprehensive characterization of both genes, we performed in silico analysis of both genes and used qRT-PCR to reveal their expression patterns during the development of F. velutipes. There are 4 and 6 exons with total length of 693 and 978 bp in fvsmt2 and fvsmt1, respectively. The deduced proteins, i.e., FVSMT1 and FVSMT2 contained 325 and 230 amino acids with molecular weight 36297 and 24894 Da, respectively. Both proteins contained a SAM-dependent catalytic domain with signature motifs (I, p-I, II, and III) defining the SAM fold. SAM-dependent catalytic domain is located either in the middle or at the N-terminal of FVSMT2 and FVSMT1, respectively. Alignment and phylogenic analysis showed that FVSMT1 is a homolog to a protein-arginine omega-N-methyltransferase, while FVSMT2 is of cinnamoyl CoA O-methyltransferase type and predicted subcellular locations of these proteins are mitochondria and cytoplasm, respectively. qRT-PCR showed that fvsmt1 and fvsmt2 expression was regulated in different developmental stages. The maximum expression levels of fvsmt1 and fvsmt2 were observed in stipe elongation, while no difference was found in mycelium and pileus. These results positively demonstrate that both the methyltransferase encoding genes are involved in the stipe elongation of F. velutipes.

• Journal of Microbiology and Biotechnology
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• v.30 no.5
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• pp.753-761
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• 2020

To determine the role of pyruvate dehydrogenase complex (PDHC) in Klebsiella pneumoniae, the growth and metabolism of PDHC-deficient mutant in glycerol-based medium were analyzed and compared with those of other strains. Under aerobic conditions, the PDHC activity was fourfold higher than that of pyruvate formate lyase (PFL), and blocking of PDHC caused severe growth defect and pyruvate accumulation, indicating that the carbon flux through pyruvate to acetyl coenzyme A mainly depended on PDHC. Under anaerobic conditions, although the PDHC activity was only 50% of that of PFL, blocking of PDHC resulted in more growth defect than blocking of PFL. Subsequently, combined with the requirement of CO₂ and intracellular redox status, it was presumed that the critical role of PDHC was to provide NADH for the anaerobic growth of K. pneumoniae. This presumption was confirmed in the PDHC-deficient mutant by further blocking one of the formate dehydrogenases, FdnGHI. Besides, based on our data, it can also be suggested that an improvement in the carbon flux in the PFL-deficient mutant could be an effective strategy to construct high-yielding 1,3-propanediol-producing K. pneumoniae strain.

• Toxicological Research
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• v.6 no.2
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• pp.167-182
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• 1990

Dietary restriction (caloric restriction) is the only intervention which has been reliably shown to extend the maximum life span of warm-blooded animals and delay the many phenomena associated with aging. It is also one of the most effective modulators of toxicity, especially cancer endpoints. In spite of the known modulator effects of caloric restriction, the biological mechanisms responsible for these effects had not been in vestigated until recently. The National Center for Toxicological Research (NCTR), in a collaborative effort with the National Institute of Aging (NIA), initiated a project whereby nine (9) combinations of rodent species/strains and diets were fed both restricted and ad libitum. The NIA's initiative was to identify biomarkers of aging whereas NCTR's initiative was to identify the biological effects associated with the profound effects caloric restriction has in protecting against both spontaneous (age-related) and chemically-induced toxic endpoints. Independent of sex or species, caloric restriction has similar effects on body temperature, oxygen consumption and $CO_2$production. Caloric restriction also decreased lipid glycolysis and metabolism in rats and mice, which suggest decreased production of metabolites which could lead to fatty acid epoxide formation. The age-associated loss of ciradian regulation of intermediate enzymes is also significantly reduced. Moreover, caloric restriction reduced the age-associated feminization of sexually dimorphic liver isozymes, increased several glucocorticoid responsive isozymes, elevated glucagon/insulin ratios, produced less microsomal superoxide and enhanced the capacity for utilzing detoxicating metabolic pathways. Calorically restricted rats have less than half the number of aflatoxin ($AFB_1$)-DNA adducts than ad libitum animals and urinary excretion of $AFB_1$ was increased significantly. Finally, DNA repair mechanisms are enhanced and oncogene expression is decreased in calorically restricted animals.

• KSBB Journal
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• v.24 no.3
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• pp.279-286
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• 2009

Streptomyces is well known for their ability to synthesize enormous varieties of antibiotics as secondary metabolites. Among them, S. avermitilis produces avermectins, a group of antiparasitic agents used in human and veterinary medicine. However, S. avermitilis also produces oligomycin, which is a potential toxic inhibitor of oxidative phosphorylation in mammalian cells. Therefore, we decided to disrupt oligomycin synthetase gene to prevent co-production of oligomycin in S. avermitilis. To create plasmid for disruption, the smallest gene of oligomycin synthetase gene cluster was obtained by PCR from S. avermitilis chromosome. Then, apramycin resistance gene was inserted in oligomycin synthetase gene for selection. After transformation of this plasmid, oligomycin synthetase gene (olmA5) in the chromosome was displaced with disruption cassette on the plasmid via homologous recombination. As a result of this gene replacement, we obtained mutants (olmA5::apra) that no longer makes the toxic oligomycin. And the mutants confirmed by PCR and HPLC analysis. However, showed no increasement of avermectin production in the mutant was observed.

• Journal of the Korean Society of Food Science and Nutrition
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• v.13 no.1
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• pp.117-126
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• 1984

Aflatoxins are toxic and carcinogenic secondary metabolites which are produced by trains of A. flavus and A. parasiticus during their growth on foods and feedstuffs. Aflatoxins are a group of closely related heterocyclic compounds of which $B_1$, $B_2$, and $G_2$ are the major members. Aflatoxins are synthesized via a polyketide pathway in which the general steps are acetate, an-thraquinones, xanthone and aflatoxins. Aflatoxin formation is favored by high moisture or high $a_w$(0.95${\sim}$0.99). The limiting $a_w$ for aflatoxin production on agricultural commodities is 0.83. Optimum temperature for aflatoxin production by the molds is $25{\sim}30^{\circ}C$ and the incubation time for the maximum production of the toxin is 7${\sim}$15 days. The limiting temperatures for aflatoxin production are ${\leq}7.5^{\circ}C\;and\;\geq40^{\circ}C$. Cycling temperatures may or may not stimulate aflatoxin production depending on the amplitude of cycling, substrate and strains of molds. Aflatoxin pro-ducing molds are aerobic organisms and thus have a requirement for oxygen. A decreasing $O_2$ concentration and/or increasing concentrations of $CO_2$ or $N_2$ depress the mold growth and aflatoxin formation. A. flavus grows competitively or associatively in the presence of other microorganisms and occasionally loses the competition with other microorganisms. Some lactic acid bacteria have been shown to reduce growth and aflatoxin production by A. parasiticus. Carbon source is the most important nutritional factors affecting aflatoxin formation by the molds. Sucrose, fructose and glucose are the most favorable carbon sources. Food substrates of plant derived products which have high carbohydrate content such as agricultural commodities and their products are most vulnerable to contamination by aflatoxins.

• Journal of Ginseng Research
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• v.38 no.3
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• pp.203-207
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• 2014

Background: There is limited understanding of the effect of dietary components on the absorption of ginsenosides and their metabolites into the blood. Methods: This study investigated the pharmacokinetics of the ginseng extract and its main constituent ginsenoside Rb1 in rats with or without pretreatment with a prebiotic fiber, NUTRIOSE, by liquid chromatography tandem mass spectrometry. When ginsenoside Rb1 was incubated with rat feces, its main metabolite was ginsenoside Rd. Results: When the intestinal microbiota of rat feces were cultured in vitro, their ginsenoside Rd-forming activities were significantly induced by NUTRIOSE. When ginsenoside Rb1 was orally administered to rats, the maximum plasma concentration (Cmax) and area under the plasma drug concentratione-time curve (AUC) for the main metabolite, ginsenoside Rd, were $72.4{\pm}31.6ng/mL$ and $663.9{\pm}285.3{\mu}g{\cdot}h/mL$, respectively. When the ginseng extract (2,000 mg/kg) was orally administered, Cmax and AUC for ginsenoside Rd were $906.5{\pm}330.2ng/mL$ and $11,377.3{\pm}4,470.2{\mu}g{\cdot}h/mL$, respectively. When ginseng extract was orally administered to rats fed NUTRIOSE containing diets (2.5%, 5%, or 10%), Cmax and AUC were increased in the NUTRIOSE receiving groups in a dose-dependent manner. Conclusion: These findings reveal that intestinal microflora promote metabolic conversion of ginsenoside Rb1 and ginseng extract to ginsenoside Rd and promote its absorption into the blood in rats. Its conversion may be induced by prebiotic diets such as NUTRIOSE.

• Korean Journal of Agricultural Science
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• v.44 no.1
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• pp.30-39
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• 2017

This study was performed to produce succinic acid from biomass by developing mutants of Cellulomonas flavigena in which the succinate dehydrogenase gene (sdh) is deleted. For development of succinate producing mutants, the upstream and downstream regions of sdh gene from C. flavigena and antibiotic resistance gene (neo, bla) were inserted into pKC1139, and the recombinant plasmids were transformed into Escherichia coli ET12567/pUZ8002 which is a donor strain for conjugation. C. flavigena was conjugated with the transformed E. coli ET12567/pUZ8002 to induce the deletion of sdh in chromosome of this bacteria by double-crossover recombination. Two mutants (C. flavigena H-1 and H-2), in which sdh gene was deleted in the chromosome, were constructed and confirmed by PCR. To estimate the production of succinic acid by the two mutants when the culture broth was fermented with biomass such as CMC, xylan, locust gum, and rapeseed straw; the culture broth was analyzed by HPLC analysis. The succinic acid in the culture broth was not detected as a fermentation products of all biomass. One of the reasons for this may be the conversion of succinic acid to fumaric acid by sdh genes (Cfla_1014 - Cfla_1017 or Cfla_1916 - Cfla_1918) which remained in the chromosomal DNA of C. flavigena H-1 and H-2. The other reason could be the conversion of succinyl-CoA to other metabolites by enzymes related to the bypass pathway of TCA cycle.

• Korean Journal of Acupuncture
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• v.31 no.4
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• pp.218-224
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• 2014

Objectives : Zizyphus jujuba fruits(ZJF), a traditional Korean medicine has various biological activities such as anti-inflammatory, anti-oxidative and neuro-protective effects. However, it is still unclear whether ZJF has any biological effect on anti-aging. In this study, we examined the effect of ZJF on lifespan and thermal stress in C. elegans. Methods and Results : ZJF water extracts were fermented for 7 days(F7-ZJF) and 14 days(F14-ZJF) by Laetiporus sulphureus to increase secondary metabolites such as aglycone of flavonoids and terpenoids. In the lifespan assay, ZJF water extracts and fermented ZJF were treated on the agar medium plate with age synchronized egg stage of C. elegans. Treatment of F7-ZJF-$200{\mu}g/mL$ with OP-50 E. coli and F14-ZJF-$200{\mu}g/mL$ with OP-50 E. coli significantly increased life span of C. elegans(N2) at thermal stress condition of $25^{\circ}C$. Moreover mRNA levels of lifespan associated HSP 16.1, HSP 70, and HSF-1 were increased at thermal stress condition of $25^{\circ}C$. However, in the equilibration temperature of $20^{\circ}C$ after stress condition of $35^{\circ}C$ for 2 hr, F-14-ZJF-$200{\mu}g/mL$ treatment decreased the levels of heat shock protein in hsp16.2/GFP C. elegans. Conclusions : Our study indicates that prolong role of fermented-ZJF in C. elegans is mediated by control HSPs production.