• Toxicological Research
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• v.13 no.1_2
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• pp.95-101
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• 1997

Ethyl carbamate (EC) is a potent teratogen in rodents and is present at low concentration in fermented foods and alcohol beverages. It has been well hypothesized that some metabolic products are responsible for the teratogenic effects of the compound. In the present study, the effects of phenobarbital (PB) on EC-induced embryotoxicity were investigated in SD rats. Six groups were constructed: EC 300 (EC 300 mg/kg/day), EC 600 (EC 600 mg/kg/day), EC 600+PB (EC 600 mg/kg/day and PB 80 mg/kg/day), PB (PB 80 mg/kg/day), DR (dietary restriction, 8 g/day/rat) and a control group. Rats of the EC 600+PB group were pretreated with phenobarbital intraperitoneally for three days to induce cytochrome P450 enzymes, followed by oral administration of EC for two consecutive days. The incidence of fetal deaths in the EC 600+PB group was higher than that of the EC 600 group(42.7 vs. 14.3%). The incidence of fetal realformations in the EC 600+PB group was higher than that of the EC 600 group (external; 7.0 vs. 4.1%, visceral; 31.4 vs. 11.3%, skeletal; 11.1 vs. 6.5%). There was no embryotoxicity in the control, EC 300, PB and DR groups. These results show that the pretreatment with phenobarbital augments EC-induced embryotoxicity in rats, indicating an evidence that metabolic activation by cytochrome P450 may be the major pathway of EC to its embryotoxic forms.

• Asian-Australasian Journal of Animal Sciences
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• v.24 no.1
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• pp.110-124
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• 2011

Anatomically separate fat depots differ in size, function, and contribution to pathological states such as the metabolic syndrome. We isolated pre-adipocytes from different adipose depots, omental, subcutaneous and intramuscular, of beef cattle, and cultured in vitro to determine the basis for the variations and attribute these variations to the inherent properties of adipocyte progenitors. The proliferating cells from all depots before the confluence were harvested and the proteome was analyzed by a functional proteomic approach, involving 2-DE and MALDI-TOF/TOF. More than 252 protein spots were identified, selected and analyzed by Image Master (ver 7.0) and MALDI-TOF/TOF. Further, our analysis showed that there were specific differences in proteome expression patterns among proliferating precursor cells from the three depots. Sixteen proteins were found to be differentially expressed and these were identified as proteins involved in cellular processes, heat shock/chaperones, redox proteins, cytoskeletal proteins and metabolic enzymes. The results also enabled us to understand the basic roles of these proteins in different inherent properties exhibited by adipose tissue depots.

• Biomolecules & Therapeutics
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• v.22 no.2
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• pp.149-154
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• 2014

Effects of diallyl sulfide (DAS) on thioacetamide-induced hepatotoxicity and immunotoxicity were investigated. When male Sprague-Dawley rats were treated orally with 100, 200 and 400 mg/kg of DAS in corn oil for three consecutive days, the activity of cytochrome P450 (CYP) 2E1-selective p-nitrophenol hydroxylase was dose-dependently suppressed. In addition, the activities of CYP 2B-selective benzyloxyresorufin O-debenzylase and pentoxyresorufin O-depentylase were significantly induced by the treatment with DAS. Western immunoblotting analyses also indicated the suppression of CYP 2E1 protein and/or the induction of CYP 2B protein by DAS. To investigate a possible role of metabolic activation by CYP enzymes in thioacetamide-induced hepatotoxicity, rats were pre-treated with 400 mg/kg of DAS for 3 days, followed by a single intraperitoneal treatment with 100 and 200 mg/kg of thioacetamide in saline for 24 hr. The activities of serum alanine aminotransferase and aspartate aminotransferase significantly elevated by thioacetamide were protected in DAS-pretreated animals. Likewise, the suppressed antibody response to sheep erythrocytes by thioacetamide was protected by DAS pretreatment in female BALB/c mice. Taken together, our present results indicated that thioacetamide might be activated to its toxic metabolite(s) by CYP 2E1, not by CYP 2B, in rats and mice.

• Parasites, Hosts and Diseases
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• v.55 no.2
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• pp.121-128
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• 2017

Protozoan viruses may influence the function and pathogenicity of the protozoa. Trichomonas vaginalis is a parasitic protozoan that could contain a double stranded RNA (dsRNA) virus, T. vaginalis virus (TVV). However, there are few reports on the properties of the virus. To further determine variations in protein expression of T. vaginalis, we detected 2 strains of T. vaginalis; the virus-infected ($V^+$) and uninfected ($V^-$) isolates to examine differentially expressed proteins upon TVV infection. Using a stable isotope N-terminal labeling strategy (iTRAQ) on soluble fractions to analyze proteomes, we identified 293 proteins, of which 50 were altered in $V^+$ compared with $V^-$ isolates. The results showed that the expression of 29 proteins was increased, and 21 proteins decreased in $V^+$ isolates. These differentially expressed proteins can be classified into 4 categories: ribosomal proteins, metabolic enzymes, heat shock proteins, and putative uncharacterized proteins. Quantitative PCR was used to detect 4 metabolic processes proteins: glycogen phosphorylase, malate dehydrogenase, triosephosphate isomerase, and glucose-6-phosphate isomerase, which were differentially expressed in $V^+$ and $V^-$ isolates. Our findings suggest that mRNA levels of these genes were consistent with protein expression levels. This study was the first which analyzed protein expression variations upon TVV infection. These observations will provide a basis for future studies concerning the possible roles of these proteins in host-parasite interactions.

• Journal of Microbiology and Biotechnology
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• v.21 no.12
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• pp.1211-1227
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• 2011

C57BL/6J mice have been widely used as a diet-induced obesity model because they trigger common features of the human metabolic syndrome. In the present study, C57BL/6J male mice were fed either a high-fat diet (HFD) or normal diet (ND) during a 24-week period, and then the age-dependent liver proteome of mice in two groups was analyzed using 2-DE combined with MALDI-TOF-MS. Among identified proteins, up-regulated proteins were subdivided to early (during the first 4 weeks) and late (20~24 weeks) markers that played a role in diet-induced obesity development. Important early markers included ketohexokinase and prohibitin, and late markers included the 75 kDa glucose-regulated protein, citrate synthase, and selenium-binding liver protein. Of these, the 75 kDa glucosere-gulated protein has already been linked to obesity; however, prohibitin protein involved in obesity was identified for the first time in this study. In order to validate the proteomic results and gain insight into metabolic changes between the two groups, we further confirmed the expression pattern of some proteins of interest by Western blot analysis. Combined results of proteomic analysis with Western blot analysis revealed that antioxidant enzymes were progressively decreased, whereas cytoskeletal proteins were time-dependently increased in HFD mice.

• Journal of Life Science
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• v.25 no.12
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• pp.1450-1457
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• 2015

To overcome the depletion of fossil fuels and environmental problems in future, the research and production of biofuels have attracted attention largely. Thermophilic microorganisms produce effective and robust enzymes which can hydrolyze plant biomass and survive under harsh bioprocessing conditions. Caldicellulosiruptor bescii, which can degrade unpretreated plants and grow on them, is the one of the best candidates for consolidated bioprocessing (CBP). C. bescii can hydrolyze pectin efficiently as well as the major plant cell wall components, cellulose and hemicelluloses. Many glycosyl hydrolases and carbohydrate lyases with multidomain structure play an important role in plant biomass decomposition. Recently genetic tools for metabolic engineering of C. bescii have developed and bioethanol production from unpretreated biomass is achieved in C. bescii. Here, we review the recent studies for biomass degradation by C. bescii and bioethanol production in C. bescii in order to provide information about metabolic engineering of themophilic bacteria and biofuel development.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.6 no.1
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• pp.96-107
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• 2006

Citrin deficiency resulting from mutations of SLC25A13is associated with two major clinical phenotypes; neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and adult-onset type 2 citrullinemia (CTLN2). In Korea, 7 cases of citrin deficiency have been diagnosed based on biochemical and molecular findings. Four NICCD cases were identified by newborn screening using MS/MS or presenting symptoms like cholestatic jaundice. They are all males, presenting with conjugated hyperbilirubinemia, elevated liver enzymes, hypoalbuminemia, mild hyperammonemia, elevated citrullin, methionine and threonine. All of them have been spontaneously recovered from hepatic manifestation by the age of 6-8 months. Mutation analysis has been performed using their genomic & cDNAs obtained from skin fibroblasts. They turned out to be compound heterozygotes carrying each of 851del4, IVS11+1G>A, and IVS13+1G>A. Three CTLN2 patients were identified. Two adult male patients presented with a sudden loss of consciousness, seizure, vomiting, hyperammonemia and citrullinemia in their twenties. They carried an IVS13+1G>A, 851del4, and IVS11+1G>A mutant alleles. The other CTLN2 patient was 52 year old female patient, manifesting lethargy, altered consciousness, irritability and hyperammonemia. Similar clinical symptoms had recurred at the delivery of first and second babies in her past medical history. She was managed by hemodialysis and survived with neurological sequellae. Also, we screened the presence of 9 common mutations in 500 Korean newborns using dried blood spot of filter papers. Only a allele carried 854del4 mutation. In conclusion, the entire picture of citrin deficiency in Korea including incidence, genotype, clinical features and natural courses, is still vague at the present time.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.14 no.1
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• pp.37-41
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• 2014

Fabry disease is an X-linked disease caused by deficiency of the lysosomal enzyme alpha-galactosidase A. Affected males present anhydrosis, acroparesthesia and angiokeratoma, and subsequently cardiac, cerebral and renal complications are followed. Females and atypical variants show heterogeneous clinical symptoms. In 2001, two recombinant enzymes were approved for Fabry disease: agalsidase alpha and agalsidase beta. Since the introduction of enzyme replacement therapy (ERT), the number of long-term follow-up studies has been reported. Long-term ERT showed effectiveness on renal function in patients with chronic kidney disease, decrease or stabilization of left ventricular mass, and improvement of pain and quality of life. However, there were limited effects on cerebrovascular events and their mortality. Current literatures on the clinical effect of ERT have reported limited datain adult patients who have already advanced disease. Therefore, further study for pre-symptomatic patients and atypical variants is needed to verify the impact of ERT. This review summarized recent progresses in ERT and limitations of long-term effect of ERT in patients with Fabry disease.

• Korean Journal of Medicinal Crop Science
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• v.24 no.5
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• pp.370-374
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• 2016

Background: Many menopausal women suffer from health problems including metabolic diseases such as dyslipidemia and osteoporosis. Thus they need natural products and functional foods particularly highly nutritional food products, that can help alleviate these diseases. This study was carried out to determine the effect of Drynariae Rhizoma water extract on the lipid and bone metabolism of ovariectomized Sprague-Dawley rats. Methods and Results: The animals were randomly divided into six dietary groups comprising SHAM-operated rats, OVX rats (normal diet), and OVX-DR rats (Drynariae Rhizoma extract). After 8 weeks, plasma, liver, and fat samples were collected to analyze the lipid metabolism, plasma Ca, alkaline phosphatase (ALP), osteocalcin and C-terminal telopeptide (CTx) concentrations, which are biochemical makers of bone metabolism. The left femurs of rats were also collected for histological analyses. OVX counteracted menopause induced body weight gain, as well as increases in triglycerides, total cholesterol, and free fatty acids. The Drynariae Rhizoma group showed low levels of triglycerides, high HDL-cholesterol, and decreased lipogenesis based on activity of the lipid-regulating enzymes (fatty acid synthase and malic enzyme). Decreased serum levels of ALP and osteocalcin were observed in Drynariae Rhizoma group. Conclusions: The results of this study show that Drynariae Rhizoma extract may effectively regulate hyperlipidemia and improve bone density.

• Journal of Ginseng Research
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• v.41 no.1
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• pp.36-42
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• 2017

Background: Some differences have been reported in the biotransformation of ginsenosides, probably due to the types of materials used such as ginseng, enzymes, and microorganisms. Moreover, most microorganisms used for transforming ginsenosides do not meet food-grade standards. We investigated the statistical conversion rate of major ginsenosides in ginsenosides model culture during fermentation by lactic acid bacteria (LAB) to estimate possible pathways. Methods: Ginsenosides standard mix was used as a model culture to facilitate clear identification of the metabolic changes. Changes in eight ginsenosides (Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, and Rg2) during fermentation with six strains of LAB were investigated. Results: In most cases, the residual ginsenoside level decreased by 5.9-36.8% compared with the initial ginsenoside level. Ginsenosides Rb1, Rb2, Rc, and Re continuously decreased during fermentation. By contrast, Rd was maintained or slightly increased after 1 d of fermentation. Rg1 and Rg2 reached their lowest values after 1-2 d of fermentation, and then began to increase gradually. The conversion of Rd, Rg1, and Rg2 into smaller deglycosylated forms was more rapid than that of Rd from Rb1, Rb2, and Rc, as well as that of Rg1 and Rg2 from Re during the first 2 d of fermentation with LAB. Conclusion: Ginsenosides Rb1, Rb2, Rc, and Re continuously decreased, whereas ginsenosides Rd, Rg1, and Rg2 increased after 1-2 d of fermentation. This study may provide new insights into the metabolism of ginsenosides and can clarify the metabolic changes in ginsenosides biotransformed by LAB.