• Title/Summary/Keyword: MDA5

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Dose-Dependent Inhibition of Melanoma Differentiation-Associated Gene 5-Mediated Activation of Type I Interferon Responses by Methyltransferase of Hepatitis E Virus

  • Myoung, Jinjong;Min, Kang Sang
    • Journal of Microbiology and Biotechnology
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    • v.29 no.7
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    • pp.1137-1143
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    • 2019
  • Hepatitis E virus (HEV) accounts for 20 million infections in humans worldwide. In most cases, the infections are self-limiting while HEV genotype 1 infection cases may lead to lethal infections in pregnant women (~ 20% fatality). The lack of small animal models has hampered detailed analysis of virus-host interactions and HEV-induced pathology. Here, by employing a recently developed culture-adapted HEV, we demonstrated that methyltransferase, a non-structural protein, strongly inhibits melanoma differentiation-associated gene 5 (MDA5)-mediated activation of type I interferon responses. Compared to uninfected controls, HEV-infected cells display significantly lower levels of $IFN-{\beta}$ promoter activation when assessed by luciferase assay and RT-PCR. HEV genome-wide screening showed that HEV-encoded methyltransferase (MeT) strongly inhibits MDA5-mediated transcriptional activation of $IFN-{\beta}$ and $NF-{\kappa}B$ in a dose-responsive manner whether or not it is expressed in the presence/absence of a tag fused to it. Taken together, current studies clearly demonstrated that HEV MeT is a novel antagonist of MDA5-mediated induction of $IFN-{\beta}$ signaling.

Antioxidant activity of vitamin C in iron-overloaded swine plasma (철분 투여한 돼지에서 비타민 C의 항산화 작용)

  • Lim, Dongjoo;Song, Hochul;Park, Junbong
    • Korean Journal of Veterinary Research
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    • v.41 no.3
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    • pp.305-310
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    • 2001
  • Iron deficient anemia in piglets could be overcome by supplementary iron. Overloaded iron induced peroxidation of cell membrane and increased malonaldehyde (MDA). Antioxidant activity of vitamin C has been studied in iron-overloaded swine plasma. Erythrocyte fragility, MDA, glutathione, vitamin A, and vitamin E were measured in swine plasma with or without iron (0~1mg/dl) and vitamin C (0~10mg/dl). Erythrocyte fragility increased from 8% to 45% in iron group and reduced from 57% to 43% in vitamin C group with dose dependant response. MDA was $0.94{\pm}0.05$ and $1.86{\pm}0.10$ nmol/ml in piglet and pig, respectively, and significantly high in pig (p<0.05). Iron increased MDA from $1.86{\pm}0.10$ to $9.46{\pm}0.04$ nmol/ml in pig, but not in piglet (p<0.05). Vitamin C reduced MDA from $9.46{\pm}0.04$ to $4.80{\pm}0.10$ nmol/ml in pig. Iron increased glutathione from $90.12{\pm}0.10$ to $108.52{\pm}5.29$ nmol/dl in pig, and vitamin C reduced glutathione from $108.52{\pm}5.29$ to $93.52{\pm}2.44$ nmol/dl (p<0.05). Vitamin A and E were $24.86{\pm}2.70$ to $138.29{\pm}6.70{\mu}g/dl$, respectively in iron group, and $35.76{\pm}0.60$ to $177.21{\pm}2.95{\mu}g/dl$, respectively in supplementary vitamin C group (p<0.05). These data indicated an antioxidant activity of vitamin C in iron-overloaded swine plasma.

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The Role of Vitamin C and Vitamin E Supplementation on Iron Contents and Biomarkers of Oxidative Stress in Blood, Liver and Brain of Aging Rats (나이에 따른 흰쥐의 혈액, 간, 뇌조직의 철분함량, 산화 스트레스 지표에 대한 비타민 C 와 비타민 E공급의 역할)

  • 황은희
    • Journal of Nutrition and Health
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    • v.33 no.5
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    • pp.507-516
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    • 2000
  • The purpose of this study was to investigate the effect of vitamin C and vitamin E supplementation on the iron contents and oxidative stress of the rats. Rats were fed 18g ascorbic acid and 300IU $\alpha$-tocopherol/kg diet, respectively. Rats were sacrificed at 1, 3, 5 and 7 month of age. The blood, liver and brain were selected for the quantitation of iron and malondialdehyde(MDA) contents, glutathione peroxidase(GSHPx), superoxided dismutase(SOD) and catalase(CAT) activity. Iron and MDA contents and GSHPx activities were increased with aging. Vitamin C and Vitamin E supplementation increased iron contents of the plasma. Vitamin C raised iron contents, but vitamin E decreased iron contents of the liver. In the brain vitamin C and vitamin E did not affect the iron level. MDA levels were decreased with vitamin C and vitamin E supplementation in the erythrocyte and liver, and vitamin C supplementation elevated MDA levels in the brain. GSHPx activity was increased with vitamin C and vitamin E supplementation. SOD activities of erythroucyte and brain were not affected with age, but in the liver, SOD activity was raised with age and vitamin C supplementation. Vitamin C and vitamin E supplementation promoted CAT activity of erythroucyte and liver, and CAT activity of brain was eleveated with vitamin addition but was decreaed with vitamin E addition. Vitamin C and vitamin E decreased iron contents of blood plasma, MDA contents of plasma and liver, and CAT activity of erythrocyte. Above results indicated that iron contents and biomarkers of oxidative stress were more affected by age than antioxidant action of vitamin C and vitamin E.

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Simultaneous determination of amphetamine-like drugs in human urine by SPE and GC/MS (고체상추출과 GC/MS를 이용한 소변 중 암페타민계 마약성분 동시분석법)

  • Cheong, Jae Chul;Kim, Jin Young;In, Moon Kyo;Cheong, Won Jo
    • Analytical Science and Technology
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    • v.21 no.1
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    • pp.41-47
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    • 2008
  • Although liquid-liquid extraction (LLE) method has been used routinely for the analysis of amphetamine-like drugs (amphetamine; AP, methamphetamine; MA, 3,4-methylenedioxyamphetamine; MDA, 3,4-methylenedioxymethamphetamine; MDMA, 3,4-methylenedioxyethylamphetamine; MDEA), a solid-phase extraction (SPE) method, which can be automated, was applied for the simultaneous determination by GC/MS in human urine. Urine samples (3 mL) and 0.1 M phosphate buffer (1 mL, pH 7.0) were extracted by an automated SPE system. The eluent was evaporated, derivatized with trifluoroacetic anhydride (TFAA), and analyzed by GC/MS. The calibration curves was linear with correlation coefficient ($r^2$) above 0.994 in the ranges of 34.0 (AP), 28.0 (MDA)~1000.0 ng/mL for AP, MDA, and 50.0~2000.0 ng/mL for MA, MDMA, and MDEA. The limits of detection ranged from 4.0 to 10.0 ng/mL, and the limits of quantitation ranged from 12.0 to 34.0 ng/mL. The relative recoveries were 93.5~107.7 %. The precisions and accuracies were 1.9~14.8 % and -8.7~14.8 %, respectively. The present method was successfully applied to identify the MA or Ecstasy (MDMA) abusers in exact as well as rapid.

LIPID PEROXIDATION AND ANTIOXIDANTS IN WORMERS EXPOSED TO LEAD (연 폭로 근로자들의 지질과산화 및 항산화상태에 관한 연구)

  • Lee, Won-Jin;Hwang, Cheon-Hyun;Kim, Cheong-Sik;Chang, Soung-Hoon;Kim, Yang-Ho;Kim, Hae-Joon
    • Journal of Preventive Medicine and Public Health
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    • v.31 no.3 s.62
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    • pp.449-459
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    • 1998
  • This study was started to find out if plasma malondialdehyde(MDA), $\alpha-tocopherol$ and erythrocyte superoxide dismutase(SOD) activity could be markers of biological activity resulting from exposed to lead in workers. Blood samples were randomly obtained from lead-exposed workers(n=29), $CO_2$, welders(n=60) and office workers(n=60). We used whole blood to analyse blood lead with atomic absorption spectrophotometer. Superoxide dismutase activity in erythrocyte was measured with spetrophotometer. MDA and $\alpha-tocopherol$ in plasma were measured with high performance liquid chromatography. Lead-exposed workers was significantly high in blood lead concentration$(29.37{\mu}g/d\ell)$ compared with welders$(6.42{\mu}g/d\ell)$ and office workers$(5.01{\mu}g/d\ell)$. The level of plasma MDA was significantly higher in the lead-exposed workers($1.87{\mu}mol/g$ cholesterol) than the welders($1.41{\mu}mol/g$ cholesterol) and office workers($1.41{\mu}mol/g$ cholesterol). Erythrocyte SOD activity in lead-exposed workers(56.80 U/g Hb) was significantly increased than those of welders(37.63 U/g Hb) and office workers(20.47 U/g Hb). The plasma $\alpha-tocopherol$ level of lead-exposed workers($4.93{\mu}g/g$ cholesterol) was statistically different from welders($4.25{\mu}g/g$ cholesterol) and office workers$4.28{\mu}g/g$ cholesterol). Neither age nor smoking was related to SOD or MDA level. Blood lead was significantly correlated with erythrocyte SOD activity(r=0.405), plasma MDA(r=0.296) and $\alpha-tocopherol$ (r=0.207). Plasma MDA was also significantly correlated with SOD (r=0.217). In multiple regression analysis, the change of MDA and SOD activity level related to the blood lead concentration. These results suggested that the increase of plasma MDA and erythrocyte SOD activity in lead-exposed workers had a close relationship with the oxidative stress induced by lead.

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Difference in Growth, SOD Activity and MDA Content Between Ozone Tolerant and Sensitive Families of Open-Pollinated Pinus densiflora (소나무 풍매차대묘의 오존 내성 및 민감성 가계간 생장, SOD 활성 및 MDA 함량 차이)

  • Lee, Jae-Cheon;Oh, Chang-Young;Han, Sim-Hee;Kim, Jang-Su
    • Journal of Korean Society of Forest Science
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    • v.95 no.3
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    • pp.323-327
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    • 2006
  • This study was conducted to understand response of damage and tolerance to ozone between ozone tolerant and sensitive families of P. densiflora which had been selected by the based on visual injury and growth. Five individuals were selected in each group, and were exposed to 100ppb ozone for 90 days. Every 30 days after ozone fumigation, diamter at root collar (ORC), superoxide dismutase (SOD) activity, and malondialdehyde (MDA) content were measured. In early state of ozone fumigation tolerant families showed three times higher relative DRC growth rate than sensitive families. And during whole fumigation period growth rate of tolerant families was superior to growth rate of sensitive families. SOD activity in sensitive families was increased 30 days after fumigation, and in accordance with fumigation period extended it was decreased continuously. MDA content in ozone treatment showed higher than in control, and MDA content of tolerant families was higher than that sensitive families. In our results tolerant families has higher antioxidative activity than sensitive families. Therefore tolerant families can restrain lipid peroxidation and damage on physiological activity.

Imidazole Antifungal Drugs Inhibit the Cell Proliferation and Invasion of Human Breast Cancer Cells

  • Bae, Sung Hun;Park, Ju Ho;Choi, Hyeon Gyeom;Kim, Hyesook;Kim, So Hee
    • Biomolecules & Therapeutics
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    • v.26 no.5
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    • pp.494-502
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    • 2018
  • Breast cancer is currently the most prevalent cancer in women, and its incidence increases every year. Azole antifungal drugs were recently found to have antitumor efficacy in several cancer types. They contain an imidazole (clotrimazole and ketoconazole) or a triazole (fluconazole and itraconazole) ring. Using human breast adenocarcinoma cells (MCF-7 and MDA-MB-231), we evaluated the effects of azole drugs on cell proliferation, apoptosis, cell cycle, migration, and invasion, and investigated the underlying mechanisms. Clotrimazole and ketoconazole inhibited the proliferation of both cell lines while fluconazole and itraconazole did not. In addition, clotrimazole and ketoconazole inhibited the motility of MDA-MB-231 cells and induced $G_1$-phase arrest in MCF-7 and MDA-MB-231 cells, as determined by cell cycle analysis and immunoblot data. Moreover, Transwell invasion and gelatin zymography assays revealed that clotrimazole and ketoconazole suppressed invasiveness through the inhibition of matrix metalloproteinase 9 in MDA-MB-231 cells, although no significant changes in invasiveness were observed in MCF-7 cells. There were no significant changes in any of the observed parameters with fluconazole or itraconazole treatment in either breast cancer cell line. Taken together, imidazole antifungal drugs showed strong antitumor activity in breast cancer cells through induction of apoptosis and $G_1$ arrest in both MCF-7 and MDA-MB-231 cells and suppression of invasiveness via matrix metalloproteinase 9 inhibition in MDA-MB-231 cells. Imidazole drugs have well-established pharmacokinetic profiles and known toxicity, which can make these generic drugs strong candidates for repositioning as antitumor therapies.

Effect of Cyanidin on Cell Motility and Invasion in MDA-MB-231 Human Breast Cancer Cells (Anthocyanin계 성분인 Cyanidin이 인체 유방암세포 MDA-MB-231의 이동성과 침윤성에 미치는 영향)

  • Chu, Su-Kyoung;Seo, Eun -Young;Kim, Woo-Kyoung;Kang, Nam-E
    • Journal of Nutrition and Health
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    • v.41 no.8
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    • pp.711-717
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    • 2008
  • Anthocyanidins, the aglycones of anthocyanins, are natural colorants belonging to the flavonoid family. Cyanidin is one of the anthocyanidins, used for their antioxidant properties. Furthermore, previous studies have shown anthocyanidin-rich material extracts or aglycone form inhibit growth and induce apoptosis of cancer cells. But, Tumor metastasis is the most important cause of cancer death, and various treatment strategies have targeted on preventing the occurrence of metastasis. This study investigated the effects of cyanidin on metastasis processes, including motility, invasion and activity of MMP-2 and MMP-9 in MDA-MB-231 human breast cancer cell lines. We cultured MDA-MB-231 cells in presence of various concentrations 0, 5, 10 and 20 ${\mu}M$ of cyanidin. The cell motility was significantly decreased dosedependently in cells treated with cyanidin (p < 0.05) and cyanidin treatment caused the significant suppression of the invasion (p < 0.05). MMP-2 and MMP-9 activities, and MMP-9 mRNA express were not affected by anthocyanin treatment. In conclusion, cyanidin inhibits cell motility, invasion in MDA-MB-231 human breast cancer cell lines.

Relationships between Obesity and Dietary Habits of Preschool Children and Their Parents in Dongducheon Based on the Nutrition Quotient (NQ) (어린이 영양지수를 활용한 동두천시 지역의 유아 및 부모의 식습관과 유아의 비만과의 관련성)

  • Kim, Ji-Myung;Song, Hye Jeong;Ahn, Young Ji
    • Korean Journal of Community Nutrition
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    • v.23 no.3
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    • pp.216-225
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    • 2018
  • Objectives: This study was conducted to investigate the associations between obesity and the children's Nutrition Quotient (NQ) and to further examine the relationships between NQ and mini dietary assessment (MDA) of their parents. Methods: The subjects were 355 children aged 3 to 5 years and their parents in Dongducheon. We collected parental-reported NQ questionnaires for children and MDA of parents. Anthropometric measurements, height, weight and BMI by BIA were measured in children. Overweight and obesity were determined according to age- and sex-specific BMI percentile from the 2007 Korean national growth chart. Statistical analyses consisted of the chi-squared test, ANOVA, partial correlations and logistic regression analysis adjustments for parents BMI. Results: Approximately 20.8% of preschool children were classified as overweight or obese. Underweight children showed a significantly higher score for balance than overweight children. The NQ of the children was $61.9{\pm}11.6$, and NQ scores and their parents' MDA did not exhibit any significant differences according to degree of obesity. After adjusting for parent's BMI, children's BMI was significantly correlated with balance and moderation among NQ factors. Parent's MDA showed significant correlation with their children's NQ, balance, diversity, moderation, regularity, practice and NQ grade, except for diversity of father. Additionally, NQ grade had a significantly increased (150.1%) odds ratio (OR) of being overweight (95% CI 1.008-2.234). Conclusions: These results show that NQ for children is influenced by their parents' MDA and BMI. Furthermore, our findings support the association between overweight prevention and improvement of NQ grade among preschool children.

Middle East Respiratory Syndrome Coronavirus-Encoded ORF8b Inhibits RIG-I-Like Receptors by a Differential Mechanism

  • Lee, Jeong Yoon;Kim, Seong-Jun;Myoung, Jinjong
    • Journal of Microbiology and Biotechnology
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    • v.29 no.12
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    • pp.2014-2021
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    • 2019
  • Middle East respiratory syndrome coronavirus (MERS-CoV) belongs to the genus Betacoronavirus and causes severe morbidity and mortality in humans especially when infected patients have underlying diseases such as chronic obstructive pulmonary disease (COPD). Previously, we demonstrated that MERS-CoV-encoded ORF8b strongly inhibits MDA5- and RIG-I-mediated induction of the interferon beta (IFN-β) promoter activities. Here, we report that ORF8b seemed to regulate MDA5 or RIG-I differentially as protein levels of MDA5 were significantly down-regulated while those of RIG-I were largely unperturbed. In addition, ORF8b seemed to efficiently suppress phosphorylation of IRF3 at the residues of 386 and 396 in cells transfected with RIG-I while total endogenous levels of IRF3 remained largely unchanged. Furthermore, ORF8b was able to inhibit all forms of RIG-I; full-length, RIG-I-1-734, and RIG-I-1-228, the last of which contains only the CARD domains. Taken together, it is tempting to postulate that ORF8b may interfere with the CARD-CARD interactions between RIG-I and MAVS. Further detailed analysis is required to delineate the mechanisms of how ORF8b inhibits the MDA5/RIG-I receptor signaling pathway.