• Molecular & Cellular Toxicology
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• v.1 no.4
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• pp.256-261
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• 2005

The recent DNA microarray technology enables us to understand gene expression profiling in cell line and animal models. The technology has potential possibility to comprehend mechanism of multiple genes were related to compounds which have toxicity in biological system. So, microarray system has been used for the prediction of toxicity through gene expression induced by toxicants. It has been shown that compounds with similar toxic mechanisms produce similar changes in gene expression in vivo system. Here we focus on the use of toxicogenomics for the determination of gene expression analysis associated with hepatotoxicity in rat liver and cell line (WB-F344). Methotrexate (MTX) is a chemotherapy agent that has been used for many years in the treatment of cancer because it affects cells that are rapidly dividing. Also it has been known the toxicity of MTX, in a MTX abortion, it stops embryonic cells from dividing and multiplying and is a non-surgical method of ending pregnancy in its early stages. We have shown DNA microarray analyses to assess MTX-specific expression profiles in vivo and in vitro. Male Sprague-Dawely VAF+ albino rats of 5-6 weeks old and WB-F344 cell line have been treated with MTX. Total RNA was isolated from Rat liver and cell line that has treated with MTX. 4.8 K cDNA microarray in house has been used for gene expression profiling of MTX treatment. We have found quite distinct gene expression patterns induced by MTX in a cell line and in vivo system.

• Development and Reproduction
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• v.11 no.3
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• pp.195-203
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• 2007

Sex determination and sex differentiation are influenced by genotype in many gonochoristic fish. Cytochrome P450 aromatase (CYP19) is the terminal enzyme in steridogenic pathway that converts androgens into estrogens. In this study, partial fragments of aromatase genes (ovarian aromatase, P450aromA and brain aromatase, P450aromB) were cloned and sequenced in Korean rockfish (Sebastes schlegeli), and gene specific primers were designed based on their sequences. Using these primers, aromatase gene expression during sex differentiation was investigated by RT-PCR. Expression of these aromatase genes were detected both in the head and body parts at 35 dab (days after birth). The number of fish that expressed the aromatase genes decreased at 52 dab, implying down-regulation of these genes. However, these genes were expressed at 59 dab in almost all fish studied here. The expression patterns of both genes are similar throughout the investigated period except for 45 dab where the expression of P450aromB was detected in more fish than that of P450aromA both in the head and body parts. Timing of sex differentiation in this species has been shown to be at around $50{\sim}65$ dab by histological analysis. However, the results from this study suggest that sex differentiation of rockfish may take place $1{\sim}2$ weeks earlier than the period proposed previously. The results also suggest that the mechanism of sex differentiation in viviparous fish may be similar to that in oviparous fish in terms of the importance of aromatase action during the critical period.

• Nutrition Research and Practice
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• v.11 no.2
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• pp.105-113
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• 2017

BACKGROUND/OBJECTIVES: A high-fat diet (HFD) induces obesity, which is a major risk factor for cardiovascular disease and cancer, while a calorie-restricted diet can extend life span by reducing the risk of these diseases. It is known that health effects of diet are partially conveyed through epigenetic mechanism including DNA methylation. In this study, we investigated the genome-wide hepatic DNA methylation to identify the epigenetic effects of HFD-induced obesity. MATERIALS AND METHODS: Seven-week-old male C57BL/6 mice were fed control diet (CD), calorie-restricted control diet (CRCD), or HFD for 16 weeks (after one week of acclimation to the control diet). Food intake, body weight, and liver weight were measured. Hepatic triacylglycerol and cholesterol levels were determined using enzymatic colorimetric methods. Changes in genome-wide DNA methylation were determined by a DNA methylation microarray method combined with methylated DNA immunoprecipitation. The level of transcription of individual genes was measured by real-time PCR. RESULTS: The DNA methylation statuses of genes in biological networks related to lipid metabolism and hepatic steatosis were influenced by HFD-induced obesity. In HFD group, a proinflammatory Casp1 (Caspase 1) gene had hypomethylated CpG sites at the 1.5-kb upstream region of its transcription start site (TSS), and its mRNA level was higher compared with that in CD group. Additionally, an energy metabolism-associated gene Ndufb9 (NADH dehydrogenase 1 beta subcomplex 9) in HFD group had hypermethylated CpG sites at the 2.6-kb downstream region of its TSS, and its mRNA level was lower compared with that in CRCD group. CONCLUSIONS: HFD alters DNA methylation profiles in genes associated with liver lipid metabolism and hepatic steatosis. The methylation statuses of Casp1 and Ndufb9 were particularly influenced by the HFD. The expression of these genes in HFD differed significantly compared with CD and CRCD, respectively, suggesting that the expressions of Casp1 and Ndufb9 in liver were regulated by their methylation statuses.

• Korean Journal of Environmental Biology
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• v.17 no.2
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• pp.129-138
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• 1999

Chlorinated aromatic compounds are one of the largest groups of environmental pollutants as a result of world-wide distribution by using them as herbicides, insecticides, fungicides, solvents, hydraulic and heat transfer fluids, plasticizers, and intermediates for chemical synthesis. Because of their toxicity, persistence, and bioaccumulation, the compounds contaminated ubiquitously in the biosphere has attracted public concerns in terms of serious influences to wild lives and a human being, such as carcinogenicity, mutagenicity, and disturbance in endocrine systems. The biological recalcitrance of the compounds is caused by the number, type, and position of the chlorine substituents as well as by their aromatic structures. In general, the carbon-halogen bonds increase the recalcitrance by increasing electronegativity of the substituent, so that the dechlorination of the compounds is focused as an important mechanism for biodegradation of chlorinated aromatics, along with the cleavage of aromatic rings. The removal of the chlorine substituents has been known as a key step for degradation of chlorinated aromatic compounds under aerobic condition. This can occur as an initial step via oxygenolytic, reductive, and hydrolytic mechanisms. The studies on the biochemistry and genetics about microbial dechlorination give us the potential informations for microbial degradation of xenobiotics contaminated in natural microcosms. Such investigations might provide biotechnological approaches to solve the environmental contamination, such as designing effective bioremediation systems using genetically engineered microorganisms.

• Journal of Food Hygiene and Safety
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• v.22 no.1
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• pp.1-14
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• 2007

The term, "food safety", has traditionally been viewed as a practical science aimed at assuring the prevention acute illnesses caused by biological microorganisms, and only to a minor extent, chronic diseases cause by chronic low level exposures to natural and synthetic chemicals or pollutants. "food safety" meant to prevent microbiological agents/toxins in/on foods, due to contamination any where from "farm to Fork", from causing acute health effects, especially to the young, immune-compromised, genetically-predisposed and elderly. However, today a broader view must also include the fact that diet, perse (nutrients, vitamins/minerals, calories), as well as low level toxins and pollutant or supplemented synthetic chemicals, can alter gene expressions of stem/progenitor/terminally-differentiated cells, leading to chronic inflammation and other mal-functions that could lead to diseases such as cancer, diabetes, atherogenesis and possibly reproductive and neurological disorders. Understanding of the mechanisms by which natural or synthetic chemical toxins/toxicants, in/on food, interact with the pathogenesis of acute and chronic diseases, should lead to a "systems" approach to "food safety". Clearly, the interactions of diet/food with the genetic background, gender, and developmental state of the individual, together with (a) interactions of other endogenous/exogenous chemicals/drugs; (b) the specific biology of the cells being affected; (c) the mechanisms by which the presence or absence of toxins/toxicants and nutrients work to cause toxicities; and (d) how those mechanisms affect the pathogenesis of acute and/or chronic diseases, must be integrated into a "system" approach. Mechanisms of how toxins/toxicants cause cellular toxicities, such as mutagenesis; cytotoxicity and altered gene expression, must take into account (a) irreversible or reversal changes caused by these toxins or toxicants; (b)concepts of thresholds or no-thresholds of action; and (c) concepts of differential effects on stem cells, progenitor cells and terminally differentiated cells in different organs. This brief Commentary tries to illustrate this complex interaction between what is on/in foods with one disease, namely cancer. Since the understanding of cancer, while still incomplete, can shed light on the multiple ways that toxins/toxicants, as well as dietary modulation of nutrients/vitamins/metals/ calories, can either enhance or reduce the risk to cancer. In particular, diets that alter the embryo-fetal micro-environment might dramatically alter disease formation later in life. In effect "food safety" can not be assessed without understanding how food could be 'toxic', or how that mechanism of toxicity interacts with the pathogenesis of any disease.

• Journal of Food Hygiene and Safety
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• v.31 no.4
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• pp.294-298
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• 2016

Natural products are attractive as the source of new drug development. Especially, numerous unknown marine bioresources are an object of attention because the ocean occupies three fourth of the earth. Survival of marine bioresources in extreme environment may induce the production of biological active compounds. As previous study, we examined over 40 specimens of marine sponges collected from Micronesia and screened their anti-proliferative activities in various cancer cell lines. Among them, we investigated Coscinoderma sp.'s activity and mechanism in human colon carcinoma HCT116 and RKO cells. Furthermore, we also used the p53-knockout of HCT116 cells and the p53 loss of RKO cells for elucidating the role of p53. Coscinoderma sp. inhibited cellular viability independently of the p53 status. Therefore, we compared the expression level of cell death-related proteins by Coscinoderma sp. in HCT16 and in HCT116 p53KO cells. Coscinoderma sp. increased p53 level and NOXA levels and induced apoptosis under the condition of p53 existence. On the other hand, Coscinoderma sp. increased p21 and mTOR levels in HCT116 p53KO cells. These results suggest that Coscinoderma sp. induced anti-proliferation effect through different pathway depending on p53 status.

• Journal of Biomedical Engineering Research
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• v.24 no.3
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• pp.183-192
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• 2003

A transformation methode of the chromaticity coordinates was proposed to calibrate the measured data obtained by a urine analysis system which implemented in our previous study. Generally. the reacted color of a reagent strip by urine analysis system often exhibit the color distortions due to nonlinear characteristics of the various devices that is the optic module mechanism. hardware, and surround circumstance. A color correction method for minimizing the color distortion play a few role in maintaining high accuracy and reproduction of the urine analysis system. In this work, we used the compensation method such as the shading correction, the characteristic curve extraction of RGB color by means of third order spline interpolation, and linear transformation using a reference color. In addition, 1931 CIE XYZ color space was used to compensate the color of the measured data by a standard reference system as colorimeter. A compensation matrix was obtained so that the output values of the urine analysis system is nearly equal to that of a standard reference system for identical color sample. Color correction obtained by a urine analysis system which implemented in our previous study exhibited a good color accuracy when it was compared with the reference data. Observed result from an experiments on ten items or a urinalysis strip that color difference or between two urine analysis system was 1.28.

• Journal of Life Science
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• v.26 no.1
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• pp.129-139
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• 2016

Exercise increases the expression and interaction of major neurotrophic factors such as brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and vascular endothelial growth factor (VEGF) at both central and peripheral tissues, which contributes to improved brain and neural plasticity and cognitive function. Previous findings have been to understand the effect of light or moderate intensity aerobic exercise on neurotrophic factors and cognitive function, not that of high intensity aerobic exercise. However, recent findings suggest that high intensity interval training is a safe, less time-consuming, efficient way to improve cardiorespiratory fitness and weight control, thus American College of Sport Medicine (ACSM)’s guidelines for exercise prescription for various adult populations also recommend the application of high intensity interval training to promote their overall health. High intensity interval training also enhances the expression of BDNF, IGF-1, and VEGF at the brain and peripheral tissues, which improves cognitive function. Increased frequency of intermittent hypoxia and increased usage of lactate as a supplementary metabolic resource at the brain and neural components are considered a putative physiological mechanism by which high intensity interval training improves neurotrophic factors and cognitive function. Therefore, future studies are required to understand how increased hypoxia and lactate usage leads to the improvement of neurotrophic factors and what the related biological mechanisms are. In addition, by comparing with the iso-caloric moderate continuous exercise, the superiority of high intensity interval training on the expression of neurotrophic factors and cognitive function should be demonstrated by associated future studies.

• Journal of Life Science
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• v.27 no.7
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• pp.834-839
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• 2017

Propolis is a natural product collected from plants by honey bees product used extensively in traditional medicine for its antioxidant, anti-inflammatory, immunomodulatory and anti-cancer effects. Propolis exhibits a broad spectrum of biological activities because it is a complex mixture of natural substances. Ovarian cancer is the second most common newly diagnosed cancer from all cancers among women in Korea and the leading cause of death from gynecological malignancies. While most ovarian cancer patients initially respond to surgical debulking and chemotherapy, patients later succumb to the disease. Thus, there is an urgent need to test novel therapeutic agents to counteract the high mortality rate associated with ovarian cancer. In this study, we investigated the anti-cancer properties and the active mechanism of Australian propolis in human epithelial ovarian cancer A2780 cells. Our data revealed that propolis showed a cytotoxic activity in a dose-dependent manner. Flow cytometric analysis for cell cycle arrest and apoptosis using propidium iodide staning and annexin V-FITC indicated that propolis could induce cycle arrest in the G0/G1 phase and apoptosis in a dose-dependent manner on human epithelial ovarian cancer cells. These results suggest that the Australian propolis is potential alternative agent on ovarian cancer prevention and treatment.

• Korean Journal of Veterinary Research
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• v.44 no.3
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• pp.379-387
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• 2004

When an organism is exposed to various toxicants chronically, reactive oxygen species(ROS) are accumulated and eventually result in several biological effects from gene expression to cell death. In the present study we investigated the oxidative damage of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin(TCDD) and/or benzo(a)pyrene (B(a)P) in C100 cells. C100 cells treated with TCDD(30 nM) and B(a)P($3{\mu}M$) underwent diverse oxidative stress as determined through thiobarbituric acid-reactive substances(TBARS) formation, DNA fragmentation, DNA single strand break(SSB) assay, immunohistochemical staining of 8-hydroxy-2'-deoxyguanosine(8-OHdG), and mRNA expressions of antioxidant enzymatic genes such as Cu/Zn-SOD gene, GPx(glutathione peroxidase 5) gene, and catalase gene. Lipid peroxidation in C100 cells was determined through measuing the formation of TBARS. For theat, the cells were pretreated with TCDD(30 nM) and/or B(a)P($3{\mu}M$) for 0.5, 1, 2 and 4 days. TBARS formation was increased in TCDD(30 nM) and B(a)P($3{\mu}M$) and mixture($30nM\;TCDD+3{\mu}M\;B(a)P$) and positive control treatment groups comparing to the controls. Mixture treatment induced more DNA fragmentation than the single treatment group at day 6. Also, SSB in all treatment groups was clearly observed when compared with the negative control group. As with the expression of antioxidant enzyme, GPx 5mRNA, B(a)P alone and mixture($30nM\;TCDD+3{\mu}M\;B(a)P$) treatment were higher comparing to those of the negative control and TCDD treatment groups. Our results suggest that exposure of C100 cells to mixture of TCDD and B(a)P leads to significant oxidative damage comparing to the exposures to the individual chemicals. Mechanisms of action are discussed. Additional studies are needed to elucidate the detailed mechanism of mixture-induced toxicity.