• International Journal of Oral Biology
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• 제35권2호
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• pp.43-49
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• 2010

Enterococcus faecalis, a gram-positive bacterium, has been implicated in endodontic infections, particularly in chronic apical periodontitis. Proinflammatory cytokines, including tumor necrosis factor-$\alpha$ (TNF-$\alpha$), are involved in the pathogenesis of these apical lesions. E. faecalis has been reported to stimulate macrophages to produce TNF-$\alpha$. The present study investigated the mechanisms involved in TNF-$\alpha$ production by a murine macrophage cell line, RAW 264.7 in response to exposure to E. faecalis. Both live and heat-killed E. faecalis induced high levels of gene expression and protein release of TNF-$\alpha$. Treatment of RAW 264.7 cells with cytochalasin D, an inhibitor of endocytosis, prevented the mRNA up-regulation of TNF-$\alpha$ by E. faecalis. In addition, antioxidant treatment reduced TNF-$\alpha$ production to baseline levels. Inhibition of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein (MAP) kinase also significantly attenuated E. faecalis-induced TNF-$\alpha$ expression by RAW 264.7 cells. Furthermore, activation of NF-${\kappa}B$ and AP-1 in RAW 264.7 cells was also stimulated by E. faecalis. These results suggest that the phagocytic uptake of bacteria is necessary for the induction of TNF-$\alpha$ in E. faecalis-stimulated macrophages, and that the underlying intracellular signaling pathways involve reactive oxygen species, ERK, p38 MAP kinase, NF-${\kappa}B$, and AP-1.

• Parasites, Hosts and Diseases
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• 제50권2호
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• pp.119-126
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• 2012

Carboxylic acids play an important role in both aerobic and anaerobic metabolic pathways of both the snail and the parasite. Monitoring the effects of infection by schistosome on Biomphalaria alexandrina carboxylic acids metabolic profiles represents a promising additional source of information about the state of metabolic system. We separated and quantified pyruvic, fumaric, malic, oxalic, and acetic acids using ion-suppression reversed-phase high performance liquid chromatography (HPLC) to detect correlations between these acids in both hemolymph and digestive gland gonad complex (DGG's) samples in a total of 300 B. alexandrina snails (150 infected and 150 controls) at different stages of infection. The results showed that the majority of metabolite pairs did not show significant correlations. However, some high correlations were found between the studied acids within the control group but not in other groups. More striking was the existence of reversed correlations between the same acids at different stages of infection. Some possible explanations of the underlying mechanisms were discussed. Ultimately, however, further data are required for resolving the responsible regulatory events. These findings highlight the potential of metabolomics as a novel approach for fundamental investigations of host-pathogen interactions as well as disease surveillance and control.

• Molecular & Cellular Toxicology
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• 제1권2호
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• pp.73-77
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• 2005

Nickel is the one of potent environmental, the occupational pollutants and the classified human carcinogens. It is a serious hazard to human health, when the metal exposure. To prevent human diseases from the heavy metals, it is seemingly important that understanding of how nickel exerts their toxicity and carcinogenic effect at a molecular and a genomic level. The process of nickel absorption has been demonstrated as phagocytosis, iron channel and diffusion. Uptaked nickel has been suggested to induce carcinogenesis via two pathways, a direct DNA damaging pathway and an indirect DNA damaging pathway. The former was originated from the ability of metal to generate Reactive Oxygen Species (ROS) and the reactive intermediates to interact with DNA directly. Ni-generated ROS or Nickel itself, interacts with DNAs and histones to cause DNA damage and chromosomal abnormality. The latter was originated from an indirect DNA damage via inhibition of DNA repair, or condensation and methylation of DNA. Cells have ability to protect from the genotoxic stresses by changing gene expression. Microarray analysis of the cells treated with nickel or nickel compounds, show the specific altered gene expression profile. For example, HIF-I (Hypoxia-Inducible Factor I) and p53 were well known as transcription factors, which are upregulated in response to stress and activated by both soluble and insoluble nickel compounds. The induction of these important transcription factors exert potent selective pressure and leading to cell transformation. Genes of metallothionein and family of heat shock proteins which have been known to play role in protection and damage control, were also induced by nickel treatment. These gene expressions may give us a clue to understand of the carcinogenesis mechanism of nickel. Further discussions on molecular and genomic, are need in order to understand the specific mechanism of nickel toxicity and carcinogenicity.

• Molecular & Cellular Toxicology
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• 제5권4호
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• pp.310-316
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• 2009

Some environmental chemicals have been shown to cause liver-toxicity as the result of bioaccumulation. Particularly, fungicides have been shown to cause varying degrees of hepatictoxicity and to disrupt steroid hormone homeostasis in in vivo models. The principal objective of this study was to evaluate the liver-toxic responses of environmental chemicals-in this case selected fungicides and parasiticides-in order to determine whether or not this agent differentially affected its toxicogenomic activities in hepatic tumor cell lines. To determine the gene expression profiles of 3 fungicides (triadimefon, myclobutanil, vinclozolin) and 1 parasiticide (dibutyl phthalate), we utilized a modified HazChem human array V2. Additionally, in order to observe the differential alterations in its time-dependent activities, we conducted two time (3 hr, 48 hr) exposures to the respective IC20 values of four chemicals. As a result, we analyzed the expression profiles of a total of 1638 genes, and we identified 70 positive significant genes and 144 negative significant genes using four fungicidic and parasiticidic chemicals, using SAM (Significant Analysis of Microarray) methods (q-value<0.5%). These genes were analyzed and identified as being related to apoptosis, stress responses, germ cell development, cofactor metabolism, and lipid metabolism in GO functions and pathways. Additionally, we found 120 genes among those time-dependently differentially expressed genes, using 1-way ANOVA (P-value<0.05). These genes were related to protein metabolism, stress responses, and positive regulation of apoptosis. These data support the conclusion that the four tested chemicals have common toxicogenomic effects and evidence respectively differential expression profiles according to exposure time.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6017-6022
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• 2012

Background: Resveratrol has been reported to have potential chemopreventive and apoptosis-inducing properties in a variety of tumor cell lines. Objective: In this study, to investigate the effects of resveratrol on protein kinase C (PKC) activity and apoptosis in human colon carcinoma cells, we used HT-29 cells and examined the $PKC{\alpha}$ and ERK1/2 signaling pathways. Methods: To test the effects of resveratrol on the growth of HT-29 cells, the cells were exposed to varying concentrations and assessed with the the MTT cell-viability assay. Fluorescence-activated cell sorter (FACS) analysis was applieded to determine the effects of resveratrol on cell apoptosis. Western blotting was performed to determine the protein levels of $PKC{\alpha}$ and ERK1/2. In inhibition experiments, HT-29 cells were treated with G$\ddot{o}$6976 or PD98059 for 30 min, followed by exposure to $200{\mu}M$ resveratrol for 72 h. Results: Resveratrol had a significant inhibitory effect on HT-29 cell growth. FACS revealed that resveratrol induced apoptosis. Western blotting showed that e phosphorylation of $PKC{\alpha}$ and ERK1/2 was significantly increased in response to resveratrol treatment. Pre-treatment with $PKC{\alpha}$ and ERK1/2 inhibitors (G$\ddot{o}$6976 and PD98059) promoted apoptosis. Conclusion: Resveratrol has significant anti-proliferative effects on the colon cancer cell line HT-29. The PKC-ERK1/2 signaling pathway can partially mediate resveratrol-induced apoptosis of HT-29 cells.

• 한국환경농학회:학술대회논문집
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• 한국환경농학회 2009년도 정기총회 및 국제심포지엄
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• pp.93-115
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• 2009

There are growing public concerns over crop and food safeties due to the elevated levels of heavy metals grown in contaminated soil. Heavy metals are classified as the chemical harmful risks for crop and food safety. With implementation of GAP, crop safety is controlled by many regulatory options for soil, irrigation water and fertilizers. Any attempt to retard the metal uptake by crops may be the best protocol to secure crop and food safety. This article reviews the management strategies for heavy metals in view of crop safety in Korea and demonstrates results from the field experiments to retard metal translocation from soil to crops by using chemical amendments and soil layer management methods. Major source of soil pollution by heavy metals has been related with mining activities. Risk assessment revealed that rice consumption and groundwater ingestion in the abandoned mining areas were the major exposure pathways for metals to human and the heavy metal showed the toxic effects on human health. Chemical amendments such as lime and slag retarded Cd uptake by rice (Oryza sativa L.) by increasing soil pH, lowering the phytoavailable Cd concentration in soil solution, immobilizing Cd in soil and converting the available Cd fractions into non-available fractions. The soil layer management methods decreased the Cd uptake by 76% and Pb by 60%. Either reversing the surface layer with subsurface layer or immobilization of metals with layer mixing with lime was considered to be the practical option for the in-situ remediation of the contaminated paddy soils. Combination of chemical soil amendments and layer management methods was efficient to retard the metal bioavailability and thus to secure crop safety for heavy metals. This protocol seems to be cheap, relatively easy to practice and practical in the agricultural fields. However, a long term monitoring work should be followed to verify the efficiency of this protocol.

• Asian Pacific Journal of Cancer Prevention
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• 제16권1호
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• pp.9-21
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• 2015

Cancer, a serious public health problem in worldwide, results from an excessive and uncontrolled proliferation of the body cells without obvious physiological demands of organs. The gastrointestinal tract, including the esophagus, stomach and intestine, is a unique organ system. It has the highest cancer incidence and cancer-related mortality in the body and is influenceed by both genetic and environmental factors. Among the various chemical elements recognized in the nature, some of them including zinc, iron, cobalt, and copper have essential roles in the various biochemical and physiological processes, but only at low levels and others such as cadmium, lead, mercury, arsenic, and nickel are considered as threats for human health especially with chronic exposure at high levels. Cadmium, an environment contaminant, cannot be destroyed in nature. Through impairment of vitamin D metabolism in the kidney it causes nephrotoxicity and subsequently bone metabolism impairment and fragility. The major mechanisms involved in cadmium carcinogenesis could be related to the suppression of gene expression, inhibition of DNA damage repair, inhibition of apoptosis, and induction of oxidative stress. In addition, cadmium may act through aberrant DNA methylation. Cadmium affects multiple cellular processes, including signal transduction pathways, cell proliferation, differentiation, and apoptosis. Down-regulation of methyltransferases enzymes and reduction of DNA methylation have been stated as epigenetic effects of cadmium. Furthermore, increasing intracellular free calcium ion levels induces neuronal apoptosis in addition to other deleterious influence on the stability of the genome.

• 한국식품영양과학회지
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• 제43권2호
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• pp.179-186
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• 2014

대사체학이 질병, 약물, 스트레스, 식이, 생활습관, 유전적 차이, 장내 미생물 등에 의해서 발생하는 비정상적인 대사 메커니즘을 규명하고 관련 바이오 마커 발굴에 중요한 역할이 증명됨에 따라, 식품 영양학과 대사체학이 융합된 영양 대사체학의 역할이 더욱 중요해지고 있다. 특히 잘못된 식생활에 따른 미래의 질병 예측이 가능해지고 있어 향후 적절한 질병 예방이나 치료를 위한 적절한 식생활이나 식이에 대한 정보를 제공함으로써 건강 증진은 물론 개인별 맞춤식이나 맞춤약물 처방을 통한 개인 맞춤형 건강관리(personalized health care) 시대가 멀지 않았다. 또한 복잡한 식생활 패턴, 대사 반응에 대한 개인 간 차이 그리고 방대한 대사체 데이터와의 관계들을 효과적으로 밝혀낼 수 있는 기술에 대한 지속적인 개발과 영양 대사체학(nutritional metabolomics)이 유전체학(genomics or transcriptomics)과 단백체학(proteomics) 기술과 융합적으로 연구가 이루어질 때 질병과 식사 섭취 사이의 관계가 더욱 투명하게 규명될 것이다.

• 한국진공학회:학술대회논문집
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• 한국진공학회 2014년도 제46회 동계 정기학술대회 초록집
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• pp.484.2-484.2
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• 2014

There are many efforts to improving the power conversion efficiencies (PCEs) of dye-sensitized solar cells (DSCs). Although DSCs have a low production cost, their low PCE and low thermal stability have limited commercial applications. This study describes the preparation of a novel multifunctional polymer gel electrolyte in which a cross-linking polymerization reaction is used to encapsulate $TiO_2$ nanoparticles toward improving the power conversion efficiency and long-term stability of a quasi-solid state DSC. A series of liquid junction dye-sensitized solar cells (DSCs) was fabricated based on polymer membrane encapsulated dye-sensitized $TiO_2$ nanoparticles, prepared using a surface-induced cross-linking polymerization reaction, to investigate the dependence of the solar cell performance on the encapsulating membrane layer thickness. The ion conductivity decreased as the membrane thickness increased; however, the long term-stability of the devices improved with increasing membrane thickness. Nanoparticles encapsulated in a thick membrane (ca. 37 nm), obtained using a 90 min polymerization time, exhibited excellent pore filling among $TiO_2$ particles. This nanoparticle layer was used to fabricate a thin-layered, quasi-solid state DSC. The thick membrane prevented short-circuit paths from forming between the counter and the $TiO_2$ electrode, thereby reducing the minimum necessary electrode separation distance. The quasi-solid state DSC yielded a high power conversion efficiency (7.6/8.1%) and excellent stability during heating at $65^{\circ}C$ over 30 days. These performance characteristics were superior to those obtained from a conventional DSC (7.5/3.5%) prepared using a $TiO_2$ active layer with the same thickness. The reduced electrode separation distance shortened the charge transport pathways, which compensated for the reduced ion conductivity in the polymer gel electrolyte. Excellent pore filling on the $TiO_2$ particles minimized the exposure of the dye to the liquid and reduced dye detachment.

• Journal of Microbiology and Biotechnology
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• 제22권4호
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• pp.571-573
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• 2012

Glyceraldehyde-3-phosphate (G-3-P), the substrate of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), is a key intermediate in several metabolic pathways. Recently, we reported that G-3-P directly inhibits caspase-3 activity in a reversible noncompetitive mode, suggesting the intracellular G-3-P level as a cell fate decision factor. It has been known that apoptotic stimuli induce the generation of NO, and NO S-nitrosylates GAPDH at the catalytic cysteine residue, which confers GAPDH the ability to bind to Siah-1, an E3 ubiquitin ligase. The GAPDH-Siah-1 complex is translocated into the nucleus and subsequently triggers the apoptotic process. Here, we clearly showed that intracellular G-3-P protects GAPDH from S-nitrosylation at above a certain level, and consequently maintains the cell survival. In case G-3-P drops below a certain level as a result of exposure to specific stimuli, G-3-P cannot inhibit S-nitrosylation of GAPDH anymore, and consequently GAPDH translocates with Siah-1 into the nucleus. Based on these results, we suggest that G-3-P functions as a molecule switch between cell survival and apoptosis by regulating S-nitrosylation of GAPDH.