• Molecular & Cellular Toxicology
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• 제2권2호
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• pp.114-119
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• 2006

Benzo[a]pyrene is a representative ecotoxicant in marine environment and a model compound of polycyclic aromatic hydrocarbons, which has an ability to bioaccumulate in aquatic organisms. This study aimed to identify molecular biomarkers suitable for assessing environmental pollution using a microarray technique. We examined the effects of benzo[a]pyrene on gene expressions in the rockfish, Sebastes schlegeli. We constructed the subtractive cDNA library with hepatic RNA from benzo[a]pyrene-exposed and non-exposed control fish. From the library 10,000 candidate clones were selected randomly and cDNA microarray was constructed. We determined benzo[a]pyrene-responsive genes using a high-density microarray. Statistical analysis showed that approximately 400 genes are significantly induced or reduced by benzo[a]pyrene treatment ($2\;{\mu}m$). Especially gene expression changes of 4 candidate clones among the up- or down-regulated genes were investigated in 6, 12 and 24 hr BaP-exposed fish groups. Many methods have been developed to monitor marine environmental status, which depend on quantifying the levels of the toxic components in polluted seawater or on ecological accessing, such as species diversity or richness. However, those methods could not provide information on physiological or genetic changes induced by such environmental stresses. Comparing with the conventional methods, these data will propose that benzo[a]pyrene-responsive genes can be useful for biological risk assessment of polycyclic aromatic hydrocarbons on marine organism at molecular level.

• Asian Pacific Journal of Cancer Prevention
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• 제16권9호
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• pp.3817-3825
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• 2015

Background: The human protein methyl-transferase DOT1L catalyzes the methylation of histone H3 on lysine 79 (H3K79) at homeobox genes and is also involved in a number of significant processes ranging from gene expression to DNA-damage response and cell cycle progression. Inhibition of DOT1L activity by shRNA or small-molecule inhibitors has been established to prevent proliferation of various MLL-rearranged leukemia cells in vitro, establishing DOT1L an attractive therapeutic target for mixed lineage leukemia (MLL). Most of the drugs currently in use for the MLL treatment are reported to have low efficacy, hence this study focused on various natural compounds which exhibit minimal toxic effects and high efficacy for the target receptor. Materials and Methods: Structures of human protein methyl-transferase DOT1L and natural compound databases were downloaded from various sources. Virtual screening, molecular docking, dynamics simulation and drug likeness studies were performed for those natural compounds to evaluate and analyze their anti-cancer activity. Results: The top five screened compounds possessing good binding affinity were identified as potential high affinity inhibitors against DOT1L's active site. The top ranking molecule amongst the screened ligands had a Glide g-score of -10.940 kcal/mol and Glide e-model score of -86.011 with 5 hydrogen bonds and 12 hydrophobic contacts. This ligand's behaviour also showed consistency during the simulation of protein-ligand complex for 20000 ps, which is indicative of its stability in the receptor pocket. Conclusions: The ligand obtained out of this screening study can be considered as a potential inhibitor for DOT1L and further can be treated as a lead for the drug designing pipeline.

• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.3977-3982
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• 2012

Inhibitors of histone deacetylase activity are emerging as a potentially important new class of anticancer agents. In this study, we assessed the anticancer effects of valproic acid (VPA) on ovarian cancer in vitro and in vivo. Cultured SKOV3 cells were treated by VPA with different concentrations and time, then the effects on cell growth, cell cycle, apoptosis, and related events were investigated. A human ovarian cancer model transplanted subcutaneously in nude mice was established, and the efficacy of VPA used alone and in combination with diammine dichloroplatinum (DDP) to inhibit the growth of tumors was also assessed. Proliferation of SKOV3 cells was inhibited by VPA in a dose and time dependent fashion. The cell cycle distribution changed one treatment with VPA, with decrease in the number of S-phase cells and increase in G1-phase. VPA could significantly inhibit the growth of the epithelial ovarian cancer SKOV3 cells in vivo without toxic side effects. Treatment with VPA combined with DDP demonstrated enhanced anticancer effects. The result of flow cytometry (FCM) indicated that after VPA in vitro and in vivo, the expression of E-cadherin was increased whereas vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) were decreased. This study suggests that VPA could be a novel attractive agent for treatment of ovarian cancer.

• Bulletin of the Korean Chemical Society
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• 제32권2호
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• pp.613-619
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• 2011

Colloidal silver nanoparticles (AgNPs) have been commercialized as the typically stabilized form via the addition of a variety of surfactants or polymers. Herein, to examine the effects of stabilizing AgNPs in suspension, we modified the surface of bare AgNPs with four type of surfactants (NaDDBS, SDS, TW80, CTAB) and polymers (PVP, PAA, PAH, CMC). The modified AgNPs was applied to compare suspension stability and nanotoxicity test using Escherichia coli (E. coli) as a model organism. Modification of AgNPs surface using chemical stabilizer may be not related with molecular weight, but chemical structure such as ionic state and functional group of stabilizer. In this study, it is noteworthy that AgNPs modified with a cationic stabilizer (CTAB, PAH) were importantly toxic to E. coli, rather than anionic stabilizers (NaDDBS, SDS). Comparing similar anionic stabilizer, i.e., NaDDBS and SDS, the result showed that lipophilicity of chemical structure can affect on E. coli, because NaDDBS, which contains a lipophilic benzene ring, accelerated the cytotoxicity of AgNPs. Interestingly, none of the stabilizers tested, including biocompatible nonionic stabilizers (i.e., TW80 and cellulose) caused a reduction in AgNP toxicity. This showed that toxicity of AgNPs cannot be reduced using stabilizers.

• 혜화의학회지
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• 제25권1호
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• pp.133-144
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• 2016

Objectives : This study was aimed to investigate the effect of ACLL extract (Artemisia capillaris Thunb, Curcuma longa L, Lycium chinense, Ligustrum lucidum Aiton complex extract) in a dyslipidemia animal model induced by a high-fat diet. Methods : ACLL extracts was administered at 200 mg/kg, and 400 mg/kg to Apoe mice, where arthritis was induced by high cholesterol diet. After mice were treated with GO for 4 weeks, we measured AST, ALT, BUN and lipid levels (total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride), atherogenic index(AI) and cardiac risk factor(CRF). Results : Serum AST, ALT, creatinine, BUN levels were not changed by ACLL extract do not show any toxic effects. Also, ACLL extract groups were found to have atherogenic Index and cardiac risk factor as well as lipid metabolism improvement (total cholesterol, LDL cholesterol and triglyceride decrease). Conclusions : We suggest that ACLL extract may have the control effects of Dyslipidemia by improving lipid metabolism.

• 한국안전학회지
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• 제21권5호
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• pp.22-27
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• 2006

Even though the interior of urban transit vehicle has been changed as a preventing measure against fire to make it inflammable, there remains a possibility of fire breaking out in case of gasoline etc being brought in the subway. However, there is also the possibility that in case if fire toxic gas is generated and hot air spreads in carriage it will prove very dangerous for people sitting inside. This is a comparative study where we compare simulation results with model examining the time and direction the fire spreads when it breaks out. Also there is vertical distribution of temperature in carriage where the fire spreads out. This study is about demonstrating how to establish smokeless system in urban vehicle, about its necessity, and about vehicle system restructuring. This study also makes an effort to find more advanced method for efficient fire safety in trains. In existing vehicles, in case of fire, the smoke can't go out when doors are closed and hence it spreads in whole train. Even though the method of using ventilation or exhaust established inside the carriage to throw smoke out is much better than the way of opening end doors in each carriage, this study is trying to do research on second way. Through simulation we see that in second case, even though not as good as the first one, smoke can exit through gates. Even though the first method is better, the second can also be uses to let fire out. We can know that in the first case as the smoke can exit out faster, it provides more safety for people. So this system provides better fire safety condition.

• Genomics & Informatics
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• 제8권1호
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• pp.50-57
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• 2010

Mercuric chloride, a model nephrotoxicant was used to elucidate time- and dose- dependent global gene expression changes associated with proximal tubular toxicity. Rat kidney cell lines NRK-52E cells were exposed for 2, 6 and 12 hours and with 3 different doses of mercuric chloride. Cell viability assay showed that mercuric chloride had toxic effects on NRK-52E cells causing 20% cell death (IC20) at $40{\mu}M$ concentration. We set this IC20 as high dose concentration and 1/5 and 1/25 concentration of LC20 were used as mid and low concentration, respectively. Analyses of microarray data revealed that 738 genes were differentially expressed (more than two-fold change and p<0.05) by low concentration of mercuric chloride at least one time point in NRK-52E cells. 317 and 2,499 genes were differentially expressed at mid and high concentration of mercuric chloride, respectively. These deregulated genes showed a primary involvement with protein trafficking (CAV2, CANX, CORO1B), detoxification (GSTs) and immunity and defense (HMOX1, NQO1). Several of these genes were previously reported to be up-regulated in proximal tubule cells treated with nephrotoxicants and might be aid in promoting the predictive biomarkers for nephrotoxicity.

• Asian Pacific Journal of Cancer Prevention
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• 제15권13호
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• pp.5149-5153
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• 2014

Background: Chlorophenols (CPs) and related phenoxyacetic acids (PAs) are pesticide groups contaminated with highly toxic 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) during production. PAs and CPs exposure is associated with risk of cancer, but the situation regarding lung cancer has not been clearly defined. We proposed a meta-analysis of published researches to evaluate relationship between chronic exposure to PAs and CPs in pesticide production workplaces and the risk of lung cancer. Materials and Methods: After searching PubMed, Scopus, Scholar Google, Web of Sciences until August 2013, the association between chronic PAs and CPs exposure in production workplace and lung cancer was studied in 15 cohort studies. The standardized mortality rate (SMR) and 95% confidence intervals (CI) were collected from the papers. We used random or fixed-effects models, Egger test, funnel plot and meta regression in our analysis. Results: Five papers with six reports were included in the final analysis. The standardized mortality rate for lung cancer from the random model was 1.18 (95% CI: 1.03-1.35, p=0.014) with moderate heterogeneity. Publication bias was not found for included studies in meta-analysis (p=0.9). Conclusions: Our findings has strengthen the evidence of lung cancer from chronic exposure to chlorophenol related compounds (PAs, CPs).

• 대한토목학회논문집
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• 제11권3호
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• pp.11-18
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• 1991

휘발성 유기물질(VOC)은 많은 경로를 통해 발생되는데, 독성이 있을뿐 아니라 발암물질을 포함하고 있으므로, 이들 물질 제거는 매우 중요하다. 본 연구에서는 휘발성 유기물질 처리를 위해 활성탄을 사용할 경우 처리와 설계를 위해 흡착능력의 연구가 반드시 필요하다. 그러므로, 본 연구에서는 사용할 화합물에 대한 가스 상태의 등온흡착선을 물리적 특성과 액화상태의 등온흡착선으로 부터 예측하였다. 이를 위해 이용된 방법이 quantitative structure-activity relationships(QSAR) 방법이다. 가스 상태의 등온흡착선을 분자연결제수($^2{\chi}$)와 헨리의 계수, 또는 용해도와 가스 상태의 평형농도에 의해서 예측 할 수 있었다. 연구결과, Freundlich 모델을 근거로한 가스 상태의 등온흡착선은 ${\log}\;a_g=0.238\;^2{\chi}+0.573\;{\log}\;H_a+4.330(r^2=0.94)$ 이었다. 결과적으로, 저흡착능력 범위에서 Freundlich 이론을 근거로한 이 방법은 시간소비적 실험을 통하지 않고도 가스 상태의 등온흡착선을 예측할 수 있다는 것을 제시하고 있다.

• 대한한의학회지
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• 제25권3호
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• pp.32-44
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• 2004

Objectives : This study was undertaken to prove the effect of GSHT on the glutamate receptor, free radical and brain damage in rats subjected to brain ischemia Methods : Levels of cultured cortical neuron death caused by toxic chemicals were measured by LDH release assay. Neuroprotective effects of GSHT on brain tissues were examined in vivo by ischemic model of middle cerebral artery (MCA) occlusion. Results : GSHT showed significant inhibitory effect on LDH release induced by NMDA-kinate-Fe/sup 2+/. GSHT remarkably decreased coma duration time in a nonfatal dose of KCN and showed higher survival rate in a fatal dose. GSHT remarkably decreased ischemic area and edema induced by the MCA blood flow block. GSHT showed high improvement of forelimb and hind limb test after MCA occlusion in neurological examination. GSHT showed no significant change after MCA occlusion in pathological observation of the normal group. Conclusions : These results indicate that GSHT can be used to treat the brain damage caused by brain ischemia. Further study will be needed about the functional mechanism, etc.