• Journal of Life Science
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• v.30 no.8
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• pp.661-671
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• 2020

The resistance of cancer cells to anti-cancer drugs is the leading cause of chemotherapy failure. The clinical use of nonsteroidal anti-inflammatory drugs (NSAIDs) has been gradually extended to cancer treatment through combination with anti-cancer drugs. In the current study, we investigated whether NSAIDs including celecoxib (CCB), 2,5-dimethyl celecoxib (DMC), and ibuprofen (IBU) could enhance the cytotoxic effects of imatinib and TNF-related apoptosis inducing ligand (TRAIL) on human cancer cells. We found that the NSAIDs potentiated TRAIL and imatinib cytotoxicity against human hepatocellular carcinoma (HCC) cell lines SNU-354, SNU-423, SNU-449, and SNU-475/TR and against leukemic K562 cells with high level of CD44 (CD44^highK562), respectively. More specifically, CCB induced endoplasmic reticulum stress via up-regulation of ATF4/CHOP which is associated with the induction of autophagy against HCC and CD44^high K562 cells. NSAID-induced autophagic activity accelerated TRAIL cytotoxicity of HCC cells through up- and down-regulation of DR5 and c-FLIP, respectively. The NSAIDs also potentiated imatinib-induced cytotoxicity and apoptosis through down-regulation of markers in CD44^highK562 cells that express a stemness phenotype. Our results suggest that the ability of NSAIDs to induce autophagy could enhance the cytotoxicity of TRAIL and imatinib, leading to a reverse resistance to these drugs in the cancer cells. In conclusion, NSAIDs in combination with low-dose TRAIL or imatinib may constitute a novel clinical strategy that maximizes therapeutic efficacy of each drug and effectively reduces the toxic side effects.

• Proceedings of the Korean Society of Crop Science Conference
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• 2017.06a
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• pp.24-24
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• 2017

Heavy metals at toxic levels have the capability to interact with several vital cellular biomolecules such as nuclear proteins and DNA, leading to oxidative stress in plants. The present study was performed to explore the metal tolerance mechanism in Sorghum seedling. Morpho-physiological and metal ions uptake changes were observed prominently in the seedlings when the plants were subjected to different concentrations of $CuSO_4$ and $CdCl_2$. The observed morphological changes revealed that the plants treated with Cu and Cd displayed dramatically altered shoot lengths, fresh weights, and relative water content. In addition, the concentration of Cu and Cd was markedly increased by treatment with Cu and Cd, and the amount of interacting ions taken up by the shoots and roots was significantly and directly correlated with the applied level of Cu and Cd. Using the 2-DE method, a total of 24 and 21 differentially expressed protein spots from sorghum leaves and roots respectively, 33 protein spots from sorghum leaves under Cd stress were analyzed using MALDI-TOF/TOF MS. However, the over-expression of GAPDH plays a significant role in assisting Sorghum bicolor to attenuate the adverse effects of oxidative stress caused by Cu, and the proteins involved in resistance to stress helped the sorghum plants to tolerate high levels of Cu. Significant changes were absorbed in the levels of proteins known to be involved in carbohydrate metabolism, transcriptional regulation, translation and stress responses. In addition, the up-regulation of glutathione S-transferase and cytochrome P450 may play a significant role in Cd-related toxicity and stress responses. The results obtained from the present study may provide insights into the tolerance mechanism of seedling leaves and roots in Sorghum under heavy metal stress.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.19 no.4
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• pp.381-389
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• 2009

Confined spaces are inherently dangerous workplace and many fatal and nonfatal accidents have been reported. Even though these accidents occur in various kinds of confined spaces, there has rarely been reported on the health hazard agent, i.e., the types of gases and their concentration ranges. Therefore in this study, we evaluated several toxic and asphyxiating gas concentrations in various confined spaces. We surveyed 57 manholes, 3 sewage treatment plants, 2 yellow radish manufacturing companies and 7 barges to measure the concentrations of oxygen($O_2$), hydrogen sulfide($H_2S$), carbon monoxide(CO), ammonia($NH_3$). Lower Explosion Limits(LEL) and Volatile Organic Compounds (VOCs). Those four types of confined spaces occupies 56% of accidents during last 9 years in Korea. In 57 manholes, the concentration varied according to the types of manholes; rainfall and sewage, and by location; residential and industrial areas. Sewage manhole in industrial area was evaluated as the most hazardous than other types of manhole like rainfall manholes, residential sewage manholes. The highest $H_2S$ concentration and the lowest $O_2$ concentration at sewage manhole in industrial area were 300 ppm, 8.7% respectively. In 3 sewage treatment plants, $H_2S$ and $NH_3$ concentrations were reached up to the 500 ppm and 200 ppm respectively. Two yellow radish manufacturing companies showed the concentrations of 316 ppm, 505.2 ppm, 90 ppm and 15.7% for $H_2S$, CO, VOCs and $O_2$, respectively. Seven barges showed 15.9%~20.9% oxygen concentration. Gas species and concentration ranges varied by the types and location of confined spaces; CO, $H_2S$, $O_2$ could be hazardous in manhole, especially manhole connected to sewage plants. CO, $H_2S$, LEL, $O_2$, $NH_3$ should be controlled in sludge silo and sluge pumping confined spaces in sewage treatment plant. The activity of lifting out radish from the storage tank was evaluated more hazardous rather than the other activities in yellow radish manufacturing industry. The employers must conduct the survey to identify all possible confined spaces in their local workplace prior to performing the tasks. At the national level to reduce the accidents in the confined spaces, we suggest that systemic approach and active education program including possible hazards, standard operation procedures, ventilation plan, and personal protective equipment in confined spaces should be implemented.

• Korean Journal of Veterinary Research
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• v.44 no.1
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• pp.49-55
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• 2004

The present study was carried out to investigate the potential acute toxicity of CKD-602 by a single intravenous dose in Beagle dogs. The test chemical was administered intravenously to male and female Beagle dogs at dose levels of 0.3, 0.5, or 2.5 mg/kg. Mortalities, clinical findings, and body weight changes were monitored for the 14-day period following the administration. At the end of 14-day observation period, all animals were sacrificed and complete gross postmortem examinations were performed. All males and females of the 2.5 mg/kg dose group were found dead between the fourth and seventh day after the injection. Treatment related clinical signs, including vomiting, anorexia, mucous stool, diarrhea, and no stool were observed. Decrease or suppression of body weight was observed in a dose-dependent manner. In autopsy, dark red discoloration of the gastrointestinal tract, atrophy of the thymus, paleness of the spleen, sporadic dark red spots of the lung and petechia of the heart were observed in dead animals of the 2.5 mg/kg dose group. There were no specific adverse effects on males and females of the 0.3 and 0.5 mg/kg dose groups, except for the transient clinical signs such as anorexia, vomiting, and mucus/no stool. On the basis of the results, it was concluded that a single intravenous injection of CKD-602 to Beagle dogs resulted in increased incidence of abnormal clinical signs and death, decreased body weight, and increased incidence of abnormal gross findings. The absolute toxic dose of this chemical was 2.5 mg/kg for both genders. The $LD_{50}$ value was 1.1 mg/kg (95% confidence limit not specified) for both genders. The no-observed-effect level (NOEL) was considered to be below 0.3 mg/kg for both genders.

• Journal of Environmental Health Sciences
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• v.20 no.1
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• pp.62-67
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• 1994

Introduction : Recently, water and environmental pollution becomes serious social problem and high technology makes this pollution accelerate. Hydrogen sulfide, the main subject of our research, is one of the most dangerous air pollutant like SO$_x$ and NO$_x$. The major contaminant in coal gasification is H$_2$S, which is very toxic, hazardous and extremely corrosive. Therefore, control of hydrogen sulfide to a safe level is essential. Although commercial desulfurization process called liquid scrubbing is effective for removal of H$_2$S, it has drawbacks, the loss of sensible heat of the gas and costly wastewater treatment. Many investigations are carried out about high-temperature removal ol H$_2$S in hot coal-derived gas using metal oxide or mixed metal qxide sorbents. It was reported that ZnO was very effective sorbent for H2S removal, but it has big flaw to vaporize elemental zinc above 600\ulcorner \ulcorner As alternative, metal oxides such as CaO, $Fe_2O_3$, TiO$_2$ and CuO were added to ZnO. Especially, different results are reported for $Fe_2O_3$ additive. Tamhankar et al. reported SiO$_2$ with 45 wt% $Fe_2O_3$ sorbent is favorable for removal of H$_2$S and regeneration.

• Proceedings of the Microbiological Society of Korea Conference
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• 2007.05a
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• pp.120-122
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• 2007

All living organisms use numerous signal-transduction pathways to sense and respond to their environments and thereby survive and proliferate in a range of biological niches. Molecular dissection of these signalling networks has increased our understanding of these communication processes and provides a platform for therapeutic intervention when these pathways malfunction in disease states, including infection. Owing to the expanding availability of sequenced genomes, a wealth of genetic and molecular tools and the conservation of signalling networks, members of the fungal kingdom serve as excellent model systems for more complex, multicellular organisms. Here, we employed Cryptococcus neoformans as a model system to understand how fungal-signalling circuits operate at the molecular level to sense and respond to a plethora of environmental stresses, including osmoticshock, UV, high temperature, oxidative stress and toxic drugs/metabolites. The stress-activated p38/Hog1 MAPK pathway is structurally conserved in many organisms as diverse as yeast and mammals, but its regulation is uniquely specialized in a majority of clinical Cryptococcus neoformans serotype A and D strains to control differentiation and virulence factor regulation. C. neoformans Hog1 MAPK is controlled by Pbs2 MAPK kinase (MAPKK). The Pbs2-Hog1 MAPK cascade is controlled by the fungal "two-component" system that is composed of a response regulator, Ssk1, and multiple sensor kinases, including two-component.like (Tco) 1 and Tco2. Tco1 and Tco2 play shared and distinct roles in stress responses and drug sensitivity through the Hog1 MAPK system. Furthermore, each sensor kinase mediates unique cellular functions for virulence and morphological differentiation. We also identified and characterized the Ssk2 MAPKKK upstream of the MAPKK Pbs2 and the MAPK Hog1 in C. neoformans. The SSK2 gene was identified as a potential component responsible for differential Hog1 regulation between the serotype D sibling f1 strains B3501 and B3502 through comparative analysis of their meiotic map with the meiotic segregation of Hog1-dependent sensitivity to the fungicide fludioxonil. Ssk2 is the only polymorphic component in the Hog1 MAPK module, including two coding sequence changes between the SSK2 alleles in B3501 and B3502 strains. To further support this finding, the SSK2 allele exchange completely swapped Hog1-related phenotypes between B3501 and B3502 strains. In the serotype A strain H99, disruption of the SSK2 gene dramatically enhanced capsule biosynthesis and mating efficiency, similar to pbs2 and hog1 mutations. Furthermore, ssk2, pbs2, and hog1 mutants are all hypersensitive to a variety of stresses and completely resistant to fludioxonil. Taken together, these findings indicate that Ssk2 is the critical interface protein connecting the two-component system and the Pbs2-Hog1 pathway in C. neoformans.

• Journal of Animal Science and Technology
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• v.58 no.7
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• pp.24.1-24.7
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• 2016

Background: Clinoptilolite is a natural zeolite with high adsorption capacity for polar mycotoxins such as aflatoxins. The efficacy of clinoptilolite in ameliorating the toxic effects of aflatoxicosis has been proven in monogastric animals, but there is no such evidence for ruminants. The aim of this study was to evaluate, under field conditions, whether the dietary administration of clinoptilolite in dairy cows could reduce the concentration of aflatoxin M1 ($AFM_1$) in bulk-tank milk, in farms with higher than or close to $0.05{\mu}g/kg$ of milk (European maximum allowed residual level). An objective of the present study was also to investigate the effect of particle size of clinoptilolite on aflatoxin binding. Methods: Fifteen commercial Greek dairy herds with AFM1 concentrations in bulk tank milk ${\geq}0.05{\mu}g/kg$ were selected. Bulk tank milk AFM1 was determined prior to the onset and on day 7 of the experiment. Clinoptilolite was added in the total mixed rations of all farms at the rate of 200 g per animal per day, throughout this period. Two different particle sizes of clinoptilolite were used; less than 0.15 mm in 9 farms (LC group) and less than 0.8 mm in 6 farms (HC group). Results: Clinoptilolite administration significantly reduced $AFM_1$ concentrations in milk in all farms tested at an average rate of 56.2 % (SD: 15.11). The mean milk $AFM_1$ concentration recorded on Day 7 was significantly (P < 0.001) lower compared to that of Day 0 ($0.036{\pm}0.0061$ vs. $0.078{\pm}0.0074{\mu}g/kg$). In LC group farms the reduction of milk $AFM_1$ concentration was significantly higher than HC group farms ($0.046{\pm}0.0074$ vs. $0.036{\pm}0.0061{\mu}g/kg$, P = 0.002). As indicated by the Pearson correlation, there was a significant and strong linear correlation among the milk $AFM_1$ concentrations on Days 0 and 7 (R = 0.95, P < 0.001). Conclusions: Dietary administration of clinoptilolite, especially of smallest particle size, at the rate of 200 g per cow per day can effectively reduce milk $AFM_1$ concentration in dairy cattle and can be used as a preventive measure for the amelioration of the risks associated with the presence of aflatoxins in the milk of dairy cows.

• Korean Journal of Food Science and Technology
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• v.45 no.3
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• pp.364-369
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• 2013

Polychlorinated biphenyls (PCBs) have been studied during the past few decades because of their potential impacts on the environment and human health. PCBs are toxic environmental pollutants and persistent organic pollutants (POPs). This study was carried out to assess the dietary exposure and risk to PCBs for the general Korean population through food intake. Various samples (n=389) covering 28 kinds of food were collected from 5 cities in Korea. The PCB content was not detected-$182.4{\mu}g/kg$ (mean of $5.4{\mu}g/kg$) in the food. The mean dietary exposure of PCBs for the general population was 9.54 ng/kg bw/day with an intake of 0.19% of tolerable daily intake (TDI) ($5{\mu}g/kg$ bw/day). Therefore, the level of overall dietary exposure to PCBs for the Korean population through food intake is below the recommended TDI levels.

• Journal of Life Science
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• v.30 no.4
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• pp.321-330
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• 2020

The aim of this study was to investigate the effect of copper (II) chloride (CuCl₂) on zebrafish. Zebrafish were exposed to various CuCl₂ concentrations and subjected to different exposure times to determine the median lethal concentration (LC₅₀) values. To evaluate stress responses, we measured whole-body cortisol levels and behavioral parameters using the open field test (OFT) or the novel tank test (NTT). The zebrafish were exposed to CuCl₂ solution at concentrations of 1.5-150 ㎍/l or a vehicle for 1 hr before behavioral tests or sample collection for whole-body cortisol. The LC₅₀ values were 30.3, 25.3, and 14.8 ㎍/l at 24, 48, and 96 hr, respectively. The NTT showed that mobility, velocity, and distance covered were significantly lower in zebrafish exposed to CuCl₂ than in the control group (p<0.05), while the turn angle was significantly higher in zebrafish exposed to a CuCl₂ concentration of 150 ㎍/l than in the control group (p<0.05). The OFT also showed that mobility, velocity, and distance covered were significantly lower and the turn angle and meandering were significantly higher in zebrafish exposed to all concentrations of CuCl₂ than in the control group (p<0.05). The whole-body cortisol levels were significantly higher in zebrafish exposed to CuCl₂ than in the control group (p<0.05). These results suggest that exposure to lethal CuCl₂ concentrations induces an intense toxic and stress response in zebrafish, causing behavioral changes and increasing whole-body cortisol levels.

• Journal of Life Science
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• v.23 no.8
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• pp.963-969
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• 2013

Although it is popularly believed that vitamin C protects cells from various genotoxicants, the degrees and mechanisms of itsprotective actions are not fully understood. In this study, vitamin C's protective effects against various genotoxicants were quantified, together with subsequent analyses on the mechanisms of these protective effects. Comet assay was employed to measure the degree of DNA damage in Chinese hamster ovary cells (CHO-K1) exposed to five genotoxicants, $H_2O_2$, $HgCl_2$, N-methyl-N-nitro-N-nitrosoguanidine (MNNG), 4-nitroquinoline-1-oxide (4NQO), and UV-irradiation. In cases cells were treated with $H_2O_2$, $HgCl_2$, and 4NQO together with vitamin C, the damage to DNA decreased to the level of the control group. In cases of UV-irradiation, the protective effect of vitamin C appeared, but did not reach the control levels. Interestingly, vitamin C did not have protective effects against the genotoxicity of MNNG. The degrees of DNA damage of cells treated with vitamin C prior to exposure togenotoxicants were 28~49% lower than those of cells treated with vitamin C after being exposed to genotoxicants. In conclusion, vitamin C had strong antioxidanteffects against genotoxicants by being a primary antioxidant blocking genotoxicity reaching the cells, rather than being a secondary antioxidant acting on post-exposure DNA repair processes. However, vitamin C's protective effects appearto be limited, as there are genotoxicants, such as MNNG, whosegenotoxicityis not affected by vitamin C. Therefore, the results of this study warrant furtherstudies on toxic mechanisms of genotoxicants and their interactions with protective mechanisms of vitamin C.