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Cariporide Enhances the DNA Damage and Apoptosis in Acid-tolerable Malignant Mesothelioma H-2452 Cells

  • Lee, Yoon-Jin;Bae, Jin-Ho;Kim, Soo-A;Kim, Sung-Ho;Woo, Kee-Min;Nam, Hae-Seon;Cho, Moon-Kyun;Lee, Sang-Han
    • Molecules and Cells
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    • v.40 no.8
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    • pp.567-576
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    • 2017
  • The $Na^+/H^+$ exchanger is responsible for maintaining the acidic tumor microenvironment through its promotion of the reabsorption of extracellular $Na^+$ and the extrusion of intracellular $H^+$. The resultant increase in the extracellular acidity contributes to the chemoresistance of malignant tumors. In this study, the chemosensitizing effects of cariporide, a potent $Na^+/H^+-exchange$ inhibitor, were evaluated in human malignant mesothelioma H-2452 cells preadapted with lactic acid. A higher basal level of phosphorylated (p)-AKT protein was found in the acid-tolerable H-2452AcT cells compared with their parental acid-sensitive H-2452 cells. When introduced in H-2452AcT cells with a concentration that shows only a slight toxicity in H-2452 cells, cariporide exhibited growth-suppressive and apoptosis-promoting activities, as demonstrated by an increase in the cells with pyknotic and fragmented nuclei, annexin V-PE(+) staining, a $sub-G_0/G_1$ peak, and a $G_2/M$ phase-transition delay in the cell cycle. Preceding these changes, a cariporide-induced p-AKT down-regulation, a p53 up-regulation, an ROS accumulation, and the depolarization of the mitochondrial-membrane potential were observed. A pretreatment with the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 markedly augmented the DNA damage caused by the cariporide, as indicated by a much greater extent of comet tails and a tail moment with increased levels of the p-histone H2A.X, $p-ATM^{Ser1981}$, $p-ATR^{Ser428}$, $p-CHK1^{Ser345}$, and $p-CHK2^{Thr68}$, as well as a series of pro-apoptotic events. The data suggest that an inhibition of the PI3K/AKT signaling is necessary to enhance the cytotoxicity toward the acidtolerable H-2452AcT cells, and it underlines the significance of proton-pump targeting as a potential therapeutic strategy to overcome the acidic-microenvironment-associated chemotherapeutic resistance.

A study on the evaluation of metal component in automatic transmission fluid by vehicle driving (차량 운행에 따른 자동변속기유(ATF) 금속분 분석평가 연구)

  • Lee, Joung-Min;Lim, Young-Kwan;Doe, Jin-Woo;Jung, Choong-Sub;Han, Kwan-Wook;Na, Byung-Ki
    • Journal of Energy Engineering
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    • v.23 no.2
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    • pp.28-34
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    • 2014
  • Automatic transmission fluid (ATF) is used for automatic transmissions in the vehicle as the characterized fluid. Recently, the vehicle manufacture usually guarantee for fluid change over 80000~100000 km mileage or no exchange, but most drivers usually change ATF below every 50000 km driving in Republic of Korea. It can cause to raise environmental contamination by used ATF and increase the cost of driving by frequently ATF change. In this study, we investigate the various physical properties such as flash point, fire point, pour point, kinematic viscosity, cold cranking simulator, total acid number, and metal component concentration for fresh and used ATF after driving (50000 km, 100000 km). The result showed that the total acid number, pour point, Fe, Al and Cu component had increased than fresh ATF, but 2 kind of used oil (50000 km and 100000km) had similar physical values and metal component concentration.

Estimation of Disaster Prevention Target Rainfall according to Urban Disaster Prevention Performance (도시방재성능에 따른 방재성능목표 강우량 산정 연구)

  • Jeong, Min-Su;Oak, Young-Suk;Lee, Young-Kune;Lee, Young-Sub;Park, Mi-Ri;Lee, Chul-Hee
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.18 no.4
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    • pp.101-110
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    • 2017
  • The National Emergency Management Agency (NEMA) presented the disaster prevention performance target rainfall (DPPTR) for disaster prevention. The estimation criteria for DPPTR is a 10 year cycle. On the other hand, the target rainfall recalculated every 10 years is difficult to reflect the current change in rainfall on climate change. In this study, the probability of precipitation using the recent rainfall data was prepared and the weights according to socio-economic criteria reflecting the urban characteristics and adjusted probability rainfall criteria were applied to the results. The difference between the existing target rainfall and recalculated result was compared. The input data for the estimated probability rainfall was selected from 6 points located in the rainfall observing station of Chungcheongnam-do, Daejeon region. As a result of the estimation, in the case of upward probability precipitation weight, some similar areas were observed. On the other hand, there were a few cases of upward or downward changes within 10 mm. Considering the rainfall variability and uncertainty due to climate change, the existing target rainfall does not present the condition properly. Therefore, hydrological designers need to calculate the target rainfall, reflecting the present condition.

Radiological Impact on Decommissioning Workers of Operating Multi-unit NPP (다수호기 원전 운영에 따른 원전 해체 작업자에 대한 방사선학적 영향)

  • Lee, Eun-hee;Kim, Chang-Lak
    • Journal of Nuclear Fuel Cycle and Waste Technology(JNFCWT)
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    • v.17 no.1
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    • pp.107-120
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    • 2019
  • The decommissioning of one nuclear power plant in a multi-unit nuclear power plant (multi-unit NPP) site may pose radiation exposure risk to decommissioning workers. Thus, it is essentially required to evaluate the exposure dose of decommissioning workers of operating multi-unit NPPs nearby. The ENDOS program is a dose evaluation code developed by the Korea Atomic Energy Research Institute (KAERI). As two sub-programs of ENDOS, ENDOS-ATM to anticipate atmospheric transport and ENDOS-G to calculate exposure dose by gaseous radioactive effluents are used in this study. As a result, the annual maximum individual dose for decommissioning workers is estimated to be $2.31{\times}10^{-3}mSv{\cdot}y^{-1}$, which is insignificant compared with the effective dose limit of $1mSv{\cdot}y^{-1}$ for the public. Although it is revealed that the exposure dose of operating multi-unit NPPs does not result in a significant impact on decommissioning workers, closer examination of the effect of additional exposure due to actual demolition work is required. The calculation method of this study is expected to be utilized in the future for planned decommissioning projects in Korea. Because domestic NPPs are located in multi-unit sites, similar situations may occur.

Ginsenoside 20(S)-protopanaxadiol induces cell death in human endometrial cancer cells via apoptosis

  • Jo, Hantae;Jang, Dongmin;Park, Sun Kyu;Lee, Mi-Gi;Cha, Byungsun;Park, Chaewon;Shin, Yong Sub;Park, Hyein;Baek, Jin-myoung;Heo, Hyojin;Brito, Sofia;Hwan, Hyun Gyu;Chae, Sehyun;Yan, Shao-wei;Lee, Changho;Min, Churl K.;Bin, Bum-Ho
    • Journal of Ginseng Research
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    • v.45 no.1
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    • pp.126-133
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    • 2021
  • Background: 20(S)-protopanaxadiol (20(S)-PPD), one of the aglycone derivatives of major ginsenosides, has been shown to have an anticancer activity toward a variety of cancers. This study was initiated with an attempt to evaluate its anti-cancer activity toward human endometrial cancer by cell and xenograft mouse models. Methods: Human endometrial cancer (HEC)-1A cells were incubated with different 20(S)-PPD concentrations. 20(S)-PPD cytotoxicity was evaluated using MTT assay. Apoptosis was detected using the annexin V binding assay and cell cycle analysis. Cleaved poly (ADP-ribose) polymerase (PARP) and activated caspase-9 were assessed using western blotting. HEC-1A cell tumor xenografts in athymic mice were generated by inoculating HEC-1A cells into the flank of BALB/c female mice and explored to validate 20(S)-PPD anti-endometrial cancer toxicity. Results: 20(S)-PPD inhibited HEC-1A cell proliferation in a dose-dependent manner with an IC50 value of 3.5 μM at 24 h. HEC-1A cells morphologically changed after 20(S)-PPD treatment, bearing resemblance to Taxol-treated cells. Annexin V-positive cell percentages were 0%, 10.8%, and 58.1% in HEC-1A cells when treated with 0, 2.5, and 5 μM of 20(S)-PPD, respectively, for 24 h. 20(S)-PPD subcutaneously injected into the HEC-1A cell xenograft-bearing mice three times a week for 17 days manifested tumor growth inhibition by as much as 18% at a dose of 80 mg/kg, which sharply contrasted to controls that showed an approximately 2.4-fold tumor volume increase. These events paralleled caspase-9 activation and PARP cleavage. Conclusion: 20(S)-PPD inhibits endometrial cancer cell proliferation by inducing cell death via a caspase-mediated apoptosis pathway. Therefore, the 20(S)-PPD-like ginsenosides are endowed with ample structural information that could be utilized to develop other ginsenoside-based anticancer agents.

Oral health belief and satisfaction after scaling experience with comprehensive dental hygiene care (포괄치위생관리(CDHC) 과정 적용에 따른 스케일링 경험 대상자의 구강건강신념과 만족도)

  • Kim, Mi-Hye;Moon, Sang-Eun;Kim, Yun-Jeong;Kim, Seon-Yeong;Cho, Hye-Eun;Kang, Hyun-Joo
    • Journal of Korean society of Dental Hygiene
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    • v.22 no.1
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    • pp.1-9
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    • 2022
  • Objectives: This study was conducted to find scaling patients' oral health belief and satisfaction by applying Comprehensive Dental Hygiene Care (CDHC) process. Methods: From July 1 to September 20, 2020, the data about 182 patients who had scaling in dental clinics and hospitals had been collected and analyzed. For data analysis, SPSS Statistics 22.0 was applied to conduct frequency analysis, chi-square, t-test, One way ANOVA and Pearson's correlation analysis. Results: Regarding oral health behavior, in the CDHC group 92.4% used oral care products (p<0.001), and 67.4% regularly visited dental clinics for oral care (p<0.001). Regarding the oral health belief according to general characteristics, in the CDHC group, persons aged '50-65' scored 2.4 (the highest), and were significantly different from those aged '20-29' as the result of post-hoc analysis (p<0.001). Regarding the oral health belief of the CDHC group according to oral health behavior, the scaling cycle '3 months' scored the highest (p<0.05). The patients' satisfaction had high correlations with benefit (p<0.01) and Importance (p<0.05) as the sub factors of the oral health belief of the CDHC group. Conclusions: CDHC positively influenced scaling patients' oral health belief and satisfaction. Therefore, it is necessary to expand CDHC, as the medium to improve oral health belief and satisfaction, to clinical settings.

The Effect of Temperature on the Development of Spodoptera frugiperda (Lepidoptera: Noctuidae) (열대거세미나방 발육에 미치는 온도의 영향)

  • Moon, Hyung Cheol;Choi, Min Kyung;Jang, Su Ji;Lee, Jang Ho;Kim, Ju Hee;Chon, Hyong Gwon
    • Korean journal of applied entomology
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    • v.61 no.2
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    • pp.349-356
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    • 2022
  • Fall armyworm, Spodoptera frugiperda, is a invasive migratory pest of native to the tropical and sub-tropical regions that has recently invaded Korea with damage to cornfield. The study was conducted to investigate the development periods of S. frugiperda on artificial diet at six different temperatures. The developmental period from eggs to adult at 18, 21, 24, 27, 30 and 32℃ was 79.8, 54.2, 34.3, 28.4, 24.6 and 24.0 days, respectivery and decreased with increasing temperature. The pupal periods of females were shorter than males. Most of the larvae developed through six instar, but the ratio of 7 or more instar increased at low temperatures. The relationship between the development rate and temperature was fitted with by linear regression analysis. The lower development threshold for egg and larva development was 12.9℃ and 11.3℃, respectively, 12.6℃ for pupae and 11.8℃ for egg-to-adult development. The effective accumulative temperature for the development of the respective life cycle stages were 37.0 DD for eggs, 286.3 DD for larvae, 132.2 DD for pupae and 456.8 DD egg-to-adult development.

Sea Surface pCO2 and Its Variability in the Ulleung Basin, East Sea Constrained by a Neural Network Model (신경망 모델로 구성한 동해 울릉분지 표층 이산화탄소 분압과 변동성)

  • PARK, SOYEONA;LEE, TONGSUP;JO, YOUNG-HEON
    • The Sea:JOURNAL OF THE KOREAN SOCIETY OF OCEANOGRAPHY
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    • v.21 no.1
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    • pp.1-10
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    • 2016
  • Currently available surface seawater partial pressure carbon dioxide ($pCO_2$) data sets in the East Sea are not enough to quantify statistically the carbon dioxide flux through the air-sea interface. To complement the scarcity of the $pCO_2$ measurements, we construct a neural network (NN) model based on satellite data to map $pCO_2$ for the areas, which were not observed. The NN model is constructed for the Ulleung Basin, where $pCO_2$ data are best available, to map and estimate the variability of $pCO_2$ based on in situ $pCO_2$ for the years from 2003 to 2012, and the sea surface temperature (SST) and chlorophyll data from the MODIS (Moderate-resolution Imaging Spectroradiometer) sensor of the Aqua satellite along with geographic information. The NN model was trained to achieve higher than 95% of a correlation between in situ and predicted $pCO_2$ values. The RMSE (root mean square error) of the NN model output was $19.2{\mu}atm$ and much less than the variability of in situ $pCO_2$. The variability of $pCO_2$ with respect to SST and chlorophyll shows a strong negative correlation with SST than chlorophyll. As SST decreases the variability of $pCO_2$ increases. When SST is lower than $15^{\circ}C$, $pCO_2$ variability is clearly affected by both SST and chlorophyll. In contrast when SST is higher than $15^{\circ}C$, the variability of $pCO_2$ is less sensitive to changes in SST and chlorophyll. The mean rate of the annual $pCO_2$ increase estimated by the NN model output in the Ulleung Basin is $0.8{\mu}atm\;yr^{-1}$ from 2003 to 2014. As NN model can successfully map $pCO_2$ data for the whole study area with a higher resolution and less RMSE compared to the previous studies, the NN model can be a potentially useful tool for the understanding of the carbon cycle in the East Sea, where accessibility is limited by the international affairs.

Soil CO2 Efflux by Thinning Treatments of a Black Pine (Pinus thunbergii Parl.) Stand Disturbed by Pine Wilt Disease (소나무재선충병 발생 곰솔임분의 간벌에 따른 토양 호흡 동태)

  • Choi, Eun-Jin;Seo, Huiyeong;Lee, Kwang-Soo;Yoo, Byung-Oh;Kim, Choonsig;Cho, Hyun-Seo
    • Journal of Korean Society of Forest Science
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    • v.105 no.1
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    • pp.12-18
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    • 2016
  • This study was carried out to investigate the change on soil $CO_2$ efflux rates, soil temperature, soil water content and soil pH by thinning intensity treatments (heavy thinning, light thinning, control) of a black pine (Pinus thunbergii Parl.) stand disturbed by pine wilt disease in Wola National Experimental Forests in Jinju, Gyeongnam province. Monthly variations of soil $CO_2$ efflux rates were not significantly different between the thinning and the control treatments (P>0.05). The annual mean soil $CO_2$ efflux rates were $0.58g\;CO_2m^{-2}h^{-1}$ for the light thinning, $0.49g\;CO_2m^{-2}h^{-1}$ for the heavy thinning and $0.45g\;CO_2m^{-2}h^{-1}$ for the control treatments, respectively. There was a significant exponential relation between soil $CO_2$ efflux rates and soil temperature, but no correlation between soil water content or soil pH and soil $CO_2$ efflux rates. The values of $Q_{10}$ were 3.40 for the light thinning, 3.20 for the heavy thinning and 3.06 for the control treatments, respectively. The results indicate that soil $CO_2$ efflux rates in a black pine stand disturbed by pine wilt disease could be affected by thinning treatments.

Sodium Salicylate(NaSaL) Induces Apoptosis of NCI-H1299 Lung Carcinoma Cells via Activation Caspase-3 Protease (NCI-H1299 폐암 세포주에서 Caspase-3 Protease 활성을 통한 Sodium Salicylate(NaSaL)의 세포고사)

  • Shim, Hyeok;Yang, Sei-Hoon;Bak, Sang-Myeon;Jeong, Eun-Taik
    • Tuberculosis and Respiratory Diseases
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    • v.53 no.5
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    • pp.485-496
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    • 2002
  • Background : Nonsteroidal anti-inflammatory drugs (NSAIDs) are useful in the chemoprevention of colon cancers. Continuous NSAID use results in a 40% to 50% reduction in the relative risk of colorectal cancer. The precise mechanism by which NSAIDs prevent and/or cause the regression of colorectal tumors is not known. Some investigators have reported that certain NSAIDs induce apoptosis and alter the expression of the cell cycle regulatory genes in some carcinoma cells when administered at a relatively high concentration. However, the possibility of NSAIDs application as chemopreventive agents in lung cancers remains to be elucidated. To address this question, the human lung cancer cell line NCI-H1299 was used to investigate whether or not NSAIDs might induce the apoptotic death of NCI-H1299 cells. Methods : A viability test was carried out using a MTT assay. Apoptosis was measured by flow cytometric analysis and unclear staining(DAPI). The talytic activity of the caspase family was measured by the fluirigenic cleavage of biosubstrates. To define the mechanical basis of apoptosis, western blot was performed to analyze the expression of the death substrates(PARP and ICAD). Results : NaSaL significantly decreased the viability of the NCI-H1299 cells, which was revealed as apoptosis characterized by an increase in the $subG_0/G_1$ population and unclear fragmentation. The catalytic activity of caspase-3 protease began to increase after 24 Hr and reached a peak 30 Hr after treatment with 10 mM NaSaL. In contrast, caspase-6, 8, and 9 proteases did not have a significantly altered enzymatic activity. Consistent with activation of caspase-3 protease, NaSaL induced the cleavage of the protease biosubstrate. Conclusion : NaSaL induces the apoptotic death of NCI-H1299 human lung cancer cells via the activation of caspase-3 protease.