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Evidence for the Association of Ce11u1ar Iron Loss in Nitric Oxide-induced Apoptosis of HL-60 Cells: Involvement of p38 Kinase, c-Jun N-terminal Kinase, Cytochrome C Release, and Caspases Pathways

  • Choi, Suck-Chei;Kim, Beom-Su;Yoon, Kwon-Ha;Song, Moon-Young;Oh, Hyun-Mee;Han, Weon-Cheol;Kim, Tae-Hyeon;Kim, Eun-Cheol;Jun, Chang Duk
    • Animal cells and systems
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    • v.6 no.2
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    • pp.171-180
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    • 2002
  • Nitric oxide has high affinity for iron, and thus it can cause intracellular iron loss. We tested the idea that intracellular iron can be the primary target of NO toxicity by comparing the signaling mechanisms involved in cell death caused by iron depletion and that caused by NO. Treatment of HL-60 cells with a NO donor, S-nitroso-N-acetyl-DL-penicillamine (SNAP), decreased the intracellular iron level rapidly as that observed with the iron chelator deferoxamine (DFO). Iron chelators such as DFO and mimosine could induce death of human leukemic HL-60 cells by a mechanism requiring activation of p38 kinase, c-Jun N-terminal kinase, caspase-3 and caspase-8. DFO and SNAP also caused release of cytochrome c from mitochondria. Inhibition of p38 kinase by a selective inhibitor, SB203580, abolished the NO and DFO-induced cell death, release of cytochrome c, and activation of caspase-3 and caspase-8, thus indicating that p38 kinase lies upstream in the cell death processes. In a parallel situation, the cells that are sensitive to NO showed similar sensitivity to DFO. Moreover, simultaneous addition of ferric citrate, an iron-containing compound, inhibited the SNAP and DFO-induced activation of caspases and also blocked the NO-mediated cell cycle arrest at $G_1$ phase. Collectively, our data implicate that the NO-induced cell death of tumor cells including HL-60 cells is mediated by depletion of iron and further suggest that activation of p38 kinase lies upstream of cytochrome c release and caspase activation involved in this apoptotic process.

Vitamin C Promoted Liver Regeneration Following Partial Hepatectomy-induced Hepatic Injury in Senescence Marker Protein-30-deficient Mice (비타민 C 투여는 간 부분절제술에 의한 간 재생을 촉진 시킴)

  • Han, Seon Young;Hwang, Meeyul;Kim, Ah-Young;Lee, Eun-Mi;Lee, Eun-Joo;Lee, Myeong-Mi;Sung, Soo-Eun;Kim, Sang-Hyeob;Jeong, Kyu-Shik
    • Journal of Life Science
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    • v.25 no.3
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    • pp.336-344
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    • 2015
  • The capacity for liver regeneration involves a variety of nutritional factors. Vitamin C has multiple metabolic and antioxidant functions. In this study, we investigated the role of vitamin C in liver regeneration following hepatectomy in senescence marker protein (SMP)-30 knockout (KO) mice. Partial hepatectomy was performed by resecting the median and left lateral lobes of mice. Vitamin C accelerated liver recovery in SMP30 KO mice treated with vitamin C (KV). The livers of the KV mice exhibited lower levels of aspartate aminotransferase and lower injury than those of the KO mice. Increased type II transforming growth factor-β receptor (TGF-βRII)-mediated regeneration signaling was accompanied by HGF and cMet in the KV but not the KO mice. Consistent with this, the expression of cell cycle regulatory proteins, including cyclin D1 and proliferating cell nuclear antigen (PCNA), increased rapidly in the KV mice. Enhanced activation of ERK and GSK-3β proteins and a significantly increased number of binuclear hepatocytes were also detected in the livers of the KV mice. Moreover, the KV mice synthesized the highest levels of albumin. These data suggest that treating SMP30 knockout mice with vitamin C resulted in earlier recovery and liver regeneration by activation of the regeneration system.

Characterization of TNNC1 as a Novel Tumor Suppressor of Lung Adenocarcinoma

  • Kim, Suyeon;Kim, Jaewon;Jung, Yeonjoo;Jun, Yukyung;Jung, Yeonhwa;Lee, Hee-Young;Keum, Juhee;Park, Byung Jo;Lee, Jinseon;Kim, Jhingook;Lee, Sanghyuk;Kim, Jaesang
    • Molecules and Cells
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    • v.43 no.7
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    • pp.619-631
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    • 2020
  • In this study, we describe a novel function of TNNC1 (Troponin C1, Slow Skeletal and Cardiac Type), a component of actin-bound troponin, as a tumor suppressor of lung adenocarcinoma (LUAD). First, the expression of TNNC1 was strongly down-regulated in cancer tissues compared to matched normal lung tissues, and down-regulation of TNNC1 was shown to be strongly correlated with increased mortality among LUAD patients. Interestingly, TNNC1 expression was enhanced by suppression of KRAS, and ectopic expression of TNNC1 in turn inhibited KRASG12D-mediated anchorage independent growth of NIH3T3 cells. Consistently, activation of KRAS pathway in LUAD patients was shown to be strongly correlated with down-regulation of TNNC1. In addition, ectopic expression of TNNC1 inhibited colony formation of multiple LUAD cell lines and induced DNA damage, cell cycle arrest and ultimately apoptosis. We further examined potential correlations between expression levels of TNNC1 and various clinical parameters and found that low-level expression is significantly associated with invasiveness of the tumor. Indeed, RNA interference-mediated down-regulation of TNNC1 led to significant enhancement of invasiveness in vitro. Collectively, our data indicate that TNNC1 has a novel function as a tumor suppressor and is targeted for down-regulation by KRAS pathway during the carcinogenesis of LUAD.

A Prospective Study of Premenstrual Dysphoric Disorder (월경전 불쾌기분장애에 관한 전향적인 연구)

  • Kim, Ji-Yun;Joe, Sook-Haeng;Kwak, Dong-Il;Park, Yong-Kyun
    • Korean Journal of Psychosomatic Medicine
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    • v.5 no.1
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    • pp.52-62
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    • 1997
  • This study was designed to determine the frequency of premenstrual dysphoric disorder in gynecological outpatients, and also attempted to compare premenstrual change characteristics, functional impairment due to premenstrual changes and frequency of risk factors reported by women with confirmed premenstrual changes$(PMC^+)$(n=17) and those without confirmed premenstrual changes$(PMC^-)$(n=23). Forty gynecological outpatients who complained of premenstrual discomforts were asked to complete questionnaires on menstrual history, obstetric-gynecological history, and premenstrual change and functional impairment. The women were also asked to complete a daily rating form based on DSM-IV diagnostic criteria for one menstrual cycle. Absolute severity method, effect size method and percent change method were used to assess changes between follicular phase and luteal phase. The results of the study were as follows: 1) The frequency of premenstrual dysphoric disorder according to each of the three methods was 5% for the absolute severity method, 15% for the effect size method, and 27.5% for the percent change method. 2) The frequently reported symptoms were as follow: physical symptoms(64.7%) : lethargy, easy fatigability, or marked lack of energy(41.2%) : decreased interest in usual activities(29.4%) ; and marked affective lability(23.5%). 3) There were no significant differences in onset ages of premenstrual changes, regularities of premenstrual changes and changes of severity and duration of premenstrual symptoms over time between women with and without confirmed premenstrual changes. However, women with confirmed premenstrual changes reported both physical and emotional symptoms as earliest symptoms most frequently, while women without confirmed premenstrual changes reported only physical symptoms most frequently. 4) functional impairment was significantly higher in women with confirmed premenstrual changes than those without confirmed premenstrual changes, but impairment was not severe. 5) No differences were found between women with and without confirmed premenstrual changes in risk factors including demographic data, menstrual and obstetric and gynecological history. These results suggest that the prevalence of premenstrual dysphoric disorder varies with scoring methods. The women with confirmed premenstrual changes reported physical symptoms most frequently(64.7%). functional impairment was significantly higher in women with confirmed premenstrual changes, but impairment was not severe.

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Fundamental Study on a Distillation Separation of a LiCl-KCl Eutectic Salt from Rare Earth Precipitates (희토류 침전물로부터 LiCl-KCl 공융염의 증류 분리에 관한 기초연구)

  • Yang, Hee-Chul;Eun, Hee-Chul;Kim, In-Tae
    • Journal of Nuclear Fuel Cycle and Waste Technology(JNFCWT)
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    • v.8 no.1
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    • pp.65-70
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    • 2010
  • The distillation rate on LiCl-KCl eutectic salt under different vacuums from 0.5-50 mmHg was first investigated by using both a non-isothermal and a isothermal thermogravimetric (TG) analysis. Based on the non-isothermal TG data, distillation rate equations as a function of the temperature could be derived. Calculated flux by these model flux equations was in agreement with the distillation rate obtained from isothermal TG analysis. A distillation rate of $10^{-4}-10^{-5}$ mole $cm^{-2}sec^{-1}$ is obtainable at temperatures less than 1300K and vacuums of 0.5-50 mmHg. About a 99% salt distillation efficiency was obtained after an hour at a temperature above 1150 K under 50 mmHg in a small scale distillation test system. An increase in the vaporizing surface area is relatively effective for removing residual salt in the remaining particles, when compared to that for the vaporizing time. Over 99.95% of total distillation efficiency was obtained for a 1-h distillation operation by increasing the inner surface area from $4.52cm^2$ to $12.56cm^2$.

The Method for Evaluating Unsaturated Hydraulic Conductivity of the Bentonite-buffer Using Relative Humidity (상대습도를 이용한 벤토나이트 완충재의 불포화 수리전도도 평가방안)

  • Lee, Hang-Bok;Kim, Jin-Seop;Choi, Young-Chul;Choi, Heui-Joo;Kim, Kyungsu
    • Journal of Nuclear Fuel Cycle and Waste Technology(JNFCWT)
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    • v.12 no.1
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    • pp.69-77
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    • 2014
  • Unsaturated hydraulic conductivity of the bentonite-buffer was evaluated using the relative humidity data. The method for calculating unsaturated hydraulic conductivity was deduced from the general analytical equation representing the movement of water in unsaturated media, which was applied to the experimental results of water infiltration tests for identifying the behavior of unsaturated hydraulic conductivity according to the water saturation. Unlike the saturated condition, the hydraulic gradient and water flux were irregularly changed, and the unsaturated hydraulic conductivity was increased with increasing the experimental time. Swelling of bentonite grains due to the water absorption increased the volume and size of pore within bentonite, resulting in the increase of water velocity and unsaturated hydraulic conductivity. This result suggested the necessity of further investigation on the correlation between the swelling degree of bentonite-buffer and unsaturated hydraulic conductivity. The method used in this study can be useful technique for evaluating long-term hydraulic performance of bentonite-buffer in the radioactive waste disposal system.

Performance Evaluation to Develop an Engineering Scale Cathode Processor by Multiphase Numerical Analysis (다상유동 전산모사를 통한 공학 규모의 cathode processor의 성능평가)

  • Yoo, Bung Uk;Park, Sung Bin;Kwon, Sang Woon;Kim, Jeong Guck;Lee, Han Soo;Kim, In Tae;Lee, Jong Hyeon
    • Journal of Nuclear Fuel Cycle and Waste Technology(JNFCWT)
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    • v.12 no.1
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    • pp.7-17
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    • 2014
  • Molten salt electrorefining process achieves uranium deposits at cathode using an electrochemical processing of spent nuclear fuel. In order to recover pure uranium from cathode deposit containing about 30wt% salt, the adhered salt should be removed by cathode process (CP). The CP has been regarded as one of the bottle-neck of the pyroprocess as the large amount of uranium is treated in this step and the operation parameters are crucial to determine the final purity of the product. Currently, related research activities are mainly based on experiments consequently it is hard to observe processing variables such as temperature, pressure and salt gas behavior during the operation of the cathode process. Hence, in this study operation procedure of cathode process is numerically described by using appropriate mathematical model. The key parameters of this research are the amount of evaporation at the distillation part, diffusion coefficient of gas phase salt in cathode processor and phase change rate at condensation part. Each of these conditions were composed by Hertz-Langmuir equation, Chapman-Enskog theory, and interphase mass flow application in ANSYS-CFX. And physical properties of salt were taken from the data base in HSC Chemistry. In this study, calculation results on the salt gas behavior and optimal operating condition are discussed. The numerical analysis results could be used to closely understand the physical phenomenon during CP and for further scale up to commercial level.

A Prediction of Specific Heat Capacity for Compacted Bentonite Buffer (압축 벤토나이트 완충재의 비열 추정)

  • Yoon, Seok;Kim, Geon-Young;Baik, Min-Hoon
    • Journal of Nuclear Fuel Cycle and Waste Technology(JNFCWT)
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    • v.15 no.3
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    • pp.199-206
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    • 2017
  • A geological repository for the disposal of high-level radioactive waste is generally constructed in host rock at depths of 500~1,000 meters below the ground surface. A geological repository system consists of a disposal canister with packed spent fuel, buffer material, backfill material, and intact rock. The buffer is indispensable to assure the disposal safety of high-level radioactive waste, and it can restrain the release of radionuclides and protect the canister from the inflow of groundwater. Since high temperature in a disposal canister is released to the surrounding buffer material, the thermal properties of the buffer material are very important in determining the entire disposal safety. Even though there have been many studies on thermal conductivity, there have been only few studies that have investigates the specific heat capacity of the bentonite buffer. Therefore, this paper presents a specific heat capacity prediction model for compacted Gyeongju bentonite buffer material, which is a Ca-bentonite produced in Korea. Specific heat capacity of the compacted bentonite buffer was measured using a dual probe method according to various degrees of saturation and dry density. A regression model to predict the specific heat capacity of the compacted bentonite buffer was suggested and fitted using 33 sets of data obtained by the dual probe method.

Determination of Radionuclide Concentration Limit for Low and Intermediate-Level Radioactive Waste Disposal Facility II: Application of Optimization Methodology for Underground Silo Type Disposal Facility (중저준위방사성폐기물 처분시설의 처분농도제한치 설정에 대한 고찰 II: 최적화 방법론 개발 및 적용)

  • Hong, Sung-Wook;Kim, Min Seong;Jung, Kang Il;Park, Jin Beak
    • Journal of Nuclear Fuel Cycle and Waste Technology(JNFCWT)
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    • v.15 no.3
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    • pp.265-279
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    • 2017
  • The Gyeongju underground silo type disposal facility, approved for use in December 2014, is in operation for the disposal of low and very low-level radioactive wastes, excluding intermediate-level waste. That is why the existing low-level radioactive waste level has been subdivided and the concentration limit value for intermediate-level waste has been changed in accordance with Nuclear Safety Commission Notice 2014-003. For the safe disposal of intermediate-level wastes, new optimization methodology for calculating the concentration limit of intermediate radioactive level wastes at an underground silo type disposal facility was developed. According to the developed optimization methodology, concentration limits of intermediate-level wastes were derived and the inventory of radioactive nuclides was evaluated. The operation and post closure scenarios were evaluated for the derived radioactive nuclide inventory and the results of all scenarios were confirmed to meet the regulatory limit. However, in case of $^{14}C$, it was confirmed that additional radioactivity limitation through a well scenario was needed in addition to the limit of disposal concentration. It was confirmed that the derived intermediate concentration limit of radioactive waste can be used as the intermediate-level waste concentration limit for the underground disposal facility. For the safe disposal of intermediate-level wastes, KORAD plans to acquire additional data from the radioactive waste generator and manage the cumulative radioactivity of $^{14}C$.

Estimation of the Groundwater Recharge Rate during a Rainy Season at a Headwater Catchment in Gwangneung, Korea (광릉 원두부 소유역에서의 우기 중 지하수 함양률 평가)

  • Choi, In-Hyuk;Woo, Nam-Chil;Kim, Su-Jin;Moon, Sang-Ki;Kim, Joon
    • Korean Journal of Agricultural and Forest Meteorology
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    • v.9 no.2
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    • pp.75-87
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    • 2007
  • Groundwater recharge rates were estimated and compared in a headwater catchment at the Gwangneung Supersite using three different methods: water-table fluctuation (WTF), mass balance, and hydrograph separation techniques. Data were obtained during the rainy season from June to September 2005. Two different WTF methods estimated the groundwater recharge rate as 25.9% and 23.6%. The mass balance calculation of chloride ions indicated recharge rates of 13.4% on average. Baseflow separation using chloride ion as a tracer from six storm hydrographs produced a 14.0% net baseflow rate on average. Because of the implicit assumption of a long-term steady state without storage change, recharge rates calculated by mass balance and hydrograph separation were smaller than those done with WTF methods, which include the amount of increased storage due to the water-level rise. Subsequently, the WTF method is superior to others in the estimation of groundwater recharge rate to comprehend the dynamic characteristics of the hydrologic cycle.