• Title/Summary/Keyword: MCL1

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Antiproliferative and Cytotoxic Effects of Resveratrol in Mitochondria-Mediated Apoptosis in Rat B103 Neuroblastoma Cells

  • Rahman, Md. Ataur;Kim, Nam-Ho;Kim, Seung-Hyuk;Oh, Sung-Min;Huh, Sung-Oh
    • The Korean Journal of Physiology and Pharmacology
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    • v.16 no.5
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    • pp.321-326
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    • 2012
  • Resveratrol, a natural compound, has been shown to possess anti-cancer, anti-aging, anti-inflammatory, anti-microbial, and neuroprotective activities. In this study, we examined the antiproliferative and cytotoxicity properties of resveratrol in Rat B103 neuroblastoma cells; although it's molecular mechanisms for the biological effects are not fully defined. Here, we examined the cellular cytotoxicity of resveratrol by cell viability assay, antiproliferation by BrdU assay, DNA fragmentation by DNA ladder assay, activation of caspases and Bcl-2 family proteins were detected by western blot analyses. The results of our investigation suggest that resveratrol increased cellular cytotoxicity of Rat B103 neuroblastoma cells in a dose-and time-dependent manner with $IC_{50}$ of 17.86 ${\mu}M$ at 48 h. On the other hand, incubation of neuroblastoma cells with resveratrol resulted in S-phase cell cycle arrests which dose-dependently and significantly reduced BrdU positive cells through the downregulation of cyclin D1 protein. In addition, resveratrol dose-dependently and significantly downregulated the expression of anti-apoptotic protein includes Bcl-2, Bcl-xL and Mcl-1 and also activates cleavage caspase-9 and-3 via the downregulation of procaspase-9 and -3 in a dose-dependent manner which indicates that involvement of intrinsic mitochondria-mediated apoptotic pathway. In conclusion, resveratrol increases cellular cytotoxicity and inhibits the proliferation of B103 neuroblastoma cells by inducing mitochondria-mediated intrinsic caspase dependent pathway which suggests this natural compound could be used as therapeutic purposes for neuroblastoma malignancies.

A Study on the Minimum Route Cost Routing Protocol for 6LoWPAN (6LoWPAN을 위한 최소경로비용 라우팅 프로토콜에 관한 연구)

  • Kim, Won-Geun;Kim, Jung-Gyu
    • Journal of Korea Society of Industrial Information Systems
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    • v.15 no.1
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    • pp.1-14
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    • 2010
  • It is recently issued scalability, mobility and external internet connection on Wire-less sensor network. The low power wireless sensor networks based on IPv6 technology 6LoWPAN technology is being standardized in the IETF. This paper for the 6LoWPAN environment based on the routing protocol LOAD, route cost applied the packet re-transmission rate which follows in Link Qualities price which uses at course expense and packet transmission Minimum route Cost routing protocol where does on the course wherethe smallest packet re-transmission becomes accomplished proposed. The technique which proposes compared and LOAD and AODV that about 13%, about 16% energy consumption is few respectively averagely, Energy of the entire network equally, used and energy effectiveness and improvement of network life time experiment led and confirmed.

Microtubule-damaging Chemotherapeutic Agent-mediated Mitotic Arrest and Apoptosis Induction in Tumor Cells (미세소관-손상 항암제 처리에 의한 세포주기의 정지 및 에폽토시스 유도)

  • Jun, Do Youn;Kim, Young Ho
    • Journal of Life Science
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    • v.26 no.3
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    • pp.376-386
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    • 2016
  • Apoptosis induction has been proposed as an efficient mechanism by which malignant tumor cells can be removed following chemotherapy. The intrinsic mitochondria-dependent apoptotic pathway is frequently implicated in chemotherapy-induced tumor cell apoptosis. Since DNA-damaging agent (DDA)-induced apoptosis is mainly regulated by the tumor suppressor protein p53, and since more than half of clinical cancers possess inactive p53 mutants, microtubule-damaging agents (MDAs), of which apoptotic effect is mainly exerted via p53-independent routes, can be promising choice for cancer chemotherapy. Recently, we found that the apoptotic signaling pathway induced by MDAs (nocodazole, 17α-estradiol, or 2-methoxyestradiol) commonly proceeded through mitotic spindle defect-mediated prometaphase arrest, prolonged Cdk1 activation, and subsequent phosphorylation of Bcl-2, Mcl-1, and Bim in human acute leukemia Jurkat T cells. These microtubule damage-mediated alterations could render the cellular context susceptible to the onset of mitochondria-dependent apoptosis by triggering Bak activation, Δψm loss, and resultant caspase cascade activation. In contrast, when the MDA-induced Bak activation was inhibited by overexpression of anti-apoptotic Bcl-2 family proteins (Bcl-2 or Bcl-xL), the cells in prometaphase arrest failed to induce apoptosis, and instead underwent mitotic slippage and endoreduplication cycle, leading to formation of populations with 8N and 16N DNA content. These data indicate that cellular apoptogenic mechanism is critical for preventing polyploid formation following MDA treatment. Since the formation of polyploid cells, which are genetically unstable, may cause acquisition of therapy resistance and disease relapse, there is a growing interest in developing new combination chemotherapies to prevent polyploidization in tumors after MDA treatment.

Effect of Organic Matter and Moisture Content on Reduction of Cr(VI) in Soils by Zerovalent Iron (영가철에 의한 토양 Cr(VI) 환원에 미치는 유기물 및 수분함량 영향)

  • Yang, Jae-E.;Lee, Su-Jae;Kim, Dong-Kuk;Oh, Sang-Eun;Yoon, Sung-Hwan;Ok, Yong-Sik
    • Korean Journal of Environmental Agriculture
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    • v.27 no.1
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    • pp.60-65
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    • 2008
  • Current soil remediation principles for toxic metals have some limitations even though they vary with different technologies. An alternative technology that transforms hazardous substances into nonhazardous ones would be environmentally beneficial. Objective of this research was to assess optimum conditions for Cr(VI) reduction in soils as influenced by ZVI(Zero-Valent Iron), organic matter and moisture content. The reduction ratio of Cr(VI) was increased from 37 to 40% as organic matter content increased from 1.07 to 1.75%. In addition, Cr(VI) concentration was reduced as soil moisture content increased, but the direct effect of soil moisture content on Cr(VI) reduction was less than 5% of the Cr(VI) reduction ratio. However, combined treatment of ZVI(5%), organic matter(1.75%) and soil moisture(30%) effectively reduced the initial Cr(VI) to over 95% within 5 days and nearly 100% after 30 days by increasing oxidation of ZVI and concurrent reduction of Cr(VI) to Cr(III). The overall results demonstrated that ZVI was effective in remediating Cr(VI) contaminated soils, and the efficiency was synergistic with the combined treatments of soil moisture and organic matter.

Hydrogeochemistry and Occurrences of Uranium and Radon in Groundwater of in Chungwon, Korea (청원지역 지하수의 우라늄과 라돈의 산출 특성과 수리지화학)

  • Lee, Byeongdae
    • Journal of Environmental Science International
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    • v.27 no.8
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    • pp.651-663
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    • 2018
  • The hydrochemistry of groundwater from 47 wells in the Chungwon area, Korea was analyzed to examine the occurrence of natural radionuclides like uranium and radon. The range of Electrical Conductivity (EC) value in the study area was $67{\sim}1,404{\mu}S/cm$. In addition to the high EC value, the content of cations and anions also tends to increase. Uranium concentrations ranged from $ND{\sim}178{\mu}g/L$ (median value, $0.8{\mu}g/L$) and radon concentrations ranged from 80~12,900 pCi/L (median value, 1,250 pCi/L). Uranium concentrations in one well, that is 2.8% of the samples, exceeded $30{\mu}g/L$, which is the Maximum Contaminant Level (MCL) proposed by the US Environmental Protection Agency (EPA), based on the chemical toxicity of uranium. Radon concentrations in three wells, that is 6% of the samples, and one well, that is 2.8% of the samples, exceeded 4,000 pCi/L (AMCL of the US EPA) and 8,100 pCi/L (Finland's guideline level), respectively. Concentrations of uranium and radon related to geology of the study area show the highest values in the groundwater of the granite area. The uranium and radon contents in the groundwater were found to be low compared to those of other countries with similar geological settings. It is likely that the measured value was lower than the actual content due to the inflow of shallow groundwater by the lack of casing and grouting.

Activation of SAPK and Increase in Bak Levels during Ceramide and Indomethacin-Induced Apoptosis in HT29 Cells

  • Kim, Ju-Ho;Oh, Sae-Ock;Jun, Sung-Sook;Jung, Jin-Sup;Woo, Jae-Suk;Kim, Yong-Keun;Lee, Sang-Ho
    • The Korean Journal of Physiology and Pharmacology
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    • v.3 no.1
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    • pp.75-82
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    • 1999
  • It has been reported that activation of sphingomyelin pathway and nonsteroidal anti-inflammatory drugs (NSAIDS) inhibit the promotion of colon carcinoma. Ceramide, a metabolite of sphingomyelin, and indomethacin were shown to induce apoptosis in colon carcinoma cells. However, the mechanisms of ceramide- and indomethacin-induced apoptosis in the colon carcinoma cells are not clearly elucidated. Recent studys showed that indomethacin-induced apoptosis in colon cancer cells through the cyclooxygenase-independent pathways, and that may be mediated by generation of ceramide. In this study, we compared effects of ceramide and indomethacin on important modulators of apoptotic processes in HT29 cells, a human colon cancer cell line. Ceramide and indomethacin induced apoptosis dose- and time- dependently. Ceramide and indomethacin increased stress-activated protein kinase (SAPK) activity, and decreased mitogen-activated protein kinase (MAPK) activity. The expression of Bak was increased by the treatment of ceramide and indomethacin. The expression of other Bcl-2 related proteins (Mcl-1, $Bcl-X_L,$ Bax) which were known to be expressed in colon epithelial cells was not changed during the ceramide- and indomethacin-induced apoptosis. Our results suggest that ceramide and indomethacin share common mechanisms for induction of apoptosis in HT29 cells.

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Os Submalleolare in Sports players (스포츠 선수에서 발생한 내과하 부골증)

  • Lee, Kyung-Tai;Young, Ki-Won;Kim, J-Young;Lim, Tai-Kang
    • Journal of Korean Foot and Ankle Society
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    • v.7 no.2
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    • pp.218-222
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    • 2003
  • Purpose: The objective of this study was to define the Os submalleolare as an any ossicles below medial malleolus of tibia and to determine the characteristics of clinical and radiological characteristics and to evaluate results of surgical treatment of Os submalleolare in sports player group. Materials and Methods: Twenty-two patients with Os submalleolare were identified between November, 1, 1998 and June, 30, 2002. Results: The mean age was 18.3 years. All patient were male and soccer players comprised 71%(20 cases). Associated disease were 8 cases(29%) of chronic ankle instabilities, one case(4%) of anterior impingement syndrome and one (4%) of plantar fascitis. The most common clinical symptom was pain during walking and sports activity and sign was tenderness around medial malleolus. Only simple radiograph could reveal presence of ossicle and differentiate with acute fracture. If symptom and sign obscured, Bone scan(7 cases) and MRI(3 cases) identify causes of pain and tenderness. As a surgical treatment, all bony fragment caused symptom and sign were eliminated and medial collateral ligament was reattached meticulously. Associated chronic ankle instability were present, modified Brostrom procedure was done simultaneously. On follow-up, The symptomatic pain were wholly disappeared at average 2.2 months (1-6months) after operation. On one year follow-up, all patients have been daily life without any complaints and have gone back to the game within three months. Conclusion: as submalleolare have relatively rare incidence in sports players and most common clinical symptom and sign is tenderness on medial malleolar area of ankle, can be diagnosed both physical examination and plain X-ray film. As a treatment, Removal of ossicle and reattachment of MCL could obtain excellent or good results.

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Inhibitory Effect of the Hexane Extract of Saussurea lappa on the Growth of LNCaP Human Prostate Cancer Cells (목향 헥산추출물의 LNCaP 전립선암세포 증식 억제 효과)

  • Park, So-Young;Kim, Eun-Ji;Lim, Do-Young;Kim, Jong-Sang;Lim, Soon-Sung;Shin, Hyun-Kyung;Yoon Park, Jung-Han
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.37 no.1
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    • pp.8-15
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    • 2008
  • Saussurea lappa (SL) has been used to reduce abdominal pain and tenesmus in traditional oriental medicine. SL and major compounds of SL, sesquiterpene lactones, have been suggested to possess various biological effects, including anti-tumor, anti-ulcer, anti-inflammatory, anti-viral and cardiotonic activities. Recently, it has been reported that ethanol extracts from roots of SL have antiproliferative effects on gastric cancer cells. To explore the possibility that SL has chemopreventive effects on prostate cancer, we examined whether the hexane extract of SL (HESL) inhibits the growth of LNCaP human prostate cancer cells. Cells were incubated with various concentrations ($0{\sim}4$ mg/L) of HESL in DMEM/F12 containing 5% charcoal stripped fetal bovine serum. HESL substantially decreased viable cell numbers and induced apoptosis of LNCaP cells in dose-dependent manners. HESL increased the levels of cleaved caspase-8, -9, -7 and -3, and poly (ADP-ribose) polymerase. HESL increased the levels of the pro-apoptotic Bak and truncated-Bid proteins whereas it had no effect on the anti-apoptotic Bcl-2, Bcl-xL, or Mcl-1. The present results indicate that HESL inhibits the growth of human prostate cancer cells by inducing apoptosis, which involves the activation of the caspase cascades.

Adsorption of Heavy Metal Cations by Fe and Al Hydroxides (철, 알루미늄 수산화물에 의한 중금속 Ion의 흡착)

  • Lee, Jyung-Jae;Chang, Sang-Moon;Choi, Jyung
    • Korean Journal of Soil Science and Fertilizer
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    • v.28 no.2
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    • pp.105-113
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    • 1995
  • Adsorption experiments of heavy metal cations by Fe- and Al-hydroxides was conducted to obtain clear information on their adsorption mechanisms. The adsorption isothermal curves of heavy metal cations by Fe- and Al-hydroxides conformed to Langmuir's equation. Increasing the crystallinity degree of Fe- and Al-hydroxides tended to decrease the adsorption capacity and binding energy of heavy metal cations. At the same crystallinity degree, Al-hydroxide showed higher adsorption capacity and energy for the heavy metal cations than Fe-hydroxide. The adsorption capacity and energy of heavy metal cations were directly related to CEC, specific surface area and charge density of hydroxides, and the sequence was in the order of $Cu^{+{+}}$ > $Zn^{+{+}}$ > $Cd^{+{+}}$. The adsorption mechanism of $M^{+{+}}$ form of heavy metal could be presumed as the specific adsorption of $M^{+{+}}$ and the desorption of two $H^+$ from the surface aquo($OH_2$) and/or hydroxo(-OH) group for each mole of $M^{+{+}}$ adsorbed. A ring structure between $M^{+{+}}$ and two surface aquo and/or hydroxo groups was postulated. Nonspecific adsorption involved the adsorption of $MCl^+$ and the desorption of one H+ from the surface aquo and/or hydroxo groups for each mole of $M^{+{+}}$ adsorbed. A single bond structure in which $MCl^+$ replaced one $H^+$ from the surface aquo and/or hydroxo groups was postulated. The ratio of specific to nonspecific adsorption increased with increasing pH.

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A Study on Comparison of Risk Estimates Among Various Exposure Scenario of Several Volatile Organic Compounds in Tap Water (음용수중 휘발성 유기오염물질의 노출경로에 따른 위해도 추정치 비교연구)

  • Chung, Yong;Shin, Dong-Chun;Kim, Jong-Man;Yang, Ji-Yeon;Park, Seong-Eun
    • Environmental Analysis Health and Toxicology
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    • v.10 no.1_2
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    • pp.21-35
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    • 1995
  • Risk assessment processes, which include processes for the estimation of human cancer potency using animal bioassay data and calculation of human exposure, entail uncertainties. In the exposure assessment process, exposure scenarios with various assumptions could affect the exposure amount and excess cancer risk. We compared risk estimates among various exposure scenarios of vinyl chloride, trichloroethylene and tetrachloroethylene in tap water. The contaminant concentrations were analyzed from tap water samples in Seoul from 1993 to 1994. The oral and inhalation cancer potencies of the contaminants were estimated using multistage, Weibull, lognormal, and Mantel-Bryan model in TOX-RISK computer software. In the first case, human excess cancer risk was estimated by the US EPA method used to set the MCL(maximum contaminant level). In the second and third case, the risk was estimated for multi-route exposure with and without adopting Monte-Carlo simulation, respectively. In the second case, exposure input parameters and cancer potencies used probability distributions, and in the third case, those values used point estimates(mean, and maximum or 95% upper-bound value). As a result, while the excess cancer risk estimated by US EPA method considering only direct ingestion tended to be underestimated, the risk which was estimated by considering multi-route exposure without Monte-Carlo simulation and then using the maximum or 95% upper-bound value as input parameters tended to be overestimated. In risk assessment for volatile organic compounds, considering multi-route exposure with adopting Monte-Carlo analysis seems to provide the most reasonable estimations.

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