• Title/Summary/Keyword: time-dependent effect

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CDST, a Derivative of Tetrahydroisoquinoline, Induced Apoptosis in HL-60 Cells through Activation of Caspase-8, Bid Cleavage and Cytochrome c Release

  • Ju, Sung-Min;Kim, Kun-Jung;Lee, Jong-Gil;Lee, Chai-Ho;Han, Dong-Min;Yun, Young-Gab;Hong, Gi-Yun;An, Won-Gun;Jeon, Byung-Hun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.19 no.3
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    • pp.802-810
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    • 2005
  • The tetrahydroisoquinolines included potent cytotoxic agents that showed antitumor activity,antimicrobial activity, and other biological properties. We studied the effect of CDST, 1-Chloromethyl-6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-sulfonic acid amide, a newly synthesized anti-cancer agent. The cytotoxic activity of CDST in HL-60 cells was increased in a dose-dependent manner. CDST, tetrahydroisoquinolines derivative, was cytotoxic to HL-60 cells, with IC50 of $80{\mu}g/ml$. Treatment of CDST to HL-60 cells showed the fragmentation of DNA in a dose- and time dependent manner, suggesting that thesecells underwent apoptosis. Treatment of HL-60 cells with CDST was induced in a dose- and time-dependent activation of caspase-3, caspase-8 and proteolytic cleavage of poly(ADP-ribose) polymerase. In caspase activity assay, caspase-3 and -8 was activated after 12 h and 6 h posttreatment, respectively. CDST also caused the release of cytochrome c from mitochondria into the cytosol. CDST-induced cytochrome c release was mediated by caspase-8-dependent cleavage of Bid and Bax translocation. These results suggest that caspase-8 induced Bid cleavage and Bax translocation, caused mitochondrial cytochrome c release, and induce caspase-3 activationduring CDST-induced apoptosis in HL-60 cells.

Study on the turbulent structure for two-dimensional recirculating flows by curvature dependent 2-equation model (曲率修正2方程式모델을 利용한 2次元 再循環 亂流 流動構造의 硏究)

  • 박상우;정명균
    • Transactions of the Korean Society of Mechanical Engineers
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    • v.11 no.3
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    • pp.444-453
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    • 1987
  • In the present study, a new computational closure model is proposed in order to contain physical models in the k- and .epsilon.- equations. The time scale of the third-order diffusive transport of turbulent kinetic energy in a curved streamline flow field is assumed as a function of a velocity time scale and a curvature time scale, the latter being derived from the analogy between buoyancy and streamline curvature effects on turbulence. The curvature time scale is represented by a combination of Brunt-Vaisala frequency of the curvature instability and the velocity time scale. Besides the modification of diffusive transport time scale, the destruction term in the dissipation rate equation is modeled to incorporate the streamline curvature effect on the dissipation rate of turbulent kinetic energy as a function of the ratio between velocity time scale and curvature time scale. The new curvature dependent 2-equation model is found to yield very good prediction accuracy for the various turbulent recirculating flows. Particurarly, the recovery of the mean velocity profile in the redeveloping region after the reattachment is correctly simulated by the present model.

Induction of Apoptosis in AGS Human Gastric Cancer Cell by Ethanol Extract of Ganoderma lucidum (영지 약침액이 인체 위암 세포 성장억제 및 세포사멸 유발에 미치는 영향)

  • Lee, Byung-Hoon;Kim, Hong-Gi;Kim, Cheol-Hong;Youn, Hyoun-Min;Song, Choon-Ho;Jang, Kyung-Jeon
    • Korean Journal of Acupuncture
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    • v.29 no.2
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    • pp.271-289
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    • 2012
  • Objectives : Ganoderma lucidum(Ganoderma or lingzhi, 靈芝) is a well-known oriental medical mushroom containing many bioactive compounds. The possible mechanisms involved in its effects on cancer cells remain to be elucidated. In the present study, the anti-proliferative and apoptotic activities of the G. lucidum ethanol extract(GEE), in AGS human gastric cancer cells were investigated. Methods : It was found that exposure of AGS cells to GEE resulted in the growth inhibition in a dose and time dependent manner as measured by trypan blue count and MTT assay. The anti-proliferative effect of GEE treatment in AGS cells was associated with morphological changes and formation of apoptotic bodies, and the flow cytometry analysis confirmed that GEE treatment increased the populations of apoptotic-sub G1 phase. Growth inhibition and apoptosis of AGS cells by GEE were connected with a concentration and time-dependent up-regulation of tumour necrosis factor-related apoptosis-inducing ligand(TRAIL) expression. Results : The levels of XIAP and survivin expression, members of IAP family proteins, were gradually down-regulated by GEE treatment. However other members of IAP family proteins such as cIAP-1 and cIAP-2 remained unchanged in GEE-treated AGS cells. GEE treatment also induced the proteolytic activation of caspase-3, caspase-8 and caspase-9 and a concomitant degradation of poly(ADP-ribose) polymerase(PARP) protein, a caspase-3 substrate protein. Additionally, GEE-induced apoptosis was associated with the inhibition of Akt activation in a concentration and time-dependent manner, and pre-treatment with LY294002, a phosphoinositide 3-kinase(PI3K)/Akt inhibitor, significantly increased GEE-induced growth inhibition and apoptosis. Conclusions : Therefore, G. lucidum has a strong potential as a therapeutic agent for preventing cancers such as gastric cancer cells.

Simulated Annealing for Two-Agent Scheduling Problem with Exponential Job-Dependent Position-Based Learning Effects (작업별 위치기반 지수학습 효과를 갖는 2-에이전트 스케줄링 문제를 위한 시뮬레이티드 어닐링)

  • Choi, Jin Young
    • Journal of the Korea Society for Simulation
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    • v.24 no.4
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    • pp.77-88
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    • 2015
  • In this paper, we consider a two-agent single-machine scheduling problem with exponential job-dependent position-based learning effects. The objective is to minimize the total weighted completion time of one agent with the restriction that the makespan of the other agent cannot exceed an upper bound. First, we propose a branch-and-bound algorithm by developing some dominance /feasibility properties and a lower bound to find an optimal solution. Second, we design an efficient simulated annealing (SA) algorithm to search a near optimal solution by considering six different SAs to generate initial solutions. We show the performance superiority of the suggested SA using a numerical experiment. Specifically, we verify that there is no significant difference in the performance of %errors between different considered SAs using the paired t-test. Furthermore, we testify that random generation method is better than the others for agent A, whereas the initial solution method for agent B did not affect the performance of %errors.

The Effects of α-Lipoic Acid in Adilution Solvents, Dose- and Time-dependent Manner on Cell Growth Blocking in 3T3-L1 (α-Lipoic acid의 희석용매, 처리농도, 처리시간에 따른 3T3-L1 지방세포 성장에 미치는 영향)

  • Seo, Eunyoung
    • Journal of the Korean Society of Food Culture
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    • v.33 no.5
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    • pp.464-471
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    • 2018
  • Purpose: This study examined the effects of ${\alpha}$-lipoic acid in diluted solvents on cell growth in 3T3-L1 cells according to the treated concentration and times. Methods: Adipocyte 3T3-L1 cell were cultured. Confluent cells underwent starvation with SFM for 1 day and then were cultured in a medium containing various concentrations 0, 100, 200, and $400{\mu}mol/L$ of ${\alpha}$-lipoic acid. The cell viability was measured using the EZ Cytox assay kit. In addition, the effect of ${\alpha}$-lipoic acid of diluted solvents on the cell growth in 3T3-L1cells was examined according to the treated concentration and times. Results: The ${\alpha}$-lipoic acid diluted ethanol inhibited cell proliferation in a dose and time dependent manner. The ${\alpha}$-lipoic acid diluted ethanol induced adipocyte 3T3-L1 cells proliferation with an adipocyte inducer. In addition, ${\alpha}$-lipoic acid inhibited adipocyte 3T3-L1 growth in a dose and time dependent manner (p<0.05). Conclusion: This study showed that a treatment with ${\alpha}$-lipoic acid diluted ethanol inhibits cell growth of, adipocyte 3T3-L1 cells induced with an adipocyte inducer, ($200{\mu}mol/L$ of ${\alpha}$-lipoic acid) treated for 48 hr.

Nonlinear fluid-structure interaction of bridge deck: CFD analysis and semi-analytical modeling

  • Grinderslev, Christian;Lubek, Mikkel;Zhang, Zili
    • Wind and Structures
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    • v.27 no.6
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    • pp.381-397
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    • 2018
  • Nonlinear behavior in fluid-structure interaction (FSI) of bridge decks becomes increasingly significant for modern bridges with increasing spans, larger flexibility and new aerodynamic deck configurations. Better understanding of the nonlinear aeroelasticity of bridge decks and further development of reduced-order nonlinear models for the aeroelastic forces become necessary. In this paper, the amplitude-dependent and neutral angle dependent nonlinearities of the motion-induced loads are further highlighted by series of computational fluid dynamics (CFD) simulations. An effort has been made to investigate a semi-analytical time-domain model of the nonlinear motion induced loads on the deck, which enables nonlinear time domain simulations of the aeroelastic responses of the bridge deck. First, the computational schemes used here are validated through theoretically well-known cases. Then, static aerodynamic coefficients of the Great Belt East Bridge (GBEB) cross section are evaluated at various angles of attack, leading to the so-called nonlinear backbone curves. Flutter derivatives of the bridge are identified by CFD simulations using forced harmonic motion of the cross-section with various frequencies. By varying the amplitude of the forced motion, it is observed that the identified flutter derivatives are amplitude-dependent, especially for $A^*_2$ and $H^*_2$ parameters. Another nonlinear feature is observed from the change of hysteresis loop (between angle of attack and lift/moment) when the neutral angles of the cross-section are changed. Based on the CFD results, a semi-analytical time-domain model for describing the nonlinear motion-induced loads is proposed and calibrated. This model is based on accounting for the delay effect with respect to the nonlinear backbone curve and is established in the state-space form. Reasonable agreement between the results from the semi-analytical model and CFD demonstrates the potential application of the proposed model for nonlinear aeroelastic analysis of bridge decks.

Anti-oxidative Effect of Chungsimyeonja-um (CSYJE) via Nrf2/HO-1 Pathway Activity in Lipopolysaccharide (LPS) Induced RAW 264.7 Macrophages (대식세포에서 Nrf2/HO-1경로를 통한 청심연자음의 항산화효과)

  • Jeon, Seon Hong;Oh, Sol La;Kim, So Jeong;Jeon, Bo Hee;Sung, Jin Young;Kim, Yong Min
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.46 no.3
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    • pp.253-263
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    • 2020
  • Reactive oxygen species (ROS) plays an important role in maintaining homeostasis. However, excessive ROS production damages cellular components such as proteins, lipids, and nucleic acids and promotes skin aging. In this study, we confirmed the antioxidant effect of CSYJE to prevent excessive oxidative stress. First, DPPH and ABTS assays were performed to confirm the antioxidant effect of CSYJE and the radical scavenging activity was confirmed depending on the concentration. As a result of performing the MTT assay to confirm the cell viability, it was confirmed that there was no cytotoxicity at a concentration of 1,000 ㎍/mL. As a result of western blotting to confirm the expression levels of the antioxidant-related proteins nuclear-E2-related factor 2 (Nrf2) and Heme oxygenase-1 (HO-1), it was confirmed that the expression was increased in a concentration-dependent manner. After inducing ROS with lipopolysaccharide (LPS), an intracellular ROS-causing substance, DCF-DA was performed to confirm the inhibitory effect of ROS production, and the inhibition of ROS production was confirmed to concentration-dependent. Real-time RT-PCR was performed to confirm the mRNA expression level of inflammatory cytokines and inflammatory mediator caused by ROS generation, mRNA expression was reduced in a dose dependent manner. Therefore, this study confirmed the antioxidant effect of CSYJE through the Nrf2/HO-1 signaling pathway, which suggests that CSYJE can be used as an antioxidant cosmetic material by inhibiting free radicals.

Effects of Ginseng Radix Against Osteoblasts Damaged by Endocrine Disrupting Chemicals (환경호르몬에 의해 손상된 골모세포에 대한 인삼의 영향)

  • Hong Gi Youn;Park Seung Taeck;Jeon Byung Hun;Seo Eun A
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.16 no.2
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    • pp.338-342
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    • 2002
  • In order to evaluate the effect of Ginseng Radix(GR) against endocrine disrupting chemicals(EDC), cultured mouse osteoblasts were preincubated with various concentrations of GR extract before the exposure of Bisphenol A for 12 hours. Cytotoxic effect of Bisphenol A was measured by the XTT assay. In addition, the protective effect of GR over Bisphenol A-induced cytotoxicity on osteoblasts was assessed by the DNA and protein synthesis in these cultures. The results were as follows : Osteoblastic cell viability was decreased in dose and time dependent manner after exposed to various concentrations of Bisphenol A. Midcytotoxicity value(MCV50) of Bisphenol A was determined at 6μM Bisphenol A after osteoblasts were grown for 12 hours in the media containing various concentrations of Bisphenol A. Amount of DNA synthesis was increased in dose-dependent manner after cultured osteblasts were pretreated with GR for 2hrs before exposure to Bisphenol A for 12 hours. Amount of protein synthesis was increased in dose-dependent manner after cultured osteoblasts were pretreated with GR for 2 hours before exposure of Bisphenol A for 12 hours. From these results, it is suggested that Bisphenol A was highly toxic by the decrease of the cell viability, and GR is effective in the prevention of Bisphenol A-induced cytotoxicity by the increase of DNA and protein syntheses in cultured mouse osteoblasts.

Relaxation Effect of Synthetic Ceramide Analogues in Cat Esophageal Smooth Muscle Cells

  • Lee, Doo-Won;Park, Sun-Young;Ryu, Jung-Su;Kim, Sung-Hyo;Im, Chae-Uk;Choi, Su-Hang;Lee, Se-Eun;Ko, Sung-Kwon;Sohn, Uy-Dong
    • The Korean Journal of Physiology and Pharmacology
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    • v.12 no.4
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    • pp.137-142
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    • 2008
  • Ceramide has emerged as a novel second messenger for intracellular signalling. It is produced from sphingomyelin and is involved in the control of cell differntiation, proliferation, and apoptosis. $C_2$-ceramide, short chain ceramide, plays a role in mediating contraction of cat esophageal smooth muscle cells. We examined the effect of synthesized ceramide analogues on the $C_2$-ceramide and ACh-induced contraction in esophageal smooth muscle cells isolated with collagenase. CY3523, CY3525, or CY3723 inhibited $C_2$-ceramide induced contraction, in a time dependent manne. Each analogue also inhibited the contraction in concentration dependent manners. CY 3523, CY 3525, and CY 3723 had no effect to the contraction induced by PMA. The inhibition with CY3523, CY3525 and CY3723 on the $C_2$-ceramide induced contraction was recovered by PMA. These analogues decreased the density of MAPK bands (p44/42 or p38) in the western blot. These results suggest that ceramide analogues can inhibit $C_2$-ceramide induced contraction via PKC and MAPK dependent pathway.

Mori Fructus Induces Cell Death through ROS-dependent Mitochondrial Apoptotic Pathway in Human Glioma Cells

  • Jang, Sang-Won;Jeong, Ji-Cheon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.5
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    • pp.1322-1329
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    • 2008
  • Mulberry has been reported to contain wide range of polyphenols and have chemopreventive activity. However, little has been known regarding the effect of mulberry fruits on cell viability in human glioma cells. The present study was undertaken to examine the effect of mulberry fruit (Mar; Fructus) on cell viability and to determine its underlying mechanism in human glioma cells. Cell viability and cell death were estimated by MTT assay and trypanblue exclusion assay, respectively. Reactive oxygen species (ROS) generation was measured using the fluorescence probe DCFH-DA. The mitochondrial transmembrane potential was measured with $DiOC_6$(3). Bax expression and cytochrome c release were measured by Western blot analysis. Caspase activity was estimated using colorimetric kit. Mori Fructus resulted in apoptotic cell death in a dose- and time-dependent manner. Mori Fructus increased ROS generation and the Mori Fructus-induced cell death was also prevented by antioxidants, suggesting that ROS generation plays a critical role in Mari Fructus-induced cell death. Western blot analysis showed that Mori Fructus treatment caused an increase in Bax expression, which was inhibited by the antioxidant N-acetylcysteine (NAC). Mori Fructus induced depolarization of mitochondrial membrane potential and its effect was inhibited by the antioxidants NAC and catalase. Mori Fructus induced cytochrome c release, which was inhibited by NAC. Caspase activity was stimulated by Mori Fructus and caspase inhibitors prevented the Mori Fructus-induced cell death. These findings suggest that Mori Fructus results in human glioma cell death through ROS-dependent mitochondrial pathway in human glioma cells.