• Title/Summary/Keyword: Cascade cycle

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Methanol Extracts of Codium fragile Induces Apoptosis through G1/S Cell Cycle Arrest in FaDu Human Hypopharynx Squamous Carcinoma Cells

  • Lee, Seul Ah;Park, Bo-Ram;Moon, Sung Min;Kim, Do Kyung;Kim, Chun Sung
    • International Journal of Oral Biology
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    • v.43 no.2
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    • pp.61-68
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    • 2018
  • Codium fragile (Suringar) Hariot is an edible green seaweed that belong to the Codiaceae family and has been used in Oriental medicine for the treatment of enterobiasis, dropsy, and dysuria. Methanol extract of codium fragile has anti-oxidant, anti-inflammatory and anti-cancer properties, although the anti-cancer effect on oral cancer has not yet been reported. In this study, we investigated the anti-cancer activity and the mechanism of cell death by methanol extracts of Codium fragile (MeCF) on human FaDu hypopharyngeal squamous carcinoma cells. Our data showed that MeCF inhibits cell viability in a dose-dependent manner, and markedly induced apoptosis, as determined by the MTT assay, Live/Dead assay, and DAPI stain. In addition, MeCF induced the proteolytic cleavage of procaspase -3, -7, -9 and poly(ADP-ribose) polymerase(PARP), and upregulated or downregulated the expression of mitochondrial-apoptosis factor, Bax(pro-apoptotic factor), and Bcl-2(anti-apoptotic factor). Futhermore, MeCF induced a cell cycle arrest at the G1/S phase through suppressing the expression of the cell cycle cascade proteins, p21, CDK4, CyclinD1, and phospho-Rb. Taken together, these results indicated that MeCF inhibits cell growth, and this inhibition is mediated by caspase- and mitochondrial-dependent apoptotic pathways through cell cycle arrest at the G1/S phase in human FaDu hypopharyngeal squamous carcinoma cells. Therefore, methanol extracts of Codium fragile can be provided as a novel chemotherapeutic drug due to its growth inhibition effects and induction of apoptosis in human oral cancer cells.

Kaempferol Activates G2-Checkpoint of the Cell Cycle Resulting in G2-Arrest and Mitochondria-Dependent Apoptosis in Human Acute Leukemia Jurkat T Cells

  • Kim, Ki Yun;Jang, Won Young;Lee, Ji Young;Jun, Do Youn;Ko, Jee Youn;Yun, Young Ho;Kim, Young Ho
    • Journal of Microbiology and Biotechnology
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    • v.26 no.2
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    • pp.287-294
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    • 2016
  • The effect of kaempferol (3,5,7,4-tetrahydroxyflavone), a flavonoid compound that was identified in barnyard millet (Echinochloa crus-galli var. frumentacea) grains, on G2-checkpoint and apoptotic pathways was investigated in human acute leukemia Jurkat T cell clones stably transfected with an empty vector (J/Neo) or a Bcl-xL expression vector (J/Bcl-xL). Exposure of J/Neo cells to kaempeferol caused cytotoxicity and activation of the ATM/ATR-Chk1/Chk2 pathway, activating the phosphorylation of p53 (Ser-15), inhibitory phosphorylation of Cdc25C (Ser-216), and inactivation of cyclin-dependent kinase 1 (Cdk1), with resultant G2-arrest of the cell cycle. Under these conditions, apoptotic events, including upregulation of Bak and PUMA levels, Bak activation, mitochondrial membrane potential (Δψm) loss, activation of caspase-9, -8, and -3, anti-poly (ADP-ribose) polymerase (PARP) cleavage, and accumulation of apoptotic sub-G1 cells, were induced without accompanying necrosis. However, these apoptotic events, except for upregulation of Bak and PUMA levels, were completely abrogated in J/Bcl-xL cells overexpressing Bcl-xL, suggesting that the G2-arrest and the Bcl-xL-sensitive mitochondrial apoptotic events were induced, in parallel, as downstream events of the DNA-damage-mediated G2-checkpoint activation. Together these results demonstrate that kaempferol-mediated antitumor activity toward Jurkat T cells was attributable to G2-checkpoint activation, which caused not only G2-arrest of the cell cycle but also activating phosphorylation of p53 (Ser-15) and subsequent induction of mitochondria-dependent apoptotic events, including Bak and PUMA upregulation, Bak activation, Δψm loss, and caspase cascade activation.

A Study on the High Efficiency Ground Source Heat Pump System (1) (부하추종형 고효율 지열히트펌프 시스템에 관한 연구 (1))

  • Koh, Deuk-Yong;Kim, Ook-Joong;Choi, Sang-Kyu;Chang, Ki-Chang
    • New & Renewable Energy
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    • v.1 no.4 s.4
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    • pp.30-37
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    • 2005
  • Cycle simulation of Ground Source Heat Pump[GSHP] system was carried out to determine the design specification of basic components such as turbo compressor and heat exchangers. Part load operation characteristics of the designed GSHP system was estimated using the compressor and heat exchanger performance data. A 50RT class turbo compressor for GSHP system is now under development, in which R134a refrigerant is adopted as working fluid. The compressor with variable cascade diffusers is designed to work both in cooling and heating modes so that it can actively keep up with the climate change with high efficiency. The normal running speeds of the compressor are 59000rpm for heating mode and 70000rpm for tooling mode respectively. It has two identical impellers at both ends of the rotor so as to minimize aero-induced thrust force effectively. GSHP system was coupled with a vortical type heat exchanger, and heat gain and heat loss from ground were evaluated per a bore hole. For the optimal integration of the heat pump system, its header for circulating fluid was combined with the ground heat exchangers in parallel and series configuration.

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Sliding Mode Control of Electric Booster System (전동 부스터의 슬라이딩 모드 제어)

  • Yang, I-Jin;Choi, Kyu-Woong;Huh, Kun-Soo
    • Journal of Institute of Control, Robotics and Systems
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    • v.18 no.6
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    • pp.519-525
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    • 2012
  • Electric brake booster systems replace conventional pneumatic brake boosters with electric motors and rotary-todisplacement mechanisms including ECU (Electronic Control Unit). Electric booster brake systems require precise target pressure tracking and control robustness because vehicle brake systems operate properly given the large range of loading and temperature, actuator saturation, load-dependent friction. Also for the implement of imbedded control system, the controller should be selected considering the limited memory size and the cycle time problem of real brake ECU. In this study, based on these requirements, a sliding mode controller has been chosen and applied considering both model uncertainty and external disturbance. A mathematical model for the electric booster is derived and simulated. The developed sliding mode controller considering chattering problem has been compared with a conventional cascade PID controller. The effectiveness of the controller is demonstrated in some braking cases.

Performance analysis of R404A refrigeration system using R744 as secondary refrigerant (R744를 2차냉매로 사용하는 R404A용 냉동시스템의 성능 분석)

  • Oh, H.K.;Son, C.H.
    • Journal of Power System Engineering
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    • v.16 no.2
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    • pp.24-29
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    • 2012
  • In this paper, an analysis on performance and exergy of R404A refrigeration system using R744 secondary refrigerant was performed numerically to optimize the design for the operating parameters. The operating parameters considered in this study include subcooling and superheating degree, internal heat exchanger and compression efficiency, evaporation and condensation temperature in the R404A refrigeration cycle and temperature difference of cascade heat exchanger. The main results are summarized as follows : The COP(coefficient of performance) of R404A refrigeration system increases with increasing evaporation temperature. The evaporation capacity of R744 as secondary refrigerant increases with the increase in evaporation pressure of R744 secondary refrigeration. And the enthalpy in the evaporator outlet of R744 increases with the increasing evaporation pressure of R744 secondary refrigeration. Therefore, it is important to analysis for the relationship between COP of R404A refrigeration system and refrigeration capacity of R744. As cascade evaporation temperature increase, the exergy loss of condenser and compressor using R404A is the largest among all components. Therefore, the exergy loss in the condenser and compressor using R404A must be decreased to enhance the COP of R404A refrigeration system with R744 secondary refrigerant.

Experimental Study of An Indirect-Refrigeration System with Carbon Dioxide (이산화탄소를 이용한 간접 냉장시스템의 실험적 연구)

  • Kim, Yoonsup;Baik, Wonkeun;Yun, Rin
    • Korean Journal of Air-Conditioning and Refrigeration Engineering
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    • v.28 no.5
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    • pp.202-207
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    • 2016
  • Experimental studies for an indirect R404A-$CO_2$ refrigeration system and a direct R404A refrigeration system were conducted. The configurations of the indirect R404A-$CO_2$ refrigeration system are a R404A refrigeration system as a top cycle and a circulating $CO_2$ system as a bottom cycle. The direct R404A system was modified from indirect R404A-$CO_2$ refrigeration system by removing circuit for $CO_2$ circulation. Various tests for both systems were conducted by changing load side brine temperature from 0 to 5 and $10^{\circ}C$ with cooling brine temperatures for R404A system at 15, 20, or $25^{\circ}C$. The indirect R404A-$CO_2$ refrigeration system showed the highest COP when load side brine temperature was at $10^{\circ}C$ in the evaporator and at cooling brine temperature of $15^{\circ}C$. The COP of 3.04 under that condition was the highest. This indirect R404A-$CO_2$ refrigeration system showed 9.02% higher COP than the direct R404A system that had increased pipeline length of 15 m, which simulated actual installation in a supermarket.

S-benzyl-cysteine-mediated Cell Cycle Arrest and Apoptosis Involving Activation of Mitochondrial-dependent Caspase Cascade through the p53 Pathway in Human Gastric Cancer SGC-7901 Cells

  • Sun, Hua-Jun;Meng, Lin-Yi;Shen, Yang;Zhu, Yi-Zhun;Liu, Hong-Rui
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6379-6384
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    • 2013
  • S-benzyl-cysteine (SBC) is a structural analog of S-allylcysteine (SAC), which is one of the major water-soluble compounds in aged garlic extract. In this study, anticancer activities and the underlying mechanisms of SBC action were investigated and compared these with those of SAC using human gastric cancer SGC-7901 cells. SBC significantly suppressed the survival rate of SGC-7901 cells in a concentration- and time-dependent manner, and the inhibitory activities of SBC were stronger than those of SAC. Flow cytometry revealed that SBC induced G2-phase arrest and apoptosis in SGC-7901 cells. Typical apoptotic morphological changes were observed by Hoechst 33258 dye assay. SBC-treatment dramatically induced the dissipation of mitochondrial membrane potential (${\Delta}{\Psi}m$), and enhanced the enzymatic activities of caspase-9 and caspase-3 whilst hardly affecting caspase-8 activity. Furthermore, Western blotting indicated that SBC-induced apoptosis was accompanied by up-regulation of the expression of p53, Bax and the down-regulation of Bcl-2. Taken together, this study suggested that SBC exerts cytotoxic activity involving activation of mitochondrial-dependent apoptosis through p53 and Bax/Bcl-2 pathways in human gastric cancer SGC-7901 cells.

Relative Apoptosis-inducing Potential of Homeopathic Condurango 6C and 30C in H460 Lung Cancer Cells In vitro -Apoptosis-induction by homeopathic Condurango in H460 cells-

  • Sikdar, Sourav;Saha, Santu Kumar;Khuda-Bukhsh, Anisur Rahman
    • Journal of Pharmacopuncture
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    • v.17 no.1
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    • pp.59-69
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    • 2014
  • Objectives: In homeopathy, it is claimed that more homeopathically-diluted potencies render more protective/curative effects against any disease condition. Potentized forms of Condurango are used successfully to treat digestive problems, as well as esophageal and stomach cancers. However, the comparative efficacies of Condurango 6C and 30C, one diluted below and one above Avogadro's limit (lacking original drug molecule), respectively, have not been critically analyzed for their cell-killing (apoptosis) efficacy against lung cancer cells in vitro, and signalling cascades have not been studied. Hence, the present study was undertaken. Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were conducted on H460-non-small-cell lung cancer (NSCLC) cells by using a succussed ethyl alcohol vehicle (placebo) as a control. Studies on cellular morphology, cell cycle regulation, generation of reactive oxygen species (ROS), changes in mitochondrial membrane potential (MMP), and DNA-damage were made, and expressions of related signaling markers were studied. The observations were done in a "blinded" manner. Results: Both Condurango 6C and 30C induced apoptosis via cell cycle arrest at subG0/G1 and altered expressions of certain apoptotic markers significantly in H460 cells. The drugs induced oxidative stress through ROS elevation and MMP depolarization at 18-24 hours. These events presumably activated a caspase-3-mediated signalling cascade, as evidenced by reverse transcriptase-polymerase chain reaction (RT-PCR), western blot and immunofluorescence studies at a late phase (48 hours) in which cells were pushed towards apoptosis. Conclusion: Condurango 30C had greater apoptotic effect than Condurango 6C as claimed in the homeopathic doctrine.

The roles of FADD in extrinsic apoptosis and necroptosis

  • Lee, Eun-Woo;Seo, Jin-Ho;Jeong, Man-Hyung;Lee, Sang-Sik;Song, Jae-Whan
    • BMB Reports
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    • v.45 no.9
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    • pp.496-508
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    • 2012
  • Fas-associated protein with death domain (FADD), an adaptor that bridges death receptor signaling to the caspase cascade, is indispensible for the induction of extrinsic apoptotic cell death. Interest in the non-apoptotic function of FADD has greatly increased due to evidence that FADD-deficient mice or dominant-negative FADD transgenic mice result in embryonic lethality and an immune defect without showing apoptotic features. Numerous studies have suggested that FADD regulates cell cycle progression, proliferation, and autophagy, affecting these phenomena. Recently, programmed necrosis, also called necroptosis, was shown to be a key mechanism that induces embryonic lethality and an immune defect. Supporting these findings, FADD was shown to be involved in various necroptosis models. In this review, we summarize the mechanism of extrinsic apoptosis and necroptosis, and discuss the in vivo and in vitro roles of FADD in necroptosis induced by various stimuli.

Comparative Studies on the Growth and Differentiation in Three Different Varieties of Hop (Hop의 생장과 분화에 대한 식품간의 차이에 관하여)

  • 임웅규
    • Journal of Plant Biology
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    • v.17 no.4
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    • pp.11-17
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    • 1974
  • The present investigation dealt with observation and experiments concerning the growth and differentiation of hop plant, using the varieties of Cascade(C), Shinshuwase(Sh), and Hallertau(H). The results were as follows: (1) Life cycle of hop plants. The annual growth period of hop plant was devided chiefly into 3 phases, dormant, vegetative and reproductive. (2) Growth of main stem. The hop vine begun to grow in the middle of May and grow vigorousely in the middle and latter of June, then gradually decline or stops at the middle of July and the early of August. (3) Growth of lateral vines. By the statistical analysis, it is judged that the varieties of H and Sh were more grown than that of C. H and Sh were not significant, but H and Sh from C were significant in 5% level. (4) Fresh weight and water content of hop cone. Hop cone in fresh weight of C variety was higher than those of other two varieties and water content of hop cone was decreased with time elapse in three races together. (5) Growing point. Histological view of hop varities in each was different. C showed form of sweet potato, H showed form of round, and Sh showed form of ellipse. (6) Shape of the leaf. C and H were 3 lobes, but Sh is 3∼5 lobes. Generally, the color is dark green. (7) Hop cones. Hop cones are as follows.

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