• 제목/요약/키워드: cascade effect

검색결과 260건 처리시간 0.031초

Cytosine Arabinoside 유도된 PC12 세포의 사망 경로 (Cytosine Arabinoside-Induced PC12 Cell Death Pathway)

  • 양보기;양병환;채영규
    • 생물정신의학
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    • 제5권2호
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    • pp.219-226
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    • 1998
  • Cytosine arabinoside(AraC) inhibits DNA synthesis and ${\beta}$-DNA polymerase, an enzyme involved in DNA repair. This, a potent antimitotic agent, is clinically used as an anticancer drug with side effect of severe neurotoxicity. Earlier reports suggested that inhibition of neuronal survival by AraC in sympathetic neuron may be due to the inhibition of a 2'-deoxycytidine-dependent process that is independent of DNA synthesis or repair and AraC induced a signal that is triggers a cascade of new mRNA and protein synthesis, leading to apoptotic cell death in cultured cerebellar granule cells. The present study would suggest whether caspase family(ICE/CED-3-like protease) involved in AraC-induced apoptosis pathway of PC12 cells. It was observed that treatment of PC12 cells with AraC led to decrease of viability by MTT assay and morphology changes, which did not suggest that AraC induced apoptosis in PC12 cells. The mRNA of caspase-1/caspase-3 were expressed in PC12 cells constitutively, and AraC did not activate caspase family. These results suggest that caspase-1/caspase-3 may not be required for AraC-induced cell death pathway in PC12 cells.

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Anticoagulant activities of oleanolic acid via inhibition of tissue factor expressions

  • Lee, Won-Hwa;Yang, Eun-Ju;Ku, Sae-Kwang;Song, Kyung-Sik;Bae, Jong-Sup
    • BMB Reports
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    • 제45권7호
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    • pp.390-395
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    • 2012
  • Oleanolic acid (OA), a triterpenoid known for its anti-inflammatory and anti-cancer properties, is commonly present in several medicinal plants but its anticoagulant activities have not been studied. Here, the anticoagulant properties of OA were determined by monitoring activated partial thromboplastin time (aPTT), prothrombin time (PT), fibrin polymerization as well as cell-based thrombin and activated factor X (FXa) generation activities. Data showed OA prolonged aPTT and PT significantly and inhibited thrombin catalyzed fibrin polymerization. In addition, OA inhibited the activities of thrombin and FXa and inhibited the generation of thrombin or FXa in human endothelial cells. OA also inhibited TNF-${\alpha}$-induced tissue factor expression on human endothelial cells. In accordance with these anticoagulant activities, OA showed an anticoagulant effect in vivo. These results indicate that OA possesses antithrombotic activities and suggest that daily consumption of a herb containing OA may be preventing thrombosis in pathological states.

유한요소 LES법에 의한 축류 회전차 팁 틈새의 유동해석 (Flow Analysis in the Tip Clearance of Axial Flow Rotor Using Finite-Element Large-Eddy Simulation Method)

  • 이명호
    • Journal of Advanced Marine Engineering and Technology
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    • 제33권5호
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    • pp.686-695
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    • 2009
  • Flow characteristics in linear axial cascade have been studied using large eddy simulation(LES) based on finite element method(FEM) to investigate details of the leakage flow in the tip clearance of axial flow rotor. STAR-CD(FVM) and PAT-Flow(FEM) have been adopted to solve the Navier-Stokes equations for the simulation of the unsteady turbulent flow. Numerical results from the present study have been compared with the existing experimental results to investigate a tip clearance effect on velocity profile and static pressure distribution on blade surface at various spanwise positions. Both simulation results agree well with the experimental data. However, it has been shown that the results of finite-element large-eddy simulation agree better with experimental data than $k-{\varepsilon}$ turbulent model based on finite volume method regarding the tip vortex geometry and static pressure distribution at the center of the tip vortex core. As a result of this study, it is shown that finite-element large-eddy simulation method can predict more exactly on the tip leakage vortex flow and behind flow field.

Taurine Activates ERK2 and Induces the Production of Nitric Oxide in Osteoblast-like UMR-106 Cells

  • Park, Sung-Youn;Kim, Harriet;Kim, Sung-Jin
    • 한국응용약물학회:학술대회논문집
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    • 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
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    • pp.145-145
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    • 1998
  • In the present study, we have demonstrated that taurine could stimulate the production of nitric oxide and the activity of ERK2 (extracellular signal regulated protein kinase or pp42 MAP kinase). Nitric oxide(NO), the product of inducible nitric oxide synthase(iNOS), is known to be implicated in the metabolism of bone. ERK cascade plays a key role in the gene expression of iNOS in osteoblastic cell. We investigated whether taurine (l-20mM) could stimulate ERK2 activity, nitric oxide production, and inducible nitric oxide synthase in osteoblast-like UMR-106 cells. Nitric oxide was measured spectophotometrically as nitrite and the activation of ERK2 and iNOS was studied using Western 145 blot analysis. Taurine increased the production of nitric oxide in a dose-dependent manner and the effect was reached to a maximum at 10 mM. The activation of iNOS were consistent with NO levels. The tyrosine phosphorylation of ERK2 was increased by taurine in a time-dependent manner. The these result suggest that taurine might stimulate the production of nitric oxide in osteoblast-like cells by the activation of ERK2 and could regulate the metabolism of bone via nitric oxide.

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Differential Gene Expression Profiling in Human Promyelocytic Leukemia Cells Treated with Benzene and Ethylbenzene

  • Sarma, Sailendra Nath;Kim, Youn-Jung;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
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    • 제4권4호
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    • pp.267-277
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    • 2008
  • Benzene and ethylbenzene (BE), the volatile organic compounds (VOCs) are common constituents of cleaning and degreasing agents, paints, pesticides, personal care products, gasoline and solvents. VOCs are evaporated at room temperature and most of them exhibit acute and chronic toxicity to human. Chronic exposure of benzene is responsible for myeloid leukemia and also ethylbenzene is also recognized as a possible carcinogen. To evaluate the BE effect on human, whole human genome 35 K oligonucleotide microarray were screened for the identification of the differential expression profiling. We identified 280 up-regulated and 201 down-regulated genes changed by more than 1.5 fold by BE exposure. Functional analysis was carried out by using DAVID bioinformatics software. Clustering of these differentially expressed genes were associated with immune response, cytokine-cytokine receptor interaction, toll-like signaling pathway, small cell lung cancer, immune response, apoptosis, p53 signaling pathway and MAPKKK cascade possibly constituting alternative or subordinate pathways of hematotoxicity and immune toxicity. Gene ontology analysis methods including biological process, cellular components, molecular function and KEGG pathway thus provide a fundamental basis of the molecular pathways through BEs exposure in human lymphoma cells. This may provides a valuable information to do further analysis to explore the mechanism of BE induced hematotoxicity.

A Study on the Effect of Inlet Boundary Condition on Flow Characteristics of a Supersonic Turbine

  • Shin, Bong-Gun;Kim, Kui-Soon;Kim, Jin-Han
    • International Journal of Aeronautical and Space Sciences
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    • 제6권1호
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    • pp.1-7
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    • 2005
  • The inlet boundary condition of computations about the supersonic turbine flow is commonly applied as far-field inlet boundary condition with specified velocity. However, the inflow condition of supersonic turbine is sometimes affected by the shocks or expansion waves propagated from leading edges of blade. These shocks and expansion waves alter the inlet boundary condition. In this case, the inlet boundary condition can not be specified Therefore, in this paper, numerical analyses for three different inlet conditions - fa-field inlet boundary condition, inlet boundary condition with a linear nozzle and inlet boundary condition with a converging-diverging nozzle - have been performed and compared with experimental results to solve the problem. It is found that the inlet condition with a linear nozzle or a converging-diverging nozzle can prevent changing of inlet boundary condition, and thus predict more accurately the supersonic flow within turbine cascade than a far-field inlet boundary condition does.

선저에 부착된 공기공동에 의한 선박의 저항감소에 관한 연구 (On the Reduction of a Ship Resistance by Attaching an Air Cavity to Its Flat Bottom)

  • 장진호;김효철
    • 대한조선학회논문집
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    • 제36권2호
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    • pp.1-8
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    • 1999
  • 선저에 부착된 공기공동에 의한 실용 선박의 저항감소 효과를 조사하기 위하여 예인수조에서 충주호 유람선에 대한 저항실험을 수행하였다. 여러 가지 형상의 공기공급 노즐에 대해서 선저에 부착된 공기공동의 관측과 저항 계측이 수행되었으며 이로부터 적절한 공기공급 노즐의 형상을 결정하였다. 선박의 빌지부 근처에서의 공기누출을 억제하기 위하여 선박의 길이방향으로 공기유출막이 스트립을 공기공급 노즐의 양 측면에 부착하였다. 또한 두 개의 공기공급 노즐을 설치하여 두 개의 공기공동을 연속하여 발생시킬 수 있었으며 이로부터 더욱 큰 저항감소 효과를 얻을 수 있었다. 효율 측면에서는 공기공급에 필요한 에너지를 고려하더라도 설계속도에서 10% 이상의 에너지절감 효과를 얻을 수 있었다.

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Autophagy Inhibition Promotes Quercetin Induced Apoptosis in MG-63 Human Osteosarcoma cells

  • Park, Sung-Jin;Yu, Su-Bin;Kim, Yong-Ho;Kim, In-Ryoung;Park, Hae-Ryoun;Park, Bong-Soo
    • International Journal of Oral Biology
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    • 제40권2호
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    • pp.85-91
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    • 2015
  • Quercetin is a natural flavonoid phytochemical that is extracted from various plants. Having an advantages due to its varied biological properties, such as anti-inflammatory, anti-viral, anti-oxidant, and anti-cancer effects, quercetin is used to treat many diseases. Recently, it has been reported that autophagy inhibition may play a key role in anti-cancer therapy. Therefore, in this study, we investigated the molecular mechanisms and anti-cancer effects of quercetin in human osteosarcoma cells via autophagy inhibition. We ascertained that quercetin inhibited cell proliferation and induced cell death, these process is demonstrated that apoptosis via the mitochondrial pathway and the caspase cascade. Quercetin also induced autophagy which was inhibited by 3-MA, autophagy inhibitor and the blockade of autophagy promoted the quercetin-induced apoptosis, confirming that autophagy is a pro-survival process. Thus, these findings demonstrate that quercetin is an effective anti-cancer agent, and the combination of quercetin and an autophagy inhibitor should enhance the effect of anti-cancer therapy.

Flos magnoliae constituent fargesin has an anti-allergic effect via ORAI1 channel inhibition

  • Hong, Phan Thi Lam;Kim, Hyun Jong;Kim, Woo Kyung;Nam, Joo Hyun
    • The Korean Journal of Physiology and Pharmacology
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    • 제25권3호
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    • pp.251-258
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    • 2021
  • Flos magnoliae (FM), the dry flower buds of Magnolia officinalis or its related species, is a traditional herbal medicine commonly used in Asia for symptomatic relief of and treating allergic rhinitis, headache, and sinusitis. Although several studies have reported the effects of FM on store-operated calcium entry (SOCE) via the ORAI1 channel, which is essential during intracellular calcium signaling cascade generation for T cell activation and mast cell degranulation, the effects of its isolated constituents on SOCE remain unidentified. Therefore, we investigated which of the five major constituents of 30% ethanoic FM (vanillic acid, tiliroside, eudesmin, magnolin, and fargesin) inhibit SOCE and their physiological effects on immune cells. The conventional whole-cell patch clamp results showed that fargesin, magnolin, and eudesmin significantly inhibited SOCE and thus human primary CD4+ T lymphocyte proliferation, as well as allergen-induced histamine release in mast cells. Among them, fargesin demonstrated the most potent inhibitory effects not only on ORAI1 (IC50 = 12.46 ± 1.300 μM) but also on T-cell proliferation (by 87.74% ± 1.835%) and mast cell degranulation (by 20.11% ± 5.366%) at 100 μM. Our findings suggest that fargesin can be a promising candidate for the development of therapeutic drugs to treat allergic diseases.

Variation in wind load and flow of a low-rise building during progressive damage scenario

  • Elshaer, Ahmed;Bitsuamlak, Girma;Abdallah, Hadil
    • Wind and Structures
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    • 제28권6호
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    • pp.389-404
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    • 2019
  • In coastal regions, it is common to witness significant damages on low-rise buildings caused by hurricanes and other extreme wind events. These damages start at high pressure zones or weak building components, and then cascade to other building parts. The state-of-the-art in experimental and numerical aerodynamic load evaluation is to assume buildings with intact envelopes where wind acts only on the external walls and correct for internal pressure through separate aerodynamic studies. This approach fails to explain the effect of openings on (i) the external pressure, (ii) internal partition walls; and (iii) the load sharing between internal and external walls. During extreme events, non-structural components (e.g., windows, doors or rooftiles) could fail allowing the wind flow to enter the building, which can subject the internal walls to lateral loads that potentially can exceed their load capacities. Internal walls are typically designed for lower capacities compared to external walls. In the present work, an anticipated damage development scenario is modelled for a four-story building with a stepped gable roof. LES is used to examine the change in the internal and external wind flows for different level of assumed damages (starting from an intact building up to a case with failure in most windows and doors are observed). This study demonstrates that damages in non-structural components can increase the wind risk on the structural elements due to changes in the loading patterns. It also highlights the load sharing mechanisms in low rise buildings.