• Title/Summary/Keyword: mechanism of action

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PHARMACOLOGICAL EFFECTS OF NOVEL QUINOLINEDIONE COMPOUNDS ON INHIBITION OF DRUG-INDUCED RELAXATION OF RAT AORTA AND THEIR PUTATIVE ACTION MECHANISM

  • Lee, Jung-Ah;Ryu, Chung-Kyu;Chung, Jin-Ho;Kim, Hwa-Jung
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.05a
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    • pp.131-131
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    • 2001
  • Two 6-(fluorinated-phenylamino)-5, 8-quinolinedione derivatives, OQ21 and OQ1, were newly synthesized as potent inhibitors of endothelial-dependent vasorelaxation. The purpose of the present study was to investigate the effect of OQ21 and OQ1 on different types of vasorelaxation and to pursue their action mechanisms. (omitted)

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Anti-tumor activity and mitochondrial stability of disulfiram in HL-60 cells (HL-60세포에서 disulfiram의 항암작용과 미토콘드리아 안정성에 대한 연구)

  • Shin, Hyowon;Han, Yong;Joo, Hong-Gu
    • Korean Journal of Veterinary Research
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    • v.59 no.4
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    • pp.195-199
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    • 2019
  • Disulfiram (DSF) is a member of the dithiocarbamate family that can bind copper. Recent studies have shown that DSF has anti-cancer activities, but the mechanism has not been clarified. Therefore, it is important to study the action mechanism of DSF to maximize its anticancer effects. A human leukemia cell line, HL-60, was used in this study. HL-60 cells were treated with DSF and the cellular metabolic activity was measured. DSF increased the cell death of HL-60 cells in annexin V-fluorescein isothiocyanate/propidium iodide staining analysis. In addition, DSF decreased the mitochondrial membrane potential (MMP) of the HL-60 cells. The cytotoxicity of DSF on HL-60 cells was observed at 0.4 μM. Interestingly, the reduction of MMP by DSF was recovered by N-acetyl-L-cysteine, an inhibitor of reactive oxygen species (ROS) production. This suggests that the decrease in MMP by DSF is closely related to the production of ROS in HL-60 cells, which indicates the relationship between the apoptosis of HL-60 cells by DSF and the role of the mitochondria. This study provides clinicians and researchers with valuable information regarding the anti-cancer activity of DSF in terms of the action mechanism.

Inhibitory effects of artemether on collagen-induced platelet aggregation via regulation of phosphoprotein inducing PI3K/Akt and MAPK

  • Lee, Dong-Ha
    • Journal of Applied Biological Chemistry
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    • v.65 no.3
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    • pp.167-172
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    • 2022
  • Pathophysiological reaction of platelets in the blood vessel is an indispensable part of thrombosis and cardiovascular disease, which is the most common cause of death in the world. In this study, we performed in vitro assays to evaluate antiplatelet activity of artemether in human platelets and attempted to identify the mechanism responsible for protein phosphorylation. Artemether is a derivative of artemisinin, known as an active ingredient of Artemisia annua, which has been reported to be effective in treating malaria, and is known to function through antioxidant and metabolic enzyme inhibition. However, the role of artemether in platelet activation and aggregation and the mechanism of action of artemether in collagen-induced human platelets are not known until now. In this study, the effect of artesunate on collagen-induced human platelet aggregation was confirmed and the mechanism of action of artemether was clarified. Artemether inhibited the phosphorylation of PI3K/Akt and Mitogen-activated protein kinases, which are phosphoproteins that are known to act in the signal transduction process when platelets are activated. In addition, artemether decreased TXA2 production and decreased granule secretion in platelets such as ATP and serotonin release. As a result, artemether strongly inhibited platelet aggregation induced by collagen, a strong aggregation inducer secreted from vascular endothelial cells, with an IC50 of 157.92 μM. These results suggest that artemether has value as an effective antithrombotic agent for inhibiting the activation and aggregation of human platelets through vascular injury.

Suppression of Prostaglandin E2-Mediated Cell Proliferation and Signal Transduction by Resveratrol in Human Colon Cancer Cells

  • Song, Su-Hyun;Min, Hye-Young;Lee, Sang-Kook
    • Biomolecules & Therapeutics
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    • v.18 no.4
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    • pp.402-410
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    • 2010
  • Although the overproduction of prostaglandin $E_2$ ($PGE_2$) in intestinal epithelial cells has been considered to be highly correlated with the colorectal carcinogenesis, the precise mechanism of action remains poorly elucidated. Accumulating evidence suggests that the PGE receptor (EP)-mediated signal transduction pathway might play an important role in this process. In the present study, we investigated the mechanism of action underlying $PGE_2$-mediated cell proliferation and the effect of resveratrol on the proliferation of human colon cancer cells in terms of the modulating $PGE_2$-mediated signaling pathway. $PGE_2$ stimulated the proliferation of several human colon cancer cells and activated growth-stimulatory signal transduction, including Akt and ERK. $PGE_2$ also increased the phosphorylation of GSK-$3{\beta}$, the translocation of ${\beta}$-catenin into the nucleus, and the expressions of c-myc and cyclin D1. Resveratrol, a cancer chemopreventive phytochemical, however, inhibited $PGE_2$-induced growth stimulation and also suppressed $PGE_2$-mediated signal transduction, as well as ${\beta}$-catenin/T cell factor-mediated transcription in human colon cancer cells. These findings present an additional mechanism through which resveratrol affects the regulation of human colon cancer cell growth.

Pinacidil causes depresor action, catecholamine release and vasorelaxation in the normotensive rat

  • Lim, Dong-Yoon;Lee, Eun-Sook
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.87.2-88
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    • 2003
  • The present study was conducted to investigate the effects of pinacidil, a potassium channel opener, on arterial blood pressure, catecholamine release and vascular contractile responses in the normotensve rats and to establish the mechanism of action. Phenylephrine (an adrenergi $_1$-receptor agonist) and high potassium (a membrane- depolarizing agent) caused greatly contractile responses in the isolated aortic strips, respectively. These phenylephrine (10$\^$-5/ M)-induced contractile responses were dose-dependently depressed in the presence of pinacidil (25 ∼ 100 ${\mu}$M). (omitted)

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The influence of Guide Pads in the High Precision Cutting Process of Burnishing Drill (고정밀 가공을 위한 Bunishing Drill의 Guide Pad 영향)

  • 김종성
    • Proceedings of the Korean Society of Precision Engineering Conference
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    • 1996.04a
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    • pp.80-84
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    • 1996
  • The effects of guide pads on burnishing action and accuracy of machined hole are investigated in drilling with burnishing drill using a speciaaly designed tool experimentally. The cutting forces are balanced at the small forward regions of guide pads. The burnishing action takes place under a high contact pressure between the bore wall and those regions. The over size mechanism of machined hole by the guide pads is discussed.

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Spherical Particles Formation in Lubricated Sliding Contact -Micro-explosion due to the Thermally-activated Wear Process-

  • Kwon, O.K.
    • Tribology and Lubricants
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    • v.11 no.5
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    • pp.1-9
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    • 1995
  • The mechanism of various spherical particles formation from wide range of tribo-systerns is suggested and deduced by the action of micro-explosion on the basis of the thermally-activated wear theory, in which the flash temperature at contact could be reached clearly upto the material molten temperature due to the secondary activation energy from the exothermic reactions involving lubricant thermo-decomposition, metals oxidation, hydrogen reactions and other possible complex thermo-reactions at the contacts. Various shapes of spherical particles generated from the tribosystem can be explained by the toroidal action of micro-explosion accompanied with the complex thermo-chemical reactions at the contact surfaces or sub-surfaces.

Progressive Collapse of Steel High-Rise Buildings Exposed to Fire: Current State of Research

  • Jiang, Jian;Li, Guo-Qiang
    • International Journal of High-Rise Buildings
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    • v.7 no.4
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    • pp.375-387
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    • 2018
  • This paper presents a review on progressive collapse mechanism of steel framed buildings exposed to fire. The influence of load ratios, strength of structural members (beam, column, slab, connection), fire scenarios, bracing systems, fire protections on the collapse mode and collapse time of structures is comprehensively reviewed. It is found that the key influencing factors include load ratio, fire scenario, bracing layout and fire protection. The application of strong beams, high load ratios, multi-compartment fires will lead to global downward collapse which is undesirable. The catenary action in beams and tensile membrane action in slabs contribute to the enhancement of structural collapse resistance, leading to a ductile collapse mechanism. It is recommended to increase the reinforcement ratio in the sagging and hogging region of slabs to not only enhance the tensile membrane action in the slab, but to prevent the failure of beam-to-column connections. It is also found that a frame may collapse in the cooling phase of compartment fires or under travelling fires. This is because that the steel members may experience maximum temperatures and maximum displacements under these two fire scenarios. An edge bay fire is more prone to induce the collapse of structures than a central bay fire. The progressive collapse of buildings can be effectively prevented by using bracing systems and fire protections. A combination of horizontal and vertical bracing systems as well as increasing the strength and stiffness of bracing members is recommended to enhance the collapse resistance. A protected frame dose not collapse immediately after the local failure but experiences a relatively long withstanding period of at least 60 mins. It is suggested to use three-dimensional models for accurate predictions of whether, when and how a structure collapses under various fire scenarios.