• Title/Summary/Keyword: time-dependent effect

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Experimental Studies on the Effect of Gamibaegi-eum

  • Kim Won-Ill
    • The Journal of Korean Medicine
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    • v.25 no.4
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    • pp.61-78
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    • 2004
  • Objective : This study was undertaken to determine whether Gamibaegi-eum (BGU) in vitro and in vivo exerts a beneficial effect against cell injury induced by reactive oxygen species (ROS) in the human intestine. Methods : Effects of BGU in vitro on cell injury were examined using Caco-2 cells, cultured human intestinal cell line. Exposure of cells to H₂O₂ induced increases in the loss of cell viability in a time and dose-dependent fashion. Results : BGU prevented H₂O₂-induced cell death and its effect was dose-dependent over a concentration range of 0.05­1%. H₂O₂-induced cell death was prevented by catalase, the hydrogen peroxide scavenger enzyme, and deferoxamine, the iron chelator. However, the potent antioxidant DPPD did not affect H₂O₂-induced cell death. H₂O₂ increased lipid peroxidation, which was inhibited by BGU and DPPD. H₂O₂ caused DNA damage in a dose-dependent manner, which was prevented by BGU, catalase, and deferoxamine, but not DPPD. BGU restored ATP depletion induced by H₂O₂. BGU inhibited generation of superoxide and H₂O₂ and scavenged directly H₂O₂. Oral administration of mepirizole in vivo at a dose of 200mg/kg resulted in ulcer lesions in the stomach and the proximal duodenum. Pretreatment of BGU(0.1%/kg, orally) and catalase (800Units/kg, i.v.) significantly decreased the size of ulcers. Mepirizole increased lipid peroxidation in the mucosa of the duodenum, suggesting an involvement of ROS. Pretreatment of BGU and catalase significantly inhibited lipid peroxidation induced by mepirizole. Morphological studies showed that mepirizole treatment causes duodenal injury and its effect is prevented by BGU. Conclusion : These results indicate that BGU exerts a protective effect against cell injury in vitro and in vivo through antioxidant action. The present study suggests that BGU may playa therapeutic role in the treatment of human gastrointestinal diseases mediated by ROS.

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The Effect of Partial Response Signaling Pulses under Wireless Communication Environments

  • Park, Won-Ho;Kong, Hyung-Yun
    • Proceedings of the IEEK Conference
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    • 1999.06a
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    • pp.57-60
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    • 1999
  • In many radio communication environments, there is a special component, called inter-symbol interference (ISI), mused by multipath time delay of signal and ISI components impose limitation of the data transmission rate. In this paper, we consider signaling pulse shapes, called partial response signaling (PRS), for minimizing the effect of ISI and show the improvement of performance by applying one of the partial-response signaling (PRS) pulses to two types of receiver system under dependent noise environments through the Monte-Carlo computer simulations.

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In vivo anti-metastatic action of Ginseng Saponins is based on their intestinal bacterial metabolites after oral administration

  • Saiki, Ikuo
    • Journal of Ginseng Research
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    • v.31 no.1
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    • pp.1-13
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    • 2007
  • We found that the main bacterial metabolite M1 is an active component of orally administered protopanxadiol-type ginsenosides, and that the anti-metastatic effect by oral administration of ginsenosides may be primarily mediated through the inhibition of tumor invasion, migration and growth of tumor cells by their metabolite M1. Pharmacokinetic study after oral administration of ginsenoside Rb1 revealed that M1 was detected in serum for 24 h by HPLC analysis but Rb1 was not detected. M1, with anti-metastatic property, inhibited the proliferation of murine and human tumor cells in a time- and concentration-dependent manner in vitro, and also induced apoptotic cell death (the ladder fragmentation of the extracted DNA). The induction of apoptosis by M1 involved the up-regulation of the cyclin-dependent kinase(CDK) inhibitor $p27^{Kip1}$ as well as the down-regulation of a proto-oncogene product c-Myc and cyclin D1 in a time-dependent manner. Thus, M1 might cause the cell-cycle arrest (G1 phase arrest) in honor cells through the up/down-regulation of these cell-growth related molecules, and consequently induce apoptosis. The nucleosomal distribution of fluorescence-labeled M1 suggests that the modification of these molecules is induced by transcriptional regulation. Tumor-induced angiogenesis (neovascularization) is one of the most important events concerning tumor growth and metastasis. Neovascularization toward and into tumor is a crucial step for the delivery of nutrition and oxygen to tumors, and also functions as the metastatic pathway to distant organs. M1 inhibited the tube-like formation of hepatic sinusoidal endothelial (HSE) cells induced by the conditioned medium of colon 26-L5 cells in a concentration-dependent manner. However, M1 at the concentrations used in this study did not affect the growth of HSE cells in vitro.

Open channel block of Kv1.4 potassium channels by aripiprazole

  • Park, Jeaneun;Cho, Kwang-Hyun;Lee, Hong Joon;Choi, Jin-Sung;Rhie, Duck-Joo
    • The Korean Journal of Physiology and Pharmacology
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    • v.24 no.6
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    • pp.545-553
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    • 2020
  • Aripiprazole is a quinolinone derivative approved as an atypical antipsychotic drug for the treatment of schizophrenia and bipolar disorder. It acts as with partial agonist activities at the dopamine D2 receptors. Although it is known to be relatively safe for patients with cardiac ailments, less is known about the effect of aripiprazole on voltage-gated ion channels such as transient A-type K+ channels, which are important for the repolarization of cardiac and neuronal action potentials. Here, we investigated the effects of aripiprazole on Kv1.4 currents expressed in HEK293 cells using a whole-cell patch-clamp technique. Aripiprazole blocked Kv1.4 channels in a concentration-dependent manner with an IC50 value of 4.4 μM and a Hill coefficient of 2.5. Aripiprazole also accelerated the activation (time-to-peak) and inactivation kinetics. Aripiprazole induced a voltage-dependent (δ = 0.17) inhibition, which was use-dependent with successive pulses on Kv1.4 currents without altering the time course of recovery from inactivation. Dehydroaripiprazole, an active metabolite of aripiprazole, inhibited Kv1.4 with an IC50 value of 6.3 μM (p < 0.05 compared with aripiprazole) with a Hill coefficient of 2.0. Furthermore, aripiprazole inhibited Kv4.3 currents to a similar extent in a concentration-dependent manner with an IC50 value of 4.9 μM and a Hill coefficient of 2.3. Thus, our results indicate that aripiprazole blocked Kv1.4 by preferentially binding to the open state of the channels.

Effects of Gamma-irradiation on Anti-diabetic and Cytotoxic Activities of Heat-treated Mistletoe (Viscum album) (감마선 조사가 열처리 겨우살이의 항당뇨 및 세포독성에 미치는 영향)

  • Park, Jong-Heum;Kim, Su-Min;Sung, Nak-Yun;Song, Du-Sup;Byun, Eui-Baek;Kim, Jae-Kyung;Song, Beom-Seok;Lee, Ju-Woon;Kim, Jae-Hun
    • Journal of Radiation Industry
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    • v.7 no.2_3
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    • pp.183-190
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    • 2013
  • Mistletoe (Viscum album) has been widely used as a functional food material for various therapeutic purposes from ancient time. In this study, we examined anti-diabetic and cytotoxic activities of heated-treated mistletoe and the effects of gamma-irradiation on its activities. Heat-treated mistletoe extract was prepared by heating during different time (3, 6, 9 and 12 h) and gamma-irradiated with different doses of 0, 10, 30, 50, 70 and 100 kGy. Heat-treated mistletoe extracts showed a concentration-dependent cytotoxicity on rat insulinoma RINm5F cells and the effect was gradually decreased as heating time increased up to 12 h. 12 h heat-treated extract was no cytotoxic. Gamma-irradiation enhanced the reduction of heat-treated mistletoe-induced cytotoxicity and the decreasing effect was an irradiating dose-dependent. In particular, all of 70 kGy irradiated and heat-treated mistletoe extracts did not showed the cytotoxicity and the effect was comparable to 12 h heat-treated mistletoe extract. Among those extracts, 3 h heat-treated mistletoe extract gradually increased the insulin secreting activity by gamma-irradiation and the effect was the best at 70 kGy, whereas 12 heat-treated extract was no effect. On the test of ${\alpha}$-glucosidase inhibitory activity, 3 h heat-treated mistletoe extract showed the concentration dependent effects and gamma-irradiation induced more activity at 70 kGy, compared to non-irradiated 3 h and 12 h heated mistletoe extracts. These results suggest that the combination of heat treatment and gamma-irradiation might be more effective than only heat-treatment for improving the anti-diabetic activity of mistletoe extract and reducing its cytotoxicity.

Panduratin A Inhibits Cell Proliferation by Inducing G0/G1 Phase Cell Cycle Arrest and Induces Apoptosis in Breast Cancer Cells

  • Liu, Qiuming;Cao, Yali;Zhou, Ping;Gui, Shimin;Wu, Xiaobo;Xia, Yong;Tu, Jianhong
    • Biomolecules & Therapeutics
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    • v.26 no.3
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    • pp.328-334
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    • 2018
  • Because of the unsatisfactory treatment options for breast cancer (BC), there is a need to develop novel therapeutic approaches for this malignancy. One such strategy is chemotherapy using non-toxic dietary substances and botanical products. Studies have shown that Panduratin A (PA) possesses many health benefits, including anti-inflammatory, anti-bacterial, anti-oxidant and anticancer activities. In the present study, we provide evidence that PA treatment of MCF-7 BC cells resulted in a time- and dose-dependent inhibition of cell growth with an $IC_{50}$ of $15{\mu}M$ and no to little effect on normal human MCF-10A breast cells. To define the mechanism of these anti-proliferative effects of PA, we determined its effect critical molecular events known to regulate the cell cycle and apoptotic machinery. Immunofluorescence and flow cytometric analysis of Annexin V-FITC staining provided evidence for the induction of apoptosis. PA treatment of BC cells resulted in increased activity/expression of mitochondrial cytochrome C, caspases 7, 8 and 9 with a significant increase in the Bax:Bcl-2 ratio, suggesting the involvement of a mitochondrial-dependent apoptotic pathway. Furthermore, cell cycle analysis using flow cytometry showed that PA treatment of cells resulted in G0/G1 arrest in a dose-dependent manner. Immunoblot analysis data revealed that, in MCF-7 cell lines, PA treatment resulted in the dose-dependent (i) induction of $p21^{WAF1/Cip1}$ and p27Kip1, (ii) downregulation of Cyclin dependent kinase (CDK) 4 and (iii) decrease in cyclin D1. These findings suggest that PA may be an effective therapeutic agent against BC.

Numerical study on the rate-dependent behavior of geogrid reinforced sand retaining walls

  • Li, Fulin;Ma, Tianran;Yang, Yugui
    • Geomechanics and Engineering
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    • v.25 no.3
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    • pp.195-205
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    • 2021
  • Time effect on the deformation and strength characteristics of geogrid reinforced sand retaining wall has become an important issue in geotechnical and transportation engineering. Three physical model tests on geogrid reinforced sand retaining walls performed under various loading conditions were simulated to study their rate-dependent behaviors, using the presented nonlinear finite element method (FEM) analysis procedure. This FEM was based on the dynamic relaxation method and return mapping scheme, in which the combined effects of the rate-dependent behaviors of both the backfill soil and the geosynthetic reinforcement have been included. The rate-dependent behaviors of sands and geogrids should be attributed to the viscous property of materials, which can be described by the unified three-component elasto-viscoplastic constitutive model. By comparing the FEM simulations and the test results, it can be found that the present FEM was able to be successfully extended to the boundary value problems of geosynthetic reinforced soil retaining walls. The deformation and strength characteristics of the geogrid reinforced sand retaining walls can be well reproduced. Loading rate effect, the trends of jump in footing pressure upon the step-changes in the loading rate, occurred not only on sands and geogrids but also on geogrid reinforced sands retaining walls. The lateral earth pressure distributions against the back of retaining wall, the local tensile force in the geogrid arranged in the retaining wall and the local stresses beneath the footing under various loading conditions can also be predicted well in the FEM simulations.

Thermal loading effects on electro-mechanical vibration behavior of piezoelectrically actuated inhomogeneous size-dependent Timoshenko nanobeams

  • Ebrahimi, Farzad;Salari, Erfan
    • Advances in nano research
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    • v.4 no.3
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    • pp.197-228
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    • 2016
  • In the present study, thermo-electro-mechanical vibration characteristics of functionally graded piezoelectric (FGP) Timoshenko nanobeams subjected to in-plane thermal loads and applied electric voltage are carried out by presenting a Navier type solution for the first time. Three kinds of thermal loading, namely, uniform, linear and non-linear temperature rises through the thickness direction are considered. Thermo-electro-mechanical properties of FGP nanobeam are supposed to vary smoothly and continuously throughout the thickness based on power-law model. Eringen's nonlocal elasticity theory is exploited to describe the size dependency of nanobeam. Using Hamilton's principle, the nonlocal equations of motion together with corresponding boundary conditions based on Timoshenko beam theory are obtained for the free vibration analysis of graded piezoelectric nanobeams including size effect and they are solved applying analytical solution. According to the numerical results, it is revealed that the proposed modeling can provide accurate frequency results of the FGP nanobeams as compared to some cases in the literature. In following a parametric study is accompanied to examine the effects of several parameters such as various temperature distributions, external electric voltage, power-law index, nonlocal parameter and mode number on the natural frequencies of the size-dependent FGP nanobeams in detail. It is found that the small scale effect and thermo-electrical loading have a significant effect on natural frequencies of FGP nanobeams.

Thermo-mechanical vibration analysis of temperature-dependent porous FG beams based on Timoshenko beam theory

  • Ebrahimi, Farzad;Jafari, Ali
    • Structural Engineering and Mechanics
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    • v.59 no.2
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    • pp.343-371
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    • 2016
  • In this paper thermo-mechanical vibration analysis of a porous functionally graded (FG) Timoshenko beam in thermal environment with various boundary conditions are performed by employing a semi analytical differential transform method (DTM) and presenting a Navier type solution method for the first time. The temperature-dependent material properties of FG beam are supposed to vary through thickness direction of the constituents according to the power-law distribution which is modified to approximate the material properties with the porosity phases. Also the porous material properties vary through the thickness of the beam with even and uneven distribution. Two types of thermal loadings, namely, uniform and linear temperature rises through thickness direction are considered. Derivation of equations is based on the Timoshenko beam theory in order to consider the effect of both shear deformation and rotary inertia. Hamilton's principle is applied to obtain the governing differential equation of motion and boundary conditions. The detailed mathematical derivations are presented and numerical investigations are performed while the emphasis is placed on investigating the effect of several parameters such as porosity distributions, porosity volume fraction, thermal effect, boundary conditions and power-low exponent on the natural frequencies of the FG beams in detail. It is explicitly shown that the vibration behavior of porous FG beams is significantly influenced by these effects. Numerical results are presented to serve benchmarks for future analyses of FG beams with porosity phases.

A 1D model considering the combined effect of strain-rate and temperature for soft soil

  • Zhu, Qi-Yin;Jin, Yin-Fu;Shang, Xiang-Yu;Chen, Tuo
    • Geomechanics and Engineering
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    • v.18 no.2
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    • pp.133-140
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    • 2019
  • Strain-rate and temperature have significant effects on the one-dimensional (1D) compression behavior of soils. This paper focuses on the bonding degradation effect of soil structure on the time and temperature dependent behavior of soft structured clay. The strain-rate and temperature dependency of preconsolidation pressure are investigated in double logarithm plane and a thermal viscoplastic model considering the combined effect of strain-rate and temperature is developed to describe the mechanical behavior of unstructured clay. By incorporating the bonding degradation, the model is extended that can be suitable for structured clay. The extended model is used to simulate CRS (Constant Rate of Strain) tests conducted on structural Berthierville clay with different strain-rates and temperatures. The comparisons between predicted and experimental results show that the extended model can reasonably describe the effect of bonding degradation on the stain-rate and temperature dependent behavior of soft structural clay under 1D condition. Although the model is proposed for 1D analysis, it can be a good base for developing a more general 3D model.