• Title/Summary/Keyword: time-dependent effect

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Interaction of Der p 2 with Toll-like Receptor 4 and its Effect on Cytokine Secretion

  • Park, Beom Seok;Lee, Na Rae;Kim, Mun Jeong;Kim, Seong Yeol;Kim, In Sik
    • Biomedical Science Letters
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    • v.21 no.3
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    • pp.152-159
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    • 2015
  • Der p 2, which is a major allergen of house dust mite, plays an important role in the pathogenesis of allergic disease. There is controversy regarding whether Der p 2 binds to Toll-like receptor 4 (TLR4), and its inflammatory effect has not yet been elucidated. In the current study, we examined the interaction of Der p 2 with TLR4 and the effect of Der p 2 on cytokine release in THP-1 cells and lymphocytes. Among house dust mite extracts, recombinant TLR4 protein interacted with Der p 2. The overall structure of Der p 2 is characteristic of the immunoglobulin superfamily and contains ten ${\beta}-strands$, forming a ${\beta}-cup$ fold with two anti-parallel ${\beta}-sheets$, and a short 310 helix. The two sheets can be separated, further allowing the formation of a large internal pocket, which is narrow and suitable for binding large flat molecules such as lipid-like molecules. Der p 2 caused increased secretion of IL-6, IL-8, and MCP-1, which are neutrophil survival factors, in human monocytic THP-1 cells in a time-dependent manner. Der p 2 also induces the release of cytokines in normal and allergic lymphocytes. Supernatant after treatment with Der p 2 inhibited neutrophil apoptosis. In coculture of lymphocytes with neutrophils, Der p 2 inhibited spontaneous apoptosis of allergic neutrophils. In summary, Der p 2 binds to TLR4 and induces an inflammatory response such as cytokine secretion in immune cells. These findings may enable elucidation of allergy pathogenesis by specific allergen of house dust mite.

Effects of Hyeolbuchukeo-tang (Xiefuzhuyutang) on NO Production in Aortic Vascular Smooth Muscle Cells (혈부축어탕이 대동맥 평골근 세포에서 NO 생성에 미치는 영향)

  • 한종민;고창보;박창민;정명수;박길래;이기남
    • The Journal of Korean Medicine
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    • v.23 no.2
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    • pp.19-27
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    • 2002
  • Objective : This study was designed to investigate the effect of Hyeolbuchukeo-tang (HCT) on NO production and the molecular mechanism of NO production modulated by HCT in the primary VSMC (vascular smooth muscle cells). Method : Primary VSMC was established from aorta and cultured VSMC used in this study. NO production of VSMC was assayed by Griess reagent and the expression of iNOS gene was assayed by Western, RT-PCR. Result : $TNF-{\gamma}$ induced NO production, but $IFN-{\gamma}$ or HCT alone did not induce NO production in cultured VSMC. However, $IFN-{\gamma}$ or HCT potentiated NO production in $TNF-{\gamma}-treated$ VSMC in a time- and dose-dependent manner. $TNF-{\gamma}$ induced the iNOS gene expression corresponding to NO production in $TNF-{\gamma}-treated$ VSMC. HCT potentiated NO production in $TNF-{\gamma}-treated$ VSMC by about 20%, but HCT did not increase the level of iNOS mRNA in $TNF-{\gamma}-treated$ VSMC. HCT slightly increased the level of iNOS protein in $TNF-{\gamma}-treated$ VSMC. Calcium ionophore A23187 decreased NO production in $TNF-{\gamma}-treated$ VSMC, but HCT attenuated the effect of A23187. Conclusion : As NO is deeply involved in the development of arteriosclerosis and dilation of blood vessels, drugs or chemicals modulating NO production in VSMC could be used for preventing and treating arteriosclerosis. Considering the effect of HCT on the modulation of NO production in VSMC, MCT has a potential capacity for preventing and treating diseases of the circulation system including arteriosclerosis.

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Hepaprotective Effect of Standardized Ecklonia stolonifera Formulation on CCl4-Induced Liver Injury in Sprague-Dawley Rats

  • Byun, Jae-Hyuk;Kim, Jun;Choung, Se-Young
    • Biomolecules & Therapeutics
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    • v.26 no.2
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    • pp.218-223
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    • 2018
  • The liver is an essential organ for the detoxification of exogenous xenobiotics, drugs and toxic substances. The incidence rate of non-alcoholic liver injury increases due to dietary habit change and drug use increase. Our previous study demonstrated that Ecklonia stolonifera (ES) formulation has hepatoprotective effect against alcohol-induced liver injury in rat and tacrine-induced hepatotoxicity in HepG2 cells. This present study was designated to elucidate hepatoprotective effects of ES formulation against carbon tetrachloride ($CCl_4$)-induced liver injury in Sprague Dawley rat. Sixty rats were randomly divided into six groups. The rats were treated orally with ES formulation and silymarin (served as positive control, only 100 mg/kg/day) at a dose of 50, 100, or 200 mg/kg/day for 21 days. Seven days after treatment, liver injury was induced by intraperitoneal injection of $CCl_4$ (1.5 ml/kg, twice a week for 14 days). The administration of $CCl_4$ exhibited significant elevation of hepatic enzymes (like AST and ALT), and decrease of antioxidant related enzymes (superoxide dismutase, glutathione peroxidase and catalase) and glutathione. Then, it leaded to DNA damages (8-oxo-2'-deoxyguanosine) and lipid peroxidation (malondialdehyde). Administration of ES formulation inhibited imbalance of above factors compared to $CCl_4$ induced rat in a dose dependent manner. Real time PCR analysis indicates that CYP2E1 was upregulated in $CCl_4$ induced rat. However, increased gene expression was compromised by ES formulation treatment. These findings suggests that ES formulation could protect hepatotoxicity caused by $CCl_4$ via two pathways: elevation of antioxidant enzymes and normalization of CYP2E1 enzyme.

Smear Effect on Consolidation Behaviors of SCP-improved Ground (SCP 개량지만의 압밀거동에 대한 스미어 효과)

  • Kim, Yun-Tae
    • Journal of the Korean Geotechnical Society
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    • v.20 no.2
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    • pp.59-66
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    • 2004
  • Sand compaction pile (SCP)-improved ground is composite soil which consists of the SCP and the surrounding soft soil. When a surcharge load is applied to composite ground, time-dependent behaviors occur in the composite soil due to consolidation according to radial flow toward the SCP. In addition, stress transfer also takes place between the SCP and the soft soil. This paper presents the numerical results of cylindrical composite ground that was conducted to investigate smear effect on consolidation behaviors of SCP-improved ground. The results showed that the smeared zone of soft clay had a significant effect on effective stress-pore water pressure response, stress transfer mechanism and stress concentration ratio of composite ground. Amount of stress transfer between the clay and the SCP was maximum in depth of z/H=0.25, and decreased with depth. Stress concentration ratio of composite ground was not constant, but depended on consolidation process. It was also found that the value of stress concentration ratio in soft clay with smeared zone was larger than that in soft clay without smeared zone.

Inhibition of Topoisomerase-mediated DNA Cleavage by Lycoperdon perlatum (말불버섯 추출물의 Topoisomerase 저해 효과)

  • Park, Mi-Jung;Cho, Kang-Jin;Kim, Jung-Bong;Kim, Dong-Hern;Kim, Yang-Sub;Seok, Soon-Ja;Kim, Sun-Yeou;Hwang, Young-Soo
    • Korean Journal of Food Science and Technology
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    • v.29 no.5
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    • pp.1057-1062
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    • 1997
  • In the course of searching for anticancer agents from 32 mushrooms, it was found that methanol extract of Lycoperdon perlatum showed inhibitory effect on topoisomerase II-mediated DNA cleavage. This active methanol extract was sequentially fractionated with hexane, chloroform, n-buthanol and water. Among the solvent-fractionated extracts, $1\;{\mu}g/mL$ hexane fraction of L. perlatum inhibited on topoisomerase II-mediated DNA cleavage. The effect of hexane fraction of L. perlatum was dose- and reaction time-dependent. The hexane fraction of L. perlatum was found to have inhibitory activity on relaxation assay of DNA topoisomerase I. The hexane fraction of cultured L. perlatum, however, had no inhibitory effect on either type of topoisomerase.

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Effect of Epimedium Koreanum Nakai on GO-Induced Neurotoxicity in Cultured Mouse Spinal Dorsal Root Ganglion Neurons (Glucose Oxidase에 의(依)하여 손상(損傷)된 배양척수감각신경절세포(培養脊髓感覺神經節細胞)에 대(對)한 음양곽(淫羊藿)의 효과(效果))

  • Park Seung-Taeck;Lee Ho-Sub;Yun Yong-Gap;Park Byung-Rim
    • Herbal Formula Science
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    • v.7 no.1
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    • pp.143-151
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    • 1999
  • To evaluate the neurotoxic effect of oxygen radicals in cultured mouse spinal dorsal root ganglion(DRG) neurons, cytotoxicity was determined by MTT assay after cultured DRG neurons were grown in the media containing various concentrations of glucose oxidase(GO). In addition, neuroprotective effect of herb extract, Epimedium Koreanum Nakai was examined by MTT assay in cultured DRG neurons. Cell viability of cultured DRG neurons was remarkably decreased by GO in dose- and time-dependent manner, and Epimedium Koreanum Nakai protected remarkably GO-induced neurotoxicity in these cultures. From the above results, it is suggested that oxygen radicals is toxic in cultured mouse DRG neurons, and herb extracts such as Epimedium Koreanum Nakai are effective in prevention of the neurotoxicity induced by oxygen radicals in cultured mouse DRG neurons.

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Study on the Binding of New Anti-ulcer Agent(IY-80843 and IY-80845) to Histamine $H_2$-Receptor in Isolated Guinea Pig Gastric Glands (새로운 항궤양제(IY-80843과 IY-80845)의 기니픽 위점막세포 $H_2$-수용체에 대한 결합반응연구)

  • 김승희;우승희;정숙영;문애리;이송득;김동연;이승룡
    • YAKHAK HOEJI
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    • v.39 no.2
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    • pp.153-160
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    • 1995
  • Receptor binding study was carried out as an in vitro assay to test the anti-ulcer effect for newly synthesized test compounds(IY-80843 and IY-80845) which were reported to have a strong anti-secretory effect in Shay-ligated rats. The histamine H$_{2}$-receptor fraction was prepared from the membranes of the isolated gastric glands in guinea pigs and $^{3}$H-cimetidine was used as a radioligand. The binding of $^{3}$H-cimetidine to the membranes of the isolated gastric glands was found to be time dependent, saturable and confined to a single population of binding sites with $K_{D}$ value of 0.13$\pm$0.03 $\mu{M}$ and B$_{max}$ value of 52.5$\pm$1.5 pmol/mg. From the competition experiments, both IY-80843 and IY-80845 were shown to have a strong blocking effect against binding of $^{3}$H-cimetidine to the histamine H$_{2}$-receptor. The IC$_{50}$, Ki, and Hill coefficient(nH) values for IY-80843 were 0.18$\pm$0.02 $\mu{M}$, 0.16$\pm$0.02 $\mu{M}$, and 0.97$\pm$0.15, respectively and those values for IY-80845 were 0.27$\pm$0.02 $\mu{M}$, 0.24$\pm$0.02 $\mu{M}$, and 0.82$\pm$0.13, respectively. The results demonstrated that the blocking effects of IY-80843 and IY-80845 were 7 and 5 times stronger than that of cimetidine, respectively. Therefore, the newly synthesized compounds, IY-80843 and IY-80845, appeared to be the highly potent competitive inhibitors of histamine on the H$_{2}$-receptor.

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Effect of Propofol, an Intravenous Anesthetic Agent, on $K_{ATP}$ Channels of Pancreatic ${\beta}-cells$ in Rats

  • Park, Eun-Jee;Song, Dae-Kyu;Cheun, Jae-Kyu;Bae, Jung-In;Ho, Won-Kyung;Earm, Yung-E
    • The Korean Journal of Physiology and Pharmacology
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    • v.4 no.1
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    • pp.25-31
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    • 2000
  • ATP-sensitive potassium channels ($K_{ATP}$ channels) play an important role in insulin secretion from pancreatic beta cells. We have investigated the effect of propofol on $K_{ATP}$ channels in cultured single pancreatic beta cells of rats. Channel activity was recorded from membrane patches using the patch-clamp technique. In the inside-out configuration bath-applied propofol inhibited the $K_{ATP}$ channel activities in a dose-dependent manner. The half-maximal inhibition dose (ED50) was $48.6{\pm}8.4\;{\mu}M$ and the Hill coefficient was $0.73{\pm}0.11.$ Single channel conductance calculated from the slope of the relationship between single channel current and pipette potential $(+20{\sim}+100\;mV)$ was not significantly altered by propofol $(control:\;60.0{\pm}2.7\;pS,\;0.1\;mM\;propofol:\;58.7{\pm}3.5\;pS).$ However, mean closed time was surely increased. Above results indicate that propofol blocks the $K_{ATP}$ channels in the pancreatic beta cells in the range of its blood concentrations during anesthesia, suggesting a possible effect on insulin secretion and blood glucose level.

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Effect of Ethanol Extracts of Cinnamon on the Proliferation and COX-2 Pathway in HT-29 Human Colon Cancer Cell Line (육계 에탄올 추출물이 HT-29 대장암 세포주의 성장 및 COX-2 기전에 미치는 영향)

  • Lee, Seung-Youn;Kim, Hee-Seok;Kim, Jeoung-Ok;Hwang, Sung-Wan;Hwang, Sung-Yeoun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.35 no.9
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    • pp.1115-1120
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    • 2006
  • The effect of cinnamon ethanol extract (CN) on HT-29 cancer cell line has been examined. CN inhibited the growth of HT-29 colon cancer cells in a concentration and time dependent manner but not the growth of CCD-112CoN normal colon cells. And CN markedly inhibited the production of $PGE_2$ and cGMP as well as the mRNA expression of COX-2. These data suggest that non toxic concentration of CN has a significant inhibition effect on the growth of HT-29 cells, probably through the inhibition of $PGE_2$ production via COX-2 inhibition, and may have value as a safe chemopreventive agent for colon cancer.

Energy-based numerical evaluation for seismic performance of a high-rise steel building

  • Zhang, H.D.;Wang, Y.F.
    • Steel and Composite Structures
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    • v.13 no.6
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    • pp.501-519
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    • 2012
  • As an alternative to current conventional force-based assessment methods, the energy-based seismic performance of a code-designed 20-storey high-rise steel building is evaluated in this paper. Using 3D nonlinear dynamic time-history method with consideration of additional material damping effect, the influences of different restoring force models and P-${\Delta}/{\delta}$ effects on energy components are investigated. By combining equivalent viscous damping and hysteretic damping ratios of the structure subjected to strong ground motions, a new damping model, which is amplitude-dependent, is discussed in detail. According to the analytical results, all energy components are affected to various extents by P-${\Delta}/{\delta}$ effects and a difference of less than 10% is observed; the energy values of the structure without consideration of P-${\Delta}/{\delta}$ effects are larger, while the restoring force models have a minor effect on seismic input energy with a difference of less than 5%, but they have a certain effect on both viscous damping energy and hysteretic energy with a difference of about 5~15%. The paper shows that the use of the hysteretic energy at its ultimate state as a seismic design parameter has more advantages than seismic input energy since it presents a more stable value. The total damping ratio of a structure consists of viscous damping ratio and hysteretic damping ratio and it is found that the equivalent viscous damping ratio is a constant for the structure, while the equivalent hysteretic damping ratio approximately increases linearly with structural response in elasto-plastic stage.