• 제목/요약/키워드: blocking effect

검색결과 904건 처리시간 0.035초

Inhibitory Effects of YP 12, A Newly Synthesized Obovatol Derivative on Rat Aortic Vascular Smooth Muscle Cell Proliferation

  • Lim, Yong;Lee, Mi-Yea;Jung, Jae-Kyung;Pyo, Myoung-Yun;Yun, Yeo-Pyo
    • 한국식품위생안전성학회지
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    • 제26권3호
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    • pp.187-191
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    • 2011
  • Platelet derived growth factor (PDGF)-BB is one of the most potent vascular smooth muscle cell(VSMC) proliferative factors, and abnormal VSMC proliferation by PDGF-BB plays an important role in the development and progression of atherosclerosis. The aim of this study was to assess the effect of YP 12, a newly synthesized obovatol derivative, on the proliferation of PDGF-BB-stimulated rat aortic VSMCs. The anti-proliferative effects of YP 12 on rat aortic VSMCs were examined by direct cell counting and by using $[^3H]$ thymidine incorporation assays. It was found that YP 12 potently inhibited the growth of VSMCs. The pre-incubation of YP 12 (1-4 ${\mu}M$) significantly inhibited the proliferation and DNA synthesis of 25 ng/ml PDGF-BB-stimulated rat aortic VSMCs in a concentration-dependent manner. In accordance with these findings, YP 12 revealed blocking of the PDGF-BB-inducible progression through G0/G1 to S phase of the cell cycle in synchronized cells. Whereas, YP 12 did not show any cytotoxicity in rat aortic VSMCs in this experimental condition by WST-1 assay. These results also show that YP 12 may have potential as an anti-proliferative agent for the treatment of restenosis and atherosclerosis.

PEGylated Erythropoietin Protects against Brain Injury in the MCAO-Induced Stroke Model by Blocking NF-κB Activation

  • Im, Jun Hyung;Yeo, In Jun;Hwang, Chul Ju;Lee, Kyung Sun;Hong, Jin Tae
    • Biomolecules & Therapeutics
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    • 제28권2호
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    • pp.152-162
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    • 2020
  • Cerebral ischemia exhibits a multiplicity of pathophysiological mechanisms. During ischemic stroke, the reactive oxygen species (ROS) concentration rises to a peak during reperfusion, possibly underlying neuronal death. Recombinant human erythropoietin (EPO) supplementation is one method of treating neurodegenerative disease by reducing the generation of ROS. We investigated the therapeutic effect of PEGylated EPO (P-EPO) on ischemic stroke. Mice were administered P-EPO (5,000 U/kg) via intravenous injection, and middle cerebral artery occlusion (MCAO) followed by reperfusion was performed to induce in vivo ischemic stroke. P-EPO ameliorated MCAO-induced neurological deficit and reduced behavioral disorder and the infarct area. Moreover, lipid peroxidation, expression of inflammatory proteins (cyclooxygenase-2 and inducible nitric oxide synthase), and cytokine levels in blood were reduced by the P-EPO treatment. In addition, higher activation of nuclear factor kappa B (NF-κB) was found in the brain after MCAO, but NF-κB activation was reduced in the P-EPO-injected group. Treatment with the NF-κB inhibitor PS-1145 (5 mg/kg) abolished the P-EPO-induced reduction of infarct volume, neuronal death, neuroinflammation, and oxidative stress. Moreover, P-EPO was more effective than EPO (5,000 U/kg) and similar to a tissue plasminogen activator (10 mg/kg). An in vitro study revealed that P-EPO (25, 50, and 100 U/mL) treatment protected against rotenone (100 nM)-induced neuronal loss, neuroinflammation, oxidative stress, and NF-κB activity. These results indicate that the administration of P-EPO exerted neuroprotective effects on cerebral ischemia damage through anti-oxidant and anti-inflammatory properties by inhibiting NF-κB activation.

Inhibitory Effects of β-Glycyrrhetinic Acid on Tumor Necrosis Factor-α Production in RAW 264.7 Cells

  • Park, Kyoung-Sik
    • Journal of Applied Biological Chemistry
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    • 제53권3호
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    • pp.147-153
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    • 2010
  • $\beta$-glycyrrhetinic acid (GA), the active principle of licorice (Glycyrrhiza glabra L.) has been reported to exhibit anti-inflammatory properties in different animal models. In this study, the effects of GA on the production of inflammatory mediators including tumor necrosis factor (TNF)-$\alpha$, interleukin (IL)-6, nitric oxide (NO), and prostaglandin E (pGE)-2 were examined in RAW 264.7 cells in vitro. Furthermore, to elucidate a possible mechanism for the inhibitory effect of GA on the production of TNF-$\alpha$, it was investigated whether the treatment of GA affects the I-${\kappa}B{\alpha}$ degradation and subsequent nuclear translocation of NF-${\kappa}B$. Various inflammatory responses were induced in the culture system by treating with a lipopolysaccharide (LPS). GA showed anti-inflammatory activities in dose-dependant manner with $IC_{50}$ of $5.4{\mu}M$ by inhibiting the production of TNF-$\alpha$ in RAW 264.7 cells. In addition, the treatment of GA blocked both I-${\kappa}B{\alpha}$ degradation and the nuclear translocation of NF-${\kappa}B$ from cytosol to nucleus. However, it did not affect the production of IL-6, NO, and PGE-2, implying the direct blocking of the production of TNF-$\alpha$ resulting from both the I-${\kappa}B{\alpha}$ degradation and the nuclear translocation of NF-${\kappa}B$. This finding might provide the underlying mechanism to explain the reported anti-inflammatory activities of GA in animal models.

ZAS3 promotes TNFα-induced apoptosis by blocking NFκB-activated expression of the anti-apoptotic genes TRAF1 and TRAF2

  • Shin, Dong-Hyeon;Park, Kye-Won;Wu, Lai-Chu;Hong, Joung-Woo
    • BMB Reports
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    • 제44권4호
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    • pp.267-272
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    • 2011
  • ZAS3 is a large zinc finger transcription repressor that binds the ${\kappa}B$-motif via two signature domains of ZASN and ZASC. A loss-of-function study showed that lack of ZAS3 protein induced accelerated cell proliferation and tumorigenesis. Conversely, gain-of-function studies showed that ZAS3 repressed $NF{\kappa}B$-activated transcription by competing with $NF{\kappa}B$ for the ${\kappa}B$-motif. Based on these observations, we hypothesize that ZAS3 promotes apoptosis by interrupting anti-apoptotic activity of $NF{\kappa}B$. Here, we present evidence that upon $TNF{\alpha}$ stimulation, ZAS3 inhibits $NF{\kappa}B$-mediated cell survival and promotes caspase-mediated apoptosis. The inhibitory effect of ZAS3 on $NF{\kappa}B$ activity is mediated by neither direct association with $NF{\kappa}B$ nor disrupting nuclear localization of $NF{\kappa}B$. Instead, ZAS3 repressed the expression of two key anti-apoptotic genes of $NF{\kappa}B$, TRAF1 and TRAF2, thereby sensitizing cells to $TNF{\alpha}$-induced cell death. Taken together, our data suggest that ZAS3 is a tumor suppressor gene and therefore serves as a novel therapeutic target for developing anti-cancer drugs.

아날로그 정합 필터를 이용한 버스트형 직렬 탐색 DS-SS 초기 동기 시스템의 성능 분석 (A Performance Analysis of Burst-format Serial Search DS-SS Acquisition System Using Analog Matched Filter)

  • 이동욱;김형근;황금찬
    • 한국통신학회논문지
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    • 제16권8호
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    • pp.710-718
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    • 1991
  • 본 논문에서는, 정합필터를 이용한 버스트형 직렬탐색 직접 시퀀스 스펙트럼 확산 초기동기 시스템의 성능분석방법을 제안하였고, 이 방법을 이용하여 아날로그 정합필터를 이용한 초기 동기시스템의 성능을 분석하였다. 특히 사용한 코드의 자기 상관 사이드로브가 초기동기 시스템의 성능에 미치는 영향을 고려하였다. 성능 분석방법으로는, 시간에 따른 시스템의 상태도를 구성하고, 오보율과 검출률, 그리고 blocked customers cleared queueing 시스템 모델에서 얻은 시스템의 봉쇄율을 시스템의 상태도에 적용함으로써, 임의의 시간에 도달하는 패킷을 잃을 확률을 얻는다. 성능 분석결과, 코드의 자기상관 사이드로브에 의해 발생하는 오보는 질렬 탐색을 사용하는 비스트 형DS-SS초기 동기 시스템의 성능에 큰 영향을 미쳤으며, 특정한 SNR/chip이상에서는 SNR/chip이 커질수록 초기 동기 시스템의 성능이 크게 저하되었다.

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저전압 플래시메모리를 위한 SONOS 비휘발성 반도체기억소자에 관한 연구 (A Study on SONOS Non-volatile Semiconductor Memory Devices for a Low Voltage Flash Memory)

  • 김병철;탁한호
    • 한국정보통신학회논문지
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    • 제7권2호
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    • pp.269-275
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    • 2003
  • 저전압 프로그래밍이 가능한 플래시메모리를 실현하기 위하여 0.35$\mu\textrm{m}$ CMOS 공정 기술을 이용하여 터널링산화막, 질화막 그리고 블로킹산화막의 두께가 각각 2.4nm, 4.0nm, 2.5nm인 SONOS 트랜지스터를 제작하였으며, SONOS 메모리 셀의 면적은 1.32$\mu$$m^2$이었다. 질화막의 두께를 스케일링한 결과, 10V의 동작 전압에서 소거상태로부터 프로그램상태로, 반대로 프로그램상태에서 소거상태로 스위칭 하는데 50ms의 시간이 필요하였으며, 최대 메모리윈도우는 1.76V이었다. 그리고 질화막의 두께를 스케일링함에도 불구하고 10년 후에도 0.5V의 메모리 윈도우를 유지하였으며, 105회 이상의 프로그램/소거 반복동작이 가능함을 확인하였다. 마지막으로 부유게이트 소자에서 심각하게 발생하고있는 과도소거현상이 SONOS 소자에서는 나타나지 않았다.

서열환경하에서의 전투복착용이 체온조절에 미치는 영향 (The Influence of Wearing Army Combat Uniform on the Thermal Responses in Heat Environment)

  • 김태규;조호현
    • 한국의류산업학회지
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    • 제16권1호
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    • pp.167-174
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    • 2014
  • The physical properties of textile materials and thermal physiological responses of the human subjects were evaluated with 4 different types of the army combat uniforms including US, German, Korean and general uniforms for this study. 8 male adults were used as the human subjects and the tests were done in the environmental chamber that was $25{\pm}0.1^{\circ}C$ of temperature, $65{\pm}5%$ of relative humidity and below 0.3 m/sec of air velocity. The test protocol consisted the rest period for 20 min., the exercise period for 20 min., the rest period for 20 min., the exercise period under wind condition for 20 min., and the recovery period for 20 min. The human subjects walked with 4.5 km/hr for 10 min., ran 7.5 km/hr for 10 min. during the first exercise period and walked and ran with the same speeds under 3.5 m/sec of the air velocity that simulated outdoor condition during the second exercise period. The test results of the study were as follows; The wind condition affected the skin and microclimate temperature of the human subjects lower compared to without wind condition, but had insignificant effect on the humidity control. The low air permeability of Korean uniform caused blocking the elimination of the humidity from the body and the regulation of body temperature. However, Korean uniforms could be the excellent one with the designs considering the ventilation of the uniforms and the textile fabrics with better air permeability.

Gametocyte Clearance in Uncomplicated and Severe Plasmodium falciparum Malaria after Artesunate-Mefloquine Treatment in Thailand

  • Tangpukdee, Noppadon;Krudsood, Srivicha;Srivilairit, Sriripun;Phophak, Nanthaporn;Chonsawat, Putza;Yanpanich, Wimon;Kano, Shigeyuki;Wilairatana, Polrat
    • Parasites, Hosts and Diseases
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    • 제46권2호
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    • pp.65-70
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    • 2008
  • Artemisinin-based combination therapy (ACT) is currently promoted as a strategy for treating both uncomplicated and severe falciparum malaria, targeting asexual blood-stage Plasmodium falciparum parasites. However, the effect of ACT on sexual-stage parasites remains controversial. To determine the clearance of sexual-stage P. falciparum parasites from 342 uncomplicated, and 217 severe, adult malaria cases, we reviewed and followed peripheral blood sexualstage parasites for 4 wk after starting ACT. All patients presented with both asexual and sexual stage parasites on admission, and were treated with artesunate-mefloquine as the standard regimen. The results showed that all patients were asymptomatic and negative for asexual forms before discharge from hospital. The percentages of uncomplicated malaria patients positive for gametocytes on days 3, 7, 14, 21, and 28 were 41.5, 13.1, 3.8, 2.0, and 2.0%, while the percentages of gametocyte positive severe malaria patients on days 3, 7, 14, 21, and 28 were 33.6, 8.2, 2.7, 0.9, and 0.9%, respectively. Although all patients were negative for asexual parasites by day 7 after completion of the artesunate-mefloquine course, gametocytemia persisted in some patients. Thus, a gametocytocidal drug, e.g., primaquine, may be useful in combination with an artesunate-mefloquine regimen to clear gametocytes, so blocking transmission more effectively than artesunate alone, in malaria transmission areas.

PHOTOCATALYTIC SYNTHESIS OF L-PIPECOLINIC ACID FROM $N_{varepsilon}$-CARBAMYL-L-LYSINE BY AQUEOUS SUSPENSION OF PLATINIZED TITANIUM(IV) OXIDE

  • Ohtani, Bunsho;Aoki, Eishiro;Iwai, Kunihiro;Nishimoto, Sei-Ichi
    • Journal of Photoscience
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    • 제1권1호
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    • pp.31-37
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    • 1994
  • Photoirradiation at > 300 nm onto a suspension of platinized TiO$_2$ (TiO$_2$-Pt) particles in an aqueous solution. of N$_{\varepsilon}$-carbamyI-L-lysine (Lys(CONH)$_2$) induced the selective N-cyclization of Lys(CONH$_2$) into almost optically pure L-pipecolinic acid (PCA) under argon atmosphere at ambient temperature. Among various TiO$_2$-Pt catalysts, a P-25 (Degussa) powder platinized via impregnation from chloroplatinic acid followed by hydrogen reduction at 753 K exhibited the highest photocatalytic activity for Lys(CONH$_2$) consumption and L-PCA production. GC-MS analyses of L-PCA obtained photocatalytically from $^{15}$N$\alpha$-Lys(CONH$_2$) revealed the selective formation $^{15}$N-substituted L-PCA. This implies that the mechanism for L-PCA production contains selective cleavage of C$_{\varepsilon}$-N bond and intramolecular alkylation at $\alpha$-amino group. Effect of pH on the rate of this photocatalytic reaction was investigated in detail and compared with the pH-dependent charge distribution in Lys(CONH$_2$) molecule. It is clarified that protonation-deprotonation of $\alpha$-amino group gives marked influence on the rate and selectivity of the photocatalytic reaction. On the basis of these results, it is concluded that the selective production of optically pure L-PCA, especially in an acidic suspension of TiO$_2$-Pt, was attributed to the enhanced protonation of $\alpha$-amino group to prevent undesirable oxidation by photogenerated positive holes and blocking of $\varepsilon$-amino group to yield racemic Schiff base intermediate.

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Ondansetron과 Droperidol의 혼합 투여가 술 후 오심과 구토 예방에 미치는 효과 (The Effect of Combination of Ondansetron and Droperidol on Prevention of Postoperative Nausea and Vomiting)

  • 김동희;조덕현
    • The Korean Journal of Pain
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    • 제14권1호
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    • pp.46-50
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    • 2001
  • Background: Ondansetron is both a central and peripheral serotonin (5HT) receptor antagonist and droperidol is a dopaminergic blocking drug which acts centrally at the chemoreceptor trigger zone. We assessed the efficacy and adverse effects of ondansetron, droperidol or both, in the prevention of postoperative emesis during postoperative intravenous patient-controlled analgesia (PCA) using butorphanol and ketorolac medication. Methods: We studied 60 women, aged 25-60 yrs, who underwent total abdominal hysterectomy (TAH), under general anesthesia using $N_2O-O_2$-enflurane. A bolus dose of 1 mg of butorphanol and 4 mg of ondansetron were given to patients and thereafter, PCA was started using 10 mg of butorphanol and 240 mg of ketorolac mixed into the 5% D/W solution (total volume; 100 ml, 1 ml of bolus dose, and 10 min of lockout interval). We also added ondansetron 4 mg (Group O, n = 20), ondansetron 4 mg and droperidol 2.5 mg (Group OD, n = 20), or droperidol 2.5 mg (Group D, n = 20) to the PCA drug. The severity of pain, nausea, vomiting, sedation and other side effects were assessed at 0, 1, 2, 6, 12, 24, 36 and 48 hr after awakening. Results: There was no difference in the incidence of nausea and vomiting between the three group [Group O: 4 (20%) and 3 (15%), respectively; Group OD: 1 (5%) and 1 (5%), respectively; Group D: 3 (15%) and 3 (15%), respectively]. Group O showed a lower sedation score than the other groups (P < 0.05). The pain score and other side effects did not show any difference between the groups. Conclusions: The combination of ondansetron and droperidol showed no clinical benefit compared with ondansetron or droperidol alone for prevention of postoperative nausea and vomiting during postoperative PCA using butorphanol and ketorolac.

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