• Title/Summary/Keyword: blocking effect

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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
    • Journal of Food Hygiene and Safety
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    • v.26 no.3
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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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    • v.28 no.2
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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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    • v.53 no.3
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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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    • v.44 no.4
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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.

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

  • 이동욱;김형근;황금찬
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.16 no.8
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    • pp.710-718
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    • 1991
  • In this pape, an analysis approach for the performance of serial search burst-format direct sequence spread-spectrum code acquisiion system using matched filter is presented. And an acquistion system using analog matched filter is analyzed by this approach. And special consideration is focused on the effect of the code autocorelation sideobes. The basic idea of thi approach is the constuction of state tansition digram at the time of random packet arrival and the calculation of the packet loss probability, which is deveoped in terms of the following parameters: the false alarm probability. the etection probability, and the probability of receiver blocking obtained from the blocked customers cleae queeing system model. The analysis results reveal that the performance of the acquisition system is degraded by the effet of the code autocorrelation sidelobes above a certain value of SN/chip.

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

  • 김병철;탁한호
    • Journal of the Korea Institute of Information and Communication Engineering
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    • v.7 no.2
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    • pp.269-275
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    • 2003
  • Polysilicon-oxide-nitride-oxide-silicon(SONOS) transistors were fabricated by using 0.35${\mu}{\textrm}{m}$ complementary metal-oxide-semiconductor(CMOS) process technology to realize a low voltage programmable flash memory. The thickness of the tunnel oxide, the nitride, and the blocking oxide were 2.4nm, 4.0nm, and 2.5nm, respectively, and the cell area of the SONOS memory was 1.32$\mu$$m^2$. The SONOS device revealed a maximum memory window of 1.76V with a switching time of 50ms at 10V programming, as a result of the scaling effect of the nitride. In spite of scaling of nitride thickness, memory window of 0.5V was maintained at the end of 10 years, and the endurance level was at least 105 program/erase cycles. Over-erase, which was shown seriously in floating gate device, was not shown in SONOS device.

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

  • Kim, Tae Gyou;Cho, Ho Hyun
    • Fashion & Textile Research Journal
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    • v.16 no.1
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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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    • v.46 no.2
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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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    • v.1 no.1
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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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The Effect of Combination of Ondansetron and Droperidol on Prevention of Postoperative Nausea and Vomiting (Ondansetron과 Droperidol의 혼합 투여가 술 후 오심과 구토 예방에 미치는 효과)

  • Kim, Dong-Hee;Cho, Duk-Hyun
    • The Korean Journal of Pain
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    • v.14 no.1
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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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