• Title/Summary/Keyword: PD-L2

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NLRC4 Inflammasome-Mediated Regulation of Eosinophilic Functions

  • Ilgin Akkaya;Ece Oylumlu;Irem Ozel;Goksu Uzel;Lubeyne Durmus;Ceren Ciraci
    • IMMUNE NETWORK
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    • v.21 no.6
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    • pp.42.1-42.20
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    • 2021
  • Eosinophils play critical roles in the maintenance of homeostasis in innate and adaptive immunity. Although primarily known for their roles in parasitic infections and the development of Th2 cell responses, eosinophils also play complex roles in other immune responses ranging from anti-inflammation to defense against viral and bacterial infections. However, the contributions of pattern recognition receptors in general, and NOD-like receptors (NLRs) in particular, to eosinophil involvement in these immune responses remain relatively underappreciated. Our in vivo studies demonstrated that NLRC4 deficient mice had a decreased number of eosinophils and impaired Th2 responses after induction of an allergic airway disease model. Our in vitro data, utilizing human eosinophilic EoL-1 cells, suggested that TLR2 induction markedly induced pro-inflammatory responses and inflammasome forming NLRC4 and NLRP3. Moreover, activation by their specific ligands resulted in caspase-1 cleavage and mature IL-1β secretion. Interestingly, Th2 responses such as secretion of IL-5 and IL-13 decreased after transfection of EoL-1 cells with short interfering RNAs targeting human NLRC4. Specific induction of NLRC4 with PAM3CSK4 and flagellin upregulated the expression of IL-5 receptor and expression of Fc epsilon receptors (FcεR1α, FcεR2). Strikingly, activation of the NLRC4 inflammasome also promoted expression of the costimulatory receptor CD80 as well as expression of immunoregulatory receptors PD-L1 and Siglec-8. Concomitant with NLRC4 upregulation, we found an increase in expression and activation of matrix metalloproteinase (MMP)-9, but not MMP-2. Collectively, our results present new potential roles of NLRC4 in mediating a variety of eosinopilic functions.

Nutritional Composition, Ginsenoside Content and Fundermental Safety Evaluation with Leaf and Stem Extract of Panax ginseng (인삼잎과 줄기 혼합 추출물의 영양성분, Ginsenoside 함량 및 기본적 안전성 평가)

  • 한종현;박성진;안종남;위재준;김기영;박성혜
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.33 no.5
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    • pp.778-784
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    • 2004
  • This study was conducted to investigate the application possibility of leaf and stem extract (LSE) from the mixture of leaf and stem of Panax ginseng. This study measured the general nutritional composition, aminoacid minerals contents and fatty acid composition of LSE. We conducted analysis of the ginsenoside content by HPLC and the cell cytotoxicity tests in normal liver and kidney cells. The approximate composition of LSE was 2.51% of carbohydrate 0.53% of crude ash,0.20% of crude fat and 0.15% of crude protein, respectively. LSE contained 102.56 mg/100 g of K ion and high contents of acidic amino acids such as glutamic acid and aspartic acid. In addition to this, it contained all essential amino acids. The major compositions of fatty acids were 39.99% of palmitic acid 14.96% of linoleic acid, 13.31% of docosatetranoic acid and 12.91% of linolenic acid, The total ginsenoside was 0.82 mg/mL, and ratio of PD/PT was 0.68. Negative effects were not found from the results of the cell toxicity respection. These results imply that leaf and stem of Panax gineng could be used as possible food resources and functional food material and feed stuff.

Clinical effect of smoking on the healing response following scaling and root planing (흡연이 비외과적 치주치료 후 치유반응에 미치는 임상적 영향)

  • Shim, Ji-Yeon;Kim, Tae-Il;Seol, Yang-Jo;Lee, Yong-Moo;Ku, Young;Rhyu, In-Chul;Chung, Chong-Pyoung;Han, Soo-Boo
    • Journal of Periodontal and Implant Science
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    • v.36 no.1
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    • pp.125-137
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    • 2006
  • 1. 목적 흡연은 치주질환의 주요한 위험 인자 중의 하나이다. 일반적으로 흡연자는 비흡연자보다 비외과적 및 외과적 치주치료에 대한 반응이 덜 효과적인 것으로 알려져 있다. 이 연구에서는 중등도의 만성 치주염이 존재하는 한국인 흡연자와 비흡연자를 대상으로 하여, 비외과적 치주치료인 치석 제거술과 치근 활택술을 시행한 후 6개윌 동안의 임상적 치유 반응을 비교해 보고자 하였다. 2. 방법 20명의 중등도 만성 치주염 환자(흡연자 10명, 비흡연자 10명)를 대상으로 치주낭 깊이(Probing Pocket Depth, PPD), 치은퇴축(GR), 치주탐침시 출혈유무(BOP), #16, 12, 24, 32, 36, 44의 치태지수(Plaque Index, Silness & $L{\"{o}}e$ 1964)를 임상변수로 측정하였다. 치주낭 깊이 (PD)와 치은퇴축(GR)은 전자 탐침(Florida $Probe^{(R)}$ Co. Gainesville, FL)을 이용하여 각 치아당 6군데를 측정하였다. 임상적 부착 수준(CAL)은 치주낭 깊이(PD)와 치은퇴축(GR)의 합으로 계산하였다. 초진시에 전악 임상 검사를 시행하였고, 초진시의 치주낭 깊이에 따라 조사 대상이 되는 치아 부위를 선정하였다. 치주적으로 건강한 부위 $(PD{\leq}3mm)$를 대조군인 1군으로 하고 치주낭 깊이가 4 mm를 초과하고 5 mm 미만인 부위를 2군, 5 mm 이상의 치주낭 깊이를 가지는 부위를 3군으로 설정하였다. 비외과적 치주치료인 치석 제거술, 치근 활택술과 구강위생 교육을 시행하였고 2개월(T1), 4개윌(T2), 6개윌(T3)에 선정된 해당 치아 부위에 대해 임상 재검사를 시행하였다. 3. 결과 BOP와 Plaque Index는 초진, 2, 4, 6개월에 흡연자와 비흡연자 간에 유의할 만한 차이가 없었으나 전반적으로 감소하는 경향이 나타났다. 대조군인 l군에 서는 흡연자와 비흡연자 간에 모든 시기에서 PD, GR, CAL에 유의할 만한 차이가 없었다. 치주낭 깊이가 4 mm를 초과하고 5 mm 미만인 2군에서는 비흡연자에서 6개월에 유의할 만한 치주낭 깊이 감소가 나타났으며, 4개월과 6개윌에 유의할 만한 부착수준의 증가가 관찰되었다(p<0.05). 치주낭 깊이가 5 mm이상인 3군에서는 비흡연자에서 치주낭 깊이 감소가 일관되게 더 많이 나타났으나 통계학적으로 유의할 만한 차이는 6개월째에서만 관찰되었다. 2군과 유사하게 치주낭 갚이 감소는 흡연자보다 비흡연자에서 0.6 mm 더 크게 나타났다. 부착수준의 획득은 2군에서는 4, 6개월째에, 3군에서는 6개월째에 비흡연자에서 유의하게 더 많이 일어났다. 초진시의 치주낭 깊이와 각 시기별 ${\Delta}PD$ 간의 상관관계에서는 치주낭 갚이가 5mm 이상인 3군에서 비흡연자의 경우 6개월째에 가장 강한 상관성이 나타났다($r_s=0.43$, p<0.05). 흡연자에서는 3군에서 어떠한 유의한 상관관계도 나타나지 않았다. 결론적으로 중등도 만성 치주염 환자를 대상으로 한 6개윌의 단기간 연구에서 비외과적 치주치료 후 흡연자에서 비흡연자보다 치주낭 깊이 감소의 개선과 부착수준의 획득이 더 적게 나타나 임상적 치유반응이 좋지 않음을 확인하였다. 이는 흡연이 숙주의 치유반응 부정적인 영향을 주기 때문으로 생각된다.

Antiviral activity of ginsenosides against coxsackievirus B3, enterovirus 71, and human rhinovirus 3

  • Song, Jae-Hyoung;Choi, Hwa-Jung;Song, Hyuk-Hwan;Hong, Eun-Hye;Lee, Bo-Ra;Oh, Sei-Ryang;Choi, Kwangman;Yeo, Sang-Gu;Lee, Yong-Pyo;Cho, Sungchan;Ko, Hyun-Jeong
    • Journal of Ginseng Research
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    • v.38 no.3
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    • pp.173-179
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    • 2014
  • Background: Ginsenosides are the major components responsible for the biochemical and pharmacological actions of ginseng, and have been shown to have various biological activities. In this study, we investigated the antiviral activities of seven ginsenosides [protopanaxatriol (PT) type: Re, Rf, and Rg2; protopanaxadiol (PD) type: Rb1, Rb2, Rc, and Rd)] against coxsackievirus B3 (CVB3), enterovirus 71 (EV71), and human rhinovirus 3 (HRV3). Methods: Assays of antiviral activity and cytotoxicity were evaluated by the sulforhodamine B method using the cytopathic effect (CPE) reduction assay. Results: The antiviral assays demonstrated that, of the seven ginsenosides, the PT-type ginsenosides (Re, Rf, and Rg2) possess significant antiviral activities against CVB3 and HRV3 at a concentration of $100{\mu}g/mL$. Among the PT-type ginsenosides, only ginsenoside Rg2 showed significant anti-EV71 activity with no cytotoxicity to cells at $100{\mu}g/mL$. The PD-type ginsenosides (Rb1, Rb2, Rc, and Rd), by contrast, did not show any significant antiviral activity against CVB3, EV71, and HRV3, and exhibited cytotoxic effects to virus-infected cells. Notably, the antiviral efficacies of PT-type ginsenosides were comparable to those of ribavirin, a commonly used antiviral drug. Conclusion: Collectively, our findings suggest that the ginsenosides Re, Rf, and Rg2 have the potential to be effective in the treatment of CVB3, EV71, and HRV3 infection.

Pharmacokinetic Analysis of Levofloxacin in Healthy Korean Volunteers

  • Kim, Seung-Yong;Chung, Youn-Bok;Pyo, Hee-Soo;Kwon, Oh-Seung
    • Journal of Pharmaceutical Investigation
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    • v.38 no.4
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    • pp.235-240
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    • 2008
  • A sensitive and simple method of determining the plasma levofloxacin (LFX, CAS 100986-85-4) concentrations in human volunteers by liquid-liquid extraction were developed and validated by using a high-performance liquid chromatography/diode array detector. The method was also applied to pharmacokinetic study of LFX. LFX was orally administered to 8 healthy male Korean volunteers at single lowest dose of 200 mg, compared to the published reports in which more than 500 mg of LFX was orally administered. LFX in human plasma was determined. The detection limit of LFX was $0.05\;{\mu}g/mL$. $C_{max}$ value was $2.48{\pm}0.67\;{\mu}g/mL$. $AUC_{0{\to}24\;hr$} and $AUC_{0{\to}{\infty}}$ were $14.52{\pm}3.35\;{\mu}g/mL$ and $16.00{\pm}3.66\;{\mu}g{\cdot}hr/mL$, respectively. The terminal half-life was $6.87{\pm}0.46\;hr$. Our pharmacokinetic parameters were very consistent with that previously reported, showing good correlation between LFX doses and AUC ($r^2=0.995$). This method can be useful for the pharmacokinetics and bioequivalence study with relatively low dose for reducing the main side effects of LFX.

Evaluation of the Potential of Retrograde Flow Competition in the Right Gastroepiploic Artery Graft for Coronary Artery Bypass Grafting (우위대망동맥을 이용한 관상동맥우회술 후 역행성 혈류 발생가능성의 연구)

  • Chung, Bong-Kyu;Sun, Kyung;Kwon, Joon;Kim, Kwang-Ho;Jung, Jae-Seung;Son, Ho-Sung;Lee, Sung-Ho;Kim, Kwang-Taik;Kim, Hyung-Mook
    • Journal of Chest Surgery
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    • v.35 no.1
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    • pp.20-26
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    • 2002
  • Background: Due to the concern of flow competition or retrograde steal, it has been generally suggested that the right gastroepiploic artery(RGEA) pedicled graft should be used in critical coronary stenosis lesion. The study was designed to evaluate the potential of retrograde flow competition in the RGEA pedicled graft by measuring the native pressure differences(PD) between the normal coronary artery and celiac arterial pressure, which would be compared with trans-stenosis pressure gradients(TSPG) in coronary artery occlusive disease. Material and Method: Between July, 1998 and February, 1999, pressures of the right coronary artery and the right gastroepiploic artery(or the celiac artery) were measured in patients with the patent right coronary artery(n=12). The PD between the arteries was compared with the TSPG in the occlusive coronary arteries(n=32). Result: The pressures of the normal right coronary artery and celiac artery were 143$\pm$23 vs. 134$\pm$17mmHg in systole(p<0.005), 74$\pm$13 vs. 73$\pm$14mmHg in diastole(p=NS), and 100$\pm$16 vs. 97$\pm$15mmHg in mean (p<0.05). The PD between the arteries were -8~25mmHg in systole, -4~7mmHg in diastole, and -1~10mmHg in mean. The TSPG measured in the occlusive coronary arteries were -4~19(7$\pm$5.8)mmHg in the lesion less than 75% stenosis vs. 7~74(27$\pm$18.3)mmHg in the 75% or over stenosis lesion(p<0.005). The normally existing pressure difference between the coronary arteries and RGEA(15~20mmHg) was significantlyless than the TSPG in .the occlusive coronary artery with 75% or over stenosis(p<0.001). Conclusion: If the pressure gradient between the RGEA and the coronary artery distal to the stenosis is the main determinant of development of retrograde flow competiton in the RGEA pedicled graft, the above data suggests that there will be little chance of competition when It is used in the coronary lesion with 75% or over stenosis.

Aspect of Blood Pressure after Oral Administration of Alcohol : Effect of Dissolved Oxygen on Blood Pressure (알코올 투여에 따른 혈압의 변화 양상 : 용존산소량에 따른 혈압 변화)

  • Song, Byung-Jeong;Lee, Byung-Yo;Chae, Jung-Woo;An, Jung-Hwa;Kwon, Kwang-Il
    • Korean Journal of Clinical Pharmacy
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    • v.22 no.3
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    • pp.228-233
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    • 2012
  • Purpose: The purpose of this study was to elucidate the effect of dissolved oxygen in alcohol to blood pressure of healthy persons. Methods: Subjects (n=30) were randomized in a double blind crossover study to receive 120 mL, 240 mL, 360 mL of alcohol (Korean spirit, 19.59 v/v%, dissolved oxygen is 8 ppm and 20 ppm). Blood alcohol concentration (BAC) and blood pressure were measured applying Lion SD-400 Alcolmeter$^{(R)}$ Breathalyser and Tensoval duo control. Pharmacokinetic parameters ($C_{max}$, $T_{max}$, $AUC_{last}$, $K_{el}$, $V_d$, Clearance) were calculated using Winnonlin$^{(R)}$ program. The difference of parameters and values were analysed by student t-test using Microsoft$^{(R)}$ Excel program. Results: The $AUC_{last}$ values of 8 ppm group and 20 ppm group in 240 ml administration were $6.15{\pm}2.60cg{\cdot}min/ml$, $5.33{\pm}1.84cg{\cdot}min/ml$ (p<0.05) and those in 360 mL were $11.93{\pm}5.70cg{\cdot}min/ml$, $10.33{\pm}4.60cg{\cdot}min/ml$ (p < 0.01), respectively. Thus, the $AUC_{last}$ was significantly decreased. On the other hands, there was a significant change in systolic blood pressure (SBP) after alcohol administration. All measured value after 360 mL of alcohol administration was significantly decreased (p < 0.01). Conclusions: The dissolved oxygen in alcoholic beverage has no effect on blood pressures but the alcohol administration has an effect on blood pressure. Thus, SBP can be used as a biomarker of alcohol administration and utilized in PK/PD modeling of alcohol.

Autocrine prostaglandin E2 signaling promotes promonocytic leukemia cell survival via COX-2 expression and MAPK pathway

  • Shehzad, Adeeb;Lee, Jaetae;Lee, Young Sup
    • BMB Reports
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    • v.48 no.2
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    • pp.109-114
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    • 2015
  • The COX-2/$PGE_2$ pathway has been implicated in the occurrence and progression of cancer. The underlying mechanisms facilitating the production of COX-2 and its mediator, $PGE_2$, in cancer survival remain unknown. Herein, we investigated $PGE_2$-induced COX-2 expression and signaling in HL-60 cells following menadione treatment. Treatment with $PGE_2$ activated anti-apoptotic proteins such as Bcl-2 and Bcl-xL while reducing pro-apoptotic proteins, thereby enhancing cell survival. $PGE_2$ not only induced COX-2 expression, but also prevented casapse-3, PARP, and lamin B cleavage. Silencing and inhibition of COX-2 with siRNA transfection or treatment with indomethacin led to a pronounced reduction of the extracellular levels of $PGE_2$, and restored the menadione- induced cell death. In addition, pretreatment of cells with the MEK inhibitor PD98059 and the PKA inhibitor H89 abrogated the $PGE_2$-induced expression of COX-2, suggesting involvement of the MAPK and PKA pathways. These results demonstrate that $PGE_2$ signaling acts in an autocrine manner, and specific inhibition of $PGE_2$ will provide a novel approach for the treatment of leukemia.

Electrical Properties of Multilayer Chip Varistors in the Response Surface Analysis (반응표면분석법에 의한 적층 칩 바리스터의 전기적 특성)

  • Yoon, Jung-Rag;Jeong, Tae-Seok;Choi, Keun-Mook;Lee, Seok-Weon
    • Journal of the Korean Institute of Electrical and Electronic Material Engineers
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    • v.20 no.6
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    • pp.496-501
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    • 2007
  • In order to enhance sintering characteristics on the $ZnO-Pr_6O_{11}$ based multilayer chip varistors (MLVs), a response surface analysis using central composite design method were carried out. As a result, varistor voltage($V_{1mA}$), nonlinear coefficient ($\alpha$), leakage current ($I_L$) and capacitance (C) were considered to be mainly affected by sintered temperature and holding time. MLVs sintered at $1200^{\circ}C$ and above $1200^{\circ}C$ revealed poor electrical characteristics, possibly due to the reaction between electrode materials(Pd) and $ZnO-Pr_6O_{11}$ based ceramics. On the sintering temperature range $1150{\sim}1175^{\circ}C$, nonlinear coefficient ($\alpha$) and leakage current ($I_L$) were shown to be $60{\sim}69$ and below $0.3{\mu}A$, respectively. In particular, MLVs sintered at $1175^{\circ}C$, 1.5 hr and $2^{\circ}C/hr$ (cooling speed) showed stable ESD(Electrical Static Discharge) characteristics under the condition of 10 times at 8 Kv with deviation varistor voltage, and deviation nonlinear coefficient were 0.3% and 0.33% (at positive), 0.55% (at negative), respectively.

Degradation of a Refractory Organic Contaminant by Photocatalytic Systems

  • Kim, Il-Kyu
    • Journal of Power System Engineering
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    • v.18 no.6
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    • pp.133-139
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    • 2014
  • In this research, the photocatalytic degradation of benzothiophene in $TiO_2$ aqueous suspension has been studied. $TiO_2$ photocatalysts are prepared by a sol-gel method. The dominant anatase-structure on $TiO_2$ particles is observed after calcining the $TiO_2$ gel at $500^{\circ}C$ for 1hr. Photocatalysts with various transition metals (Nd, Pd and Pt) loading are tested to evaluate the effect of transition metal impurities on photodegradation. The photocatalytic degradation in most cases follows first-order kinetics. The maximum photodegradation efficiency is obtained with $TiO_2$ dosage of 0.4g/L. The photodegradation efficiency with Pt-$TiO_2$ is higher than pure $TiO_2$ powder. The optimal content value of Pt is 0.5wt.%. Also we investigate the applicability of $H_2O_2$ to increase the efficiency of the $TiO_2$ photocatalytic degradation of benzothiophene. The optimal concentration of $H_2O_2$ is 0.05. The effect of pH is investigated; we obtain the maximum photodegradation efficiency at pH 9. Hydroxy-benzothiophenes and dihydroxy-benzothiophenes are identified as reaction intermediates. It is proposed that benzothiophene is oxidized by OH radical to sequentially form hydroxyl-benzothiophenes, dihydroxybenzothiophenes, and benzothiophenedione.