• 제목/요약/키워드: PD-L2

검색결과 280건 처리시간 0.028초

Oxytocin-induced endothelial nitric oxide dependent vasorelaxation and ERK1/2-mediated vasoconstriction in the rat aorta

  • Xu, Qian;Zhuo, Kunping;Zhang, Xiaotian;Zhang, Yaoxia;Xue, Jiaojiao;Zhou, Ming-Sheng
    • The Korean Journal of Physiology and Pharmacology
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    • 제26권4호
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    • pp.255-262
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    • 2022
  • Oxytocin is a neuropeptide produced primarily in the hypothalamus and plays an important role in the regulation of mammalian birth and lactation. It has been shown that oxytocin has important cardiovascular protective effects. Here we investigated the effects of oxytocin on vascular reactivity and underlying the mechanisms in human umbilical vein endothelial cells (HUVECs) in vitro and in rat aorta ex vivo. Oxytocin increased phospho-eNOS (Ser 1177) and phospho-Akt (Ser 473) expression in HUVECs in vitro and the aorta of rat ex vivo. Wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K), inhibited oxytocin-induced Akt and eNOS phosphorylation. In the rat aortic rings, oxytocin induced a biphasic vascular reactivity: oxytocin at low dose (10-9-10-8 M) initiated a vasorelaxation followed by a vasoconstriction at high dose (10-7 M). L-NAME (a nitric oxide synthase inhibitor), endothelium removal or wortmannin abolished oxytocin-induced vasorelaxation, and slightly enhanced oxytocin-induced vasoconstriction. Atosiban, an oxytocin/vasopressin 1a receptor inhibitor, totally blocked oxytocin-induced relaxation and vasoconstriction. PD98059 (ERK1/2 inhibitor) partially inhibited oxytocin-induced vasoconstriction. Oxytocin also increased aortic phospho-ERK1/2 expression, which was reduced by either atosiban or PD98059, suggesting that oxytocin-induced vasoconstriction was partially mediated by oxytocin/V1aR activation of ERK1/2. The present study demonstrates that oxytocin can activate different signaling pathways to cause vasorelaxation or vasoconstriction. Oxytocin stimulation of PI3K/eNOS-derived nitric oxide may participate in maintenance of cardiovascular homeostasis, and different vascular reactivities to low or high dose of oxytocin suggest that oxytocin may have different regulatory effects on vascular tone under physiological or pathophysiological conditions.

향부자(香附子)의 염증 억제 작용을 통한 항파킨슨 효과 (Anti-parkinsonian effect of Cyperi Rhizoma via inhibition of neuroinflammatory action)

  • 김효근;심여문;오명숙
    • 대한본초학회지
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    • 제28권5호
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    • pp.21-28
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    • 2013
  • Objectives : The aim of this study was to investigate the neuroprotective effects and mechanisms of Cyperi Rhizoma extracts (CRE) using in vitro and in vivo models of Parkinson's disease (PD). Methods : We evaluated the neuroprotective effect of CRE against 1-methyl-4-phenylpyridinium (MPP+) toxicity using tyrosine hydroxylase immunohistochemistry (IHC) in primary rat mesencephalic dopaminergic neurons. In addition, the effect of CRE was evaluated in mice PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). For evaluations, C57bl/6 mice were orally treated with CRE 50 mg/kg for 5 days and were injected intraperitoneally with MPTP (20 mg/kg) at 2 h intervals on the last day. To identify the CRE affects on MPTP-induced neuronal loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) and striatum of mice, the behavioral tests and IHC analysis were carried out. Also, we conducted nitric oxide (NO) and tumor necrosis factor-alpha (TNF-${\alpha}$) assay in dopaminergic neurons and IHC using glial markers in SNpc of mice to assess the anti-inflammation effects. Results : In primary mesencephalic culture system, CRE protected dopaminergic cells against $10{\mu}M$ MPP+-induced toxicity at 0.2 and $1.0{\mu}g/mL$. In the behavior tests, CRE treated group showed improved motor deteriorations than those in the MPTP only treated group. CRE significantly protected striatal dopaminergic damage from MPTP-induced neurotoxicity in mice. Moreover, CRE inhibited productions of NO and TNF-${\alpha}$ in dopaminergic culture system and activation of astrocyte and microglia in SNpc of the mice. Conclusion : We concluded that CRE shows anti-parkinsonian effect by protecting dopaminergic neurons against MPP+/MPTP toxicities through anti-inflammatory actions.

실외 실험적 온난화 및 강수 처리에 따른 소나무와 낙엽송 유묘의 초기 생장 특성 (The Early Growth Performances of Pinus densiflora and Larix kaempferi Seedlings Under Open-field Experimental Warming and Precipitation Manipulation)

  • 권보람;조민석;양아람;장한나;안지애;손요환
    • 한국산림과학회지
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    • 제109권1호
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    • pp.31-40
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    • 2020
  • 본 연구는 기후변화와 관련하여 양묘과정에서 온도와 강수 변화에 따른 주요 침엽수의 생존 및 생장 특성 변화를 알아보고자 수행하였다. 소나무와 낙엽송 노지묘(1-0)를 대상으로 대조구 기준 3℃의 온도를 상승시키거나 ±40%의 강수를 조절한 6처리 생육환경[온도 2처리(대조: TC, 증가: TW) × 강수 3처리(대조: PC, 감소: PD, 증가: PI)] 실외 실험구를 조성하였으며, 생존율, 근원경, 묘고, 물질생산량 및 묘목품질지수 변화를 조사하여 이원분산분석을 수행하였다. 소나무는 온도와 강수 처리에 따른 생존율 차이가 없었지만, 강수가 증가할수록 묘목품질지수가 낮아지는 경향을 보였다. 낙엽송은 온도 상승과 강수 감소에 따라 고사율이 증가하였으며, 묘목품질지수는 두 요인 간 상호작용을 보이면서 온도대조-강수증가 처리구에서 가장 낮게 나타났다. 따라서 양묘과정에서 소나무는 강수 증가, 낙엽송은 온도 증가 또는 강수 감소에서 낮은 묘목 생산량과 품질이 예상되며, 기후변화에 따른 두 수종의 특이적 민감도를 확인할 수 있었다. 향후 지구온난화와 가뭄·폭우 등의 강수 변화에 의해 수종별 묘목 생존과 품질의 변화가 예상되기 때문에 각 수종의 생육 반응 특성에 따른 적합한 양묘시업 대응 전략이 필요할 것으로 판단된다.

무전해Ni도금에 의한 선택적 CONTACT HOLE 충진 (Selective Contact Hole Filling by Electroless Ni Plating)

  • 김영기;우찬희;박종완;이원해
    • 한국재료학회:학술대회논문집
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    • 한국재료학회 1992년도 춘계학술발표회
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    • pp.26-27
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    • 1992
  • 반도체 기억소자 contact hole의 선택적 충진의 최적 조건을 연구하기 위하여 무전해Ni도금방법을 채택하여 실리콘의 활성화와 선택적 도금의 공정조건이 Contact Hole 도금피막의 제반 특성에 미치는 영향을 조사하였다. p형 실리콘 100 소지 표면의 활성화 처리는 RCA처리에 의해 먼저 표면을 세척한 다음 온도, PdCl$_2$농도, 시간. 교반의 영향을 조사하였다 전처리의 최적조건은 7$0^{\circ}C$, 0.5M HF, ImM PdCl$_2$, 2mM EDTA, 90second이었다. 무전해도금은 NiS0$_4$.6$H_2O$를 DMAB를 환원제로 하여 온도, DMAB 농도, pH, 도금시간의 영향을 조사하였다. 무전해 도금 피막은 비교적 우수한 접촉저 항을 나타냈다. 1$\mu$m의 도금막을 얻는 데 본 실험조건에서 DMAB의 농도가 8mM일 때 30 분이 소요되었다. 도금막의 표면은 온도가 낮을수록 pH가 높을수록 평활하였고,특히 온도 6$0^{\circ}C$와 pH6.8에서 가장 우수하였다. 미세경도는 600Hv 정도였으며, 결정립의 크기 가 증가할수록 저항과 미세경도가 감소하였다.

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Curcumin Inhibits TGF-β1-Induced MMP-9 and Invasion through ERK and Smad Signaling in Breast Cancer MDA-MB-231 Cells

  • Mo, Na;Li, Zheng-Qian;Li, Jing;Cao, You-De
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권11호
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    • pp.5709-5714
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    • 2012
  • Objective: To evaluate the effects of curcumin on matrixmetalloproteinase-9 (MMP-9) and invasion ability induced by transforming growth factor-${\beta}1$ (TGF-${\beta}1$) in MDA-MB-231 cells and potential mechanisms. Methods: Human breast cancer MDA-MB-231 cells were used with the CCK-8 assay to measure the cytotoxicity of curcumin. After treatment with 10 ng/ml TGF-${\beta}1$, with or without curcumin (${\leq}10{\mu}M$), cell invasion was checked by transwell chamber. The effects of curcumin on TGF-${\beta}1$-stimulated MMP-9 and phosphorylation of Smad2, extracellular-regulated kinase (ERK), and p38 mitogen activated protein kinases (p38MAPK) were examined by Western blotting. Supernatant liquid were collected to analyze the activity of MMP-9 via zymography. Following treatment with PD98059, a specific inhibitor of ERK, and SB203580, a specific inhibitor of p38MAPK, Western blotting and zymography were employed to examine MMP-9 expression and activity, respectively. Results: Low dose curcumin (${\leq}10{\mu}M$) did not show any obvious toxicity to the cells, while $0{\sim}10{\mu}mol/L$ caused a concentration-dependent reduction in cell invasion provoked by TGF-${\beta}1$. Curcumin also markedly inhibited TGF-${\beta}1$-regulated MMP-9 and activation of Smad2, ERK1/2 and p38 in a dose- and time-dependent manner. Additionally, PD98059, but not SB203580, showed a similar pattern of inhibition of MMP-9 expression. Conclusion: Curcumin inhibited TGF-${\beta}1$-stimulated MMP-9 and the invasive phenotype in MDA-MB-231 cells, possibly associated with TGF-${\beta}$/Smad and TGF-${\beta}$/ERK signaling.

Manual Contouring Based Volumetric Evaluation for Colorectal Cancer with Liver Limited Metastases: A Comparison with RECIST

  • Fang, W.J.;Lam, K.O.;Ng, S.C.Y.;Choi, C.W.;Kwong, D.L.W.;Zheng, S.S.;Lee, V.H.F.
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권7호
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    • pp.4151-4155
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    • 2013
  • Background: To compare response evaluation criteria in solid tumours (RECIST) and volumetric evaluation (VE) for colorectal cancer with liver-limited metastasis. Patients and Methods: VE of liver metastases was performed by manual contouring before and after chemotherapy on 45 pairs of computed tomography (CT) images in 36 patients who suffered from metastatic colorectal cancer (mCRC) with liver metastasis only. Cohen kappa was used to compare the agreement between VE and RECIST. Pearson correlation was performed for their comparison after cubic root transformation of the aggregate tumor volumes. Logistic regression was done to identify clinical and radiographic factors to account for the difference which may be predictive in overall response (OR). Results: There were 16 partial response (PR), 23 stable disease (SD) and 6 progressive disease (PD) cases with VE, and 14 PR, 23 SD and 8 PD with RECIST. VE demonstrated good agreement with RECIST (${\chi}$=0.779). Discordant objective responses were noted in 6 pairs of comparisons (13.3%). Pearson correlation also showed excellent correlation between VE and RECIST ($r^2$=0.966, p<0.001). Subgroup analysis showed that VE was in slightly better agreement with RECIST for enlarging lesions than for shrinking lesions ($r^2$=0.935 and $r^2$=0.780 respectively). No factor was found predictive of the difference in OR between VE and RECIST. Conclusions: VE exhibited good agreement with RECIST. It might be more useful than RECIST in evaluation shrinking lesions in cases of numerous and conglomerate liver metastases.

Evaluation of interleukin-$1{\beta}$ and 8 in gutka chewers with periodontitis among a rural Indian population

  • Jacob, Pulikottil Shaju;Nath, Sonia;Patel, Ritu Prabha
    • Journal of Periodontal and Implant Science
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    • 제44권3호
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    • pp.126-133
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    • 2014
  • Purpose: Smokeless tobacco-based oral-use products like gutka are popular in India. Gutka usage leads to increased periodontal destruction and inflammation; however, the relevant mechanism remains unknown. This study aimed to elucidate the role of gutka in periodontitis by examining its effect on the levels of interleukin (IL) $1{\beta}$ and IL-8 from the gingival crevicular fluid (GCF). Methods: A total of 45 patients were enrolled in this study. Thirty patients with periodontitis (15 gutka chewers [GCP] and 15 nongutka chewers [NGC]) and 15 periodontally healthy controls (HC) were selected. The full-mouth plaque index (PI), gingival index (GI), probing depth (PD), clinical attachment level (CAL), and recession (RC) were recorded. The IL-$1{\beta}$ and IL-8 levels in the GCF of all subjects were assessed through an enzyme-linked immunosorbent assay (Quantikine). Results: The IL-$1{\beta}$ and IL-8 levels were not significantly higher in the GCP group (IL-$1{\beta}$, $369.01{\pm}273.44{\mu}L$; IL-8, $205.97{\pm}196.78{\mu}L$) as compared to those in the NGC group (IL-$1{\beta}$, $195.57{\pm}96.85{\mu}L$; IL-8, $178.61{\pm}149.35{\mu}L$). More gingival RC and loss of attachment was seen among the GCP group (RC: $2.02{\pm}0.31$, P=0.013; CAL: $4.60{\pm}0.56$, P<0.001) than among the NGC group (RC, $1.21{\pm}1.15$; CAL, $3.70{\pm}0.32$); however, PD was deeper among the NGC subjects (P=0.002). PI and GI were significantly higher for the periodontitis group (P<0.001) when compared to the HC, but there was no difference among gutka chewers and non-chewers (P=0.22 and P=0.89). A positive correlation was found between the IL-8 levels and the duration of gutka chewing (r=-0.64, P<0.01). Conclusions: Gutka chewing leads to increased gingival RC and clinical loss of attachment. There was no effect seen in the proinflammatory cytokine levels in the GCF of gutka users.

Effects of Ginseng Saponins on the Development and Loss of Morphine Tolerance and Dependence

  • Kim, Hack-Seang;Oh, Sei-Kwan;Choi, Kang-Ju;Park, Jung-Sup
    • 생약학회지
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    • 제17권2호
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    • pp.139-147
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    • 1986
  • Ginseng saponins(GS), protopanaxadiol saponins(PD) and protopanaxatriol saponins (PT) were tested for the inhibition of the development of morphine tolerance and dependence antagonism of morphine analgesia and the loss of morphine tolerance and dependence in mice The results were as follows: 1. Inhibition of the development of morphine tolerance and dependence. 2. Antagonism of morphine analgesia. 3. Increase in the loss of morphine tolerance and dependence. Antagonism of morphine by ginseng saponins and its reversal by L-DOPA and 5-HTP suggest some possibility that catecholamines and serotonin levels might be associated with the results.

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Synthesis and Antiviral Activity of 2'(β)-Hydroxymethylated Carbodine Analogues Against Hepatitis C Virus

  • Hong, Joon-Hee;Oh, Chang-Hyun
    • Bulletin of the Korean Chemical Society
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    • 제30권11호
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    • pp.2626-2630
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    • 2009
  • 2'($\beta$)-Hydroxymethylated adenosine is a potent and selective inhibitor of hepatitis C virus (HCV) replication. It targets the RNA-dependent RNA polymerase of HCV, NS5B. Synthesis and antiviral evaluation of carbocyclic versions are described. The cyclopentene intermediate ($9\beta$) was successfully synthesized through sequential Johnson-Claisen orthoester rearrangement and ring-closing metathesis (RCM). Coupling of bases via a Pd(0) catalyst, selective dihydroxylation, and desilylation yielded the target nucleoside analogues. The compounds 17 and 18 were assayed for their ability to inhibit HCV RNA replication in a subgenomic replicon Huh7 cell line and showed moderate antiviral activity with toxicity up to 20.0 and 24.7 ${\mu}g/mL$, respectively.

프라다 아오야마 에피센터 건축에서 나타나는 환경과 사물과 통합되는 다층적 물질성의 표면에 관한 연구 (A Study on the Integration of Objects and Environment in the Surface with Changing Materiality of Prada Aoyama Epicenter)

  • 김희범;강재혁;최원아
    • 대한건축학회논문집:계획계
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    • 제34권2호
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    • pp.33-40
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    • 2018
  • The purpose of this study was to analyze integration of the surface of Prada Aoyama Epicenter by Herzog & de Meuron. To understand various aspects of surfaces & constituents related, each elevations are analyzed minutely by distance both inside and outside. The results of this study were as follows; the individual surface of Prada Aoyama Epicenter sets a multi-layered relationship with the actual environment. Their architectural surface still has a significance in presenting a way of creating a building along with everyday surroundings.