• Clinical and Experimental Pediatrics
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• 제48권5호
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• pp.539-544
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• 2005

목 적 : 일반적인 혈관염에서의 sE-selectin의 역할을 고려할 때 가와사끼병에서도 중요한 역할을 할 것으로 예측하였다. 이에 가와사끼병의 진단지표로서의 가치 및 관상동맥병변의 합병을 예측하는 인자로서의 가능성이 있는지를 알아보고자 하였다. 방 법 : 1999년 1월부터 2004년 8월까지 건양대학교병원과 대전성모병원에 열성질환으로 입원한 환아 중 25명을 대조군으로 하였으며 같은 기간에 가와사끼병으로 입원하여 면역글로불린 치료를 받은 환아 23명을 대상으로 하여 관상동맥병변을 보인 5명과 보이지 않은 18명으로 나누었으며 치료 전, 면역글로불린 투여 후 2일, 2주, 4주째에 혈액을 채취해 효소면역측정법(ELISA)을 통해 혈청 sE-selectin 농도를 측정하였다. 결 과 : 1) 치료 전의 혈청 sE-selectin 농도는 가와사끼병 환자군에서 $22.89{\pm}12.53ng/mL$로 대조군의 $10.65{\pm}3.42ng/mL$에 비해 통계학적으로 유의하게 상승되어 있었다. 2) 가와사끼병 환자군에서 혈청 sE-selectin의 농도는 면역글로불린 투여 이후 급격히 감소하는 경향을 보였으며 이는 관상동맥병변의 유무에 따른 차이를 보이지 않았다. 3) 혈청 sE-selectin 농도는 다른 염증지표들 중 백혈구, CRP, 혈색소, 단백질, 알부민과 역상관관계를 보였으며, 그 외 ESR, 혈소판, 발열기간과는 유의한 상관관계를 보이지 않았다. 4) 가와사끼병 환자들 중 관상동맥병변에 대한 위험요인을 분석한 결과 치료 전의 혈청 sE-selectin과 혈색소치가 통계적으로 유의한 위험요인으로 나타났다($39.44{\pm}15.08ng/mL$ vs.$19.00{\pm}17.18ng/mL$, $9.98{\pm}0.46g/dL$ vs. $10.98{\pm}0.78g/d$L). 결 론: 가와사끼병 환자에서 혈청 sE-selectin은 다른 열성 질환에 비해 의미있게 상승하는 것으로 나타나 감별진단에 도움이 될 것으로 생각되며 특히, 관상동맥병변의 합병을 예측하는 인자로서의 가능성을 보였다.

• Clinical and Experimental Pediatrics
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• 제57권12호
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• pp.533-537
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• 2014

Purpose: Obesity is related to systemic inflammatory processes causing cardiovascular complications. Intercellular adhesion molecule-1 (ICAM-1), CD40 ligand (CD40L), P-selectin are newly described mediators of inflammation and have a significant effect in atherosclerosis. Adiponectin has shown anti-inflammatory effects in adults. The aim of this study was to evaluate the relationship between adiponectin and inflammatory mediators in children and adolescents. Methods: Fifty children or adolescents, twenty two with a body mass index (BMI) over 95th percentile, and twenty eight with a BMI below 75th percentile were included in the study. Serum soluble ICAM-1 (sICAM-1), P-selectin, CD40L, lipid profiles, aspartate aminotransferase, alanine aminotransferase, glucose and insulin were measured to evaluate associations with adiponectin. Comparison of these variables was performed between the obese and the nonobese group. Results: We found a adiponectin to be significant lower and sICAM-1 significant higher in the obese group compared to the nonobese group, but there were no significant differences in P-selectin and soluble CD40L. Adiponectin was negatively associated with ICAM-1 and P-selectin in the obese group. Conclusion: Negative associations of adiponectin with ICAM-1 and P-selectin in obese children and adolescents suggest that serum adiponectin level may represent the inflammatory status.

• Asian Pacific Journal of Cancer Prevention
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• 제17권12호
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• pp.5273-5280
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• 2016

Objective: To evaluate stromal cells of the bone marrow microenvironment (BMM) in bone marrow trephine biopsy (BMTB) specimens, with a focus on fibronectin, tumor necrosis factor- alpha (TNF-${\alpha}$) and L-selectin in Non-Hodgkin's lymphoma (NHL) patients, before and after therapy. Materials and Methods: A total of 80 de novo NHL patients, 64 with B-cell lymphomas 80%, (follicular cell lymphoma (FCL) in 32, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in 12, and diffuse large cell lymphoma in 20) and 16 with T-cell lymphomas (20%) all diagnosed as T-Lymphoblastic lymphomas, were evaluated before and after therapy. For comparison, 25 age and sex matched BM donors, were included as a control group. BMTB material and BM aspirates were taken for morphological assessment of stromal cells, the plasma of these samples being examined for $TNF{\alpha}$ and L-selectin by ELISA, and fibronectin by radial immunodiffusion (RID). Results: BM stromal cells comprising reticular macrophages and fibroblasts were elevated in 53.3% of NHL cases at diagnosis, while BM fibronectin levels were decreased and BM $TNF{\alpha}$ and L-selectin were higher than in controls (p<0.05). In NHL cases, elevated values of BM $TNF{\alpha}$ and BM L-selectin were associated with signs of aggressive disease, including >1 extra nodal sites, detectable B symptoms, high grade, BM and CNS invasion, and a high International prognostic index (IPI) (p<0.05). Conclusion: BMM components, $TNF{\alpha}$, L-selectin and fibronectin, in NHL can be useful in evaluating disease activity, extent and response to treatment and as prognostic markers according to the IPI.

• 한국임상수의학회지
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• 제19권3호
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• pp.299-302
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• 2002

Selectin은 조직 염증반응의 초기화에 관여하는 결합 단백질이며, 맥관내피에서 백혈구의 rolling과 tethering을 매개한다. 따라서 selectin inhibitor를 이용하여, 이들 selectin의 수용체인 sLex 에 대한 block을 유도함으로서 염증반응의 초기화를 억제할 수 있다는 가정하에, 본 연구에서는 장기이식 후 reperfusion에서 발생하는 손상에 대한 selectin inhibitor의 효과를 알아보았다. Beagle 견을 사용하여 신장이식을 실시하였다 공여 신장은 60분의 warm ischemia를 유도한 후 UW solution으로 관류하고 24시간동안 냉장보관하여 자가이식하였으며, 반대쪽 신장은 적출하였다. 술 후 7일동안 혈청 creatinine치를 측정하였다 2차실험으로, 12마리의 Beagle견을 사용하여 4시간의 reperfusion 후 조직학적 변화와 myeloperoxidase의 활성을 조사하였다. 각 실험의 대조군은 생리 식염수를,비교군은 TBC1269 (selectin inhibitor)를 신장 적출 전과 신장이식 수술 후 reperfusion 직전에 각각 투여하였다. 혈청 creatinine은 신장이식후 급격히 증가 하였으나, 두군 사이에 유의적인 차이는 없었다. 신장피질의 백혈구 침윤은, 4시간 reperfusion후 생리식염수를 투여받은 군에서 2배의 유의적인 증가를 보였다. 그러나, TBC 1269로 처리한 군에서는 백혈구의 침윤이 유의적인 억제를 보였으며, 허혈에의한 조직학적 변화도 유의적으로 적었다. 개의 신장이식 수술에서 Selectin의 차단은 warm renal ischemia에서 기인된 손상을 개선하지는 못하나, 백혈구의 침윤을 억제하므로 delayed graft function과 관련된 술 후 염증반응의 초기화를 억제하는 효과가 있는 것으로 사료된다.

• 대한의생명과학회지
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• 제23권4호
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• pp.310-320
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• 2017

Ginseng has been widely used for traditional medicine in eastern Asia and is known to have inhibitory effects on cardiovascular disease (CVD) such as thrombosis, atherosclerosis, and myocardial infarction. Because, platelet is a crucial mediator of CVD, many studies are focusing on inhibitory mechanism of platelet functions. Among platelet activating molecules, thromboxane $A_2$ ($TXA_2$) and P-selectin play a central role in CVD. $TXA_2$ leads to intracellular signaling cascades and P-selectin plays an important role in platelet-neutrophil and platelet-monocyte interactions leading to the inflammatory response. In this study, we investigated the inhibitory mechanisms of total saponin fraction from Korean red ginseng (KRG-TS) on $TXA_2$ production and P-selectin expression. Thrombin-elevated $TXA_2$ production and arachidonic acid release were decreased by KRG-TS dose (25 to $150{\mu}g/mL$)-dependently via down regulation of microsomal cyclooxygenase-1 (COX-1), $TXA_2$ synthase (TXAS) activity and dephosphorylation of cytosolic phospholipase $A_2$ ($cPLA_2$). In addition, KRG-TS suppressed thrombin-activated P-selectin expression, an indicator of granule release via dephosphorylation of mitogen-activated protein kinases (MAPK). Taken together, we revealed that KRG-TS is a beneficial novel compound inhibiting $TXA_2$ production and P-selectin expression, which may prevent platelet aggregation-mediated thrombotic disease.

• Journal of Menopausal Medicine
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• 제24권3호
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• pp.176-182
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• 2018

Objectives: Menopause is associated with adverse metabolic changes in plasma lipoprotein and inflammation markers. Estrogens have beneficial effects on lipid metabolism and inflammation. Isoflavones (ISO) have structurally similar to estradiol. Our objective was analize the effect of soy-ISO on serum lipid and inflammatory markers (sP-selectin and sCD40L) in postmenopausal women. Methods: A 12-week randomized, double-blind, placebo-controlled intervention with soy-ISO (50 mg, twice daily) was conducted in 35 healthy postmenopausal women (55-72 years old). The women were divided in 2 groups: 20 were allocated to soy-ISO, and 15 to a placebo group. Results: The changes of total cholesterol (TC), triglycerides, low-density lipoproteins-cholesterol (LDL-C), high-density lipoprotein-cholesterol, Apo-A1, sP-selectin and sCD40L in 2 groups before and after 12-week treatment showed no statistical significance. In subgroup analysis, soy-ISO supplementation significantly decreased the levels of TC, LDL-C and sCD40L in women under 65 years old, and with null effects on serum lipid and inflammation markers in women over 65 years old. Conclusions: Soy-ISO did not significantly favorable effects on the lipid profile and inflammatory markers in postmenopausal women. However, in women under 65 years of age, soy-ISO significantly decreased the TC, LDL-C and sCD40L, whereas, no effects on lipid profile and inflammation markers in women over 65 years old were observed.

• Archives of Pharmacal Research
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• 제28권1호
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• pp.55-60
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• 2005

Leukocyte adhesion to the vascular endothelium is a critical initiating step in inflammation and atherosclerosis. We have herein studied the effect of manassantin A (1) and S (2), dineolignans, on interaction of THP-1 monocytic cells and human umbilical vein endothelial cells (HUVEC) and expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in HUVEC. When HUVEC were pretreated with 1 and 2 followed by stimulation with $TNF-{\alpha}$, adhesion of THP-1 cells to HUVEC decreased in dose-dependent manner with $IC_{50}$ values of 5 ng/mL and 7 ng/mL, respectively, without cytotoxicity. Also, 1 and 2 inhibited $TNF-{\alpha}-induceda$ up-regulation of ICAM-1, VCAM-1 and E-selectin. The present findings suggest that 1 and 2 prevent monocyte adhesion to HUVEC through the inhibition of ICAM-1, VCAM-1 and E-selectin expression stimulated by $TNF-\alpha$, and may imply their usefulness for the prevention of atherosclerosis relevant to endothelial activation.

• KSBB Journal
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• 제22권4호
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• pp.249-254
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• 2007

동백잎의 열수 추출물이 신생혈관 생성억제 효과가 강하게 나타남으로써 이들 추출물에 대한 독성 시험을 HUVECs를 사용하여 검토한 바는 200 ug/mL에서도 독성이 없는 것으로 나타났으며, 1.5, 3.0, 15 및 30 ug/mL으로 농도가 증가함에 따라 각각 30.7%, 38.5%, 53.8% 그리고 70.0%의 신생혈관 생성억제율을 보였다. 세포부착 저해효과는 C. japonica leaf (CJL)의 농도가 50, 100, $200{\mu}g{/well}$으로 증가할 때 E-selectin이 46.7%, 66.7% 그리고 86.76%, VCAM-1이 23.0%, 61.5% 그리고 84.6%, ICAM-1이 11.0%, 55.5% 그리고 88.8%로 나타났다. C. japonica leaf (CJL)의 성분 증가에 따라 발현이 감소되는 것을 보아 농도가 증가함에 따라 cell adhesion의 저해 효과가 높아짐을 알 수 있었다. 신호전달의 기전규명은 western blot으로 행하였으며 CJL의 농도가 증가함에 따라 밴드의 발현이 약해지는 것을 관찰할 수 있다. 따라서 신호전달 분자인 VEGFR-2, $\beta$-catenin, Pl3-K는 CJL에 의해 신호전달이 차단되는 것을 볼 수 있고, 이는 NF-${\kappa}$B를 억제함으로서 신생혈관 생성을 저해하는 것으로 확인되었다. 따라서 동백잎은 신생혈관 생성에 의존하고 있는 것으로 알려진 암 등의 치료와 암전이의 억제, 류마치스성 관절염, 그리고 항비만제제로서 개발될 수 있음을 시사한다.

• Food Science and Biotechnology
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• 제17권6호
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• pp.1197-1202
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• 2008

Present study investigated the effects of the 70% ethanol extracts of tissue-cultured mountain ginseng (TCMG), Korean red ginseng (KRG), and Panax ginseng (PG) on agonist-induced platelet aggregation and activation in human whole blood. The $IC_{50}$ values for TCMG, KRG, and PG were 1.159, 3.695, and 4.978mg/mL for collagen-induced aggregation, 0.820, 2.030, and 4.743mg/mL for arachidonic acid-induced aggregation, and 1.070, 2.617, and 2.954 mg/mL for ADP-induced aggregation, respectively. Also, this study assessed the effects of the most active extract, TCMG, on markers of platelet activation by determining receptor expression on platelet membranes in healthy subjects, including expression of GPIIb/IIIa-like (PAC-1) and P-selectin (CD62), by flow cytometry. A significant decrease in PAC-l expression (p=0.018) was observed in the presence of TCMG. These results show that TCMG has potent anti-platelet activity.

• 대한한방부인과학회지
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• 제32권3호
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• pp.20-31
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• 2019

Objectives: The seeds from Arctium lappa have been considered for its various pharmacological properties, which include anti-carcinogenic, anti-inflammatory, anti-diabetic, and anti-viral activities. Methods: In the present study, we investigated the anti-inflammatory effect of the ethanol extract from the seeds of Arctium lappa L (EAL) on cytokine-induced vascular inflammation in human umbilical vein endothelial cells (HUVEC). Results: Pretreatment with EAL significantly decreased tumor necrosis factor alpha ($TNF-{\alpha}$)-induced cell adhesion molecules expression such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial-selectin (E-selectin) in a dose-dependent manner. Cell adhesion assay showed that pretreatment with EAL suppressed HUVEC-monocyte adhesion by $TNF-{\alpha}$ over $1{\mu}g/ml$ concentration. We investigated the involvement of nuclear transcription factor kappa-B ($NF-{\kappa}B$) in $TNF-{\alpha}$-induced vascular inflammation. $NF-{\kappa}B$ p65 nuclear expression was induced by $TNF-{\alpha}$, however, pretreatment with EAL was attenuated that nuclear translocation. In cytoplasm, EAL was also attenuated $TNF-{\alpha}$-induced decrease of inhibitor of ${\kappa}B-{\alpha}$ ($I{\kappa}B-{\alpha}$) expression. Moreover, EAL significantly decreased $TNF-{\alpha}$-induced production of intracellular reactive oxygen species (ROS). Conclusions: Taken together, our findings suggest that seeds of Arctium lappa L could be a therapeutic herb for prevention of cardiovascular diseases throughout the inhibition of vascular endothelial inflammation.