• Biomolecules & Therapeutics
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• 제21권1호
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• pp.54-59
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• 2013

In this study, we investigated the effect of (-)-epigallocatechin-3-gallate (EGCG), a major component of green tea catechins from green tea leaves, on activities of cyclooxygenase (COX)-1 and thromboxane synthase (TXAS), thromboxane $A_2$ ($TXA_2$) production associated microsomal enzymes. EGCG inhibited COX-1 activity to 96.9%, and TXAS activity to 20% in platelet microsomal fraction having cytochrome c reductase (an endoplasmic reticulum marker enzyme) activity and expressing COX-1 (70 kDa) and TXAS (58 kDa) proteins. The inhibitory ratio of COX-1 to TXAS by EGCG was 4.8. These results mean that EGCG has a stronger selectivity in COX-1 inhibition than TXAS inhibition. In special, a nonsteroid anti-inflammatory drug aspirin, a COX-1 inhibitor, inhibited COX-1 activity by 11.3% at the same concentration ($50{\mu}M$) as EGCG that inhibited COX-1 activity to 96.9% as compared with that of control. This suggests that EGCG has a stronger effect than that of aspirin on inhibition of COX-1 activity. Accordingly, we demonstrate that EGCG might be used as a crucial tool for a strong negative regulator of COX-1/$TXA_2$ signaling pathway to inhibit thrombotic disease-associated platelet aggregation.

• 대한본초학회지
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• 제26권4호
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• pp.125-132
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• 2011

Objectives : An aim of study is to investigate effects of curculiginis rhizoma in vitro (factor Xa (FXa) inhibitor assay, prothrombinase assay, prothrombin time (PT) assay, activated partial thromboplastin time (aPTT) assay) and in vivo experiment (blood clotting time, thromboxane B2 content assay in serum and weight of thrombus by AV-shunt rat model). Methods : We gained a human serum and used serum in vitro study such as factor X activity (FXa) inhibition, prothrombinase inhibition, prothrombin time (PT) and activated partial thromboplastin time. Fifteen SD rats were divided into three groups (intact control group and two experimental group treated with extract of Curculiginis Rhizoma(ECR)). Rats were orally administrated DW (intact control group), 600 mg/kg concertration of ECR and 200 mg/kg concertration of ECR. After one hour, we anesthetized rats and made arteriovenous (AV) shunt rat models to study weights of thrombus, took a hole blood to study content of thromboxane B2 and blood clotting time. Results : In vitro, ECR increased a inhibitory activity of FXa, prothrombinase and aPTT compared than intact control group. Especially ECR made significant increase of FXa and prothrombinase inhibitory activity (p<0.05, p<0.01). And PT were increased in ECR control group compared with intact control group. In vivo, a blood clotting time of experiment group treated with ECR 600 mg/kg were significantly increased compared with that of intact control group (p<0.05) and content of thromboxane B2 was significantly decreased in group treated with ECR 600 mg/kg in seum. The weight of thrombus were significantly reduced in group treated with ECR 600 mg/kg compared with intact control group (p<0.05). But in vivo experiment study, those of group treated with ECR 200 mg/kg were reduced compared with those of intact control group without statistical significance. Conclusions : ECR has a antithromboic activity in internal course with inhibitory activity of FXa and prothrombinase in vitro, it required to research more study for effective compounds.

• Journal of Periodontal and Implant Science
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• 제52권3호
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• pp.230-241
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• 2022

Purpose: The purpose of this study was to evaluate failed implants and reimplantation survival and to identify the relative risk factors for implant re-failure. Methods: Ninety-one dental implants were extracted between 2006 and 2020 at the National Health Insurance Service Ilsan Hospital, including 56 implants in the maxilla and 35 implants in the mandible that were removed from 77 patients. Patient information (e.g., age, sex, and systemic diseases) and surgical information (e.g., the date of surgery and location of the implants and bone grafts) were recorded. If an implant prosthesis was used, prosthesis information was also recorded. Results: In total, 91 first-time failed dental implants in 77 patients were analyzed. Of them, 69 implants in 61 patients received reimplantation after failure. Sixteen patients (22 implants) refused reimplantation or received reimplantation at a different site. Eight of the 69 reimplants failed again. The 1-year survival rate of the 69 reimplants was 89.4%. Age at reimplantation and smoking significantly increased the risk of reimplantation failure. However, a history of taking anti-thrombotic agents showed a statistically significant negative association with reimplantation failure. Of the failed implants, 66% showed early failure and 34% showed late failure of the initial implantation. All 8 re-failed implants showed early failure. Only 3 of these 8 failed reimplants were re-tried and the second reimplants all survived. Conclusions: The total survival rate of implants, which included reimplants and second reimplants was 99.2%, although the survival rate of the initial implantations was 96.3%. Previous failure did not affect the success of the next trial. Reimplantation failure was more strongly affected by patient factors than by implant factors. Therefore, each patient's specific factors need to be meticulously controlled to achieve successful reimplantation.

• Journal of Ginseng Research
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• 제46권5호
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• pp.683-689
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• 2022

Background: Since ginsenosides exert an anti-thrombotic activity, blood flow-improving effects of DK-MGAR101, an extract of mountain ginseng adventitious roots (MGAR) containing various ginsenosides, were investigated in comparison with an extract of Korean Red Ginseng (ERG). Methods: In Sprague-Dawley rats orally administered with DK-MGAR101 or ERG, oxidative carotid arterial thrombosis was induced with FeCl₃ (35%), and their blood flow and occlusion time were measured. To elucidate underlying mechanisms, the cytoprotective activities on rat aortic endothelial cells (RAOECs) exposed to hydrogen peroxide (H₂O₂) were confirmed. In addition, the inhibitory activities of DK-MGAR101 and ERG on agonist-induced platelet aggregation, thromboxane B₂ production, and ATP granule release from stimulated platelets as well as blood coagulation were analyzed. Results: DK-MGAR101 containing high concentrations of Rb1, Rg1, Rg3, Rg5, and Rk1 ginsenosides (55.07 mg/g) was more effective than ERG (ginsenosides 8.45 mg/g) in protecting RAOECs against H₂O₂ cytotoxicity. DK-MGAR101 was superior to ERG not only in suppressing platelet aggregation, thromboxane B₂ production, and granule release, but also in delaying blood coagulation, FeCl₃-induced arterial occlusion, and thrombus formation. Conclusions: The results indicate that DK-MGAR101 prevents blood vessel occlusion by suppressing platelet aggregation, thrombosis, and blood coagulation, in addition to endothelial cell injury.

• Journal of Ginseng Research
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• 제47권6호
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• pp.706-713
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• 2023

Background and objective: The ability to inhibit aggregation has been demonstrated with synthetically derived ginsenoside compounds G-Rp (1, 3, and 4) and ginsenosides naturally found in Panax ginseng 20(S)-Rg3, Rg6, F4, and Ro. Among these compounds, Rk3 (G-Rk3) from Panax ginseng needs to be further explored in order to reveal the mechanisms of action during inhibition. Methodology: Our study focused to investigate the action of G-Rk3 on agonist-stimulated human platelet aggregation, inhibition of platelet signaling molecules such as fibrinogen binding with integrin α_IIbβ₃ using flow cytometry, intracellular calcium mobilization, dense granule secretion, and thromboxane B₂ secretion. In addition, we checked the regulation of phosphorylation on PI3K/MAPK pathway, and thrombin-induced clot retraction was also observed in platelets rich plasma. Key Results: G-Rk3 significantly increased amounts of cyclic adenosine monophosphate (cAMP) and led to significant phosphorylation of cAMP-dependent kinase substrates vasodilator-stimulated phosphoprotein (VASP) and inositol 1,4,5-trisphosphate receptor (IP₃R). In the presence of G-Rk3, dense tubular system Ca²⁺ was inhibited, and platelet activity was lowered by inactivating the integrin αIIb/β₃ and reducing the binding of fibrinogen. Furthermore, the effect of G-Rk3 extended to the inhibition of MAPK and PI3K/Akt phosphorylation resulting in the reduced secretion of intracellular granules and reduced production of TXA₂. Lastly, G-Rk3 inhibited platelet aggregation and thrombus formation via fibrin clot. Conclusions and implications: These results suggest that when dealing with cardiovascular diseases brought upon by faulty aggregation among platelets or through the formation of a thrombus, the G-Rk3 compound can play a role as an effective prophylactic or therapeutic agent.

• Journal of Nutrition and Health
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• 제46권3호
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• pp.226-238
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• 2013

Omega-3 polyunsaturated fatty acids are essential fatty acids because humans cannot synthesize them de novo and must obtain them in their diet. Fish and fish oil are rich sources of omega-3 fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Significant evidence of the beneficial role of dietary intake of omega-3 fatty acids in blood flow has been reported and putative mechanisms for improvement of blood flow include anti-thrombotic effects, lowered blood pressure, improved endothelial function, and anti-atherogenic effects. Edible oils containing omega-3 fatty acids were registered as functional ingredients in the Korea Health Functional Food Code. Although omega-3 fatty acids have been evaluated by the Korea Food and Drug Administration (KFDA) based on scientific evidence, periodic re-evaluation may be needed because emerging data related to omega-3 fatty acids have accumulated. Therefore, in this study, we re-evaluated scientific evidence for the effect of omega-3 fatty acids as a functional ingredient in health functional food on improvement of blood flow. A comprehensive literature search was conducted for collection of relevant human studies using the Medline and Cochrane, KISS, and IBIDS databases for the years 1955-2012. Search keywords were used by combination of terms related to omega-3 fatty acids and blood flow. The search was limited to human studies published in Korean, English, and Japanese. Using the KFDA's evidence based evaluation system for scientific evaluation of health claims, 112 human studies were identified and reviewed in order to evaluate the strength of the evidence supporting a relation between omega-3 fatty acids and blood flow. Among 112 studies, significant effects on improvement of blood flow were reported in 84 studies and the daily intake amount was ranged from 0.1 to 15 g. According to this methodology of systematic review, we concluded that there was possible evidence to support a relation between omega-3 fatty acid intake and blood flow. However, because inconsistent results have recently been reported, future studies should be monitored.

• Journal of Chest Surgery
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• 제44권3호
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• pp.208-214
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• 2011

Background: Periprocedural treatment with high-dose statins is known to have cardioprotective and pleiotropic effects, such as anti-thrombotic and anti-inflammatory actions. We aimed to assess the efficacy of high-dose rosuvastatin loading in patients with stable angina undergoing off-pump coronary artery bypass grafting (OPCAB). Materials and Methods: A total of 142 patients with stable angina who were scheduled to undergo surgical myocardial revascularization were randomized to receive either pre-treatment with 60-mg rosuvastatin (rosuvastatin group, n=71) or no pre-treatment (control group, n=71) before OPCAB. The primary endpoint was the 30-day incidence of major adverse cardiac events (MACEs). The secondary endpoint was the change in the degree of myocardial ischemia as evaluated with creatine kinase-myocardial band (CK-MB) and troponin T (TnT). Results: There were no significant intergroup differences in preoperative risk factors or operative strategy. MACEs within 30 days after OPCAB occurred in one patient (1.4%) in the rosuvastatin group and four patients (5.6%) in the control group, respectively (p=0.37). Preoperative CK-MB and TnT were not different between the groups. After OPCAB, the mean maximum CK-MB was significantly higher in the control group (rosuvastatin group $10.7{\pm}9.75$ ng/mL, control group $14.6{\pm}12.9$ ng/mL, p=0.04). Furthermore, the mean levels of maximum TnT were significantly higher in the control group (rosuvastatin group $0.18{\pm}0.16$ ng/mL, control group $0.39{\pm}0.70$ ng/mL, p=0.02). Conclusion: Our findings suggest that high-dose rosuvastatin loading before OPCAB surgery did not result in a significant reduction of 30-day MACEs. However, high-dose rosuvastatin reduced myocardial ischemia after OPCAB.

• 생명과학회지
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• 제19권7호
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• pp.976-982
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• 2009

고대부터 식품으로 많이 이용되어 왔던 마늘의 성분중의 하나인 alliin의 혈관 생리활성을 조사하기 위해 다양한 실험을 수행하였다. Alliin은 혈관내피세포의 증식과 이동을 증진시키는 기능이 있으며, 이는 alliin이 혈관형성을 촉진하고 혈관의 상처 치유에 도움을 줄 수 있음을 의미한다. 또한 alliin은 염증반응을 일으키는 과정에 나타나는 THP-1 세포의 혈관내피세포 부착을 억제하며, 혈전을 형성하는 THP-1 동종세포간 응집을 억제하는 기능도 갖고 있음이 확인되었다. 이와 같은 alliin의 세포 기능은 혈관의 주요 질환인 동맥경화의 발생 및 뇌졸증이나 심근경색의 원인이 되는 혈전의 형성 등을 억제할 수 있음을 의미한다. 한편 혈관의 주요 조절자 중의 하나인 산화질소의 생산에는 alliin이 관여하지 않음을 확인하였다. 종합해 보면, alliin은 혈관세포의 여러 가지 생리기능을 조절하는 혈관생리기능 개선제로 활용할 가능성이 있는 물질이다.

• The Korean Journal of Physiology and Pharmacology
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• 제25권1호
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• pp.59-68
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• 2021

Arterial thrombosis and its associated diseases are considered to constitute a major healthcare problem. Arterial thrombosis, defined as blood clot formation in an artery that interrupts blood circulation, is associated with many cardiovascular diseases. Oxidative stress is one of many important factors that aggravates the pathophysiological process of arterial thrombosis. Apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ref-1) has a multifunctional role in cells that includes the regulation of oxidative stress and anti-inflammatory function. The aim of this study was to investigate the therapeutic effect of adenovirus-mediated Ref-1 overexpression on arterial thrombosis induced by 60% FeCl3 solution in rats. Blood flow was measured to detect the time to occlusion, thrombus formation was detected by hematoxylin and eosin staining, reactive oxygen species (ROS) levels were detected by high-performance liquid chromatography, and the expression of tissue factor and other proteins was detected by Western blot. FeCl3 aggravated thrombus formation in carotid arteries and reduced the time to artery occlusion. Ref-1 significantly delayed arterial obstruction via the inhibition of thrombus formation, especially by downregulating tissue factor expression through the Akt-GSK3β-NF-κB signaling pathway. Ref1 also reduced the expression of vascular inflammation markers ICAM-1 and VCAM-1, and reduced the level of ROS that contributed to thrombus formation. The results showed that adenovirus-mediated Ref-1 overexpression reduced thrombus formation in the rat carotid artery. In summary, Ref-1 overexpression had anti-thrombotic effects in a carotid artery thrombosis model and could be a target for the treatment of arterial thrombosis.

• 생명과학회지
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• 제21권10호
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• pp.1355-1363
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• 2011

많은 임상 실험을 통해 마늘(Allium sativum)이 심혈관 질환에 유효한 효과가 알려져 있다. 흑마늘(AGE)은 항산화, 항염증, 항암 효과 등 다양한 생물학적 효과가 보고되었다. 그러나, 흑마늘의 심혈관계 질환과의 상관관계에 대한 연구는 아직 미흡한 실정이다. 흑마늘과 그 유래 성분이 혈소판에 미치는 영향을 조사하였다. 백서의 혈액을 얻어, 흑마늘과 그 유래 성분의 thrombin에 의해 유도되는 혈소판 응집에 대한 억제 효과를 조사한 결과, 흑마늘과 diallyl sulphides는 농도의존적으로 혈소판 응집을 억제함을 관찰하였다. 또한 in vivo 실험에서도 마늘 오일과 S-Allylmercapto-cystein (SAMC)는 thrombin과 ADP에 의해 유도되는 혈소판 응집을 유의성 있게 억제하는 것을 관찰하였다. 흑마늘 유래 SAMC와 diallyl sulphides가 혈소판 응집 억제 효과를 나타내는 것을 확인할 수 있었다. 이러한 결과는 흑마늘이 심혈관계 질환의 예방을 위한 건강보조식품으로의 새로운 가능성을 제시한다.