• BMB Reports
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• 제44권8호
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• pp.506-511
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• 2011

Mammalian Target of Rapamycin (mTOR) is a serine/threonine kinase and that forms two multiprotein complexes known as the mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). mTOR regulates cell growth, proliferation and survival. mTORC1 is composed of the mTOR catalytic subunit and three associated proteins: raptor, mLST8/$G{\beta}L$ and PRAS40. mTORC2 contains mTOR, rictor, mLST8/$G{\beta}L$, mSin1, and protor. Here, we discuss mTOR as a promising anti-ischemic agent. It is believed that mTORC2 lies down-stream of Akt and acts as a direct activator of Akt. The different functions of mTOR can be explained by the existence of two distinct mTOR complexes containing unique interacting proteins. The loss of TSC2, which is upstream of mTOR, activates S6K1, promotes cell growth and survival, activates mTOR kinase activities, inhibits mTORC1 and mTORC2 via mTOR inhibitors, and suppresses S6K1 and Akt. Although mTOR signaling pathways are often activated in human diseases, such as cancer, mTOR signaling pathways are deactivated in ischemic diseases. From Drosophila to humans, mTOR is necessary for Ser473 phosphorylation of Akt, and the regulation of Akt-mTOR signaling pathways may have a potential role in ischemic disease. This review evaluates the potential functions of mTOR in ischemic diseases. A novel mTOR-interacting protein deregulates over-expression in ischemic disease, representing a new mechanism for controlling mTOR signaling pathways and potential therapeutic strategies for ischemic diseases.

• 대한한의학회지
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• 제29권2호
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• pp.1-6
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• 2008

Objectives: This study aimed to investigate the seasonal variation in stroke types, ischemic stroke subtypes, stroke risk factors and Sasang constitutions. Methods: 226 patients with acute stroke within 14 days onset were included, who were admitted to Kyunghee Oriental Medical Center from November 2005 to October 2006. The year was subdivided into four parts: spring (March-May); summer (June-August); fall (September-November); and winter (December-February). Stroke types, ischemic stroke subtypes, stroke risk factors and Sasang constitutions in the four groups were examined. Results: Ischemic stroke was most frequent in summer, whereas hemorrhagic stroke was most frequent in winter. There was no significant difference in seasonal variation of stroke. The frequency of ischemic heart disease among stroke risk factors was significantly high in spring (p=0.031). The frequency of hypertension, diabetes mellitus, atrial fibrillation, and hyperlipidemia did not differ among seasons. There was no significant difference in Sasang constitution among seasons. Frequency of small vessel occlusion was highest in summer. Large artery atherosclerosis was frequent in spring and summer,but seasonal variation of ischemic stroke subtypes did not show statistical difference. Conclusion: Acute stroke demonstrates seasonal characteristics according to stroke types, ischemic stroke subtypes, risk factors for stroke, and Sasang constitutions. These results have important clinical implications in stroke prevention.

• 대한한의학회지
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• 제28권4호
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• pp.8-12
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• 2007

Objectives : This study aimed to investigate the circadian variation in stroke types, ischemic stroke subtypes, and Sasang constitutions. Methods : 295 patients with acute stroke within 14 days onset were included, who were admitted to Kyunghee Oriental Medical Center from October 2005 to May 2007. The stroke onset time was subdivided into four groups of 6-hour intervals in a day. Stroke types, ischemic stroke subtypes, and Sasang constitutions in four groups were examined. Results : Most ischemic stroke occurred between 6:01-12:00 hours (30.2%). For ischemic stroke subtypes, the peak period of small-vessel occlusion was between 6:01-12:00 hours (33.2%), large-artery atherosclerosis was most common between 12:01-18:00 hours (39.5%), and cardiac embolism was most frequent between 18:01-24:00 hours (50%). In terms of Sasang constitution, Soyeumin and Taeyeumin were most common between 6:01-12:00 hours (36.4% versus 41.5%, respectively), but the peak time of Soyangin was between 12:01-18:00 hours (35.2%). Conclusion :Most ischemic stroke events occurred in the mid-to-late morning hours in the present study and there was a circadian variation of onset in ischemic stroke subtypes and Sasang constitution.

• 대한한의학회지
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• 제28권2호통권70호
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• pp.241-246
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• 2007

Objectives : This study investigated stroke types, ischemic stroke subtypes, risk factors for stroke, stroke complications and Sasang constitutions in two groups divided by age according to the weakness of shingi (shenqi): younger (40 to 63 years) and older (= 64 years). Methods : 165 male patients with acute stroke within 14 days onset were included, who were admitted to Kyunghee Oriental Medical Center from October 2005 to May 2007. Stroke types, ischemic stroke subtypes, risk factors for stroke, stroke complications and Sasang constitutions in two age groups were examined. Results : Mean ages were $53.01{\pm}6.16$ and $70.95{\pm}6.37$ years for the younger 77 patients and older 88 subjects, respectively. There were no significant differences in stroke type, ischemic stroke subtypes, stroke complications and Sasang constitutions. Current smoking was more frequent in the younger age group (P= 0.005). Conclusion : Age does not seem to influence stroke types, ischemic stroke subtypes, stroke risk factors (except current smoking), stroke complications or Sasang constitutions.

• Biomolecules & Therapeutics
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• 제28권3호
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• pp.240-249
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• 2020

Despite the therapeutic effect of mesenchymal stem cells (MSCs) in ischemic diseases, pathophysiological conditions, including hypoxia, limited nutrient availability, and oxidative stress restrict their potential. To address this issue, we investigated the effect of melatonin on the bioactivities of MSCs. Treatment of MSCs with melatonin increased the expression of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α). Melatonin treatment enhanced mitochondrial oxidative phosphorylation in MSCs in a PGC-1α-dependent manner. Melatonin-mediated PGC-1α expression enhanced the proliferative potential of MSCs through regulation of cell cycle-associated protein activity. In addition, melatonin promoted the angiogenic ability of MSCs, including migration and invasion abilities and secretion of angiogenic cytokines by increasing PGC-1α expression. In a murine hindlimb ischemia model, the survival of transplanted melatonin-treated MSCs was significantly increased in the ischemic tissues, resulting in improvement of functional recovery, such as blood perfusion, limb salvage, neovascularization, and protection against necrosis and fibrosis. These findings indicate that the therapeutic effect of melatonin-treated MSCs in ischemic diseases is mediated via regulation of PGC-1α level. This study suggests that melatonin-induced PGC-1α might serve as a novel target for MSC-based therapy of ischemic diseases, and melatonin-treated MSCs could be used as an effective cell-based therapeutic option for patients with ischemic diseases.

• 생명과학회지
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• 제32권7호
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• pp.567-577
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• 2022

최근 인구 고령화로 인해 허혈성 심장질환, 허혈성 뇌졸중, 말초 동맥 질환 등의 허혈성 혈관질환의 유병률이 지속적으로 증가하고 있다. 허혈성 질환에 대한 현재 표준화된 치료법은 약물 요법 및 수술을 통한 재관류요법이다. 재관류요법은 손상된 동맥의 기능을 회복시킬 수 있지만 허혈로 인해 손상된 주변 조직의 기능 회복에 있어 효율적이지 않다. 그러므로 허혈 질병을 안전하고 효과적으로 치료하고 주변 조직의 기능을 회복시킬 수 있는 새로운 치료전략의 개발이 필요하다. 이러한 한계를 극복하기 위해 손상된 부위를 재생하는 줄기세포 기반 치료가 허혈성 혈관질환의 유망한 전략으로 연구되어 왔다. 다양한 조직에서 분리할 수 있는 중간엽줄기세포(MSC)는 면역 조절, 혈관 신생 촉진 및 다양한 관련 인자의 분비를 통해 손상된 조직을 재생함으로써 허혈성 질환의 치료에 유망한 것으로 나타났다. 또한, 줄기세포 치료 효과를 높이기 위해 3D 배양법을 이용하거나 세포 프라이밍(Cell Priming)과 같은 MSC 기능을 강화하여 이식 효율을 높이는 새로운 접근법이 연구되고 있다. 이 논문에서는 MSC를 허혈성 질환 치료에 사용하는 다양한 전략을 제공하고 허혈성 부위에서 MSC의 분화(Differentiation), 증식(Proliferation) 및 생착(Engraftment)과 같은 이식의 문제에 대해 논의한다.

• BMB Reports
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• 제50권10호
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• pp.504-509
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• 2017

Ischemia is a serious disease, characterized by an inadequate blood supply to an organ or part of the body. In the present study, we evaluated the effects of the anti-microbial peptide SR-0379 on the stem cell-mediated therapy of ischemic diseases. The migratory and tube-forming abilities of human endothelial progenitor cells (EPCs) were enhanced by treatment with SR-0379 in vitro. Intramuscular administration of SR-0379 into a murine ischemic hindlimb significantly enhanced blood perfusion, decreased tissue necrosis, and increased the number of blood vessels in the ischemic muscle. Moreover, co-administration of SR-0379 with EPCs stimulated blood perfusion in an ischemic hindlimb more than intramuscular injection with either SR-0379 or EPCs alone. This enhanced blood perfusion was accompanied by a significant increase in the number of CD31- and ${\alpha}$-SMA-positive blood vessels in ischemic hindlimb. These results suggest that SR-0379 is a potential drug candidate for potentiating EPC-mediated therapy of ischemic diseases.

• 대한한의학회지
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• 제24권4호
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• pp.19-24
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• 2003

Background and Purposes : Smoking is a well-known risk factor for ischemic stroke. It may contribute to s1Toke by inducing the aggregation of platelets and formation of atheroma, reducing cerebral blood flow, and increasing fibrinogen. However, the relative risk varies according to different ethnicity and area. Therefore, we performed this study to assess the risk of smoking for ischemic s1Toke in Korea. Methods : Cigarette smoking habit was studied in 308 patients with ischemic s1Toke and in 348 age- and sex-matched control subjects who had no history of stroke using case control methods. In multiple logistic regression analysis, smoking had a significant value of odds ratio adjusted for hypertension, diabetes mellitus, and hyperlipidemia. Results : The adjusted odds ratio (AOR) and 95％ confidence interval (CI) was significant in the medium smokers (AOR, 1.92; 95％ CI, 1.11 to 3.33: p< 0.05) and heavy smokers (AOR, 2.80; 95％ CI, 1.64 to 4.78: p< 0.05). Furthermore, the OR was higher in hypertensive subjects than in normotensive subjects compared to non-smokers (AOR, 1.98; 95％ CI, 1.01 to 3.85: p< 0.05). Conclusions : Our findings suggest that smoking is an independent risk factor for ischemic stroke in Korea.

• 한국방사선학회논문지
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• 제1권1호
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• pp.17-23
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• 2007

연구배경: 뇌혈관 질환은 지역 및 인종에 따라 발생양상의 차이를 보이는 것으로 알려져 있다. 그러므로 뇌혈관질환의 진단, 치료, 및 예방적인 목적에 활용하기 위한 특정지역의 발생양상을 파악하는 것은 매우 중요하다. 본 논문에서는 계절별, 성별, 연령별, 출혈성 뇌혈관질환과 허혈성뇌혈관질환 발생양상을 정량적으로 분석하고자 한다. 방 법: 연구대상은 일개 대학교병원 신경외과와 신경과에 출혈성 뇌혈관질환과 허혈성뇌혈관질환으로 입원한 환자 1603명을 대상으로 하였다. 연구대상 환자에 대해서 뇌혈관질환의 유형, 발생연도, 성별, 뇌혈관질환이 발생한 계절을 조사하였다. 자료의 산술적인 분석은 마이크로소프트사의 엑셀 2003을 이용하였고, t-test는 MICROCAL사에서 제공하는 ORIGIN 6.0을 이용하였다. 결 과: 연구대상 기간인 4년 동안의 출혈성 뇌혈관질환과 허혈성뇌혈관질환의 발생비는 38.55%, 61.45%이었다. 출혈성 뇌혈관질환의 발병 연령의 평균과 표준편차 $58.20{\pm}12.60$이었고, 40대, 50대, 60대, 70대에서 각각 20% 정도로 비슷하게 발병하였다. 이에 비하여 허혈성뇌혈관질환은 발병 연령의 평균과 표준편차는 $65.01{\pm}13.59$이었고, 출혈성뇌질환에 비하여 평균 연령이 높게 나타났고, 발생 연령분포에서도 60대 15.53%, 70대 37.06%, 80대 27.72%이었다. 출혈성 뇌혈관질환이 발병이 많이 나타난 계절은 겨울, 여름, 봄, 가을 순이었고, 출혈성 뇌혈관질환이 발병이 많이 나타난 계절은 봄, 여름, 겨울, 가을이었다. 일반적으로 알려진 겨울철 출혈성 뇌혈관질환 많이 나타났다. 출혈성 뇌혈관질환과 허혈성뇌혈관질환 환자의 남녀비율은 52.09% 47.91%로 나타났다. 결 론: 연구대상을 출혈성 뇌혈관질환과 허혈성뇌혈관질환으로 일개 대학교병원에 입원한 환자만을 대상으로 하였으므로 전체 뇌혈관 질환에 대한 결과를 대변한다고 볼 수 없다. 그러나 의료종사자에게서 일반적으로 알려진 계절별, 성별, 연령별, 출혈성 뇌혈관질환과 허혈성뇌혈관질환 발생비를 통계적으로 분석하였다는데 연구논문의 의의가 있다. 본 논문에서 출혈성 뇌혈관질환과 허혈성뇌혈관질환의 발생률은 38.55%, 61.45%로 허혈성뇌혈관질환의 비중이 높아지고 있다. 적절한 뇌혈관질환의 예방 및 질환관리계획을 세우기 위해서는 장기적인 뇌혈관질환의 역학조사가 필요할 것이다.

• 대한한의학회지
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• 제28권4호
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• pp.1-7
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• 2007

Objectives : This study investigated stroke types, ischemic stroke subtypes, risk factors for stroke, stroke complications and Sasang constitutions in both sexes. Methods : 307 patients with acute stroke within 14 days onset were included, who were admitted to Kyunghee Oriental Medical Center from October 2005 to May 2007. Stroke types, ischemic stroke subtypes, risk factors for stroke, stroke complications and Sasang constitutions in both sexes were examined. Results : Mean age was higher among women than men (64.82${\pm}$10.21 years versus 62.18${\pm}$11.52 years for the 137 female and 170 male patients, respectively, p=0.037). There were no significant differences in stroke type, ischemic stroke subtypes, or stroke risk factors except smoking and Sasang constitutions. Current smoking was more frequent in male patients (p<0.001). Stroke complications, especially urinary tract infection (UTI), were significantly more common in women (p=0.002). Conclusion : Sex does not seem to influence stroke types, ischemic stroke subtypes, or stroke risk factors except current smoking and Sasang constitutions. UTI should be taken into consideration to manage female stroke patients. Smoking cessation is indicated to prevent stroke in men.