• BMB Reports
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• v.44 no.8
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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.

• The Journal of Korean Medicine
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• v.29 no.2
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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.

• The Journal of Korean Medicine
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• v.28 no.4
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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.

• The Journal of Korean Medicine
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• v.28 no.2 s.70
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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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• v.28 no.3
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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.

• Journal of Life Science
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• v.32 no.7
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• pp.567-577
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• 2022

Recently, the prevalence of ischemic diseases, such as ischemic heart disease, cerebral ischemia, and peripheral arterial disease, has been continuously increasing due to the aging population. The current standardized treatment for ischemic diseases is reperfusion therapy through pharmacotherapy and surgical approaches. Although reperfusion therapy may restore the function of damaged arteries, it is not effective at restoring the function of the surrounding tissues that have been damaged due to ischemia. Therefore, it is necessary to develop a new treatment strategy that can safely and effectively treat ischemic damage and restore the function of surrounding tissues. To overcome these limitations, stem cell-based therapy to regenerate the damaged region has been studied as a promising strategy for ischemic vascular diseases. Mesenchymal stem cells (MSCs) can be isolated from diverse tissues and have been shown to be promising for the treatment of ischemic disease by regenerating damaged tissues through immunomodulation, the promotion of angiogenesis, and the secretion of various relevant factors. Moreover, new approaches to enhancing MSC function, such as cell priming or enhancing transplantation efficiency using a 3D culture method, have been studied to increase stem cell therapeutic efficacy. In this review, we provide various strategies by which MSCs are used to treat ischemic diseases, and we discuss the challenges of MSC transplantation, such as the differentiation, proliferation, and engraftment of MSCs at the ischemic site.

• BMB Reports
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• v.50 no.10
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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.

• The Journal of Korean Medicine
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• v.24 no.4
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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.

• Journal of the Korean Society of Radiology
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• v.1 no.1
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• pp.17-23
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• 2007

Background: Cerebrovascular diseases are known to show different patterns of incidence among regions and races. Therefore, it is very important to determine the incidence pattern of a specific area in order to diagnose, treat and prevent cerebrovascular diseases. The objective of the present study is to analyze quantitatively the incidence ratios of hemorrhagic and ischemic cerebrovascular diseases by season, by gender and by age. Methods: The subjects of this study were 1603 patients hospitalized for hemorrhagic or ischemic cerebrovascular diseases at the Department of Neurosurgery or the Department of Neurology of a University Hospital. Statistical analysis of data used Excel 2003 of Microsoft, and t-test was conducted using ORIGIN 6.0 of MICROCAL. Results: In the subjects, the incidence ratios of hemorrhagic and ischemic cerebrovascular diseases for four years, the period of this research, were 38.55% and 61.45%, respectively. The mean and standard deviation of age when hemorrhagic cerebrovascular diseases occurred were 58.20 and 12.60, respectively, and the percentages of subjects in their 40s, 50s, 60s and 70s were all around 20%. On the contrary, the mean and standard deviation of age when ischemic cerebrovascular diseases occurred were 65.01 and 13.59, respectively. The average age of patients with ischemic cerebrovascular diseases was older than that of patients with hemorrhagic brain diseases, and the percentages of those in their 60s, 70s and 80s were 15.53%, 37.06% and 27.72%, respectively. The season when hemorrhagic cerebrovascular diseases appeared most frequently was winter, which was followed by summer, spring and autumn. The season when hemorrhagic cerebrovascular diseases appeared most frequently was spring, which was followed by summer, winter and autumn. Conclusions: In this study, the incidence rates of hemorrhagic and ischemic cerebrovascular diseases were 38.55% and 61.45%, showing the rising percentage of ischemic cerebrovascular diseases. For making adequate prevention and disease control plans, it is considered necessary to make a long-term epidemiological investigation of cerebrovascular diseases.

• The Journal of Korean Medicine
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• v.28 no.4
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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.