• Title/Summary/Keyword: Endothelial function

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Inhibition of LPA5 Activity Provides Long-Term Neuroprotection in Mice with Brain Ischemic Stroke

  • Sapkota, Arjun;Park, Sung Jean;Choi, Ji Woong
    • Biomolecules & Therapeutics
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    • v.28 no.6
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    • pp.512-518
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    • 2020
  • Stroke is a leading cause of long-term disability in ischemic survivors who are suffering from motor, cognitive, and memory impairment. Previously, we have reported suppressing LPA5 activity with its specific antagonist can attenuate acute brain injuries after ischemic stroke. However, it is unclear whether suppressing LPA5 activity can also attenuate chronic brain injuries after ischemic stroke. Here, we explored whether effects of LPA5 antagonist, TCLPA5, could persist a longer time after brain ischemic stroke using a mouse model challenged with tMCAO. TCLPA5 was administered to mice every day for 3 days, starting from the time immediately after reperfusion. TCLPA5 administration improved neurological function up to 21 days after tMCAO challenge. It also reduced brain tissue loss and cell apoptosis in mice at 21 days after tMCAO challenge. Such long-term neuroprotection of TCLPA5 was associated with enhanced neurogenesis and angiogenesis in post-ischemic brain, along with upregulated expression levels of vascular endothelial growth factor. Collectively, results of the current study indicates that suppressing LPA5 activity can provide long-term neuroprotection to mice with brain ischemic stroke.

DENTAL MANAGEMENT OF LEUKOCYTE DEFICIENCY IN A CHILD WITH SEVERE ORAL INVOLVEMENT (백혈구 접착 결핍 증후군 환아의 치과적 처치)

  • Kim, Hyun-Jin;Lee, Nan-Young;Lee, Sang-Ho
    • The Journal of Korea Assosiation for Disability and Oral Health
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    • v.3 no.1
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    • pp.26-30
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    • 2007
  • Leukocyte adhesion deficiency(LAD) is a rare autorecessive defect of phagocytic function resulting from a lack of leukocyte cell surface expression of ${\beta}_2$ integrin molecules(CD 18) that are essential for leukocyte adhesion to endothelial cells and chemotaxis. As a results, patients with LAD suffer from severe bacterial infections and impaired wound healing. A small number of patients with leukocyte adhesion deficiency-1 have a milder defect, with residual expression of CD18. These patients tend to survive beyond infancy; they manifest progressive severe periodontitis, alveolar bone loss, periodontal pocket formation, and partial or total premature loss of the primary and permanent dentitions. In this report, we report on a 7 year old girl with severe oral involvement. The most import focus should be to control infections to reduce the risk for future infection.

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Subtilisin QK, a Fibrinolytic Enzyme, Inhibits the Exogenous Nitrite and Hydrogen Peroxide Induced Protein Nitration, inVitro and inVivo

  • Ko, Ju-Ho;Yan, Junpeng;Zhu, Lei;Qi, Yipeng
    • BMB Reports
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    • v.38 no.5
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    • pp.577-583
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    • 2005
  • Subtilisin QK, which is newly identified as a fibrinolytic enzyme from Bacillus subtilis QK02, has the ability of preventing nitrotyrosine formation in bovine serum albumin induced by nitrite, hydrogen peroxide and hemoglobin in vitro verified by ELISA, Western-blot and spectrophotometer assay. Subtilisin QK also attenuates the fluorescence emission spectra of bovine serum albumin in the course of oxidation caused by nitrite, hydrogen peroxide and hemoglobin. Furthermore, subtilisin QK could suppress the transformation of oxy-hemoglobin to met-hemoglobin caused by sodium nitrite, but not the heat-treated subtilisn QK. Compared with some other fibrinolytic enzymes and inactivated subtilisin QK treated by phenylmethylsulfonylfluoride, the ability of inhibiting met-hemoglobin formation of subtilisin QK reveals that the anti-oxidative ability of subtilisin QK is not concerned with its fibrinolytic function. Additionally, nitrotyrosine formation in proteins from brain, heart, liver, kidney, and muscle of mice that is intramuscular injected the mixture of nitrite, hydrogen peroxide and hemoglobin is attenuated by subtilisin QK. Subtilisin QK can also protect Human umbilical vein endothelial cell (ECV-304) from the damage caused by nitrite and hydrogen peroxide.

Study on Clinical Diseases of Blood Stasis Pattern (어혈증(瘀血證)의 임상 질환 범위에 대한 고찰)

  • Park, Mi Sun;Kim, Yeong Mok
    • Herbal Formula Science
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    • v.21 no.1
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    • pp.1-15
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    • 2013
  • Objectives : This article is a study on to which categories of modern diseases blood stasis patterns are assigned and the meaning of blood stasis interpreted with perspectives of Korean Medicine and modern medicine. Methods : We reviewed "Neijing", "Shanghanlun", "Yilingaicuo", "Xuezhenglun" and other books and modern clinical papers related with blood stasis. Results : 1. Blood stasis patterns are related with disorders of hemorrheology, hemodynamics, platelet function, microcirculation, microelements and endothelial damage. 2. From the types of syndrome differentiation, diverse diseases classified in type of qi deficiency with blood stasis and type of blood stasis due to qi stagnation are reported, which reflects qi and blood are closely connected. And many diseases are classified in type of kidney deficiency with blood stasis, which has something in common with chronic diseases can achieve effect from treatment considering blood stasis. 3. Diseases related with kidney involve menopausal disorder, mazoplasia, prostatitis, erectile dysfunction, chronic nephritis, renal calculus, osteoporosis and bursitis. Diseases related with heart involve coronary artery disease, arrhythmia and cerebral thrombosis. Diseases related with spleen involve gastritis, colonitis and digestive organ ulcer. Diseases related with liver involve hepatitis, hyperthyroidism and stroke. Diseases related with lung involve neurodermatitis, bronchitis and paranasal sinusitis. Conclusions : Blood stasis pattern which is one of the areas to draw medicine's attention has broad clinical application.

Effects of the Velocity Waveform of the Physiological Flow on the Hemodynamics in the Bifurcated Tube

  • Roh, Hyung-Woon;Kim, Jae-Soo;Suh, Sang-Ho
    • Journal of Mechanical Science and Technology
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    • v.17 no.2
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    • pp.296-309
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    • 2003
  • The periodicity of the physiological flow has been the major interest of analytic research in this field up to now Among the mechanical forces stimulating the biochemical reaction of endothelial cells on the wall, the wall shear stresses show the strongest effect to the biochemical product. The objective of present study is to find the effects of velocity waveform on the wall shear stresses and pressure distribution along the artery and to present some correlation of the velocity waveform with the clinical observations. In order to investigate the complex flow phenomena in the bifurcated tube, constitutive equations, which are suitable to describe the rheological properties of the non-Newtonian fluids, are determined, and pulsatile momemtum equations are solved by the finite volume prediction. The results show that pressure and wall shear stresses are related to the velocity waveform of the physiological flow and the blood viscosity. And the variational tendency of the wall shear stresses along the flow direction is very similar to the applied sinusoidal and physiological velocity waveforms, but the stress values are quite different depending on the local region. Under the sinusoidal velocity waveform, a Newtonian fluid and blood show big differences in velocity. pressure, and wall shear stress as a function of time, but the differences under the physiological velocity waveform are negligibly small.

Biphasic Effects of Rosiglitazone on Agonist-induced Regulation of Vascular Contractility (항당뇨약 Rosiglitazone의 혈관 수축성에 대한 이중성 조절)

  • Park, Jin-Gun;Je, Hyun-Dong
    • YAKHAK HOEJI
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    • v.51 no.5
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    • pp.301-306
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    • 2007
  • Rosiglitazone ($Avandia^{(R)}$) represents a new class of antidiabetic drugs which are $PPAR{\gamma}$ agonists. The present study was undertaken to determine whether the new antidiabetic rosiglitazone influences on the agonist-induced regulation of vascular smooth muscle contraction as an antihypertensive and, if so, to investigate the related mechanism. Endothelium-denuded arterial rings from male Sprague-Dawley rats were used and isometric contractions were recorded using a computerized data acquisition system. Rosiglitazone decreased Rho-kinase activating agonist (NaF or thromboxane $A_2$ mimetic)-induced contraction but not depolarization- or phorbol ester-induced contraction. Surprisingly, it slightly potentiated the latter contraction possibly opening a voltage-dependent calcium channel by its chemical structure on 50 mM KCI- or $1{\mu}M$ phorbol 12,13-dibutyrate-induced vasoconstriction. In conclusion, this study provides the evidence and possible related mechanism concerning the biphasic effect of an antidiabetic rosiglitazone as a possible antihypertensive on the agonistinduced contraction in rat aortic rings regardless of endothelial function.

Blood-Brain Barrier Interfaces and Brain Tumors

  • Lee Sae-Won;Kim Woo-Jean;Park Jeong-Ae;Choi Yoon-Kyung;Kwon Yoo-Wook;Kim Kyu-Won
    • Archives of Pharmacal Research
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    • v.29 no.4
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    • pp.265-275
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    • 2006
  • In the developing brain, capillaries are differentiated and matured into the blood-brain barrier (BBB), which is composed of cerebral endothelial cells, astrocyte end-feet, and pericytes. Since the BBB regulates the homeostasis of central nervous system (CNS), the maintenance of the BBB is important for CNS function. The disruption of the BBB may result in many brain disorders including brain tumors. However, the molecular mechanism of BBB formation and maintenance is poorly understood. Here, we summarize recent advances in the role of oxygen tension and growth factors on BBB development and maintenance, and in BBB dysfunction related with brain tumors.

Role of ginseng in the neurovascular unit of neuroinflammatory diseases focused on the blood-brain barrier

  • Kim, Minsu;Mok, Hyejung;Yeo, Woon-Seok;Ahn, Joong-Hoon;Choi, Yoon Kyung
    • Journal of Ginseng Research
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    • v.45 no.5
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    • pp.599-609
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    • 2021
  • Ginseng has long been considered as an herbal medicine. Recent data suggest that ginseng has antiinflammatory properties and can improve learning- and memory-related function in the central nervous system (CNS) following the development of CNS neuroinflammatory diseases such as Alzheimer's disease, cerebral ischemia, and other neurological disorders. In this review, we discuss the role of ginseng in the neurovascular unit, which is composed of endothelial cells surrounded by astrocytes, pericytes, microglia, neural stem cells, oligodendrocytes, and neurons, especially their blood-brain barrier maintenance, anti-inflammatory effects and regenerative functions. In addition, cell-cell communication enhanced by ginseng may be attributed to regeneration via induction of neurogenesis and angiogenesis in CNS diseases. Thus, ginseng may have therapeutic potential to exert cognitive improvement in neuroinflammatory diseases such as stroke, traumatic brain injury, multiple sclerosis, Parkinson's disease, and Alzheimer's disease.

Inhibitory effects of artemether on collagen-induced platelet aggregation via regulation of phosphoprotein inducing PI3K/Akt and MAPK

  • Lee, Dong-Ha
    • Journal of Applied Biological Chemistry
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    • v.65 no.3
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    • pp.167-172
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    • 2022
  • Pathophysiological reaction of platelets in the blood vessel is an indispensable part of thrombosis and cardiovascular disease, which is the most common cause of death in the world. In this study, we performed in vitro assays to evaluate antiplatelet activity of artemether in human platelets and attempted to identify the mechanism responsible for protein phosphorylation. Artemether is a derivative of artemisinin, known as an active ingredient of Artemisia annua, which has been reported to be effective in treating malaria, and is known to function through antioxidant and metabolic enzyme inhibition. However, the role of artemether in platelet activation and aggregation and the mechanism of action of artemether in collagen-induced human platelets are not known until now. In this study, the effect of artesunate on collagen-induced human platelet aggregation was confirmed and the mechanism of action of artemether was clarified. Artemether inhibited the phosphorylation of PI3K/Akt and Mitogen-activated protein kinases, which are phosphoproteins that are known to act in the signal transduction process when platelets are activated. In addition, artemether decreased TXA2 production and decreased granule secretion in platelets such as ATP and serotonin release. As a result, artemether strongly inhibited platelet aggregation induced by collagen, a strong aggregation inducer secreted from vascular endothelial cells, with an IC50 of 157.92 μM. These results suggest that artemether has value as an effective antithrombotic agent for inhibiting the activation and aggregation of human platelets through vascular injury.

Effects of sleep deprivation on coronary heart disease

  • Wei, Ran;Duan, Xiaoye;Guo, Lixin
    • The Korean Journal of Physiology and Pharmacology
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    • v.26 no.5
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    • pp.297-305
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    • 2022
  • The presence of artificial light enables humans to be active 24 h a day. Many people across the globe live in a social culture that encourages staying up late to meet the demands of various activities, such as work and school. Sleep deprivation (SD) is a severe health problem in modern society. Meanwhile, as with cardiometabolic disease, there was an obvious tendency that coronary heart disease (CHD) to become a global epidemic chronic disease. Specifically, SD can significantly increase the morbidity and mortality of CHD. However, the underlying mechanisms responsible for the effects of SD on CHD are multilayered and complex. Inflammatory response, lipid metabolism, oxidative stress, and endothelial function all contribute to cardiovascular lesions. In this review, the effects of SD on CHD development are summarized, and SD-related pathogenesis of coronary artery lesions is discussed. In general, early assessment of SD played a vital role in preventing the harmful consequences of CHD.