• Environmental Analysis Health and Toxicology
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• v.21 no.1 s.52
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• pp.71-79
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• 2006

Epidemiologic studies have showed a close correlation between arsenic exposure and heart disease such as, cardiovascular problem, ischemic heart disease, infarction, atherosclerosis and hypertension in human. It may increase the mortality of high risk group with heart disease. Regarding the mechanism studies of heart failure, blood vessel, vascular smooth muscle cells and endothelial cells have long been focused as the primary targets in arsenic exposure but there are only a few studies on the cardiomyocytes. In this study, the generation of oxidative stress by low dose of arsenic trioxide was investigated in rat cardiomyocytes. By direct measurement of reactive oxygen species and fluorescent microscopic observation using fluorescent dye 2',7'-dichlorofluorescin diacetate, reactive oxygen species were found to be generated without cell death, where cells are treated with 0.1 ppm arsenic for 24 hours. With the induction of reactive oxygen species, GSH level was decreased by the same treatment. However, DNA damage did not seem to be serious by DAPI staining, while high dose of arsenic (2 ppm for 24 hrs) caused fragmentation of DNA. To identify the molecular biomarkers of low-dose arsenic exposure, gene expression was also investigated with whole genome microarray. As results, 9,022 genes were up-regulated including heme oxygenase-l and glutathione S-transrerase, which are well-known biomarkers of oxidative stress. 9,404 genes were down-regulated including endothelial type gp 91-phox gene by the treatment of 0.1 ppm arsenic for 24 hours. This means that biological responses of cardiomyocytes may be altered by ROS induced by low level arsenic without cell death, and this alteration may be detected clearly by molecular biomarkers such as heme oxygenase-1.

• Proceedings of the Korean Society of Developmental Biology Conference
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• 2003.10a
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• pp.71-71
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• 2003

Human umbilical cord blood cells(HUCBC) are rich in mesenchymal progenitor cells, endothelial cell precursors and hematopoietic cells. HUCBC have been used as a source of transplantable stem and progenitor cells. However, little is known about survival and development of HUCBC transplantation in the CNS. Estrogen has a neuroprotective potential against oxidative stress-induced cell death so has an effect on reducing infarct size of ischemic brain. We investigated the potential use of HUCBC as donor cells and tested whether estrogen mediates intravenously infused HUCBC enter and survive in ischemic brain. PKH26 labeled mononuclear fraction of HUCBC were injected into the tail vein of ischemic OVX rat brain with or without $17\beta$-estradiol valerate(EV). Under fluorescence microscopy, labeled cells were observed in the brain section. Significantly more cells were found in the ischemic brain than in the non-ischemic brain. HUCBC transplanted into ischemic brain could migrate and survive. Some of cells have shown neuronal like cells in hippocampus, striatum and cortex tissues. These result suggest that estrogen reduces ischemic damage and increases the migration of human umbilical cord blood cells. This Study was supported by the Korea Science and Engineering Foundation(KOSEF) though the Biohealth Products Research Center(BPRC), Inje University, Korea.

• Journal of Nutrition and Health
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• v.30 no.3
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• pp.244-251
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• 1997

The effects of Artemisia princeps var orientalis(mugwort), Circium japonicum var ussuriense (Unggungqui) on cadiovascular system in hyperlipidemic rats were investgated. Thirty rats devided into 5 experimental groups, were fed with the diet contained 1% chlesterol, 0.25% sodium cholate, 10% coconut oil and 5% lard by the same method of previous paper1). Contractile and relaxation responses in the isolated artria and thoracic aortae were measured and the morphological changes of the aortic endotherium from the rats were inspected. The responses of the right atrial to isoproterenol were significantly lower value in Ungungqui powder diet group(UP) and mugwort powder diet group(MP) than the control. The contraction force by injectin of phenylephrine and calcium in isolated thoracic aortae was significantly low value in the UP and the MP groups compaired to the control. The relaxation rate by acetylcholine in isolated thoracic aortae represented significantly higher value in UP than control. The morphological changes of endothelial cell suface was smallest in UP and the damage of endothelium by retarded in MP. Although Ungungqui and mugwort extract diet groups(UE, ME) were advanced, those were less than control.

• Radiation Oncology Journal
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• v.12 no.3
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• pp.285-293
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• 1994

Purpose : The study was designed to investigate the effect of cis-dichlorodiammineplatinum(II)(cis-DDP) on the radiation-induced cardiomyopathy in the rat. Materials and Methods : The myocardial damage was assessed by histopathologic changes. In radiation alone group, radiation dose ranged from 10-40 Gy X-ray in a single dose and in combined group, cis-dichlorodiammineplatinum(II) at a dose of 6 mg/kg was given intraperitoneally immediately after irradiation of same dose with X-ray alone group. Results : The early changes by radiation included congestion, inflammatory cell infiltrations and fibrosis in myocardial interstitium with focal myocardial necrosis, which was noted in 10 Gy group, Myocardial fibrosis was increased by increasing dose of radiation but myocardial necrosis was not Proportional to radiation dose. cis-DDP alone group showed minimal degeneration of myocardium with surrounded by inflammatory cell infiltrations. In combined group, myocardial fibrosis in 10 Gy group were similar to radiation alone group, but 30 Gy and 40 Gy groups showed severer changes. Electron microscopic examination showed disruption of Z-band and edema of mitochondria with decreased matrix density in 20 Gy radiation group which were severer in 40 Gy radiation group. Combined group showed endothelial changes and disruption of Z-band worse than radiation alone group as well as increased connective tissue, which was considered as a hallmark of late change in radiation-induced heart disease. Conclusion : This results showed minimal enhancement of the radiation-induced cardiomyopathy in rats by cis-DDP.

• Journal of environmental and Sanitary engineering
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• v.7 no.2
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• pp.95-110
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• 1992

Much progress has been made in understanding the subcellular events of the human lung injuries after acute exposure to environmental air pollutants. Host of those events represent oxidative damages mediated by reactive oxygen species such as superoxide, hydrogen peroxide, and the hydroxy, free radical. Recently, nitric oxide (NO) was found to be endogenously produced by endothelial cells and cells of the reticulo-endothelial system as endothelialderived relaxation factor (EDRF) which is a vasoactive and neurotransmitter substance. Together with superoxide, NO can form another strong oxidant, peroxonitrite. The relative importance of exogenous sources of $N0/N0_2$ and endogenous production of NO by the EDRF producing enzymes in the oxidative stresses to the heman lung has to be elucidated. The exact events leading to chronic irreversible damage are still yet to be known. From chronic exposure to oxidant gases, progressive epithelial and interstitial damages develop. Type I epithelial cells become thicker and cover a smaller average alveolar surface area while thee II cells proliferate instead. Under acute damages, the extent of loss of the alveolar epithelial cell lining, especially type II cells appears to be a good predictor of the ensuing irreversible damage to alveolar compartment. Interstitial matrix undergo remodeling during chronic exposure with increased collagen fibers and interstitial fibroblasts. However, Inany of these changes can be reversed after cessation of exposure. Among chronic lung injuries, genetic damages and repair responses received particular attention in view of the known increased lung cancer risks from exposure to several air pollutants. Heavy metals from foundry emission, automobile traffics, and total suspended particulate, especially polycystic aromatic hydrocarbons have been positively linked with the development of lung cancer. Asbestos in another air pollutant with known risk of lung cancer and mesothelioma, but asbestos fibers are nonauthentic in most bioassays. Studies using the electron spin resonance spin trapping method show that the presence of iron in asbestos accelerates the production of the hydroxy, radical in vitro. Interactions of these reactive oxygen species with particular cellular components and disruption of cell defense mechanisms still await further studies to elucidate the carcinogenic potential of asbestos fibers of different size and chemical composition. The distribution of inhaled pollutants and the magnitude of their eventual effects on the respiratory tract are determined by pollutant-independent physical factors such as anatomy of the respiratory tract and level and pattern of breathing, as well as by pollutant-specific phyco-chemical factors such as the reactivity, solubility, and diffusivity of the foreign gas in mucus, blood and tissue. Many of these individual factors determining dose can be quantified in vitro. However, mathematical models based on these factors should be validated for its integrity by using data from intact human lungs.

• Journal of Ginseng Research
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• v.48 no.5
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• pp.464-473
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• 2024

Background: The effects of individual panaxadiol saponin and panaxatriol saponin on rodent models of Parkinson's disease (PD) have been recognized. However, it is not clear whether purified total ginsenosides as an entirety has effect against PD in rat model. This study compared the protective effects of a purified panaxadiol saponin fraction (PDSF), a purified panaxatriol saponin fraction (PTSF), and their mixtures against the rotenone (ROT)-induced PD in rats. Methods: Potential effects of PDSF, PTSF, and their mixtures against motor dysfunction and impairments of nigrostriatal dopaminergic neurons (DN), blood-brain barrier (BBB), cerebrovascular endothelial cells (CEC), and glial cells were measured in the models of ROT-induced PD rats and cell damage. Pro-inflammatory NF-kB p65 (p65) activation was localized in DN and other cells in the striatum. Results: PDSF and PTSF had a dose-dependent effect against motor dysfunction with a larger effective dose range for PDSF. PDSF protected CEC, glial cells, and DN in models of PD rats and cell damage, while PTSF had no such protections. Chronic ROT exposure potently activated p65 in CEC with enhanced pro-inflammatory and decreased anti-inflammatory factors and impaired BBB in the striatum, PDSF almost completely blocked the ROT-induced p65 activation and maintained both anti- and pro-inflammatory factors at normal levels and BBB integrity, but PTSF aggravated the p65 activation with impaired BBB. Furthermore, PTSF nullified all the effects of PDSF when they were co-administrated. Conclusion: PDSF had significant protective effect against the ROT-induced PD in rats by protecting CEC, glial cells, and DN, likely through inhibiting NF-κB p65 in CEC from triggering neuroinflammation, and also directly protecting glial cells and neurons against ROT-induced toxicity. PDSF has great potential for preventing and treating PD.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.1
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• pp.20-24
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• 2006

This study was designed to investigate the protective effect of Sanyakbojungbangam-tang Ethanol Extracts (SB Et-OH) on the cisplatin-induced apoptosis of human endothelial cell line ECV304 cells. After cells were treated with cisplatin, MTT assay was performed for cell viability test. To explore the mechanism of cytotoxicity, we used the several measures of apoptosis to determine whether this processes was involved in cisplatin-induced cell damage in ECV304 cells. Also, cells were treated with SB Et-OH and then, followed by the addition of cisplatin. Cisplatin decreased the viability of ECV304 cells in a dose-dependent manner and increased the caspase-3 enzyme activity ECV304 cells treated cisplatin were revealed as apoptosis characterized by nuclear staining. SB Et-OH protected ECV304 cells from cisplatin-induced nuclear fragmentation and chromatin condensation. Also, SB Et-OH inhibited the activation of caspase-3 pretense and the cleavage of poly(ADP-ribose) polymerase (PARP) in cisplatin-treated ECV304 cells. According to above results, SB Et-OH may protect ECV304 cells from the apoptosis induced by cisplatin.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.5
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• pp.437-448
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• 2023

Diabetic ulcer is usually seen in people with uncontrolled blood sugar. Reportedly, many factors such as impaired glucose metabolism, and macrovascular and microvascular diseases caused angiogenesis disorders and delayed the healing of diabetic ulcers, thus affecting the body's metabolism, nutrition, and immune function. This study aimed to explore the effect of paeonol on skin wound healing in diabetic rats and the related mechanism. A rat model of diabetic ulcer was established. High glucose-treated mouse skin fibroblasts were co-cultured with M1 or M2-polarized macrophages treated with or without paeonol. H&E and Masson staining were used to reveal inflammatory cell infiltration and collagen deposition, respectively. Immunohistochemistry visualized the expression of Ki67, CD31, and vascular endothelial growth factor (VEGF). Western blot was used to detect interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-4, IL-10, CD31, VEGFA, and collagen I/III. The expression of iNOS and arginase 1 was revealed by immunofluorescence staining. Paeonol treatment augmented collagen deposition and the expression of Ki67, CD31, VEGF, and macrophage M2 polarization markers (IL-4 and IL-10) and reduced wound area, inflammatory cell infiltration, and macrophage M1 polarization markers (IL-1β and TNF-α) in the ulcerated area. In vitro, paeonol treatment promoted M2-polarization and repressed M1-polarization in macrophages, thereby improving the repair of cell damage induced by high glucose. Paeonol accelerates the healing of diabetic ulcers by promoting M2 macrophage polarization and inhibiting M1 macrophage polarization.

• 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.

• Proceedings of the KOSOMBE Conference
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• v.1996 no.11
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• pp.7-10
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• 1996

The purpose of this experimental investigation is to examine the influence of the catheter on local pressure changes and flow rate in an arterial branch model similar to the femoral artery of man. Effects of branch to main lumen flow rate ratios and the locations of catheter tip were found to be significant on the local pressure changes. Relatively large pressure drops due to obstruction effects may induce endothelial cell damage, which have been reported to be the primary cause of the initiation of the atherosclerosis.