• Journal of Life Science
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• v.18 no.6
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• pp.796-803
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• 2008

Mutations in the APP gene lead to enhanced cleavage by ${\beta}-$ and ${\gamma}-secretase$, and increased $A{\beta}$ formation, which are closely associated with Alzheimer's disease (AD)-like neuropathological changes. Recent studies have shown that exercise training can ameliorate pathogenic phenotypes ($A{\beta}-42$, BDNF, GLUT-1 and HSP70) in experimental models of Alzheimer's disease. Here, we have used NSE/APPsw transgenic mice to investigate directly whether exercise training ameliorates pathogenic phenotypes within Alzheimer's brains. Sixteen weeks of exercise training resulted in a reduction of $A{\beta}-42$ peptides and also facilitated improvement of cognitive function. Furthermore, GLUT -1 and BDNF proteins produced by exercise training may protect brain neurons by inducing the concomitant expression of genes that encode proteins (HSP-70) which suppress stress induced neuron cell damages from APPsw transgenic mice. Thus, the improved cognitive function by exercise training may be mechanistically linked to a reduction of $A{\beta}-42$ peptides, possibly via activation of BDNF, GLUT-1, and HSP-70 proteins. On the basis of the evidences presented in this study, exercise training may represent a practical therapeutic management strategy for human subjects suffering from Alzheimer's disease.

• Tunnel and Underground Space
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• v.30 no.4
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• pp.382-393
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• 2020

The engineered barrier system of high-level radioactive waste disposal must maintain its performance in the long term, because it must play a role in slowing the rate of leakage to the surrounding rock mass even if a radionuclide leak occurs from the canister. In particular, it is very important to clarify gas dilation flow phenomenon clearly, that occurs only in a medium containing a large amount of clay material such as a bentonite buffer, which can affect the long-term performance of the bentonite buffer. Accordingly, DECOVALEX-2019 Task A was conducted to identify the hydraulic-mechanical mechanism for the dilation flow, and to develop and verify a new numerical analysis technique for quantitative evaluation of gas migration phenomena. In this study, based on the conventional two-phase flow and mechanical behavior with effective stresses in the porous medium, the hydraulic-mechanical model was developed considering the concept of damage to simulate the formation of micro-cracks and expansion of the medium and the corresponding change in the hydraulic properties. Model verification and validation were conducted through comparison with the results of 1D and 3D gas injection tests. As a result of the numerical analysis, it was possible to model the sudden increase in pore water pressure, stress, gas inflow and outflow rate due to the dilation flow induced by gas pressure, however, the influence of the hydraulic-mechanical interaction was underestimated. Nevertheless, this study can provide a preliminary model for the dilation flow and a basis for developing an advanced model. It is believed that it can be used not only for analyzing data from laboratory and field tests, but also for long-term performance evaluation of the high-level radioactive waste disposal system.

• Reproductive and Developmental Biology
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• v.31 no.3
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• pp.199-205
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• 2007

The present study was carried out to assess the effect of superovulation response and efficiency of embryo production induced with injection of FSH dissolved in polyethylene glycol (PEG) in Hanwoo. Eighty-eight cows were divided into four groups. In group 1, cattle were intramuscularly treated with twice-daily administration of 50mg FSH for 4 days. Group 2 and 3 were subcutaneously single injection of 400mg and 200mg FSH dissolved in 30% PEG, respectively. Group 4 were subcutaneously single injection of 200 mg FSH dissolved in 30% PEG at 7 day after CIDR insertion. The number of corpus luteum (CL) in group 2 resulted in significantly (p<0.05) higher compared to group 1, 3 and 4 (18.5 vs. 11.2, 13.1 and 13.9, respectively). However, the number of total ova $(7.9{\sim}10.4)$, transferable embryos $(3.7{\sim}4.7)$, degenerate embryos $(1.9{\sim}3.5)$ and unfertilized ova $(1.8{\sim}2.7)$ did not differ among treatment groups. No difference was observed in pregnancy rate after transferring the recovered embryos among groups $(36.0{\sim}50.0%)$. In addition, blood progesterone concentrations at embryo recovery did not differ among all groups. In conclusion, although no differences were observed in the number of total ova, transferable embryos and pregnancy rate after transfer, a single injection of reduced dose of FSH (200mg FSH) at 7 day after CIDR insertion is more practical for superovulation treatments than frequent injection because of reduction of stress in Hanwoo and decreases of cost and laber.

• Applied Microscopy
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• v.40 no.2
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• pp.89-99
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• 2010

Fibroblasts are the most common cells in connective tissue and are responsible for the synthesis of extracellular matrix components. The fibrosis associated with chronic inflammation and injury may contribute to cholangiocarcinoma pathogenesis, particularly through an increase in extracellular matrix components, which participate in the regulation of bile duct differentiation during development. Mitochondria produce ATP through oxidative metabolism to provide energy to the cell under physiological conditions. Also, mitochondrial dysfunction and oxidative stress have been implicated in cellular senescence and aging. Alternations in mitochondrial structure and function are early events of programmed cell death or apoptosis and mitochondria appear to be a central regulator of apoptosis in most somatic cell. Clonorchis sinensis, one of the most important parasite of the human bile duct in East Asia, arouses epithelial hyperplasia and ductal fibrosis. Isolated fibroblast from the bile ducts of rats infected by C. sinensis showed increase of cytoplasmic process. In addition, decrease of cellular proliferation was observed in fibroblasts which was isolated from normal rat bile duct and then cultured in media containing C. sinensis excretory-secretory product. However, the effects of C. sinensis infection on the mitochondrial enzyme distribution is not clearly reported yet. Therefore, we investigated the structural change of C. sinensis infected bile duct and mitochondrial enzyme distribution of the cultured fibroblast isolated from the C. sinensis infected rat bile duct. As a result, C. sinensis infected SD rat bile ducts showed the features of chronic clonorchiasis, such as ductal connective and epithelial tissue dilatation, or ductal fibrosis. In addition, fibroblast in ductal connective tissue was damaged by physical effect of fibrotic tissue and chemical stimulation. Immunohistochemically detected mitochondrial electron transferase (ATPase, COXII, Porin) was decreased in C. sinensis infected rat bile duct and cultured fibroblast from infected rat bile duct. It can be hypothesized that the reason why number of electron transferase decrease in fibroblast isolated from the rat bile duct infected with C. sinensis is because dysfunction of electron transport system is occurred mitochondrial dysfunction, increase of ROS (reactive oxygen species) and apoptosis after chemical damage on the cell caused by C. sinensis infection. Overall, C. sinensis infection induces fibrotic change of ductal connective tissue, mutation of cellular metabolism in fibroblast and mitochondrial dysfunction. Consequently, ductal fibrosis inhibits fibroblast proliferation and decreases mitochondrial electron transferase on fibroblast cytoplasm. It was assumed that the structure of bile duct could not normalized and ductal fibrosis was maintained for a long period of time according to fibroblast metamorphosis and death induced by mitochondrial dysfunction.

• Journal of Life Science
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• v.26 no.1
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• pp.101-108
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• 2016

The aim of this study was to evaluate the relationships between the expression of Heat shock protein70 (HSP70), Raf-1 and Bcl-2-associated athanogene-1 (BAG1) protein in diffuse type gastric carcinoma and examine association of HSP70, Raf-1 and BAG1 expression with various clinic-pathological factors and survival. Heat shock protein70 is induced in the cells in response to various stress conditions, including carcinogens. Overexpression of heat shock protein 70 has been observed in many types of cancer. The proto-oncoprotein Raf is pivotal for mitogen-activated protein kinase (MAPK) signaling, and its aberrant activation has been implicated in multiple human cancers. Overexpression of BAG1 protein has been documented in some type of human cancer. BAG1 has been reported to interact with protein involved with a variety of signal pathway, and regulation of cell differentiation, survival and apoptosis. These interaction partners include HSP70 and Raf-1. The percentage of tumors exhibiting HSP70 positivity was significantly in cases of positive lymph node metastasis (64.9%) compared to cases without lymph node metastasis (35.1%, p=0.007). HS70 expression was correlated with pathological N-stage (p=0.006). Expression of BAG1 was detected in the majority of diffuse type gastric carcinoma tissues (71.7%), especially in younger patients (80% vs 52.6%, p=0.035). Furthermore BAG1 expression was correlated with tumor size (p=0.020). Raf-1 expression was found to be significantly associated with tumor size (p=0.005). The result indicate that HSP70 was significantly correlated the progression of diffuse type gastric cancer. Expression of BAG1 and Raf-1 may be used as diagnostic markers for gastric carcinoma.

• Sleep Medicine and Psychophysiology
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• v.20 no.2
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• pp.75-81
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• 2013

Objectives: There are a lot of studies that analyze the interaction between the emotion of disgust and the functional brain images using fMRI and PET. But studies using sLORETA (standardized low resolution brain electromagnetic tomography) almost do not exist. The aim of this research is to explore the relationship of the emotion of disgust and the cortical activation using sLORETA analysis. Methods: Forty five healthy young adults ($27.1{\pm}2.6$ years) participated in the study. While they were watching 4 neutral images and 4 disgusting images associated with mutilation selected from the international affective picture system (IAPS), participants' EEGs were taken for 30 seconds per one picture. Through these obtained EEG data, sLORETA analysis was performed to compare EEGs associated with neutral and negative images. Results: During looking for visual disgusting stimulus, all participants reported unpleasantness, arousal and stress. In sLORETA analysis, the decrease of current density in theta wave was shown at left frontal superior gyrus (BA10) and middle gyrus (BA10, 11). This voxel cluster consists of a total of 11 voxels and the threshold of t value indicating statistically significant decreases in the current density (p<0.05) was -1.984. There were no differences between male and female in the degree of being disgusted by the stimuli. Conclusion: This finding may suggest that the activation of dorsolateral prefrontal cortex might be associated with regulating disgust emotion.

• Journal of Life Science
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• v.20 no.3
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• pp.444-452
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• 2010

The purpose of this study was to investigate the effects of treadmill exercise on $A{\beta}$-42, cytochrome c, SOD-1, 2 and Sirt-3 protein expressions in brain cytosol and mitochondria in mutant (N141I) presenilin-2 transgenic mice with Alzheimer's disease (AD). The mice were divided into four groups (Non-Tg-sedentary, n=5; Non-Tg treadmill exercise, n=5; Tg-sedentary, n=5; Tg treadmill exercise, n=5). To evaluate the neuroprotective effect of treadmill exercise, Non-Tg and Tg mice were subjected to exercise training on a treadmill for 12 wk, after which their brain cytosol and mitochondria were evaluated to determine whether any changes in the cognitive performance, $A{\beta}$-42 protein, cytochrome c protein, anti-oxidant enzymes (SOD-1, SOD-2) and Sirt-3 protein had occurred. The results indicated that treadmill exercise resulted in amelioration in cognitive deficits of Tg mice. In addition, the expressions of mitochondrial $A{\beta}$-42 and cytosolic cytochrome c protein were decreased in the brains of Tg mice after treadmill exercise, whereas antioxidant enzymes, SOD-l and SOD-2 were significantly increased in response to treadmill exercise. Furthermore, treadmill exercise significantly increased the expression of Sirt-3 protein in Non-Tg and Tg mice. Taken together, these results suggest that treadmill exercise is a simple behavioral intervention which can sufficiently improve cognitive performance and inhibit $A{\beta}$-induced oxidative stress in AD.

• Food Science of Animal Resources
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• v.33 no.2
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• pp.258-267
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• 2013

This study was conducted to determine the antioxidative and neuroprotective effect of pig skin extracts (PS) and pig skin gelatin hydrolysates (LPS) using a human neuroblastoma cell line (SH-SY5Y). The extraction yield of PS was 3 fold higher than that of LPS. The protein content of PS was about 10 fold higher than that of LPS (p<0.05). Also LPS increased antioxidative activity dose dependently, and the activity was significantly higher than PS at all concentration (p<0.05). DPPH radical scavenging activity of LPS at 50 mg/mL was 92.97%, which was similar to $1{\mu}M$ vitamin C as a positive control. ABTS radical scavenging activity of LPS (20 mg/mL) was 89.83% and oxygen radical absorbance capacity of LPS at 1 mg/mL was $141.39{\mu}M$ Trolox Equvalent/g. No significant change of human neuroblastoma cells was determined by MTT test. Cell death by oxidative stress induced by $H_2O_2$ and amyloid beta 1-42 ($A{\beta}_{1-42}$) was protected by LPS rather than PS. Acetylcholine esterase was significantly inhibited, by up to 33.62% by LPS at 10 mg/mL. Therefore, these results suggest that pig skin gelatin hydrolysates below 3 kDa have potential to be used as anti-oxidative and neuroprotective functional additives in the food industry, while further animal test should be determined in the future.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.3
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• pp.393-400
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• 2011

This study investigates the effects of a hangover beverage (MIX) that contains minerals (highly-salty mineral water, HSMW) and several medicinal plant extracts, on antioxidant and alcohol-metabolizing enzymes in alcohol administered Sprague-Dawley rats. HSMW is pumped from below the sedimentary rock layer of Dadaepo, Busan, South Korea, which is 1,050 m below the land surface; it tastes salty, like sea water. In terms of medicinal plant extracts, the total phenolic and flavonoid contents of Rubus coreanus and Cornus officinalis were measured as being significantly higher than those in Curcuma longa. The results suggest that treatment with MIX significantly increases superoxide dismutase (SOD) activity and DPPH radical scavenging activity. In the 10% HSMW-, for MIX- and company product (CP)-treated groups, the concentration of blood alcohol was significantly reduced 1~5 hr after alcohol loading, compared to that in the control group. In hepatic alcohol-metabolizing enzyme activities, alcohol dehydrogenase (ADH) activity was found to be higher in the MIX- and CP-treated groups than in controls, whereas acetaldehyde dehydrogenase (ALDH) activity was significantly higher in the CP-treated groups than other groups. This study concludes, therefore, that MIX (HSMW) minerals, like as Zn, Ca, Mg, Mn, and others stimulate alcohol-metabolizing enzymes, while the antioxidants of plant extracts prevent the damage otherwise incurred by alcohol toxicity. These results suggest that the hangover beverage (MIX) alleviates alcohol hangover symptoms by stimulating activities related to hepatic alcohol-metabolizing enzymes and antioxidant effects.

• Tuberculosis and Respiratory Diseases
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• v.48 no.6
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• pp.887-897
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• 2000

Background : Since the exact pathogenesis of sepsis-induced ARDS has not been elucidated, the mechanisms of enhanced neutrophilic respiratory burst were probed in endotoxin primed neutrophils associated with the roles of phospholipase A2(PLA2), platelet activating factor(PAF) and apoptosis. Methods : In isolated fresh human neutrophils, effects of the inhibition of PLA2 and PAF on the apoptosis were examined by the method of Annexin-FITC/dual PIflow cytometry. The roles of PLA2 and PAF on the neutrophilic respiratory burst were also examined by measuring oxidant generation in cytochrome-c reduction assay. Activities of the PLA2 and lysoPAF acetyltransferase (lysoPAF AT) of the neutrophils were determined to understand the effect of endotoxin on these enzymatic activities which may be related to the neutrophilic respiratory burst and apoptosis. In addition, the role roles of PLA2 and PAF in neutrophilic adhesion to bovine endothelial cells were examined in vitro by neutrophil adhesion assay. To investigate the effect of oxidants on pulmonary surfactant, cytochemical ultrastructural microscopy was performed. To inhibit PLA2 and PAF, non-specific PLA2 inhibitor mepacrine (100 nM) and WEB 2086 (100 nM) or ketotifen fumarate (10 ${\mu}g$/ml) were used respectively in all in vitro experimental sets. WEB 2086 is PAF receptor antagonist, and ketotifen fumarate is a lyso PAF AT inhibitor. Results: The mapacrine treatment, provided and the endotoxin (ETX) treatment, resulted in increased apoptosis of neutrophils (p<0.001) while treatments of WEB 2086 and ketotifen did not. The inhibition of PLA2 and PAF decreased (p<0.001) production of oxidants from PMA-stimulated neutrophils. While endotoxin increased the PLA2 activity of neutrophils (p<0.01), mepacrine supressed (p<0.001) the activity, provided after treatment of ETX. The lyso PAF actyltransferase activity (lyso PAF AT) increased (p<0.01) after treatment of ETX. In contrast, mepacrine, WEB 2086 and ketotifen showed a tendency of decreasing the activity after treatment of ETX. The treatment of ETX incresed (p<0.001) neutrophil adhesion to endothelial cells, which was reversed by inhibition of PLA2 and PAF (p<0.01). The binding of oxidants to pu1monary surfactant was identified histologically. Conclusions : The enhanced neutrophilic respiratory burst by ETX plays a pivotal role in the pathogenesis of ARDS in terms of oxidayive oxidative stress. Increased production of oxidants from neutrophils is mediated by the activations of PLA2 and lyso PAF AT.