• Reproductive and Developmental Biology
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• v.31 no.2
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• pp.71-76
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• 2007

Previous studies have shown that BMI-1026 is a potent inhibitor of the cyclin-dependent kinases (cdk). In cell culture, the compound also arrests G2/M strongly and G1/S and S weakly. Two key kinases, cdk1 (p34cdc2 kinase) and mitogen-activated protein (MAP) kinase (erk1 and 2), perform crucial roles during oocyte maturation and, later, metaphase II (MII) arrest. In mammalian oocytes, both kinases are activated gradually around the time of germinal vesicle breakdown (GVBD) and maintain high activity in eggs arrested at metaphase II. In this study, we examined the effects of BMI-1026 on GVBD and MII arrest in mouse oocytes. BMI-1026 inhibited GVBD of immature oocytes and activated MII-arrested oocytes in a concentration-dependent manner, with more than 90% of oocytes exhibiting GVBD inhibition and MII activation at 100 nM This is approximately 500$\sim$1,000 times more potent than the activity reported for the cdk inhibitors roscovitine (${\sim}50{\mu}M$) and butyrolactone (${\sim}100{\mu}M$). Based on the results of previous in vitro kinase assays, we expected BMI-1026 to inhibit only cdk1 activation in oocytes and eggs, not MAP kinase. However, in our cell-based system, it inhibited the activity of both kinases. We also found that the effect of BMI-1026 is reversible. Our results suggest that BMI-1026 inhibits GVBD and activates MII-arrested oocytes efficiently and reversibly and that it also inhibits both cdk1/histone HI kinase and MAP kinase in mouse oocytes.

• International Journal of Automotive Technology
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• v.1 no.1
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• pp.35-41
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• 2000

The crashworthiness of vehicles with finite element methods depends on the geometry modeling and the material properties. The vehicle body structures are generally composed of various members such as frames, stamped panels and deep-drawn parts from sheet metals. In order to ensure the impact characteristics of auto-body structures, the dynamic behavior of sheet metals must be examined to provide the appropriate constitutive relation. In this paper, high strain-rate tensile tests have been carried out with a tension type split Hopkinson bar apparatus specially designed for sheet metals. Experimental results from both static and dynamic tests with the tension split Hopkinson bar apparatus are interpolated to construct the Johnson-Cook and a modified Johnson-Cook equation as the constitutive relation, that should be applied to simulation of the dynamic behavior of auto-body structures. Simulation of auto-body structures has been carried out with an elasto-plastic finite element method with explicit time integration. The stress integration scheme with the plastic predictor-elastic corrector method is adopted in order to accurately keep track of the stress-strain relation for the rate-dependent model accurately. The crashworthiness of the structure with quasi-static constitutive relation is compared to the one with the rate-dependent constitutive model. Numerical simulation has been carried out for frontal frames and a hood of an automobile. Deformed shapes and the Impact energy absorption of the structure are investigated with the variation of the strain rate.

• The Journal of Internal Korean Medicine
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• v.25 no.1
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• pp.81-91
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• 2004

Objectives : The aim of this study is to investigate the inhibitory effect of Chungganhaeju-Tang on alcohol induced human hepatic cell apoptosis by synthesis of glutathione. Methods : The amount of glutathione in HepG2 cell was measured with colorimetric glutathione assay kit and glutathione-conjugated CDNB(1-chloro-2,4-dinitrobenzene) at $37^{\circ}C$ and then measured by spectrometry to assess the activity of glutathione S-transferase. Results : The synthesis of glutathione and the activity of glutathione S-transferase in HepG2 cell were promoted by Chungganhaeju-Tang and increased in dose/time-dependent manner. Chungganhaeju-Tang inhibited apoptosis induced by ethanol and acetaldehyde dependent to treatment dosage. In Buthione sulfoximine, a glutathione synthesis inhibitor, treated case, the synthesis of glutathione was inhibited and in Chungganhaeju-Tang treated case, the synthesis of glutathione is promoted with or without Buthione sulfoximine. The present findings suggest that Chungganhaeju-Tang inhibits alcohol induced apoptosis by synthesis of glutathione in HepG2 cell. Conclusions : The result indicates that Chungganhaeju-Tang protects human hepatic cell by glutathione synthesis and made the liver recover from alcohol induced damage.

• The Journal of Korean Medicine
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• v.27 no.4
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• pp.162-173
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• 2006

The water-extracts of Scutellaria barbata Don (SBDE) were isolated from Chinese medicinal plant sources. The extracts showed strong growth-inhibitory activity and cancer chemopreventive activity on the growth and DNA incorporation of MG63 human osteosarcoma and K562 human leukemia cell lines. The growth of human cancer cells was inhibited in the presence of the extracts (20, 50 and 100 ${\mu}$g/ml), and the effects were concentration-dependent and incubation time-dependent up to 8 days. When 50 ${\mu}$g/ml of the extracts was added to the media of MG63 and K562, cell growth after 8 days or 6 days of incubation was retarded by 93.2 to 97.3% of the control group. Morphological changes of MG63 and K562 cell lines were observed. As the concentration of the extracts increased up to 50 ${\mu}$g/ml, degree of cell aggregation decreased. Moreover, the DNA incorporation of the cells which were labeled with [3H] thymidine was significantly reduced after 3 days of incubation at $37^{\circ}C$ with the extract. Therefore, it is suggested that the extract is highly effective on inhibition of cancer cell growth. The extract also inhibited gene expression of IGF-II in transcriptional level. Since IGF-II works as a mitogenic effector on MG63 and K562 cell lines, these results suggest that the growth inhibition is in part mediated through the inhibition of IGF-II gene expression.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2753-2758
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• 2012

Rubia cordifolia Linn, which belongs to the Rubiaceae family, is a well-known herb used in Ayurvedic medicine. In the present study, we investigated the influence of a methanolic extract (RC) on the induction of apoptosis in HEp-2 (human laryngeal carcinoma) cell line, as evidenced by cytotoxicity, morphological changes and modification in the levels of pro-oxidants. Inhibition of cell proliferation and lactate dehydrogenase (LDH) release increased in a time and dose-dependent manner. Further, reduced glutathione (GSH), glutathione transferase (GST) and protein levels decreased and lipid peroxidation increased significantly on RC treatment in a dose dependent manner when compared to controls. Based on the results we determined the optimal dose as 30mg/ ml and the apoptotic effect of RC extract (30 mg/ml) on HEp-2 cells was confirmed by fluorescent microscopy and transmission electron microscopy (TEM) based on morphological and ultrastructural changes. RC extract suppressed the proliferation of HEp-2 oral cancer cells inducing apoptotic cell death in vitro. These results point to potential of RC extract as an agent for the treatment of laryngeal squamous cell carcinoma.

• Nutrition Research and Practice
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• v.3 no.3
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• pp.192-199
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• 2009

Cadmium intoxication has been associated with the dysregulation of iron homeostasis. In the present study, we investigated the effect of cadmium on the expression of ferroportin 1 (FPN1), an important iron transporter protein that is involved in iron release from macrophages. When we incubated cadmium with J774 mouse macrophage cells, FPN1 mRNA levels were significantly increased in a dose- and time-dependent manner. Furthermore, the cadmium-induced FPN1 mRNA expression was associated with increased levels of FPN1 protein. On the other hand, cadmium-mediated FPN1 mRNA induction in J774 cells was completely blocked when cells were co-treated with a transcription inhibitor, acitomycin D. Also, cadmium directly stimulated the activity of the FPN1-promoter driven luciferase reporter, suggesting that the cadmium up-regulates FPN1 gene expression in a transcription-dependent manner. Finally, cadmium exposure to J774 macrophages increased intracellular reactive oxygen species (ROS) levels by ${\sim}2$-fold, compared to untreated controls. When J774 cells were co-treated with antioxidant N-acetylcystein, the cadmium-induced FPN1 mRNA induction was significantly attenuated. In summary, the results of this study clearly demonstrated that cadmium increased FPN1 expression in macrophages through a mechanism that involves ROS production, and suggests another important interaction between iron and cadmium metabolism.

• Journal of Korean Academy of Nursing
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• v.14 no.2
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• pp.84-92
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• 1984

This article examined relationships between selected variables, such as demographic background, care, treatment variables, environmental characteristics, and patient's daily behavior and mood change. Relationship were determined between independent variabltherapeutic-rapeutie approach, demographic data, environmental management approach-,and dependent variable-patient's daily behavioral and mood change. 35 patients selected within some criteria in a psychiatric ward, were obserbed during 5 weeks by use of Wyatt's Behavior & Mood Rating Scale ac-cording to the object of the study. At the same time, the frequence of the care and treatment were collected. Criteria for sample selection and independent variables as an influential factor to the patient behavioral change, based on a literature revienw and clinical experiences. Pearson's correlation and multiple regression analysis were used to determine the influfntial factors to the patient behavioral change. Systematic reading (r=.8324), Psychiatrist's individual interview (r=.5764), tranquilizer (r=.3441) and hospitalization processing date (r=.4143) were related with patient's behavioral change. That is these 4 variables can be said to influence to the patient's behavior and mood. A stepwise multiple regression analysis of the effect of the independent varibles of systematic reading, psychintrists individual interview, tranquilizer and hospitalization processing date on the dependent variable, patient's behavioral change was carried out. Systematic reading with on R²of. 69 revealed to be the main influential factor to the patient's behavior and mood change, as the next factor psychiatrist individual interview. A total inclusion of these factors revealed a 73% prediction for the patient's behavior and mood change. But the most influential factor was the interaction of the systematic reading and psychiatrist's individual interview.

• International Journal of Oral Biology
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• v.41 no.4
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• pp.231-236
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• 2016

Inhibition of Rho-associated coiled coil-containing kinase (ROCK) has been reported to promote differentiation of neuronal cells. Here, we examined the effect of Y-27632, a ROCK inhibitor, on the outgrowth of neurites in PC12 cells. Y-27632 caused a rapid induction of neurite outgrowth in PC12 cells in a time-dependent manner. The neurite outgrowth, triggered by Y-27632, was accompanied by Rac1 activation, and was attenuated by Rac1 inhibitor NSC23766, in a concentration-dependent manner. Y-27632 also induced an increase in the production of reactive oxygen species (ROS). Pretreatment with N-acetylcysteine, an ROS scavenger, inhibited the ROS generation and neurite outgrowth in response to Y-27632. These results indicate that the activation of Rac1 and the generation of ROS contribute to the neurite outgrowth triggered by Y-27632 in PC12 cells.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2001.11a
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• pp.91-91
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• 2001

Nramp2, also known as DMT1 and DCT1, is a 12-transmembrane domain protein responsible for dietary iron uptake as well as metal ions such as lead, manganese, zinc, copper, nickel, cadmium, and cobalt. High expression of DMT1 increase lead uptake, and DMT1-dependent lead transport was H -dependent and inhibited by iron ions. The molecular mechanism of lead transport in CNS is as yet unknown. although interactions between iron and lead at the level of absorption have been known for some time. The process of lead uptake into astrocytes was not known yet. Nramp2 may mediate transport of heavy metal into astrocytes. We investigated whether Nramp2 mediate transport of lead into astrocytes. And we do whether Nramp2 was expressed highly by deprivation of iron in Astrocytes, and lead uptake into astrocytes was influenced by expression of Nramp2. Immortalized human fetal astrocyte(SV-FHA) cells were cultured in medium containing Dulbecco's modified Eagle's medium and treated with Deferoxamine. Northern blot analysis was done for determining mRNA level of DMT1 and lead uptake assay was done in incubation condition of pH 5.5 and 7.4.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.102-102
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• 2003

The inhibitors of prostaglandin biosynthesis and nitric oxide production by corresponding inducible isozyme have been considered as potential anti-inflammatory and cancer chemopreventive agents. In our continuous search for cancer chemopreventive agents from natural products, we have evaluated the inhibitory potential of PGE$_2$and NO production in lipopolysaccharide (LPS)-induced mouse macrophage RAW264.7 cells. As a result, pinosylvin (3,5-dihydroxy-trans-stilbene), a stilbenoid, mainly found from the heartwood and leaves of the Pinus sylvestris, showed potential inhibitory activity of LPS-induced PGE$_2$and NO production in a dose-dependent manner. Pinosylvin also suppressed the LPS-induced iNOS protein expression. Further study revealed that pinosylvin exhibited antioxidant activity by the DPPH free radical scavenging potential and inhibitory effect of xanthine oxidase activity. In addition, pinosylvin inhibited COX -2 overexpressed human colon cancer cell (HT-29) growth in a time- and dose-dependent manner. These findings suggest that pinosylvin might be a promising candidate for developing cancer chemopreventive agent.