• Development and Reproduction
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• v.4 no.2
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• pp.243-250
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• 2000

To find the mechanism underlying the ADP-induced increase in the outward current in ovulated mouse oocytes, we examined changes in voltage-dependent currents using the whole cell voltage clamp technique and the internal perfusion technique. Eggs were collected from the oviduct of superovulated mice with PMSG and hCG. Membrane potential was held at -60 mV (or -80 mV in the case of recording $Ca^{2＋}$ currents) and step depolarizations or hyperpolarizations were applied for 300 ms. By step depolarizations, outward currents comprising steady-state and time-dependent components were elicited. They were generated in response to the positive potential more than 20 mV with severe outward rectification and were blocked by external TEA, a specific $K^{＋}$ channel blocker, suggesting that they be carried via $K^{＋}$ channels. Internally-perused 5 mM ADP gradually increased outward $K^{＋}$ currents (IK) 1 min after perfusion of ADP and reached slowly to maximum (150~170％) 5 min later over the positive potential range, implying that ADP might not be acted directly to the $K^{＋}$ channels. IK were decreased by 5 mM ATP without affecting the steady-state component of outward current. In contrast to the effect of ADP and ATP on IK, both effect of ATP and ADP on inward $Ca^{2＋}$ currents (ICa) could not be detected due to the continuous decrease in current amplitudes with time-lapse ("run-down" phenomena). To check if there is a G protein-involved regulation in the ionic current of mouse oocytes, 1 mM GTP was applied to the cytoplasmic side, and the outward current and inward currents were recorded. ICa was promptly increased in the presence of GTP whereas IK was not changed. from these results, it is concluded that the ATP-dependent regulation is likely linked in the ADP-induced increase in the outward $K^{＋}$ current, and G protein-involved cellular signalling might affect ion channels carrying $Ca^{2＋}$ and $K^{＋}$ in mouse oocytes.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.1
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• pp.124-129
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• 2005

Resveratrol, a phytoalexin found at high levels in grapes and in grape products such as red wine, has been reported to possess a wide range of biological and pharmacological activities including anti-oxident, anti-inflammatory, anti-mutagenic, and anti-carcinogenic effects, but its molecular mechanism is poorly understood. In this study, we examined the effects of resveratrol on lipopolysaccharide (LPS)-induced growth inhibitory activity and cell growth-regulatory gene products in astroglioma C6 cells to elucidate its possible mechanism for anti-cytotoxicity. It is shown that LPS induced time-dependent growth inhibition and morphological changes of C6 cells, which were recovered by pre-treatment with resveratrol. The anti-proliferative effect of LPS was associated with the induction of tumor suppressor p53 and cyclin-dependent kinase (Cdk) inhibitor p21 (WAF1/CIP1) expression assessed by RT-PCR and Western blot analysis in time-dependent manner in C6 cells. In addition, the pro-apoptotic Bax expression was also up-regulated in LPS-treated C6 cells without alteration of anti-apoptotic Bcl-2 and Bcl-XL expression. However, resveratrol significantly inhibited LPS-induced p53, p21 and Bax levels, suggesting that the modulation of p53, p21 and Bax levels could be one of the possible pathways by which resveratrol functions as anti-cytotoxic agent.

• Biomolecules & Therapeutics
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• v.24 no.4
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• pp.395-401
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• 2016

Endochondral bone formation is the process by which mesenchymal cells condense into chondrocytes, which are ultimately responsible for new bone formation. The processes of chondrogenic differentiation and hypertrophy are critical for bone formation and are therefore highly regulated. The present study was designed to investigate the effect of aloe-emodin on chondrogenic differentiation in clonal mouse chondrogenic ATDC5 cells. Aloe-emodin treatment stimulated the accumulation of cartilage nodules in a dose-dependent manner. ATDC5 cells were treated with aloe-emodin and stained with alcian blue. Compared with the control cells, the ATDC5 cells showed more intense alcian blue staining. This finding suggested that aloe-emodin induced the synthesis of matrix proteoglycans and increased the activity of alkaline phosphatase. Aloe-emodin also enhanced the expressions of chondrogenic marker genes such as collagen II, collagen X, BSP and RunX2 in a time-dependent manner. Furthermore, examination of the MAPK signaling pathway showed that aloe-emodin increased the activation of extracellular signal-regulated kinase (ERK), but had no effect on p38 and c-jun N-terminal kinase (JNK). Aloe-emodin also enhanced the protein expression of BMP-2 in a time-dependent manner. Thus, these results showed that aloe-emodin exhibited chodromodulating effects via the BMP-2 or ERK signaling pathway. Aloe-emodin may have potential future applications for the treatment of growth disorders.

• The Korean Journal of Zoology
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• v.36 no.3
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• pp.342-346
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• 1993

The protein level of cytoskeletons in cultured myoblasts was found to gradually decrease during the course of myogenesis. This decrease, however, could be prevented by treatiag the ceils with calpeptin (benzyloxycarbonyl-Leu-nLeu-H), a cell penetrating inhibitor of calpain. In contrast, E-64, which also is a potent inhibitor of calpain but can not be transported into the cells, showed little or no effect. In addition, the treatment of calpeptin was found to stabilize a number of specific cytoskeletal proteins from degradation but without any effect on the pattern of total cells proteins. Furthermore, calpeptin, but not E-64, blocked myoblast fusion in a dose-dependent manner. These results suggest that calpain is responsible for the myogenic time-dependent loss of cytoskeletal proteins and that the degradative process is associated with myoblast fusion. These results also suggest that the differential effects of the calpain inhibitors depend on the permeabIlity of the drugs across the cell membrane.

• Environmental Analysis Health and Toxicology
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• v.27
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• pp.10.1-10.7
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• 2012

Objectives: In recent years, a number of structurally diverse Histone deacetylase (HDAC) inhibitors have been identified and these HDAC inhibitors induce growth arrest, differentiation and/or apoptosis of cancer cells in vitro and in vivo. This study aimed at investigating the antitumor activity of newly synthesized HDAC inhibitor, 3-(4-dimethylamino phenyl)-N-hydroxy-2-propenamide (IN-2001) using human breast cancer cells. Methods: We have synthesized a new HDAC inhibitor, IN-2001, and cell proliferation inhibition assay with this chemical in estrogen receptor-positive human breast cancer MCF-7 cells. Cell cycle analysis on MCF-7 cells treated with IN-2001 was carried out by flow cytometry and gene expression was measured by RT-PCR. Results: In MCF-7 cells IN-2001 showed remarkable anti-proliferative effects in a dose- and time-dependent manner. In MCF-7 cells, IN-2001 showed a more potent growth inhibitory effect than that of suberoylanilide hydroxamic acid. These growth inhibitory effects were related to the cell cycle arrest and induction of apoptosis. IN-2001 showed accumulation of cells at $G_2$/M phase and of the sub-$G_1$ population in a time-dependent manner, representing apoptotic cells. IN-2001-mediated cell cycle arrest was associated with HDAC inhibitor-mediated induction of CDK inhibitor expression. In MCF-7 cells, IN-2001 significantly increased $p21^{WAF1}$ expression. Conclusions: In summary, cyclin-dependent kinase (CDK) induced growth inhibition, possibly through modulation of cell cycle and apoptosis regulatory proteins, such as CDK inhibitors, and cyclins. Taken together, these results provide an insight into the utility of HDAC inhibitors as a novel chemotherapeutic regime for hormone-sensitive and insensitive breast cancer.

• Physical Therapy Rehabilitation Science
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• v.3 no.1
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• pp.33-37
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• 2014

Objective: Low intensity pulsed ultrasound (LIPUS) has been shown to accelerate cell proliferation and tissue healing in both animal models and clinical trials. However, details of the clinical effects of LIPUS have not been well characterized. The aim of this study was to investigate the effect of LIPUS on mitogen-activated protein kinase (MAPK) activation in rat articular chondrocytes. Design: Cross-sectional study. Methods: Chondrocyte were cultured in six well cell culture plates for 72 hours at $37^{\circ}C$ with 5% $CO_2$, and then exposed to LIPUS at 1.5 MHz frequency and $30-mW/cm^2$ power. Changes in chondrocyte activities were evaluated in response to oxydative stress in dose-dependent (0 and 300 uM) and time-dependent (0-24 hr) manner. The cell viability were analyzed using MTT [3-(4.5-dimethylthiazol-2-yl)-2.5 diphenyltetrazolium bromide]. The expression of p38 MAPK was measured using western blotting. Results: Oxidative stress was induced in rat chondrocytes using hydrogen peroxide ($H_2O_2$). The cell viability was decreased in chondrocytes after the $H_2O_2$ dose and time-dependent treatment. The p38 MAPK phosphorylation occurred at a significantly increased rate after $H_2O_2$ treated (p<0.05). Expression of p38 MAPK was decreased in the p38 inhibitor groups compared with the oxidative stress-induced chondrocyte damage via the p38 MAPK signaling pathways (p<0.05). Conclusions: It could be concluded that LIPUS can inhibit oxidative stress-induced chondrocyte damage via the p38 MAPK signaling pathways.

• Smart Structures and Systems
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• v.14 no.6
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• pp.1031-1054
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• 2014

Real-time hybrid simulation (RTHS) of a stacked wood shear wall retrofitted with a rate-dependent seismic energy dissipation device (viscous damper) was conducted at the newly constructed Structural Engineering Laboratory at the University of Alabama. This paper describes the implementation process of the RTHS focusing on the controller scheme development. An incremental approach was adopted starting from a controller for the conventional slow pseudodynamic hybrid simulation and evolving to the one applicable for RTHS. Both benchmark-scale and full-scale tests are discussed to provide a roadmap for future RTHS implementation at different laboratories and/or on different structural systems. The developed RTHS controller was applied to study the effect of a rate-dependent energy dissipation device on the seismic performance of a multi-story wood shear wall system. The test specimen, setup, program and results are presented with emphasis given to inter-story drift response. At 100% DBE the RTHS showed that the multi-story shear wall with the damper had 32% less inter-story drift and was noticeably less damaged than its un-damped specimen counterpart.

• Journal of Pharmacopuncture
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• v.20 no.3
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• pp.207-212
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• 2017

Objectives: Study of the mechanisms involved in cancer progression suggests that cyclooxygenase enzymes play an important role in the induction of inflammation, tumor formation, and metastasis of cancer cells. Thus, cyclooxygenase enzymes could be considered for cancer chemotherapy. Among these enzymes, cyclooxygenase 2 (COX-2) is associated with liver carcinogenesis. Various COX-2 inhibitors cause growth inhibition of human hepatocellular carcinoma cells, but many of them act in the COX-2 independent mechanism. Thus, the introduction of selective COX-2 inhibitors is necessary to achieve a clear result. The present study was aimed to determine the growth-inhibitory effects of new analogues of chalcone epoxide as selective COX-2 inhibitors on the human hepatocellular carcinoma (HepG2) cell line. Methods: Estimation of both cell growth and the amount of prostaglandin E2 (PGE2) production were used to study the effect of selective COX-2 inhibitors on the hepatocellular carcinoma cell. Cell growth determination has done by MTT assay in 24 h, 48 h and 72 h, and PGE2 production has estimated by using ELYSA kit in 48 h and 72 h. Results: The results showed growth inhibition of the HepG2 cell line in a concentration and time-dependent manner, as well as a reduction in the formation of PGE2 as a product of COX-2 activity. Among the compounds those analogues with methoxy and hydrogen group showed more inhibitory effect than others. Conclusion: The current in-vitro study indicates that the observed significant growth-inhibitory effect of chalcone-epoxide analogues on the HepG2 cell line may involve COX-dependent mechanisms and the PGE2 pathway parallel to the effect of celecoxib. It can be said that these analogues might be efficient compounds in chemotherapy of COX-2 dependent carcinoma specially preventing and treatment of hepatocellular carcinomas.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.31 no.1
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• pp.7-12
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• 2005

Purpose: CKD-602, a newly developed water-soluble campthotecin analogue, is a anticancer agent which act as a DNA topoisomerase I inhibitor. CKD-602 is known as more potent and tolerable agent. The main purposes of this study were to measure the cytotoxic effect of CKD-602 on the oral cancer cell lines and to evaluate the apoptotic aspect of dead cells. Materials and Methods: To determine the cytotoxic effect of CKD-602 on the oral cancer cell lines in comparison with various cell lines, such as lung cancer and colon cancer cell lines, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay was performed. And apoptosis was analyzed using fluorescence-activated cell sorting(FACS) system. Results: CKD-602 decreased the viability of malignant cells in a dose dependent manner and in a time dependent manner. CKD-602 showed excellent cytotoxicity to the oral cancer cell lines. Also, apoptotic portion was increased in a dose dependent manner. Conclusion: These findings indicated that CKD-602 induced apoptotic cell death in the various cell lines including oral cancer cell lines. From the results, it was suggested that CKD-602 would be a potential therapeutic agent for the oral cancer. More successive researches on the anticancer effect of CKD-602 should be performed.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.21 no.6
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• pp.603-610
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• 2020

This study examined the mental health-related factors of Korean adolescents, especially focusing on the influence of internet use. This study analyzed the raw data from the 14th Korea Youth Risk Behavior Survey, 2018. The study population was 60,040, with 50.7% male students and 49.3% female students, and 49.7% high school students and 50.3% middle school students. The dependent variables were stress, sadness and despair, suicidal ideation, suicidal plan, and suicidal attempt. The independent variables were gender and age, health behaviors, and time using the internet. Logistic regression analysis was applied to derive the related factors. For all dependent variables, the main contributing variables were gender, grade, economic status, and academic performance. The mental health of adolescents was related to various factors. In particular, the time using the internet was linearly related to the degree of stress, and a higher student group of time using the internet had a more significant effect on sadness, despair, suicidal thoughts, and suicidal plans. In conclusion, the time using the internet has harmful effects on the mental health of Korean adolescents.