• BMB Reports
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• v.42 no.12
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• pp.806-811
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• 2009

Recently, various phenolic acid phenethyl ureas (PAPUs) have been synthesized from phenolic acids by Curtius rearrangement for the development of more effective anti-oxidants. In this study, we examined the anti-tumor activity and cellular mechanism of the synthetic compound (E)-1-(3,4-dihydroxyphenethyl)-3-styrylurea (PAPU1) using melanoma B16/F10 and M-3 cells. Results showed that PAPU1 inhibited the cell proliferation and viability, but did not induce cytotoxic effects on primary cultured fibroblasts. PAPU1 induced apoptotic cell death rather than necrosis in melanoma cells, a result clearly proven by the shift of cells into sub-$G_1$ phase of the cell cycle and by the substantial increase in cells positively stained with TUNEL or Annexin V. Collectively, this study revealed that PAPU1 induced apoptosis in a caspase-dependent manner, suggesting a potential role as a cancer chemopreventive agent for melanoma cells.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.2
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• pp.193-201
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• 2018

Connective tissue growth factor (CTGF) is a novel fibrotic mediator, which is considered to mediate fibrosis through extracellular matrix (ECM) synthesis in diabetic cardiovascular complications. Statins have significant immunomodulatory effects and reduce vascular injury. We therefore examined whether fluvastatin has anti-fibrotic effects in vascular smooth muscle cells (VSMCs) and elucidated its putative transduction signals. We show that advanced glycation end products (AGEs) stimulated CTGF mRNA and protein expression in a time-dependent manner. AGE-induced CTGF expression was mediated via ERK1/2, JNK, and Egr-1 pathways, but not p38; consequently, cell proliferation and migration and ECM accumulation were regulated by CTGF signaling pathway. AGE-stimulated VSMC proliferation, migration, and ECM accumulation were blocked by fluvastatin. However, the inhibitory effect of fluvastatin was restored by administration of CTGF recombinant protein. AGE-induced VSMC proliferation was dependent on cell cycle arrest, thereby increasing G1/G0 phase. Fluvastatin repressed cell cycle regulatory genes cyclin D1 and Cdk4 and augmented cyclin-dependent kinase inhibitors p27 and p21 in AGE-induced VSMCs. Taken together, fluvastatin suppressed AGE-induced VSMC proliferation, migration, and ECM accumulation by targeting CTGF signaling mechanism. These findings might be evidence for CTGF as a potential therapeutic target in diabetic vasculature complication.

• Advances in Traditional Medicine
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• v.7 no.2
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• pp.141-149
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• 2007

Madhuca indica has been used ethnomedically in Indian folks. In the present study we have investigated anti-inflammatory, anti-ulcer and hypoglycaemic effect of ethanolic extract (EE) and crude alkaloid extract of Madhuca indica seed cake on albino rats. The study showed that the EE had a significant, dose dependent anti-edematogenic, anti-ulcerogenic and hypoglycaemic activity, whereas the crude alkaloid extract exhibited a significant only. Both the extracts possess dose dependent inhibitory activity on carrageenan-induced edema, inhibiting prostaglandins or mediators involved in prostaglandin synthesis, the second phase of inflammation. The EE was significantly effective in protecting pylorus-ligation-induced gastric ulcers at a higher dose level. The active principle of EE seems to be a selective inhibitor of the COX II (prostaglandin synthesis) without important effect on COX I since, EE exhibited both anti-edematogenic and anti-ulcerogenic effect. The EE was effective in reducing the plasma glucose level in normal albino rats in a dose dependent manner, producing hypoglycaemic effect by stimulating the release of insulin from the ${\beta}-cells$ and/or increasing the uptake of glucose from the plasma.

• Journal of The Korean Astronomical Society
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• v.15 no.2
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• pp.71-77
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• 1982

According to the star formation rate and metal enrichment rate given by the disk-halo model of Lee and Ann (1981), the two different forms of time-dependent initial mass function (IMF) and the present day mass function (PDMF) of nearby stars have been examined. It was shown that the constraint for the initial rapid metal enrichment requires the time-dependence of IMF at the very early phase ($t{\lesssim}5{\times}10^8$ yrs) of the solar neighborhood. The computed PDMF's show that the PDMF is nearly independent of any specific functional form of IMF as long as the latter includes a Gaussian distribution of log m. This result is due to the very small fractional mass $({\times}5%)$ of stars formed at the very early period during which the IMF is time-dependent. The computed PDMF suggests the presence of more numerous low mass stars than shown in Miller and Scalo's (1979) PDMF, supporting the possibility of the existence of low-velocity M dwarfs. According to the number distribution of stars with respect to [Fe/H], the mean age of these low mass star must be very old so as to yield the mean metal abundance $\bar{[Fe/H]}{\approx}-0.15$ for the stars in the solar neighborhood.

• The Journal of Internal Korean Medicine
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• v.29 no.1
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• pp.42-66
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• 2008

Aconiti Tuber is a traditional medicinal plant generally used in Oriental medicine therapy. In this study, we investigated the biochemical mechanisms of anti-proliferative effects by the methanol extract of Aconiti tuber (MEBJ) in Caki-1 human renal cell carcinoma cells. It was found that MEBJ could inhibit, in a dose-dependent manner, cell growth which was associated with apoptotic cell death such as formation of apoptotic bodies, DNA fragmentation and increased populations of apoptotic-sub G1 phase. Apoptosis of Caki-1 cells by MEBJ was associated with an up-regulation of pro-apoptotic Bax expression, and a down-regulation of anti-apoptotic Bcl-2 in a dose-dependent manner; however, the levels of IAP family were not affected. MEBJ treatment also induced the proteolytic activation of caspase-3 and -8, and a inhibition of poly(ADP-ribose) polymerase (PARP) and $PLC{\gamma}1$ protein. Furthermore, MEBJ treatment caused a dose-dependent inhibition of iNOS and cyclooxygenase-2 (Cox-2). Though further studies will be needed to identify the active compounds that confer the anti-cancer activity of MEBJ, the present findings provide important new insights into the possible molecular mechanisms of the apoptotic activity of MEBJ in cancer cells.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.4
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• pp.419-425
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• 1998

To clarify the effect of extracellular ATP in cultured C6 glioma cells, ATP-induced cytosolic free calcium ($[Ca^{2+}]_i$) mobilization and cell proliferation were investigated. ATP-induced $[Ca^{2+}]_i$ increased in a dose-dependent manner $(10^{-7}\;M{\sim}10^{-3}\;M)$. ATP-induced $[Ca^{2+}]_i$ increases were slightly slowed in extracellular calcium-free conditions especially in sustained phase. ATP-induced $[Ca^{2+}]_i$ increment was also inhibited by the pretreatment of U73122, a phospholipase C (PLC) inhibitor, in a time-dependent manner. Suramin, a putative $P_{2Y}$ receptor antagonist, dose-dependently weakened ATP-induced $[Ca^{2+}]_i$ mobilization. Significant increases in cell proliferation were observed at 2, 3, and 4 days after ATP was added. Stimulated cell proliferation was also observed with adenosine at days 2 and 3. This cell proliferation was significantly inhibited by the treatment with suramin. Ionomycin also stimulated cell proliferation in a concentration-dependent manner. In conclusion, we suggest that extracellular ATP stimulates C6 glioma cell proliferation via intracellular free calcium mobilization mediated by purinoceptor.

• International Journal of Industrial Entomology and Biomaterials
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• v.27 no.2
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• pp.228-236
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• 2013

Breast cancer is one of the most common cancers among women worldwide. Recently anticancer agents have been developed using natural substances. To evaluate the anticancer effect of hydrolysates of silk fibroin (HSF), we investigated the effect of HSF on cell viability and apoptosis of a breast cancer cell line, MCF-7, induced through the mitochondrial pathway. The result showed that HSF decreased cell viability in MCF-7 cells in a dose- and time-dependent manner, resulting in an increase in the sub-G1 phase cell population. HSF increased the level of the pro-apoptotic Bax protein and decreased the levels of the anti-apoptotic Bcl-2 protein. In addition, HSF induced apoptosis in MCF-7 cells through a mitochondria-dependent pathway by increasing levels of cytochtome c, and cleavage of PARP. Taken together, these findings suggest that HSF inhibits the proliferation of MCF-7 breast cancer cells through a mitochondria and caspase dependent apoptotic pathway.

• Publications of The Korean Astronomical Society
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• v.30 no.2
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• pp.545-548
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• 2015

Most high energy cosmic rays (CRs) are thought to be produced by diffusive shock acceleration (DSA) in supernova remnants (SNRs) within the Galaxy. Plasma and MHD simulations have shown that the self-excitation of MHD waves and amplification of magnetic fields via plasma instabilities are an integral part of DSA for strong collisionless shocks. In this study we explore how plasma processes such as plasma instabilities and wave-particle interactions can affect the energy spectra of CR protons and electrons, using time-dependent DSA simulations of SNR shocks. We demonstrate that the time-dependent evolution of the shock dynamics, the self-amplified magnetic fields and $Alfv{\acute{e}nic$ drift govern the highest energy end of the CR energy spectra. As a result, the spectral cutoffs in nonthermal X-ray and ${\gamma}$-ray radiation spectra are regulated by the evolution of the highest energy particles, which are injected at the early phase of SNRs. We also find that the maximum energy of CR protons can be boosted significantly only if the scale height of the magnetic field precursor is long enough to contain the diffusion lengths of the particles of interests. Thus, detailed understandings of nonlinear wave-particle interactions and time-dependent DSA simulations are crucial for understanding the nonthermal radiation from CR acceleration sources.

• Transactions of the Korean Society of Automotive Engineers
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• v.15 no.6
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• pp.177-182
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• 2007

In this paper, automotive hydraulic pipeline systems are modeled in which a straight blocked pipe, two pipes with sudden expansion or contraction are connected in series and terminated with a chamber. The frequency response characteristics of these composite pipeline systems are investigated experimentally. The theoretical analysis for various pipe configurations is base on transfer matrix method with frequency dependent viscous friction distributed parameter pipeline model. The gain and phase of transfer functions are included for comparison with experimental results. There is close agreement between the results of experimental and theoretical determination of pressure response in automotive hydraulic pipeline systems.

• The Transactions of The Korean Institute of Electrical Engineers
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• v.59 no.6
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• pp.1173-1178
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• 2010

In this note, a systematic design of a new robust nonlinear integral variable structure controller based on state dependent nonlinear form is presented for the control of uncertain more affine nonlinear systems with mismatched uncertainties and matched disturbance. After an affine uncertain nonlinear system is represented in the form of state dependent nonlinear system, a systematic design of a new robust nonlinear integral variable structure controller is presented. To be linear in the closed loop resultant dynamics and remove the reaching phase problems, the linear integral sliding surface is suggested. A corresponding control input is proposed to satisfy the closed loop exponential stability and the existence condition of the sliding mode on the linear integral sliding surface, which will be investigated in Theorem 1. Through a design example and simulation studies, the usefulness of the proposed controller is verified.