• Journal of Life Science
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• v.21 no.6
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• pp.851-857
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• 2011

Sulforaphane (SFN) is an isothiocyanate, isolated from glucoraphanin in broccoli and other cruciferaous vegetables. Recent studies have revealed that SFN induces anti-proliferation and apoptosis by cell cycle arrest in various cancer cells. In this study, we investigated the effect of SFN induced apoptosis in chondrosarcoma HTB-94 cells. SFN caused suppression of proliferation and apoptosis in a dose-dependent manner as determined by cell phenotype, MTT assay and FACS analysis in HTB-94 cells. Treatment of SFN led to caspase-3 activation and p53 accumulation as determined by Western blot analysis. Also, SFN significantly induced DNA fragmentation and nuclear degradation though activation of caspase-3, as detected by DNA electrophoresis and immunostaining, respectively. Our results indicate that SFN-induced apoptosis was regulated by p53 and caspase-3 dependent pathways. Furthermore, SFN may act as a potent anti-proliferation agent, and as a promising candidate for molecular-targeting chemotherapy against human chondrosarcoma cells.

• Journal of Life Science
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• v.16 no.5
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• pp.759-766
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• 2006

Acute promyelocytic leukemia (APL) is a myeloid leukemia caused by over-expression of fusion protein, PML/RAR$({\alpha})$, which was the result of chromosomal translocation and induces the blockage of differentiation of affected promyelocytes. Pharmacological dose of retinoic acid induces the activation of and subsequent degradation of PML/RAR$({\alpha})$ fusion protein, and then APL cells undergo through the normal differentiation pathway. Arsenic trioxide has proved effective in causing remission of acute promyelocytic leukemia by inducing apoptosis of this tumor cells, whereas the heterogeneity of cellular susceptibility to this cytotoxic agent limited its usage on more types of tumors in clinic. This work showed that arsenic trioxide could induce apoptosis of a panel of acute promyelocytic leukemic cell lines, all-trans-retinoic acid (ATRA) sensitive NB4 cells and ATRA resistant UF-1 cell. They were investigated with regard to the correlation between the inherent or intrinsic cellular level of GSH and the apoptotic susceptibility of the cells to arsenic trioxide. We manifested, in two cell types, the inherently existed difference in intracellular GSH level reactive to the arsenic trioxide, and a positive correlation between the GSH level and their apoptotic sensitivity to arsenic trioxide. And it showed that arsenic trioxide could differentiate promyelocytic cancer cells to the cells possessed of dendritic cell surface markers. Unravelling the cause of the different susceptibility between leukemic cells and proving that promyelocyte could be differentiated to dendritic cells by arsenic trioxide will help not only to understand the mechanism underlying the complete remission of acute promyelocytic leukemia induced by arsenic trioxide, but also to expand its clinical usage.

• Journal of Pharmaceutical Investigation
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• v.36 no.4
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• pp.271-276
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• 2006

Felodipine, a calcium-antagonist of dihydropyridine type, is a poorly water soluble drug and has very low bioavailability. As preceding studies, use of solid dispersion systems and surfactants(solubilizers) has been suggested to increase dissolution and to improve bioavailability of felodipine. But in case of solid dispersion systems, large amount of toxic organic solvents should be used and manufacturing process time become longer than conventional process. In case of using surfactants, as time elapsed, decreasing of dissolution rate of felodipine due to crystallization has been reported. In this study, Copovidon as a hydrophilic polymer and $Transcutol^{\circledR}$ as a surfactant were combined to formulations if order to increase dissolution of felodipine and conventional wet granulation process were applied to manufacturing of formulations. The effect of Copovidon and $Transcutol^{\circledR}$ on the dissolution oi felodipine was investigated in-vitro. When Copovidon and $Transcutol^{\circledR}$ used simultaneously, the dissolution rate of felodipine was prominently increased compared with when used separately and the maximum increase in the dissolution of felodipine was 5.8 fold compared to control. This is most probably due to synergy effect by combination of Copovidon and $Transcutol^{\circledR}$. Felodipine sustained release tablets were successfully formulated using several grades of HPMC as a release retarding agent. The stability of felodipine sustained release tablet was evaluated after storage at accelerated condition($40^{\circ}C/75%\;RH$) for 6months in HDPE(High density polyethylene) bottle. Neither significant degradation nor change of dissolution rate for felodipine was observed after 6months. In conclusion, felodipine sustained release tablet was successfully formulated and dissolution of felodipine, poorly water soluble drug, was prominently increased and also stability was guaranteed by using combination system of hydrophilic polymer and surfactant.

• Journal of the Korea institute for structural maintenance and inspection
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• v.12 no.5
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• pp.161-168
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• 2008

The freeze-thaw deterioration and chloride attack, which are the typical degradation factors for durability of marine concrete, are significantly affected by pore structures in terms of penetration and diffusion. These pore structures of concrete are closely related to the types and amount of AE agent, used to guarantee the resistance of freeze-thaw deterioration, and the elapsed time before concrete pouring. This paper evaluates the durability of concrete based on the results of tests on cylinder specimens and core specimens from mock-up members with different air content of 4~6% and 8~10%, respectively. According to the test results, the air content of hardened concrete is 2.5~5.2% at 7 days and 2.4~5.1% at 28 days. These air contents are about half of the initial values just after the concrete mixing. Judging from the amount of scale after the freeze-thaw test completed, air content of 8~10% is slightly more beneficial against the deterioration of concrete than air content of 4~6%. Meanwhile, the core specimens from mock-up members exhibit somewhat unfavorable freeze-thaw deterioration and chloride migration characteristic compared with the cylinder specimens tested in the laboratory under the same mixing condition, as to show 106% in freeze-thaw test and 160% in chloride diffusion coefficient test, respectively.

• Journal of Internet Computing and Services
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• v.21 no.5
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• pp.1-7
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• 2020

Deep neural networks(DNN), which are used as approximation functions in reinforcement learning (RN), theoretically can be attributed to realistic results. In empirical benchmark works, time difference learning (TD) shows better results than Monte-Carlo learning (MC). However, among some previous works show that MC is better than TD when the reward is very rare or delayed. Also, another recent research shows when the information observed by the agent from the environment is partial on complex control works, it indicates that the MC prediction is superior to the TD-based methods. Most of these environments can be regarded as 5-step Q-learning or 20-step Q-learning, where the experiment continues without long roll-outs for alleviating reduce performance degradation. In other words, for networks with a noise, a representative network that is regardless of the controlled roll-outs, it is better to learn MC, which is robust to noisy rewards than TD, or almost identical to MC. These studies provide a break with that TD is better than MC. These recent research results show that the way combining MC and TD is better than the theoretical one. Therefore, in this study, based on the results shown in previous studies, we attempt to exploit a random balance with a mixture of TD and MC in RL without any complicated formulas by rewards used in those studies do. Compared to the DQN using the MC and TD random mixture and the well-known DQN using only the TD-based learning, we demonstrate that a well-performed TD learning are also granted special favor of the mixture of TD and MC through an experiments in OpenAI Gym.

• Journal of Life Science
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• v.25 no.2
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• pp.249-255
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• 2015

Schisandrae fructus [Schizandra chinensis (Turcz.) Baillon] is a medicinal herb widely used for treating various inflammatory and immune diseases in East Asian countries. The Schisandrae Semen essential oil (SSeo) from this plant has pharmacological activities, including antioxidant, antimicrobial, and antitumoral activities. Nevertheless, the biological activities and underlying molecular mechanisms of the potential anti-cancer effects of this oil remain unclear. In the present study, we investigated the potential inhibition of apoptosis signaling pathways by SSeo in human leukemia U937 cells and evaluated the underlying molecular mechanism. Exposure to SSeo resulted in a concentration-dependent growth inhibition due to apoptosis, which was verified by DNA fragmentation, the presence of apoptotic bodies, and an increase in the sub-G1 ratio. Induction of apoptotic cell death by SSeo was correlated with the down-regulation of members of the inhibitor of apoptosis protein (IAP) family (including X-linked inhibitor of apoptosis protein (XIAP), cIAP-1, and surviving) and anti-apoptotic Bcl-2, and with up-regulation of death receptor (DR) 4 and DR5, depending on dosage. SSeo treatment also induced Bid truncation, mitochondrial dysfunction, proteolytic activation of caspase-3, -8 and -9, and concomitant degradation of activated caspase-3 target proteins such as poly (ADP-ribose) polymerase. Taken together, these findings suggest that SSeo may be a potential chemotherapeutic agent for use in the control of human leukemia cells. Further studies are needed to identify its active compounds.

• Journal of Life Science
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• v.23 no.4
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• pp.518-528
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• 2013

Scutellaria baicalensis, belonging to the family Labiatae, is widely distributed in Korea, China, Mongolia, and eastern Siberia. It has been used in traditional medicine for various diseases, such as dysentery, pyrexia, jaundice, and carbuncles. In addition, S. baicalensis is reported to possess various beneficial pharmacological activities, including anti-inflammatory, antidiabetic, antiviral, antihypertension, antioxidant, and anticancer effects. However, the molecular mechanisms of its anticancer activity have not been clearly elucidated. In the present study, we investigated the proapoptotic effects of ethanol extract of S. baicalensis (EESB) on human renal cell carcinoma Caki-1 cells. The anti-proliferative activity of EESB was associated with apoptosis induction, which was associated with the up-regulation of death receptor 4, the Fas ligand, and Bax and the down-regulation of Bid, XIAP, and cIAP-1 proteins. EESB treatment also induced mitochondrial dysfunction, proteolytic activation of caspase-3, -8, and -9 and degradation of caspase-3 substrate proteins, such as poly (ADP-ribose) polymerase, ${\beta}$-catenin, and phospholipase C-${\gamma}1$. However, pretreatment of a pan-caspase inhibitor, z-VAD-fmk, significantly attenuated the EESB-induced apoptosis. Taken together, these findings suggest that EESB may be a potential chemotherapeutic agent. Further studies will be needed to identify the active compounds that confer the anticancer activity of S. baicalensis.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.5
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• pp.649-659
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• 2011

To examine the anti-cancer effects of Lepidium virginicum L., the anti-proliferative and pro-apoptotic effects of a water extract of L. virginicum leaves (WELVL) and of L. virginicum roots (WELVR) were investigated in HCT116 human colon carcinoma cells. The treatment of HCT116 cells with WELVL and WELVR resulted in the inhibition of growth and morphological changes in a concentration-dependent manner by inducing apoptosis. The growth inhibition and apoptosis induction by WELVR was stronger than that of WELVL thus, we determined that WELVR was the more optimal extract for this study. The increased apoptotic events in HCT116 cells caused by WELVR were associated with an up-regulation of Fas ligand, Bax, and Bad expression, a down-regulation of Bcl-2, Bcl-$_XL$, and Bid expression, and a decrease in the mitochondrial membrane potential (MMP, ${\Delta}{\psi}m$). WELVR treatment induced the proteolytic activation of caspase-3, -8, and -9, and the degradation of caspase-3 substrate proteins, such as poly (ADP-ribose) polymerase (PARP), ${\beta}$-catenin, and phospholipase C-${\gamma}1$ (PLC-${\gamma}1$). In addition, apoptotic cell death induced by WELVR was correlated with a down-regulation of inhibitors of the apoptosis protein (IAP) family, such as the X-linked inhibitor of apoptosis protein (XIAP), cIAP-1, and cIAP-2. These findings suggest that the WELVR-induced inhibition of cell proliferation is associated with the induction of apoptotic cell death. WELVR may be a potential chemotherapeutic agent for the control of HCT116 human colon carcinoma cells.

• Journal of Ginseng Research
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• v.36 no.2
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• pp.161-168
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• 2012

The abnormal maturation and ossification of articular chondrocytes play a central role in the pathogenesis of osteoarthritis (OA). Inhibiting the enzymatic degradation of the extracellular matrix and maintaining the cellular phenotype are two of the major goals of interest in managing OA. Ginseng is frequently taken orally, as a crude substance, as a traditional medicine in Asian countries. Ginsenoside $Rb_1$, a major component of ginseng that contains an aglycone with a dammarane skeleton, has been reported to exhibit various biological activities, including anti-inflammatory and anti-tumor effects. However, a chondroprotective effect of ginsenoside $Rb_1$ related to OA has not yet been reported. The purpose of this study was to demonstrate the chondroprotective effect of ginsenoside $Rb_1$ on the regulation of pro-inflammatory factors and chondrogenic genes. Cultured rat articular chondrocytes were treated with 100 ${\mu}M$ ginsenoside $Rb_1$ and/or 500 ${\mu}M$ hydrogen peroxide ($H_2O_2$) and assessed for viability, reactive oxygen species production, nitric oxide (NO) release, and chondrogenic gene expression. Ginsenoside $Rb_1$ treatment resulted in reductions in the levels of pro-inflammatory cytokine and NO in $H_2O_2$-treated chondrocytes. The expression levels of chondrogenic genes, such as type II collagen and SOX9, were increased in the presence of ginsenoside $Rb_1$, whereas the expression levels of inflammatory genes related to chondrocytes, such as MMP1 and MMP13, were reduced by approximately 50%. These results suggest that ginsenoside $Rb_1$ has potential for use as a therapeutic agent in OA patients.

• Journal of Adhesion and Interface
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• v.15 no.3
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• pp.100-108
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• 2014

In this work, a series of molar ratios composed with YD-128 and DDM were chosen based on the viscosity analysis. The mixtures of YD-128 and DDM with the different molar ratios were cured at $170^{\circ}C$ for 15 min followed by post cure at $190^{\circ}C$ for two hours. The thermal properties of the cured samples were investigated with DSC, TGA, DMA, and TMA. The conversion ratio of the mixtures of YD-128 and DDM (1 : 1.1) was calculated by dividing ${\Delta}H$ obtained from DSC experiments for each cured sample by ${\Delta}H$. The TGA data of the cured samples showed that the thermal stability and thermal degradation activation energy were proportional to the amount of DDM in the mixtures. However, the highest tan ${\delta}$, and the lowest thermal expansion data with DMA and TMA respectively were obtained from the stoichiometric mixture of YD-128 and DDM. Furthermore, the different ratio of mixtures were applied to test specimens to be cured at $170^{\circ}C$ to measure single lap shear strength with universal testing machine.