$N^1$-(2, 5-dimethoxyphenyl)-$N^8$-hydroxyoctanediamide (N25) is a novel SAHA cap derivative of HDACi, with a patent (No. CN 103159646). This invention is a hydroxamic acid compound with a structural formula of $RNHCO(CH_2)6CONHOH$ (wherein R=2, 5dimethoxyaniline), a pharmaceutically acceptable salt which is soluble. In the present study, we investigated the effects of N25 with regard to drug distribution and molecular docking, and anti-proliferation, apoptosis, cell cycling, and $LD_{50}$. First, we designed a molecular approach for modeling selected SAHA derivatives based on available structural information regarding human HDAC8 in complex with SAHA (PDB code 1T69). N25 was found to be stabilized by direct interaction with the HDAC8. Anti-proliferative activity was observed in human glioma U251, U87, T98G cells and human lung cancer H460, A549, H1299 cells at moderate concentrations ($0.5-30{\mu}M$). Compared with SAHA, N25 displayed an increased antitumor activity in U251 and H460 cells. We further analyzed cell death mechanisms activated by N25 in U251 and H460 cells. N25 significantly increased acetylation of Histone 3 and inhibited HDAC4. On RT-PCR analysis, N25 increased the mRNA levels of p21, however, decreased the levels of p53. These resulted in promotion of apoptosis, inducing G0/G1 arrest in U251 cells and G2/M arrest in H460 cells in a time-dependent and dose-dependent manner. In addition, N25 was able to distribute to brain tissue through the blood-brain barrier of mice ($LD_{50}$: 240.840mg/kg). In conclusion, our findings demonstrate that N25 will provide an invaluable tool to investigate the molecular mechanism with potential chemotherapeutic value in several malignancies, especially human glioma.
Although many logistics companies are interested in project logistics, the existing research has been limited to the growth potential of project logistics market and the high barrier and importance of project logistics. This study analyzes using DEA the operational efficiency of forwarding companies registered in major overseas construction EPC companies and performing logistics services for overseas plant construction projects. For efficiency analysis, Super-SBM analysis and Malmquist analysis are used among DEA analysis techniques. As a result of the Super-SBM analysis, DMU 5 ranked first at 1.807. DMU 5 is more efficient than the other large corporations because it has the stable supply of its parent company H and the smallest input and output variables among the large corporations. As a result of Malmquist analysis, TCI, which is a technological development, showed a fluctuation while TECI showed a relatively stable variation. In addition, there is a difference in scale between major companies and small and medium sized companies. So, it is necessary to identify the efficiency improvement strategy for each group and apply it to the practical work.
Given the proliferation of social network services, it has become important to understand its user's continued use behavior. As users' privacy concerns in SNS have been identified as a critical barrier against forming this continued intention, many studies have focused on inducing continued intention by mitigating privacy concerns. However, this paper suggests to approach users' continued intention not only from the perspective of mitigating privacy concerns but also from the perspective of increasing potential benefits. Under the theoretical framework of privacy calculus model, we conducted cross sectional survey on 150 Facebook and 150 KakaoTalk users. The result suggests that trust mediates the relationships between privacy concerns and continued intention and between network externality and continued intention, and the influence of support for network formation on continued intention. The effect of network externality on continued intention, however, is not significant among Facebook users while it is significant among KakaoTalk users.
Objectives : For the screening of neuroprotective effects of medicinal herbs, the complex system of animal models suffer some disadvantages in controlling critical parameters such as blood pressure and body temperature. Additionally, application of drugs to the appropriate brain area sometimes is difficult, due to poor permeability though the blood brain barrier, and so potential protective effects might be masked. Methods : Organotypic hippocampal slice culture (OHSC) method has the advantages of being relatively easy to prepare and of maintaining the general structure, including tissue integrity and the connections between cells. Drugs can easily be applied and neuronal damage can easily be quantified by using tissues and culture media. This study demonstrates neuroprotective effects of Puerariae radix (葛根, PR), Salviae miltiorrhizae radix (丹蔘, SR), Rhei rhizoma (大黃, RR), and Bupleuri radix (柴胡, BR). These were screenedand compared to MK-801, antagonist of NMDA receptors, by using OHSC of 1 week-old Sprague-Dawley rats. Oxygen/glucose deprivation (OGD) were conducted in an anaerobic chamber $(85%\;N_2,\;10%\;CO_2\;and\;5%\;H_2)$ in a deoxygenated glucose-free medium for 60 minutes. Water extracts of each herbs were treated to culture media with $5\;{\mu}g/ml$ for 48 hours. Results : Neuronal cell death in the cultures was monitored by densitometric measurements of the cellular uptake of propidium iodide (PI). PI fluorescence images were obtained at 48 hours after the OGD and medicinal herb treatment. Also TUNEL-positive cells in the CAI and DG regions and LDH concentrations in culture media were measured at 48 hours after the OGD. According to measured data, MK-801, PR, SR and BR demonstrated significant neuroprotective effect against excessive neuronal cell death and apoptosis induced by the OGD insult. Especially, PR revealed similar neuroprotective effect to MK-801 and RR demonstrated weak neuroprotective effect. Conclusions : These results suggest that OHSC can be a suitable method for screening of neuroprotective effects of medicinal herbs. (This work was supported by the research program of Dongguk University and Grant 01-PJ9-PG1-01CO03-0003 from Ministry of Health & Welfare.)
Background: Saponins from Panax japonicus (SPJ) are the most abundant and main active components of P. japonicus, which replaces ginseng roots in treatment for many kinds of diseases in the minority ethnic group in China. Our previous studies have demonstrated that SPJ has the effects of anti-inflammation through the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-${\kappa}B$) signaling pathways. The present study was designed to investigate whether SPJ can modulate intestinal tight junction barrier in aging rats and further to explore the potential mechanism. Methods: Aging rats had been treated with different doses (10 mg/kg, 30 mg/kg, and 60 mg/kg) of SPJ for 6 mo since they were 18 mo old. After the rats were euthanized, the colonic samples were harvested. Levels of tight junctions (claudin-1 and occludin) were determined by immunohistochemical staining. Levels of proinflammatory cytokines (interleukin-$1{\beta}$ and tumor necrosis factor-${\alpha}$) were examined by Western blot. NF-${\kappa}B$ and phosphorylation of MAPK signaling pathways were also determined by Western blot. Results: We found that SPJ increased the expression of the tight junction proteins claudin-1 and occludin in the colon of aging rats. Treatment with SPJ decreased the levels of interleukin-$1{\beta}$ and tumor necrosis factor-${\alpha}$, reduced the phosphorylation of three MAPK isoforms, and inhibited the expression of NF-${\kappa}B$ in the colon of aging rats. Conclusion: The studies demonstrated that SPJ modulates the damage of intestinal epithelial tight junction in aging rats, inhibits inflammation, and downregulates the phosphorylation of the MAPK and $NF-{\kappa}B$ signaling pathways.
Journal of the Korean Applied Science and Technology
/
v.30
no.1
/
pp.173-182
/
2013
Atopic dermatitis is a chronic, relapsing inflammatory skin disease associated with dysfunction of skin barrier and cutaneous hyper-reactivity to environmental triggers. In the previous study, cytotoxicity, antioxidant, anti-inflammatory and anti-allergic activities were investigated for various herbal extracts such as Aloe vera L. (AV), Viola mandshurica W. Becker (VM), Punica granatum L. (PG), and Dendrobium nobile L. (DN) in order to develop effective therapeutic herbal extracts for atopic dermatitis, In this study, anti-inflammatory activities of these herb extracts in lipopolysaccharide (LPS)-induced macrophage RAW264.7 cells were further examined to find the underlying molecular mechanisms. The RT-PCR (reverse transcription polymerase chain reaction) analysis showed that PG, DN and AV inhibited effectively the gene expression of pro-inflammatory cytokines IL-6 and IL-$1{\beta}$ in LPS-stimulated macrophages, while VM did not. The transfection and luciferase analysis exhibited that all herbal extracts hindered the activation of transcription nuclear factor kappa B (NF-${\kappa}B$). The western blot analysis indicated that AV blocked the activation of only JNK MAP (c-Jun N-terminal kinase mitogen-activated protein) kinase not p38 MAP kinase, while VM, PG and DN did not show the activation of both JNK and p38 MAP kinases. These results suggest that AV, VM, PG, and DN have anti-inflammatory activities and thus have the potential to reduce and alleviate the symptoms of atopic dermatitis.
Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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2001.05a
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pp.667-671
/
2001
The Instant Messenger(IM) is the most popular personal communication tool today. IM is a tool that can substitute E-mail for a person, and can secure the user for a company. Further, it is claimed as it has a limitless potential. However, there has been several reports on security issues. It has known that the transmitting message is not secured for the attacks, and hacking tools has been developed. In addition, several reports has been made regards to the vulnerability. In other words, anyone can been through and manipulate the messages that are sent or received via IM. This is a barrier for the IM to be developed as a corporate's strategic tool, and furthermore, it will create serious personal privacy issue. IETF IMPP Working Group is preparing a standard mutual relationship between IM. However, it is complicated due to the American On-Lines's absence, whom has ensured the most number of IM users. There was a discussion only about the form of the transmitting data, but it is insufficient state to discuss the security service for general. In this paper, I design and implement the Secure Instant Messaging System, to solve the IM's vulnerability and the security issue presented above.
Journal of Physiology & Pathology in Korean Medicine
/
v.30
no.2
/
pp.109-115
/
2016
Hataedock is a Korean medical treatment that administers herbal extracts orally to newborn infants. This method is used for alleviating harmful heat and excreting fetal wastes by meconium. The purpose of this study was to evaluate anti-inflammatory effect of Hataedock method with Douchi on 2,4-dinitrofluorobenzene (DNFB)-induced atopic dermatitis (AD). The 3-week-old NC/Nga mice were divided into 3 groups: the control group (Ctrl), the AD-induced group (AE), and the Hataedock-treated group (GT). Only the GT group was treated with Hataedock at the 3rd week. After 28 days from Hataedock treatment, we induced AD-like dermatitis to the AE and GT group by DNFB. The effects of Hataedock were evaluated by immunohistochemical method. In the epithelium, PKC-positive reaction of the GT group was decreased by 57%. In the dermal papillae, IL-4-positive reaction was decreased by 34%. In the dermis, the distribution of degranulated mast cells was decreased and substance P-positive reaction was decreased by 49%. In the skin tissue, edema was decreased and MMP-9-positive reaction was decreased by 71%. Tissue damage such as epithelial cell hyperplasia, infiltration of granulocyte and lymphocyte, and capillary distribution were also decreased. The Hataedock method with Douchi maintained skin barrier and inhibited skin-damaging factors via regulating Th2 differentiation. In conclusion, Hataedock has a potential for preventative treatment of AD. Further studies are necessary to investigate the immune-regulating mechanism and verify the safety and efficacy of the Hataedock method.
Kim, Jae-Yup;Park, Sun-Ha;Choi, Jung-Woo;Shin, Jun-Young;Sung, Yung-Eun
Proceedings of the Korean Vacuum Society Conference
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2011.08a
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pp.71-71
/
2011
Dye-sensitized solar cells (DSCs) have drawn great academic attention due to their potential as low-cost renewable energy sources. DSCs contain a nanostructured TiO2 photoanode, which is a key-component for high conversion efficiency. Particularly, one-dimensional (1-D) nanostructured photoanodes can enhance the electron transport for the efficient collection to the conducting substrate in competition with the recombination processes. This is because photoelectron colletion is determined by trapping/detrapping events along the site of the electron traps (defects, surface states, grain boundaries, and self-trapping). Therefore, 1-D nanostructured photoanodes are advantageous for the fast electron transport due to their desirable features of greatly reduced intercrystalline contacts with specified directionality. In particular, anodic TiO2 nanotube (NT) electrodes recently have been intensively explored owing to their ideal structure for application in DSCs. Besides the enhanced electron transport properties resulted from the 1-D structure, highly ordered and vertically oriented nanostructure of anodic TiO2 NT can contribute additional merits, such as enhanced electrolyte diffusion, better interfacial contact with viscous electrolytes. First, to confirm the advantages of 1-D nanostructured material for the photoelectron collection, we compared the electron transport and charge recombination characteristics between nanoparticle (NP)- and nanorod (NR)-based photoanodes in DSCs by the stepped light-induced transient measurements of photocurrent and voltage (SLIM-PCV). We confirmed that the electron lifetime of the NR-based photoanode was much longer than that of the NP-based photoanode. In addition, highly ordered and vertically oriented TiO2 NT photoanodes were prepared by electrochemical anodization method. We compared the photovoltaic properties of DSCs utilizing TiO2 NT photoanodes prepared by one-step anodization and two-step anodization. And, to reduce the charge recombination rate, energy barrier layer (ZnO, Al2O3)-coated TiO2 NTs also applied in DSC. Furthermore, we applied the TiO2 NT photoanode in DSCs using a viscous electrolyte, i.e., cobalt bipyridyl redox electrolyte, and confirmed that the pore structure of NT array can enhance the performances of this viscous electrolyte.
Journal of the Korea Institute of Information and Communication Engineering
/
v.5
no.2
/
pp.357-364
/
2001
The Instant Messenger(IM) is the most popular personal communication tool today. IM is a tool that can substitute E-mail for a person, and can secure the user for a company. Further, it is claimed as it has a limitless potential. However, there has been several reports on security issues. It has known that the transmitting message is not secured for the attacks, and hacking tools has been developed. In addition, several reports has been made regards to the vulnerability. In other words, anyone can peep through and manipulate the messages that are sent or received via IM. This is a barrier for the IM to be developed as a corporate's strategic tool, and furthermore, it will create serious personal privacy issue. IETF IMPP Working (:roup is preparing a standard mutual relationship between IM. However, it is complicated due to the American On-Lines's absence, whom has ensured the most number of IM users. There was a discussion only about the form of the transmitting data, but it is insufficient state to discuss the security service for general. In this paper, 1 design and implement the Secure Instant Messaging System, to solve the IM's vulnerability and the security issue presented above.
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