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      • Effects of dextrorotatory morphinans on brain Na<sup>+</sup> channels expressed in Xenopus oocytes

        Lee, J.H.,Shin, E.J.,Jeong, S.M.,Lee, B.H.,Yoon, I.S.,Lee, J.H.,Choi, S.H.,Kim, Y.H.,Pyo, M.K.,Lee, S.M.,Chae, J.S.,Rhim, H.,Oh, J.W.,Kim, H.C.,Nah, S.Y. North-Holland ; Elsevier Science Ltd 2007 european journal of pharmacology Vol.564 No.1

        We previously demonstrated that dextromethorphan (DM; 3-methoxy-17-methylmorphinan) analogs have neuroprotective effects. Here, we investigated the effects of DM, three of its analogs (DF, 3-methyl-17-methylmorphinan; AM, 3-allyloxy-17-methoxymorphian; and CM, 3-cyclopropyl-17-methoxymorphinan) and one of its metabolites (HM; 3-methoxymorphinan), on Na<SUP>+</SUP> channel activity. We used the two-microelectrode voltage-clamp technique to test the effects of DM, DF, AM, CM and HM on Na<SUP>+</SUP> currents (I<SUB>Na</SUB>) in Xenopus oocytes expressing cRNAs encoding rat brain Nav1.2 α and β1 or β2 subunits. In oocytes expressing Na<SUP>+</SUP> channels, DM, DF, AM and CM, but not HM, induced tonic and use-dependent inhibitions of peak I<SUB>Na</SUB> following low- and high-frequency stimulations. The order of potency for the inhibition of peak I<SUB>Na</SUB> was AM-CM > DM=DF. The DM, DF, AM and CM-induced tonic inhibitions of peak I<SUB>Na</SUB> were voltage-dependent, dose-dependent and reversible. The IC<SUB>50</SUB> values for DM, DF, AM and CM were 116.7+/-14.9, 175.8+/-16.9, 38.6+/-15.5, and 42.5+/-8.5 μM, respectively. DM and its analogs did not affect the steady-state activation and inactivation voltages. AM and CM, but not DM and DF, inhibited the plateau I<SUB>Na</SUB> more effectively than the peak I<SUB>Na</SUB> in oocytes expressing inactivation-deficient I1485Q-F1486Q-M1487Q (IFMQ3) mutant channels; the IC<SUB>50</SUB> values for AM and CM in this system were 8.4+/-1.3 and 8.7+/-1.3 μM, respectively, for the plateau I<SUB>Na</SUB> and 43.7+/-5.9 and 32.6+/-7.8 μM, respectively, for the peak I<SUB>Na</SUB>. These results collectively indicate that DM and its analogs could be novel Na<SUP>+</SUP> channel blockers acting on the resting and open states of brain Na<SUP>+</SUP> channels.

      • Stent linker effect in a porcine coronary restenosis model

        Park, J.k.,Lim, K.S.,Bae, I.H.,Nam, J.P.,Cho, J.H.,Choi, C.,Nah, J.W.,Jeong, M.H. Elsevier 2016 Journal of the mechanical behavior of biomedical m Vol.53 No.-

        In this study, we aimed to evaluate the mechanical effects of different stent linker designs on in-stent restenosis in porcine coronary arteries. We fabricated stents with an open-cell structure composed of nine main cells and three linker structures in model 1 (I-type), model 2 (S-types) and model 3 (U-types)) as well as Model 4, which is similar to a commercial bare metal stent design. The stent cells were 70mm thick and wide, with a common symmetrical wave pattern. As the radial force increased, the number of main cells increased and the length of linker decreased. Radial force was higher in model 1, with a linear I-linker, than in models with S- or U-linkers. The flexibility measured by three-point bending showed a force of 1.09N in model 1, 0.35N in model 2, 0.19N in model 3, and 0.31N in model 4. The recoil results were similar in all models except model 4 and were related to the shape of the main cells. The foreshortening results were related to linker shape, with the lowest foreshortening observed in model 3 (U-linker). Restenosis areas in the porcine restenosis model 4 weeks after implantation were 35.4+/-8.39% (model 1), 30.4+/-7.56% (model 2), 40.6+/-9.87% (model 3) and 45.1+/-12.33% (model 4). In-stent restenosis rates measured by intravascular ultrasound (IVUS) and micro-computed tomography (micro-CT) showed similar trends as percent area stenosis measured by micro-CT. Model 2, with optimized flexibility and radial force due to its S-linker, showed significantly reduced restenosis in the animal model compared to stents with different linker designs. These results suggest that the optimal stent structure has a minimum radial force for vascular support and maximum flexibility for vascular conformability. The importance of the effects of these differences in stent design and their potential relationship with restenosis remains to be determined.

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        Caspase-cleaved tau exhibits rapid memory impairment associated with tau oligomers in a transgenic mouse model

        Kim, Y.,Choi, H.,Lee, W.,Park, H.,Kam, T.I.,Hong, S.h.,Nah, J.,Jung, S.,Shin, B.,Lee, H.,Choi, T.Y.,Choo, H.,Kim, K.K.,Choi, S.Y.,Kayed, R.,Jung, Y.K. Blackwell Science ; Academic Press 2016 Neurobiology of disease Vol.87 No.-

        <P>In neurodegenerative diseases like AD, tau forms neurofibrillary tangles, composed of tau protein. In the AD brain, activated caspases cleave tau at the 421th Asp, generating a caspase-cleaved form of tau, TauC3. Although TauC3 is known to assemble rapidly into filaments in vitro, a role of TauC3 in vivo remains unclear. Here, we generated a transgenic mouse expressing human TauC3 using a neuron-specific promoter. In this mouse, we found that human TauC3 was expressed in the hippocampus and cortex. Interestingly, TauC3 mice showed drastic learning and spatial memory deficits and reduced synaptic density at a young age (2-3 months). Notably, tau oligomers as well as tau aggregates were found in TauC3 mice showing memory deficits. Further, i.p. or i.c.v. injection with methylene blue or Congo red, inhibitors of tau aggregation in vitro, and i.p. injection with rapamycin significantly reduced the amounts of tau oligomers in the hippocampus, rescued spine density, and attenuated memory impairment in TauC3 mice. Together, these results suggest that TauC3 facilitates early memory impairment in trans genic mice accompanied with tau oligomer formation, providing insight into the role of TauC3 in the AD pathogenesis associated with tau oligomers and a useful AD model to test drug candidates. (C) 2015 Elsevier Inc. All rights reserved.</P>

      • Swelling of Rubber under Nonuniform Stresses and Internal Migration of Swelling Liquid When the Stresses Are Removed

        Nah, C.,Lee, G.-B.,Lim, C. I.,Ahn, J.-H.,Gent, A. N. American Chemical Society 2011 Macromolecules Vol.44 No.6

        <P>As shown by Treloar, the degree of swelling of a rubber sample is strongly affected by applied stress. His work suggests that the degree of swelling will vary from point to point in a sample, in accordance with the local stress field. Thus, when rubber sheets are bent, they are expected to swell more on the tension side and less on the compression side, and when the bending constraint is removed, recovery toward the initial flat state is expected to be only partial at first and then followed by a slow further recovery. These effects are explored here for natural rubber sheets swollen by dodecane. The measured “set” following release from bending is found to be in accord with simple swelling theory. The time dependence of later recovery is shown to be in agreement with the rate of diffusion of the swelling liquid. It is concluded that internal migration of compatible liquids will cause temporary delays in deformation kinetics and make a significant contribution to energy losses. Also, the bending experiment itself appears to provide a simple and generally applicable method for determining the internal diffusion coefficients of absorbed liquids.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/mamobx/2011/mamobx.2011.44.issue-6/ma102528t/production/images/medium/ma-2010-02528t_0009.gif'></P>

      • Advanced glycation end products increases matrix metalloproteinase-1, -3, and -13, and TNF-α in human osteoarthritic chondrocytes

        Nah, S.S.,Choi, I.Y.,Yoo, B.,Kim, Y.G.,Moon, H.B.,Lee, C.K. North-Holland Pub ; Elsevier Science Ltd 2007 FEBS letters Vol.581 No.9

        We investigated the effects of advanced glycation end products (AGE) which accumulate in articular cartilage with age in human osteoarthritic chondrocytes. We found AGE-BSA significantly increased MMP-1, -3, and -13, and TNF-α in a dose-dependent manner. AGE-BSA-stimulated JNK, p38, and ERK and NF-κB activity. The stimulatory effect of AGE-BSA on MMP-1, -3, and -13 were reversed by treatment with specific JNK, p38 inhibitors, suggesting JNK and p38 are involved in AGE-BSA-induced MMPs and TNF-α. We also observed that NF-κB is involved in AGE-BSA-induced TNF-α. Pretreatment with soluble receptor for AGE (sRAGE) also reduced AGE-stimulated MMPs and TNF-α, implicating the involvement of receptor for AGE (RAGE). In conclusion, accumulation of AGE may have a role in the development of osteoarthritis by increasing MMP-1, -3, and -13, and TNF-α.

      • SCISCIESCOPUS

        Potential anti-inflammatory natural products from marine algae

        Fernando, I.P.S.,Nah, J.W.,Jeon, Y.J. Elsevier Science B.V 2016 Environmental toxicology and pharmacology Vol.48 No.-

        Inflammatory diseases have become one of the leading causes of health issue throughout the world, having a considerable influence on healthcare costs. With the emerging developments in natural product, synthetic and combinatorial chemistry, a notable success has been achieved in discovering natural products and their synthetic structural analogs with anti-inflammatory activity. However, many of these therapeutics have indicated detrimental side effects upon prolonged usage. Marine algae have been identified as an underexplored reservoir of unique anti-inflammatory compounds. These include polyphenols, sulfated polysaccharides, terpenes, fatty acids, proteins and several other bioactives. Consumption of these marine algae could provide defense against the pathophysiology of many chronic inflammatory diseases. With further investigation, algal anti-inflammatory phytochemicals have the potential to be used as therapeutics or in the synthesis of structural analogs with profound anti-inflammatory activity with reduced side effects. The current review summarizes the latest knowledge about the potential anti-inflammatory compounds discovered from marine algae.

      • Electrocatalytic activity of chemically deposited Cu<sub>x</sub>S thin film for counter electrode in quantum dots-sensitized solar cells

        Lim, I.,Lee, D.Y.,Patil, S.A.,Shrestha, N.K.,Kang, S.H.,Nah, Y.C.,Lee, W.,Han, S.H. Elsevier Science Publishers 2014 Materials chemistry and physics Vol.148 No.3

        The compact (c-Cu<SUB>x</SUB>S) and the porous (p-Cu<SUB>x</SUB>S) with particle decorated films of coppers-ulfidearesynthesized using a chemical bath deposition technique, and the films are characterized using electrochemical techniques. In addition, the chemically deposited Cu<SUB>x</SUB>S films are investigated as a counter electrode in quantum dots-sensitized solar cells (QSSCs). The available redox active reaction sites of the p-Cu<SUB>x</SUB>S film are found to be 57.9% higher than those available in the c-Cu<SUB>x</SUB>S film. From the electrochemical impedance spectroscopy, the effective diffusion coefficients of the polysulfide electrolyte in the c-Cu<SUB>x</SUB>S and p-Cu<SUB>x</SUB>S films are estimated to be 3.67 x 10<SUP>-5</SUP> and 6.35 x 10<SUP>-5</SUP> cm<SUP>2</SUP> s<SUP>-1</SUP>, respectively. These results can be ascribed to the improvement in the available redox active reaction sites and the electrocatalytic activity of the Cu<SUB>x</SUB>S counter electrode. As compared to the c-Cu<SUB>x</SUB>S film, the p-Cu<SUB>x</SUB>S film as a counter electrode exhibits an enhanced photovoltaic performance of the QSSCs with the power conversion efficiency of 3.17%, short-circuit current of 11.89 mA c<SUP>-</SUP>m<SUP>2</SUP>, open-circuit voltage of 0.50 V, and fill factor of 53.29. The improved performance of the QSSCs is ascribed to the improvements on the available redox active reaction sites, electrocatalytic activity and the diffusion coefficients, which are directly related to the surface morphology of the sulfide films.

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