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      • Graft Architectured Rod–Coil Copolymers Based on Alternating Conjugated Backbone: Morphological and Optical Properties

        Lee, Wonho,Kim, Jin-Seong,Kim, Hyeong Jun,Shin, Jae Man,Ku, Kang Hee,Yang, Hyunseung,Lee, Junhyuk,Bae, Jung Gun,Lee, Won Bo,Kim, Bumjoon J. American Chemical Society 2015 Macromolecules Vol.48 No.16

        <P>Controlling the self-assembly of conjugated copolymers is of great importance in tuning their physical and optoelectronic properties, offering potential pathways to greatly enhance the performance of organic electronics. Here, we report the synthesis of rod-coil graft copolymers containing an electroactive conjugated rod-like backbone and polymer coils as grafts and demonstrate the control of their ordered nanostructures. As a model system, we synthesized light-emitting poly(fluorene-alt-phenylene) (PFP) alternating copolymers and then grafted poly(2-vinylpyridine) (P2VP) chains with different lengths via a 'click' reaction to produce a series of PFP-g-P2VP graft copolymers with various P2VP volume fractions (f(P2VP)). Interestingly, PFP-g-P2VP rod coil copolymers assembled into well-ordered cylinders and lamellae depending on f(P2VP) values that resembled those of the coil coil type block copolymers, but with very different f(P2VP) values for the morphological transitions (i.e., cylinders to lamellae). The morphological behavior of these graft copolymers was investigated using self-consistent-field theory simulations. Furthermore, by fully exploiting the controlled nanostructures of PFP-g-P2VP and the strong emitting properties of the PFP backbone, we developed multicolor colloidal particles that emit a broad range color spectrum from blue, white, and orange light. Our synthetic approach paves a new method for modulating the self-assembled nanostructures of rod coil copolymers and their optoelectronic properties.</P>

      • Percutaneous bleomycin sclerotherapy: a useful therapeutic option for ganglionic cysts

        ( Won-ku Lee ),( Woo-il Kim ),( Min-young Yang ),( Hyun-chang Ko ),( Byung-soo Kim ),( Moon-bum Kim ),( Hoon-soo Kim ) 대한피부과학회 2019 대한피부과학회 학술발표대회집 Vol.71 No.2

        Background: Ganglion cysts are mucin-filled cysts and commonly affect joint capsules or tendon sheaths of the distal extremities. Treatment options include aspiration, cryotherapy, sclerotherapy, and surgery, but have shown increased rates of recurrence and scarring. Objectives: To assess the efficacy and safety of intralesional bleomycin injection in treating ganglion cysts. Methods: We performed intralesional injection of bleomycin in 15 patients with 17 ganglion cysts. At each session, 1% bleomycin of 0.5 to 2 mL was injected into a lesion after extracting gelatinous material of similar amount. The procedure was repeated every 2 months if the cyst persisted. Changes in lesions and adverse reactions were recorded, and therapeutic efficacy was evaluated. Results: Of the 17 lesions treated with bleomycin injection, 80% responded. No serious complications related to the joint or tendon were observed. Conclusion: Our patients showed good tolerance without major adverse effects. Bleomycin as an intralesional sclerosant for ganglion cyst is easily available, costeffective, cosmetically excellent, and more tolerable than surgery. This procedure can be performed easily by any dermatologist in the outpatient clinic. Therefore, we suggest that bleomycin sclerotherapy can be an effective and safe therapeutic option for ganglion cysts, and decreases the need for invasive surgery.

      • SCIESCOPUSKCI등재

        Bone regeneration effects of human allogenous bone substitutes: a preliminary study

        Lee, Deok-Won,Koo, Ki-Tae,Seol, Yang-Jo,Lee, Yong-Moo,Ku, Young,Rhyu, In-Chul,Chung, Chong-Pyoung,Kim, Tae-Il Korean Academy of Periodontology 2010 Journal of Periodontal & Implant Science Vol.40 No.3

        Purpose: The purpose of this study was to compare the bone regeneration effects of cortical, cancellous, and cortico-cancellous human bone substitutes on calvarial defects of rabbits. Methods: Four 8-mm diameter calvarial defects were created in each of nine New Zealand white rabbits. Freeze-dried cortical bone, freeze-dried cortico-cancellous bone, and demineralized bone matrix with freeze-dried cancellous bone were inserted into the defects, while the non-grafted defect was regarded as the control. After 4, 8, and 12 weeks of healing, the experimental animals were euthanized for specimen preparation. Micro-computed tomography (micro-CT) was performed to calculate the percent bone volume. After histological evaluation, histomorphometric analysis was performed to quantify new bone formation. Results: In micro-CT evaluation, freeze-dried cortico-cancellous human bone showed the highest percent bone volume value among the experimental groups at week 4. At week 8 and week 12, freeze-dried cortical human bone showed the highest percent bone volume value among the experimental groups. In histologic evaluation, at week 4, freeze-dried cortico-cancellous human bone showed more prominent osteoid tissue than any other group. New bone formation was increased in all of the experimental groups at week 8 and 12. Histomorphometric data showed that freeze-dried cortico-cancellous human bone showed a significantly higher new bone formation percentile value than any other experimental group at week 4. At week 8, freeze-dried cortical human bone showed the highest value, of which a significant difference existed between freeze-dried cortical human bone and demineralized bone matrix with freeze-dried cancellous human bone. At week 12, there were no significant differences among the experimental groups. Conclusions: Freeze-dried cortico-cancellous human bone showed swift new bone formation at the 4-week healing phase, whereas there was less difference in new bone formation among the experimental groups in the following healing phases.

      • SCISCIESCOPUS

        Efficacy and Tolerability of Blonanserin in the Patients With Schizophrenia: A Randomized, Double-blind, Risperidone-Compared Trial

        Yang, Jaewon,Bahk, Won-Myong,Cho, Hyun-Sang,Jeon, Yang-Whan,Jon, Duk-In,Jung, Hee-Yeon,Kim, Chan-Hyung,Kim, Hee-Cheol,Kim, Yong-Ku,Kim, Young-Hoon,Kwon, Jun-Soo,Lee, Sang-Yeol,Lee, Seung-Hwan,Yi, Jung Lippincott Williams Wilkins, Inc. 2010 Clinical neuropharmacology Vol.33 No.4

        OBJECTIVES:: The objective of this study was to evaluate the efficacy and tolerability of blonanserin for the treatment of Korean patients with schizophrenia using a double-blind risperidone-compared design. METHODS:: Patients aged 18 to 65 years with schizophrenia were randomly assigned to blonanserin or risperidone treatment for 8 weeks. The efficacy was assessed using the mean change in Positive and Negative Syndrome Scale score total scores from baseline to week 8. Safety assessments included monitoring of vital signs, a physical examination, laboratory tests, and adverse events. RESULTS:: Of 206 randomly enrolled patients, 103 receiving blonanserin and 103 receiving risperidone were included in the analysis. In this study, noninferiority between blonanserin and risperidone was demonstrated. The mean change in the Positive and Negative Syndrome Scale total score at the final evaluation time point was −23.48 ± 19.73 for the blonanserin group and −25.40 ± 18.38 for the risperidone group. Adverse events, which occurred less frequently in the blonanserin than in the risperidone group, included dysarthria (P = 0.0288), dizziness (P = 0.0139), increased alanine aminotransferase and aspartate aminotransferase (P = 0.0095 and P = 0.0032, respectively), and increased level blood prolactin (P = 0.0012). On the other hand, the adverse events that occurred more frequently in the blonanserin than in the risperidone group was hand tremor (P = 0.0006). CONCLUSIONS:: Blonanserin was effective in the treatment of Korean patients with schizophrenia compared with risperidone and was more tolerable with a better safety profile, particularly with respect to prolactin elevation. These findings suggest that blonanserin is useful in the treatment of schizophrenia.

      • Identification of N-(5-(phenoxymethyl)-1,3,4-thiadiazol-2-yl)acetamide derivatives as novel protein tyrosine phosphatase epsilon inhibitors exhibiting anti-osteoclastic activity

        Ku, Bonsu,Yun, Hye-Yeoung,Lee, Kyung Won,Shin, Ho-Chul,Lee, Sang-Rae,Kim, Chang Hyen,Park, Hwangseo,Yi, Kyu Yang,Lee, Chang Hoon,Kim, Seung Jun Elsevier 2018 Bioorganic & medicinal chemistry Vol.26 No.18

        <P><B>Abstract</B></P> <P>Cytosolic protein tyrosine phosphatase epsilon (cyt-PTPε) plays a central role in controlling differentiation and function of osteoclasts, whose overactivation causes osteoporosis. Based on our previous study reporting a number of cyt-PTPε inhibitory chemical compounds, we carried out a further and extended analysis of our compounds to examine their effects on cyt-PTPε-mediated dephosphorylation and on osteoclast organization and differentiation. Among five compounds showing target selectivity to cyt-PTPε over three other phosphatases <I>in vitro</I>, two compounds exhibited an inhibitory effect against the dephosphorylation of cellular Src protein, the cyt-PTPε substrate. Moreover, these two compounds caused destabilization of the podosome structure that is necessary for the bone-resorbing activity of osteoclasts, and also attenuated cellular differentiation of monocytes into osteoclasts, without affecting cell viability. Therefore, these findings not only verified anti-osteoclastic effects of our cyt-PTPε inhibitory compounds, but also showed that cyt-PTPε expressed in osteoclasts could be a putative therapeutic target worth considering.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

      • VipD of <i>Legionella pneumophila</i> Targets Activated Rab5 and Rab22 to Interfere with Endosomal Trafficking in Macrophages

        Ku, Bonsu,Lee, Kwang-Hoon,Park, Wei Sun,Yang, Chul-Su,Ge, Jianning,Lee, Seong-Gyu,Cha, Sun-Shin,Shao, Feng,Heo, Won Do,Jung, Jae U.,Oh, Byung-Ha Public Library of Science 2012 PLoS pathogens Vol.8 No.12

        <▼1><P>Upon phagocytosis, <I>Legionella pneumophila</I> translocates numerous effector proteins into host cells to perturb cellular metabolism and immunity, ultimately establishing intracellular survival and growth. VipD of <I>L. pneumophila</I> belongs to a family of bacterial effectors that contain the N-terminal lipase domain and the C-terminal domain with an unknown function. We report the crystal structure of VipD and show that its C-terminal domain robustly interferes with endosomal trafficking through tight and selective interactions with Rab5 and Rab22. This domain, which is not significantly similar to any known protein structure, potently interacts with the GTP-bound active form of the two Rabs by recognizing a hydrophobic triad conserved in Rabs. These interactions prevent Rab5 and Rab22 from binding to downstream effectors Rabaptin-5, Rabenosyn-5 and EEA1, consequently blocking endosomal trafficking and subsequent lysosomal degradation of endocytic materials in macrophage cells. Together, this work reveals endosomal trafficking as a target of <I>L. pneumophila</I> and delineates the underlying molecular mechanism.</P></▼1><▼2><P><B>Author Summary</B></P><P><I>Legionella pneumophila</I> is a pathogen bacterium that causes Legionnaires' disease accompanied by severe pneumonia. Surprisingly, this pathogen invades and replicates inside macrophages, whose major function is to detect and destroy invading microorganisms. How <I>L. pneumophila</I> can be “immune” to this primary immune cell has been a focus of intensive research. Upon being engulfed by a macrophage cell, <I>L. pneumophila</I> translocates hundreds of bacterial proteins into this host cell. These proteins, called bacterial effectors, are thought to manipulate normal host cellular processes. However, which host molecules and how they are targeted by the bacterial effectors are largely unknown. In this study, we determined the three-dimensional structure of <I>L. pneumophila</I> effector protein VipD, whose function in macrophage was unknown. Ensuing analyses revealed that VipD selectively and tightly binds two host signaling proteins Rab5 and Rab22, which are key regulators of early endosomal vesicle trafficking. These interactions prevent the activated form of Rab5 and Rab22 from binding their downstream signaling proteins, resulting in the blockade of endosomal trafficking in macrophages. The presented work shows that <I>L. pneumophila</I> targets endosomal Rab proteins and delineates the underlying molecular mechanism, providing a new insight into the pathogen's strategies to dysregulate normal intracellular processes.</P></▼2>

      • SCISCIESCOPUS

        CADPE Suppresses Cyclin D1 Expression in Hepatocellular Carcinoma by Blocking IL-6-induced STAT3 Activation.

        Won, Cheolhee,Lee, Chang Seok,Lee, Jin-Ku,Kim, Tack-Joong,Lee, Kwang-Ho,Yang, Young Mok,Kim, Yong-Nyun,Ye, Sang-Kyu,Chung, Myung-Hee Potamitis Press 2010 Anticancer research Vol.30 No.2

        <P>The initiation and growth of hepatocellular carcinoma (HCC) are closely linked to chronic inflammation. Not only is cyclin D1 overexpressed, but it is also related to aggressive progression in HCC. However, the mechanism of expression cyclin D1, a cell-cycle regulator of paramount importance, in the tumor microenvironment remains unknown. Here, we investigated the mechanism of cyclin D1 expression induced by interleukin-6 (IL-6) and whether 3-[3,4-dihydroxy-phenyl]-acrylic acid 2-[3,4-dihydroxy-phenyl]-ethyl ester (CADPE), a derivate of caffeic acid, suppresses cyclin D1 expression. CADPE significantly inhibited IL-6-induced signal transducer and activator of transcription 3 (STAT3) activity in the Huh7 HCC cell line and attenuated IL-6-induced cyclin D1 transcription. Moreover, overexpression of constitutively active STAT3 increased cyclin D1 transcriptional activity and protein expression, whereas overexpression of a dominant-negative STAT3 deletion mutant (STAT3 (1-588)) reduced cyclin D1 transcriptional activity. In addition, CADPE effectively deacetylated histone 4 and prevented STAT3 recruitment to the cyclin D1 promoter, consistent with a role for the CADPE target, STAT3, in the regulation of cyclin D1 transcription. Collectively, these results indicate that CADPE suppresses cyclin D1 expression in HCC cells by blocking both IL-6-mediated STAT3 activation and recruitment of STAT3 to the cyclin D1 promoter.</P>

      • Simvastatin suppresses RANTES-mediated neutrophilia in polyinosinic–polycytidylic acid-induced pneumonia

        Lee, Chang Seok,Yi, Eun Hee,Lee, Jin-Ku,Won, Cheolhee,Lee, Young Ju,Shin, Min Kyung,Yang, Young Mok,Chung, Myung-Hee,Lee, Jung Weon,Sung, Sang-Hyun,Ye, Sang-Kyu ERS Journals Ltd 2013 The European respiratory journal Vol.41 No.5

        <P>Recently, statins have been shown to have anti-inflammatory effects on lung inflammatory diseases. However, the mechanisms of action of simvastatin in viral pneumonia have yet to be elucidated, although viral infection remains a considerable health threat. In this study, we hypothesised that simvastatin inhibits polyinosinic–polycytidylic acid (poly I:C)-induced airway inflammation, such as RANTES (regulated on activation, normal T-cell expressed and secreted) expression and inflammatory cell recruitment.</P><P>In bronchial cells, the effect of simvastatin on poly I:C-induced RANTES expression and signal transducer and activator of transcription (STAT)3-mediated signal transduction was determined using an ELISA and short hairpin (sh)RNA system. In a poly I:C-induced pneumonia mouse model, immunological changes in the lungs after simvastatin inhalation, such as inflammatory cell recruitment and cytokine/chemokine release, were examined.</P><P>In poly I:C-stimulated bronchial cells, RANTES secretion was increased by STAT3 activation, and simvastatin suppressed poly I:C-induced STAT3 activation, resulting in inhibition of RANTES expression. In BALB/c mice stimulated with inhaled poly I:C, RANTES expression and neutrophil infiltration into the airway were elevated. However, simvastatin treatment attenuated STAT3 activation, RANTES release and subsequent neutrophilia in the lungs.</P><P>These findings suggest that simvastatin inhibits airway inflammation, but there are other mechanisms that need to be fully elucidated.</P>

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