Seoul National UniversitySeoul

Seoul National, South Korea

Seoul National UniversitySeoul

Seoul National, South Korea
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Jeon O.-C.,Seoul National UniversitySeoul | Seo D.-H.,Yonsei University | Seo D.-H.,Fraunhofer Institute for Non-Destructive Testing | Kim H.-S.,Yonsei University | And 3 more authors.
European Journal of Pharmaceutical Sciences | Year: 2016

We assessed the possibility of changing the route of administration of zoledronic acid to an oral dosage form and its therapeutic efficacy in an estrogen-deficient osteoporosis rat model. To enhance oral bioavailability, we formed an ionic complex by electrostatic conjugation of zoledronic acid with lysine-linked deoxycholic acid (Lys-DOCA, an oral absorption enhancer). After forming the complex, the characteristic crystalline features of pure zoledronic acid disappeared completely in the powder X-ray diffractogram and differential scanning calorimetry thermogram, indicating that zoledronic acid existed in an amorphous form in the complex. In vitro permeabilities of zoledronic acid/Lys-DOCA (1:1) (ZD1) and zoledronic acid/Lys-DOCA (1:2) (ZD2) complex across Caco-2 cell monolayers were 2.47- and 4.74-fold higher than that of zoledronic acid, respectively. Upon intra-jejunal administration to rats, the intestinal absorption of zoledronic acid was increased significantly and the resulting oral bioavailability of the ZD2 complex was determined to be 6.76 ± 2.59% (0.548 ± 0.161% for zoledronic acid). Ovariectomized (OVX) rats showed 122% increased bone mineral density versus the OVX control at 12 weeks after treatment with once weekly oral administration of ZD2 complex (16 μg/kg of zoledronic acid). Furthermore, rats treated with ZD2 complex orally showed significant improvement in the parameters of trabecular microarchitecture and bone strength: 149% higher bone volume fraction (BV/TV), 115% higher trabecular number (Tb.N), and 56% higher mean maximum load (Fmax) than in the OVX group. The trabecular microstructure and bone mechanical properties in the oral zoledronic acid group were not significantly changed compared with the OVX control. Thus, the oral ZD2 complex inhibited osteoporosis progression effectively by promoting osteogenesis and trabecular connectivity. The oral ZD2 complex would be expected to improve patient compliance by replacing the conventional injectable form and expand the indications, to include prophylaxis for osteoporosis and bone metastases. © 2015 Elsevier B.V.


Park W.H.,Kyung Hee University | Kang S.,Kyung Hee University | Piao Y.,Kyung Hee University | Pak C.J.,Kyung Hee University | And 4 more authors.
Journal of Ethnopharmacology | Year: 2015

Abstract Ethnopharmacological relevance The root of Bupleurum falcatum L. (BF) has been used in traditional Korean and Chinese medicines for over 2000 years to treat infections, fever, and chronic liver diseases. Among the many active compounds in BF ethanol extract (BFE), saikosaponins exert pharmacological activities including anti-inflammatory effects. Activated microglial cells release a variety of pro-inflammatory substances, leading to neuronal cell death and neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. The aim of the present study was to investigate the mechanism of the anti-neuroinflammatory effects of BFE using lipopolysaccharide (LPS)-stimulated microglial cells and LPS-intraperitoneal injected C57BL/6 mice. Materials and methods Dried roots of BF were extracted with 70% ethanol (tenfold volume) on a stirring plate for 24 h at room temperature to prepare BFE. Pure saikosaponins (SB3, SB4, and SD) were prepared by solvent extraction and column chromatography fractionation. BV2 murine microglial cells were treated with BFE or saikosaponins for 4 h and stimulated with LPS. Generation of nitric oxide (NO), inflammatory cytokines, and reactive oxygen species (ROS) from activated microglial cells were monitored. The effects of BFE on NF-κB activation were determined using RT-PCR, reporter assay, and immunostaining. The in vivo effects of BFE were also assessed by immunohistochemical staining of tissue sections from LPS-injected mouse brains. Results Treatment with BFE or saikosaponins dose-dependently attenuated LPS-induced production of NO, iNOS mRNA, and ROS by 30-50%. They reduced LPS-mediated increases in the mRNA levels of IL-6, IL-1β, and TNF-α by approximately 30-70% without affecting cell viability, and decreased LPS-mediated NF-κB activity via reducing p65/RELA mRNA, transcriptional activity, and nuclear localization of NF-κB. BFE also reduced LPS-induced activation of microglia and astrocytes in the hippocampus and substantia nigra of LPS-injected mice. Conclusion Our data suggest that BFE may be effective for reducing neuroinflammation-mediated neurodegeneration through suppressing NF-κB-mediated inflammatory pathways. © 2015 Elsevier Ireland Ltd.


Chuah W.H.,Seoul National UniversitySeoul | Zhang W.L.,Inha University | Choi H.J.,Inha University | Seo Y.,Seoul National UniversitySeoul
Macromolecules | Year: 2015

The sedimentation stability of a carbonyl iron (CI)-based magnetorheological (MR) fluid was improved by wrapping CI particles with a polystyrene (PS) foam layer. The PS layer on the CI particles was synthesized via conventional dispersion polymerization and was subsequently foamed using a supercritical carbon dioxide fluid to produce core-shell structured particles. The density of particles decreased after the PS-layer wrapping and subsequent PS-layer foaming. The surface morphology was observed by scanning electron microscope (SEM) and the specific surface areas were determined by Brunauer-Emmett-Teller (BET) adsorption measurements. Both modifications (PS-layer wrapping and foaming) increased the surface roughness of the particles, yet preserved particle's spherical shape. The effect of the volume expansion after modification on the magnetorheological properties was investigated by using a vibrating sample magnetometer (VSM) and a rotational rheometer. All suspensions tested presented similar MR behaviors with the only difference in their yield stress strengths. Finally, the sedimentation properties of the synthesized particles was examined using a Turbiscan apparatus. MR fluids containing the newly developed CI particles wrapped with the foamed PS layer exhibited remarkably improved stability against sedimentation due to the reduced mismatch in density between the particles and the carrier medium. © 2015 American Chemical Society.


Diederich M.,Seoul National UniversitySeoul | Cerella C.,Laboratoire Of Biologie Moleculaire Et Cellulaire Du Cancer
Seminars in Cancer Biology | Year: 2016

Natural compounds are the fundament of pharmacological treatments and more than 50% of all anticancer drugs are of natural origins or at least derived from scaffolds present in Nature. Over the last 25 years, molecular mechanisms triggered by natural anticancer compounds were investigated. Emerging research showed that molecules of natural origins are useful for both preventive and therapeutic purposes by targeting essential hallmarks and enabling characteristics described by Hanahan and Weinberg. Moreover, natural compounds were able to change the differentiation status of selected cell types. One of the earliest response of cells treated by pharmacologically active compounds is the change of its morphology leading to ultra-structural perturbations: changes in membrane composition, cytoskeleton integrity, alterations of the endoplasmic reticulum, mitochondria and of the nucleus lead to formation of morphological alterations that are a characteristic of both compound and cancer type preceding cell death. Apoptosis and autophagy were traditionally considered as the most prominent cell death or cell death-related mechanisms. By now multiple other cell death modalities were described and most likely involved in response to chemotherapeutic treatment. It can be hypothesized that especially necrosis-related phenotypes triggered by various treatments or evolving from apoptotic or autophagic mechanisms, provide a more efficient therapeutic outcome depending on cancer type and genetic phenotype of the patient. In fact, the recent discovery of multiple regulated forms of necrosis and the initial elucidation of the corresponding cell signaling pathways appear nowadays as important tools to clarify the immunogenic potential of non-canonical forms of cell death induction. © 2016 Elsevier Ltd


Choi K.,Seoul National UniversitySeoul | Jo J.H.,Seoul National UniversitySeoul
Journal of Sedimentary Research | Year: 2015

Morphodynamics of intertidal channels were monitored in order to understand their implication on the architecture of inclined heterolithic stratification (IHS) in the open-coast Yeochari macro tidal flat on southern Ganghwa Island in Gyeonggi Bay, west coast of Korea. The tidal flat is divisible into narrow salt marshes in the upper intertidal zone, a concave-up upper to middle intertidal zone with small tidal creeks, and a channelized lower intertidal zone. Channels in the lower intertidal zone are 200-600 m wide and 1-2.5 m deep at bankful stage. They are sinuous in planform and have well-defined point bars and cutbanks. IHS is exposed along the cutbanks. High-precision leveling of the tidal channel bank unveiled that a point bar in the lower intertidal zone migrated about 400 m in 39 months. Channel migration is pronounced during the summer rainy season, when the point bar migrated as fast as 40 m per month, which led to rapid sediment accumulation of as much as 40 cm per month. In contrast, channel migration rate during winter is notably reduced, down to less than 1 m per month. Point-bar geometry alternates between a concave-up profile in summertime and a convex-up profile during the remainder of the year. Enhanced ebb currents during the rainy season, due to increased runoff discharge caused by heavy precipitation, accelerated point-bar migration. Remarkable rill erosion induced by heavy precipitation especially during low tide led to the rapid accumulation of sediment at the lower part of the point bar and the channel base, creating concave-up point-bar geometry. During the remainder of the year, the point bar retains a convex-up profile by continued sedimentation with insignificant rill erosion. Wave activity, particularly during winter, seems to facilitate deposition in the upper part of the point bar by providing more sediment into the channel. The present study illuminates the fact that the stratigraphic architecture of IHS of intertidal origin is controlled largely by monsoonal weather and to a lesser degree by tidal process even in a macrotidal environment. Careful examination of IHS geometry may hint at the depositional setting in terms of tidal frame (intertidal versus subtidal) and climate regime (monsoonal versus non-monsoonal). Copyright © 2015, SEPM (Society for Sedimentary Geology).


Jackie Oh S.,Washington University in St. Louis | Han S.,Seoul National UniversitySeoul | Lee W.,Seoul National UniversitySeoul | Lockhart A.C.,University of Washington
Expert Opinion on Investigational Drugs | Year: 2016

Introduction: Esophageal cancer is the third most common cancer of the gastrointestinal tract. Despite new therapies, the prognosis for patients with these cancers remains poor with 5-year survival rates lower than 15%. Recently, immunotherapy has increasingly gained attention as a novel treatment strategy for advanced esophageal cancer. Areas covered: Recent success of immunotherapy in treating other solid tumors has shed light on the utility of these approaches for esophageal cancers. Here, the authors focus on antibody-based, adoptive-cell-therapy-based, and vaccine-based immunotherapies, and briefly address their rationale, clinical data, and implications. Expert opinion: Immunotherapy is now established to be a key treatment modality that can improve the outcomes of many cancer patients and appears to be ushering in a new era in cancer treatment. Checkpoint inhibitor drugs have shown preliminary favorable results in esophageal cancer treatment. Adoptive cell therapy and vaccine studies have also shown some promise in various clinical studies. Future endeavors will need to focus on identifying patients who are likely to benefit from immunotherapy, monitoring and managing immune responses and designing optimal combination strategies where immunotherapy agents are combined with other traditional treatment modalities. © 2016 Informa UK Limited, trading as Taylor & Francis Group.


Yi D.-G.,Seoul National UniversitySeoul | Huh W.-K.,Seoul National UniversitySeoul
FEBS Letters | Year: 2015

Abstract Ugp1, a UDP-glucose pyrophosphorylase, is essential for various cellular activities in Saccharomyces cerevisiae because its product, UDP-glucose, is a sole glucosyl donor in several metabolic pathways. Here, we report that Msn2/4 play a crucial role in the regulation of UGP1 expression. Msn2/4 bound to three stress response elements in the UGP1 promoter in a protein kinase A (PKA)-dependent manner. Several stresses induced UGP1 transcription, suggesting that the regulation of UGP1 mediated by Msn2/4 is involved in general stress response. Furthermore, the phosphate response (PHO) pathway also controlled Msn2/4-dependent regulation of UGP1, providing a novel link between the PKA and PHO pathways. Our data suggest that signals of the PKA, PHO and stress response pathways regulate UGP1 expression via Msn2/4 in S. cerevisiae. © 2015 Federation of European Biochemical Societies.


Min J.-Y.,Seoul National UniversitySeoul | Min K.-B.,Ajou University
Circulation Journal | Year: 2014

Background: We explored whether reduced lung function is a predictor of mortality due to cardiovascular or coronary artery disease (CVD or CAD), and, if this hypothesis is correct, whether C-reactive protein (CRP), a systemic inflammatory marker, is responsible for this association in a general population-based cohort.Methods and Results: We used the Third Nutrition and Health Examination Survey (NHANES III) database and the NHANES III Linked Mortality File. A total of 13,310 participants ≥20 years of age who completed a spirometric test at baseline examination were included. On comparison of the participants in the lowest forced vital capacity percent predicted (FVC% pred) quartile with those in the highest quartile, the hazard ratio (HR) was 2.1 (95% CI: 1.7–2.6) for cardiovascular mortality and 2.2 (95% CI: 1.6–3.2) for coronary mortality. A similar association was observed for forced expiratory volume in 1 s percent predicted (FEV1% pred). When the participants with the highest FVC% pred or FEV1% pred (Q4) and low CRP (≤0.22 mg/dl) were defined as the reference group, the adjusted HR for cardiovascular mortality was significantly increased in the individuals with the lowest spirometric volume (Q1), and the risk was prominent in individuals with high CRP (>0.22 mg/dl).Conclusions: There is a significant association between lung function parameters and death from CVD and CAD in the general population. © 2014 THE JAPANESE CIRCULATION SOCIETY.


Bailey J.A.,Seoul National UniversitySeoul | Jang Y.-C.,Seoul National UniversitySeoul | Lee W.,Seoul National UniversitySeoul | Park S.,Seoul National UniversitySeoul
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

We report the standard model evaluation of the indirect CP violation parameter εK using inputs determined from lattice QCD: the kaon bag parameter B^K, ξ0, |Vus| from the Kℓ3 and Kμ2 decays, and |Vcb| from the axial current form factor for the exclusive decay B¯→D∗ℓν¯ at zero-recoil. The theoretical expression for εK is thoroughly reviewed to give an estimate of the size of the neglected corrections, including long distance effects. The Wolfenstein parametrization (|Vcb|,λ,ρ¯,η¯) is adopted for Cabibbo-Kobayashi-Maskawa matrix elements which enter through the short distance contribution of the box diagrams. For the central value, we take the unitarity triangle apex (ρ¯,η¯) from the angle-only fit of the UTfit collaboration and use Vus as an independent input to fix λ. We find that the standard model prediction of εK with exclusive Vcb (lattice QCD results) is lower than the experimental value by 3.4σ. However, with inclusive Vcb (results of the heavy quark expansion), there is no gap between the standard model prediction of εK and its experimental value. For the calculation of εK, we perform the renormalization group running to obtain ηcc at next-to-next-to-leading-order; we find ηccNNLO=1.72(27). © 2015 American Physical Society. © 2015 American Physical Society.


Hahm T.S.,Seoul National UniversitySeoul
Plasma Science and Technology | Year: 2015

Bulk ion heating rate from nonlinear Landau damping of high mode number Toroidal Alfvén Eigenmodes (TAEs) is calculated in the frame work of weak turbulence theory. The heating rate is lower than the nonlinear spectral transfer rate to more stable modes, but relatively insensitive to the details of linear damping mechanisms.

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