• Title/Summary/Keyword: BK 21 Project

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Pine bark extract (Pycnogenol®) suppresses cigarette smoke-induced fibrotic response via transforming growth factor-β1/Smad family member 2/3 signaling

  • Ko, Je-Won;Shin, Na-Rae;Park, Sung-Hyeuk;Kim, Joong-Sun;Cho, Young-Kwon;Kim, Jong-Choon;Shin, In-Sik;Shin, Dong-Ho
    • Laboraroty Animal Research
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    • v.33 no.2
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    • pp.76-83
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    • 2017
  • Chronic obstructive pulmonary diseases (COPD) is an important disease featured as intense inflammation, protease imbalance, and air flow limitation and mainly induced by cigarette smoke (CS). In present study, we explored the effects of $Pycnogenol^{(R)}$ (PYC, pine bark extract) on pulmonary fibrosis caused by CS+lipopolysaccharide (LPS) exposure. Mice were treated with LPS intranasally on day 12 and 26, followed by CS exposure for 1 h/day (8 cigarettes per day) for 4 weeks. One hour before CS exposure, 10 and 20 mg/kg of PYC were administered by oral gavage for 4 weeks. PYC effectively reduced the number of inflammatory cells and proinflammatory mediators caused by CS+LPS exposure in bronchoalveolar lavage fluid. PYC inhibited the collagen deposition on lung tissue caused by CS+LPS exposure, as evidenced by Masson's trichrome stain. Furthermore, transforming growth $factor-{\beta}1$ ($TGF-{\beta}1$) expression and Smad family member 2/3 (Smad 2/3) phosphorylation were effectively suppressed by PYC treatment. PYC markedly reduced the collagen deposition caused by CS+LPS exposure, which was closely involved in $TGF-{\beta}1$/Smad 2/3 signaling, which is associated with pulmonary fibrotic change. These findings suggest that treatment with PYC could be a therapeutic strategy for controlling COPD progression.

MR-based Partial Volume Correction for $^{18}$F-PET Data Using Hoffman Brain Phantom

  • Kim, D. H.;Kim, H. J.;H. K. Jeong;H. K. Son;W. S. Kang;H. Jung;S. I. Hong;M. Yun;Lee, J. D.
    • Proceedings of the Korean Society of Medical Physics Conference
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    • 2002.09a
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    • pp.322-323
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    • 2002
  • Partial volume averaging effect of PET data influences on the accuracy of quantitative measurements of regional brain metabolism because spatial resolution of PET is limited. The purpose of this study was to evaluate the accuracy of partial volume correction carried out on $^{18}$ F-PET images using Hoffman brain phantom. $^{18}$ F-PET Hoffman phantom images were co-registered to MR slices of the same phantom. All the MR slices of the phantom were then segmented to be binary images. Each of these binary images was convolved in 2 dimensions with the spatial resolution of the PET. The original PET images were then divided by the smoothed binary images in slice-by-slice, voxel-by-voxel basis resulting in larger PET image volume in size. This enlarged partial volume corrected PET image volume was multiplied by original binary image volume to exclude extracortical region. The evaluation of partial volume corrected PET image volume was performed by region of interests (ROI) analysis applying ROIs, which were drawn on cortical regions of the original MR image slices, to corrected and original PET image volume. From the ROI analysis, range of regional mean values increases of partial volume corrected PET images was 4 to 14%, and average increase for all the ROIs was about 10% in this phantom study. Hoffman brain phantom study was useful for the objective evaluation of the partial volume correction method. This MR-based correction method would be applicable to patients in the. quantitative analysis of FDG-PET studies.

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Actin Depolymerizing Factor Destrin Regulates Cilia Development and Function during Vertebrate Embryogenesis

  • Youni Kim;Hyun-Kyung Lee;Kyeong-Yeon Park;Tayaba Ismail;Hongchan Lee;Hyun-Shik Lee
    • Development and Reproduction
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    • v.28 no.3
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    • pp.109-119
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    • 2024
  • The actin cytoskeleton plays fundamental roles in ciliogenesis and the actin depolymerizing factor destrin regulates actin dynamics by treadmilling actin filaments and increasing globular actin pools. However, the specific developmental roles of destrin in ciliogenesis have not been fully elucidated. Here, we investigated the function of destrin in ciliogenesis using Xenopus laevis and human retinal pigmented epithelial (hRPE1) cells. We discovered the loss of destrin increased the number of multiciliated cells in the Xenopus epithelium and impeded cilia motility. Additionally, destrin depletion remarkably reduced the length of primary cilia in the Xenopus neural tube and hRPE1 cells by affecting actin dynamics. Immunofluorescence using markers of ciliary components indicated that destrin controls the directionality and polarity of basal bodies and axonemal elongation by modulating actin dynamics, independent of basal body docking. In conclusion, destrin plays a significant role during vertebrate ciliogenesis regulating both primary and multicilia development. Our data suggest new insights for understanding the roles of actin dynamics in cilia development.

Precipitation Hardening by Holding After Simulated Complete Firing in a Metal-Ceramic Alloy of Pd-Au-Ag-Sn System (금속-세라믹용 Pd-Au-Ag-Sn계 합금의 모의소성 후 계류에 따른 석출경화)

  • Kim, Min-Jung;Shin, Hye-Jung;Kwon, Yong-Hoon;Kim, Hyung-Il;Seol, Hyo-Joung
    • Korean Journal of Dental Materials
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    • v.43 no.4
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    • pp.343-349
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    • 2016
  • This experiment was carried out to examine whether the post-firing heat treatment is effective in increasing the hardness of metal-ceramic alloy of the Pd-Au-Ag-Sn system. Precipitation hardening by holding at $600^{\circ}C$ after simulated complete porcelain firing in a metal-ceramic alloy of the Pd-Au-Ag-Sn system was examined by observing the change in hardness, crystal structure, and microstructure using a hardness test, X-ray diffraction (XRD), and field emission scanning electron microscopy (FE-SEM). The hardness of the alloy increased apparently by holding the specimen at $600^{\circ}C$ for 30 min after simulated complete porcelain firing. The formation of fine grain interior precipitates during holding at $600^{\circ}C$ caused the formation of lattice strain in the grain interior, resulting in apparent hardening. The faster cooling rate (stage 0) during simulated complete porcelain firing resulted in more effective precipitation hardening during holding at $600^{\circ}C$. From the above results, an appropriate post-firing heat treatment, such as holding at $600^{\circ}C$ for 30 min after complete porcelain firing may increase the durability of metal-ceramic prostheses composed of Pd-Au-Ag-Sn alloy.

The hardening effect by ice-quenching after oxidation of a Pd-Ag-Sn-Au metal-ceramic alloy during porcelain firing simulation (금속-세라믹용 Pd-Ag-Sn-Au계 합금의 모의소성 시 산화처리 후 급랭에 의한 경화 효과)

  • Shin, Hye-Jeong;Kim, Min-Jung;Kwon, Yong-Hoon;Kim, Hyung-Il;Seol, Hyo-Joung
    • Korean Journal of Dental Materials
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    • v.44 no.3
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    • pp.197-206
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    • 2017
  • The hardening effect by ice-quenching after oxidation of a Pd-Ag-Sn-Au metal-ceramic alloy during porcelain firing simulation was investigated by means of hardness test, field emission scanning electron microscopic observations, and X-ray diffraction analysis. The hardness decreased by ice-quenching after oxidation, which was induced by the homogenization of the ice-quenched specimen. The decreased hardness by ice-quenching after oxidation was recovered from the wash stage which was the first stage of the remaining firing process for bonding porcelain. After wash stage, the hardness of the ice-quenched specimens decreased during the subsequent porcelain firing process. But the final hardness of the ice-quenched specimens after oxidation was higher than that of the specimens cooled at stage 0 after oxidation. The increase in hardness of the specimens during the first firing process was caused by the lattice strains generated at the interface between the face-centered cubic Pd-Ag-rich matrix and the face-centered tetragonal Pd3(Sn, Ga, In) precipitate. The decrease in hardness of the specimens during the remaining firing process was caused by the microstructural coarsening.

Selective Ring-opening Fluorination of Epoxide: An Efficient Synthesis of 2'-C-Fluoro-2'-C-methyl Carbocyclic Nucleosides

  • Liu, Lian-Jin;Kim, Si-Wouk;Lee, Won-Jae;Hong, Joon-Hee
    • Bulletin of the Korean Chemical Society
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    • v.30 no.12
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    • pp.2989-2992
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    • 2009
  • An efficient synthetic route of novel 2′(${\alpha}$)-C-fluoro-2′(${\beta}$)-C-methyl carbocyclic nucleoside analogues is described. The key fluorinated intermediate 7 was prepared from the epoxide intermediate 5 via selective ring-opening of epoxide. Coupling of 7 with nucleosidic bases under the Mitsunobu reactions followed by deprotection afforded the target carbocyclic nucleoside analogues. The synthesized compounds were evaluated as inhibitors of the hepatitis C virus (HCV) in Huh-7 cell line in vitro.

Voluntary stand-up physical activity enhances endurance exercise capacity in rats

  • Seo, Dae Yun;Lee, Sung Ryul;Kwak, Hyo-Bum;Seo, Kyo Won;McGregor, Robin A;Yeo, Ji Young;Ko, Tae Hee;Bolorerdene, Saranhuu;Kim, Nari;Ko, Kyung Soo;Rhee, Byoung Doo;Han, Jin
    • The Korean Journal of Physiology and Pharmacology
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    • v.20 no.3
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    • pp.287-295
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    • 2016
  • Involuntary physical activity induced by the avoidance of electrical shock leads to improved endurance exercise capacity in animals. However, it remains unknown whether voluntary stand-up physical activity (SPA) without forced simulating factors improves endurance exercise capacity in animals. We examined the effects of SPA on body weight, cardiac function, and endurance exercise capacity for 12 weeks. Twelve male Sprague-Dawley rats (aged 8 weeks, n=6 per group) were randomly assigned to a control group (CON) or a voluntary SPA group. The rats were induced to perform voluntary SPA (lifting a load equal to their body weight), while the food height (18.0 cm) in cages was increased progressively by 3.5 every 4 weeks until it reached 28.5 cm for 12 weeks. The SPA group showed a lower body weight compared to the CON group, but voluntary SPA did not affect the skeletal muscle and heart weights, food intake, and echocardiography results. Although the SPA group showed higher grip strength, running time, and distance compared to the CON group, the level of irisin, corticosterone, genetic expression of mitochondrial biogenesis, and nuclei numbers were not affected. These findings show that voluntary SPA without any forced stimuli in rats can effectively reduce body weight and enhance endurance exercise capacity, suggesting that it may be an important alternative strategy to enhance endurance exercise capacity.

Time-dependent proteomic and genomic alterations in Toll-like receptor-4-activated human chondrocytes: increased expression of lamin A/C and annexins

  • Ha, Seung Hee;Kim, Hyoung Kyu;Nguyen, Thi Tuyet Anh;Kim, Nari;Ko, Kyung Soo;Rhee, Byoung Doo;Han, Jin
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.5
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    • pp.531-546
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    • 2017
  • Activation of Toll-like receptor-4 (TLR-4) in articular chondrocytes increases the catabolic compartment and leads to matrix degradation during the development of osteoarthritis. In this study, we determined the proteomic and genomic alterations in human chondrocytes during lipopolysaccharide (LPS)-induced inflammation to elucidate the underlying mechanisms and consequences of TLR-4 activation. Human chondrocytes were cultured with LPS for 12, 24, and 36 h to induce TLR-4 activation. The TLR-4-induced inflammatory response was confirmed by real-time PCR analysis of increased interleukin-1 beta ($IL-1{\beta}$), interleukin-6 (IL-6), and tumor necrosis factor alpha ($TNF-{\alpha}$) expression levels. In TLR-4-activated chondrocytes, proteomic changes were determined by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-mass spectroscopy analysis, and genomic changes were determined by microarray and gene ontology analyses. Proteomics analysis identified 26 proteins with significantly altered expression levels; these proteins were related to the cytoskeleton and oxidative stress responses. Gene ontology analysis indicated that LPS treatment altered specific functional pathways including 'chemotaxis', 'hematopoietic organ development', 'positive regulation of cell proliferation', and 'regulation of cytokine biosynthetic process'. Nine of the 26 identified proteins displayed the same increased expression patterns in both proteomics and genomics analyses. Western blot analysis confirmed the LPS-induced increases in expression levels of lamin A/C and annexins 4/5/6. In conclusion, this study identified the time-dependent genomic, proteomic, and functional pathway alterations that occur in chondrocytes during LPS-induced TLR-4 activation. These results provide valuable new insights into the underlying mechanisms that control the development and progression of osteoarthritis.

Enhanced Activity of Flavin-containing Monooxygenase in Human Subjects with High Body Mass Index and in Obese Mice Fed a High-fat Diet

  • Ko, Jeong-Hyeon;Lee, Tong-Joo;Park, Chang-Shin;Jang, Eun-Hee;Oh, Yun-Mi;Kang, Ju-Hee
    • Molecular & Cellular Toxicology
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    • v.4 no.1
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    • pp.5-10
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    • 2008
  • The effect of obesity on the drug-metabolizing enzymes remains an important issue for clinician since obesity is a world wide epidemic problem. However, little is known about the effects of obesity on flavincontaining monooxygenase (FMO) production and activity. We show here for the first time that in vivo FMO activity determined by urinary ranitidine (RA) metabolites ratio in human, was higher in subjects with a high body mass index (BMI, kg/$m^2$, 21.97-30.32) than in those with an intermediate BMI (range 19.38-21.83). Moreover, there was a significant correlation between FMO activity and BMI in 209 subjects. In high fat diet-induced obese mice, we also observed that the hepatic expression of FMO (225% of lean mice) and the activity measured by the RA Noxidation rate ($513{\pm}58.1$ vs. $349{\pm}66.0$ pmol/hr per mg protein) were significantly higher than in lean mice fed a control diet. Unknown factors rather than leptin or insulin appeared to regulate the hepatic FMO production. Thus, FMO activity may be increased in obese or overweight individuals. Moreover, the regulation of FMO activity in subjects with morbid obesity, with or without complications and its clinical implications, should be investigated further.

Assessment of neovascularization during bone healing using contrast-enhanced ultrasonography in a canine tibial osteotomy model: a preliminary study

  • Jeon, Sunghoon;Jang, Jaeyoung;Lee, Gahyun;Park, Seungjo;Lee, Sang-kwon;Kim, Hyunwook;Choi, Jihye
    • Journal of Veterinary Science
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    • v.21 no.1
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    • pp.10.1-10.12
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    • 2020
  • Blood perfusion of skeletal muscle and callus was evaluated using contrast-enhanced ultrasonography (CEUS) in a canine osteotomy model to determine the applicability of CEUS in the assessment of neovascularization during fracture healing and to compare the vascular signals on CEUS between external skeletal fixation and cast-applied dogs. In 6 Beagle dogs, a simple transverse osteotomy was performed at the left tibial shaft and external skeletal fixation (n = 3) or a cast (n = 3) was applied. Radiography, power Doppler ultrasonography (power Doppler), and CEUS were performed until complete union was achieved. On CEUS, vascular changes were quantitatively evaluated by measuring peak intensity (PI) and time to PI in the soft tissue and callus and by counting the vascular signals. Vascular signals from the soft tissue were detected on power Doppler and CEUS on day 2. Significantly more vascular signals were detected by CEUS than by power Doppler. On CEUS, PI in the surrounding soft tissue was markedly increased after the fracture line appeared indistinctively changed on radiography in all dogs. In the cast-applied dogs, vascular signals from the periosteal and endosteal callus were detected on CEUS before mineralized callus was observed on radiography. CEUS was useful in assessing the vascularity of soft tissue and callus, particularly in indirect fracture healing, and provided indications of a normally healing fracture.