• Journal of Nutrition and Health
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• v.56 no.6
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• pp.602-614
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• 2023

Purpose: The balance between synthesis and degradation of proteins plays a critical role in the maintenance of skeletal muscle mass. Mitochondrial dysfunction has been closely associated with skeletal muscle atrophy caused by aging, cancer, and chemotherapy. Polygalacin D is a saponin derivative isolated from Platycodon grandiflorum (Jacq.) A. DC. This study aimed to investigate the effects of polygalacin D on myoblast differentiation and muscle atrophy in association with mitochondrial function in in vitro and in zebrafish models in vivo. Methods: C2C12 myoblasts were cultured in differentiation media containing different concentrations of polygalacin D, followed by the immunostaining of the myotubes with myosin heavy chain (MHC). The mRNA expression of markers related to myogenesis, muscle atrophy, and mitochondrial function was determined by real-time quantitative reverse transcription polymerase chain reaction. Wild type AB^* zebrafish (Danio rerio) embryos were treated with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) with or without polygalacin D, and immunostained to detect slow and fast types of muscle fibers. The Tg(Xla.Eef1a1:mitoEGFP) zebrafish expressing mitochondria-targeted green fluorescent protein was used to monitor mitochondrial morphology. Results: The exposure of C2C12 myotubes to 0.1 ng/mL of polygalacin D increased the formation of MHC-positive multinucleated myotubes (≥ 8 nuclei) compared with the control. Polygalacin D significantly increased the expression of MHC isoforms (Myh1, Myh2, Myh4, and Myh7) involved in myoblast differentiation while it decreased the expression of atrophic markers including muscle RING-finger protein-1 (MuRF1), mothers against decapentaplegic homolog (Smad)2, and Smad3. In addition, polygalacin D promoted peroxisome proliferator-activated receptor-gamma coactivator (Pgc1α) expression and reduced the level of mitochondrial fission regulators such as dynamin-1-like protein (Drp1) and mitochondrial fission 1 (Fis1). In a zebrafish model of FOLFIRI-induced muscle atrophy, polygalacin D improved not only mitochondrial dysfunction but also slow and fast muscle fiber atrophy. Conclusion: These results demonstrated that polygalacin D promotes myogenesis and alleviates chemotherapy-induced muscle atrophy by improving mitochondrial function. Thus, polygalacin D could be useful as nutrition support to prevent and ameliorate muscle wasting and weakness.

• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.729-741
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• 1997

Background : We have recently reported that airway epithelial cells can produce RANTES and IL-8 in response to the stimulation of tubercle bacilli suggesting a certain role of airway epithelial cells in the pathogenesis of pulmonary tuberculosis. The pathogenesis of tuberculosis is determined by several factors including phagocytosis, immunological response of host, and virulence of tubercle bacilli. Interestingly, there have been reports suggesting that difference in immunological response of host according to the virulence of tubercle bacilli may be related with the pathogenesis of tuberculosis. We, therefore, studied the expressions and productions of RANTES and IL-8 in airway epithelial cells in response to tubercle bacilli(H37Rv, virulent strain and H37Ra, avirulent strain), in order to elucidate the possible pathophysiology of pulmonary tuberculosis. Methods : Peripheral blood monocytes were isolated from normal volunteers. Peripheral blood monocytes (PBM) were stimulated with LPS($10{\mu}g/ml$), H37Rv, or H37Ra($5{\times}10^5$ bacilli/well) along with normal control for 24 hours. A549 cells were stimulated with supernatants of cultured PBM for 24 hours. ELISA kit was used for the measurement of $TNF{\alpha}$ and IL-$1{\beta}$ production in supernatants of cultured PBM and for the measurement of RANTES and IL-8 in supernatants of cultured A549 cells. Northern blot analysis was used for the measurement of RANTES and IL-8 mRNA expression in cultured A549 cells. Results : $TNF{\alpha}$ and IL-$1{\beta}$ productions were increased in cultured PBM stimulated with LPS or tubercle bacilli(H37Rv or H37Ra) compared with the control. There was, however, no difference in $TNF{\alpha}$ and IL-$1{\beta}$ production between cultured PBM stimulated with H37Rv and H37Ra. RANTES and IL-8 expressions and productions were also increased in cultured A549 cells stimulated with LPS or tubercle bacilli compared with the control. RANTES and IL-8 mRNA expressions were significantly increased in cultured A549 cells stimulated with H37Ra-conditioned media(CM) compared with A549 cells stimulated with H37Rv-CM (p<0.05). However, there was no difference in RANTES and IL-8 productions between A549 cells stimulated with H37Rv-CM and H37Ra-CM. Conclusion : Airway epithelial cells can produce the potent chemokines such as RANTES and IL-8, in response to the stimulation of tubercle bacilli. These results suggest that airway epithelial cells may play a certain role in the pathogenesis of pulmonary tuberculosis. However, the role of airway epithelial cells in the pathogenesis of tuberculosis according to the virulence of tubercle bacilli was not clear in this study.

• Tuberculosis and Respiratory Diseases
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• v.51 no.4
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• pp.303-314
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• 2001

Background : Matrix metalioproteinase(MMP)-2 and MMP-9 have been known to play an important role in cell migration and the tissue remodeling process by type IV collagen lysis, a major component of the basement membrane. Intra-alveolar fibrosis, secondary to an injury to the basement membrane of the alveolar epithelial lining, is a major process in the pathogenesis of idiopathic pulmonary fibrosis(IPF). Therefore, MMP-2 and MMP-9 was hypothesized to play an important role in IPF pathogenesis. As a result, their level may reflect the activity or prognosis. Method : Forty one progressive IPF patients(age $59.82{\pm}1.73$ years, M:F=23:18), 16 patients with stable IPF for more than one year without therapy(age : $63.6{\pm}2.8$ years, M:F=13:3), and 7 normal controls were enrolled in this study. The MMP-2 and MMP-9 levels in the BAL fluid and alveolar macrophage conditioned media(AM-CM) were measured by zymography and the TIMP-1 level was measured by ELISA. Results : 1) The MMP-2 level in BALF was highest in the progressive IPF group ($1.36{\pm}0.28$) followed by the stable group ($0.46{\pm}0.13$) and the controls ($0.08{\pm}0.09$), which was statistically significant. The MMP-9 level of the IPF ($0.31{\pm}0.058$) and the stable group ($0.22{\pm}0.078$) were higher than that of the control group ($0.002{\pm}0.004$). In the AM-CM, only MMP-9 was detected, which was significantly higher in IPF group ($0.80{\pm}0.1O$) than in the control group($0.23{\pm}0.081$). The TIMP-1 level was also higher in both the IPF ($36.34{\pm}8.62\;{\mu}g/ml$) and stable group ($20.83{\pm}8.53\;{\mu}g/ml$) compared to the control group ($2.80{\pm}1.05\;{\mu}g/ml$) (p<0.05). 3) There was a correlation between the MMP-2 level in the BALF with the total cell number(r=0.298) and neutrophils(r=0.357) (p<0.05), and the MMP-9 level with the number of neutrophils (r=0.407) and lymphocytes (r=0.574)(p<0.05). The TIMP-1 level correlated with the total number of cell (r=0.338, p<0.05) and neutrophils(r=0.449, p=0.059). Conclusion : Both MMP and TIMP appear to play an important role in IPF pathogenesis, and their level may reflect the disease activity.

• Korean Journal of Environmental Biology
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• v.22
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• pp.54-62
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• 2004

We examined the impacts of anthyopogenic pollutant (benzo〔a〕pyrene) on the growth and photosynthesis of five marine phytoplankton species (Skeletonema costatum, Heterosigma akashiwo, Prorocentrum dentatum, P. minimum, Aknshiwo sanguinea), which are dominant in Korean coastal water. After the 72 h exposure to benzo〔a〕pyrene, the dramatic decrease in cell numbers was observed in the range of 1 to 10 $\mu\textrm{g}$ L$^{-1}$ for S. costatum, P. minimum, P. dentatum, whereas for A. sanguinea and H. akashiwo at the low concentrations 0.1 to 1 $\mu\textrm{g}$ L$^{-1}$ . Among the 5 phytoplankton species, the highest growth inhibition concentration ($IC_{50}$/) was 6.20 $\mu\textrm{g}$ L$^{-1}$ for P. minimum, followed by 2.14 $\mu\textrm{g}$ L$^{-1}$ for P. dentatum, 1.68 $\mu\textrm{g}$ L$^{-1}$ for S. costatum, 0.74 $\mu\textrm{g}$ L$^{-1}$ for H. akashiwo, 0.10 $\mu\textrm{g}$ L$^{-1}$ for A. sanguinea. The five species exposed to the low concentration of 1 $\mu\textrm{g}$ L$^{-1}$ were recovered after transferring to new media, but the species exposed to the high concentrations of 10 and 100 $\mu\textrm{g}$ L$^{-1}$ were not recovered, with the exception of P. minimum. Those results indicate that the thecate dinoflagellate P. minimum is most tolerant to the chemical and the athecate dinoflagellate A. sanguinea is not. Geneyally, the cell-specific photosynthetic capacity of H. akashiwo exposed to the low concentrations of 0.1 and 1 $\mu\textrm{g}$ L$^{-1}$ was higher than that of the cells in the control, whereas the cells exposed to the high concentrations of 5 and 10 $\mu\textrm{g}$ L$^{-1}$ showed the negligible photosynthetic level by the first few days of the experiment. In the case of the cells exposed to the concentration of 5 $\mu\textrm{g}$ L$^{-1}$ , after 12 days of the experiment the photosynthetic capacity was increased toward the end of the experiment. This indicates that H. akashiwo may utilize the benzo〔a〕pyrene as a carton source for its growth when exposed to low concentrations. Results suggest that anthropogenic pollutants such as benzo〔a〕pyrene may have significant influence on the succession of phytoplankton species composition and the primary production in coastal marine environments.

• Journal of Distribution Research
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• v.15 no.4
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• pp.61-85
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• 2010

Introduction: Diffusion is process by which an innovation is communicated through certain channel overtime among the members of a social system(Rogers 1983). Bass(1969) suggested the Bass model describing diffusion process. The Bass model assumes potential adopters of innovation are influenced by mass-media and word-of-mouth from communication with previous adopters. Various expansions of the Bass model have been conducted. Some of them proposed a third factor affecting diffusion. Others proposed multinational diffusion model and it stressed interactive effect on diffusion among several countries. We add a spatial factor in the Bass model as a third communication factor. Because of situation where we can not control the interaction between markets, we need to consider that diffusion within certain market can be influenced by diffusion in contiguous market. The process that certain type of retail extends is a result that particular market can be described by the retail life cycle. Diffusion of retail has pattern following three phases of spatial diffusion: adoption of innovation happens in near the diffusion center first, spreads to the vicinity of the diffusing center and then adoption of innovation is completed in peripheral areas in saturation stage. So we expect spatial effect to be important to describe diffusion of domestic discount store. We define a spatial diffusion model using multinational diffusion model and apply it to the diffusion of discount store. Modeling: In this paper, we define a spatial diffusion model and apply it to the diffusion of discount store. To define a spatial diffusion model, we expand learning model(Kumar and Krishnan 2002) and separate diffusion process in diffusion center(market A) from diffusion process in the vicinity of the diffusing center(market B). The proposed spatial diffusion model is shown in equation (1a) and (1b). Equation (1a) is the diffusion process in diffusion center and equation (1b) is one in the vicinity of the diffusing center. $$\array{{S_{i,t}=(p_i+q_i{\frac{Y_{i,t-1}}{m_i}})(m_i-Y_{i,t-1})\;i{\in}\{1,{\cdots},I\}\;(1a)}\\{S_{j,t}=(p_j+q_j{\frac{Y_{j,t-1}}{m_i}}+{\sum\limits_{i=1}^I}{\gamma}_{ij}{\frac{Y_{i,t-1}}{m_i}})(m_j-Y_{j,t-1})\;i{\in}\{1,{\cdots},I\},\;j{\in}\{I+1,{\cdots},I+J\}\;(1b)}}$$ We rise two research questions. (1) The proposed spatial diffusion model is more effective than the Bass model to describe the diffusion of discount stores. (2) The more similar retail environment of diffusing center with that of the vicinity of the contiguous market is, the larger spatial effect of diffusing center on diffusion of the vicinity of the contiguous market is. To examine above two questions, we adopt the Bass model to estimate diffusion of discount store first. Next spatial diffusion model where spatial factor is added to the Bass model is used to estimate it. Finally by comparing Bass model with spatial diffusion model, we try to find out which model describes diffusion of discount store better. In addition, we investigate the relationship between similarity of retail environment(conceptual distance) and spatial factor impact with correlation analysis. Result and Implication: We suggest spatial diffusion model to describe diffusion of discount stores. To examine the proposed spatial diffusion model, 347 domestic discount stores are used and we divide nation into 5 districts, Seoul-Gyeongin(SG), Busan-Gyeongnam(BG), Daegu-Gyeongbuk(DG), Gwan- gju-Jeonla(GJ), Daejeon-Chungcheong(DC), and the result is shown