• Biomolecules & Therapeutics
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• v.32 no.4
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• pp.432-441
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• 2024

Systemic sclerosis is an autoimmune disease characterized by inflammatory reactions and fibrosis. Myofibroblasts are considered therapeutic targets for preventing and reversing the pathogenesis of fibrosis in systemic sclerosis. Although the mechanisms that differentiate into myofibroblasts are diverse, transforming growth factor β (TGF-β) is known to be a key mediator of fibrosis in systemic sclerosis. This study investigated the effects of extracellular vesicles derived from human adipose stem cells (ASC-EVs) in an in vivo systemic sclerosis model and in vitro TGF-β1-induced dermal fibroblasts. The therapeutic effects of ASC-EVs on the in vivo systemic sclerosis model were evaluated based on dermal thickness and the number of α-smooth muscle actin (α-SMA)-expressing cells using hematoxylin and eosin staining and immunohistochemistry. Administration of ASC-EVs decreased both the dermal thickness and α-SMA expressing cell number as well as the mRNA levels of fibrotic genes, such as Acta2, Ccn2, Col1a1 and Comp. Additionally, we discovered that ASC-EVs can decrease the expression of α-SMA and CTGF and suppress the TGF-β pathway by inhibiting the activation of SMAD2 in dermal fibroblasts induced by TGF-β1. Finally, TGF-β1-induced dermal fibroblasts underwent selective death through ASC-EVs treatment. These results indicate that ASC-EVs could provide a therapeutic approach for preventing and reversing systemic sclerosis.

• Journal of Ginseng Research
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• v.39 no.3
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• pp.230-237
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• 2015

Background: Colorectal cancer (CRC) is a leading cause of death worldwide. Chronic gut inflammation is recognized as a risk factor for tumor development, including CRC. American ginseng is a very commonly used ginseng species in the West. Methods: A genetically engineered $Apc^{Min/+}$ mouse model was used in this study. We analyzed the saponin composition of American ginseng used in this project, and evaluated its effects on the progression of high-fat-diet-enhanced CRC carcinogenesis. Results: After oral ginseng administration (10-20 mg/kg/d for up to 32 wk), experimental data showed that, compared with the untreated mice, ginseng very significantly reduced tumor initiation and progression in both the small intestine (including the proximal end, middle end, and distal end) and the colon (all p < 0.01). This tumor number reduction was more obvious in those mice treated with a low dose of ginseng. The tumor multiplicity data were supported by body weight changes and gut tissue histology examinations. In addition, quantitative real-time polymerase chain reaction analysis showed that compared with the untreated group, ginseng very significantly reduced the gene expression of inflammatory cytokines, including interleukin-$1{\alpha}$ (IL-$1{\alpha}$), IL-$1{\beta}$, IL-6, tumor necrosis factor-${\alpha}$, granulocyte-colony stimulating factor, and granulocyte-macrophage colony-stimulating factor in both the small intestine and the colon (all p < 0.01). Conclusion: Further studies are needed to link our observed effects to the actions of the gut microbiome in converting the parent ginsenosides to bioactive ginseng metabolites. Our data suggest that American ginseng may have potential value in CRC chemoprevention.

• Clinical and Experimental Reproductive Medicine
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• v.38 no.4
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• pp.193-202
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• 2011

Objective: We found previously that $interferon$ $regulatory$ factor ($Irf$)-1 is a germinal vesicle (GV)-selective gene that highly expressed in GV as compared to metaphase II oocytes. To our knowledge, the function of $Irf-1$ in oocytes has yet to be examined. The present study was conducted to determine the relationship between retinoic acid (RA) and RA-mediated expression of $Irf-1$ and the mouse oocyte maturation. Methods: Immature cumulus-oocyte-complexes (COCs) were collected from 17-day-old female mice and cultured $in$ $vitro$ for 16 hours in the presence of varying concentrations of RA (0-10 ${\mu}M$). Rate of oocyte maturation and activation was measured. Gene expression was measured by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) and cytokine secretion in the medium was measured by Bio-Plex analysis. Apoptosis was analyzed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Results: The rates of oocyte maturation to metaphase II and oocyte activation increased significantly with RA treatment (10 nM-1 ${\mu}M$). With 100 nM RA treatment, lowest level of $Irf-1$ mRNA and cumulus cell's apoptosis was found. Among 23 cytokines measured by Bio-Plex system, the substantial changes in secretion of tumor necrosis factor-${\alpha}$, macrophage inflammatory protein-$1{\beta}$, eotaxin and interleukin-12 (p40) from COCs in response to RA were detected. Conclusion: We concluded that the maturation of oocytes and $Irf-1$ expression are negatively correlated, and RA enhances the developmental competence of mouse immature oocytes $in$ $vitro$ by suppressing apoptosis of cumulus cells. Using a mouse model, results of the present study provide insights into improved culture conditions for $in$ $vitro$ oocyte maturation and relevant cytokine production and secretion in assisted reproductive technology.

• Journal of Environmental Science International
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• v.10 no.1
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• pp.21-25
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• 2001

The Keum river has been utilized for drinking water supply of several city including Kunsan city and is deepening pollution state due to numerous municipal and industrial discharges. The concentration BOD in river is affected by the organic loading from a tributary and the algae biomass that largely happen to under eutrophication state. In the eutrophic water mass such as the Keum river, the autochthonous BOD was very important part for making a decision of water quality management, because it was accounted for majority of the total BOD. The predict of water quality has important meaning for management of water quality pollution of the Keum river. The purpose of this study will manage and predict water quality of the Keum river using QUAL-2E model considering the autochthonous BOD. The estimation of autochthonous BOD represented that the relationship between BOD and chlorophyll a. The regression equation was shown to be autochthonous BOD=$\beta$(sub)5$\times$chlorophyll a. The results of this study may be summarized as followed; The QUAL-2E model was calibrated with the data surveyed in the field of the study area in June, 1998. The calculated value by QUAL-2E model are in good agree to measured value within relative error of 7.80~20.33%. Especially, in the case of the considering autochthonous BOD, the calculated value of BOD were fairly good coincided with the observed values within relative error of 15%. But the case of not considering autochthonous BOD, relative error of BOD was shown to be 43.2%. In order to attain II grade of water quality standard in Puyo station which has a intake facility of water supply, we reduced to the pollutants loading of tributaries. In the case of removed 100% BOD of tributaries, the BOD of Puyo station was 4.07mg/$\ell$, belong to III grade of water quality standard. But in the case of removed 88% nutrient of tributaries, it was satisfied to II grade of water quality standard as below 3mg/$\ell$ of BOD. For estimation of autochthonous BOD in Keum river, we are performed simulating in accordance with reduction of nutrient load(50~100%) under conditions removal 90% organic load. Occupancy of autochthonous BOD according to nutrient loading reductions were varied from 25.97~79.51%. Occupancy of autochthonous BOD was shown to be a tendency to increasing in accordance with reduction of nutrient loading. Showing the above results, the nutrient that one of the growing factor of algae was important role in decision of BOD in the Keum river. For the water quality management of the Keum river, therefore, it is necessary to considering autochthonous BOD and to construction of advanced sewage treatment plant for nutrient removal.

• Journal of Korean Medicine Rehabilitation
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• v.25 no.1
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• pp.27-44
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• 2015

Objectives This study was carried out to find the effects of Gami-cheongyulsaseub-tang (hereinafter referred to GCST) on the inhibition of zymosan-induced pain in rats and collagen II-induced arthritis (CIA) in DBA/1J mouse. Methods As an acute inflammatory pain model, peripheral inflammation was induced by intraplantar injection of zymosan into the right hind paw in rats and then the hyperalgesia and pain regulating factors in spinal cord were analyzed. As a chronic inflammation model, the mixture of collagen II and complete Freund's adjuvant was treated into mice to establish rheumatoid arthritis and then body weight, thickness of hind paw, pathological change of spleen, immunological rheumatoid factor (IgG1, IgG2a, IgG2b, IgM and anti-collagen II), pro-inflammatory cytokines, and bone injury were analyzed. Results In the acute inflammatory pain model, GCST significantly inhibited the thermal and mechanical hyperalgesia and the pain regulating factors, including Fos, CD11b, PKA and PKC, in the spinal cord with a dose-dependent manner. In the chronic rheumatoid arthritis model, GCST administration decreased arthritic index and paw edema as compared with CIA control group. In particular, GCST reduced significantly the serum levels of total IgG2a, IgG2b, IgM, and specific anti-collagen II, but not total IgG1. GCST also resulted in the attenuation of bone injury and spleen enlargement/adhesion in CIA mice. Moreover, the secretion of pro-inflammatory cytokines TNF-${\alpha}$ and IL-$1{\beta}$ in CIA mice was significantly reduced by GCST in a dose-dependent manner. Conclusions Comparison of the results in this study showed that GCST had anti-nociceptive and immunomodulatory effects. These data imply that GCST can be used as an effective drug for not only rheumatoid arthritic pain but also other auto-immune diseases.

• Molecules and Cells
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• v.43 no.4
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• pp.408-418
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• 2020

The sinus node (SN) is located at the apex of the cardiac conduction system, and SN dysfunction (SND)-characterized by electrical remodeling-is generally attributed to idiopathic fibrosis or ischemic injuries in the SN. SND is associated with increased risk of cardiovascular disorders, including syncope, heart failure, and atrial arrhythmias, particularly atrial fibrillation. One of the histological SND hallmarks is degenerative atrial remodeling that is associated with conduction abnormalities and increased right atrial refractoriness. Although SND is frequently accompanied by increased fibrosis in the right atrium (RA), its molecular basis still remains elusive. Therefore, we investigated whether SND can induce significant molecular changes that account for the structural remodeling of RA. Towards this, we employed a rabbit model of experimental SND, and then compared the genome-wide RNA expression profiles in RA between SND-induced rabbits and sham-operated controls to identify the differentially expressed transcripts. The accompanying gene enrichment analysis revealed extensive pro-fibrotic changes within 7 days after the SN ablation, including activation of transforming growth factor-β (TGF-β) signaling and alterations in the levels of extracellular matrix components and their regulators. Importantly, our findings suggest that periostin, a matricellular factor that regulates the development of cardiac tissue, might play a key role in mediating TGF-β-signaling-induced aberrant atrial remodeling. In conclusion, the present study provides valuable information regarding the molecular signatures underlying SND-induced atrial remodeling, and indicates that periostin can be potentially used in the diagnosis of fibroproliferative cardiac dysfunctions.

• Journal of Acupuncture Research
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• v.34 no.2
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• pp.1-18
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• 2017

Objectives : The purpose of this study was to evaluate the effects of water extracts of Eucommiae cortex (EC), Psoraleae semen (PS), and their combination on receptor activator of nuclear factor-kappa-B ligand (RANKL)-induced osteoclast differentiation. Methods : We assayed the protein expression levels of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), c-Fos, mitogen-activated protein kinases (MAPKs), and ${\beta}-actin$ in cell lysates using western blotting. Similarly, mRNA expression levels of NFATc1, c-Fos, tartrateresistant acid phosphate (TRAP), and glyceraldehyde-3-phosphate dehydrogenase, spermatogeni (GAPDHS) from bone marrow macrophages (BMMs) were analyzed using reverse transcription-polymerase chain reaction (RT-PCR). Furthermore, we determined the anti-osteoporotic effects of the water extracts of EC, PS, and their combination in a lipopolysaccharide (LPS)-induced bone-loss mouse model. Results : The in vitro data revealed showed that the combination of EC and PS extract showed a more remarkable inhibition of osteoclast differentiation than each herb did alone. The combination downregulated the induction of c-Fos, NFATc1, and TRAP by suppressing the phosphorylation of p38 and c-Jun N-terminal kinases (JNKs) and inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells ($NF-{\kappa}B$). Lastly, the in vivo data showed that PS reduced the LPS-induced bone erosion. Conclusion : The result of this study suggests that EC and PS could be potential therapeutic agents for bone loss diseases such as osteoporosis.

• Journal of Ginseng Research
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• v.40 no.4
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• pp.437-444
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• 2016

Background: Although Korean Red Ginseng (KRG) has been traditionally used for a long time, its anti-inflammatory role and underlying molecular and cellular mechanisms have been poorly understood. In this study, the anti-inflammatory roles of KRG-derived components, namely, water extract (KRG-WE), saponin fraction (KRG-SF), and nonsaponin fraction (KRG-NSF), were investigated. Methods: To check saponin levels in the test fractions, KRG-WE, KRG-NSF, and KRG-SF were analyzed using high-performance liquid chromatography. The anti-inflammatory roles and underlying cellular and molecular mechanisms of these components were investigated using a macrophage-like cell line (RAW264.7 cells) and an acute gastritis model in mice. Results: Of the tested fractions, KGR-SF (but not KRG-NSF and KRG-WE) markedly inhibited the viability of RAW264.7 cells, and splenocytes at more than 500 mg/mL significantly suppressed NO production at $100{\mu}g/mL$, diminished mRNA expression of inflammatory genes such as inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-${\alpha}$, and interferon-${\beta}$ at $200{\mu}g/mL$, and completely blocked phagocytic uptake by RAW264.7 cells. All three fractions suppressed luciferase activity triggered by interferon regulatory factor 3 (IRF3), but not that triggered by activator protein-1 and nuclear factor-kappa B. Phospho-IRF3 and phospho-TBK1 were simultaneously decreased in KRG-SF. Interestingly, all these fractions, when orally administered, clearly ameliorated the symptoms of gastric ulcer in HCl/ethanol-induced gastritis mice. Conclusion: These results suggest that KRG-WE, KRG-NSF, and KRG-SF might have anti-inflammatory properties, mostly because of the suppression of the IRF3 pathway.

• Journal of The Korean Association For Science Education
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• v.22 no.5
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• pp.1010-1029
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• 2002

The purpose of this research was to survey middle school students' preference for science and its causal factors, so as to analyze the causal relationships between them. Preference for science and its causal factors were defined theoretically, and a theoretical model was constructed to measure them and analyze the causal relationship by structural equation modeling. According to the theoretical model and a pilot test, a questionnaire was developed with three parts; the background information of a respondent, the preference for science, and the causal factors of preference. The questionnaire was administered to one class per grade of randomly selected 8 middle schools from 4 areas across the country, and 819 students' data were collected. Preference for science was defined as a state of mind. It revealed to what extent, and how, one likes science. It consisted of 3 categories - 'emotional response', 'behavioral volition', 'valuational comprehension', and each category was divided into two subcategories. Causal factors affecting the preference for science consisted of three categories - personal, educational and social factors, and each was divided into 2 or 3 subcategories. Middle school students' preference for science was middling as a total. Curiosity about contents of science and valuation of science were high, comparatively, but behavioral volition about science was especially low. Students' responses to the causal factors were relatively high in every educational factor and sociocultural valuation of social factors, but relatively low in socioeconomic rewards of social factors, and especially low in personal factors. The causal relationship about the preference for science was investigated by multiple regression analysis and path analysis, using the structural equation model. Multiple regression analysis about the preference for science and its causal factors revealed important factors. The important factors were personal ability, the personal traits, rewards in school science, and contents of school science in order of magnitude of standardized regression coefficient ${\beta}$. Stepwise regression analysis with each of the subcategories of the preference for science as dependent variables showed what factors were important in each subcategory. According to the result of structural equation modeling, personal factors affected 'emotional response' and 'behavioral volition' directly, and social factors affected 'valuational comprehension' directly. Educational factors affected all categories of the preference for science by influencing not only 'emotional response' and 'valuational comprehension' directly, but also 'behavioral volition' indirectly. The way to promote middle school students' preference for science was suggested, based on the analysis result.

• Korean Journal of Clinical Pharmacy
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• v.25 no.4
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• pp.238-245
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• 2015

Background: Pharmacy schools newly adopted a 6-year program strengthening clinical knowledge since 2011 in Korea. The clinical training under the guidance of preceptors at hospital sites is a requisite for pharmacy students during the last year of undergraduate course. It has been rarely studied on the hospital pharmacists' perspective regarding being a preceptor or teaching pharmacy students. Objectives: This study aimed to examine the hospital pharmacists' intention toward student training and to identify the relevant factors among the individual pharmacists' characteristics and working environment within the theoretical frame of the Theory of Planned Behavior (TPB). Method: A mail-survey was conducted for pharmacists working in tertiary hospitals in Seoul and Incheon. The survey questionnaire consisting of 131 questions with a 5-likert scale was developed for investigating pharmacists' attitude, subjective norm, perceived behavioral control and the intention to teach pharmacy students as well as other demographic variables. To estimate the construct validity of components, factor analysis was conducted and Cronbach's alpha was calculated to estimate the reliability of the observed variables. Statistical analyses of one-way variance analysis and multiple regression analysis were performed using SPSS 18.0. Results: The survey response rate was 53% (116/210) and the three constructs of attitude (r = .519), subjective norm (r = .233) and perceived control (r = .392) have appropriate correlations with the intention, proving the appropriateness of using the TPB model. Pharmacists working in inpatient (mean = 3.45) and outpatient clinics (mean = 3.34) generally showed positive intention for teaching. The attitude (${\beta}=.432$, p < 0.01) and perceived control (${\beta}=.270$, p < .01) constructs were significant predictors of the intention. Both age (r = 0.246, p = 0.017) and length of career (r = 0.310, p = 0.002) were positively related with the perceived control. Conclusion: Hospital pharmacists showed generally positive intention to provide student training in spite of the concern on their limited perceived behavioral control. Future research to find the actual barriers pharmacists faced in educating students need to be conducted.