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      • KCI등재

        Astragalus membranaceus promotes differentiation and mineralization in human osteoblast-like SaOS-2 cells

        Huh, Jeong-Eun,Kim, Nam-Jae,Yang, Ha-Ru,Cho, Eun-Mi,Baek, Yong-Hyeon,Choi, Do-Young,Kim, Deog-Yoon,Cho, Yoon-Je,Kim, Kang-Il,Park, Dong-Suk,Lee, Jae-Dong The Korean AcupunctureMoxibustion Medicine Society 2005 대한침구의학회지 Vol.22 No.2

        Background & Object : The differentiation of osteoblasts controlled by various growth factors and matrix proteins expression in bone. The aim of this study was to identify the Astragalus membranaceus that may induce the osteogenic activity in human osteoblast-like SaOS-2 cells. Methods : The osteogenic activity of Astragalus membranaceus were evaluated by WST-8 assay, ALP activity, RT-PCR analysis of VEGF, OCN, OPN, Col I mRNA, and ELISA or colorimetric analysis, and mineralization by Alizarin red staining in SaOS-2 cells. Results : Astragalus membranaceus had no effect on viability of osteoblastic cells, and dose dependently increased alkaline phosphatase (ALP) activity. Astragalus membranaceus markedly increased mRNA expression for vascular endothelial growth factor (VEGF), osteocalcin (OCN), osteopontin (OPN), and type I collagen (Col 1) in SaOS-2 cells. Extracellular accumulation of proteins such as VEGF, and Col I was increased in a dose-dependent manner. Also, Astragalus membranaceus significantly induced mineralization in the culture of SaOS-2 cells. Conclusion : This study showed that Astragalus membranaceus not affect on viability, but it enhanced ALP activity, VEGF, bone matrix proteins such as OCN, OPN and Col I, and mineralization in SaOS-2 cells. These results propose that Astragalus membranaceus plays an important role in osteoblastic bone formation, and possibly lead to the development of bone-forming drug.

      • SCISCIESCOPUS

        Impact of central haemodynamics on left ventricular function in individuals with an exaggerated blood pressure response to exercise

        Shim, Chi Young,Hong, Geu-Ru,Park, Sungha,Yang, Woo-In,Choi, Donghoon,Chung, Namsik,Ha, Jong-Won Wolters Kluwer Health, Inc. All rights reserved. 2015 Journal of Hypertension Vol.33 No.3

        OBJECTIVE:: The impact of exaggerated blood pressure response (EBPR) to exercise on left ventricular function and the mechanism of its association are poorly understood. This study investigated the impact of arterial stiffening on left ventricular function in individuals with an EBPR to exercise. We hypothesized that individuals with low pulse pressure (PP) amplification during exercise would have worse left ventricular function than those with high PP amplification in individuals with an EBPR to exercise. METHODS:: Fifty-nine individuals with an EBPR to exercise (18 men, age 57 ± 12 years) and 59 age and sex-matched controls were studied. Radial artery tonometry was performed at rest and immediately after exercise during supine bicycle exercise echocardiography. RESULTS:: There were no differences in left ventricular structure or function between individuals with an EBPR to exercise and controls. When individuals with an EBPR to exercise were divided into two groups on the basis of PP amplification after exercise [Group 1 (n = 30), high PP amplification after exercise; Group 2 (n = 29), low PP amplification after exercise], group 2 showed larger left atrial volume and lower early diastolic (e’) and systolic (S’) mitral annular velocities. Left ventricular apical rotation was also exaggerated in group 2. In multiple regression, PP amplification after exercise was an independent determinant of e’ (&bgr; = 0.16, P = 0.019) and S’ (&bgr; = 0.25, P = 0.009) in individuals with an EBPR to exercise. CONCLUSION:: In individuals with an EBPR to exercise, the degree of left ventricular dysfunction is variable. EBPR to exercise in the presence of arterial stiffening contributes to the deterioration of left ventricular function.

      • KCI등재
      • KCI등재

        Effects of Aralia cordata Thunb. on Proteoglycan Release, Type II Collagen Degradation and Matrix Metalloproteinase Activity in Rabbit Articular Cartilage Explants

        Baek, Yong-Hyeon,Seo, Byung-Kwan,Lee, Jae-Dong,Huh, Jeong-Eun,Yang, Ha-Ru,Cho, Eun-Mi,Choi, Do-Young,Kim, Deog-Yoon,Cho, Yoon-Je,Kim, Kang-Il,Park, Dong-Suk The Korean AcupunctureMoxibustion Medicine Society 2005 대한침구의학회지 Vol.22 No.2

        Background & Objective: Articular cartilage is a potential target for drugs designed to inhibit the activity of matrix metalloproteinases (MMPs) to stop or slow the destruction of the proteoglycan and collagen in the cartilage extracellular matrix. The purpose of this study was to investigate the effects of Aralia cordata Thunb. in inhibiting the release of glycosaminoglycan (GAG), the degradation of collagen, and MMP activity in rabbit articular cartilage explants. Methods : The cartilage-protective effects of Aralia cordata Thunb. were evaluated by using glycosaminoglycan degradation assay, collagen degradation assay, colorimetric analysis of MMP activity, measurement of lactate dehydrogenase activity and histological analysis in rabbit cartilage explants culture. Results : Interleukin-la (IL-1a) rapidly induced GAG, but collagen was much less readily released from cartilage explants. Aralia cordata Thunb. significantly inhibited GAG and collagen release in a concentration-dependent manner. Aralia cordata Thunb. dose-dependently inhibited MMP-3 and MMP-13 expression and activities from IL-1a-treated cartilage explants cultures when tested at concentrations ranging from 0.02 to 0.2 mg/ml. Aralia cordata Thunb. had no harmful effect on chondrocytes viability or cartilage morphology in cartilage explants. Histological analysis indicated that Aralia cordata Thunb. reduced the degradation of the cartilage matrix compared with that of IL -1a-treated cartilage explants.

      • KCI등재
      • KCI등재

        High-glutathione mesenchymal stem cells isolated using the FreSHtracer probe enhance cartilage regeneration in a rabbit chondral defect model

        Gun Hee Cho,Bae Hyun Cheol,조원영,정의만,Hee Jung Park,Ha Ru Yang,Sun Young Wang,You Jung Kim,Shin Dong-Myung,Hyung-Min Chung,In Gyu Kim,한혁수 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00

        Background Mesenchymal stem cells (MSCs) are a promising cell source for cartilage regeneration. However, the function of MSC can vary according to cell culture conditions, donor age, and heterogeneity of the MSC population, resulting in unregulated MSC quality control. To overcome these limitations, we previously developed a fluorescent real-time thiol tracer (FreSHtracer) that monitors cellular levels of glutathione (GSH), which are known to be closely associated with stem cell function. In this study, we investigated whether using FreSHtracer could selectively separate high-functioning MSCs based on GSH levels and evaluated the chondrogenic potential of MSCs with high GSH levels to repair cartilage defects in vivo. Methods Flow cytometry was conducted on FreSHtracer-loaded MSCs to select cells according to their GSH levels. To determine the function of FreSHtracer-isolated MSCs, mRNA expression, migration, and CFU assays were conducted. The MSCs underwent chondrogenic differentiation, followed by analysis of chondrogenic-related gene expression. For in vivo assessment, MSCs with different cellular GSH levels or cell culture densities were injected in a rabbit chondral defect model, followed by histological analysis of cartilage-regenerated defect sites. Results FreSHtracer successfully isolated MSCs according to GSH levels. MSCs with high cellular GSH levels showed enhanced MSC function, including stem cell marker mRNA expression, migration, CFU, and oxidant resistance. Regardless of the stem cell tissue source, FreSHtracer selectively isolated MSCs with high GSH levels and high functionality. The in vitro chondrogenic potential was the highest in pellets generated by MSCs with high GSH levels, with increased ECM formation and chondrogenic marker expression. Furthermore, the MSCs’ function was dependent on cell culture conditions, with relatively higher cell culture densities resulting in higher GSH levels. In vivo, improved cartilage repair was achieved by articular injection of MSCs with high levels of cellular GSH and MSCs cultured under high-density conditions, as confirmed by Collagen type 2 IHC, Safranin-O staining and O’Driscoll scores showing that more hyaline cartilage was formed on the defects. Conclusion FreSHtracer selectively isolates highly functional MSCs that have enhanced in vitro chondrogenesis and in vivo hyaline cartilage regeneration, which can ultimately overcome the current limitations of MSC therapy.

      • KCI등재

        Effects of Aralia cordata Thunb. on Proteoglycan Release, Type II Collagen Degradation and Matrix Metalloproteinase Activity in Rabbit Articular Cartilage Explants

        Baek, Yong-Hyeon,Seo, Byung-Kwan,Lee, Jae-Dong,Huh, Jeong-Eun,Yang, Ha-Ru,Cho, Eun-Mi,Choi, Do-Young,Kim, Deog-Yoon,Cho, Yoon-Je,Kim, Kang-Il,Park, Dong-Suk The Korean Acupuncture Moxibustion Medicine Societ 2005 대한침구의학회지 Vol.33 No.4

        Background & Objective: Articular cartilage is a potential target for drugs designed to inhibit the activity of matrix metalloproteinases (MMPs) to stop or slow the destruction of the proteoglycan and collagen in the cartilage extracellular matrix. The purpose of this study was to investigate the effects of Aralia cordata Thunb. in inhibiting the release of glycosaminoglycan (GAG), the degradation of collagen, and MMP activity in rabbit articular cartilage explants. Methods : The cartilage-protective effects of Aralia cordata Thunb. were evaluated by using glycosaminoglycan degradation assay, collagen degradation assay, colorimetric analysis of MMP activity, measurement of lactate dehydrogenase activity and histological analysis in rabbit cartilage explants culture. Results : Interleukin-la (IL-1a) rapidly induced GAG, but collagen was much less readily released from cartilage explants. Aralia cordata Thunb. significantly inhibited GAG and collagen release in a concentration-dependent manner. Aralia cordata Thunb. dose-dependently inhibited MMP-3 and MMP-13 expression and activities from IL-1a-treated cartilage explants cultures when tested at concentrations ranging from 0.02 to 0.2 mg/ml. Aralia cordata Thunb. had no harmful effect on chondrocytes viability or cartilage morphology in cartilage explants. Histological analysis indicated that Aralia cordata Thunb. reduced the degradation of the cartilage matrix compared with that of IL -1a-treated cartilage explants.

      • Prognostic significance of interventricular septal thickness in patients with AL amyloidosis

        Cho, Hyunsoo,Kim, Soo-Jeong,Shim, Chi Young,Hong, Geu-Ru,Ha, Jong-Won,Kim, Yu Ri,Yang, Woo Ick,Chung, Haerim,Jang, Ji Eun,Cheong, June-Won,Min, Yoo Hong,Kim, Jin Seok Elsevier 2017 Leukemia research Vol.60 No.-

        <P><B>Abstract</B></P> <P>The major prognostic determinant of immunoglobulin light chain (AL) amyloidosis is cardiac involvement. However, the role of interventricular septal thickness (IVST), which reflects the extent of cardiac involvement, remains unclear. Therefore, we analyzed 77 patients with newly diagnosed AL amyloidosis and evaluated the prognostic role of IVST. Fifty patients (64.9%) had cardiac involvement and 17 patients (22.1%) showed IVST >15mm. Among all patients, the revised Mayo Clinic Stage III–IV and IVST >15mm were independently associated with inferior overall survival (OS) in a multivariable analysis. IVST >15mm was also adversely prognostic for OS in a subgroup of advanced-stage (revised Mayo Clinic stage III–IV) patients in a multivariable analysis (<I>P</I> <0.001). Furthermore, advanced-stage patients with IVST >15mm did not show survival benefit from treatment with bortezomib-based regimens and/or autologous stem-cell transplantation (ASCT). Our study demonstrated that IVST >15mm is adversely prognostic independent of the revised Mayo Clinic staging system in patients with AL amyloidosis. In addition, the degree of IVST might be used as a useful prognostic indicator that can guide the management of patients with AL amyloidosis especially at an advanced stage.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Cardiac involvement is the major prognostic determinant of AL amyloidosis. </LI> <LI> Interventricular septal thickness (IVST) >15mm was an important prognostic factor. </LI> <LI> IVST >15mm was also adversely prognostic in advanced stage patients. </LI> <LI> IVST might be used as a useful prognostic indicator in AL amyloidosis. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>Differences in overall survival (OS) according to the interventricular septal thickness (IVST) and the new four-factor model, incorporating IVST into the revised Mayo Clinic staging system; patients are grouped by the presence of 0–1 (low-risk), 2–3 (intermediate-risk), or 4 (high-risk) of the following risk factors: IVST >15mm, troponin-T≥0.025ng/mL, N-terminal pro-brain natriuretic peptide ≥1800pg/mL, and difference between involved and uninvolved free light chains≥18mg/dL.</P> <P>[DISPLAY OMISSION]</P>

      • KCI등재

        Hypoxic condition enhances chondrogenesis in synovium-derived mesenchymal stem cells

        Hyun Cheol Bae,Hee Jung Park,Sun Young Wang,Ha Ru Yang,Myung Chul Lee,한혁수 한국생체재료학회 2018 생체재료학회지 Vol.22 No.4

        Background: The chondrogenic differentiation of mesenchymal stem cells (MSCs) is regulated by many factors, including oxygen tensions, growth factors, and cytokines. Evidences have suggested that low oxygen tension seems to be an important regulatory factor in the proliferation and chondrogenic differentiation in various MSCs. Recent studies report that synovium-derived mesenchymal stem cells (SDSCs) are a potential source of stem cells for the repair of articular cartilage defects. But, the effect of low oxygen tension on the proliferation and chondrogenic differentiation in SDSCs has not characterized. In this study, we investigated the effects of hypoxia on proliferation and chondrogenesis in SDSCs. Method: SDSCs were isolated from patients with osteoarthritis at total knee replacement. To determine the effect of oxygen tension on proliferation and colony-forming characteristics of SDSCs, A colony-forming unit (CFU) assay and cell counting-based proliferation assay were performed under normoxic (21% oxygen) or hypoxic (5% oxygen). For in vitro chondrogenic differentiation, SDSCs were concentrated to form pellets and subjected to conditions appropriate for chondrogenic differentiation under normoxia and hypoxia, followed by the analysis for the expression of genes and proteins of chondrogenesis. qRT-PCR, histological assay, and glycosoaminoglycan assays were determined to assess chondrogenesis. Results: Low oxygen condition significantly increased proliferation and colony-forming characteristics of SDSCs compared to that of SDSCs under normoxic culture. Similar pellet size and weight were found for chondrogensis period under hypoxia and normoxia condition. The mRNA expression of types II collagen, aggrecan, and the transcription factor SOX9 was increased under hypoxia condition. Histological sections stained with Safranin-O demonstrated that hypoxic conditions had increased proteoglycan synthesis. Immunohistochemistry for types II collagen demonstrated that hypoxic culture of SDSCs increased type II collagen expression. In addition, GAG deposition was significantly higher in hypoxia compared with normoxia at 21 days of differentiation. Conclusion: These findings show that hypoxia condition has an important role in regulating the synthesis ECM matrix by SDSCs as they undergo chondrogenesis. This has important implications for cartilage tissue engineering applications of SDSCs.

      • Uncaria rhynchophylla Induces Angiogenesis in Vitro and in Vivo

        Choi, Do-Young,Huh, Jeong-Eun,Lee, Jae-Dong,Cho, Eun-Mi,Baek, Yong-Hyeon,Yang, Ha-Ru,Cho, Yoon-Je,Kim, Kang-Il,Kim, Deog-Yoon,Park, Dong-suk EAST-WEST MEDICAL RESEARCH INSTITUTE KYUNG HEE UNI 2005 東西醫學硏究所 論文集 Vol.2005 No.-

        Angiogenesis consists of the proliferation, migration, and differentiation of endothelial cell and angiogenic factors and matrix protein interactions modulate this process. The aim of this study was to determine the angiogenic properties of Uncaria rhynchophylla. Uncaria rhynchophylla significantly enhanced human umbilical vein endothelial cells (HUVECs) proliferation in a dose-dependent manner. Neutralization of vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF) by monoclonal antibody suppressed the Uncaria rhynchophylla stimulatory effect on proliferation. In addition, Uncaria rhynchophylla significantly increased chemotactic-migration on gelatin and tubular structures on Matrigel of HUVECs in a dose-dependent manner. Interestingly, Uncaria rhynchophylla dose-dependently increased VEGF, and bFGF gene expression and protein secretion of HUVEC. The angiogenic activity of Uncaria rhynchophylla was confirmed using an in vivo Matrigel angiogenesis model, showing promotion of blood vessel formation. These results suggest that Uncaria rhynchophylla could potentially used to accelerate vascular wound healing or to promote the growth of collateral blood vessel in ischemic tissues.

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