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Chen F.-P.,Keelung Chang Gung Memorial Hospital | Hu C.-H.,National Taiwan Ocean University | Wang K.-C.,Chang Gung University
Climacteric | Year: 2013

Objective To determine whether estrogen regulates mesenchymal stem cell (MSC) activity in bone marrow from osteoporotic postmenopausal women. Methods MSCs were collected from bone marrows which were aspirated simultaneously during iliac bone graft procedures in spine fusion surgery in osteoporotic postmenopausal women. We investigated proliferation, differentiation, osteogenic activity, and estrogen receptor (ER) α and β mRNA expression of primary culture MSCs isolated from four osteoporotic postmenopausal women, treated in vitro with or without 17β-estradiol. The expression of alkaline phosphatase (ALP), osteocalcin, interleukin-6, ERα and ERβ mRNA was evaluated. Results The expression of ALP and osteocalcin mRNA was detected during the cultures of MSCs and was observed to increase up to day 20. As compared with MSCs not treated with estradiol, a significant increase in DNA content, ERα mRNA, and ALP mRNA expression was observed in cultures with estradiol. The mRNA expression of osteocalcin and interleukin-6 was significantly lower in MSCs treated with estradiol than those without estradiol. There was no significant difference in the mRNA expression of ERβ between MSCs cultured with and without estradiol. Conclusions In the proper environment, MSCs from osteoporotic women can differentiate into osteoblasts and estrogen enhances the osteogenic activity possibly via ERα activity. © 2012 International Menopause Society.

Lee C.-H.,Chang Gung Memorial Hospital | Lin Y.-J.,Resource Center for Clinical Research | Lin C.-C.,Chang Gung Memorial Hospital | Yen C.-L.,Keelung Chang Gung Memorial Hospital | And 6 more authors.
Liver International | Year: 2015

Background & Aims: Thrombocytosis is associated with metastasis in many human cancers. Most hepatocellular carcinomas (HCC) develop in cirrhotic livers, which are characterized by thrombocytopenia. We aimed to elucidate the pretreatment platelet count in prediction of extrahepatic metastasis of HCC during the follow-up. Methods: Three cohorts containing 1660, 480 and 965 HCC patients enrolled from three hospitals were used for discovery and validation respectively. Pretreatment clinical factors associated with extrahepatic metastasis during follow-up up to 5 years were identified using multivariate Cox regression model. Results: In early-stage HCC (BCLC stage 0-A), pretreatment platelet count (hazard ratio [HR], 1.04 per 10,000/μl; 95% CI, 1.01-1.07; P = 0.010) and serum alpha-foetoprotein (AFP) >100 ng/ml (HR, 1.70; 95% CI, 1.04-2.78; P = 0.033) were the only two independent factors associated with extrahepatic metastasis. Receiver operating characteristic evidenced that pretreatment platelet count predicted metastasis better than AFP did. Survival tree analysis identified platelet counts <118,000/μl (HR, 0.49; 95% CI, 0.38-0.63; P < 0.001) or >212,000/μl (HR, 2.12; 95% CI, 1.67-2.70; P < 0.001) to categorize patients into low and high risk of metastasis subgroups, which were verified using both validation cohorts. Conclusions: Pretreatment platelet count is a reliable marker to predict extrahepatic metastasis of early-stage HCC following curative treatment. Cirrhotic thrombocytopenia contributes to relatively low metastasis incidence of HCC than many other cancers. High platelet count identifies a subgroup of HCC patients at high risk of metastasis, who might benefit from adjuvant therapies following initial curative treatment. © 2015 John Wiley & Sons A/S.

Li W.-C.,Keelung Chang Gung Memorial Hospital | Lee Y.-Y.,National Yang Ming University | Lee Y.-Y.,Taipei Veterans General Hospital | Chen I.-C.,Chiayi Chang Gung Memorial Hospital | And 3 more authors.
Liver International | Year: 2013

Background: Hepatitis B/C viruses cause liver disease and metabolic disturbances. Aims: The purpose of this study was to evaluate the association between hepatitis B/C infection and metabolic syndrome (MS). Methods: In total, 26 305 subjects were included in this multicentre, cross-sectional study. Systolic and diastolic blood pressures, body mass index and waist circumference were measured. Total cholesterol, high- and low-density lipoprotein cholesterol, triglyceride, fasting blood glucose and uric acid were determined, and hepatitis B serum antigen (HBsAg) and anti-HCV antibodies were assayed using commercial kits. Results: MS was diagnosed in 2712 (23.0%) females, including 131 and 166 positive for HBsAg and anti-HCV respectively. In the men, 4594 (31.6%) were diagnosed with MS, including 326 positive for HBsAg and 131 positive for anti-HCV. No significant difference in the prevalence of MS was identified in any group, except men and women >45 years who were anti-HCV positive. Various metabolic alterations in both men and women >45 years were noted, including waist circumference, body mass index, fasting blood glucose and systolic and diastolic blood pressure. Notably, high- and low-density lipoproteins were significantly lower in positive subjects compared to those weakly positive and/or negative for anti-HCV. Conclusions: There were obvious metabolic derangements in patients coinflicted with MS and hepatitis C infections, particularly those >45 years of age. There is a pressing need to identify strategies to improve/resolve metabolic derangements to maximize sustained virological response rates in patients infected with HCV (and potentially HBV). © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Shyu Y.-C.,National Yang Ming University | Shyu Y.-C.,Taipei Medical University Hospital | Shyu Y.-C.,Academia Sinica, Taiwan | Lee T.-L.,Academia Sinica, Taiwan | And 14 more authors.
Developmental Cell | Year: 2014

Erythropoiesis is a highly regulated process during which BFU-E are differentiated into RBCs through CFU-E, Pro-E, PolyCh-E, OrthoCh-E, and reticulocyte stages. Uniquely, most erythroid-specific genes are activated during the Pro-E to Baso-E transition. We show that a wave of nuclear import of the erythroid-specific transcription factor EKLF occurs during the Pro-E to Baso-E transition. We further demonstrate that this wave results from a series of finely tuned events, including timed activation of PKCθ, phosphorylation of EKLF at S68 by P-PKCθ(S676), and sumoylation of EKLF at K74. The latter EKLF modifications modulate its interactions with a cytoplasmic ankyrin-repeat-protein FOE and importinβ1, respectively. The role of FOE in the control of EKLF nuclear import is further supported by analysis of the subcellular distribution patterns of EKLF in FOE-knockout mice. This study reveals the regulatory mechanisms of the nuclear import of EKLF, which may also be utilized in the nuclear import of other factors. © 2014 Elsevier Inc.

Lee M.-S.,National Taiwan Ocean University | Yen C.-L.,Keelung Chang Gung Memorial Hospital | Ueng S.-K.,National Taiwan Ocean University
IET Image Processing | Year: 2012

In this study, a novel speckle reduction method is proposed for ultrasound images. This denoising method is designed to preserve both the edges and structural details of the image. Speckle noise is suppressed, without smearing the edges, by extending the smoothness of the image in the wavelet-based Hölder spaces. A comparison of smoothing speckles with the other well-known methods is provided via the size of Besov norm. The authors validate the proposed method using synthetic data, simulated and real ultrasound images. Experiments demonstrate the performance improvement of the proposed method over other state-of-the-art methods in terms of image quality and edge preservation indices. © 2012 The Institution of Engineering and Technology.

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