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Wang S.-Y.,Chi Mei Medical Center | Wang S.-Y.,Chang Gung University | Wei Y.-H.,National Yang Ming University | Wei Y.-H.,Mackay Medical College | And 5 more authors.
PLoS ONE | Year: 2015

Tumor cells display a shift in energy metabolism from oxidative phosphorylation to aerobic glycolysis. A subset of papillary thyroid carcinoma (PTC) is refractory to surgery and radioactive iodine ablation. Doxorubicin and sorafenib are the drugs of choice for treating advanced thyroid cancer but both induce adverse effects. In this study, we assessed the anti-cancer activity of 2-deoxy-D-glucose (2-DG) alone and in combination with doxorubicin or sorafenib in PTC cell lines with (BCPAP) and without (CG3) the BRAFV600E mutation. BCPAP cells were more glycolytic than CG3 cells, as evidenced by their higher extracellular L-lactate production, lower intracellular ATP level, lower oxygen consumption rate (OCR), and lower ratio of OCR/extracellular acidification rate. However, dose-dependent reduction in cell viability, intracellular ATP depletion, and extracellular L-lactate production were observed after 2-DG treatment. Regression analysis showed that cell growth in both cell lines was dependent on ATP generation. 2-DG increased the chemosensitivity of BCPAP and CG3 cell lines to doxorubicin and sorafenib. These results demonstrate that the therapeutic effects of low combined doses of 2-DG and doxorubicin or sorafenib are similar to those of high doses of doxorubicin or sorafenib alone in PTC cell lines regardless of the BRAFV600E mutation. © 2015 Wang et al.

Lee B.-S.,National Taiwan University | Lee C.-C.,National Taiwan University | Lin H.-P.,Mackay Memorial HospitalTaipei | Lin H.-P.,University of Taipei | And 5 more authors.
Carbohydrate Polymers | Year: 2016

Currently used guided tissue regeneration (GTR) membranes are mainly used as a barrier to prevent epithelial cells growth into defects before new bone formation. The aim of this study was to develop a tri-layer functional chitosan (CS) membrane with epigallocatechin-3-gallate (EGCG) grafted on the outer layer for bactericidal activity, and lovastatin was included in the middle layer for controlled release. Successful EGCG grafting was demonstrated using Fourier transform infrared spectroscopy and EGCG grafting significantly enhanced adhesion and proliferation of human gingival fibroblasts. The release duration of lovastatin reached 21 days. CS-Lovastatin1 produced the highest alkaline phosphatase activity and EGCG14-CS exhibited the best bactericidal activity against periodontopathic bacteria. Finally, the EGCG14-CS-Lovastatin1 membrane showed a higher percentage of bone regeneration than BioMend® and control groups in one-walled defects of beagle dogs. These results suggest that the EGCG14-CS-Lovastatin1 membrane has the potential to be used as a novel GTR membrane. © 2016 Elsevier Ltd

Liao Y.-Y.,National Yang Ming University | Yang Y.-R.,National Yang Ming University | Cheng S.-J.,Mackay Memorial HospitalTaipei | Wu Y.-R.,Chang Gung Memorial Hospital | And 4 more authors.
Neurorehabilitation and Neural Repair | Year: 2015

Background. Obstacle crossing is a balance-challenging task and can cause falls in people with Parkinson's disease (PD). However, programs for people with PD that effectively target obstacle crossing and dynamic balance have not been established. Objective. To examine the effects of virtual reality-based exercise on obstacle crossing performance and dynamic balance in participants with PD. Methods. Thirty-six participants with a diagnosis of PD (Hoehn and Yahr score ranging 1 to 3) were randomly assigned to one of three groups. In the exercise groups, participants received virtual reality-based Wii Fit exercise (VRWii group) or traditional exercise (TE group) for 45 minutes, followed by 15 minutes of treadmill training in each session for a total of 12 sessions over 6 weeks. Participants in the control group received no structured exercise program. Primary outcomes included obstacle crossing performance (crossing velocity, stride length, and vertical toe obstacle clearance) and dynamic balance (maximal excursion, movement velocity, and directional control measured by the limits-of-stability test). Secondary outcomes included sensory organization test (SOT), Parkinson's Disease Questionnaire (PDQ39), fall efficacy scale (FES-I), and timed up and go test (TUG). All outcomes were assessed at baseline, after training, and at 1-month follow-up. Results. The VRWii group showed greater improvement in obstacle crossing velocity, crossing stride length, dynamic balance, SOT, TUG, FES-I, and PDQ39 than the control group. VRWii training also resulted in greater improvement in movement velocity of limits-of-stability test than TE training. Conclusions. VRWii training significantly improved obstacle crossing performance and dynamic balance, supporting implementation of VRWii training in participants with PD. © American Society of Neurorehabilitation.

Chien C.-Y.,Mackay Memorial HospitalTaipei | Chien C.-Y.,Mackay Medical College | Chien C.-Y.,Nursing and Management CollegeTaipei | Liu C.-C.,Mackay Medical College | And 19 more authors.
PLoS ONE | Year: 2015

Background Carotid artery remodeling is known to be associated with a variety of cardiovascular diseases. However, there is limited information regarding gender differences in carotid remodeling. We sought to investigate the associations among blood pressure (BP), carotid artery remodeling and cardiac geometries, and further explore gender differences. Materials and Methods In a large cohort of asymptomatic adults undergoing routine health screening with repeated observations, we related measures of carotid artery diameter (CCAD) to various BP components, cardiac geometries and blood N-terminal pro-brain natriuretic peptide (NT-proBNP) level, both from baseline cross-sectional and longitudinal dataset using generalized estimating equations (GEE). Results A total of 2,914 person-visits (baseline: n=998, mean age: 47 ± 8.9 years, 34% female) were studied (median: 6 ± 1.73 years follow up). We observed that CCAD was larger in men (p<0.01) and positively related to baseline age or all blood pressure components (including systolic BP [SBP], diastolic BP [DBP] and pulse pressure [PP], all p<0.01) even after accounting for clinical covariates, which did not change significantly at follow up (repeat-visit longitudinal GEE models). At baseline, per each increased unit of CCAD was associated with elevated LV mass index (β-coef: 6.72, with odds ratio [OR]: 1.47, 95% CI: 1.06 to 2.07 for ventricular hypertrophy; AUROC: 0.65, CCAD cut-off: 7.25mm) and NT-proBNP (β-coef: 5.35, OR: 4.22, 95% CI: 1.42 to 12.6 for >=300pg/mL; AUROC: 0.79, CCAD cut-off: 7.95mm, all p<0.05), which remained significant in multi-variate and longitudinal models. There was a prominent sex interaction (p for interaction with age and systolic BP: 0.004 and 0.028 respectively), where the longitudinal associations of age and systolic BP with increasing CCAD as more pronounced in women than men. Conclusion These data demonstrated that carotid artery remodeling may parallel subclinical biomarker of cardiac dysfunction, and further showed greater effects of aging and higher blood pressure on such remodeling process in women than men. Further study is warranted to understand how this predisposition of elderly hypertensive women to vascular remodeling may play a role in clinical settings. © 2015 Chien et al.

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