Cheuk-Kwan Sun

E-Da Hospital, Kao-hsiung-shih, Kaohsiung, Taiwan

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Publications (130)346.27 Total impact

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    ABSTRACT: Impact of early bone marrow-derived mesenchymal stem cell (BMDMSC) implantation on left ventricular (LV) function after AMI was studied.Twelve mini-pigs were equally divided into placebo (AMI through left coronary artery ligation) and cell-treated groups [BMDMSCs (3.0 × 10(7)) implanted into infarct area (IA)] with myocardium harvested by post-AMI day 90. Six healthy animals served as controls.On post-AMI day 90, magnetic resonance imaging showed a lower LV ejection fraction but higher LV dimensions in the placebo group (P < 0.003) that also had increased IAs but reduced wall thickness (P < 0.005). Pro-apoptotic gene expressions (Bax, caspase-3) and apoptotic nucleus number in IAs and peri-IAs were highest in the placebo group (P < 0.001). Inflammatory biomarker expressions (MMP-9, oxidized protein, CD40+ cells) were highest, whereas those of angiogenesis (VEGF, CD31+ cells, SDF-1α, CXCR4) and myocardium-preservation (connexin43, troponin-I, cytochrome-C) were lowest in the placebo group (P < 0.01).BMDMSC implantation preserved LV function and alleviated remodeling at post-AMI day 90.
    International heart journal. 06/2014;
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    ABSTRACT: This study investigated the pro-fibrogenic role of high mobility group box 1 (HMGB1) peptides in liver fibrogenesis. An animal model of carbon tetrachloride (CCl4)-induced liver fibrosis was used to examine the serum HMGB1 levels and its intrahepatic distribution. The increased serum HMGB1 levels were positively correlated with elevation of transforming growth factor-β1 (TGF-β1) and collagen deposition during fibrogenesis. The cytoplasmic distribution of HMGB1 was noted in the parenchymal hepatocytes of fibrotic livers. In vitro studies confirmed that exposure to hydrogen peroxide and CCl4 induced an intracellular mobilization and extracellular release of nuclear HMGB1 peptides in clone-9 and primary hepatocytes, respectively. An uptake of exogenous HMGB1 by hepatic stellate cells (HSCs) T6 cells indicated a possible paracrine action of hepatocytes on HSCs. Moreover, HMGB1 dose-dependently stimulated HSC proliferation, up-regulated de novo synthesis of collagen type I and α-smooth muscle actin (α-SMA), and triggered Smad2 phosphorylation and its nuclear translocation through a TGF-β1-independent mechanism. Blockade with neutralizing antibodies and gene silencing demonstrated the involvement of the receptor for advanced glycation end-products (RAGE), but not toll-like receptor 4, in cellular uptake of HMGB1 and the HMGB1-mediated Smad2 and ERK1/2 phosphorylation as well as α-SMA up-regulation in HSC-T6 cells. Furthermore, anti-RAGE treatment significantly ameliorated CCl4-induced liver fibrosis. In conclusion, the nuclear HMGB1 peptides released from parenchymal hepatocytes during liver injuries may directly activate HSCs through stimulating HSC proliferation and transformation, eventually leading to the fibrotic changes of livers. Blockade of HMGB1/RAGE signaling cascade may constitute a therapeutic strategy for treatment of liver fibrosis.
    Biochimica et biophysica acta. 06/2014;
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    ABSTRACT: This study tested whether adipose-derived mesenchymal stem cells (ADMSC) embedded in platelet-rich fibrin (PRF) scaffold is superior to direct ADMSC implantation in improving left ventricular (LV) performance and reducing LV remodeling in a rat acute myocardial infarction (AMI) model of left anterior descending coronary artery (LAD) ligation. Twenty-eight male adult Sprague Dawley rats equally divided into group 1 [sham control], group 2 (AMI only), group 3 (AMI+direct ADMSC implantation), and group 4 (AMI+PRF-embedded autologous ADMSC) were sacrificed on day 42 after AMI. LV systolic and diastolic dimensions and volumes, and infarct/fibrotic areas were highest in group 2, lowest in group 1 and significantly higher in group 3 than in group 4, whereas LV performance and LV fractional shortening exhibited a reversed pattern (p<0.005). Protein expressions of inflammation (oxidative stress, IL-1β, MMP-9), apoptosis (mitochondrial Bax, cleaved PARP), fibrosis (Smad3, TGF-β), and pressure-overload biomarkers (BNP, MHC-β) displayed a pattern similar to that of LV dimensions, whereas anti-inflammatory (IL-10), anti-apoptotic (Bcl-2), and anti-fibrotic (Smad1/5, BMP-2) indices showed a pattern similar to that of LV performance among the four groups (all p<0.05). Angiogenesis biomarkers at protein (CXCR4, SDF-1α, VEGF), cellular (CD31+, CXCR4+, SDF-1α+), and immunohistochemical (small vessels) levels, and cardiac stem cell markers (C-kit+, Sca-1+) in infarct myocardium were highest in group 4, lowest in group 1, and significantly higher in group 3 than in group 2 (all p<0.005). PRF-embedded ADMSC is superior to direct ADMSC implantation in preserving LV function and attenuating LV remodeling.
    International journal of cardiology 03/2014; · 6.18 Impact Factor
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    ABSTRACT: Introduction to Computer Science (ICS), which is a compulsory theoretical course for freshmen of the electrical engineering (EE) department, lays the foundation for more advanced courses. Nevertheless, since ICS covers a wide variety of concepts that are difficult to completely comprehend, incomplete understanding and a loss of learning incentive are possible problems. The aim of implementing hands-on practice (HOP) activities was to prepare the students for the actual hardware manipulation in the field of EE and also to enhance their performance in the future advanced practice courses. Through organizing optional evening hands-on practice (HOP) activities, this study investigated whether the first-year college students who participated in HOP would exhibit a better understanding in ICS compared to those who did not. The enrollment in HOP was optional in which the performance did not affect the score in the ICS course. The results showed that HOP participants not only had significantly higher academic scores (p < 0.05), but were also less stressed toward the ICS course (p < 0.05) than the non-participants. The former also showed increased interest in accepting challenges (e.g. Two HOP participants later entered the National Microcomputer Design Competition and were awarded the third prize). In conclusion, the introduction of optional HOP for freshmen of electrical engineering not only alleviated the stress that they face in response to the ICS course, but also improved the students' academic performance and class attendance rate as well as raising their interest and boosting their confidence in further challenges in the field of electrical engineering.
    Computers & Education. 01/2014; 70:1–8.
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    ABSTRACT: This study investigates the therapeutic potential of intracoronary tacrolimus against acute myocardial infarction (AMI) in minipigs with serial cardiac magnetic resonance (CMR) and changes at histological and protein levels. Twelve minipigs subjected to permanent left anterior descending artery ligation were randomized as tac-treated group (n = 6, with intracoronary tacrolimus treatment) and controls (n = 6). CMR with cine and late gadolinium enhancement (LGE) studies were performed on postoperative days 2, 5, and 21. There were no significant differences in left ventricular function (LVF), contractility, and LGE between the two groups on day 2. On day 5, the tac-treated group showed a significantly higher ejection fraction, smaller infarct, and lower day-5/day-2 infarct ratio than controls. On day 21, the controls demonstrated further deterioration of LVF and infarct. Contrastingly, the tac-treated animals demonstrated preservation of LVF, contractility, significantly smaller infarct, and lower day-21/day-2 infarct ratios compared with those on day 5 and controls. The in vivo CMR results were correlated with in vitro findings on histology, immunostaining, and Western blotting which revealed significantly less fibrosis, higher vascularities, less CD68+ and CD40+ inflammatory cells, lower expressions of inflammatory (MMP-9, NF-κB, and TNF-α), and apoptotic (Bax, Caspase-3, c-PARP) biomarkers, respectively, in tac-treated AMI minipigs than controls.
    BioMed Research International 01/2014; 2014:524078. · 2.88 Impact Factor
  • Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 01/2014; · 4.91 Impact Factor
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    ABSTRACT: Celecoxib, a COX-2 inhibitor and non-steroidal anti-inflammatory drug, can prevent several types of cancer, including hepatocellular carcinoma (HCC). Here we show that celecoxib suppressed the self-renewal and drug-pumping functions in HCC cells. Besides, celecoxib depleted CD44+/CD133+ hepatic cancer stem cells (hCSC). Prostaglandin E2 (PGE2) and CD133 overexpression did not reverse the celecoxib-induced depletion of hCSC. Also, celecoxib inhibited progression of rat Novikoff hepatoma. Moreover, a 60-day celecoxib program increased the survival rate of rats with hepatoma. Histological analysis revealed that celecoxib therapy reduced the abundance of CD44+/CD133+ hCSCs in hepatoma tissues. Besides, the hCSCs depletion was associated with elevated apoptosis and blunted proliferation and angiogenesis in hepatoma. Celecoxib therapy activated peroxisome proliferator-activated receptor γ (PPARγ) and up-regulated PTEN, thereby inhibiting Akt and disrupting hCSC expansion. PTEN gene delivery by adenovirus reduced CD44/CD133 expression in vitro and hepatoma formation in vivo. This study suggests that celecoxib suppresses cancer stemness and progression of HCC via activation of PPARγ/PTEN signaling.
    Oncotarget 12/2013; · 6.64 Impact Factor
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    ABSTRACT: This study tested the hypothesis that tissue plasminogen activator (tPA) is crucial for regulating endothelial progenitor cell (EPC) mobilization from bone marrow to circulation in murine critical limb ischemia (CLI) by ligating the left femoral artery. Wild-type (C57BL/6) (n=40) mice were equally divided into group 1A (sham control), group 2A (CLI), group 3A [control-tPA (4.0mg/kg)] and group 4A [CLI-tPA (intravenously at 3h after CLI)]. Similarly, tPA knock-out (tPA(-/-)) mice (n=40) were equally divided into group 1B (sham control), group 2B (CLI), group 3B [control-tPA (4.0mg/kg)], and group 4B (CLI-tPA). The circulating levels of EPCs (C-kit/CD31+, Sca-1/KDR+, CXCR4/CD34+) were lower in groups 1B and 2B than in groups 1A and 2A, respectively (all p<0.01), and were reversed after tPA treatment (3B vs. 3A or 4B vs. 4A, p>0.05) at 6h and 18h post-CLI. Levels of these biomarkers decreased again 14days after CLI in tPA(-/-) mice compared to those in wild-type between the respective groups (all p<0.01). Laser Doppler flowmetry showed a higher ratio of ischemic-to-normal blood flow in 2A than in 2B and in 4A than in 4B by day 14 after CLI (all p<0.05). Angiogenesis at protein (CXCR4, SDF-1α, VEGF) and cellular (CXCR4+, SDF-1α+, and CD31+ cells) levels was highest in animals with CLI-tPA, significantly higher in mice with CLI only than in sham controls for both wild-type and tPA(-/-) mice (p<0.01). tPA played an essential role in augmenting circulating EPCs, angiogenesis, and blood flow in the ischemic limb in a murine model.
    International journal of cardiology 11/2013; · 6.18 Impact Factor
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    ABSTRACT: This study tested the hypothesis that exendin-4 and sitagliptin can effectively protect kidney from acute ischemia-reperfusion (IR) injury. Adult SD-rats (n = 48) equally divided into group 1 (sham control), group 2 (IR injury), group 3 [IR + sitagliptin 600 mg/kg at post-IR 1, 24, 48 hr)], and group 4 [IR + exendin-4 10 mum/kg at 1 hr after procedure] were sacrificed after 24 and 72 hrs (n = 6 at each time from each group) following clamping of bilateral renal pedicles for 60 minutes (groups 2--4). Serum creatinine level and urine protein to creatinine ratio were highest in group 2 and lowest in group 1 (all p < 0.001) without notable differences between groups 3 and 4. Kidney injury score, expressions of inflammatory biomarkers at mRNA (MMP-9, TNF-alpha, IL-1beta, PAI-1), protein (TNF-alpha, NF-kappaB and VCAM-1), and cellular (CD68+) levels in injured kidneys at 24 and 72 hr showed an identical pattern compared to that of creatinine level in all groups (all p < 0.0001). Expressions of oxidized protein, reactive oxygen species (NOX-1, NOX-2), apoptosis (Bax, caspase-3 and PARP), and DNA damage marker (gammaH2AX+) of IR kidney at 24 and 72 hrs exhibited a pattern similar to that of inflammatory mediators among all groups (all p < 0.01). Renal expression of glucagon-like peptide-1 receptor, and anti-oxidant biomarkers at cellular (GPx, GR) and protein (NQO-1, HO-1, GPx) levels at 24 and 72 hr were lowest in group 1, significantly lower in group 2 than in groups 3 and 4 (all p < 0.01). Exendin-4 and sitagliptin provided significant protection for the kidneys against acute IR injury.
    Journal of Translational Medicine 10/2013; 11(1):270. · 3.46 Impact Factor
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    ABSTRACT: This study tested the hypothesis that combined therapy with nicorandil and colchicine is superior to either alone in attenuating monocrotaline (MCT)-induced rat pulmonary arterial hypertension (PAH). Adult male Sprague-Dawley rats (n=50) were equally randomized into group 1 (sham control), group 2 [MCT (60 mg/kg i.p.)], group 3 [MCT-Nicorandil (5.0 mg/kg/day)], group 4 [MCT-Colchicine (1.0 mg/kg/day)], and group 5 (MCT-Nicorandil-Colchicine). Drugs were given on day 5. All animals were sacrificed on day 90 after MCT administration. Right ventricular systolic blood pressure (RVSBP) and RV weight were increased in group 2 compared to group 1, reduced in groups 3 and 4 compared to group 2, and further reduced in group 5, whereas arterial-oxygen saturation showed an opposite pattern (all p<0.001). Pulmonary damage severity (thickened alveolar septum and pulmonary arteriolar wall, decreased alveolar-sac numbers), number of CD3+ cells, and protein expressions of inflammatory (MMP-9, NF-κB, VCAM-1, angiotensin II-receptor), apoptotic (Bax, caspase 3, cleaved PARP), and fibrotic (TGF-β, Smad3) biomarkers showed an identical pattern compared to that of RVSBP, whereas pulmonary expressions of anti-apoptotic (Bcl-2) and anti-fibrotic (BMP-2, Smad1/5) biomarkers displayed a reverse pattern (all p<0.01). The protein expressions of RV damage markers (BNP, caspase 3) were increased, whereas expression of biomarker for RV functional preservation (Cx43) was reduced in group 2 compared with group 1, elevated in groups 3 and 4 compared to group 2, and further increased in group 5 (all p<0.01). Combined therapy with nicorandil and colchicine is superior to either alone in attenuating MCT-induced PAH in rats.
    European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 08/2013; · 2.61 Impact Factor
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    ABSTRACT: Using frequency and rank order statistics (FROS), this study analyzed the fluctuations in arterial waveform amplitudes recorded from an air pressure sensing system before and after reactive hyperemia (RH) induction by temporary blood flow occlusion to evaluate the vascular endothelial function of aged and diabetic subjects. The modified probability-weighted distance (PWD) calculated from the FROS was compared with the dilatation index (DI) to evaluate its validity and sensitivity in the assessment of vascular endothelial function. The results showed that the PWD can provide a quantitative determination of the structural changes in the arterial pressure signals associated with regulation of vascular tone and blood pressure by intact vascular endothelium after the application of occlusion stress. Our study suggests that the use of FROS is a reliable noninvasive approach to the assessment of vascular endothelial degeneration in aging and diabetes.
    Physica A: Statistical Mechanics and its Applications 08/2013; 392(15):3122–3131. · 1.68 Impact Factor
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    ABSTRACT: We tested the hypothesis that sitagliptin is capable of increasing blood flow in the rat critical limb ischemia (CLI) model by enhancement of angiogenesis. Adipose tissue from adult-male Fischer 344 rats (n = 6) were cultured in endothelial progenitor cell culture medium for 14 d with (25 μmol/L) or without sitagliptin. CLI was induced by ligation of the left femoral artery. Rats (n = 32) were equally separated into four groups: untreated controls (group 1), sitagliptin (4 mg/kg per day; group 2), CLI (group 3) and CLI with sitagliptin (group 4). In vitro, 7 and 14 d after cell culture, endothelial progenitor cell biomarkers assessed by flow cytometry (Sca-1/CD31+, CXCR4+, c-kit+ and CD34+ cells) and Western blot (vascular endothelial growth factor, CXCR4 and stromal-derived factor [SDF]-1α) were remarkably higher in group 4 than in the other groups (all P < 0.01). In vivo, 2 and 14 d after the CLI procedure, circulating angiogenic cell (Sca-1/CD31+, Sca-1+ and CD31+) numbers were significantly higher in group 4 than in the other groups (all P < 0.001). Additionally, the messenger RNA and protein expression of angiogenic biomarkers (CXCR4, SDF-1α and vascular endothelial growth factor), immunofluorescent staining of angiogenic cells (CXCR4+, SDF-1α+, CD31+, von Willebrand factor + cells) and immunohistochemical staining of small vessel numbers in the ischemic area were significantly higher in group 4 than in the other groups (all P < 0.01). Furthermore, laser Doppler showed that the ratio of ischemic/normal blood flow was remarkably higher group 4 than in group 3 by days 14 and 28 after the CLI procedure (all P < 0.01). Sitagliptin therapy enhances circulating angiogenic cell numbers, angiogenesis and blood flow in the CLI area.
    Cytotherapy 07/2013; · 3.06 Impact Factor
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    ABSTRACT: INTRODUCTION: This study tested the hypothesis that cyclosporine (CsA)-supported syngeneic adipose-derived mesenchymal stem cell (ADMSC) therapy offered superior attenuation of acute ischemia-reperfusion (IR) kidney injury than either therapy alone. METHODS: Adult Sprage-Dawley (SD) rats (n=40) were equally divided into group 1 (sham controls), group 2 (IR injury), group 3 [IR + CsA (20 mg/kg at 1 and 24 hr after procedure)], group 4 [syngeneic ADMSC (1.2x106) at 1, 6 and 24 h after procedure], and group 5 (IR + CsA-ADMSC). RESULTS: By 72 h after IR procedure, creatinine level and the ratio of urine protein to creatinine were highest in group 2 and lowest in group 1, significantly higher in groups 3 and 4 than in group 5 (all P<0.05 for inter-group comparisons), but they showed no differences between groups 3 and 4 (P>0.05). The inflammatory biomarkers at mRNA (matrix metalloproteinase-9 (MMP-9), regulated upon activation normal T cell expressed and presumably secreted (RANTES), tumor necrosis factor-alpha (TNF-alpha)), protein (TNF-alpha, nuclear factor kappa-B (NF-kappaB), intercellular adhesion molecule-1 (ICAM-1), platelet-derived growth factor (PDGF)), and cellular (CD68+) levels of IR kidney showed a similar pattern compared to that of creatinine in all groups (all P<0.05 for inter-group comparisons). The protein expressions of oxidative stress (oxidized protein), reactive oxygen species (ROS) (NADPH oxidases NOX-1, NOX-2), apoptosis (Bcl-2--associated X protein (Bax), caspase-3 and poly (ADP-ribose) polymerase (PARP)) and DNA damage markers (phosphorylated H2A histone family member X (gammaH2AX+), proliferating cell nuclear antigen (PCNA+) cells) exhibited a pattern similar to that of inflammatory mediators amongst all groups (all P<0.05 for inter-group comparisons). Expressions of anti-oxidant biomarkers at cellular (glutathione peroxidase (GPx), glutathione reductase (GR), heme oxygenase-1 (HO-1)) and protein (NADPH dehydrogenase (quinone)-1 (NQO-1), HO-1, endothelial nitric oxide synthase (eNOS)) levels, and endothelial progenitor cell markers (C-X-C chemokine receptor type 4 (CXCR4+), stromal cell-derived factor-1alpha (SDF-1alpha+)) were lowest in groups 1 and 2, higher in groups 3 and 4, and highest in group 5 (all P<0.05 for inter-group comparisons). CONCLUSIONS: Combination therapy using cyclosporine-plus-ADMSCs offers improved protection against acute IR kidney injury.
    Stem Cell Research & Therapy 05/2013; 4(3):62. · 3.65 Impact Factor
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    ABSTRACT: Statin therapy is known to down-regulate inflammatory activities in atheromatous tissues of animals. The aims of this study were to examine the regulatory role of interleukin-18 (IL-18) in the connexin 43 (Cx43) and the proliferation of cultured aortic smooth muscle cells (SMCs) as well as to elucidate the underlying therapeutic mechanism of simvastatin. Vytorin therapy significantly alleviated high-cholesterol diet-induced hypercholesterolemia, suppressed neointimal hyperplasia, macrophage infiltration, and Cx43 and IL-18 expression in rabbit aortic walls. In vitro study using an aortic SMC line showed that IL-18 up-regulated constitutive Cx43 expression and potentiated tumor necrosis factor-α (TNF-α)-triggered Akt and MAPK signaling pathways. Simvastatin treatment alone reduced constitutive Cx43 levels and prevented the TNF-α-induced IL-18 up-regulation. Mechanistic investigation using kinase-specific inhibitors showed that simvastatin pretreatment attenuated TNF-α-elicited Akt and ERK1/2 phosphorylation, whereas PI3K and all MAPK activities were also implied in the additive effect of TNF-α and IL-18 on Cx43 up-regulation. Proliferation assay indicated that IL-18 stimulated SMC proliferation and synergized the TNF-α-stimulated cell proliferation. Likewise, simvastatin treatment suppressed the SMC over-proliferation induced not only by TNF-α alone, but also by simultaneous treatment with TNF-α and IL-18. The suppression of simvastatin in SMC proliferation was not mediated through mitochondrial related pro-apoptogenesis under both scenarios. In conclusion, simvastatin attenuates the additive effects of TNF-α and IL-18 on Cx43 up-regulation and over-proliferation of aortic SMCs, mainly through the blockade of Akt signaling pathway. These findings may fortify the rationale underlying the atheroprotective mechanism of statin therapy.
    Cytokine 04/2013; · 2.52 Impact Factor
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    ABSTRACT: It is known that aging and type 2 diabetes mellitus contribute to atherosclerosis and autonomic dysfunction. By using the air pressure sensing system (APSS), peak-peak intervals (PPIs) of wrist arterial waveforms from baseline and reactive hyperemia (RH) were obtained. Through frequency domain analysis of heart rate variability (HRV) and non-linear Poincaré method, the HRV of healthy young individuals (Group 1, n=25), healthy upper middle-aged individuals (Group 2, n=22), and patients with type 2 diabetes (Group 3, n=28) were assessed. By using the standard deviation (SD) of the instantaneous PPI variability (SD1)/the SD of the long PPI variability (SD2) ratio (SSR), PPIs of the same individuals before and after RH induction were compared. Reduced SSR1-10 was noted only in patients with diabetes. Moreover, a significient correlation between SSR1-10 and endothelial function was observed in all subjects (r=0.290, p=0.033) after RH. However, no correlation with low-frequency to high-frequency power ratio (LHR) was noted before and after RH. In conclusion, according to our results, campared to the baseline, there were more significant changes of SSR1-10 after RH in patients with diabetes; and, a significient correlation between SSR1-10 and endothelial function at the moment of RH was noted.
    Journal of Theoretical Biology 04/2013; · 2.35 Impact Factor
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    ABSTRACT: INTRODUCTION: We hypothesized that dipeptidyl peptidase-IV (DPP4) may impair angiogenesis, endothelial function, and the circulating number of endothelial progenitor cells (EPC) in a model of critical limb ischemia (CLI) through ligating the left femoral artery using DPP4-deficient rats. METHODS: Adult male DPP4-deficient (DPP4D) rats (n = 18) were equally divided into CLI only (DPP4D-CLI) and CLI treated by granulocyte colony-stimulating factor (GCSF) (DPP4D-CLI-GCSF). For comparison, age-matched wild-type (WT) Fischer 344 rats (n = 18) were randomized into two groups receiving identical treatment compared to their DPP4-deficient counterparts and labeled as WT-CLI (n = 9) and WT-CLI-GCSF (n = 9), respectively. RESULTS: The circulating number of EPCs (CD31+, CD34+, CD133, C-kit+) was significantly lower in DPP4-deficient than in WT rats on post-CLI days 1 and 4 (all P <0.01). The ratio of ischemia/normal blood flow was remarkably lower in DPP4D-CLI-GCSF rats than in WT-CLI-GCSF animals on post-CLI Day 14 (all P <0.01). Protein expressions of pro-angiogenic factors (endothelial nitric oxide synthase (eNOS), CXCR4, SDF-1alpha, vascular endothelial growth factor (VEGF)) were remarkably higher in WT-CLI than in DPP4D-CLI rats, and higher in WT-CLI-GCSF than in DPP4D-CLI-GCSF animals (all P <0.01). Moreover, the numbers of small vessel in the ischemic area were substantially higher in WT-CLI-GCSF than in DPP4D-CLI-GCSF rats (P <0.001). Furthermore, vasorelaxation and nitric oxide production of the normal femoral artery were significantly reduced in DPP4-deficient than in WT Fischer rats (all P <0.01). CONCLUSIONS: Contrary to our hypothesis, DPP4-deficient rats were inferior to age-matched WT Fischer rats in terms of angiogenesis, endothelial function, circulating EPC number and response to GCSF, suggesting a positive role of DPP4 in maintaining vascular function and tissue perfusion in this experimental setting.
    Stem Cell Research & Therapy 03/2013; 4(2):31. · 3.65 Impact Factor
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    ABSTRACT: Abstract Despite the importance of translational medicine in cardiovascular research, rat vascular endothelial function and sympathetic activity assessment remains challenging. This study consisted of two parts: part A examined the consistency of reactive hyperemia-elicited dilatation index (DI) before (DIOriginal) and after (DIEEMD) ensemble empirical mode decomposition (EEMD) using Wistar-Kyoto (WKY) rats (n=7). Part B compared the endothelial function and heart rate variability of normal WKY rats (group 1, n=9) with those of spontaneously hypertensive rats (group 2, n=9) at two time points of development. The SD1/SD2 ratio (SSR) was obtained from Poincaré plot analysis to evaluate sympathetic activities. Using a Bland-Altman plot, part A of the study demonstrated a lower agreement of DIOriginal than that of DIEEMD. In part B, despite no significant difference in DIEEMD between the two groups at age 10 weeks, DIEEMD was higher in group 1 (2.25±0.63 vs. 1.43±0.41 for groups 1 and 2, respectively, p=0.004) at 20 weeks. Although no notable change in SSR existed in group 1 between the two time points, a significant difference existed in group 2 (p<0.001). In conclusion, using algorithms of Poincaré plot analysis and EEMD, the impact of age and hypertension on rat vascular endothelial function and heart rate variability can be reliably assessed.
    Biomedizinische Technik/Biomedical Engineering 02/2013; · 1.16 Impact Factor
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    ABSTRACT: We hypothesized that the long-term therapeutic effect of combined sildenafil and bone marrow-derived endothelial progenitor cells (BMDEPCs) on monocrotaline (MCT)-induced rat pulmonary arterial hypertension (PAH) is superior to either treatment alone. Male Sprague-Dawley rats (n = 40) were equally divided into normal controls, MCT (65 mg/kg, subcutaneously) only, MCT + sildenafil (25 mg/kg/day, orally), MCT + BMDEPCs (2.0 × 10(6) autologous cells, intravenously) and MCT + sildenafil+ BMDEPCs. BMDEPCs and sildenafil were given on day 21 after MCT administration. Animals were sacrificed by day 90 after MCT administration. The apoptotic (caspase 3, Bax) and inflammatory (tumor necrosis factor-α, matrix metalloproteinase-9) biomarkers in right ventricle and lung and pulmonary expressions of fibrotic biomarkers (transforming growth factor-β, p-Smad3) and connexin 43 protein were lower in monotherapy groups (i.e., MCT + sildenafil and MCT + BMDEPCs) and further decreased in normal controls and combined treatment groups (i.e., MCT + sildenafil + BMDEPCs) compared with untreated animals (i.e., MCT only) (all P < 0.01). Expressions of anti-fibrotic biomarkers (bone morphogenetic protein-2, p-Smad1/5) and numbers of alveolar sacs and arterioles in lung were higher in monotherapy groups and further increased in normal controls and combined treatment groups compared with untreated animals (all P < 0.005). In right ventricle, connexin 43 and α-myosin heavy chain (MHC) expressions were higher in the monotherapy groups and further elevated in normal controls and combined treatment groups compared with untreated animals, whereas β-MHC exhibited the opposite pattern (all P < 0.01). Right ventricular systolic pressure and weight were lower in the monotherapy animals and further reduced in normal controls and combined treatment groups compared with untreated animals (all P < 0.0001). Combined therapy with BMDEPCs and sildenafil was superior to either treatment alone in attenuating rodent MCT-induced PAH.
    Cytotherapy 02/2013; 15(2):209-23. · 3.06 Impact Factor
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    ABSTRACT: BACKGROUND: The Objective Structured Clinical Examination (OSCE) has been widely applied as a high-stakes examination for assessing physicians' clinical competency. In 1992, OSCE was first introduced in Taiwan, and the authorities announced that passing the OSCE would be a prerequisite for step-2 medical licensure examination in 2013. This study aimed to investigate the impacts of the announced national OSCE policy on implementation of OSCE at the institutional level. Further, the readiness and the recognition of barriers toward a high-stakes examination were explored. METHODS: In 2007 and 2010, the year before and after the announcement of high-stakes OSCE policy in 2008, respectively, questionnaires on the status of OSCE implementation were distributed to all hospitals with active OSCE programs in Taiwan. Information on OSCE facilities, equipment, station length, number of administrations per year, and the recognition of barriers to the success of implementing an OSCE were collected. The missing data were completed by telephone interviews. The OSCE format, administration, and facilities before and after the announcement of the nationwide OSCE policy were compared. RESULTS: The data were collected from 17 hospitals in 2007 and 21 in 2010. Comparing the OSCE formats between 2007 and 2010, the number of stations increased and the station length decreased. The designated space and the equipment for OSCE were also found to have been improved. As for the awareness of OSCE implementation barriers, the hospital representatives concerned mostly about the availability and quality of standardized patients in 2007, as well as space and facilities in 2010. CONCLUSIONS: The results of this study underscored an overall increase in the number of OSCE hospitals and changes in facilities and formats. While recruitment and training of standardized patients were the major concerns before the official disclosure of the policy, space and facilities became the focus of attention after the announcement. The study results highlighted the influence of government policy on different aspects of OSCE implementation in Taiwanese training institutes that showed high level of support as reflected in the improved hardware and the change in OSCE format to serve the summative purpose.
    BMC Medical Education 01/2013; 13(1):8. · 1.41 Impact Factor
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    ABSTRACT: Although previous studies have shown the successful use of pressure-induced reactive hyperemia as a tool for the assessment of endothelial function, its sensitivity remains questionable. This study aims to investigate the feasibility and sensitivity of a novel multiscale entropy index (MEI) in detecting subtle vascular abnormalities in healthy and diabetic subjects. Basic anthropometric and hemodynamic parameters, serum lipid profiles, and glycosylated hemoglobin levels were recorded. Arterial pulse wave signals were acquired from the wrist with an air pressure sensing system (APSS), followed by MEI and dilatation index (DI) analyses. MEI succeeded in detecting significant differences among the four groups of subjects: healthy young individuals, healthy middle-aged or elderly individuals, well-controlled diabetic individuals, and poorly controlled diabetic individuals. A reduction in multiscale entropy reflected age- and diabetes-related vascular changes and may serve as a more sensitive indicator of subtle vascular abnormalities compared with DI in the setting of diabetes.
    Computational and Mathematical Methods in Medicine 01/2013; 2013:645702. · 0.79 Impact Factor

Publication Stats

729 Citations
346.27 Total Impact Points

Institutions

  • 2014
    • E-Da Hospital
      Kao-hsiung-shih, Kaohsiung, Taiwan
  • 2011–2014
    • I-Shou University
      Kao-hsiung-shih, Kaohsiung, Taiwan
  • 2010–2013
    • National Pingtung University of Science and Technology
      • Department of Life Science
      P’ing-tung-chieh, Taiwan, Taiwan
  • 2007–2013
    • Chang Gung Memorial Hospital
      • • Division of Cardiology
      • • Division of General Surgery
      Taipei, Taipei, Taiwan
  • 2010–2012
    • National Dong Hwa University
      • Department of Electrical Engineering
      Hualian, Taiwan, Taiwan
  • 2009–2010
    • National Sun Yat-sen University
      • Department of Biological Science
      Kaohsiung, Kaohsiung, Taiwan
    • Kaohsiung Medical University
      • College of Medicine
      Kaohsiung, Kaohsiung, Taiwan
    • Chang Gung University
      • Department of Internal Medicine
      Hsin-chu-hsien, Taiwan, Taiwan