Hon-Kan Yip

Chang Gung University, Hsin-chu-hsien, Taiwan, Taiwan

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Publications (240)710.22 Total impact

  • Critical Care 12/2015; 19(1). · 5.04 Impact Factor
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    ABSTRACT: Sitagliptin, a new antidiabetic drug that inhibits dipeptidyl peptidase (DPP)-4 enzyme activity, has been reported to possess neuroprotective property. We tested the protective effects of sitagliptin against chronic cerebral hypoperfusion (CHP) in mice after bilateral carotid artery stenosis (BCAS). Thirty C57BL/6 mice were divided into three groups: sham control (n = 10), CHP (n = 10) and CHP-sitagliptin (orally 600 mg/kg/day) (n = 10). Working memory was assessed with novel-object recognition test. MRI was performed at day 0 and day 90 after BCAS procedure prior to sacrifice. Immunohistochemical (IHC) staining showed significantly enhanced white matter lesions, microglia activation and astrocytosis of white matter in CHP group than in sham control, but the changes were significantly suppressed after sitagliptin treatment (all P < 0.01). The mRNA expressions of inflammatory [tumour necrosis factor-alpha (TNF-α), monocyte chemoattractant protein (MCP-1) and matrix metalloproteinase (MMP)-2] and apoptotic (Bax) biomarkers showed an identical pattern, whereas the anti-inflammatory (interleukin, IL-10) and antiapoptotic (Bcl-2) biomarkers showed an opposite pattern compared with that of IHC among all groups (all P < 0.01). The protein expressions of oxidative stress (NOX-I, NOX-II, nitrotyrosin, oxidized protein), inflammatory [nuclear factor-kappa B (NF-κB), TNF-α and MMP-2], apoptotic [mitochondrial Bax, cleaved poly(ADP-ribose) polymerase (PARP)] and DNA-damage (γ-H2AX) markers showed an identical pattern, while expression pattern of antiapoptotic marker (Bcl-2) was opposite to that of IHC (all P < 0.01). Glycogen-like peptide-1 receptor protein expression progressively increased from sham control to CHP-sitagliptin (P < 0.01). The short-term working-memory loss and MRI/diffusion tensor imaging (DTI) showed a pattern identical to that of IHC in all groups (all P < 0.01). Sitagliptin protected against cognitive impairment and brain damage in a murine CHP model.
    Journal of hypertension. 02/2015;
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    ABSTRACT: Aim:Sitagliptin, an oral glucose-lowering agent, has been found to produce cardiovascular protection possibly via anti-inflammatory and anti-atherosclerotic activities of glucagon-like peptide-1 receptor (GLP-1). The aim of this study was to investigate whether sitagliptin protected the kidney function from acute ischemia-reperfusion (IR) injury in rats.Methods:Adult male SD rats were categorized into 4 groups: sham control, IR injury, IR+sitagliptin (300 mg/kg) and IR+sitagliptin (600 mg/kg). Acute renal IR injury of both kidneys was induced by clamping the renal pedicles for 1 h. The drug was orally administered at 1, 24 and 48 h after acute IR. Blood samples and 24-h urine were collected before and at 72 h after acute IR. Then the rats were sacrificed, and the kidneys were harvested for biochemical and immunohistochemical studies.Results:Acute IR procedure markedly increased serum levels of creatinine and BUN and the ratio of urine protein to creatinine. The kidney injury score, inflammatory biomarkers (MMP-9, TNF-α and NF-κB) levels and CD68+ cells in IR kidneys were considerably increased. The expression of oxidized protein, reactive oxygen species (NOX-1, NOX-2) and apoptosis proteins (Bax, caspase-3, PARP) in IR kidneys was also significantly upregulated. All these pathological changes were suppressed by sitagliptin in a dose-dependent manner. Furthermore, the serum GLP-1 level, and the expression of GLP-1 receptor, anti-oxidant biomarkers (HO-1 and NQO-1 cells, as well as SOD-1, NQO-1 and HO-1 proteins), and angiogenesis markers (SDF-1α+ and CXCR4+ cells) in IR kidneys were significantly increased, and further upregulated by sitagliptin.Conclusion:Sitagliptin dose-dependently protects rat kidneys from acute IR injury via upregulation of serum GLP-1 and GLP-1 receptor expression in kidneys.
    Acta Pharmacologica Sinica 12/2014; · 2.50 Impact Factor
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    ABSTRACT: Background We investigated whether attenuating dipeptidyl peptidase-IV (DPP4) enzyme activity protected rat heart from ischemia-reperfusion (IR) injury (40-min left anterior descending coronary artery ligation followed by 72 h reperfusion).Methods and resultsAdult male Fischer 344 rats (n¿=¿24) were equally divided into sham-control (WT-SC), WT-IR, and WT-IR-Sita (oral sitagliptin 400 mg/kg/day for 3 days) groups, whereas adult male DPP4-deficiency (DPP4D) rats (n¿=¿16) were equally divided into DPP4D-SC and DPP4D-IR groups. Animals were sacrificed at 72 h after reperfusion with collection of heart specimens. Infarct area (H&E), collagen deposition (Sirius-red stain), fibrotic area (Masson's trichrome), and fluorescent-ROS intensity (H2DCFDA-labeling myocardium) of left ventricle were significantly higher in WT-IR than those in other groups, significantly higher in WT-IR-Sita and DPP4D-IR groups than in WT-SC and DPP4D-SC groups (all p¿<¿0.001), but there was no difference between the latter two groups. Protein expressions of oxidative stress (oxidized protein), reactive oxygen species (NOX-1, NOX-2), inflammation (TNF-¿, NF-¿B, MMP-9, VCAM-1), apoptosis (mitochondrial Bax, cleaved caspase-3 and PARP), myocardial damage markers (cytosolic cytochrome-C, ¿-H2AX), and number of inflammatory cells (CD14+, CD68+, CD40+ cells) showed a pattern identical to that of histological changes among all groups (all p¿<¿0.005), whereas markers of anti-apoptosis (Bcl-2) and mitochondrial integrity (mitochondrial cytochrome-C) as well as left ventricular ejection fraction showed an opposite pattern (all p¿<¿0.001). Protein expressions of anti-oxidants (HO-1, NQO-1), angiogenesis factors (SDF-1¿, CXCR4), and glycogen-like-peptide-1-receptor were significantly higher inWT-IR-Sita and DPP4D-IR than those in other groups (all p¿<¿0.001).Conclusion Abrogation of DPP4 activity protects against myocardial IR injury and preserved heart function.
    Journal of translational medicine. 12/2014; 12(1):357.
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    ABSTRACT: Aim: Cardiac and renal diseases are common disorders that frequently coexist. We tested the hypothesis that the levels of circulating endothelial-derived apoptotic microparticles (EDA-MPs; CD31(+)CD42b(-)AN(-)V(+)) and platelet-derived apoptotic microparticles (PDA-MPs; CD31(+)CD42b(+)AN(-)V(+)) are useful biomarkers for predicting the presence of cardiorenal disease (CRD). Methods: A total of 68 patients with chronic kidney disease (CKD) and angina pectoris (CKD-AP) undergoing cardiac catheterization were prospectively enrolled into group 1, 10 patients with coronary artery disease (CAD) without CKD were enrolled into group 2 (CAD(+)CKD(-)) and 10 patients without CAD and CKD were enrolled into group 3 (CAD(-)CKD(-)). Results: The serum creatinine levels were significantly higher, whereas the estimated glomerular filtration rates (eGFRs) were significantly lower, in group 1 than in the other two groups (all p<0.02). The circulating levels of EDA-MPs and PDA-MPs did not differ between the patients with and without CKD (all p>0.2). However, the circulating levels of EDA-MPs and PDA-MPs were significantly higher in group 2 than in groups 1 and 3 (all p<0.03). In addition, differences were noted in the circulating EDA-MP and PDA-MP levels between groups 1 and 3, although without statistical significance (all p>0.09). Meanwhile, among the CKD patients, the subgroup analysis showed that the levels of MPs were significantly higher in those with CAD than in those without (all p=0.001), while a multivariate analysis demonstrated that CAD was the only factor independently predictive of high levels of circulating EDA-MPs and PDA-MPs (p=0.033). Conclusions: The link with increased circulating levels of MPs is more consistent in patients with CAD than in those with CKD.
    Journal of atherosclerosis and thrombosis 10/2014; · 2.77 Impact Factor
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    ABSTRACT: This study evaluated the feasibility, safety, and prognostic outcome in patients with significant unprotected left main coronary artery (ULMCA) disease undergoing stenting.
    PLoS ONE 10/2014; 9(10):e109281. · 3.53 Impact Factor
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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 07/2014; 2014:524078. · 2.71 Impact Factor
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    ABSTRACT: Background Ad hoc percutaneous coronary intervention (PCI) which performed immediately after diagnostic catheterization has become the most common way of coronary intervention. However, limited data is available on in-hospital and long-term outcome comparing ad hoc and staged chronic total occlusion (CTO) PCI. Our aim of the study was to figure the short-term and long-term outcome after ad hoc or staged CTO PCI. Methods This retrospective analysis included consecutive 512 patients underwent 561 CTO PCI procedures between January 2002 and December 2009. Patient basic demographics, lesion characteristics, interventional procedure, devices used and in-hospital outcomes were compared between ad hoc and staged CTO PCI groups. 3-year clinical outcomes included all-cause mortality, cardiac mortality, myocardial infarction (MI), the need for coronary artery bypass graft surgery (CABG), major adverse cardiac events (MACE) and target vessel revascularization (TVR) were compared. Time-to-event analyses were performed using Kaplan-Meier statistics. Results Four hundred and fifty-one patients (80.4%) were enrolled in ad hoc CTO PCI group. Final successful revascularization was higher in ad hoc CTO PCI group compared with staged CTO PCI group (82.9 vs. 77.3%, p = 0.17) without statistical significance. There was no significant difference between ad hoc CTO PCI and staged CTO PCI groups in in-hospital outcomes such as all-cause mortality, cardiac death, myocardial infarction, urgent bypass surgery, urgent PCI or complications. Patients with ad hoc CTO PCI had lower rate of all-cause mortality (6.2% vs. 6.5%, p = 0.89), the need for CABG (1.9% vs. 2.1%, p = 0.89) but higher rate of cardiac mortality (1.7% vs. 0.0%, p = 0.21), MI (1.0% vs. 0.0%, p = 0.34), MACE (24.1% vs. 17.5%, p = 0.19) and TVR (17.8% vs. 10.0%, p = 0.069) without statistical significance in 3-year clinical outcomes. Conclusion 3-year clinical outcomes compared with ad hoc CTO PCI and staged CTO PCI had insignificant differences between: all-cause mortality, cardiac mortality, MI, the need for CABG, MACE and TVR.
    IJC Heart & Vessels. 07/2014; 4.
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    ABSTRACT: Background. This study tested the hypothesis that circulating microparticles (MPs) are useful biomarkers for predicting one-year mortality in patients with end-stage non-small cell lung cancer (ES-NSCLC). Methods and Results. One hundred seven patients were prospectively enrolled into the study between April 2011 and February 2012, and each patient received regular follow-up after enrollment. Levels of four MPs in circulation, (1) platelet-derived activated MPs (PDAc-MPs), (2) platelet-derived apoptotic MPs (PDAp-MPs), (3) endothelial-derived activated MPs (EDAc-MPs), and (4) endothelial-derived apoptotic MPs (EDAp-MPs), were measured just after the patient was enrolled into the study using flow cytometry. Patients who survived for more than one year were categorized into group 1 (n = 56) (one-year survivors) and patients who survived less than one year were categorized into group 2 (n = 51) (one-year nonsurvivors). Male gender, incidence of liver metastasis, progression of disease after first-line treatment, poor performance status, and the Charlson comorbidity index were significantly higher in group 2 than in group 1 (all P < 0.05). Additionally, as measured by flow cytometry, only the circulating level of EDAc-MPs was found to be significantly higher in group 2 than in group 1 (P = 0.006). Multivariate analysis demonstrated that circulating level of EDAc-MPs along with brain metastasis and male gender significantly and independently predictive of one-year mortality (all P < 0.035). Conclusion. Circulating EDAc-MPs may be a useful biomarker predictive of one-year morality in ES-NSCLC patients.
    BioMed Research International 06/2014; 2014:173401. · 2.71 Impact Factor
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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; · 1.13 Impact Factor
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    ABSTRACT: We tested the hypothesis that clopidogrel and cilostazol combination therapy could effectively attenuate systemic inflammatory reaction, facilitate proliferation of circulating endothelial progenitor cell (EPC), and improve the clinical outcomes of critical limb ischemia (CLI) in patients unsuitable for surgical revascularization or percutaneous transluminal angioplasty (PTA). A total 55 patients (mean age, 72 years; 56% female) were consecutively enrolled. Clopidogrel and cilostazol combination therapy was administered throughout the study period. As compared with the baseline, circulating endothelial progenitor cell level (as shown by flow cytometry) was significantly increased (p < 0.003), whereas the CLI-related ulcers and painfulness were significantly improved (all p < 0.01) by day 90 after treatment. On the other hand, after clopidogrel and cilostazol combination therapy, galectin-3 level, lipoprotein-associated phospholipase A2 gene expression, and RhoA/ROCK-related protein expression in peripheral blood mononuclear cells were significantly suppressed (all p < 0.01). Eventually, by day 90, 5 patients (9.1%) died of other etiologies, 3 (5.5%) withdrew from the study, 6 (10.9%) required amputation, and the remaining 41 had satisfactory clinical improvement with complete wound healing in 9 (16.4%) patients. The results of the present study highlight that clopidogrel and cilostazol combination therapy may be considered to be an alternative method for treating patients with CLI unsuitable for surgical revascularization or PTA.
    Journal of Translational Medicine 04/2014; 12(1):101. · 3.99 Impact Factor
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    ABSTRACT: We tested the hypothesis that, as compared with conventional door-to-balloon, shortened door-to-balloon time would further improve 30-day outcome in ST-elevation myocardial infarction (STEMI) patients undergoing primary stenting. Retrospective cohort study SETTING:: Academic tertiary care hospital with approximately 2600 beds PATIENTS:: Between January 2008 and December 2009, 266 ST-elevation myocardial infarction patients underwent primary stenting with conventional Door-to-baloon were consecutively enrolled as group 1, while 293 ST-elevation myocardial infarction patients underwent primary stenting with shortened door-to-balloon between January 2010 and December 2011 were consecutively enrolled as group 2. Shorten door-to-balloon time. The results showed that time from chest pain onset to door did not differ between two groups (p > 0.1), whereas door-to-balloon time was significantly reduced in group 2 compared with that in group 1 (p < 0.0001). The prevalences of successful reperfusion, acute and subacute stent thrombosis, 30-day death or combined endpoint (defined as congestive heart failure ≥ New York Heart Association functional class 3 or 30-d death), and left ventricular function did not differ between two groups (all p > 0.05), whereas the peak creatine phosphokinase level was significantly reduced in group 2 (< 0.05). Further analysis showed that shortening the chest pain-to-reperfusion time to less than 240 minutes was the most important factor in improving left ventricular function (p < 0.001) and 30-day combined endpoint. Multivariate analysis showed that congestive heart failure greater than or equal to New York Heart Association functional class 3, poor left ventricular function, and age (all p < 0.001) along with unsuccessful reperfusion (p = 0.25) were independently predictive of 30-day mortality. Shortening the duration between chest pain onset and reperfusion to less than 4.0 hours was critical in reducing myocardial necrosis and improving heart function and 30-day mortality.
    Critical care medicine 04/2014; · 6.15 Impact Factor
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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: Aims: Contrast-induced nephropathy (CIN) is a leading cause of morbidity and mortality in patients undergoing percutaneous coronary intervention (PCI). Limited data, however, are available on predictors of CIN in PCI for chronic total occlusion (CTO) lesions. The aim of the study was to determine the risk of developing CIN in patients undergoing CTO PCI by studying the effects of clinical variables, interventional techniques, and CTO lesion characteristics on renal function. Methods and results: This retrospective analysis included consecutive patients referred for CTO PCI between January 2002 and December 2009. CIN was defined as an elevated serum creatinine level ≥25% of baseline serum creatinine level at 48-72 hours after procedure. Patient characteristics, Mehran score, lesion characteristics, interventional procedure, and devices used were compared between CIN and non-CIN groups. For the 516 patients eligible for analysis, the incidence of CIN was 5.4% (28/516). Two patients needed transient haemodialysis (0.4%, 2/516). Analysis of risk using Mehran scoring found that the incidence of CIN was 0.5% (1/207) among low-risk patients, 3.4% (7/205) among moderate-risk patients, 15.9% (14/88) among high-risk patients and 37.5% (6/16) among very high-risk patients. The Mehran score high-risk group (11-15) and the very high-risk group (≥16) were definitely predictors of CIN after CTO PCI (OR: 27.022 [95% CI: 2.787-262.028, p=0.004]; OR: 32.512 [95% CI: 2.149-491.978, p=0.012]). Severe tortuosity was the only predictor of CIN after CTO PCI in angiographic and procedural findings (OR: 6.621 [95% CI: 1.090-40.227, p=0.040]). Conclusions: Being in the Mehran score high-risk group (11-15) or the very high-risk group (≥16) and severe tortuosity were predictors of CIN after CTO PCI.
    EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 02/2014; 9(10):1173-80. · 3.17 Impact Factor
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    ABSTRACT: Objective. It has been reported that leukocyte ROCK activity is elevated in patients after ischemic stroke, but it is unclear whether leukocyte ROCK activity is associated with clinical outcomes following acute stroke events. The objective of this study is to investigate if leukocyte ROCK activity can predict the outcomes in patients with acute ischemic stroke. Materials and Methods. We enrolled 110 patients of acute ischemic stroke and measured the leukocyte ROCK activity and plasma level of inflammatory cytokines to correlate the clinical outcomes of these patients. Results. The leukocyte ROCK activity at 48 hours after admission in acute ischemic stroke patients was higher as compared to a risk-matched population. The leukocyte ROCK activity significantly correlated with National Institute of Health Stroke Scale (NIHSS) difference between admission and 90 days after stroke event. Kaplan-Meier survival estimates showed lower stroke-free survival during follow-up period in patients with high leukocyte ROCK activity or plasma hsCRP level. Leukocyte ROCK activity independently predicted the recurrent stroke in patients with atherosclerotic stroke. Conclusions. This study shows elevated leukocyte ROCK activity in patients with ischemic stroke as compared to risk-matched subjects and is an independent predictor for recurrent stroke.
    BioMed research international. 01/2014; 2014:214587.
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    ABSTRACT: This study investigated whether combining melatonin and apoptotic adipose-derived mesenchymal stem cells (A-ADMSC) was superior to ADMSC alone in ameliorating sepsis-induced acute lung injury. Adult male Sprague-Dawley rats (n=50) were randomized equally into five groups: sham controls (SC), sepsis induced by cecal-ligation and puncture (CLP), CLP-melatonin, CLP-A-ADMSC, and CLP-melatonin-A-ADMSC. Circulating interleukin (IL)-6 at 6, 18, and 72 hrs, were highest in CLP and lowest in SC groups, higher in CLP-melatonin than CLP-A-ADMSC and CLP-melatonin-A-ADMSC groups, higher in CLP-A-ADMSC than CLP-melatonin-A-ADMSC groups (all p<0.001). Immune reactivity (indicated by circulating cytotoxic-, and regulatory-T cells) and WBC count at 72 h exhibited the same pattern as that of circulating IL-6 (all p<0.001). Changes in histological scoring of lung parenchyma and the number of CD68+ and CD14+ cells showed a similar pattern compared to that of IL-6 level in all groups (all p<0.001). Changes in protein expressions of inflammatory (oxidative stress, RANTES, TNF-α, NF-κB, MMP-9, MIP-1, IL-1β), apoptotic (cleaved caspase 3 and PARP, mitochondrial Bax), fibrotic (Smad3, TGF-β) markers and those of reactive-oxygen-species (NOX-1, NOX-2) displayed an identical pattern compared to that of circulating IL-6 in all groups (all p<0.001). Anti-oxidative capacities (GR+, GPx+, HO-1, NQO-1+) and angiogenesis marker (CXCR4+ cells) were lowest in SC group but highest in CLP-melatonin-A-ADMSC group, lower in CLP than CLP-melatonin and CLP-A-ADMSC groups, and lower in CLP-melatonin than CLP-A-ADMSC groups (all p<0.001). In conclusion, combined melatonin and A-ADMSC were superior to A-ADMSC alone in protecting the lung from sepsis-induced injury.
    American Journal of Translational Research 01/2014; 6(5):439-58. · 3.23 Impact Factor
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    ABSTRACT: We investigated whether extracorporeal shock wave (ECSW) therapy can attenuate cyclophosphamide (CYP)-induced acute interstitial cystitis (AIC) in rats. Eighteen male-adult Sprague-Dawley rats were equally divided into group 1 (sham control), group 2 (AIC induced by 150 mg/kg CYP by intra-peritoneal injection) and group 3 (AIC + ECSW 200 impulses at 0.11 mJ/mm(2) to the urinary bladder at 3 and 24 h after CYP treatment). Smooth-muscle cells co-culture with menadione (25 µM) with and without ECSW treatment was performed. Western-blot results demonstrated that ECSW significant attenuated oxidative stress and inflammatory reactions in this in-vitro studies (all p < 0.001). 24-hour urine amount and microscopic findings of red-blood-cell count (i.e., hematuria) were higher in group 2 than in groups 1 and 3, and significantly higher in group 3 than in group 1 (all p < 0.001). The urine levels of albumin and interleukin-6 showed an identical pattern of hematuria among all three groups (all p < 0.001). The cellular and mRNA expressions of macrophage migration inhibitory factor (MIF)+, CD74+, CD68+, substance p+, and Cox-2+ cells in the bladder tissue exhibited an identical pattern of hematuria among all groups (all p < 0.0001). The integrity of epithelial layer and collagen-deposition area as stained by Sirius red displayed an opposite pattern of hematuria among the three groups (p < 0.0001). The protein expression of IL-12, iNOS, TNF-α, NF-κB, MMP-9, NOX-1, NOX-2, RANTES, and Oxyblot displayed an identical pattern of hematuria among all groups (all p < 0.01). ECSW therapy markedly attenuated CYP-induced AIC through inhibitions of the inflammation and oxidative stress.
    American Journal of Translational Research 01/2014; 6(6):631-48. · 3.23 Impact Factor
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    ABSTRACT: We tested the hypothesis that Lipofectamine siRNA delivery to deplete transient receptor potential cation channel (TRPC) 1 protein expression can suppress hypoxia-induced pulmonary arterial hypertension (PAH) in mice. Adult male C57BL/6 mice were equally divided into group 1 (normal controls), group 2 (hypoxia), and group 3 (hypoxia + siRNA TRPC1). By day 28, right ventricular systolic pressure (RVSP), number of muscularized arteries, right ventricle (RV), and lung weights were increased in group 2 than in group 1 and reduced in group 3 compared with group 2. Pulmonary crowded score showed similar pattern, whereas number of alveolar sacs exhibited an opposite pattern compared to that of RVSP in all groups. Protein expressions of TRPCs, HIF-1α, Ku-70, apoptosis, and fibrosis and pulmonary mRNA expressions of inflammatory markers were similar pattern, whereas protein expressions of antifibrosis and VEGF were opposite to the pattern of RVSP. Cellular markers of pulmonary DNA damage, repair, and smooth muscle proliferation exhibited a pattern similar to that of RVSP. The mRNA expressions of proapoptotic and hypertrophy biomarkers displayed a similar pattern, whereas sarcomere length showed an opposite pattern compared to that of RVSP in all groups. Lipofectamine siRNA delivery effectively reduced TRPC1 expression, thereby attenuating PAH-associated RV and pulmonary arteriolar remodeling.
    Stem cells international. 01/2014; 2014:316214.
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    ABSTRACT: We tested the hypothesis that apoptotic adipose-derived mesenchymal stem cells (A-ADMSC) are superior to healthy (H)-ADMSC in attenuating cecal ligation puncture (CLP)-induced sepsis-mediated lung and kidney injuries. Adult male rats divided into group 1 (sham controls), group 2 (CLP), group 3 [CLP + H-ADMSC administered at 0.5, 6, and 18 hours after CLP], and group 4 [CLP + A-ADMSC administered as in group 3] were sacrificed 72 hours after CLP with blood, lung, and kidney collected for studies. White blood cell (WBC) count, circulating TNF-α and creatinine levels were higher in groups 2 and 3 than in groups 1 and 4 (all P < 0.001). Kidney and lung damage scores were highest in group 2, lowest in group 1, significantly higher in group 3 than in group 4 (all P < 0.0001). Protein expressions of inflammatory (ICAM-1, MMP-9, TNF-α, NF-κB), oxidative, and apoptotic (Bax, caspase-3, PARP) biomarkers were higher in groups 2 and 3 than groups 1 and 4, whereas anti-apoptotic (Bcl-2) and mitochondrial integrity (cytochrome-C) biomarkers were lower in groups 2 and 3 than in groups 1 and 4 (all P < 0.001). Expressions of anti-oxidant biomarkers at protein (GR, GPx, NQO-1, HO-1) and cellular (GR, GPx) levels were highest in group 4 (all P < 0.001). The number of inflammatory cells (CD3+) in lungs and levels of DNA damage marker (γ-H2AX) in kidneys were higher in groups 2 and 3 than in groups 1 and 4 (all P < 0.001). A-ADMSC therapy was superior to H-ADMSC therapy in protecting major organs from damage in rats with CLP-induced sepsis syndrome.
    Stem Cell Research & Therapy 12/2013; 4(6):155. · 4.63 Impact Factor
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    ABSTRACT: Idiopathic azygos vein aneurysm (AVA) is rare. This retrospective study evaluated the imaging features and outcomes in 10 cases of idiopathic AVA. We retrospectively evaluated 10 patients with surgically proven or typical imaging features of idiopathic AVA encountered in our institution between 1990 and 2012. Chest roentgenography and computed tomography (CT) were performed in all 10 patients, and magnetic resonance imaging (MRI) was performed in 4 of these patients. The clinical features, AVA morphologic characteristics, and outcomes were analyzed. Chest roentgenograms showed a right paratracheal nodule or mediastinal mass in 7 cases. CT and MRI disclosed 4 thrombosed saccular AVAs (short axis, 3-6 cm; mean, 4.7 cm) and 6 fusiform AVAs (short axis, 2.2-3 cm; mean 2.7 cm). Two large saccular AVAs that presented with chest tightness were resected shortly after diagnosis. One saccular AVA manifested as a pulmonary embolism, whereas the remaining AVA was asymptomatic; they showed 25% to 40% short-axis growth in a 3- to 5-year interval before subsequent AVA resection. Conversely, all 6 fusiform AVAs were asymptomatic and found incidentally, remaining rather stable with less than 8% short-axis growth during 3 to 8 years of follow-up. Compared with fusiform AVAs, saccular AVAs were larger and had a greater frequency of AVA-related symptoms, intralesional thromboses, and greater than 20% short-axis growth during the follow-up period. Saccular AVAs are larger than fusiform aneurysms, presenting with greater frequency of chest symptoms, intralesional thrombosis, considerable lesion growth, and need for surgical intervention. In contrast, fusiform AVAs are asymptomatic and rather stable in long-term follow-up.
    The Annals of thoracic surgery 12/2013; · 3.45 Impact Factor

Publication Stats

2k Citations
710.22 Total Impact Points

Institutions

  • 2008–2014
    • Chang Gung University
      • • College of Medicine
      • • Department of Internal Medicine
      Hsin-chu-hsien, Taiwan, Taiwan
  • 2001–2014
    • Chang Gung Memorial Hospital
      • • Division of Cardiology
      • • Department of Internal Medicine
      • • Division of Neurosurgery
      T’ai-pei, Taipei, Taiwan
  • 2007–2013
    • I-Shou University
      Kao-hsiung-shih, Kaohsiung, Taiwan
  • 2010–2012
    • National Pingtung University of Science and Technology
      • Department of Life Science
      P’ing-tung-chieh, Taiwan, Taiwan
    • National Sun Yat-sen University
      • Department of Biological Science
      Kaohsiung, Kaohsiung, Taiwan
    • Mackay Memorial Hospital
      T’ai-pei, Taipei, Taiwan
  • 2011
    • National Dong Hwa University
      • Department of Electrical Engineering
      Hualian, Taiwan, Taiwan
  • 2007–2010
    • Suez Canal University
      • Department of Cardiology
      Ismailia, Muhafazat al Isma`iliyah, Egypt