Chia-Hua Kuo

Taipei University, T’ai-pei, Taipei, Taiwan

Are you Chia-Hua Kuo?

Claim your profile

Publications (225)726.58 Total impact

  • PLoS ONE 05/2015; 10(5):e0127440. DOI:10.1371/journal.pone.0127440 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Epidemiological studies and experimental data have shown that the incidences of hepatocellular carcinoma in men are more frequent than in women. Evidence suggests that imbalance of hormones, including estrogen, androgen, prolactin, and growth hormone, modifies liver tumorigenesis. In this present study, we investigated how estrogen and estrogen receptor 2, ESR2, regulates the cell cycle mechanism in Hep3B hepatocellular carcinoma cell line. Our results showed that ESR2 overexpression in the presence of 10⁻⁸ M 17-β-estradiol downregulated c-myc and cyclin D1 expression and simultaneously upregulated p27 expression. However, flow cytometry and MTT assays showed only minor G1 phase arrest without affecting cell viability. Taken together, these observations indicate that ESR2 is required to lower tumorigenesis in males by altering cell cycle proteins in a ligand-dependent manner.
    The Chinese journal of physiology 04/2015; 58(2). DOI:10.4077/CJP.2015.BAC239 · 1.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cardiomyocyte hypertrophy is an adaptive response of heart to various stress conditions. During the period of stress accumulation, transition from physiological hypertrophy to pathological hypertrophy results in the promotion of heart failure. Our previous studies found that ZAK, a sterile alpha motif and leucine zipper containing kinase, was highly expressed in infarcted human hearts and demonstrated that overexpression of ZAK induced cardiac hypertrophy. This study evaluates, cellular events associated with the expression of two doxycycline (Dox) inducible Tet-on ZAK expression systems, a Tet-on ZAK WT (wild-type), and a Tet-on ZAK DN (mutant, Dominant-negative form) in H9c2 myoblast cells; Tet-on ZAK WT was found to increase cell size and hypertrophic marker BNP in a dose-dependent manner. To ascertain the mechanism of ZAK-mediated hypertrophy, expression analysis with various inhibitors of the related upstream and downstream proteins was performed. Tet-on ZAK WT expression triggered the p38 and JNK pathway and also activated the expression and nuclear translocation of p-GATA4 and p-c-Jun transcription factors, without the involvement of p-ERK or NFATc3. However, Tet-on ZAK DN showed no effect on the p38 and JNK signaling cascade. The results showed that the inhibitors of JNK1/2 and p38 significantly suppressed ZAK-induced BNP expression. The results show the role of ZAK and/or the ZAK downstream events such as JNK and p38 phosphorylation, c-Jun, and GATA-4 nuclear translocation in cardiac hypertrophy. ZAK and/or the ZAK downstream p38, and JNK pathway could therefore be potential targets to ameliorate cardiac hypertrophy symptoms in ZAK-overexpressed patients.
    Molecular and Cellular Biochemistry 04/2015; DOI:10.1007/s11010-015-2389-z · 2.39 Impact Factor
  • Source
  • [Show abstract] [Hide abstract]
    ABSTRACT: Huntington's disease is an autosomal dominant neurodegenerative disease caused by a CAG repeat expansion in the huntingtin gene. Heart disease is the second leading cause of death in patients with Huntington's disease. This study was to evaluate whether cardiac Fas-dependent and mitochondria-dependent apoptotic pathways are activated in transgenic mice with Huntington's disease. Sixteen Huntington's disease transgenic mice (HD) and sixteen wild-type (WT) littermates were studied at 10.5 weeks of age. The cardiac characteristics, myocardial architecture, and two major apoptotic pathways in the excised left ventricle from mice were measured by histopathological analysis, Western blotting, and TUNEL assays. The whole heart weight and the left ventricular weight decreased significantly in the HD group, as compared to the WT group. Abnormal myocardial architecture, enlarged interstitial spaces, and more cardiac TUNEL-positive cells were observed in the HD group. The key components of Fas-dependent apoptosis (TNF-alpha, TNFR1, Fas ligand, Fas death receptors, FADD, activated caspase-8, and activated caspase-3) and the key components of mitochondria-dependent apoptosis (Bax, Bax-to-Bcl-2 ratio, cytosolic cytochrome c, activated caspase-9, and activated caspase-3) increased significantly in the hearts of the HD group. Cardiac Fas-dependent and mitochondria-dependent apoptotic pathways were activated in transgenic mice with Huntington's disease, which might provide one of possible mechanisms to explain why patients with Huntington's disease will develop heart failure.
    Cardiovascular toxicology 03/2015; DOI:10.1007/s12012-015-9318-y · 2.06 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Consumption of deep sea minerals (DSM), such as magnesium, calcium, and potassium, is known to reduce hypercholesterolemia-induced myocardial hypertrophy and cardiac-apoptosis and provide protection against cardiovascular diseases. Heart diseases develop as a lethal complication among diabetic patients usually due to hyperglycemia-induced cardiac-apoptosis that causes severe cardiac-damages, heart failure, and reduced life expectancy. In this study, we investigated the potential of DSM and its related cardio-protection to increase the life expectancy in diabetic rats. In this study, a heart failure rat model was developed by using streptozotocin (65 mg kg−1) IP injection. Different doses of DSM-1× (37 mg kg−1 day−1), 2× (74 mg kg−1 day−1) and 3× (111 mg kg−1 day−1), were administered to the rats through gavages for 4 weeks. The positive effects of DSM on the survival rate of diabetes rats were determined with respect to the corresponding effects of MgSO4. Further, to understand the mechanism by which DSM enhances the survival of diabetic rats, their potential to regulate cardiac-apoptosis and control cardiac-dysfunction were examined. Echocardiogram, tissue staining, TUNEL assay, and Western blotting assay were used to investigate modulations in the myocardial contractile function and related signaling protein expression. The results showed that DSM regulate apoptosis and complement the cardiomyocyte proliferation by enhancing survival mechanisms. Moreover DSM significantly reduced the mortality rate and enhanced the survival rate of diabetic rats. Experimental results show that DSM administration can be an effective strategy to improve the life expectancy of diabetic subjects by improving cardiac-cell proliferation and by controlling cardiac-apoptosis and associated cardiac-dysfunction. © 2014 Wiley Periodicals, Inc. Environ Toxicol, 2014.
    Environmental Toxicology 03/2015; DOI:10.1002/tox.22086 · 3.23 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Present study examined the effects of conjugated linoleic acid (CLA) supplementation on glycogen resynthesis in exercised human skeletal muscle. Twelve male participants completed a cross-over trial with CLA (3.8 g/day for 8 week) or placebo supplements by separation of 8 weeks. CLA is a mixture of trans-10 cis-12 and cis-9 trans-11 isomers (50:50). On experiment day, all participants performed 60-min cycling exercise at 75% VO2 max, then consumed a carbohydrate meal immediately after exercise and recovered for 3 h. Biopsied muscle samples from vastus lateralis were obtained immediately (0 h) and 3 h following exercise. Simultaneously, blood and gaseous samples were collected for every 30 min during 3-h recovery. Results showed significantly increased muscle glycogen content with CLA after a single bout of exercise (P < 0.05). Muscle glucose transporter type 4 expression was significantly elevated immediately after exercise, and this elevation was continued until 3 h after exercise in CLA trial. However, P-Akt/Akt ratio was not significantly altered, while glucose tolerance was impaired with CLA. Gaseous exchange data showed no beneficial effect of CLA on fat oxidation, instead lower non-esterified fatty acid and glycerol levels were found at 0 h. Our findings conclude that CLA supplementation can enhance the glycogen resynthesis rate in exercised human skeletal muscle.
    Journal of Sports Sciences 03/2015; 33(9):915-23. DOI:10.1080/02640414.2014.970219 · 2.10 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The purpose of the study was to determine the effect of ginseng-based steroid Rg1 on TNF-alpha and IL-10 gene expression in human skeletal muscle against exercise challenge, as well as on its ergogenic outcomes. Randomized double-blind placebo-controlled crossover trials were performed, separated by a 4-week washout. Healthy young men were randomized into two groups and received capsule containing either 5 mg of Rg1 or Placebo one night and one hour before exercise. Muscle biopsies were conducted at baseline, immediately and 3 h after a standardized 60-min cycle ergometer exercise. While treatment differences in glycogen depletion rate of biopsied quadriceps muscle during exercise did not reach statistical significance, Rg1 supplementations enhanced post-exercise glycogen replenishment and increased citrate synthase activity in the skeletal muscle 3 h after exercise, concurrent with improved meal tolerance during recovery (P<0.05). Rg1 suppressed the exercise-induced increases in thiobarbituric acids reactive substance (TBARS) and reversed the increased TNF-alpha and decreased IL-10 mRNA of quadriceps muscle against the exercise challenge. PGC-1 alpha and GLUT4 mRNAs of exercised muscle were not affected by Rg1. Maximal aerobic capacity (VO2max) was not changed by Rg1. However, cycling time to exhaustion at 80% VO2max increased significantly by ~20% (P<0.05). Our result suggests that Rg1 is an ergogenic component of ginseng, which can minimize unwanted lipid peroxidation of exercised human skeletal muscle, and attenuate pro-inflammatory shift under exercise challenge.
    PLoS ONE 01/2015; 10(1):e0116387. DOI:10.1371/journal.pone.0116387 · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Aging is associated with physiological or pathological left ventricular hypertrophy (LVH) cardiac changes. Secondhand smoke (SHS) exposure is associated with pathological LVH. The action mechanism in cardiac concentric hypertrophy from SHS exposure is understood, but the transition contributed from SHS exposure is not. To determine whether exposure to SHS has an impact on age-induced LVH we examined young and old hamsters that underwent SHS exposure in a chamber for 30 mins. Morphological and histological studies were then conducted using hematoxylin and eosin (H&E) and Masson's trichrome staining. Echocardiographic analysis was used to determine left ventricular wall thickness and function. LVH related protein expression levels were detected by western blot analysis. The results showed that both young and aged hamsters exposed to SHS exhibited increased heart weights and left ventricular weights, left ventricular posterior wall thickness and intraventricular septum systolic and diastolic pressure also increased. However, left ventricular function systolic and diastolic pressure deteriorated. H&E and Masson's trichrome staining results showed LV papillary muscles were ruptured, resulting in lower cardiac function at the myocardial level. LV muscle fiber arrangement was disordered and collagen accumulation occurred. Concentric LVH related protein molecular markers increased only in young hamsters exposed to SHS. However, this declined with hamster age. By contrast, eccentric LVH related proteins increased in aging hamsters exposed the SHS. Pro-inflammatory proteins, IL-6, TNF-alpha, JAK1, STAT3, and SIRTI expression increased in aging hamsters exposed to SHS. We suggest that SHS exposure induces a pro-inflammatory response that results in concentric transition to aging eccentric LVH.
    BMC Cardiovascular Disorders 12/2014; 14(1):195. DOI:10.1186/1471-2261-14-195 · 1.50 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Dammarane steroids (DS) are a class of chemical compounds present in Panax ginseng. Here, we evaluated the effect of 10 weeks of DS supplementation on inflammatory modulation in the soleus muscle following eccentric exercise (EE)-induced muscle damage (downhill running). Eighty rats were randomized into 4 groups of DS supplementation (saline, 20, 60, 120 mg/kg body weight). Inflammatory markers were measured at rest and again 1 h after EE. At rest, NFκB signaling, TNF-alpha and IL-6 mRNAs, 3-nitrotyrosine, glutathione peroxidase, and GCS (glutamylcysteine synthetase) levels were significantly elevated in the skeletal muscle of DS-treated rats in a dose-dependent manner. Additionally, there were no detectable increases in the number of necrotic muscle fibers or CD68+ M1 macrophages. However, muscle strength, centronucleation, IL-10 mRNA expression, and the number of CD163+ M2 macrophages increased significantly over controls with DS treatment in rat soleus muscle. Under EE-challenged conditions, significant increases in muscle fiber necrosis, CD68+ M1 macrophage distribution, and 3-nitrotyrosine were absent in rats that received low and medium doses (20 and 60 mg/kg) of DS treatment, suggesting that DS possess anti-inflammatory action protecting against a muscle-damaging challenge. However, this protective activity was diminished when a high dose of DS (120 mg/kg) was administered, suggesting that DS possess hormetic properties. In conclusion, our study provides new evidence suggesting that DS is an ergogenic component of ginseng that potentiate inflammation at baseline but that produce anti-inflammatory effects on skeletal muscle following muscle-damaging exercise. Furthermore, high doses should be avoided in formulating ginseng-based products.
    PLoS ONE 12/2014; 9(12):e114649. DOI:10.1371/journal.pone.0114649 · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Impaired antioxidant system and structural changes in hippocampus are considered as key instigators of neurodegenerative diseases. The present study aimed to investigate the antioxidant and tissue protective properties of Bacopa monniera whole-plant extract (BME) against aluminum (Al)- induced oxidative stress and hippocampus damage in rats. Male Wistar rats were evenly divided into four groups, nine in each and labeled as control, Al treated (10 mg/kg), BME administered (40 mg/kg) and combination of both Al plus BME (Al+BME) treated groups. After one month of treatment by oral administration, antioxidant status was determined, and structural changes in the hippocampus were evaluated by electron microscopy. Al-induced increased oxidative damage in the hippocampus was revealed by elevated thiobarbituric acid reactive substances (TBARS). This increased lipid peroxidation was associated with significantly decreased antioxidant enzyme activities, such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). However, aluminum intoxicated rats treated with BME for 30 days showed significantly restored antioxidant enzyme activities along with decreased TBARS (P < 0.01). Further evidences from electron micrographs clearly indicated that Al-induced vacuolation, lipofuscin deposition and pyramidal cell degeneration in the hippocampus was attenuated with co-administration of the whole-plant extract. Our results demonstrate that structural derangement in hippocampus by aluminum is directly proportionate with increased lipid peroxidation. Nevertheless, B. monniera treatment potentiates the antioxidant status and suppressed the tissue damage induced by Al-intoxication. These findings suggest that B. monniera whole-plant extracts can be considered as a possible remedy to counteract aluminum-associated neurological disorders.
    The Chinese journal of physiology 10/2014; 57(5). DOI:10.4077/CJP.2014.BAC221 · 1.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Exercise training is considered a benefit to heart function, but the benefit in aging hearts remains unknown. Activation of the PI3K-Akt survival pathway and suppression of Fas/FADD/caspase-8 apoptotic signaling by exercise training in hearts from young subjects have been described in our previous studies. However, the mechanisms are still unclear and need to be explored in aging hearts. Thus, 18-month-old rats were used as a model and underwent swimming exercise training, resveratrol treatment (15 mg/kg/day), or exercise training with resveratrol treatment for 1 month. The results showed that heart function in each group improved. However, the 18-month-old rats in the exercise-only group experienced the slightly inevitable impact of increased TNF-α, cell apoptosis, and fibrosis. In the protein analysis, the PI3K-Akt pathway was slightly increased with exercise training and resveratrol treatment, but Sirtuin 1 (SIRT1) was only highly activated with resveratrol treatment in the aged rat hearts. Moreover, the exercise training plus resveratrol group benefited from SIRT1 and PI3K-Akt dual pathways and blocked FOXO3 accumulation. Our experimental results strongly suggest that resveratrol treatment improves the beneficial effects of exercise training in aging rat hearts.
    Journal of the American Aging Association 10/2014; 36(5):9705. DOI:10.1007/s11357-014-9705-5 · 3.45 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Danggui (Radix Angelicae Sinensis) is an herb often used in Traditional Chinese medicine. It is used to promote blood flow and has been used in the treatment of myocardial ischemia-reperfusion injury in animal models. Angiotensin II (Ang II) has been shown to play important roles in mediating cardiovascular diseases, and may cause cardiac hypertrophy and apoptosis. This study aimed to investigate whether Danggui has protective effects on Ang II-induced apoptosis in H9c2 cardiomyoblast cells and study the mechanisms involved.
    BMC Complementary and Alternative Medicine 09/2014; 14(1):358. DOI:10.1186/1472-6882-14-358 · 1.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Dilong is an earthworm extract with a dense nutritional content, widely used in Chinese herbal medicine to remove stasis and stimulate wound healing. Earthworm extracts are traditionally used by indigenous people throughout the world. How this Dilong inhibits Lipopolysaccharide (LPS)-induced cardiomyoblast cell apoptosis is still unclear. This study investigates the Dilong extract effect on LPS-induced apoptosis in H9c2 cardiomyoblast cells. LPS (1 μg/ml) administration for 24 h induced apoptosis in H9c2 cells. Cell apoptosis was detected using MTT, LDH, TUNEL assay and JC-1 staining. Western blot analysis was used to detect pro-apoptotic and anti-apoptotic proteins. Dilong extract totally blocked the LPS impact, leading to the activation of anti-apoptotic proteins, Bcl-2 and Bcl-xL, stabilized the mitochondria membrane and down-regulated the extrinsic and intrinsic pro-apoptotic proteins, TNF-α, active caspase-8, t-Bid, Bax, active caspase-9 and active caspase-3. Dilong could potentially serve as a cardio protective agent against LPS-induced H9c2 cardiomyoblast cell apoptosis.
    Cardiovascular Toxicology 09/2014; 15(2). DOI:10.1007/s12012-014-9281-z · 2.06 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Chen, Chung-Yu, Chien-Wen Hou, Jeffrey R. Bernard, Chiu-Chou Chen, Ta-Cheng Hung, Lu-Ling Cheng, Yi-Hung Liao, and Chia-Hua Kuo. Rhodiola crenulata- and Cordyceps sinensis-based supplement boosts aerobic exercise performance after short-term high altitude training. High Alt Med Biol 15:371-379, 2014.-High altitude training is a widely used strategy for improving aerobic exercise performance. Both Rhodiola crenulata (R) and Cordyceps sinensis (C) supplements have been reported to improve exercise performance. However, it is not clear whether the provision of R and C during high altitude training could further enhance aerobic endurance capacity. In this study, we examined the effect of R and C based supplementation on aerobic exercise capacity following 2-week high altitude training. Alterations to autonomic nervous system activity, circulatory hormonal, and hematological profiles were investigated. Eighteen male subjects were divided into two groups: Placebo (n=9) and R/C supplementation (RC, n=9). Both groups received either RC (R: 1400 mg+C: 600 mg per day) or the placebo during a 2-week training period at an altitude of 2200 m. After 2 weeks of altitude training, compared with Placebo group, the exhaustive run time was markedly longer (Placebo: +2.2% vs. RC: +5.7%; p<0.05) and the decline of parasympathetic (PNS) activity was significantly prevented in RC group (Placebo: -51% vs. RC: -41%; p<0.05). Red blood cell, hematocrit, and hemoglobin levels were elevated in both groups to a comparable extent after high altitude training (p<0.05), whereas the erythropoietin (EPO) level remained higher in the Placebo group (∼48% above RC values; p<0.05). The provision of an RC supplement during altitude training provides greater training benefits in improving aerobic performance. This beneficial effect of RC treatment may result from better maintenance of PNS activity and accelerated physiological adaptations during high altitude training.
    High Altitude Medicine & Biology 09/2014; 15(3):371-379. DOI:10.1089/ham.2013.1114 · 1.82 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This study investigates the molecular mechanisms by which Alpiniae oxyphyllae fructus (AOF) promotes neuron regeneration. A piece of silicone rubber was guided across a 15 mm gap in the sciatic nerve of a rat. This nerve gap was then filled with different concentrations of AOF extract (0-200 mg/ml). We investigated the role of MAPK (ERK1/2, JNK and p38) pathways for AOF-induced matrix-degrading proteolytic enzyme (PAs and MMP2/9) production in RSC96 Schwann cells. The results showed that AOF increased the expressions of uPA, tPA, MMP-9, and MAPKs in vivo. In vitro, our results show that treatment with AOF extract induces ERK1/2, JNK, and p38 phosphorylation to activate the downstream PAs and MMPs signaling expression. AOF-stimulated ERK1/2, JNK, and p38 phosphorylation attenuated by individual pretreatment with siRNAs or inhibitors (U0126, SP600125 and SB203580), resulting in migration and uPA-related signal pathway inhibition. Taken together our data suggests the MAPKs (ERK1/2, JNK and p38), PAs (uPA, tPA), MMP (MMP2, MMP9) regenerative and migration signaling pathway of Schwann cells regulated by AOF extract might play a major role in Schwann cell migration and damaged peripheral nerve regeneration.
    The International journal of artificial organs 04/2014; DOI:10.5301/ijao.5000313 · 1.45 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Ischemic heart damage usually triggers cardiomyopathological remodeling and fibrosis, thus promoting the development of heart functional failure. Mesenchymal stem cells (MSCs) are a heterogeneous group of cells in culture, with multipotent and hypoimmunogenic characters to aid tissue repair and avoid immune responses, respectively. Numerous experimental findings have proven the feasibility, safety, and efficiency of MSC therapy for cardiac regeneration. Despite that the exact mechanism remains unclear, the therapeutic ability of MSCs to treat ischemia heart diseases has been tested in phase I/II clinical trials. Based on encouraging preliminary findings, MSCs might become a potentially efficacious tool in the therapeutic options available to treat ischemic and nonischemic cardiovascular disorders. The molecular mechanism behind the efficacy of MSCs on promoting engraftment and accelerating the speed of heart functional recovery is still waiting for clarification. It is hypothesized that cardiomyocyte regeneration, paracrine mechanisms for cardiac repair, optimization of the niche for cell survival, and cardiac remodeling by inflammatory control are involved in the interaction between MSCs and the damaged myocardial environment. This review focuses on recent experimental and clinical findings related to cellular cardiomyoplasticity. We focus on MSCs, highlighting their roles in cardiac tissue repair, transdifferentiation, the MSC niche in myocardial tissues, discuss their therapeutic efficacy that has been tested for cardiac therapy, and the current bottleneck of MSC-based cardiac therapies.
    Cell Transplantation 04/2014; 23(4):513-29. DOI:10.3727/096368914X678436 · 3.57 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Chemotherapy is usually applied to treat colon cancer but leads to chemoresistance, and increased metastasis and invasion. The main focus of this study is to observe effects of resistance to irinotecan (CPT-11) on metastasis, invasion and autophagy in CPT-11 resistant (CPT-11-R) LoVo colon cancer cells. CPT-11, a topoisomerase I inhibitor and a first-line chemotherapeutic drug, is used to treat colon cancer. CPT-11-R cells were constructed in a step-wise fashion with increasing CPT-11 doses. The CPT-11-R strain had a significantly lower expression of Wnt/β-catenin pathway, but induced an EGFR/IKKα/β/NF-κB pathway with elevated cell cycle, metastasis and basal autophagy.
    Cancer letters 04/2014; 349(1). DOI:10.1016/j.canlet.2014.03.023 · 5.02 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate whether chronic cocaine abuse will increase cardiac Fas-dependent and mitochondria-dependent apoptotic pathways, thirty-two male Wistar rats at 3-4 months of age were randomly divided into a vehicle-treated group (phosphate-buffered saline, PBS, 0.5 mL, SQ per day) and a cocaine-treated group (Cocaine, 10 mg/kg, SQ per day). After 3 months of treatment, the excised left ventricles were measured by H&E staining, Western blotting, DAPI staining and TUNEL assays. More cardiac TUNEL-positive apoptotic cells were observed in the Cocaine group than the PBS group. Protein levels of TNF-alpha, Fas ligand, Fas death receptor, FADD, activated caspase-8, and activated caspase-3 (Fas-dependent apoptosis) extracted from excised hearts in the Cocaine group were significantly increased, compared to the PBS group. Protein levels of cardiac Bax, cytosolic cytochrome c, t-Bid-to-Bid, Bak-to-Bcl-xL, Bax-to-Bcl-2 ratio, activated caspase-9, and activated caspase-3 (mitochondria-dependent apoptosis) were significantly increased in the Cocaine group, compared to the PBS group. Chronic cocaine exposure appeared to activate the cardiac Fas-dependent and mitochondria-dependent apoptosis, which may indicate a possible mechanism for the development of cardiac abnormalities in humans with chronic cocaine abuse.
    International Journal of Molecular Sciences 04/2014; 15(4):5988-6001. DOI:10.3390/ijms15045988 · 2.34 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Dizziness is a common clinical symptom frequently referred to general neurologists and practitioners. Exercise intervention, in the form of vestibular rehabilitation, is known as an effective clinical management for dizziness. This intervention is reported to have a functional role in correcting dizziness, improving gaze stability, retraining balance and gait, and enhancing physical fitness. Dizziness is known to be highly related to inflammation and oxidative stress. SIRT1 is a major molecule for the regulation of inflammation and mitigation of oxidative stress in chronic diseases such as atherosclerosis and chronic obstructive pulmonary disease. However, the bio-molecular roles of SIRT1 involved in the pathogenesis of dizziness are still largely unclear. In this study, a total of 30 subjects were recruited (15 patients with chronic dizziness, and 15 age/gender matched non-dizzy control subjects). The dizzy subjects group received 18 sessions of 30-min vestibular training. We found that the mRNA and protein expression levels of SIRT1 in the blood samples of chronic dizzy patients were repressed compared with those of healthy controls. After vestibular training, the dizzy patients had significant symptomatic improvements. The SIRT1 expression and its downstream genes (PPAR-γ and PGC-1α) were upregulated after vestibular exercises in dizzy subjects. Notably, the catalytic activity of SIRT1, NADPH and antioxidant enzyme activities were also activated in dizzy patients after vestibular training. Furthermore, vestibular exercise training reduced oxidative events and p53 expression in patients with dizziness. This study demonstrated that vestibular exercise training improved dizziness symptoms, and mechanisms for alleviation of chronic dizziness may partly involve the activation of the SIRT1 axis and the repression of redox status.
    Frontiers in Aging Neuroscience 03/2014; 6:27. DOI:10.3389/fnagi.2014.00027 · 2.84 Impact Factor

Publication Stats

686 Citations
726.58 Total Impact Points

Institutions

  • 2013–2015
    • Taipei University
      T’ai-pei, Taipei, Taiwan
    • China Medical University (ROC)
      臺中市, Taiwan, Taiwan
  • 2003–2014
    • Taipei Physical Education College
      T’ai-pei, Taipei, Taiwan
  • 2012
    • Fu Jen Catholic University
      T’ai-pei, Taipei, Taiwan
  • 2011
    • National Taiwan Sport University
      Hsin-chu-hsien, Taiwan, Taiwan
  • 2010
    • Kainan University
      Taoyuan City, Taiwan, Taiwan
    • China Medical University Hospital
      臺中市, Taiwan, Taiwan
    • National Yang Ming University
      • Department and Institute of Physiology
      Taipei, Taipei, Taiwan
  • 2009
    • Wan Fang Hospital
      T’ai-pei, Taipei, Taiwan
    • Asia University
      • Department of Health and Nutrition Biotechnology
      臺中市, Taiwan, Taiwan
    • Jen-Teh Junior College Of Medicine, Nursing And Management
      Miao-li-chieh, Taiwan, Taiwan
  • 2008
    • Changhua Christian Hospital
      Chang-hua Pei-pu, Taiwan, Taiwan
  • 2003–2006
    • Shih Hsin University
      Kao-hsiung-shih, Kaohsiung, Taiwan
  • 2005
    • Vanung University
      T’ai-pei, Taipei, Taiwan
  • 2004
    • Chang Gung Memorial Hospital
      • Department of Physical Medicine and Rehabilitation
      Taipei, Taipei, Taiwan
    • University of Texas at Austin
      • Department of Kinesiology and Health Education
      Texas City, TX, United States