2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

S

Expression of glycolytic enzymes in ovarian cancers and evaluation of the glycolytic pathway as a strategy for ovarian cancer treatment

Table S2. Spearman correlation of the expression of four glycolytic enzymes in a cohort of 380 ovarian cancers. Spearman rho correlation values (top value) along with the respective adjusted P value (bottom value) of statistically significant correlations thresholded at FDR P < 0.01 are summarised. (DOCX 21 kb

A Novel Role for Aquaporin-5 in Enhancing Microtubule Organization and Stability

Aquaporin-5 (AQP5) is a water-specific channel located on the apical surface of airway epithelial cells. In addition to regulating transcellular water permeability, AQP5 can regulate paracellular permeability, though the mechanisms by which this occurs have not been determined. Microtubules also regulate paracellular permeability. Here, we report that AQP5 promotes microtubule assembly and helps maintain the assembled microtubule steady state levels with slower turnover dynamics in cells. Specifically, reduced levels of AQP5 correlated with lower levels of assembled microtubules and decreased paracellular permeability. In contrast, overexpression of AQP5 increased assembly of microtubules, with evidence of increased MT stability, and promoted the formation of long straight microtubules in the apical domain of the epithelial cells. These findings indicate that AQP5-mediated regulation of microtubule dynamics modulates airway epithelial barrier properties and epithelial function

Predictors of pulmonary function response to treatment with salmeterol/fluticasone in patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and responses to therapies are highly variable. The aim of this study was to identify the predictors of pulmonary function response to 3 months of treatment with salmeterol/fluticasone in patients with COPD. A total of 127 patients with stable COPD from the Korean Obstructive Lung Disease (KOLD) Cohort, which were prospectively recruited from June 2005 to September 2009, were analyzed retrospectively. The prediction models for the FEV(1), FVC and IC/TLC changes after 3 months of treatment with salmeterol/fluticasone were constructed by using multiple, stepwise, linear regression analysis. The prediction model for the FEV(1) change after 3 months of treatment included wheezing history, pre-bronchodilator FEV(1), post-bronchodilator FEV(1) change and emphysema extent on CT (R = 0.578). The prediction models for the FVC change after 3 months of treatment included pre-bronchodilator FVC, post-bronchodilator FVC change (R = 0.533), and those of IC/ TLC change after 3 months of treatment did pre-bronchodilator IC/TLC and post-bronchodilator FEV(1) change (R = 0.401). Wheezing history, pre-bronchodilator pulmonary function, bronchodilator responsiveness, and emphysema extent may be used for predicting the pulmonary function response to 3 months of treatment with salmeterol/fluticasone in patients with COPD

Contributors of the Severity of Airflow Limitation in COPD Patients

Background: Although airway obstruction in chronic obstructive pulmonary disease (COPD) is due to pathologic processes in both the airways and the lung parenchyma, the contribution of these processes, as well as other factors, have not yet been evaluated quantitatively. We therefore quantitatively evaluated the factors contributing to airflow limitation in patients with COPD. Methods: The 213 COPD patients were aged >45 years, had smoked >10 pack-years of cigarettes, and had a post-bronchodilator forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) <0.7. All patients were evaluated by medical interviews, physical examination, spirometry, bronchodilator reversibility tests, lung volume, and 6-minute walk tests. In addition, volumetric computed tomography (CT) was performed to evaluate airway wall thickness, emphysema severity, and mean lung density ratio at full expiration and inspiration. Multiple linear regression analysis was performed to identify the variables independently associated with FEV1 - the index of the severity of airflow limitation. Results: Multiple linear regression analysis showed that CT measurements of mean lung density ratio (standardized coefficient β=-0.46; p<0.001), emphysema severity (volume fraction of the lung less than -950 HU at full inspiration; β=-0.24; p<0.001), and airway wall thickness (mean wall area %; β=-0.19, p=0.001), as well as current smoking status (β=-0.14; p=0.009) were independent contributors to FEV1. Conclusion: Mean lung density ratio, emphysema severity, and airway wall thickness evaluated by volumetric CT and smoking status could independently contribute to the severity of airflow limitation in patients with COPD

Loss of aquaporin-4 expression and putative function in non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>Aquaporins (AQPs) have been recognized to promote tumor progression, invasion, and metastasis and are therefore recognized as promising targets for novel anti-cancer therapies. Potentially relevant AQPs in distinct cancer entities can be determined by a comprehensive expression analysis of the 13 human AQPs.</p> <p>Methods</p> <p>We analyzed the presence of all AQP transcripts in 576 different normal lung and non-small cell lung cancer (NSCLC) samples using microarray data and validated our findings by qRT-PCR and immunohistochemistry.</p> <p>Results</p> <p>Variable expression of several AQPs (AQP1, -3, -4, and -5) was found in NSCLC and normal lung tissues. Furthermore, we identified remarkable differences between NSCLC subtypes in regard to AQP1, -3 and -4 expression. Higher transcript and protein levels of AQP4 in well-differentiated lung adenocarcinomas suggested an association with a more favourable prognosis. Beyond water transport, data mining of co-expressed genes indicated an involvement of AQP4 in cell-cell signalling, cellular movement and lipid metabolism, and underlined the association of AQP4 to important physiological functions in benign lung tissue.</p> <p>Conclusions</p> <p>Our findings accentuate the need to identify functional differences and redundancies of active AQPs in normal and tumor cells in order to assess their value as promising drug targets.</p

Chinese herb mix Tiáo-Gēng-Tāng possesses antiaging and antioxidative effects and upregulates expression of estrogen receptors alpha and beta in ovariectomized rats

<p>Abstract</p> <p>Background</p> <p>Herb mixtures are widely used as an alternative to hormonal therapy in China for treatment of the menopausal syndrome. However, composition of these herb mixtures are complex and their working mechanism is often unknown. This study investigated the effect of Tiáo-Gēng-Tāng (TG-decoction), a Chinese herbal mixture extract, in balancing female hormones, regulating expression of estrogen receptors (ERs), and preventing aging-related tissue damage.</p> <p>Methods</p> <p>Ovariectomized 5-month-old female rats were used to model menopause and treated with either TG-decoction or conjugated estrogen for 8 weeks. Estradiol (E₂), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured in serum and in the hypothalamus. Hypothalamic expression of estrogen receptor (ER) alpha and beta were studied by real-time PCR and western blotting. Total antioxidant capacity (T-AOC), oxidation indicator superoxide dismutase (SOD) activity and tissue damage parameter malondialdehyde (MDA) were measured using standard assays. Aging-related ultrastructural alterations in mitochondria were studied in all animals by transmission electron microscopy.</p> <p>Results</p> <p>TG-decoction-treatment elevated E₂and lowered FSH in serum of ovariectomized rats. The potency and efficacy of TG-decoction on the hypothalamus was generally weaker than that of conjugated estrogens. However, TG-decoction was superior in upregulating expression of ERα and β. TG-decoction increased hypothalamic SOD and T-AOC levels and decreased MDAlevels and mitochondrial damage in hypothalamic neurons.</p> <p>Conclusions</p> <p>TG-decoction balances female hormones similarly to conjugated estrogens but less effectively. However, it is superior in up regulating ERα and β and exhibits antioxidative antiaging activities. Whilst it shares similar effects with estrogen, TG-decoction also seems to have distinctive and more complex functions and activities.</p

Peroxisome Proliferator-Activated Receptor-Gamma Agonists Suppress Tissue Factor Overexpression in Rat Balloon Injury Model with Paclitaxel Infusion

The role and underlying mechanisms of rosiglitazone, a peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonist, on myocardial infarction are poorly understood. We investigated the effects of this PPAR-γ agonist on the expression of tissue factor (TF), a primary molecule for thrombosis, and elucidated its underlying mechanisms. The PPAR-γ agonist inhibited TF expression in response to TNF-α in human umbilical vein endothelial cells, human monocytic leukemia cell line, and human umbilical arterial smooth muscle cells. The overexpression of TF was mediated by increased phosphorylation of mitogen-activated protein kinase (MAPK), which was blocked by the PPAR-γ agonist. The effective MAPK differed depending on each cell type. Luciferase and ChIP assays showed that transcription factor, activator protein-1 (AP-1), was a pivotal target of the PPAR-γ agonist to lower TF transcription. Intriguingly, two main drugs for drug-eluting stent, paclitaxel or rapamycin, significantly exaggerated thrombin-induced TF expression, which was also effectively blocked by the PPAR-γ agonist in all cell types. This PPAR-γ agonist did not impair TF pathway inhibitor (TFPI) in three cell types. In rat balloon injury model (Sprague-Dawley rats, n = 10/group) with continuous paclitaxel infusion, the PPAR-γ agonist attenuated TF expression by 70±5% (n = 4; P<0.0001) in injured vasculature. Taken together, rosiglitazone reduced TF expression in three critical cell types involved in vascular thrombus formation via MAPK and AP-1 inhibitions. Also, this PPAR-γ agonist reversed the paclitaxel-induced aggravation of TF expression, which suggests a possibility that the benefits might outweigh its risks in a group of patients with paclitaxel-eluting stent implanted