Bisoprolol (B) exerts potential cardioprotective effects against myocardial ischemia/reperfusion (I/R) injury. Unfolded protein response (UPR) attenuates I/R injury induced apoptosis by reducing oxidative damage and inflammation response. The current study investigated whether the protective effects of bisoprolol resulted from modulating UPR and anti-inflammatory during myocardial I/R condition and elucidated its potential mechanisms. Sprague-Dawley rats were treated with B in the absence or presence of the injected UPR activator dithiothreitol (DTT) and then subjected to myocardial I/R surgery. In vitro, cultured H9C2 cells were pretreated with B or DTT and then subjected to simulate ischemia reperfusion (SIR) operation. Bisoprolol conferred cardioprotective effects by improving postischemic cardiac function, decreasing infarct size, reducing apoptotic index, diminishing serum creatine kinase and lactate dehydrogenase levels, suppressing TNF-α and IL-6 secretion, inhibiting UPR signal pathways and downregulating caspase-12 and caspase-3 expressions. Consistently, B conferred similar antioxidative and anti-inflammatory effects against SIR injury in cultured H9C2 cardiomyocytes. Pretreatment with DTT or C/EBP homologous protein (CHOP) overexpression mediated by lentivirus administration both abolished these effects. In summary, our results demonstrate that Bisoprolol protects myocardium cells against ischemia/reperfusion injury partly by attenuating unfolded protein response.

PurposeQuantitative image analysis in previous research in obstructive sleep apnea syndrome (OSAS) has focused on the upper airway or several objects in its immediate vicinity and measures of object size. In this paper, we take a more general approach of considering all major objects in the upper airway region and measures pertaining to their individual morphological properties, their tissue characteristics revealed by image intensities, and the 3D architecture of the object assembly. We propose a novel methodology to select a small set of salient features from this large collection of measures and demonstrate the ability of these features to discriminate with very high prediction accuracy between obese OSAS and obese non-OSAS groups.Materials and MethodsThirty children were involved in this study with 15 in the obese OSAS group with an apnea-hypopnea index (AHI) = 14.4 ± 10.7) and 15 in the obese non-OSAS group with an AHI = 1.0 ± 1.0 (p<0.001). Subjects were between 8–17 years and underwent T1- and T2-weighted magnetic resonance imaging (MRI) of the upper airway during wakefulness. Fourteen objects in the vicinity of the upper airways were segmented in these images and a total of 159 measurements were derived from each subject image which included object size, surface area, volume, sphericity, standardized T2-weighted image intensity value, and inter-object distances. A small set of discriminating features was identified from this set in several steps. First, a subset of measures that have a low level of correlation among the measures was determined. A heat map visualization technique that allows grouping of parameters based on correlations among them was used for this purpose. Then, through T-tests, another subset of measures which are capable of separating the two groups was identified. The intersection of these subsets yielded the final feature set. The accuracy of these features to perform classification of unseen images into the two patient groups was tested by using logistic regression and multi-fold cross validation.ResultsA set of 16 features identified with low inter-feature correlation (< 0.36) yielded a high classification accuracy of 96% with sensitivity and specificity of 97.8% and 94.4%, respectively. In addition to the previously observed increase in linear size, surface area, and volume of adenoid, tonsils, and fat pad in OSAS, the following new markers have been found. Standardized T2-weighted image intensities differed between the two groups for the entire neck body region, pharynx, and nasopharynx, possibly indicating changes in object tissue characteristics. Fat pad and oropharynx become less round or more complex in shape in OSAS. Fat pad and tongue move closer in OSAS, and so also oropharynx and tonsils and fat pad and tonsils. In contrast, fat pad and oropharynx move farther apart from the skin object.ConclusionsThe study has found several new anatomic bio-markers of OSAS. Changes in standardized T2-weighted image intensities in objects may imply that intrinsic tissue composition undergoe...

Background/Aims: Toll-like receptors (TLRs) have been implicated in myocardial ischemia/ reperfusion (I/R) injury. We examined the effect of CpG-oligodeoxynucleotide (ODN) on myocardial I/R injury. Methods: Male Sprague-Dawley rats were treated with either CpG-ODN or control ODN 1 h prior to myocardial ischemia (30 min) followed by reperfusion. Rats treated with phosphate-buffered saline (PBS) served as I/R controls (n = 8/group). Infarct size was determined by 2,3,5-triphenyltetrazolium chloride and Evans blue straining. Cardiac function was examined by echocardiography before and up to 14 days after myocardial I/R. Results: CpG-ODN administration significantly increased infarct size and reduced cardiac function and survival rate after myocardial I/R, compared to the PBS-treated I/R group. Control-ODN did not alter I/R-induced myocardial infarct size, cardiac dysfunction, and survival rate. Additionally, CpG-ODN promoted I/R-induced myocardial apoptosis and cleaved caspase-3 levels in the myocardium. CpG-ODN increased TLR9 activation and p38 phosphorylation in the myocardium. In vitro data also suggested that CpG-ODN treatment induced TLR9 activation and p38 phosphorylation. Importantly, p38 mitogen-activated protein kinase (MAPK) inhibition abolished CpG-ODN-induced cardiac injury. Conclusion: CpG-ODN, the TLR9 ligand, accelerates myocardial I/R injury. The mechanisms involve activation of the TLR9-p38 MAPK signaling pathway.

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