Description: Background: The role of beta-adrenergic stimulation on viral myocarditis has been investigated in animal models of viral myocarditis. Excess stimulation of beta-adrenergic receptors by catecholamines causes phosphorylation/activation of cAMP response element binding protein (CREB) by the cAMP signaling pathway. CREB as an important regulator of gene expression mediates the cardiovascular remodeling process and promotes anti-inflammatory immune responses. However, the CREB expression and phosphorylation have not been studied, and the effects of carvedilol (a nonselective beta-adrenoceptor antagonist) on the CREB has not been investigated in the setting of acute viral myocarditis. Methods: This study was therefore designed to examine the effects of carvedilol on the transcriptional factor CREB in a murine model of acute viral myocarditis. In a coxsackievirus B3 murine myocarditis model (Balb/c), effects of carvedilol on plasma noradrenaline, heart rate and blood pressure, myocardial histopathological changes and fibrosis, cardiomyocyte apoptosis, cardiac CREB and phosphorylated CREB, cytokine levels, and viral RNA were studied. Results: The expression and phosphorylation of CREB were decreased with concomitant increase of IL-6 and TNF-alpha in murine coxsackievirus-induced acute viral myocarditis. The levels of IL-6 and TNF-alpha were correlated with the expression of CREB or phosphorylated CREB. Carvedilol increased the cardiac CREB expression and phosphorylation and decreased the plasma catecholamine levels and the production of IL-6 and TNF-alpha with amelioration of acute viral myocarditis. Conclusion: These results show that CREB may be involved in the pathophysiology of viral myocarditis and carvedilol exerts some of its beneficial effects by increasing the CREB expression and phosphorylation.

Description: Background: Previous epidemiological studies have presented conflicting evidence regarding associations between interleukin-1 (IL-1) polymorphisms and sepsis susceptibility. We have performed a meta-analysis to evaluate possible associations between IL-1 polymorphisms and sepsis risk. Methods: Eligible literature was retrieved from PubMed, Embase and Web of Knowledge databases until Jun 15, 2013. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random-effects model in the overall and subgroup analysis based on ethnicity, sepsis severity and quality score. Results: Eighteen studies addressing five IL-1 polymorphisms were included in this meta-analysis. For IL-1A-889 (rs1800587) polymorphism, significant association was observed in overall comparison for allelic effect (OR = 1.47, 95%CI = 1.01-2.13, P = 0.04). There were no significant associations between either IL-1B-511 (rs16944) or IL-1B-31 (rs1143627) and sepsis susceptibility in overall or subgroup analyses. For IL-1B + 3594 (rs143634) polymorphism, genotype TT decreased sepsis risk in overall analysis (OR = 0.59, 95%CI = 0.36-0.97, P = 0.04), as well as in Caucasian (OR = 0.57, 95%CI = 0.34-0.95, P = 0.03) and sepsis (OR = 0.55, 95%CI = 0.31-0.97, P = 0.04) subgroup analysis. For IL-1RN VNTR polymorphism, significant association was observed in overall comparison for allelic effect (OR = 1.40, 95%CI = 1.01-1.95, P = 0.04). Furthermore, the effect sizes of IL-1RN VNTR on sepsis risk increased with disease severity (septic shock OR 〉 severe sepsis OR 〉 sepsis OR). Conclusions: Our meta-analysis indicated that IL-1A-889, IL-1B + 3954 and IL-1RN VNTR might be associated with sepsis susceptibility. However, further studies with larger sample sizes and from homogenous populations would be necessary to validate these findings.

Description: To extract, purify, and identify the effective constituents of aqueous extract of Fructus Chebulae Immaturus, and analyze the bactericidal effects of total tannins.

Description: Background: Protein phosphorylation is one of the most important post-translational modifications involved in the regulation of plant growth and development as well as diverse stress response. As a member of the Poaceae, Brachypodium distachyon L. is a new model plant for wheat and barley as well as several potential biofuel grasses such as switchgrass. Vegetative growth is vital for biomass accumulation of plants, but knowledge regarding the role of protein phosphorylation modification during vegetative growth, especially in biofuel plants, is far from comprehensive. Results: In this study, we carried out the first large-scale phosphoproteome analysis of seedling leaves in Brachypodium accession Bd21 using TiO2 microcolumns combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) and MaxQuant software. A total of 1470 phosphorylation sites in 950 phosphoproteins were identified, and these phosphoproteins were implicated in various molecular functions and basic cellular processes by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Among the 950 phosphoproteins identified, 127 contained 3 to 8 phosphorylation sites. Conservation analysis showed that 93.4% of the 950 phosphoproteins had phosphorylation orthologs in other plant species. Motif-X analysis of the phosphorylation sites identified 13 significantly enriched phosphorylation motifs, of which 3 were novel phosphorylation motifs. Meanwhile, there were 91 phosphoproteins with both multiple phosphorylation sites and multiple phosphorylation motifs. In addition, we identified 58 phosphorylated transcription factors across 21 families and found out 6 significantly over-represented transcription factor families (C3H, Trihelix, CAMTA, TALE, MYB_related and CPP). Eighty-four protein kinases (PKs), 8 protein phosphatases (PPs) and 6 CESAs were recognized as phosphoproteins. Conclusions: Through a large-scale bioinformatics analysis of the phosphorylation data in seedling leaves, a complicated PKs- and PPs- centered network related to rapid vegetative growth was deciphered in B. distachyon. We revealed a MAPK cascade network that might play the crucial roles during the phosphorylation signal transduction in leaf growth and development. The phosphoproteins and phosphosites identified from our study expanded our knowledge of protein phosphorylation modification in plants, especially in monocots.

Description: Background: A higher prevalence of chronic atrophic gastritis (CAG) occurs in younger adults in Asia. We used Stomach Age to examine the different mechanisms of CAG between younger adults and elderly individuals, and established a simple model of cancer risk that can be applied to CAG surveillance. Methods: Stomach Age was determined by FISH examination of telomere length in stomach biopsies. Deltapsim was also determined by flow cytometry. Sixty volunteers were used to confirm the linear relationship between telomere length and age while 120 subjects were used to build a mathematical model by a multivariate analysis. Overall, 146 subjects were used to evaluate the validity of the model, and 1,007 subjects were used to evaluate the relationship between prognosis and Deltaage (calculated from the mathematical model). ROC curves were used to evaluate the relationship between prognosis and Deltaage and to determine the cut-off point for Deltaage. Results: We established that a tight linear relationship between the telomere length and the age. The telomere length was obvious different between patients with and without CAG even in the same age. Deltapsim decreased in individuals whose Stomach Age was greater than real age, especially in younger adults. A mathematical model of Stomach Age (real age + Deltaage) was successfully constructed which was easy to apply in clinical work. A higher Deltaage was correlated with a worse outcome. The criterion of Deltaage 〉3.11 should be considered as the cut-off to select the subgroup of patients who require endoscopic surveillance. Conclusion: Variation in Stomach Age between individuals of the same biological age was confirmed. Attention should be paid to those with a greater Stomach Age, especially in younger adults. The Deltaage in the Simple Model can be used as a criterion to select CAG patients for gastric cancer surveillance.

Description: Background: In recent years, catheter ablation has increasingly been used for ablation of idiopathicpremature ventricular complexes (PVCs) or ventricular tachycardias (IVTs). However, themapping and catheter ablation of the arrhythmias originating from the vicinity of tricuspidannulus (TA) may not be fully understood. This study aimed to investigate electrophysiologiccharacteristics and effects of radiofrequency catheter ablation (RFCA) for patients withsymptomatic PVCs and IVTs originating from the vicinity of TA. Methods: Characteristics of body surface electrocardiogram (ECG) and electrophysiologic recordingswere analyzed in 35 patients with symptomatic PVCs/ IVTs originating from the vicinity ofTA. RFCA was performed using pace mapping and activation mapping. Results: Among the 35 patients with PVCs/IVTs arising from the vicinity of TA, complete eliminationof PVCs/IVTs could be achieved by RFCA in 32 patients (success rate 91.43%) during amedian follow-up period of 21 months. PVCs/IVTs originating from the vicinity of TA haddistinctive ECG characteristics that were useful for identifying the precise origin. An rSpattern was recorded in lead V1 in 93.1% of patients with PVCs/IVTs from the free wall ofTA, vs 16.7% of patients with PVCs/IVTs from the septal TA, whereas a QS pattern in leadV1 occurred in 83.3% of patients with PVCs/IVTs from the septal TA vs 6.9% of patientswith PVCs from the free wall of the TA. The precordial R wave transition occurred by leadV3 or earlier in all patients with PVCs/IVTs originating from the septal portion of the TA, ascompared to transition beyond V3 in all patients with PVCs/IVTs from the free wall of theTA. Conclusions: RFCA is an effective curative therapy for symptomatic PVCs/IVTs originating from thevicinity of TA. There are specific characteristics in ECG and the ablation site could belocated by ECG analysis.

Description: Background: Radiofrequency catheter ablation (RFCA) has been used for the ablation of premature ventricular contractions (PVCs) or ventricular tachycardia (VT). To date, the mapping and catheter ablation of the arrhythmias originating from the left ventricular outflow tract (LVOT) has not been specified. This study investigates the electrocardiogram (ECG) feature of PVCs or VT originating from the LVOT. Moreover, the treatment outcome of RFCA is analyzed. Methods: Mapping and ablation were performed on the supravalvular or subvalvular aorta in 52 cases with PVCs/VT originating from the LVOT. The data were compared with those from 104 patients with PVCs/VT originating from the right ventricular outflow tract (RVOT). A differential procedure was prepared based on the comparison of the ECG features of PVCs/VT originating from the RVOT, LVOT, and their different parts. Results: Among 52 cases with PVCs originating from the LVOT, 47 were successfully treated by RFCA, with a success rate of 90.38%. Several differences among the 12-lead ECG features were observed from the RVOT and LVOT in the left and right coronary sinus groups, as well as under the left coronary sinus group (left fibrous trigone): (1) If the precordial leads transition 0 are considered as the diagnostic parameters of PVCs/VT originating from the LVOT, then the sensitivity, specificity, as well as positive and negative predictive values are 94.12%, 93.00%, 87.27%, and 96.88%, respectively; (2) The analysis of different subgroups of the LVOT are as follows: (a) A mainly positive wave of r or m pattern was recorded in the lead I in 72.73% of patients in the right coronary sinus group, versus 12.90% of patients in the left coronary sinus group, and 0% in the under left coronary sinus group. (b) All patients in the right coronary sinus group presented waves of RII〉RIII and QSaVR〉QSaVL, whereas most patients in the other two groups showed waves of RIII〉RIIand QSaVL〉QSaVR. (c) Most patients in the under left coronary sinus group in lead V1 had a mainly positive wave (R) (77.78%), whereas those in the right (81.82%) and left (62.50%) coronary sinus groups had mainly negative waves (rS). Conclusions: RFCA is a safe and effective curative therapy for PVCs/VT originating from the LVOT. The 12-lead ECG features of the LVOT from different origins exhibit certain distinctions.

Description: Background: To explore the feasibility of a new method of achieving a permanent A-V block animal model. Methods: 16 beagles were randomly divided into two groups based on the method of their pre-implanted biventricular pacemakers. (1) In the first group (8 beagles), the A-V block model was achieved by ablating his-bundle potential at the site of the left ventricular superior-septum, under the aortic sinus, through femoral artery. (2) In the second group (8 beagles), the A-V block model was achieved by ablating his-bundle potential at the triangle of Koch, through femoral vein. A complete A-V block model was achieved as a standard in this study. The success rates, intraoperative arrhythmias, operative and X-ray exposure time, intraoperative bleeding amount were assessed in this two groups, both animal models were followed up for four weeks and then fasted to monitor myocardial pathological changes. Results: The success rate of the first group, which with fewer intraoperative arrhythmias, and less operative and X-ray exposure time, was significantly higher than the second group. Conclusions: Compared with traditional animal method, our new method of ablating his-bundle potential at the left ventricle from the femoral artery has a higher success rate, fewer occurrence of malignant arrhythmias, and less operation and X-ray time. Thus, our new method should be preferred in the building of Permanent A-V Block Model.

Description: Background: Suberoylanilide hydroxamic acid (SAHA) is a member of the hydroxamic acid class of the newly developed histone deacetylase inhibitors. Recently, Suberoylanilide hydroxamic acid has attracted increasing attention because of its antitumor activity and synergistic effects in combination with a variety of traditional chemotherapeutic drugs. Paclitaxel (PTX), is a natural anticancer drugs; however, resistance to paclitaxel has become a major challenge to the efficacy of this agent. The purpose of this study was to investigate the effects of the combined application of these two drugs on the paclitaxel-resistant ovarian cancer OC3/P cell line. Methods: In the present study, the effects of Suberoylanilide hydroxamic acid or/and paclitaxel on OC3/P cells cultured in vitro were analyzed in terms of cell viability, migration, cell-cycle progression and apoptosis by CCK-8, wound healing and flow cytometry assays. Changes in cell ultrastructure were observed by transmission electron microscopy. The expression of genes and proteins related to proliferation, apoptosis and drug resistance were analyzed by quantitative real-time polymerase chain reaction and Western blot analyses. Results: There was no cross-resistance of the paclitaxel-resistant ovarian cancer OC3/P cells to Suberoylanilide hydroxamic acid. Suberoylanilide hydroxamic acid combined with paclitaxel significantly inhibited cell growth and reduced the migration of OC3/P cells compared with the effects of Suberoylanilide hydroxamic acid or paclitaxel alone. Q-PCR showed the combination of Suberoylanilide hydroxamic acid and paclitaxel reduced intracellular bcl-2 and c-myc gene expression and increased bax gene expression more distinctly than the application of SAHA or paclitaxel alone. Moreover, the level of mdr1 gene expression in cells treated with Suberoylanilide hydroxamic acid was lower than that of the control group (P