MiR-455-3p regulates glioma cell proliferation by targeting PAX6

Purpose: To investigate the role of miR-455-3p in gliomas. Method: Quantitative real-time polymerase chain reaction was used to measure miR-455-3p and paired box 6 (PAX6) levels in glioma cell lines. Western blot analysis was used to determine the expression of cell cycle regulators. In addition to over-expression, silencing of miR-455-3p or PAX6 was performed to study the functions of miR-455-3p in gliomas. Results: The levels of miR-455-3p were significantly up-regulated in glioma cell lines (p < 0.05), while miR-455-3p over-expression increased glioma cell proliferation and interfered with the progress of the cell cycle (p < 0.01). Furthermore, endogenous miR-455-3p silencing prevented glioma cell proliferation by regulating cell cycle progression (p < 0.05).The results also showed that PAX6 controlled the cell cycle while PAX6 silencing selectively regulated p21 expression (p < 0.01). Furthermore, miR-455-3p and PAX6 influenced p53 expression. Re-introduction of PAX6 expressing vector into glioma cells rescued the pro-tumoral effect of miR-455-3p overexpression. Conclusion: These findings demonstrate the role of miR-455-3p as a tumour oncogene in gliomas via regulation of the cell cycle, indicating that miR-455-3p might act as a new treatment strategy for glioma cell tumours and a predictor of survival in glioma patients

Desipramine Pretreatment Improves Sympathetic Remodeling and Ventricular Fibrillation Threshold after Myocardial Ischemia

Abnormal increase in sympathetic nerve sprouting was responsible for the ventricular arrhythmogenesis after myocardial infarction. This study investigated whether the norepinephrine transporter inhibitor, desipramine, can modulate sympathetic remodeling and ventricular fibrillation threshold (VFT) after myocardial ischemia-reperfusion. Rats were administered desipramine (0.8 mg/kg, IV) before or after myocardial ischemia. VFT, infarct size, tyrosine hydroxylase (TH) and growth-associated protein 43 (GAP43)-positive nerve fibers were measured after one week. The VFT of preischemic treatment group was 11.0±2.65 V and significantly higher than that of control ischemic group (7.2±1.30 V, P<0.05). Infarct size in the preischemic treatment group (23.3±2.4%) was significantly lower than that in the control ischemic group (30.8±1.3%, P<0.05) and the delayed application group (27.1±2.6%, P<0.05). The density of TH and GAP43-positive nerve fibers in the control ischemic group was significantly higher than that in the other three groups (P<0.05). The density of nerve fibers improved after desipramine treatment. Moreover, there was a negative correlation between the VFT and both TH and GAP43-positive nerve fiber density in the infarct border zone (P<0.05). Desipramine treatment before acute myocardial ischemia can decrease infarct size, improve sympathetic remodeling, and increase VFT and electrical stability of ischemic hearts. Desipramine appears to cause myocardial ischemic preconditioning

Advances in the Application of Pulsed Field Ablation for Arrhythmia Treatment

The increased application of catheter ablation to treat cardiac arrhythmias has contributed to continued exploration of safe and effective tissue ablation tools in the field of electrophysiology. Pulsed field ablation (PFA), a novel recently developed non-thermal energy-based technique, uses trains of microsecond duration high-amplitude pulses to ablate target cells. Several preclinical and clinical studies have demonstrated that PFA is a promising tool for cardiac ablation to treat arrhythmia. In addition to being an effective tissue ablation technique, PFA is safe, because it avoids damage to the surrounding cells/tissues. This review focuses on efficacy and safety outcomes reported in preclinical and clinical studies evaluating the effects of PFA on arrhythmia, and discusses limitations and potential future directions of PFA

Prevention and Reversal of Atrial Fibrillation Inducibility and Autonomic Remodeling by Low-Level Vagosympathetic Nerve Stimulation

ObjectivesWe hypothesized that autonomic atrial remodeling can be reversed by low-level (LL) vagosympathetic nerve stimulation (VNS).BackgroundPreviously, we showed that VNS can be antiarrhythmogenic.MethodsThirty-three dogs were subjected to electrical stimulation (20 Hz) applied to both vagosympathetic trunks at voltages 10% to 50% below the threshold that slowed sinus rate or AV conduction. Group 1 (n = 7): Programmed stimulation (PS) was performed at baseline and during 6-h rapid atrial pacing (RAP). PS allowed determination of effective refractory period (ERP) and AF inducibility measured by window of vulnerability (WOV). LL-VNS was continuously applied from the 4th to 6th hours. Group 2 (n = 4): After baseline ERP and WOV determinations, 6-h concomitant RAP+LL-VNS was applied. Sustained AF was induced by injecting acetylcholine (ACh) 10 mM into the anterior right ganglionated plexus (Group 3, n = 10) or applying ACh 10 mM to right atrial appendage (Group 4, n = 9).ResultsGroup 1: The ERP progressively shortened and the ΣWOV (sum of WOV from all tested sites) progressively increased (p < 0.05) during 3-h RAP then returned toward baseline during 3-h RAP+LL-VNS (p < 0.05). Group 2: 6-h concomitant RAP+LL-VNS did not induce any significant change in ERP and ΣWOV. Group 3 and Group 4: AF duration (AF-D) and cycle length (AF-CL) were markedly altered by 3-h LL-VNS (Group 3: baseline: AF-D = 389 ± 90 s, AF-CL = 45.1 ± 7.8 ms; LL-VNS: AF-D = 50 ± 15 s, AF-CL = 82.0 ± 13.7 ms [both p < 0.001]; Group 4: baseline: AF-D = 505 ± 162 s, AF-CL = 48.8 ± 6.6 ms; LL-VNS: AF-D = 71 ± 21 s, AF-CL = 101.3 ± 20.9 ms [both p < 0.001]).ConclusionsLL-VNS can prevent and reverse atrial remodeling induced by RAP as well as suppress AF induced by strong cholinergic stimulation. Inhibition of the intrinsic cardiac autonomic nervous system by LL-VNS may be responsible for these salutary results

Incremental Metabolic Benefits from Cryoablation for Paroxysmal Atrial Fibrillation: Insights from Metabolomic Profiling

Background: Cryoablation (CRYO) is a novel catheter ablation technique for atrial fibrillation (AF). However, uncertainty persists regarding the role of metabolic modifications associated with CRYO. This study was aimed at exploring whether CRYO influences the metabolic signature – a possibility not previously investigated. Methods: Paired serum samples from patients with AF (n = 10) were collected before and 24 h after CRYO. Untargeted metabolomic analysis was conducted with LC-MS. Univariate and multivariate analyses were applied to identify differential metabolites between samples. Pathway enrichment and Pearson correlation analyses were performed to reveal the perturbed metabolic pathways and potential interactions. Results: Levels of 19 metabolites showed significant changes between baseline and 24 h after CRYO. Pathway analysis revealed that the perturbed metabolites were enriched in unsaturated fatty acid biosynthesis, retrograde endocannabinoid signaling, and neuroactive ligand-receptor interactions. Pearson correlation analysis indicated strong correlations among differential metabolites, biochemical markers, and clinical indicators. Conclusions: CRYO induces systemic changes in the serum metabolome in patients with paroxysmal AF and provides potential metabolic benefits. Our findings might enable enhanced understanding of the pathophysiology and metabolic mechanisms involved in catheter ablation

Identification and Antioxidant Properties of Phenolic Compounds during Production of Bread from Purple Wheat Grains

Phenolic profiles and antioxidant properties of purple wheat varieties were investigated to document the effects of bread-making. Bread crust and crumb along with samples collected after mixing, 30 min fermenting, 65 min fermenting, and baking were examined. Free phenolic content (105.4 to 113.2 mg FAE/100 g) significantly (p &lt; 0.05) increased during mixing, fermenting, and baking (65% to 68%). Bound phenolics slightly (p &gt; 0.05) decreased after 30 min fermentation (7% to 9%) compared to the dough after mixing, but increased significantly (p &lt; 0.05) during 65 min fermenting and baking (16% to 27%). Their antioxidant activities followed a similar trend as observed for total phenolic content. The bread crust demonstrated increased free (103% to 109%) but decreased bound (2% to 3%) phenolic content, whereas bread crumb exhibited a reversal of these results. Total anthocyanin content (TAC) significantly (p &lt; 0.05) decreased by 21% after mixing; however, it gradually increased to 90% of the original levels after fermenting. Baking significantly (p &lt; 0.05) decreased TAC by 55%, resulting in the lowest value for bread crust (0.8 to 4.4 mg cyn-3-glu equiv./100 g). p-Hydroxybenzoic, vanillic, p-coumaric, and ferulic acids were detected in free-phenolic extracts, while protocatechuic, caffeic syringic, and sinapic were additional acids in bound-phenolic extracts. Cyanidin-3-glucoside was the detectable anthocyanin in purple wheat. Bread-making significantly (p &lt; 0.05) increased the phenolic content and antioxidant activities; however, it compromised the anthocyanin content of purple wheat bread

Comparison of Antioxidant Properties of Refined and Whole Wheat Flour and Bread

Antioxidant properties of refined and whole wheat flour and their resultant bread were investigated to document the effects of baking. Total phenolic content (TPC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and oxygen radical absorbance capacity (ORAC) were employed to determine the content of ethanol extractable phenolic compounds. HPLC was used to detect the presence of phenolic acids prior to their confirmation using LC-MS/MS. Whole wheat flour showed significantly higher antioxidant activity than refined flour (p &lt; 0.05). There was a significant effect of the bread-making process with the TPC of whole wheat bread (1.50–1.65 mg/g) and white bread (0.79–1.03 mg/g) showing a respective reduction of 28% and 33% of the levels found in whole wheat and refined flour. Similarly, baking decreased DPPH radical scavenging capacity by 32% and 30%. ORAC values, however, indicated that baking increased the antioxidant activities of whole wheat and refined flour by 1.8 and 2.9 times, respectively. HPLC analysis showed an increase of 18% to 35% in ferulic acid after baking to obtain whole and refined wheat bread containing 330.1 and 25.3 µg/g (average), respectively. Whole wheat flour and bread were superior to refined flour and bread in in vitro antioxidant properties

A Method for Safety Evaluation of Train Braking System Considering Multiple Types of Preventive Maintenance Cycles

The train braking system with redundant components has an essential effect on driver safety. In this paper, we consider the failure of K-out-of-N brake motors during operation and the redundant recovery by preventive maintenance. Two Continuous Time Markov Chains (CTMC) are used to model the working process and the preventive maintenance process of the braking system corresponding to the real situation of the train. Considering the maintenance effect of intermittent daily and cyclical overhaul with nested relationships, a new operation risk assessment model of the K-out-of-N system is developed to evaluate the effectiveness of the preventive maintenance of the train. Some safety parameters are solved based on the two coupled preventive maintenance periods, which conveniently design the safety of the train braking system. Finally, a case study illustrates the effectiveness of the safety evaluation method. The results show that we can trade off the effects of the multiple PM intervals on train safety considering the redundancy structure of the braking system by the proposed model

A Method for Safety Evaluation of Train Braking System Considering Multiple Types of Preventive Maintenance Cycles

The train braking system with redundant components has an essential effect on driver safety. In this paper, we consider the failure of K-out-of-N brake motors during operation and the redundant recovery by preventive maintenance. Two Continuous Time Markov Chains (CTMC) are used to model the working process and the preventive maintenance process of the braking system corresponding to the real situation of the train. Considering the maintenance effect of intermittent daily and cyclical overhaul with nested relationships, a new operation risk assessment model of the K-out-of-N system is developed to evaluate the effectiveness of the preventive maintenance of the train. Some safety parameters are solved based on the two coupled preventive maintenance periods, which conveniently design the safety of the train braking system. Finally, a case study illustrates the effectiveness of the safety evaluation method. The results show that we can trade off the effects of the multiple PM intervals on train safety considering the redundancy structure of the braking system by the proposed model