Long noncoding RNAs (lncRNAs) have been confirmed to be potential prognostic markers in a variety of cancers and to interact with microRNAs (miRNAs) as competing endogenous RNAs (ceRNAs) to regulate target gene expression. However, the role of lncRNA-mediated ceRNAs in breast cancer (BC) remains unclear. In the present study, a ceRNA network was generated to explore their role in BC. The expression profiles of mRNAs, miRNAs and lncRNAs in 1,109 BC tissues and 113 normal breast tissues were obtained from The Cancer Genome Atlas database (TCGA). A total of 3,198 differentially expressed (DE) mRNAs, 150 differentially DEmiRNAs and 1,043 DElncRNAs were identified between BC and normal tissues. A lncRNA-miRNA-mRNA network associated with BC was successfully constructed based on the combined data obtained from RNA databases, and comprised 97 lncRNA nodes, 24 miRNA nodes and 74 mRNA nodes. The biological functions of the 74 DEmRNAs were further investigated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The results demonstrated that the DEmRNAs were significantly enriched in two GO biological process categories; the main biological process enriched term was ‘positive regulation of GTPase activity’. By KEGG analysis, four key enriched pathways were obtained, including the ‘MAPK signaling pathway’, the ‘Ras signaling pathway’, ‘prostate cancer’, and the ‘FoxO signaling pathway’. Kaplan-Meier survival analysis revealed that six DElncRNAs (INC AC112721.1, LINC00536, MIR7-3HG, ADAMTS9-AS1, AL356479.1 and LINC00466), nine DEmRNAs (KPNA2, RACGAP1, SHCBP1, ZNF367, NTRK2, ORS1, PTGS2, RASGRP1 and SFRP1) and two DEmiRNAs (hsa-miR-301b and hsa-miR-204) had significant effects on overall survival in BC. The present results demonstrated the aberrant expression of INC AC112721.1, AL356479.1, LINC00466 and MIR7-3HG in BC, indicating their potential prognostic role in patients with BC.

Objective: To evaluate the feasibility, safety, and effectiveness of a novel, absorbable atrial septal defect (ASD) closure device made of poly-L-lactic acid (PLLA) in a swine model of ASD and for the first time in humans.Methods: A preclinical safety study was conducted using a swine model of ASD. In a clinical setting, five pediatric patients underwent ASD closure with the PLLA device with fluoroscopic and transthoracic echocardiography guidance. The procedural results and clinical outcomes at 1 day, 30 days, 3 months, and 6 months after closure were analyzed. Results:The 24-and 36-month follow-up results of the preclinical study demonstrated that the PLLA device exhibited good endothelialization and degradability in the swine model. In the clinical study, successful device implantation was achieved in all five patients (median age, 3.6 years; range, 3.1-6.5 years). The mean defect size was (13.6 ± 2.7) mm. Follow-up at 30 days, 3 months, and 6 months was completed in all five cases. The complete defect closure rates with no residual shunt at 30 days, 3 months, and 6 months follow-up were 60% (3/5), 80% (4/5), and 80% (4/5), respectively. No device dislodgement, significant aortic valve or mitral valve regurgitation, new onset cardiac arrhythmia, or other adverse events were reported. Conclusion:The study results demonstrated that it is feasible to implant the PLLA device for closure of small to medium sized ASDs without significant residual shunts or severe adverse events in humans. The PLLA device exhibited good endothelialization and degradability in the swine model at 24 and 36 months. Further studies to evaluate long-term safety and effectiveness with the device in a large cohort of patients are warranted. K E Y W O R D Sabsorbable implants, catheterization closure, congenital heart defect, device

Activation of NMDA receptor initiates a Ca2+ influx that stimulates the production of NO by neuronal nitric oxide synthase (nNOS). A physical coupling of the NMDA receptor and nNOS occurs by an intermediary adaptor protein PSD95 (post synaptic density 95). CAPON, a protein rich in PVN competes with PSD95 for interaction with nNOS. Previously, we showed a decreased expression of nNOS and enhanced expression of NMDA NR1 within the PVN of rats with HF. To further elucidate the underlying mechanism of upregulation of NMDA NR1 with a concomitant downregulation of nNOS, we measured the levels of CAPON in left coronary ligation‐induced HF model of rats. CAPON expression is augmented by 22% in rats with HF. Previously we showed that Angiotensin II receptor (AT1) blocker, losartan (LOS) treatment in rats with HF normalized the changes in expression of NR1 and nNOS protein in the PVN. Consistent with these data, LOS treatment (10 mg/kg/day in the drinking water for three weeks) in rats with HF normalized protein expression of the CAPON in the PVN. Studies in neuronal NG108‐15 hybrid cell line treated with Ang II (6.25–100 μM) for 24h revealed 30% increase in CAPON expression at highest dose as compared to untreated cell samples. Co‐treatment with LOS (1μM) for 24h significantly, ameliorates the increased CAPON expression to Ang II. Immunostaining revealed colocalization of CAPON and nNOS in NG108 cell line as well as in PVN. These data suggest that perhaps the disparate changes in NR1 (upregulation) and nNOS (downregulation) may be due to an over expression of CAPON and this over expression of CAPON may be mediated by increased Ang II influence in rats with HF.

Our recent studies revealed that, in a dual‐phase response induced by non‐selective nicotinic stimulation, the bradycardic phase of the response was blocked by a selective agonist to α4β2 nicotinic cholinergic receptors (nAchRs). This study was to further investigate the functional role of this subtype of nAchRs in regulation of heart rate. In urethane‐anesthetized male Swiss Webster mice, the intravenous injection of an α4β2 nAchRs agonist, varenicline, induced a quick and pronounced bradycardic response without sympathetic responses. This bradycardic response was prolonged after the administration of a cholinesterase inhibitor, neostigmine and eliminated by a muscarinic receptor antagonist, atropine, suggesting that this response is associated with acetylcholine (Ach) action and is mediated via muscarinic receptors. These data suggest that α4β2 nAchRs may be located in the intracardial ganglia where the receptors play a role in regulation of Ach release.This work was supported by American Heart Association grant No. 0835256N and NIH grant No. 1R03AG033291. Varenicline compound was provided by Pfizer Inc.