Recent Development of Biodegradable Occlusion Devices for Intra-Atrial Shunts.

Atrial septal defect (ASD) is the third most common type of structural congenital heart defect. Patent foramen ovale (PFO) is an anatomical anomaly in up to 25% of the general population. With the innovation of occlusion devices and improvement of transcatheter techniques, percutaneous closure has become a first-line therapeutic alternative for treatment of ASD and PFO. During the past few decades, the development of biodegradable occlusion devices has become a promising direction for transcatheter closure of ASD/PFO due to their biodegradability and improved biocompatibility. The purpose of this review is to comprehensively summarize biodegradable ASD/PFO occlusion devices, regarding device design, materials, biodegradability, and evaluation of animal or clinical experiments (if available). The current challenges and the research direction for the development of biodegradable occluders for congenital heart defects are also discussed.

Metal-Ligand Cooperation in Cp*Ir-Pyridylpyrrole Complexes: Rational Design and Catalytic Activity in Formic Acid Dehydrogenation and CO2 Hydrogenation under Ambient Conditions.

Interconversion between CO2 + H2 and FA/formate is the most promising strategy for the fixation of carbon dioxide and reversible hydrogen storage; however, FA dehydrogenation and CO2 hydrogenation are usually studied separately using different catalysts for each reaction. This report describes of the catalysis of [Cp*Ir(N∧N)(X)]n+ (Cp* = 1,2,3,4,5-pentamethylcyclopentadienyl; X = Cl, n = 0; X = H2O, n = 1) bearing a proton-responsive N∧N pyridylpyrrole ligand for both reactions. Complex 2-H2O catalyzes FA dehydrogenation at 90 °C with a TOFmax of 45 900 h-1. Its catalysis is more active in aqueous solution than in neat solution under base-free conditions. These complexes also catalyze CO2 hydrogenation in the presence of base to formate under atmospheric pressure (CO2/H2 = 0.05 MPa/0.05 MPa) at 25 °C with a TOF value of 4.5 h-1 in aqueous solution and with a TOF value of 29 h-1 in a methanol/H2O mixture solvent. The possible mechanism is proposed by intermediate characterization and KIE experiments. The extraordinary activity of these complexes are mainly attributed to the metal-ligand cooperative effect of the the pyrrole group to accept a proton in the dehydrogenation of formic acid and assist cooperative heterolytic H-H bond cleavage in CO2 hydrogenation.

Efficient Electrochemical Water Oxidation Mediated by Pyridylpyrrole-Carboxylate Ruthenium Complexes.

Spurred by the rapid growth of Ru-based complexes as molecular water oxidation catalysts (WOCs), we propose novel ruthenium(II) complexes bearing pyridylpyrrole-carboxylate (H2ppc) ligands as members of the WOC family. The structure of these complexes has 4-picoline (pic)/dimethyl sulfoxide (DMSO) in [Ru(ppc)(pic)2(dmso)] and pic/pic in [Ru(ppc)(pic)3] as axial ligands. Another ppc2- ligand and one pic ligand are located at the equatorial positions. [Ru(ppc)(pic)2(dmso)] behaves as a WOC as determined by electrochemical measurement and has an ultrahigh electrocatalytic current density of 8.17 mA cm-2 at 1.55 V (vs NHE) with a low onset potential of 0.352 V (vs NHE), a turnover number of 241, a turnover frequency of 203.39 s-1, and kcat of 16.34 s-1 under neutral conditions. The H2O/pic exchange of the complexes accompanied by oxidation of a ruthenium center is the initial step in the catalytic cycle. The cyclic voltametric measurements of [Ru(ppc)(pic)2(dmso)] at various scan rates, Pourbaix diagrams (plots of E vs pH), and kinetic studies suggested a water nucleophilic attack mechanism. HPO42- in a phosphate buffer solution is invoked in water oxidation as the proton acceptor.

Zinc complexes supported by pyridine-N-oxide ligands: synthesis, structures and catalytic Michael addition reactions.

New dipyridylpyrrole N-oxide ligands HL1 and HL2 are designed and synthesized via oxidation of 2-(5-(pyridin-2-yl)-1H-pyrrol-2-yl)pyridine (Hdpp) by using 3-chloroperbenzoic acid (m-CPBA) in CH2Cl2. The treatment of ZnEt2 with two equiv. of HL1 and HL2 affords [Zn(L1)2] and [Zn(L2)2] in medium yield, respectively. These ligands and zinc complexes are fully characterized by NMR, IR, UV-vis and ESI-MS spectroscopy and X-ray diffraction analysis. The structure of HL1 and HL2 shows a planar geometry. The intramolecular hydrogen-bond interactions between the imino hydrogen and N-oxide oxygen atom are observed. In [Zn(L1)2] and [Zn(L2)2], two ligands chelate to the zinc metal with a cross perpendicular geometry. The zinc complexes were employed as a highly efficient catalyst for the thiol-Michael addition of thiols to α,ß-unsaturated ketones in EtOH at room temperature. The loading of the catalyst is lowered to 0.01 mol%. The catalytic mechanism was proposed based on NMR and ESI-MS experiments.

MicroRNA-29a suppresses cardiac fibroblasts proliferation via targeting VEGF-A/MAPK signal pathway.

Cardiac fibroblasts proliferation is the most important pathophysiological character of cardiac fibrosis while the underlying mechanisms are still incompletely known. MicroRNAs (miRNAs) regulate gene expression by binding to specific sites. Studies have been indicated that miRNA-29a play a key role in cardiac fibrosis. VEGF-A carries out its functions through MAPK signaling pathway in cardiac fibrosis. Existing proofs predict that the VEGF-A is one of the potential targets of miRNA-29a. We therefore probe the role of miRNA-29a and its latent target VEGF-A during cardiac fibrosis. In our study, miRNA-29a was down-regulated while VEGF-A was up-regulated in cardiac fibrosis tissues. The rat cardiac fibroblasts that were transfected with miRNA-29a inhibitor exhibited low-expression of miRNA-29a, enhanced VEGF-A protein and mRNA expression. Nevertheless, the cardiac fibroblasts transfected with miRNA-29a mimics obtained the opposite expression result. Furthermore, over-expression of miRNA-29a suppresses cardiac fibroblasts proliferation. In conclusion, these results suggested that miRNA-29a suppresses cardiac fibrosis and fibroblasts proliferation via targeting VEGF-A/MAPK signal pathway implicating that miRNA-29a might play a role in the treatment of cardiac fibrosis.

DNMT3A silencing RASSF1A promotes cardiac fibrosis through upregulation of ERK1/2.

Cardiac fibrosis contributes to the pathogenesis of atrial fibrillation (AF). The molecular mechanisms underlying the cardiac fibrosis remain unclear. However, Ras association domain family 1 isoform A (RASSF1A) is a regulatory tumor suppressor, which is important for pathogenesis of cardiac fibrosis and fibroblasts activation. Moreover, DNA methylation plays a central role in the maintenance of cardiac fibrosis. DNA methyltransferases 3A (DNMT3A) is a critical participant in the epigenetic silencing of regulatory genes. Here, we report that the downregulation of RASSF1A in cardiac fibrosis is associated with DNMT3A. Treatment of cardiac fibroblasts with DNMT3A inhibitor 5-AzadC blocked proliferation. 5-AzadC also prevented the loss of RASSF1A expression that occurs during activated cardiac fibroblasts. To determine the underlying molecular mechanisms, we hypothesized that cardiac fibrosis is controlled by DNMT3A. We demonstrated that downregulation of RASSF1A is associated with cardiac fibrosis and fibroblasts activation. Knockdown of DNMT3A elevated RASSF1A expression in activated cardiac fibroblasts. Moreover, we investigated the effect of RASSF1A on the Ras/ERK pathway. Upregulation of p-ERK1/2 was detected in activated cardiac fibroblasts with decreased RASSF1A expression. Our results have shown that DNMT3A likely plays an essential role in RASSF1A mediated upregulation of ERK1/2 in rat cardiac fibrosis. DNMT3A and RASSF1A may serve as a new mechanism for cardiac fibrosis.