Astaxanthin Alleviates the Process of Cardiac Hypertrophy by Targeting the METTL3/Circ_0078450/MiR-338-3p/GATA4 Pathway.

Astaxanthin (ASX) is a natural antioxidant with preventive and therapeutic effects on various human diseases. However, the role of ASX in cardiac hypertrophy and its underlying molecular mechanisms remain unclear.Cardiomyocytes (AC16) were used with angiotensin-II (Ang-II) to mimic the cardiac hypertrophy cell model. The protein levels of hypertrophy genes, GATA4, and methyltransferase-like 3 (METTL3) were determined by western blot analysis. Cell size was assessed using immunofluorescence staining. The expression of circ_0078450, miR-338-3p, and GATA4 were analyzed by quantitative real-time PCR. Also, the interaction between miR-338-3p and circ_0078450 or GATA4 was confirmed by dual-luciferase reporter and RIP assays, and the regulation of METTL3 on circ_0078450 was verified by MeRIP and RIP assays.ASX reduced the hypertrophy gene protein expression and cell size in Ang-II-induced AC16 cells. Circ_0078450 was promoted under Ang-II treatment, and ASX reduced circ_0078450 expression in Ang-II-induced AC16 cells. Circ_0078450 could sponge miR-338-3p to positively regulate GATA4 expression, and GATA4 overexpression overturned the suppressive effect of circ_0078450 knockdown on Ang-II-induced cardiomyocyte hypertrophy. Also, the inhibitory effect of ASX on Ang-II-induced cardiomyocyte hypertrophy could be reversed by circ_0078450 or GATA4 overexpression. In addition, METTL3 mediated the m6A methylation of circ_0078450 to enhance circ_0078450 expression. Moreover, METTL3 knockdown suppressed Ang-II-induced cardiomyocyte hypertrophy by inhibiting circ_0078450 expression.Our data showed that ASX repressed cardiac hypertrophy by regulating the METTL3/circ_0078450/miR-338-3p/GATA4 axis.

Postoperative adverse cardiac events in acute myocardial infarction with high thrombus load and best time for stent implantation.

BACKGROUND: Myocardial infarction is one of the most common types of coronary heart disease. It is mainly caused by the rupture of coronary atherosclerotic plaque, which leads to platelet agglutination and thrombosis. The occlusion of coronary arteries and vessels leads to insufficient myocardial blood supply, subsequently causing cardiac interstitial fibrosis, gradual enlargement of ventricles, and heart failure, which affects the quality of life and safety of patients. AIM: To investigate the effects of emergency percutaneous interventional therapy (PCI) and delayed stenting in acute myocardial infarction with high thrombotic load and identify factors related to major adverse cardiovascular events (MACE). METHODS: A total of 164 patients with acute myocardial infarction and high thrombotic load who received PCI were included. Of them, 92 patients were treated with delayed stent implantation (delayed group) and 72 patients received emergency PCI (immediate group). Myocardial perfusion after stent implantation was compared between the two groups. Patients were followed up for 12 mo, and the occurrence of MACE was used as the endpoint. Univariate and multivariate models were used to analyze the factors affecting MACE occurrence. RESULTS: After stent implantation, 66 (71.74%) patients in the delayed group and 40 (55.56%) patients in the immediate group had thrombolysis in myocardial infarction (TIMI) flow grade 3 (P < 0.05), while 61 (66.30%) patients in the delayed group and 39 (54.17%) patients in the immediate group reached TIMI myocardial perfusion grade 3 (P > 0.05). MACE occurred in 29 patients. There were statistically significant differences between the MACE and non-MACE groups in diabetes rate, TIMI grading, stent implantation timing, intraoperative use of tirofiban, and the levels of white blood cells (WBC), neutrophils, red blood cell distribution width (RDW), and uric acid, and high-sensitivity C-reactive protein (hs-CRP) at admission (P < 0.05). Logistic regression analysis showed that TIMI grade 3 and intraoperative use of tirofiban effectively reduced the risk of MACE (P < 0.05), while immediate stent implantation, increased WBC, hs-CRP and RDW on admission increased the risk of MACE (P < 0.05). CONCLUSION: Delayed stent implantation outweighs emergency PCI in improving postoperative myocardial perfusion in acute myocardial infarction with high thrombotic load, and effectively reduces MACE in these patients.

Mechanism of Isosorbide Dinitrate Combined with Exercise Training Rehabilitation to Mobilize Endothelial Progenitor Cells in Patients with Coronary Heart Disease.

it was to explore effect of isosorbide dinitrate combined with exercise training and rehabilitation on endothelial progenitor cells (EPCs) in coronary heart disease. EPCs were isolated and cultured from peripheral blood of coronary heart disease patients, and morphology and surface markers were detected. Then, 116 patients were rolled into treatment group (isosorbide dinitrate + exercise rehabilitation training) and control group (isosorbide dinitrate). Characteristics of EPCs cells after treatment were compared. The mononuclear cells were round and small in size and were not evenly distributed in the culture plate. EPCs cells grew as colonies after 8d-culture, and the surrounding cells grew outward in a germinating manner with colonies as the center, forming multiple cell populations. Positive rates of EPCs surface markers CD133, CD34, and vascular endothelial growth factor receptor (KDR) were 11.25±3.07%, 48.18±9.13%, and 76.36±8.27%, respectively. Proliferation activity of EPCs in the treatment group was dramatically higher versus controls at day three, five, and seven (P<0.05). Adhesion ability of EPCs in treatment group was dramatically higher than controls at day three, five, and seven (P<0.05). Migration ability of EPCs in treatment group was dramatically higher versus control group at day three, five, and seven (P<0.05). In short, isosorbide dinitrate plus exercise rehabilitation greatly enhanced the proliferation activity, adhesion ability, and migration ability of EPCs cells, which also played a beneficial role in the repair of endothelial injury, with notable effects.

Plasmonic-3D photonic crystals microchip for surface enhanced Raman spectroscopy.

Plasmonic-dielectic hybrid substrates of Ag-islands on three-dimensional photonic crystals are fabricated through magnetron sputtering of silver onto hydrophobized silica photonic crystals, free from etching process. Without typical "hot-spots" such as nanogaps, significant Raman enhancements can be achieved, attributed to the enhanced electromagnetic field and scattering of the plasmonic nanoparticles as well as the enhanced light-matter interaction by the slow photon effects. The detection limit for adenine by the hybrid substrates reaches nM level, with a calculated enhancement factor of 1.13 × 107, which is three orders of magnitude higher than the conventional noble metal film over nanosphere (FON) control group. Furthermore, microchips based on the hybrid substrates are facilely achieved, enabling micro-detection through super hydrophobic concentration. The facile fabrication and effective Raman enhancements make the Ag-islands on 3D photonic crystals promising candidates in the field of chemical sensors, Raman mapping and bioassays.

Regio- and Diastereoselective Cross-Dehydrogenative Coupling of Tetrahydropyridines with 1,3-Dicarbonyl Compounds.

A regio- and diastereoselective cross-dehydrogenative coupling of N-carbamoyl tetrahydropyridines with a variety of 1,3-dicarbonyl compounds is described. The method exhibits good functional group tolerance, diastereoselectively generating cis-2,6- or cis-2,4-substituted tetrahydropyridines by using different types of 1,3-dicarbonyls. Moreover, a two-step sequence involving diastereoselective cross-dehydrogenative coupling followed by epimerization was also developed, allowing facile access to trans-2,6-substituted tetrahydropyridines as single isomers. Applications in natural product synthesis and divergent analogue preparation were further demonstrated.