Exosomes-Mediated LncRNA ZEB1-AS1 Facilitates Cell Injuries by miR-590-5p/ETS1 Axis Through the TGF-ß/Smad Pathway in Oxidized Low-density Lipoprotein-induced Human Umbilical Vein Endothelial Cells.

ABSTRACT: Atherosclerosis is a chronic lipid-induced inflammation of the vessel wall. Oxidized low-density lipoprotein was confirmed to drive the onset of atherogenesis. Zinc finger e-box-binding homeobox 1 antisense 1 (ZEB1-AS1) is a long noncoding RNA that is involved in human diseases, including atherosclerosis. In this study, the role of exosomes-mediated ZEB1-AS1 and its underlying mechanisms in atherosclerosis were explored in oxidized low-density lipoprotein (ox-LDL)-treated human umbilical vein endothelial cells (HUVECs). Exosomes were extracted from HUVECs. Quantitative real-time polymerase chain reaction was conducted to measure the expression of ZEB1-AS1, microRNA-590-5p (miR-590-5p), or erythroblastosis virus E26 oncogene homolog 1 (ETS1) in cells or exosomes. Cell proliferation and apoptosis were assessed by MTT assay and flow cytometry analysis, respectively. Western blot was performed to detect apoptosis-related factors, ETS1, and TGF-ß/Smad pathway protein levels. The secretion of inflammatory factors in supernatant was detected by ELISA assay. Oxidative stress damage indicators were used to assess cellular damage. Relationship between miR-590-5p and ZEB1-AS1 or ETS1 was analyzed. Our data indicated that ox-LDL-induced exosomes-mediated ZEB1-AS1 in HUVECs. Ox-LDL treatment resulted in limited proliferation, proapoptosis, inflammation, and oxidative stress damage, whereas knockdown of ZEB1-AS1 could reverse these effects. Mechanically, ZEB1-AS1 sponged miR-590-5p to regulate ETS1 expression. MiR-590-5p knockdown inverted effects above of si-ZEB1-AS1 on HUVECs under ox-LDL exposure. Moreover, ETS1 reversed miR-590-5p-induced effects and activated the TGF-ß/Smad pathway in ox-LDL-treated HUVECs. Taken together, our findings demonstrated that exosomes-mediated ZEB1-AS1 enhanced cell injuries by miR-590-5p/ETS1 axis through the TGF-ß/Smad pathway in ox-LDL-induced HUVECs, suggesting that inhibiting ZEB1-AS1 might be an effective way for atherosclerosis treatment.

The association between the MELD-XI score and heart failure in patients with acute myocardial infarction after coronary artery stenting-a retrospective study.

Background: The model for end-stage liver disease (MELD) score is a marker used to evaluate end-stage liver disease in patients with liver failure and is suggested to be valuable in evaluating heart diseases such as heart failure. Because patients with heart failure and myocardial infarction often use anticoagulants, there is an impact on the international normalized ratio (INR). Therefore, removing the INR from MELD score to form MELD-XI score may help to more accurately evaluate the cardiac function in patients with heart failure. This study was conducted to examine the predictive value of MELD-XI score in patients with acute myocardial infarction after coronary artery stenting, as there is a lack of literature in this area. Methods: The data of 318 patients with acute myocardial infarction admitted to The People's Hospital of Dazu from January 2018 to January 2021 was retrospectively collected. According to the MELD-XI score on admission, the patients were divided into a high-MELD-XI score group (n=159) and a low-MELD-XI score group (n=159). The patients were followed up for 1 year after surgery to observe the long-term prognosis and the long-term prognosis of the 2 groups was compared. Results: Compared with that in the low-MELD-XI score group, the left ventricular ejection fraction in the high-MELD-XI score group was significantly reduced (51.61%±7.66% vs. 60.48%±5.94%; P<0.001), while the level of N-terminal pro-B-type natriuretic peptide (NT-proBNP) increased significantly (821.58±461.81 vs. 723.51±335.16 ng; P=0.031). The MELD-XI score had a certain predictive value for heart failure in patients with acute myocardial infarction after coronary artery stenting, and the area under the curve was 0.730 (95% CI: 0.670-0.791; P<0.001). The MELD-XI score had a predictive value for death in patients with acute myocardial infarction after coronary artery stenting, and the area under the curve was 0.704 (95% CI: 0.564-0.843; P=0.022). MELD-XI score was significantly negatively correlated with left ventricular ejection fraction in patients with acute myocardial infarction after coronary artery stenting (r=-0.444; P<0.001). Conclusions: MELD-XI could evaluate the cardiac function of patients with acute myocardial infarction after coronary artery stenting, which was valuable in predicting the prognosis.

Yu-Shiba-Rusinov states assisted by asymmetric Coulomb repulsion in a bipartite molecular device.

Interfacing magnetism with superconducting condensates are promising candidates holding Majorana bound states with which fault-tolerant quantum computation could be implemented. Within this field, understanding the detailed dynamics is important both for fundamental reasons and for the development of innovative quantum technologies. Herein, motivated by a molecular magnet Tb2Pc3interacting with a superconducting Pb(111) substrate, which results in spin-orbital Yu-Shiba-Rusinov (YSR) states, as is affirmed by a theoretical simulation with the aid of the numerical renormalization group technique (see Xiaet al2022Nat. Commun.136388), we study the YSR states and quantum phase transitions (QPTs) in a bipartite molecular device adsorbed on ans-wave superconducting substrate. We highlight the effect of asymmetric Coulomb repulsion by computing the spectrum function and spin correlation function in various parameter regimes. We demonstrate that if one impurity is non-interacting, there are no YSR states in both impurities with any repulsion value in the other impurity. Whereas if the repulsion in one impurity is strong, the YSR states are observed in both impurities, and a QPT arises as the repulsion in the other impurity sweeps, assisted by the competition between the superconducting singlet (Cooper pair) and the Kondo singlet. The evolution of YSR states distinguishes from the single impurity case and can be well interpreted by the energy scales of the isotropic superconducting gap parameter, as well as the two Kondo temperatures. Our findings provide theoretical insights into the phase diagram of two magnetic impurities on a superconducting host and shine light on the effects induced by asymmetric Coulomb repulsion on many-body interactions.