Dual Antioxidant DH-217 Mitigated Cerebral Ischemia-Reperfusion Injury by Targeting IKKß/Nrf2/HO-1 Signal Axis.

Antioxidants represent a potential therapy for cerebral ischemia-reperfusion injury (CIRI). Compounds which exhibit both direct and indirect antioxidative activity may potentially exert improved effects. Hence, we aimed to assess whether the dual antioxidant DH-217, a derivative of DHAP clinically used to treat coronary heart disease, can reduce oxidative stress damage and elucidate the underlying mechanism. Hydrogen peroxide (H2O2)-induced and Middle Cerebral Artery Occlusion (MCAO)-induced damages were used to imitate oxidative stress. The antioxidation of DH-217 was determined by MTT, ROS, colony and DPPH assay. Besides, immunofluorescence, Real-Time PCR Analyses, western blotting and si-RNA/Plasmid-induced protein expression were used for mechanism validation. DPPH scavenging assay evidenced DH-217 was a well free radical scavenger. Cell survival assay also showed that DH-217 had a significant cytoprotection through direct and indirect clearance mechanisms. Further, it clearly inhibited oxidative stress-induced IkappaB kinase beta (IKKß) phosphorylation and increased heme oxygenase-1 (HO-1) expression. Significantly, these antioxidant beneficial effects were reversed by HO-1 inhibitor, si-nuclear erythroid 2-related factor 2 (Nrf2) and IKKß plasmid. Meanwhile, DH-217 had a good neuroprotective effect on CIRI rats. The dual antioxidant DH-217 has potential reference value for drug development of CIRI. Furthermore, inhibition of IKKß phosphorylation and activation of Nrf2/HO-1 could be a promising antioxidant pathway. Dual antioxidant DH-217 not only has the ability of directly scavenging ROS, but also can clear it by targeting IKKß/Nrf2/HO-1 signal axis. Inhibition of IKKß phosphorylation and activation of Nrf2/HO-1 may be a promising antioxidant pathway for CIRI.

Clinical features and prognosis of acute myocardial infarction caused by non-tumor origin coronary artery embolism.

BACKGROUND: Several studies have indicated that acute myocardial infarction (AMI) secondary to coronary artery embolism (CE) has a poor prognosis. However, in the latter studies, CE of tumor origin accounts for a considerable proportion of cases and the clinical features and contribution to overall prognosis of non-tumor CE are unknown and therefore the subject of this study. METHODS: We retrospectively studied 2006 consecutive patients with AMI at our medical center from January 2014 to October 2018. Non-tumor CE was diagnosed based on angiographic, biochemical, and imaging criteria. Patients were divided into two groups: patients without CE (control) and patients with non-tumor CE. RESULTS: Atrial fibrillation was the most frequent etiology (n = 32, 69.6%) in the non-tumor CE group (n = 46). Compared with the control group, the non-tumor CE group had (all p < 0.05): higher incidence of atrial fibrillation; larger left atrial diameter, left ventricular end-diastolic diameter and left ventricular end-systolic diameter; lower left ventricular ejection fraction, ST-segment-elevation myocardial infarction incidence and low density lipoprotein cholesterol level; lower incidence of multivessel coronary stenosis, level of culprit lesion stenosis and proportion of angioplasty; higher ratio of manual thrombectomy and antithrombotic drugs alone therapy; lower thrombolysis in myocardial infarction (TIMI) grade and higher corrected TIMI frame counts (CTFC) after reperfusion; and statistically similar overall survival at median 864 (interquartile range, 413-1272) days. CONCLUSIONS: The overall incidence of non-tumor CE was 2.3%, with atrial fibrillation as its most common etiology. Midterm overall survival was similar between AMI patients secondary to non-tumor CE and those without CE.

Synthesis and anti-myocarditis activity in a multifunctional lanthanide microporous metal-organic framework with 1D helical chain building units.

A new microporous lanthanide metal-organic framework, {[Yb(BTB)(H2O) (DEF)2}n (1, DEF=N,N-Diethylformamide), with 1D nano-sized channels has been constructed by bridging helical chain secondary building units with 1,3,5-benzenetrisbenzoic acid (H3BTB) ligand. Structural characterization suggests that this complex crystallizes in the hexagonal space group P6122 and possesses 1D triangular channels with coordinated water molecules pointing to the channel center. In addition, anti-myocarditis properties of compound 1 were evaluated in vivo. The results showed that compound 1 can improve hemodynamic parameters of, and it may be a good therapeutic option for heart failure in the future.

Synthesis and anti-myocarditis activity in a multifunctional lanthanide microporous metal-organic framework with 1D helical chain building units

A new microporous lanthanide metal-organic framework, {[Yb(BTB)(H2O) (DEF)2}n (1, DEF=N,N-Diethylformamide), with 1D nano-sized channels has been constructed by bridging helical chain secondary building units with 1,3,5-benzenetrisbenzoic acid (H3BTB) ligand. Structural characterization suggests that this complex crystallizes in the hexagonal space group P6122 and possesses 1D triangular channels with coordinated water molecules pointing to the channel center. In addition, anti-myocarditis properties of compound 1 were evaluated in vivo. The results showed that compound 1 can improve hemodynamic parameters of, and it may be a good therapeutic option for heart failure in the future.