RESUMO
Navafenterol is a new compound with both muscarinic receptor antagonist and β2 receptor agonist effects in a single molecule, who is being developed for the treatment of chronic obstructive airway disease such as chronic obstructive pulmonary disease and asthma. These pilot clinical studies found that it can significantly improve lung function and symptoms, and is safe and well tolerated. Common treatment emergent adverse events include headache, nasopharyngitis, and dizziness. It may become a next-generation bronchodilator for chronic obstructive airway disease. This review introduced the prospective of Navafenterol.
RESUMO
BACKGROUND:Bone marrow mesenchymal stem cel transplantation for myocardial infarction becomes popularized in recent years, but transplanted cels cannot survive and proliferate under early inflammatory reaction or local ischemia/hypoxia microenvironment, eventualy hampering the therapeutic outcomes. OBJECTIVE:To investigate the therapeutic effect of PTEN-silenced bone marrow mesenchymal stem cels on acute myocardial infarction. METHODS:(1) Bone marrow mesenchymal stem cels from Sprague-Dawley rats were randomly assigned to receive no treatment, NCsiRNA transfection using Lipofectamin2000orPTEN siRNA transfection using Lipofectamin2000. Cel growth curves were described using MTT method to detect cel cycle using flow cytometry. (2) Thirty Sprague-Dawley rats were selected to prepare myocardial infarction models that were randomized into three groups (n=10 per group): blank control, negative control and RNAi group. Six hours after modeling, bone marrow mesenchymal stem cels transfected with nothing, NCsiRNA and PTEN siRNA were respectively injected into the infarcted center of the left ventricular anterior wal in these three rat groups. After 4 weeks, al rats were subjected to cardiac function detection using echocardiography, and the survival and proliferation of bone marrow mesenchymal stem cels in the rats were observed by fluorescence microscopy. RESULTS AND CONCLUSION:Compared with the other two groups, a significant increase in the absorbance values at different culture time, the proportion of cels in S+G2phase, and the number ofbone marrow mesenchymal stem cels in the myocardial tissue was found in the RNAi group (alP< 0.05). Additionaly, the left ventricular ejection fraction and left ventricular shortening fraction were significantly reduced in the RNAi group than the blank control and negative control groups at 4 weeks after cel transplantation (P< 0.05). Bothin vivoandin vitroexperimental findings showed that PTEN silencing could effectively improve cel survival and proliferation in the infarcted myocardium. Moreover, in thein vivoexperiment, an overt improvement in rat’s cardiac function was achieved.
RESUMO
Objective Dexmedetomidine is known to have a neuroprotective effect.The aim of this study was to investigate the effects of dexmedetomidine on ketamine-induced apoptosis of primarily cultured cortical neurons and its action mechanisms. Methods Rat cortical neurons were primarily cultured for 7 days and treated with ketamine (100μmol/L) and different concentrations of dexmedetomi-dine (0.001, 0.01, 0.1, and 1 μmol/L) for 24 hours, followed by measurement of the viability of the neurons by MTT assay.The neurons were divided into four groups:vehicle control, ketamine ( trea-ted with 100 μmol/L ketamine), dexmedetomidine+ketamine (DD+K, treated with 0.1 μmol/L DD and 100 μmol/L ketamine), and LY294002 ( treated with 0.1 μmol/L DD, 100 μmol/L ketamine, and 10 μmol/L LY294002) .After 24 hours of treatment, the apoptosis rate of the neurons was determined by Hoechst33258 staining, and the expressions of pAkt and cleaved-caspase-3 in the neu-rons detected by Western blot. Results The apoptosis rate of neurons was dramatically increased in the LY294002 and ketamine groups in comparison with the vehicle control and DD+K groups ([36.8 ±4.4] and [43.4 ±4.5]%vs [7.5 ±1.1] and [16.4 ± 3.6]%, P<0.01), the pAkt level remarkably decreased (0.26 ±0.02 and 0.15 ±0.01 vs 0.61 ±0.05 and 0.50 ±0.04, P<0.01), and the expression of cleaved caspase-3 significantly upregulated in the former two as compared with the latter two groups (0.40 ±0.02 and 0.65 ±0.03 vs 0.10 ±0.02 and 0.12 ±0.01, P<0.01). Conclusion Dexmedetomidine exerts a neuroprotec-tive effect against ketamine-induced apoptosis of neurons by activating the PI3K-Akt signaling pathway.
