ABSTRACT
Ischemic stroke is one of the leading causes of death worldwide. In the post-stroke stage, cardiac dysfunction is common and is known as the brain-heart interaction. Diabetes mellitus worsens the post-stroke outcome. Stroke-induced systemic inflammation is the major causative factor for the sequential complications, but the mechanism underlying the brain-heart interaction in diabetes has not been clarified. The NLRP3 (NLR pyrin domain-containing 3) inflammasome, an important component of the inflammation after stroke, is mainly activated in M1-polarized macrophages. In this study, we found that the cardiac dysfunction induced by ischemic stroke is more severe in a mouse model of type 2 diabetes. Meanwhile, M1-polarized macrophage infiltration and NLRP3 inflammasome activation increased in the cardiac ventricle after diabetic stroke. Importantly, the NLRP3 inflammasome inhibitor CY-09 restored cardiac function, indicating that the M1-polarized macrophage-NLRP3 inflammasome activation is a pathway underlying the brain-heart interaction after diabetic stroke.
ABSTRACT
Ischemic stroke is one of the leading causes of death worldwide. In the post-stroke stage, cardiac dysfunction is common and is known as the brain-heart interaction. Diabetes mellitus worsens the post-stroke outcome. Stroke-induced systemic inflammation is the major causative factor for the sequential complications, but the mechanism underlying the brain-heart interaction in diabetes has not been clarified. The NLRP3 (NLR pyrin domain-containing 3) inflammasome, an important component of the inflammation after stroke, is mainly activated in M1-polarized macrophages. In this study, we found that the cardiac dysfunction induced by ischemic stroke is more severe in a mouse model of type 2 diabetes. Meanwhile, M1-polarized macrophage infiltration and NLRP3 inflammasome activation increased in the cardiac ventricle after diabetic stroke. Importantly, the NLRP3 inflammasome inhibitor CY-09 restored cardiac function, indicating that the M1-polarized macrophage-NLRP3 inflammasome activation is a pathway underlying the brain-heart interaction after diabetic stroke.
ABSTRACT
Pheromone-binding proteins transport hydrophobic pheromones through the aqueous medium to their receptors. The odorant-binding protein (OBP) of Culex quinquefasciatus (CquiOBP1), which binds to an oviposition pheromone (5R,6S)-6-acetoxy-5-hexadecanolide (MOP), plays a key role in sensing oviposition cues. However, so far the mechanism of MOP release from the protein is unclear. Therefore, in this contribution the process and pathway of the MOP release from CquiOBP1 are determined by conventional molecular dynamics, essential dynamics (ED), and ED sampling. The detailed analysis of the release process suggests the intrinsic flexibility of MOP, the distribution of contacts with MOP and local conformational changes of CquiOBP1 is crucial.
Subject(s)
Insect Proteins/chemistry , Molecular Dynamics Simulation , Pheromones/chemistry , Pyrones/chemistry , Receptors, Odorant/chemistry , Animals , Binding Sites , Culex , Ligands , Protein Binding , Protein Structure, Secondary , Protein Structure, TertiaryABSTRACT
Molecular dynamics simulations were performed for investigating the thermal stability of the extremely thermophilic Thermoanaerobacter tengcongensis ribose binding protein (tteRBP) and the mesophilic homologous Escherichia coli ribose binding protein (ecRBP). The simulations for the two proteins were carried out under the room temperature (300 K) and the optimal activity temperature (tteRBP 375 K and ecRBP 329 K), respectively. The comparative analyses of the trajectories show that the two proteins have stable overall structures at the two temperatures; further analyses indicate that they both have strong side-chain interactions and different backbone flexibilities at the different temperatures. The tteRBP 375 K and ecRBP 329 K have stronger internal motion and higher flexibility than tteRBP 300 K and ecRBP 300 K, respectively, it is noted that the flexibility of tteRBP is much higher than that of ecRBP at the two temperatures. Therefore, tteRBP 375 K can adapt to high temperature due to its higher flexibility of backbone. Combining with the researches by Cuneo et al., it is concluded that the side-chain interactions and flexibility of backbone are both the key factors to maintain thermal stability of the two proteins. An animated Interactive 3D Complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:JBSD:22.
Subject(s)
Bacterial Proteins/chemistry , Molecular Dynamics Simulation , Periplasmic Binding Proteins/chemistry , Algorithms , Bacterial Proteins/metabolism , Escherichia coli Proteins/chemistry , Hydrogen Bonding , Periplasmic Binding Proteins/metabolism , Protein Binding , Protein Conformation , Ribose/chemistry , Ribose/metabolism , Thermoanaerobacter/enzymologyABSTRACT
Objective To explore the relationship of vascular endothelial growth factor(VEGF),IFN-? and IL-4 and effect of Bude-sonide on their in asthmatic rats.Methods Thirty-six male SD rats were randomly divided into 3 groups:asthma group,Budesonide-treatment group and control group.On the first day of the experiment and the 8th day,the rat models of the asthma group and Budesonid treatment group were allergized by the OVA/Al(OH)3 through intraperitoneal injection,respectively.And starting from the 15th day,they were challenged by the OVA through atomization for 2 weeks.Control group was allergized and challenged by NS atomization.Budesonid treatment group was interfered in Budesonide inhalation before suscitation in 0.5 h.After 12 h the same inhal done was again in Budesonide group.Twenty-four hours after the last challenge,the rats in 3 groups were sacrificed,and blood and bronchoalveolar lavage fluid(BALF) were collected.The concentrations of IL-4,IFN-? and VEGF in serum and BALF were measured by enzyme-linked immunosorbent assay.Results The concentrations of IL-4 in serum and BALF in asthma group and Budesonide treatment group were significantly increased than those in control group(P
