ABSTRACT
Cardiac-resident macrophages (CRMs) play important roles in homeostasis, cardiac function, and remodeling. Although CRMs play critical roles in cardiac regeneration of neonatal mice, their roles are yet to be fully elucidated. Therefore, this study aimed to investigate the dynamic changes of CRMs during cardiac ontogeny and analyze the phenotypic and functional properties of CRMs in the promotion of cardiac regeneration. During mouse cardiac ontogeny, four CRM subsets exist successively: CX3CR1+CCR2-Ly6C-MHCII- (MP1), CX3CR1lowCCR2lowLy6C-MHCII- (MP2), CX3CR1-CCR2+Ly6C+MHCII- (MP3), and CX3CR1+CCR2-Ly6C-MHCII+ (MP4). MP1 cluster has different derivations (yolk sac, fetal liver, and bone marrow) and multiple functions population. Embryonic and neonatal-derived-MP1 directly promoted cardiomyocyte proliferation through Jagged-1-Notch1 axis and significantly ameliorated cardiac injury following myocardial infarction. MP2/3 subsets could survive throughout adulthood. MP4, the main population in adult mouse hearts, contributed to inflammation. During ontogeny, MP1 can convert into MP4 triggered by changes in the cellular redox state. These findings delineate the evolutionary dynamics of CRMs under physiological conditions and found direct evidence that embryonic and neonatal-derived CRMs regulate cardiomyocyte proliferation. Our findings also shed light on cardiac repair following injury.
ABSTRACT
Background: Stroke is a leading cause of death all around the world, and ischemic stroke is considered to be the most common stroke type. Toll-like receptors [TLRs] are important molecules for detection of both pathogen invasion and tissue damage. In this regard, the purpose of this study was to assess the expression level of TLR2 on monocytes in patients with ischemic stroke and to evaluate the expression change profile following high-mobility group box 1 [HMGB1] stimulation
Methods: A total of 30 patients with ischemic stroke were enrolled from November 2013 to September 2014. The real-time PCR and ELISA assays were applied to detect the concentrations of TLR2 mRNAs
Results: TLR2 expression was found to be increased in patients with ischemic stroke, as compared to the healthy control group [P<0.001]. Also, anti-TLR2 antibodies were able to decrease the expression levels of IL-17, IL-6 and IL-33. This result implies that the enhanced TLR2 pathway and Th17 cell polarization may be due to HMGB1 stimulation in ischemic stroke
Conclusion: Further clinical studies are needed for development of a new treatment strategy to inhibit the HMGB1 pathway, thus preventing the inflammation in ischemic stroke patients
ABSTRACT
Antifungal drug resistance and few numbers of available drugs limit therapeutic options against fungal infections. The present study was designed to discover new antifungal drugs. This study was carried out in two separate steps, that is, in silico lead identification and in vitro assaying of antifungal potential. A structural data file of a ternary complex of fusicuccin [legend], C terminus of H[+]-ATPase and 14-3-3 regulatory protein [lo9F.pdb file] was used as a model. Computational screening of a virtual 3D database of drug-like molecules was performed and selected small molecules, resembling the functional part of the ligand performing ligand docking, were tested using ArgusLab [4.0.1]. Two lead compounds, 3-Cyclohexan propionic acid [CXP] and 4-phenyl butyric acid [PBA] were selected according to their ligation scores. Standard Strains of Candida albicans and Saccharomyces cerevisiae were used to measure the antifungal potential of the two identified lead compounds against the fungi using micro-well plate dilution assay. Ligation scores for CXP and PBA were -9.33744 and -10.7259 kcal/mol, respectively, and MIC and MFC of CXP and PBA against the two yeasts were promising. The evidence from the present study suggests that CXP and PBA possess potentially antifungals properties
ABSTRACT
IL-4 is a cytokine that induces differentiation of naive helper T cells into Th2 cells. Once activated by IL-4, Th2 cells subsequently produce additional IL-4. To examine the effect of IL-4 on IL-17 production and its effect in Collagen-Induced Arthritis [CIA] mice. Method: In this study, a chicken collagen-II-induced experimental arthritis [CIA] model was used in DBA/1 mice to investigate the relationship between IL-4 and IL-17 as well as other inflammatory factors. On the 38th day after the mice were induced with CIA, the expression of IL-17 and IL-4 as well as IFN-gamma and IL-13 in sera of the mice was measured by QRT-PCR and ELISA. The result of QRT-PCR analysis of IL-17 and IL-4 mRNA levels in the spleen showed that IL-17 is increased significantly at the onset of CIA in the spleen [p<0.01]. Meanwhile, IL-17 is generally reduced at the peak of CIA but IL-4 is increased significantly at this peak in the spleen [p<0.05] when the weight of the animal was taken into consideration. IL-4 can be involved in the production of IL-17 at especially the peak of CIA. These results imply that the inhibition of IL-17 may decrease the expression of IL-lp and IL-6 production which will result in the aggravation of arthritis