9 research outputs found

    YAP/TAZ deficiency reprograms macrophage phenotype and improves infarct healing and cardiac function after myocardial infarction

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    Adverse cardiac remodeling after myocardial infarction (MI) causes structural and functional changes in the heart leading to heart failure. The initial post-MI pro-inflammatory response followed by reparative or anti-inflammatory response is essential for minimizing the myocardial damage, healing, and scar formation. Bone marrow-derived macrophages (BMDMs) are recruited to the injured myocardium and are essential for cardiac repair as they can adopt both pro-inflammatory or reparative phenotypes to modulate inflammatory and reparative responses, respectively. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are the key mediators of the Hippo signaling pathway and are essential for cardiac regeneration and repair. However, their functions in macrophage polarization and post-MI inflammation, remodeling, and healing are not well established. Here, we demonstrate that expression of YAP and TAZ is increased in macrophages undergoing pro-inflammatory or reparative phenotype changes. Genetic deletion of YAP/TAZ leads to impaired pro-inflammatory and enhanced reparative response. Consistently, YAP activation enhanced pro-inflammatory and impaired reparative response. We show that YAP/TAZ promote pro-inflammatory response by increasing interleukin 6 (IL6) expression and impede reparative response by decreasing Arginase-I (Arg1) expression through interaction with the histone deacetylase 3 (HDAC3)-nuclear receptor corepressor 1 (NCoR1) repressor complex. These changes in macrophages polarization due to YAP/TAZ deletion results in reduced fibrosis, hypertrophy, and increased angiogenesis, leading to improved cardiac function after MI. Also, YAP activation augmented MI-induced cardiac fibrosis and remodeling. In summary, we identify YAP/TAZ as important regulators of macrophage-mediated pro-inflammatory or reparative responses post-MI

    Green Synthesis and Characterization of Silver Nanoparticles from Azadirachta indica Leaf Extract and its Antibacterial Study

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    Nanotechnology is the emerging branch in the field of science. The current study was conducted on plant-derived material for the green synthesis of silver nanoparticles (AgNPs) using neem leaf extract. The flavonoid and terpenoids found in the extract behaved as a reducing and capping agent. Here, the formation of NPs occurred by the bioreduction of Ag salts into AgNPs by the addition of leaf extract. The reduction was validated by the change in color that is from pale green to brown. The ion to NP reduction occurred due to the natural reducing agent in the neem leaf extract. The functional group presents in the extract and AgNPs are investigated using Fourier transform infrared. The synthesized NPs have undergone characterization by ultraviolet spectrometry between 300 and 700 nm. The peak was spotted at 308 nm. Antibacterial properties of AgNPs were studied against Bacillus subtilis, Pseudomonas aeruginosa, and Staphylococcus aureus. From these results, it can be effectively reported that plant extract can be used in the synthesis of AgNPs and could be used for better results in future in the field of medicine, nano-related works, and so on

    Semaphorin 3E/PlexinD1 Signaling Is Required for Cardiac Ventricular Compaction.

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    10.1172/jci.insight.125908JCI insight416e12590

    Hippo Signaling Mediators Yap and Taz Are Required in the Epicardium for Coronary Vasculature Development

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    Summary: Formation of the coronary vasculature is a complex and precisely coordinated morphogenetic process that begins with the formation of epicardium. The epicardium gives rise to many components of the coronary vasculature, including fibroblasts, smooth muscle cells, and endothelium. Hippo signaling components have been implicated in cardiac development and regeneration. However, a role of Hippo signaling in the epicardium has not been explored. Employing a combination of genetic and pharmacological approaches, we demonstrate that inhibition of Hippo signaling mediators Yap and Taz leads to impaired epicardial epithelial-to-mesenchymal transition (EMT) and a reduction in epicardial cell proliferation and differentiation into coronary endothelial cells. We provide evidence that Yap and Taz control epicardial cell behavior, in part by regulating Tbx18 and Wt1 expression. Our findings show a role for Hippo signaling in epicardial cell proliferation, EMT, and cell fate specification during cardiac organogenesis. : Singh et al. show that Hippo signaling components are expressed in proepicardial and epicardial cells and are required for coronary vasculature development. Yap and Taz regulate epicardial cell proliferation, EMT, and cell fate specification, in part by regulating Tbx18 and Wt1 expression. Keywords: epicardium, proepicardium, Hippo signaling, Yap, Taz, epithelial to mesenchymal transition (EMT

    Problematizing the dominant: the emergence of alternative cultural voices in Fiji rugby

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    Today’s indigenous Fijian culture is often said to be represented by ratuism, religion and rugby. Rugby is widely described as Fiji’s ‘national’ sport, with a considerable degree of social significance. That rugby is listed alongside two powerful institutions(ratuism and religion) in the life of indigenous Fijians is a clear indication of the central cultural importance of the sport. In this paper, drawing upon the existing literature as well as our own research data, we outline the key aspects of the dominant rugby discourse in relation to ratuism and religion, along with exploring some of rugby’s main alternative cultural ‘functions’. Employing a cultural studies approach, our main goal is to interpret and (re)present some of the chief alternative discourses in Fiji rugby and to discuss their role in the formation of dominant and emergent cultural practices
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