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The precise mechanism by which glucocorticoid receptor (GR) regulates the transcription of its target genes is largely unknown. This is, in part, due to the lack of structural and functional information about GR's N-terminal activation function domain, AF1. Like many steroid hormone receptors (SHRs), the GR AF1 exists in an intrinsically disordered (ID) conformation or an ensemble of conformers...
A.V. Adamopoulos∗1, S. Likothanassis2, N.G. Pavlidis3, and M.N Vrahatis3 1 Medical Physics Laboratory, Department of Medicine, Democritus University of Thrace, GR-68100 Alexandroupolis, Hellas 2 Pattern Recognition Laboratory, Department of Computer Engineering and Informatics, University of Patras, GR-26500 Patras, Hellas 3 Computational Intelligence Laboratory (CI Lab), University of Patras A...
Background/Aims:. The aim of this study was to elucidate the effects of glucose restriction (GR) on cell replicative senescence in vitro by human diploid fibroblasts IMR-90. Methods: IMR-90 cells were cultured under 40, 60% GR or high glucose medium and biomarkers of cell senescence were compared with cells cultured in normal glucose medium (5.5 mM glucose). The impact of different concentratio...
Type 1 diabetes is a common metabolic disorder accompanied by increased blood glucose levels along with glucocorticoid and cognitive deficits. The disease is also thought to be associated with environmental changes in brain and constantly induces oxidative stress in patients. Therefore, glucocorticoid-mediated negative feedback mechanisms involving the glucocorticoid receptor (GR) binding site ...
The effect of dexamethasone (DEX) on glucocorticoid receptor (GR)-mediated gene expression was examined in the brain of young and aged rats. Electrophoretic mobility shift assays showed that DEX treatment led to an increase of glucocorticoid response element (GRE) binding activity in aged rats, whereas in young animals GRE binding activity was decreased. Western blot analysis and reverse transc...
Monocyte chemoattractant protein 1 (MCP-1) plays a pivotal role in many inflammatory processes, including the progression of atherosclerosis and the response of the arterial wall to injury. We previously demonstrated that dexamethasone (Dex) inhibits MCP-1 mRNA accumulation in smooth muscle cells by decreasing its half-life. The effect of Dex was dependent upon the glucocorticoid receptor (GR) ...
Glucocorticoids (GC) are the primary therapy for idiopathic nephrotic syndrome (NS). Recent evidence has identified glomerular podocytes as a potential site of GC action in this disease. The objectives of this study were to determine the presence of key components of the glucocorticoid receptor (GR) complex and the functionality of this signaling pathway in podocytes and to explore potential op...
Interferon regulatory factor-8 modulates the development of tumour-induced CD11b+Gr-1+ myeloid cells
Tumour-induced myeloid-derived suppressor cells (MDSC) promote immune suppression and mediate tumour progression. However, the molecular basis for the generation of MDSC, which in mice co-express the CD11b(+) and Gr-1(+) cell surface markers remains unclear. Because CD11b(+)Gr-1(+) cells expand during progressive tumour growth, this suggests that tumour-induced events alter signalling pathways ...
Amphotericin B (AmB) has been the first-line treatment for visceral leishmaniasis (VL), a neglected protozoan disease, especially in regions like Bihar, India, where resistance to antimonials is widespread. However, adverse drug reactions are a major limiting factor. We evaluated a novel formulation of AmB conjugated to amine-modified graphene (f-Gr) for safety and efficacy over conventional Am...
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