Evolution of Nuclear Receptors and Ligand Signaling: Toward a Soft Key-Lock Model?

Evolution of Nuclear Receptors and Ligand Signaling: Toward a Soft Key-Lock Model? Curr Top Dev Biol. 2017;125:1-38 Authors: Holzer G, Markov GV, Laudet V Abstract Nuclear receptors (NRs) are a family of ligand-regulated transcription factors that modulate a wide variety of physiological functions in a ligand-dependent manner. The first NRs were discovered as receptors of well-known hormones such as 17β-estradiol, corticosteroids, or thyroid hormones. In these cases a direct activation of the receptor transcriptional activity by a very specific ligand, with nanomolar affinity, was demonstrated, providing a strong conceptual framework to understand the mechanism of action of these hormones. However, the discovery that some NRs are able to bind different ligands with micromolar affinity was a first sign that the univocal relationship between a specific receptor (e.g., TR) and a specific ligand (e.g., thyroid hormone) should not be generalized to the whole family. These discussions about the nature of NR ligands have been reinforced by the study of the hormone/receptor couple evolution. Indeed when the ligand is not a protein but a small molecule derived from a biochemical pathway, a simple coevolution mechanism between the ligand and the receptor cannot operate. We and others have recently shown that the ligands acting for a given NR early on during evolution were often different from the classical mammalian ligands. This suggests that the NR/ligand e...
Source: Current Topics in Developmental Biology - Category: Biology Authors: Tags: Curr Top Dev Biol Source Type: research

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Publication date: Available online 16 August 2018Source: Colloids and Surfaces B: BiointerfacesAuthor(s): Zhao Yin Ng, Jin-Ying Wong, Jithendra Panneerselvam, Thiagarajan Madheswaran, Pradeep Kumar, Viness Pillay, Alan Hsu, Nicole Hansbro, Mary Bebawy, Peter Wark, Philip Hansbro, Kamal Dua, Dinesh Kumar ChellappanAbstractCurcumin a component of turmeric, which is derived from Curcuma longa is used as a coloring agent and as a dietary spice for centuries. Extensive studies have been done on the anti-inflammatory activity of curcumin along with its molecular mechanism involving different signalling pathways. However, the phy...
Source: Colloids and Surfaces B: Biointerfaces - Category: Biochemistry Source Type: research
Conclusions: In critically ill patients with sepsis, corticosteroids possibly result in a small reduction in mortality while also possibly increasing the risk of neuromuscular weakness.
Source: Critical Care Medicine - Category: Emergency Medicine Tags: Feature Articles Source Type: research
Authors: Galluzzo A, Imazio M Abstract INTRODUCTION: Medical therapy of pericardial diseases is moving forward to the road of evidence-based medicine and has improved in the last years because of the first randomized clinical trials in the area as well as new therapeutic options for recurrent pericarditis. Areas covered: The present review will focus on more recent advances with a special emphasis on the treatment of pericarditis, the area with more significant improvements in the last years. Medline/Pubmed Library were systematically screened with two specific key searches: "pericarditis AND therapy" and...
Source: Expert Review of Cardiovascular Therapy - Category: Cardiology Tags: Expert Rev Cardiovasc Ther Source Type: research
Conclusions: This study demonstrated significant in vivo supraspinatus tenotoxicity following a single injection of combination local anesthetic/ corticosteroid when compared to saline controls. Level of Evidence: Level II. PMID: 30104932 [PubMed - in process]
Source: Iowa orthopaedic journal - Category: Orthopaedics Tags: Iowa Orthop J Source Type: research
ConclusionsAlthough these results suggest that control of inflammation could have a beneficial effect on the lipid profile through an increase in HDL cholesterol levels, the observed protective effect on cardiovascular disease events by tumor necrosis factor blockers is likely to be explained by other mechanisms than changes in lipid levels or short-term effects on atherosclerosis of the carotid artery.
Source: Current Therapeutic Research - Category: Drugs & Pharmacology Source Type: research
Conclusion Our data indicated that both adherence to ICS and device handling errors contributed to asthma control in this population. PMID: 30101909 [PubMed - as supplied by publisher]
Source: Internal Medicine - Category: Internal Medicine Tags: Intern Med Source Type: research
Authors: Ohara N, Hirokawa M, Kobayashi M, Ikeda Y, Yoneoka Y, Seki Y, Akiyama K, Tani T, Terajima K, Ozawa T Abstract A 69-year-old Japanese man with a history of suprasellar surgery and irradiation developed bradykinesia and mild fatigue without muscle weakness, myalgia, pyramidal or extrapyramidal signs, parkinsonian symptoms, or ataxia. An endocrinological work-up revealed anterior hypopituitarism associated with secondary adrenal insufficiency. Higher brain function tests indicated an impaired frontal lobe function. The patient's bradykinesia, fatigue, and frontal lobe dysfunction improved within 2 weeks after...
Source: Internal Medicine - Category: Internal Medicine Tags: Intern Med Source Type: research
ConclusionsOur cases highlight that paediatricians should be aware of the clinical presentations of and therapeutic approaches for DRESS syndrome, especially in children receiving long-term antibiotic treatment. The removal of the offending drug is crucial and may be the only life-saving measure. In more aggressive cases, corticosteroid or other immunosuppressive drugs should be considered to achieve the best outcome.
Source: Italian Journal of Pediatrics - Category: Pediatrics Source Type: research
Source: BMJ Comments - Category: General Medicine Source Type: forums
Conditions:   Keloid;   Alopecia Areata;   Acne;   Hypertrophic Scar;   Epidermal Inclusion Cyst;   Frontal Fibrosing Alopecia;   Lichen Plano-Pilaris;   Keratoacanthoma;   Plaque Psoriasis;   Lichen Simplex Chronicus;   Prurigo Nodularis;   Nummular Eczema;   Granuloma Annulare;   M orphea;   Lichen Planus Interventions:   Drug: Corticosteroid with lidocaine;   Drug: Corticosteroid with normal saline Sponsor:   Vanderbilt Uni...
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
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