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Glucocorticoid receptor

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https://www.readbyqxmd.com/read/27919827/pkc%C3%AE-ii-mediated-cross-talk-of-trpv1-cb2-modulates-the-glucocorticoid-induced-osteoclast-overactivity
#1
Giulia Bellini, Marco Torella, Iolanda Manzo, Chiara Tortora, Livio Luongo, Francesca Punzo, Nicola Colacurci, Bruno Nobili, Sabatino Maione, Francesca Rossi
In this study, we investigated the role of the endovanilloid/endocannabinoid system in the glucocorticoid-induced osteoclast overactivity. Receptorial and enzymatic component of the endovanilloid/endocannabinoid system are expressed in bone cells, and dysregulated when bone mass is reduced. Moreover, blockade or desensitization of vanilloid receptor 1 (TRPV1) and/or stimulation of cannabinoid receptor 2 (CB2) are beneficial for reducing number and activity of the bone cells modulating resorption, the osteoclasts...
December 2, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27919657/synthesis-of-novel-steroidal-agonists-partial-agonists-and-antagonists-for-the-glucocorticoid-receptor
#2
Zhuang Jin, Hua Lin, Sathish Srinivasan, Jerome C Nwachukwu, Nelson Bruno, Patrick R Griffin, Kendall W Nettles, Theodore M Kamenecka
Adverse effects of glucocorticoids could be limited by developing new compounds that selectively modulate anti-inflammatory activity of the glucocorticoid receptor (GR). We have synthesized a novel series of steroidal GR ligands, including potent agonists, partial agonists and antagonists with a wide range of effects on inhibiting secretion of interleukin-6. Some of these new ligands were designed to directly impact conformational stability of helix-12, in the GR ligand-binding domain (LBD). These compounds modulated GR activity and glucocorticoid-induced gene expression in a manner that was inversely correlated to the degree of inflammatory response...
November 15, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27918221/neutrophilic-inflammation-in-asthma-mechanisms-and-therapeutic-considerations
#3
Hun Soo Chang, Tae-Hyeong Lee, Ji Ae Jun, Ae Rin Baek, Jong-Sook Park, So My Koo, Yang-Ki Kim, Ho Sung Lee, Choon-Sik Park
Neutrophilic airway inflammation represents a pathologically distinct form of asthma and frequently appears in symptomatic adulthood asthmatics. However, clinical impacts and mechanisms of the neutrophilic inflammation have not been thoroughly evaluated up to date. Areas covered: Currently, distinct clinical manifestations, triggers, and molecular mechanisms of the neutrophilic inflammation (namely Toll-like receptor, Th1, Th17, inflammasome) are under investigation in asthma. Furthermore, possible role of the neutrophilic inflammation is being investigated in respect to the airway remodeling...
December 5, 2016: Expert Review of Respiratory Medicine
https://www.readbyqxmd.com/read/27916557/histone-acetylation-and-histone-deacetylation-in-neuropathic-pain-an-unresolved-puzzle
#4
REVIEW
Ravneet Kaur Khangura, Anjana Bali, Amteshwar Singh Jaggi, Nirmal Singh
Chronic pain is broadly classified into somatic, visceral or neuropathic pain depending upon the location and extent of pain perception. Evidences from different animal studies suggest that inflammatory or neuropathic pain is associated with altered acetylation and deacetylation of histone proteins, which result in abnormal transcription of nociceptive processing genes. There have been a number of studies indicating that nerve injury up-regulates histone deacetylase enzymes, which leads to increased histone deacetylation and induce chronic pain...
December 2, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27915167/examining-fkbp5-mrna-expression-in-human-ipsc-derived-neural-cells
#5
Richard Lieberman, Henry R Kranzler, Eric S Levine, Jonathan Covault
In peripheral blood leukocytes, FKBP5 mRNA expression is upregulated following glucocorticoid receptor activation. The single nucleotide polymorphism rs1360780 in FKBP5 is associated with psychiatric illness and has functional molecular effects. However, examination of FKBP5 regulation has largely been limited to peripheral cells, which may not reflect regulation in neural cells. We used 27 human induced pluripotent stem cell lines (iPSCs) derived from 20 subjects to examine FKBP5 mRNA expression following GR activation...
November 24, 2016: Psychiatry Research
https://www.readbyqxmd.com/read/27914612/dexamethasone-induced-diuresis-is-associated-with-inhibition-of-the-renin-angiotensin-aldosterone-system-in-rats
#6
Chao Liu, Ning Ge, Jian-Long Zhai, Jian-Xin Zhang
In heart failure (HF) patients, diuretics remain the cornerstone of therapy to relieve fluid retention. However, the resulting volume loss activates the renin-angiotensin-aldosterone system (RAAS), which blunts the decline in volume depletion and blood pressure. RAAS activation, in turn, compromises the diuretic decongesting effect. Although corticosteroids can induce potent diuresis in HF patients, the effects of corticosteroids on RAAS activation remain unclear. Therefore, we assessed the effects of dexamethasone (Dex) on urine output and plasma angiotensin II and aldosterone levels in rats following water deprivation-induced dehydration, following induction of chronic HF (CHF), and following induction of CHF and volume expansion therapy...
December 2016: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/27913746/anti-trachea-inflammatory-effects-of-diosgenin-from-dioscorea-nipponica-through-interactions-with-glucocorticoid-receptor-%C3%AE
#7
Yang Junchao, Wang Zhen, Wang Yuan, Xu Liying, Jiang Libin, Zhu Yuanhong, Zhao Wei, Chen Ruilin, Zhai Lu
Asthma is a heterogeneous disease characterized by symptoms of chronic inflammation and airway structural and functional changes. It affects about 300 million people worldwide and causes 250 000 deaths annually, but its symptoms can be greatly relieved by regular use of inhaled glucocorticoids (GCs). GCs exert their function through interacting with glucocorticoid receptors (GRs). Diosgenin is a naturally occurring steroidal saponin abundantly present in many medicinal plants, including Dioscorea nipponica, which shares a similar steroidal structure with GC...
December 2, 2016: Journal of International Medical Research
https://www.readbyqxmd.com/read/27911748/actions-of-steroids-new-neurotransmitters
#8
Lauren M Rudolph, Charlotte A Cornil, Melinda A Mittelman-Smith, Jennifer R Rainville, Luke Remage-Healey, Kevin Sinchak, Paul E Micevych
Over the past two decades, the classical understanding of steroid action has been updated to include rapid, membrane-initiated, neurotransmitter-like functions. While steroids were known to function on very short time spans to induce physiological and behavioral changes, the mechanisms by which these changes occur are now becoming more clear. In avian systems, rapid estradiol effects can be mediated via local alterations in aromatase activity, which precisely regulates the temporal and spatial availability of estrogens...
November 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27906831/bos-is-associated-with-increased-cytotoxic-pro-inflammatory-cd8-t-nkt-like-and-nk-cells-in-the-small-airways
#9
Greg Hodge, Sandra Hodge, Aeneas Yeo, Phan Nguyen, Emily Hopkins, Holmes-Liew Cl, Paul N Reynolds, Mark Holmes
BACKGROUND: Immunosuppression therapy following lung transplantation fails to prevent bronchiolitis obliterans syndrome (BOS) in many patients, primarily a disease of the small airways. We have reported that BOS is associated with a lack of suppression of cytotoxic mediators, and pro-inflammatory cytokines, in peripheral blood T, NKT-like (particularly CD8+) and NK cells. We also showed a loss of glucocorticoid receptor (GCR) in pro-inflammatory lymphocytes following transplant. It is unknown whether these pro-inflammatory lymphocytes target the small and/or large airways in BOS...
December 1, 2016: Transplantation
https://www.readbyqxmd.com/read/27906551/ald1613-a-novel-long-acting-monoclonal-antibody-to-control-acth-driven-pharmacology
#10
Andrew L Feldhaus, Katie Anderson, Benjamin Dutzar, Ethan Ojala, Patricia Dianne McNeill, Pei Fan, Jenny Mulligan, Sam Marzolf, Charlie Karasek, Michelle Scalley-Kim, Erica Stewart, Jens Billgren, Vanessa Rubin, Kathleen Schneider, David Jurchen, Kathy Snow, Shaun Barnett, Barbara Bengtsson, Brian Baker, John A Latham, Dan Allison, Leon F Garcia-Martinez
ACTH is the primary regulator of adrenal glucocorticoid production. Elevated levels of ACTH play a critical role in disease progression in several indications including congenital adrenal hyperplasia and Cushing's disease. We have generated a specific, high affinity, neutralizing monoclonal antibody (ALD1613) to ACTH. In vitro, ALD1613 neutralizes ACTH-induced signaling via all five melanocortin receptors and inhibited ACTH-induced cAMP accumulation in a mouse adrenal cell line (Y1). ALD1613 administration to wild-type rats significantly reduced plasma corticosterone levels in a dose dependent manner...
December 1, 2016: Endocrinology
https://www.readbyqxmd.com/read/27903902/role-of-the-chromatin-landscape-and-sequence-in-determining-cell-type-specific-genomic-glucocorticoid-receptor-binding-and-gene-regulation
#11
Michael I Love, Matthew R Huska, Marcel Jurk, Robert Schöpflin, Stephan R Starick, Kevin Schwahn, Samantha B Cooper, Keith R Yamamoto, Morgane Thomas-Chollier, Martin Vingron, Sebastiaan H Meijsing
The genomic loci bound by the glucocorticoid receptor (GR), a hormone-activated transcription factor, show little overlap between cell types. To study the role of chromatin and sequence in specifying where GR binds, we used Bayesian modeling within the universe of accessible chromatin. Taken together, our results uncovered that although GR preferentially binds accessible chromatin, its binding is biased against accessible chromatin located at promoter regions. This bias can only be explained partially by the presence of fewer GR recognition sequences, arguing for the existence of additional mechanisms that interfere with GR binding at promoters...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27903230/glucocorticoid-receptor-interacting-co-regulators-putative-candidates-for-future-drug-targeting-therapy
#12
Alessia Di Silvestre, Marianna Lucafò, Sara De Iudicibus, Alessandro Ventura, Stefano Martelossi, Gabriele Stocco, Giuliana Decorti
Glucocorticoids (GCs) are largely used in different inflammatory, autoimmune and proliferative diseases. To date their mechanism of action is not completely clear and more studies are necessary, in particular to explain the great interindividual variability in clinical response. In this panorama the glucocorticoid receptor (GR) has an important role: in fact it regulates the pharmacological response thanks to the capability to interact with different molecules (DNA, RNA, ncRNA and proteins) that are known to influence its activity...
November 29, 2016: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/27903154/type-2-diabetes-mellitus-and-cancer-the-role-of-pharmacotherapy
#13
Gadi Shlomai, Brian Neel, Derek LeRoith, Emily Jane Gallagher
Purpose Type 2 diabetes mellitus (T2DM) is becoming increasingly prevalent worldwide. Epidemiologic data suggest that T2DM is associated with an increased incidence and mortality from many cancers. The purpose of this review is to discuss the links between diabetes and cancer, the effects of various antidiabetic medications on cancer incidence and mortality, and the effects of anticancer therapies on diabetes. Design This study is a review of preclinical and clinical data regarding the effects of antidiabetic medications on cancer incidence and mortality and the effects of anticancer therapies on glucose homeostasis...
December 10, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27901049/glucocorticoid-receptor-and-histone-deacetylase-6-mediate-the-differential-effect-of-dexamethasone-during-osteogenesis-of-mesenchymal-stromal-cells-mscs
#14
Marilyn G Rimando, Hao-Hsiang Wu, Yu-An Liu, Chien-Wei Lee, Shu-Wen Kuo, Yin-Ping Lo, Kuo-Fung Tseng, Yi-Shiuan Liu, Oscar Kuang-Sheng Lee
Lineage commitment and differentiation of mesenchymal stromal cells (MSCs) into osteoblasts in vitro is enhanced by a potent synthetic form of glucocorticoid (GC), dexamethasone (Dex). Paradoxically, when used chronically in patients, GCs exert negative effects on bone, a phenomenon known as glucocorticoid-induced osteoporosis in clinical practice. The mechanism on how GC differentially affects bone precursor cells to become mature osteoblasts during osteogenesis remains elusive. In this study, the dose and temporal regulation of Dex on MSC differentiation into osteoblasts were investigated...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27900869/-evaluation-of-five-years-of-treatment-of-erdheim-chester-disease-with-anakinra-case-report-and-overview-of-literature
#15
Zdeněk Adam, Hana Petrášová, Zdeněk Řehák, Renata Koukalová, Marta Krejčí, Luděk Pour, Eva Vetešníková, Aleš Čermák, Sabina Ševčíková, Petr Szturz, Zdeněk Král, Jiří Mayer
: Erdheim-Chester disease is a histiocytic neoplasm of diseases from the group of non-Langerhans-cell histiocytoses, formed by infiltrates of foamy histiocytes. These pathological histiocytes produce pro-inflammatory cytokines. Therefore Erdheim-Chester disease is called inflammatory histiocytary neoplasm. The disease is accompanied by clinical symptoms of systemic inflammatory response, i.e. B symptoms. Imaging examinations detect typical osteosclerotic changes affecting diaphyses and metaphyses of the lower long bones and fibrotic changes which affect the aorta wall and the vessels leading from it...
2016: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/27898652/natural-mineral-rich-water-ingestion-by-ovariectomized-fructose-fed-sprague-dawley-rats-effects-on-sirtuin-1-and-glucocorticoid-signaling-pathways
#16
Jugal Kishore Das, Milton Severo, Cidália Dionísio Pereira, Emília Patrício, José Magalhães, Rosário Monteiro, Delminda Neves, Maria João Martins
OBJECTIVE: Prevention or induction of metabolic disorders and obesity depend on estrogen signaling and/or exogenous factors, such as mineral content in diet. The protective effects of a Portuguese natural mineral-rich water against the induction of metabolic syndrome in fructose-fed male Sprague-Dawley rats have been reported. The present study was designed to assess the impact of this mineral-rich water on fructose-fed estrogen-deficient female Sprague-Dawley rats. METHODS: Ovariectomized rats had access to tap (TWO) or mineral-rich (MWO) waters, with and without 10% fructose (10-wk treatment)...
November 28, 2016: Menopause: the Journal of the North American Menopause Society
https://www.readbyqxmd.com/read/27897427/structure-based-drug-design-of-mineralocorticoid-receptor-antagonists-to-explore-oxosteroid-receptor-selectivity
#17
Anneli Nordqvist, Gavin O'Mahony, Maria Fridén-Saxin, Marlene Fredenwall, Anders Hogner, Kenneth L Granberg, Anna Aagaard, Stefan Bäckström, Anders Gunnarsson, Tim Kaminski, Yafeng Xue, Anita Dellsén, Eva Hansson, Pia Hansson, Ida Ivarsson, Ulla Karlsson, Krister Bamberg, Majlis Hermansson, Jennie Georgsson, Bo Lindmark, Karl Edman
The mineralocorticoid receptor (MR) is a nuclear hormone receptor involved in regulation of body fluid and electrolyte homeostasis. In this study we explore selectivity triggers for a series of non-steroidal MR antagonists to improve selectivity over other members of the oxosteroid receptor family. A biaryl sulfonamide compound was identified in a high-throughput screening (HTS) campaign. The compound bound to MR with a pKi=6.6, but displayed poor selectivity over the glucocorticoid receptor (GR) and the progesterone receptor (PR)...
November 29, 2016: ChemMedChem
https://www.readbyqxmd.com/read/27895155/investigations-of-glucocorticoid-action-in-gn
#18
Christoph Kuppe, Claudia van Roeyen, Katja Leuchtle, Nazanin Kabgani, Michael Vogt, Marc Van Zandvoort, Bart Smeets, Jürgen Floege, Hermann-Josef Gröne, Marcus J Moeller
For several decades, glucocorticoids have been used empirically to treat rapid progressive GN. It is commonly assumed that glucocorticoids act primarily by dampening the immune response, but the mechanisms remain incompletely understood. In this study, we inactivated the glucocorticoid receptor (GR) specifically in kidney epithelial cells using Pax8-Cre/GR(fl/fl) mice. Pax8-Cre/GR(fl/fl) mice did not exhibit an overt spontaneous phenotype. In mice treated with nephrotoxic serum to induce crescentic nephritis (rapidly progressive GN), this genetic inactivation of the GR in kidney epithelial cells exerted renal benefits, including inhibition of albuminuria and cellular crescent formation, similar to the renal benefits observed with high-dose prednisolone in control mice...
November 28, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27889894/glucocorticoid-induced-leucine-zipper-in-central-nervous-system-health-and-disease
#19
REVIEW
Mythily Srinivasan, Debomoy K Lahiri
The central nervous system (CNS) is a large network of intercommunicating cells that function to maintain tissue health and homeostasis. Considerable evidence suggests that glucocorticoids exert both neuroprotective and neurodegenerative effects on the CNS. Glucocorticoids act by binding two related receptors in the cytoplasm, the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). The glucocorticoid receptor complex mediates cellular responses by transactivating target genes and by protein: protein interactions...
November 26, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27888798/mir-103-inhibits-proliferation-and-sensitizes-hemopoietic-tumor-cells-for-glucocorticoid-induced-apoptosis
#20
Shlomit Kfir-Erenfeld, Noa Haggiag, Moshe Biton, Polina Stepensky, Nathalie Assayag-Asherie, Eitan Yefenof
Glucocorticoid (GC) hormones are an important ingredient of leukemia therapy since they are potent inducers of lymphoid cell apoptosis. However, the development of GC resistance remains an obstacle in GC-based treatment. In the present investigation we found that miR-103 is upregulated in GC-sensitive leukemia cells treated by the hormone. Transfection of GC resistant cells with miR-103 sensitized them to GC induced apoptosis (GCIA), while miR-103 sponging of GC sensitive cells rendered them partially resistant...
November 18, 2016: Oncotarget
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