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https://www.readbyqxmd.com/read/28107661/targeting-nf-kb-signaling-with-polymeric-hybrid-micelles-that-co-deliver-sirna-and-dexamethasone-for-arthritis-therapy
#1
Qin Wang, Hao Jiang, Yan Li, Wenfei Chen, Hanmei Li, Ke Peng, Zhirong Zhang, Xun Sun
The transcription factor NF-kB plays a pivotal role in the pathogenesis of rheumatoid arthritis. Here we attempt to slow arthritis progression by co-delivering the glucocorticoid dexamethasone (Dex) and small-interfering RNA targeting NF-kB p65 using our previously developed polymeric hybrid micelle system. These micelles contain two similar amphiphilic copolymers: polycaprolactone-polyethylenimine (PCL-PEI) and polycaprolactone-polyethyleneglycol (PCL-PEG). The hybrid micelles loaded with Dex and siRNA effectively inhibited NF-kB signaling in murine macrophages more efficiently than micelles containing either Dex or siRNA on their own...
January 11, 2017: Biomaterials
https://www.readbyqxmd.com/read/28105134/increased-circulating-il-9-producing-cd8-t-cells-are-associated-with-eosinophilia-and-high-feno-in-allergic-asthmatics
#2
Wei Wang, Zhen-Shun Cheng, Yi-Fei Chen, Yu-Hui Lin
Allergic asthma is a chronic airway disorder mediated by Th2 cells. It has been shown that IL-9-producing CD8(+) cytotoxic T (Tc9) cells promote the subsequent onset of allergic airway inflammation in mice mediated by abnormal Th2 immunity. Whether Tc9 cells are associated with the immunopathogenesis of asthmatic patients remains unknown. In the present study, peripheral blood mononuclear cells (PBMCs) were separated by Ficoll-Hypaque gradient centrifugation from all subjects. The frequency of Tc9 cells was measured by flow cytometry...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28105104/glucocorticoids-regulate-the-proliferation-of-t-cells-via-mirna-155-in-septic-shock
#3
Ying Chen, Guang Wang, Zhongmin Liu, Shiji Wang, Yushan Wang
Although previous studies have evaluated the roles of glucocorticoids and lymphocytes in septic shock, the precise mechanism remains unclear. The present study focused on investigating the influence of glucocorticoids on micro (mi)RNA-155 expression levels and the proliferation of T lymphocytes in septic shock. T cells were harvested from in the peripheral blood of patients with septic shock and healthy volunteers and were cultured in vitro. miRNA-155 levels and cell proliferation rates were subsequently analyzed...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28104732/iatrogenic-cushing-s-syndrome-due-to-topical-ocular-glucocorticoid-treatment
#4
Daisuke Fukuhara, Toshihiko Takiura, Hiroshi Keino, Annabelle A Okada, Kunimasa Yan
Iatrogenic Cushing's syndrome (CS) is a severe adverse effect of systemic glucocorticoid (GC) therapy in children, but is extremely rare in the setting of topical ocular GC therapy. In this article, we report the case of a 9-year-old girl suffering from idiopathic uveitis who developed CS due to topical ocular GC treatment. She was referred to the ophthalmology department with a complaint of painful eyes, at which time she was diagnosed with bilateral iridocyclitis and started on a treatment of betamethasone sodium phosphate eye drops...
January 19, 2017: Pediatrics
https://www.readbyqxmd.com/read/28103963/sex-differences-in-early-life-programming-of-the-hypothalamic-pituitary-adrenal-axis-in-humans-suggest-increased-vulnerability-in-females-a-systematic-review
#5
T Carpenter, S M Grecian, R M Reynolds
Fetal glucocorticoid overexposure is a key mechanism linking early development with later-life disease. In humans, low birth weight associates with increased fasting cortisol, hypothalamic-pituitary-adrenal (HPA) axis reactivity, and with cardiovascular risk and cognitive decline. As there are sex differences in these adult diseases, we hypothesized that there may be sex differences in programming of the HPA axis in response to prenatal stressors. We conducted a systematic review following Meta-Analysis of Observational Studies in Epidemiology and Preferred Reporting Items for Systematic Reviews and Meta-Analysis...
January 20, 2017: Journal of Developmental Origins of Health and Disease
https://www.readbyqxmd.com/read/28102225/glucocorticoid-receptor-signalling-activates-yap-in-breast-cancer
#6
Giovanni Sorrentino, Naomi Ruggeri, Alessandro Zannini, Eleonora Ingallina, Rebecca Bertolio, Carolina Marotta, Carmelo Neri, Elisa Cappuzzello, Mattia Forcato, Antonio Rosato, Miguel Mano, Silvio Bicciato, Giannino Del Sal
The Hippo pathway is an oncosuppressor signalling cascade that plays a major role in the control of cell growth, tissue homoeostasis and organ size. Dysregulation of the Hippo pathway leads to aberrant activation of the transcription co-activator YAP (Yes-associated protein) that contributes to tumorigenesis in several tissues. Here we identify glucocorticoids (GCs) as hormonal activators of YAP. Stimulation of glucocorticoid receptor (GR) leads to increase of YAP protein levels, nuclear accumulation and transcriptional activity in vitro and in vivo...
January 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28102022/the-flavonoid-7-4-dihydroxyflavone-prevents-dexamethasone-paradoxical-adverse-effect-on-eotaxin-production-by-human-fibroblasts
#7
Changda Liu, Nan Yang, Xiaoke Chen, Jody Tversky, Jixun Zhan, Mirna Chehade, Rachel L Miller, Xiu-Min Li
Eotaxin/CCL-11 is a major chemoattractant that contributes to eosinophilic inflammation in asthma. Glucocorticoids inhibit inflammation, but long-time exposure may cause paradoxical adverse effects by augmenting eotaxin/CCL-11production. The aim of this study was to determine if 7,4'-dihydroxyflavone (7,4'-DHF), the eotaxin/CCL11 inhibitor isolated from Glycyrrhiza uralensis, reduces in vitro eotaxin production induced by long-time dexamethasone (Dex) exposure, and if so, to elucidate the mechanisms of this inhibition...
January 19, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28101914/prenatal-stress-exposure-generates-higher-early-survival-and-smaller-size-without-impacting-developmental-rate-in-a-pacific-salmon
#8
Pauline M Capelle, Christina A D Semeniuk, Natalie M Sopinka, John W Heath, Oliver P Love
Prenatal exposure to elevated glucocorticoids can act as a signal of environmental stress, resulting in modifications to offspring phenotype. While "negative" phenotypic effects (i.e., smaller size, slower growth) are often reported, recent research coupling phenotype with other fitness-related traits has suggested positive impacts of prenatal stress. Using captive Chinook salmon (Oncorhynchus tshawytscha), we treated eggs with biologically relevant cortisol levels-low (300 ng mL(-1) ), high (1,000 ng mL(-1) ), or control (0 ng mL(-1) )-to examine the early-life impacts of maternally transferred stress hormones on offspring...
January 18, 2017: Journal of Experimental Zoology. Part A, Ecological Genetics and Physiology
https://www.readbyqxmd.com/read/28101786/evaluation-of-t-regulatory-lymphocytes-transcription-factors-in-htlv-1-associated-myelopathy-tropical-spastic-paraparesis-ham-tsp-patients
#9
Sanaz Ahmadi Ghezeldasht, Hamed Sadeghian, Mahmoud Reza Azarpazhooh, Seyyed Ali Akbar Shamsian, Houshang Rafatpanah, Mahmood Mahmoodi, Seyyed Abdolrahim Rezaee
HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an aggressive neurological disease. The CD4(+)CD25(+) T cell population plays pivotal roles in the maintenance of immunological tolerance and prevention of such autoimmune diseases. In the current study, proviral load (PVL), factor forkhead box p3 (Foxp3), and glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) gene expression and regulatory T cells (Tregs) counts of 21 HAM/TSP patients and 16 HTLV-1 healthy carriers (ACs) were measured using real-time PCR, TaqMan method, and flow cytometry...
January 18, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/28101171/effect-of-glucocorticoid-on-cytokines-tlr9-and-tlr7-in-peripheral-blood-for-patients-with-uveitis
#10
Hong-Pei Cui, Yu-Xi Pei, Guan-Feng Li, Yan-Rui Lou
The effect of glucocorticoid on cytokines Toll-like receptor (TLR)9 and TLR7 in peripheral blood of patients with uveitis was explored. Forty-six patients with uveitis admitted to our hospital from April 2014 to April 2015 were selected as the research observational group. Thirty-five able-bodied individuals in the same period were selected as the control group. To treat uveitis, the observational group was injected with glucocorticoid (1-2 mg/kg/day) daily, while the control group did not receive any treatment...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28100283/genetic-influences-on-hormonal-markers-of-chronic-hypothalamic-pituitary-adrenal-function-in-human-hair
#11
E M Tucker-Drob, A D Grotzinger, D A Briley, L E Engelhardt, F D Mann, M Patterson, C Kirschbaum, E K Adam, J A Church, J L Tackett, K P Harden
BACKGROUND: Cortisol is the primary output of the hypothalamic-pituitary-adrenal (HPA) axis and is central to the biological stress response, with wide-ranging effects on psychiatric health. Despite well-studied biological pathways of glucocorticoid function, little attention has been paid to the role of genetic variation. Conventional salivary, urinary and serum measures are strongly influenced by diurnal variation and transient reactivity. Recently developed technology can be used to measure cortisol accumulation over several months in hair, thus indexing chronic HPA function...
January 19, 2017: Psychological Medicine
https://www.readbyqxmd.com/read/28100016/validation-of-an-enzyme-immunoassay-and-comparison-of-fecal-cortisol-metabolite-levels-in-black-and-gold-howler-monkeys-alouatta-caraya-inhabiting-fragmented-and-continuous-areas-of-the-humid-chaco-region-argentina
#12
Verónica Inés Cantarelli, Maria Amparo Perez-Rueda, Martin M Kowalewski, Gabriela F Mastromonaco, Marina Flavia Ponzio
In the last years, the study of how environmental stimuli influence the physiology and specifically the endocrinology of an organism became increasingly important, relying mainly on the quantification of glucocorticoids to monitor animal welfare. Most studies investigating cortisol levels in primates were focused on the impact of social stressors; however, a major concern for the conservation of howler monkeys is the increased habitat fragmentation led by the advancement of the agricultural frontier. We compared fecal cortisol metabolite levels (FGCM) in howler monkeys (Alouatta caraya) living in fragmented and continuous forests of the Argentine humid Chaco region, throughout the warm season (spring-summer)...
January 18, 2017: American Journal of Primatology
https://www.readbyqxmd.com/read/28099820/new-and-developing-non-adrenoreceptor-small-molecule-drugs-for-the-treatment-of-asthma
#13
Neil C Thomson
Introduction Inhaled corticosteroids (ICS) alone or in combination with an inhaled long-acting beta2-agonist (LABA) are the preferred long-term treatment for adults and adolescents with symptomatic asthma. Additional drugs include leukotriene-receptor antagonists, slow-release theophylline and the long-acting muscarinic antagonist (LAMA) tiotropium (approved in 2015). There is a need for more effective therapies, as many patients continue to have poorly controlled asthma. Areas covered New and developing long-acting non-adrenoreceptor synthetic drugs for the treatment of symptomatic chronic asthma despite treatment with an ICS alone or combined with a LABA...
January 18, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28099816/new-treatment-options-and-emerging-drugs-for-axial-spondyloarthritis-biological-and-targeted-synthetic-agents
#14
Eric Toussirot
Ankylosing spondylitis (AS) and axial spondyloarthritis (ax SpA) are chronic inflammatory diseases mainly involving the axial skeleton. Pharmacological treatments for AS and ax SpA usually include local glucocorticoid injections, NSAIDs and anti-TNFa agents. Since around 30% to 40% of patients are non responders or intolerant to anti-TNFa agents, we need new therapeutic options for AS and ax SpA. Areas covered: This review describes the new biological agents that can be used or are in development for AS or ax SpA as well as emerging synthetic targeted drugs...
January 18, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28099275/characterization-regulation-and-targeting-of-erythroid-progenitors-in-normal-and-disordered-human-erythropoiesis
#15
Brian M Dulmovits, Jimmy Hom, Anupama Narla, Narla Mohandas, Lionel Blanc
PURPOSE OF REVIEW: The erythroid progenitors burst-forming unit-erythroid and colony-forming unit-erythroid have a critical role in erythropoiesis. These cells represent a heterogeneous and poorly characterized population with modifiable self-renewal, proliferation and differentiation capabilities. This review focuses on the current state of erythroid progenitor biology with regard to immunophenotypic identification and regulatory programs. In addition, we will discuss the therapeutic implications of using these erythroid progenitors as pharmacologic targets...
January 17, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28099107/case-238-spontaneous-pneumothorax-secondary-to-intrapulmonary-necrobiotic-rheumatoid-nodule
#16
Ammar A Chaudhry, Maryam Gul, Abbas A Chaudhry, William Moore
History A 54-year-old white woman with a history of rheumatoid arthritis who was taking glucocorticoids and methotrexate presented to the emergency department in December with worsening shortness of breath and chest heaviness for 1 week. She reported additional symptoms of weakness, headache, and arthralgia primarily involving her bilateral hands, wrist, ankles, and feet. She denied experiencing fevers, syncope or presyncope, focal neurologic deficits, chest pain, nausea, vomiting, unintentional weight loss, or recent trauma...
February 2017: Radiology
https://www.readbyqxmd.com/read/28098234/maternal-cortisol-stimulates-neurogenesis-and-affects-larval-behaviour-in-zebrafish
#17
Carol Best, Deborah M Kurrasch, Mathilakath M Vijayan
Excess glucocorticoid transferred from stressed mother to the embryo affects developing vertebrate offspring, but the underlying programming events are unclear. In this study, we tested the hypothesis that increased zygotic glucocorticoid deposition, mimicking a maternal stress scenario, modifies early brain development and larval behaviour in zebrafish (Danio rerio). Cortisol was microinjected into the yolk at one cell-stage, to mimic maternal transfer, and the larvae [96 hours post-fertilization (hpf)] displayed increased activity in light and a reduction in thigmotaxis, a behavioural model for anxiety, suggesting an increased propensity for boldness...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28097725/increased-cortical-porosity-in-women-with-hip-fracture
#18
D Sundh, A G Nilsson, M Nilsson, L Johansson, D Mellström, M Lorentzon
BACKGROUND: Hip fractures cause increased mortality and disability and consume enormous healthcare resources. Only 46% of hip fracture patients have osteoporosis at the total hip according to dual-energy X-ray absorptiometry (DXA) measurement. Cortical porosity increases with ageing and is believed to be important for bone strength. OBJECTIVE: To investigate whether older women with hip fracture have higher cortical porosity than controls, and if so whether this difference is independent of clinical risk factors and areal bone mineral density (aBMD)...
January 18, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28097680/development-of-a-novel-algorithm-for-detecting-glucocorticoid-induced-diabetes-mellitus-using-a-medical-information-database
#19
T Imatoh, K Sai, K Hori, K Segawa, J Kawakami, M Kimura, Y Saito
WHAT IS KNOWN AND OBJECTIVE: Glucocorticoid-induced diabetes mellitus (GIDM) increases the risk of diabetes mellitus (DM)-related complications but is generally difficult to detect in clinical settings. The criteria for diagnosing GIDM have not been established. Recently, medical information databases (MIDs) have been used in post-marketing surveillance (PMS) studies. We conducted a pharmacoepidemiological study to develop an algorithm for detecting GIDM using MID. METHODS: We selected 1214 inpatients who were newly prescribed with a typical glucocorticoid, prednisolone, during hospitalization from 2008 to 2014 from an MID of Hamamatsu University Hospital in Japan...
January 18, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28097391/-tapering-and-termination-of-immunosuppressive-therapy-systemic-lupus-erythematosus
#20
REVIEW
M Aringer, N Leuchten, R Fischer-Betz
Similar to patients with other rheumatic diseases, patients with systemic lupus erythematosus (SLE) nowadays can also have the desire to terminate immunosuppressive and immunomodulatory medications. In order to provide appropriate advice to patients, the two main issues are the risk of severe adverse events under long-term therapy with any drug and the perceived risk of a flare, in particular of severe flares. The risks of long-term therapy vary greatly between drugs, ranging from severe unacceptable risks with cyclophosphamide and higher dose glucocorticoids to low risks usually outweighed by long-term benefits with hydroxychloroquine...
January 17, 2017: Zeitschrift Für Rheumatologie
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