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Total 48 results found since Jan 2013.

Src siRNA prevents corticosteroid-associated osteoporosis in a rabbit model
In an established steroid-associated osteonecrosis (SAON) rabbit model we found recently that blockage Src by siRNA could improve reconstructive repair of osteonecrosis via enhancing osteogenesis and inhibiting bone resorption. The current study investigated if blocking Src was able to prevent steroid-associated osteoporosis (SAOP) in the same SAON animal model. Rabbits were treated with pulsed lipopolysaccharide (LPS) and corticosteroid methylprednisolone (MPS). At 2, 4, 6weeks after induction, Src siRNA, control siRNA and saline were intramedullary injected into proximal femur, respectively.
Source: Bone - November 17, 2015 Category: Orthopaedics Authors: Li-Zhen Zheng, Xin-Luan Wang, Hui-Juan Cao, Shi-Hui Chen, Le Huang, Ling Qin Tags: Original Full Length Article Source Type: research

Oligonucleotides —A Novel Promising Therapeutic Option for IBD
Conclusions In this review, we focused on recent and past approaches to test the therapeutic efficacy of oligonucleotide based therapies in IBD. The combining mechanistic mode of oligonucleotide based therapeutics is a targeted action on specific pro-inflammatory molecules, which are over activated in IBD patients and contribute significantly to disease pathogenesis. The proposed high selectivity of the agents is derived from its mode of action, that aims to specifically block certain inflammatory molecular patterns, without a general systemic effect on other molecular targets. It would be important for each oligonucleot...
Source: Frontiers in Pharmacology - April 23, 2019 Category: Drugs & Pharmacology Source Type: research

New cholesterol drug shows promise
Conclusion Media headlines reporting on this phase I trial concentrated on the secondary outcome (that ALN-PCS reduced LDL cholesterol levels). However, these results will need to be confirmed during phase II and phase III clinical trials, which will involve more participants who would normally receive cholesterol-lowering treatment. While it is tempting to focus on the results of the cholesterol levels, phase I clinical trials are designed to test the safety of a new drug to make sure it is safe enough to test further. They also aim to determine what the highest tolerable dose is, so the appropriate one can be used in la...
Source: NHS News Feed - October 3, 2013 Category: Consumer Health News Tags: Heart/lungs Medical practice Medication Source Type: news

Enhanced expression of SAM‐pointed domain–containing Ets‐like factor in Chronic rhinosinusitis with nasal polyps
ConclusionsOur findings suggested that SPDEF may be regarded as a promising therapeutic target for modulating mucus hypersecretion in CRSwNP. Level of EvidenceN/A. Laryngoscope, 2014
Source: The Laryngoscope - November 6, 2014 Category: ENT & OMF Authors: Jing Bai, Beiping Miao, Xingmei Wu, Xi Luo, Renqiang Ma, Jia Zhang, Lei Li, Jianbo Shi, Huabin Li Tags: Allergy/Rhinology Source Type: research

Esculentoside A Attenuates Allergic Airway Inflammation via Activation of the Nrf-2 Pathway
Conclusions: This is the first study to illustrate that EsA acts as a novel Nrf-2 activator, which modulates the oxidative stress pathway to improve lung injury and ameliorate the development of airway inflammation.Int Arch Allergy Immunol 2015;167:280-290
Source: International Archives of Allergy and Immunology - October 24, 2015 Category: Allergy & Immunology Source Type: research

SOCS and Herpesviruses, With Emphasis on Cytomegalovirus Retinitis
Christine I. Alston1,2 and Richard D. Dix1,2* 1Department of Biology, Viral Immunology Center, Georgia State University, Atlanta, GA, United States 2Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA, United States Suppressor of cytokine signaling (SOCS) proteins provide selective negative feedback to prevent pathogeneses caused by overstimulation of the immune system. Of the eight known SOCS proteins, SOCS1 and SOCS3 are the best studied, and systemic deletion of either gene causes early lethality in mice. Many viruses, including herpesviruses such as herpes simplex virus and cytomega...
Source: Frontiers in Immunology - April 10, 2019 Category: Allergy & Immunology Source Type: research

Enhancement of cell surface expression and receptor functions of membrane progestin receptor alpha (mPRα) by progesterone receptor membrane component 1 (PGRMC1): evidence for a role of PGRMC1 as an adaptor protein for steroid receptors.
Abstract A variety of functions have been proposed for progesterone receptor membrane component 1 (PGRMC1), including acting as a component of a membrane progestin receptor and as an adaptor protein. Here we show that stable over expression of human PGRMC1 in progesterone receptor-negative breast cancer cell lines causes increased expression of PGRMC1 and membrane progesterone receptor alpha (mPRα) on cell membranes which is associated with increased specific [(3)H]progesterone binding. The membrane progestin binding affinity and specificity were characteristic of mPRα, with a Kd of 4.7 nM and high affinity for ...
Source: Endocrinology - January 1, 2014 Category: Endocrinology Authors: Thomas P, Pang Y, Dong J Tags: Endocrinology Source Type: research

Inactivation of histone deacetylase 1 (hdac1) but not hdac2 is required for the glucocorticoid-dependent ccaat/enhancer binding protein α (c/ebpα) expression and preadipocyte differentiation.
In this study, we sought to demonstrate using two different strategies the definite role of HDACl in adipogenesis. By using siRNA-mediated knockdown of HDAC1 and by generating an enzymatically inactive HDAC1D181A by site-directed mutagenesis, we were able to show that HDAC1, but not HDAC2, suppresses GR-potentiated preadipocyte differentiation by decreasing C/ebpα and Pparγ expression levels at the onset of differentiation. Finally, we demonstrate that HDAC1D181A acts as a dominant negative mutant of HDACl during adipogenesis by modulating C/EBPβ transcriptional activity on the C/ebpα promoter. PMID: 25203139 [Pub...
Source: Endocrinology - September 9, 2014 Category: Endocrinology Authors: Kuzmochka C, Abdou HS, Haché RJ, Atlas E Tags: Endocrinology Source Type: research

Activation of GX sPLA2 by Furin-like Proprotein Convertases Lipids
In this study, using a FLAG epitope-tagged pro-GX sPLA2 expression construct (FLAG-pro-GX sPLA2), we determined that adrenocorticotropic hormone (ACTH) enhanced FLAG-pro-GX sPLA2 processing and phospholipase activity secreted by Y1 adrenal cells. ACTH increased the expression of furin and PCSK6, but not other members of the PC family, in Y1 cells. Overexpression of furin and PCSK6 in HEK 293 cells significantly enhanced FLAG-pro-GX sPLA2 processing, whereas siRNA-mediated knockdown of both PCs almost completely abolished FLAG-pro-GX sPLA2 processing in Y1 cells. Expression of either furin or PCSK6 enhanced the ability of G...
Source: Journal of Biological Chemistry - March 20, 2015 Category: Chemistry Authors: Layne, J. D., Shridas, P., Webb, N. R. Tags: Cell Biology Source Type: research

Sphingosine 1-phosphate Increases COX-2 Expression and PGE2 Secretion: Effects on β2-adrenergic Receptor Desensitization.
Abstract Tachyphylaxis of the β2-adrenergic receptor limits the efficacy of bronchodilatory β2-agonists in respiratory disease. Cellular studies in airway smooth muscle (ASM) have shown that inflammatory mediators and infectious stimuli reduce β2-adrenergic responsiveness in a cyclooxygenase 2 (COX-2)-mediated, prostaglandin E2 (PGE2)-dependant manner. Herein we show that sphingosine 1-phosphate (S1P), a bioactive sphingolipid that plays an important role in pathophysiology of asthma, also induces β2-adrenergic receptor desensitization in bronchial ASM cells and exerts hyporesponsiveness to β2-agonist. We tre...
Source: Am J Respir Cell Mol... - June 22, 2015 Category: Respiratory Medicine Authors: Rumzhum NN, Rahman MM, Oliver BG, Ammit AJ Tags: Am J Respir Cell Mol Biol Source Type: research

30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Mineralocorticoid receptor null mice: informing cell-type-specific roles
The mineralocorticoid receptor (MR) mediates the actions of two important adrenal corticosteroid hormones, aldosterone and cortisol. The cell signalling roles of the MR in vivo have expanded enormously since the cloning of human MR gene 30 years ago and the first MR gene knockout in mice nearly 20 years ago. Complete ablation of the MR revealed important roles postnatally for regulation of kidney epithelial functions, with MR-null mice dying 1–2 weeks postnatally from renal salt wasting and hyperkalaemia, with elevated plasma renin and aldosterone. Generation of tissue-selective MR-deficient mice using Cre recombinas...
Source: Journal of Endocrinology - June 20, 2017 Category: Endocrinology Authors: Cole, T. J., Young, M. J. Tags: Thematic Review Source Type: research

Regulation of Corticosteroidogenic Genes by MicroRNAs.
This study demonstrates that corticosteroidogenesis is regulated at multiple points by several microRNAs and that certain of these microRNAs are differentially expressed in tumorous adrenal tissue, which may contribute to dysregulation of corticosteroid secretion. These findings provide new insights into the regulation of corticosteroid production and have implications for understanding the pathology of disease states where abnormal hormone secretion is a feature. PMID: 28852406 [PubMed]
Source: International Journal of Endocrinology - September 1, 2017 Category: Endocrinology Tags: Int J Endocrinol Source Type: research

Nrf2 Signaling Pathway Mediates the Antioxidative Effects of Taurine Against Corticosterone-Induced Cell Death in HUMAN SK-N-SH Cells.
Abstract Substantial evidence has shown that elevated circulating corticosteroids or chronic stress contributes to neuronal cell death, cognitive and mental disorders. However, the underlying mechanism is still unclear. Taurine is considered to protect neuronal cells from apoptotic cell death in neurodegenerative diseases and neuropsychiatric disorders. In the present study, the protective effects of taurine against corticosterone (CORT)-induced oxidative damage in SK-N-SH neuronal cells were investigated. The results showed that CORT significantly induced cell death, which was blocked by pretreatment with taurine...
Source: Neurochemical Research - October 23, 2017 Category: Neuroscience Authors: Sun Q, Jia N, Yang J, Chen G Tags: Neurochem Res Source Type: research

Engineering of budesonide-loaded lipid-polymer hybrid nanoparticles using a quality-by-design approach
This study shows the importance of systematic formulation design for understanding the effect of formulation parameters on the characteristics of LPNs, eventually resulting in the identification of an OOS.Graphical abstract
Source: International Journal of Pharmaceutics - July 25, 2018 Category: Drugs & Pharmacology Source Type: research

Th1 Cytokines, TNF α and IFNγ, Promote Corticosteroid Resistance in Developing Human Airway Smooth Muscle.
Th1 Cytokines, TNFα and IFNγ, Promote Corticosteroid Resistance in Developing Human Airway Smooth Muscle. Am J Physiol Lung Cell Mol Physiol. 2018 Oct 18;: Authors: Britt RD, Thompson MA, Sasse SK, Pabelick CM, Gerber AN, Prakash YS Abstract Corticosteroids are commonly used to manage wheezing and asthma in pediatric populations. Although corticosteroids are effective in alleviating airway diseases, some children with more moderate-severe asthma phenotypes show corticosteroid (CS) resistance and exhibit significant airflow obstruction, persistent inflammation, and more frequent exacerbations. Previo...
Source: Am J Physiol Lung Ce... - October 18, 2018 Category: Respiratory Medicine Authors: Britt RD, Thompson MA, Sasse SK, Pabelick CM, Gerber AN, Prakash YS Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research