Unlocking the therapeutic potential of the glucocorticoid receptor (GR) has motivated a search for small molecules that selectively modulate its ability to activate or repress gene transcription. Recently, breakthrough studies in the field of genomics have reinvigorated debate over longstanding transcriptional models explaining how GR controls tissue-specific gene expression. Here, we highlight these genomic studies with the dual goals of advancing understanding of nuclear receptor-mediated transcription and stimulating thought on the development of anti-inflammatory and immunosuppressive ligands for GR that have reduced harmful effects on metabolism.
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http://dx.doi.org/10.1016/j.tem.2017.04.001 | DOI Listing |
Drug Des Devel Ther
January 2025
Center of Expertise for Lupus-, Vasculitis- and Complement-Mediated Systemic Diseases (Luvacs), Department of Internal Medicine - Nephrology Section, Leiden University Medical Center, Leiden, the Netherlands.
Recently, avacopan has been approved for the treatment of ANCA-associated vasculitis (AAV). Avacopan is an inhibitor of the C5a-receptor, which plays an important role in chemotaxis and the amplification loop of inflammation in AAV. In the most recent, international guidelines avacopan is recommended as steroid-sparing agents for the management of AAV.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Biochemistry and Molecular Biology, Gene Engineering Drug and Biotechnology Beijing Key Laboratory, Beijing Normal University, Beijing 100875, China.
Hypertension is a multifactorial and complex disease influenced by genetic and environmental factors, and it has become one of the most serious public health challenges. This study aimed to investigate the changes in hypertension based on urinary proteome. The stroke-prone spontaneously hypertensive rats (SHRSPs) model was used to examined urinary proteome changes during the development of hypertension.
View Article and Find Full Text PDFArthritis Res Ther
January 2025
Department of Rheumatology and Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Background: The objective of this study was to investigate the therapeutic effectiveness and safety profile of Eltrombopag, a thrombopoietin receptor agonist, as prolonged therapy in refractory CTD-ITP patients.
Methods: We conducted a pilot observational study of Eltrombopag in CTD-ITP patients who were unresponsive to or intolerant of conventional medications. Eltrombopag was administered orally at 25-75 mg/qd and adjusted on the basis of tolerance and efficacy until a minimum dosage of 25 mg/qd was reached.
Neuroscience
January 2025
Research Center of Physiology, Semnan University of Medical Sciences, Semnan, Iran; Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran. Electronic address:
Corticosteroid signaling plays a critical role in modulating the neural systems underlying reward and addiction, but the specific contributions of glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs) in the medial prefrontal cortex (mPFC) to opioid reward and dopaminergic plasticity remain unclear. Here, we investigated the effects of intra-mPFC injection of corticosteroid receptor ligand (corticosterone; CORT), glucocorticoid receptor antagonist (RU38486; RU), and mineralocorticoid receptor antagonist (spironolactone; SP) on morphine-induced conditioned place preference (CPP) and dopamine transporter (DAT) expression in the mPFC. Adult male Wistar rats received intra-mPFC injections of CORT, RU, SP, or their respective vehicles prior to morphine CPP conditioning.
View Article and Find Full Text PDFZhong Nan Da Xue Xue Bao Yi Xue Ban
July 2024
Department of Endocrinology, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China.
Immune checkpoint inhibitors (ICPis) significantly improves survival in a number of cancer patients by blocking immunosuppressive molecules and reactivating the function of effector T cells to specifically kil tumor cells. This article reports a case of secondary hypoadrenocorticism caused by programmed death 1 (PD-1) inhibitor related hypophysitis. A 65-year-old male patient received immunotherapy for right lung squamous cell carcinoma invading the chest wall (cT4N2M0) for 4 times.
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