The hypothalamic-pituitary-adrenal (HPA) axis activation and glucocorticoid responses are critical for survival from a number of bacterial, viral and toxic insults, demonstrated by the fact that removal of the HPA axis or GR blockade enhances mortality rates. Replacement with synthetic glucocorticoids reverses these effects by providing protection against lethal effects. Glucocorticoid resistance/insensitivity is a common problem in the treatment of many diseases. Much research has focused on the molecular mechanism behind this resistance, but an area that has been neglected is the role of infectious agents and toxins. We have recently shown that the anthrax lethal toxin is able to repress glucocorticoid receptor function. Data suggesting that the glucocorticoid receptor may be a target for a variety of toxins is reviewed here. These studies have important implications for glucocorticoid therapy.
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http://dx.doi.org/10.3390/toxins2061357 | DOI Listing |
Clin Exp Hepatol
March 2024
Department of Pediatric Hepatology, Gastroenterology and Nutrition, National Liver Institute, Menoufia University, Shebin El-Kom, Menoufia, Egypt.
Aim Of The Study: This study was performed to investigate the hepatic expression of glucocorticoid receptors (GR) and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in pediatric autoimmune hepatitis (AIH) patients and its relation to the steroid response.
Material And Methods: This study included 100 patients diagnosed with AIH on immunosuppressive therapy with different responses to treatment. The patients were subjected to full history taking and thorough clinical examination, laboratory investigations, abdominal ultrasound and liver biopsy for histopathological evaluation and assessment of the hepatic expression of GR and 11β-HSD1.
BMC Rheumatol
January 2025
Department of Nephrology and Rheumatology, Aichi Medical University, 1-1 Karimata, Yazako, Nagakute, Aichi, 480-1195, Japan.
Background: Avacopan, an oral C5a receptor antagonist, demonstrated efficacy as an alternative to glucocorticoid therapy in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in the phase 3 ADVOCATE trial. However, limited real-world data exist on the outcomes and experiences associated with avacopan use for AAV in Japan.
Methods: We performed a single-centre retrospective analysis and evaluated 21 patients with newly diagnosed or relapsed AAV who received avacopan.
Adv Protein Chem Struct Biol
January 2025
Department of Life Sciences, Kristu Jayanti College, Autonomous, Bengaluru, Karnataka, India. Electronic address:
Nuclear receptors (NRs) are ligand-activated transcription factors that regulate gene expression in response to physiological signals, such as hormones and other chemical messengers. These receptors either activate or repress the transcription of target genes, which in turn promotes or suppresses physiological processes governing growth, differentiation, and homeostasis. NRs bind to specific DNA sequences and, in response to ligand binding, either promote or hinder the assembly of the transcriptional machinery, thereby influencing gene expression at the transcriptional level.
View Article and Find Full Text PDFJ Cereb Blood Flow Metab
January 2025
Multidisciplinary Brain Protection Program (MBPP), Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA.
Cardiac arrest (CA) is a life-threatening condition that requires immediate medical attention. Considerable advances in resuscitation have led to an increasing number of patients who survive the initial arrest event. However, among this growing patient population, morbidity and mortality rates remain strikingly high.
View Article and Find Full Text PDFChin Med J Pulm Crit Care Med
December 2024
Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Background: Glucocorticoid-induced transcript 1 (GLCCI1) has been reported to be associated with the efficiency of inhaled glucocorticoids in patients with asthma. This study aimed to investigate the role of GLCCI1 in the regulation of nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) by the phosphatidylinositol 3-kinase (PI3K) pathway in the pathogenesis of allergic asthma.
Methods: The expression levels of genes encoding GLCCI1, NLRP3 inflammasome components, and PI3K pathway-related indicators were detected in cells isolated from induced sputum from patients with asthma and healthy controls.
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