Assessing individual responses to glucocorticoid drug therapies that compromise immune status and affect survival outcomes in neuro-oncology is a great challenge. Here we introduce a blood-based neutrophil dexamethasone methylation index (NDMI) that provides a measure of the epigenetic response of subjects to dexamethasone. This marker outperforms conventional approaches based on leukocyte composition as a marker of glucocorticoid response. The NDMI is associated with low CD4 T cells and the accumulation of monocytic myeloid-derived suppressor cells and also serves as prognostic factor in glioma survival. In a non-glioma population, the NDMI increases with a history of prednisone use. Therefore, it may also be informative in other conditions where glucocorticoids are employed. We conclude that DNA methylation remodeling within the peripheral immune compartment is a rich source of clinically relevant markers of glucocorticoid response.
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http://dx.doi.org/10.1038/s41467-022-33215-x | DOI Listing |
Curr Rheumatol Rev
January 2025
Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, Egypt.
Introduction/objectives: Genetic variations could explain individual responses to drugs. This case-control study aimed to investigate the association between the multidrug resistance 1 (MDR1) gene exonic single nucleotide variants (SNVs), rs1128503/C1236T and rs1045642/C3435T, and the response to intravenous methylprednisolone in Egyptian patients with active systemic lupus erythematosus (SLE).
Method: Real-time polymerase chain reaction was used.
Psychoneuroendocrinology
December 2024
Hotchkiss Brain Institute, Mathison Centre for Mental Health Research and Education, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada; Department of Cell Biology and Anatomy & Psychiatry, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. Electronic address:
Management of stress and anxiety is often listed as the primary motivation behind cannabis use. Human research has found that chronic cannabis use is associated with increased basal cortisol levels but blunted neuroendocrine responses to stress. Preclinical research has demonstrated mixed effects of Δ-tetrahydrocannabinol (THC; the psychoactive constituent of cannabis), much of which is suggestive of dose-dependent effects; however, the predominance of this work has employed an injection method to deliver cannabis.
View Article and Find Full Text PDFPNAS Nexus
January 2025
Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, 3501 Fifth Avenue, Pittsburgh, PA 15261, USA.
Bronchopulmonary dysplasia, the most prevalent chronic lung disease of prematurity, is often treated with glucocorticoids (GCs) such as dexamethasone (DEX), but their use is encumbered with several adverse somatic, metabolic, and neurologic effects. We previously reported that systemic delivery of the GC prodrug ciclesonide (CIC) in neonatal rats activated glucocorticoid receptor (GR) transcriptional responses in lung but did not trigger multiple adverse effects caused by DEX. To determine whether limited systemic metabolism of CIC was solely responsible for its enhanced safety profile, we treated neonatal rats with its active metabolite desisobutyryl-ciclesonide (Des-CIC).
View Article and Find Full Text PDFBMC Rheumatol
January 2025
GSK Saudi Arabia, Value Evidence and Outcomes, Jeddah, Saudi Arabia.
Background: The real-world effectiveness of intravenous (IV) belimumab in treating systemic lupus erythematosus (SLE) has been demonstrated in various countries through the OBSErve (evaluation Of use of Belimumab in clinical practice SEttings) program. Here we describe the clinical effectiveness of IV belimumab for treating SLE in real-world clinical practice in the Russian Federation.
Methods: In the retrospective, observational OBSErve Russia study (GSK Study 215349), eligible physicians enrolled adults with SLE receiving IV belimumab as part of their standard care.
Neuroimage
January 2025
School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, China. Electronic address:
Background: Although epigenomic and environment interactions (Epigenome × Environment; Epi × E) might constitute a novel mechanism underlying reward processing direct evidence is still scarce. We conducted the first longitudinal study to investigate the extent to which DNA methylation of a stress-related gene-NR3C1-interacts with childhood maltreatment in association with young adult reward responsiveness (RR) and the downstream risk of depressive (anhedonia dimension in particular) and anxiety symptoms.
Method: A total of 192 Chinese university students aged 18∼25 (M = 21.
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