Characterisation and differential expression of Atlantic salmon, Salmo salar, corticosteroid receptor paralogues following poly I:C and Vibrio anguillarum stimulations.

Feeding entrainment of the primary and accessory loops of the molecular circadian clock and epigenetic processes in zebrafish brain: the importance of the glucocorticoid signalling.

ObjectiveTo evaluate the effectiveness of a lower initial glucocorticoid (GC) dose (0.4-0.6mg/kg/day) compared to the conventional dose (0.8-1.2mg/kg/day) in achieving complete renal response (CRR) at 12months in Japanese patients with proliferative lupus nephritis (LN).MethodsThis multicentre, retrospective observational study analyzed data from 344 Japanese patients diagnosed with LN (class III or IV ± V) via renal biopsy. Patients were divided into two groups based on their initial dose of GC. 1:1 propensity score matching (PSM) based on key baseline variables, 23 patients were included in each group. The primary endpoint was CRR at 12months, defined according to the BLISS-LN trial criteria. A non-inferiority margin of -10% was prespecified.ResultsAfter PSM, the CRR rate at 12months was 87.0% in the low-dose group and 73.9% in the conventional-dose group (risk difference: 13.1%; 95% confidence interval [CI]: -9.4% to 35.6%), confirming statistical non-inferiority. While GC doses differed significantly during the initial 3months, they became comparable between the groups after 6months.ConclusionA reduced initial GC dose of 0.4-0.6mg/kg/day achieved renal outcomes comparable to conventional dosing in Japanese patients with LN. Given the risks of GC toxicity, these findings may support the potential for lower-dose GC strategies in LN treatment.

The stress-myopia pathway: A pivotal hub in myopia pathogenesis.

ObjectivesTo compare the treatments used for the first episode of lupus nephritis (LN) in two Latin American cohorts (historical and contemporary) over a 25-year period, and their associations with clinical outcomes.MethodsPatients with biopsy-confirmed first LN episode were classified as non-proliferative (class V) or proliferative (classes III/IV). Sociodemographic, clinical, and treatment variables were described. Propensity score matching was used to examine the associations with four outcomes: mortality, damage accrual (SDI), hospitalization, and end-stage renal disease (ESRD).ResultsA total of 532 SLE patients were included: 362 from GLADEL 1.0 (historical cohort) and 170 from GLADEL 2.0. (contemporary). Compared to GLADEL 1.0, patients in GLADEL 2.0 received lower doses of oral glucocorticoids (GC), more frequently GC pulses and antimalarials but less frequently cyclophosphamide. An increase in the use of mycophenolate mofetil and other immunosuppressants was also observed. In the logistic regression models, SDI was associated with baseline SDI and GC pulses, whereas belonging to the GLADEL 2.0 was a protective factor. Mortality was associated with Mestizo ethnicity and partial health coverage; antimalarial was identified as a protective factor. Hospitalizations were associated with baseline SLEDAI and SDI, follow-up time, and lower educational level. Belonging to the GLADEL 2.0 cohort was protective against the occurrence of ESRD.ConclusionsPatients in the contemporary cohort benefited from advances in treatment strategies, with less cumulative damage and progression to ESRD, although mortality remained unchanged. These improvements likely reflect the increased use of newer therapies, more targeted approaches, in line with current treatment guidelines, and better access to specialized care.

The attitude towards using glucocorticosteroids (GCs) for the management of patients with systemic lupus erythematosus (SLE) has undergone drastic changes over the last decades. While the role of GCs for the rapid control of inflammation is uncontested, the former 'dogma' that GCs must never be withdrawn due to fear of severe flares was proven wrong and replaced by a strategy that invites both tapering GCs to 0 and questioning whether they even need to be initiated at all in individual patients. Moreover, the daily prednisone equivalent dose acceptable for long-term use is limited to ≤ 5 mg in current recommendations. These changes are a consequence of a substantial body of evidence that links higher GC doses to infections, cardiovascular events and other damage, and an increasing number of studies showing that GC withdrawal is feasible in many SLE patients who are in remission. Despite methodological concerns, with observational data inherently prone to confounding by indication, the worldwide experience of the last decades suggests that the limit of 5 mg daily is justified. Moreover, current strategies and novel medications have made it a reality for many SLE patients, to actually maintain the goal of remission or low disease activity on not >5 mg of prednisone per day.

Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a frequently encountered complication in orthopedic practice, yet its precise pathogenic mechanisms remain incompletely understood. Dysregulation of bone metabolism induced by glucocorticoids (GCs) is considered a key contributing factor. 3,4-Dimethoxychalcone (3,4DC), an organic compound, has shown potential biological activities, but its role in the context of GIONFH has not been elucidated. This study investigates the protective effects and underlying mechanisms of 3,4DC against dexamethasone (Dex)-induced ferroptosis and its therapeutic potential in GIONFH.A rat model of GIONFH was established through intraperitoneal administration of Dex, and invitro studies were performed by culturing osteoblasts (OBs) under Dex treatment conditions. To evaluate the effects of 3,4DC on Dex-treated OBs, we employed C11-BODIPY and FerroOrange staining, assessed mitochondrial function, and analyzed protein expression via Western blot and immunofluorescence. The impact of 3,4DC on the bone microarchitecture of the femoral head in rats was further examined using micro-CT, H&E staining, as well as immunofluorescence and immunohistochemistry at both imaging and histological levels. Our results indicate that 3,4DC effectively inhibits Dex-induced ferroptosis and attenuates the development of GIONFH. Invitro, 3,4DC treatment significantly increased glutathione (GSH) levels while reducing malondialdehyde (MDA) production, lipid peroxidation, and mitochondrial reactive oxygen species (ROS) accumulation. Furthermore, 3,4DC enhanced STAT3 phosphorylation, upregulated glutathione peroxidase 4 (GPX4) and osteogenesis-related proteins, and promoted bone formation. Mechanistically, 3,4DC activated the STAT3/Nrf2 signaling pathway. Notably, silencing STAT3 with siRNA abrogated the protective effects of 3,4DC in Dex-treated OBs.3,4DC alleviates GIONFH by activating the STAT3/Nrf2 signaling pathway, thereby suppressing ferroptosis and may have potential clinical applications.

Exogenous Cushing's syndrome (CS) is most commonly caused by therapeutic glucocorticoids (GC), but rare and atypical sources can mimic endogenous GC. This narrative review provides a concise overview of these uncommon causes and their diagnostic implications. A PubMed search was performed using the keywords "Cushing syndrome," "factitious Cushing syndrome," "herbal medicine", "supplements" and "endocrine disruption" on March 9th, 2026. Additional articles were identified through manual screening of reference lists. No restrictions were applied regarding language or study design, and the most relevant publications were selected. Three main categories of rare exogenous CS were identified. First, herbal or traditional remedies adulterated with undeclared GC. Second, compounds with GC-like activity, which activate the glucocorticoid receptor and suppress the hypothalamic-pituitary-adrenal axis. Third, factitious CS due to covert GC self-administration, often associated with psychiatric or caregiver-fabricated conditions. Diagnosis can be challenging; advanced analytical methods, including liquid chromatography-tandem mass spectrometry (LC-MS/MS) and liquid chromatography-high resolution mass spectrometry (LC-HRMS), are essential to detect synthetic or undeclared GC and differentiate these cases from endogenous hypercortisolism. Rare exogenous causes of CS represent important diagnostic challenges. Careful evaluation of patient history, combined with the use of LC-MS/MS or LC-HRMS, is crucial to identify these conditions, prevent misdiagnosis, and avoid unnecessary diagnostic or surgical interventions.

Self-management and patient education are cornerstones in managing adrenal insufficiency (AI), to prevent adrenal crisis (AC). Glucocorticoid (GC) education group meetings are increasingly being incorporated into regular healthcare. However, few studies have evaluated its effectiveness. Multicentre pre-post intervention study conducted at four university hospitals in Sweden between 2015 and 2019. A total of 254 patients with AI along with 138 relatives were included. Participants attended a GC education group meeting led by an endocrinologist. Detailed guidance was provided on when and how to adjust GC doses to prevent AC together with instructions and supervised practice of hydrocortisone injections. Questionnaires on self-management were completed by both patients and relatives before the session and again six months later. In addition, patients also completed two HRQoL instruments. Patients with AI felt relatively safe and informed about their GC treatment at baseline. However, many lacked adequate knowledge on dose adjustments, including high-risk situations for AC. At follow up, 194 patients (76.4%) and 94 relatives (68.1%) completed the questionnaires. Both patients and relatives showed significant improvements in perceived safety and management of high-risk scenarios for AC. However, some knowledge gaps persisted. The education effort did not result in significant changes in HRQoL. Structured GC education group meetings enhance the knowledge of patients and their relatives to manage AI safely. We consider this a valuable component of AI care.

Glucocorticoid monotherapy versus combination with methotrexate or tocilizumab in giant cell arteritis: efficacy and safety at 78 weeks in a retrospective cohort study.

Longitudinal noninvasive in vivo imaging is essential for studying brain physiology and pathological mechanisms. Advances in transcranial optical windows, including thinned-skull and optical clearing techniques, have markedly improved imaging depth and resolution when combined with multiphoton microscopy. However, their optical performance often deteriorates rapidly, and quantitative studies on long-term stability and the causes of image quality loss remain limited. In this work, current transcranial window approaches are systematically investigated using multiphoton excited fluorescence microscopy (MPEFM) and adaptive optics, examining longevity, imaging quality and optical aberrations. These results reveal that progressive skull regrowth is a fundamental limitation across all window types, leading to substantial declines in signal quality and resolution. To address these challenges, a localized glucocorticoid (GC) delivery strategy that significantly extends window performance for up to one month is developed. Furthermore, it is demonstrated that a GC-loaded hydrogel sealing method effectively suppressed skull regrowth while preserving optimal optical properties, offering a potential and practical route to chronic, high-fidelity transcranial imaging. These findings provide mechanistic insight into window degradation and establish a framework for sustained and, long-term in vivo brain imaging.

To examine the role of low-dose glucocorticoids (GCs) in major relapse, hospitalisation and damage accumulation risk during maintenance therapy in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAVs). Retrospective cohort study of newly diagnosed patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) followed in three tertiary referral centres. We recorded relapses (Birmingham Vasculitis Activity Score increase >0), increases in Vasculitis Damage Index (VDI) and hospitalisations. We used time-varying and mixed-effects Cox models to examine the effect of GCs on the risk of major relapses, VDI accumulation and hospitalisations. Sensitivity analysis was also conducted to address potential confounding. 171 patients (GPA: 107, MPA: 64, median age: 61 years) were included with a median follow-up of 88.2 months (803.4 patient years (PY)). We recorded 65 major relapses (8.1/100 PY) in 48 patients (28%), 65 events of new damage (8.1/100 PY) and 132 hospitalisations (16.4/100 PY). By multivariable analysis, rituximab use was associated with a lower risk (HR=0.21, 95% CI 0.09 to 0.47, p=0.0001) while disease activity at diagnosis was associated with an increased risk (HR=1.17, 95% CI 1.03 to 1.33, p=0.013) of major relapses. Low-dose GCs were not associated with a reduced major relapse risk (HR=0.96, 95% CI 0.88 to 1.05, p=0.36) but they were associated with a risk of damage accumulation (HR=1.52, 95% CI 1.19 to 1.93, p=0.0007) and hospitalisations (HR=1.24, 95% CI 1.06 to 1.45, p=0.006). Higher GC exposure during maintenance therapy was not significantly associated with a lower major relapse risk whereas it was associated with damage accrual and hospitalisation. These findings may support decision making regarding long-term GC use in patients with GPA/MPA.

Prenatal glucocorticoids and long-term brain vulnerability: GR signaling, epigenetic programming, and crosstalk with peripheral tissues.

Glucocorticoid receptor (GR) is a member of the nuclear hormone receptor family, which acts as a transcription factor when bound by glucocorticoid (GC) ligands. GR is expressed in nearly all tissue types and regulates essential processes such as inflammation, immune regulation and metabolism. Given its ubiquitous role, GR has frequently been associated with a wide range of illnesses, particularly in the fields of allergy, pulmonary, dermatology, rheumatology, or ophthalmology. It was reported that GCs either contribute to their development or serve as part of their treatment, making them the most prescribed drugs worldwide. GR activity and signaling is finely regulated by a network of post-translational modifications (PTMs). Indeed, PTMs can alter GR behavior and function by modifying its localization, stability, interaction with other proteins and transcriptional activity. Aside from the well-characterized phosphorylation events, additional PTMs are implicated in GR activity and their dysregulation has been described in various diseases. This review provides an integrated overview of current knowledge on GR PTMs, highlighting both mechanistic insights and their relevance in disease. We will present how aberrant PTMs contribute to extremely prevalent diseases, such as cancer, chronic inflammatory diseases, Alzheimer's disease and other neurological diseases. Special attention will be given to the specific readers of these PTMs and to the enzymes catalyzing these modifications, as they represent promising therapeutic targets.

Lung adenocarcinoma (LUAD) shows marked heterogeneity, limiting the effectiveness of traditional classifications. We integrated bulk transcriptomic data from TCGA and multicenter cohorts with spatial transcriptomics for in situ validation. Analysis of glucocorticoid (GC) and mitophagy pathways identified 127 core genes, enabling a novel molecular subtyping and survival risk model that predicted prognosis and correlated with immune infiltration. High mobility group AT-hook 1 (HMGA1) emerged as a key regulator of tumor metabolism, immune evasion, and therapy resistance. Spatial transcriptomics with RCTD-based deconvolution showed a tumor-enriched and heterogeneous HMGA1 expression pattern and a positive spatial association with epithelial cell proportion in tumor sections. Single-cell RNA-seq analysis further resolved HMGA1 enrichment to tumor epithelial cells, and CIBERSORTx projection linked the HMGA1-high tumor epithelial cell state to poor prognosis and increased proliferation. Functional assays showed that high HMGA1 expression conferred sensitivity to metabolic inhibitors but resistance to proteasome inhibitors, while HMGA1 knockout suppressed tumor growth and enhanced anti-PD-1 efficacy. By integrating bulk modeling with spatial validation, this study establishes a GC-mitophagy-based classification and highlights HMGA1 as a promising biomarker for prognostic stratification and personalized immunotherapy in LUAD.

Glucocorticoids (GC) remain the first-line treatment for many autoimmune, inflammatory and allergic conditions, but the prevalence of glucocorticoid-induced hyperglycaemia (GIH) in paediatric patients has not been established. Furthermore, specific recommendations for the timing and frequency of glucose monitoring during high-dose GC therapy are also missing. Our objective was to describe the glycaemic patterns in children receiving high doses of systemic GC using continuous glucose monitoring (CGM) and to describe the risk factors for GIH. This prospective observational study was performed between December 2021 and December 2024 at the Department of Paediatrics of the Tartu University Children's Clinic. Paediatric patients, who received GC treatment due to an underlying condition at a dose of at least 1 mg/kg/day prednisolone-equivalent were monitored with a iPro 2 or a Guardian 4 CGM system during their GC treatment course. CGM data were analyzed retrospectively. The following parameters were evaluated: time in range (TIR, percentage of reading in the range 3.9-10 mmol/L) time above range (TAR, percentage of readings above 10 mmol/L) and mean sensor glucose (SG). CGM profiles of 10 patients were analysed (2 boys, 8 girls). The average age of the participants was 10,5 years (range from 4 to 17 years). The average duration of glucose monitoring with CGM was 5 days (/- 2 days). Seven out of ten patients experienced GIH defined as SG above 10 mmol/L. The average coefficient of variation of the participants was 21% (range from 15 to 26%). Patients with GIH spent on average 1,5 hours per day with glucose values above 10 mmol/L which attributes to TAR of 6% ( +/- 9%). The highest SG values during 24 hours were observed between 16:00- 23:00 for patients receiving oral prednisolone and intravenous methylprednisolone. Two thirds of investigated subjects developed GC-induced hyperglycaemia. Participants experienced episodes of hyperglycaemia regardless of the route of GC administration. Higher SG measurements were registered during evening hours compared to early morning and this should be taken into account in the screening for GC-induced hyperglycaemia.

Given the high rate of cardiovascular comorbidities in anti-HMG-CoA reductase (HMGCR)-immune-mediated necrotizing myopathy (IMNM), a glucocorticosteroids (GC)-free treatment approach remains an appealing strategy. While intravenous immunoglobulins (IVIg) represents an effective therapy in most subgroups of idiopathic inflammatory myositis (IIM), there remains limited evidence supporting the use subcutaneous immunoglobulins (SCIg), a potentially safer, more convenient and cost-effective alternative. We present a case of a 68-year-old male of European descent with a 2-year history of progressive proximal bilateral lower extremity weakness. He had been treated for his dyslipidemia with atorvastatin for 2 years, then with rosuvastatin for 2 additional years until discontinued a year before our assessment. His other comorbidities included hypertension and diabetes mellitus type II. Physical examination demonstrated proximal weakness of his bilateral hip flexors and deltoids, and no rash. His creatine kinase (CK) was elevated at 1644IU/L. Electromyography revealed a generalized myopathic disorder with proximal predominance and muscle biopsy of the right quadriceps showed typical findings of an IMNM. Serum HMG-CoA reductase antibody was positive. Due to accumulating evidence supporting the effectiveness of IVIg in anti-HMGCR-IMNM, even without concomitant GC or other immunosuppressive agent, we opted for a GC-free approach through shared-decision making in light of patient's preference regarding potential GC side effects with his comorbidities. As he lived a considerable distance from any center, where IVIg infusions could be offered, and given the patient was unable to drive himself due to his symptoms we opted for SCIg (0.5g/kg/week). Within 1 month, his CK decreased and weakness resolved. SCIg monotherapy was tapered over 3 years and this patient remains in remission 7 years after SCIg initiation. The patient did not have any adverse effects related to SCIg use. To our knowledge, this is the first case report describing a successful corticosteroid-free management of anti-HMGCR immune-mediated necrotizing myopathy using SCIg as monotherapy. This case highlights the potential for steroids-free induction and maintenance strategies in IMNM. Larger studies are required to confirm the effectiveness and safety of SCIg in IMNM and other subtypes of IIM, and to provide guidelines for dosing recommendations.

Air pollution, but not physiological stress, is associated with genomic damage of invasive grey squirrels from urban and agricultural areas.

A cell-intrinsic glucocorticoid biosynthesis and sensing circuit maintains a homeostatic Th17 cell state.

Lupus nephritis (LN) is a kidney injury caused by systemic lupus erythematosus (SLE) and can lead to serious impairment of renal function. Glucocorticoid (GC) combined with cyclophosphamide (CTX) is currently a commonly used treatment for LN; however, it is associated with several limitations, including a high proportion of refractory cases, a high recurrence rate after remission, and a long treatment cycle. The purpose of this study was to evaluate the safety and efficacy of Tacrolimus (Tac) combined with GC in the treatment of lupus nephritis. This retrospective cohort study included 112 pediatric LN patients at Inner Mongolia Autonomous Region People's Hospital (January 2022 to June 2025), divided into two groups (n = 56 each): Tac group [Tac+ GC] and CTX group (CTX + GC), with a treatment duration of 6 months. Primary endpoints included post-treatment overall response rate, pre/post-treatment renal function, and disease activity scores. Secondary endpoints included immune-inflammatory markers, immune function parameters, anti-dsDNA antibody positivity rate (pre/post-treatment), and adverse reaction incidence. Baseline characteristics showed no significant difference between the two groups (P > 0.05). Post-treatment, the Tac group had a significantly higher complete remission rate than the CTX group (P < 0.05). Both groups exhibited improved renal function, reduced immune-inflammatory markers, immunoglobulins, and anti-dsDNA positivity (P < 0.05), and increased complement C3 and C4 levels (P < 0.05). The Tac group showed more pronounced improvements and a lower overall adverse reaction incidence (P < 0.05). Tac combined with GC can improve renal function and immune-inflammatory status in children with lupus nephritis, with good safety.