Search Results (33,587)

Purpose: The aims of this study were to evaluate the feasibility of time-restricted eating (TRE) in patients with Cushing’s disease (CD) and assess its effects on body weight and metabolic parameters. Methods: Twelve CD patients in remission with obesity were enrolled in a TRE program restricting food intake to 10:00–18:00. Anthropometric data, glycemic and lipid profiles, and circadian cortisol secretion were assessed at baseline and post-intervention. Serum cortisol levels were measured at multiple time points to evaluate diurnal patterns. Results: Nine patients completed the study. Over the 12-week period, participants showed a significant reduction in body weight, with median values decreasing from 93.8 kg [83.1–106.5] to 82.6 kg [76.9–100.3] (p = 0.011). Body mass index (BMI) also declined from 37.6 kg/m² [34.2–39.7] to 34.4 kg/m² [32.6–38.3] (p = 0.012). No statistically significant changes were observed in fasting glucose, HbA1c, or lipid parameters. Notably, 24 h urinary free cortisol levels significantly decreased (p = 0.01), and serum cortisol showed a downward trend at all measured time points, with the most pronounced reductions during mid-day and evening hours. No clinical or biochemical evidence of CD relapse was observed during the 12-month follow-up. Conclusions: Time-restricted eating is a feasible and well-tolerated dietary approach for patients with CD in remission, promoting weight loss and modest improvements in metabolic markers and cortisol rhythmicity. Full article

Background/Objectives: Celiac disease (CD) is a chronic, immune-mediated enteropathy induced by dietary gluten exposure in genetically predisposed individuals. Along with non-celiac gluten sensitivity (NCGS), these disorders present with multiple intestinal and extra-intestinal symptoms leading to multisystemic involvement, with complications documented in the oral cavity as well. Persistent immune activation and dysregulation, chronic inflammation, nutrient deficiencies, xerostomia, and microbial dysbiosis found in CD and NCGS constitute shared pathological findings, providing biological plausibility for an association with periodontitis. Methods: A narrative literature review was conducted based on a systematic search of four databases (PubMed, Scopus, Web of Science, Cochrane Library) and the gray literature through January 2026. A comprehensive set of clinical, radiographic, biochemical and immunological parameters was assessed. Two reviewers independently screened and selected studies, with disagreements resolved by consensus. Results: A total of 15 studies met the eligibility criteria and were included in the review. Available evidence, mainly derived from cross-sectional observational studies, remains limited, methodologically heterogeneous, and largely inconclusive. Across adult and pediatric populations, findings do not consistently demonstrate a clinically meaningful association between CD or NCGS and periodontal inflammation, irrespective of gluten-free diet (GFD) adherence. Observed differences, when reported, are modest and inconsistent, and can be mainly attributed to oral hygiene behaviors and dental visit patterns. Conclusions: Despite considerable biological plausibility linking gluten-related disorders with periodontal inflammation, current evidence does not support a definitive conclusion regarding the impact of CD or NCGS on periodontal health. Full article

Background: B7-H3, a type I transmembrane glycoprotein belonging to the B7 superfamily, is an attractive target for antitumor therapies. B7-H3 demonstrates aberrant overexpression in various types of solid tumors while showing limited and low expression in normal human organs. Various types of treatment targeting B7-H3 have been reported. Among these treatments, antibody–drug conjugates (ADCs) have shown potent activity, and several clinical trials, including DS7300a and MGC018, are currently ongoing. Methods: Here, we constructed CD276-8 ADC, composed of the anti-B7-H3 antibody CD276-8 with moderate affinity, an enzymatically cleavable tetra-peptide-based linker and DXd. Characteristics, including in vitro binding affinity and internalization activity, were assessed by bio-layer interferometry (BLI), flow cytometry and high content analysis (HCA). The cytotoxicity of CD276-8 ADC was evaluated in cell lines expressing B7-H3. Pharmacokinetic profiles and antitumor activity were evaluated in mouse models in vivo. Finally, the developability of CD276-8 ADC was assessed with plasma stability, accelerated stability and freeze–thaw studies using LC-MS and HPLC. Results: Characterization in vitro demonstrated the moderate affinity and acceptable internalization activity of CD276-8 ADC. In addition, CD276-8 ADC exhibited potent antitumor activities in B7-H3-positive cell line-derived xenograft (CDX) models with acceptable pharmacokinetic profiles, although it showed less potent cytotoxicity in various cell lines in vitro, indicating acceptable developability. Conclusions: We developed CD276-8 ADC, a B7-H3-targeting ADC with moderate affinity, which delivers the TOP1 inhibitor DXd. This design combined moderate affinity and acceptable pharmacokinetics, resulting in potent antitumor efficacy in vivo. Our study suggests that affinity optimization could be a useful consideration for enhancing ADC efficacy, positioning CD276-8 ADC as a promising therapeutic for B7-H3-expressing solid tumors. Full article

Erythropoiesis is tightly regulated by lineage-specific transcription factors that govern erythroid commitment, proliferation, and differentiation. A core erythroid transcriptional network, together with non-DNA-binding cofactors, occupies regulatory regions of genes essential for erythroid development. This process is further shaped by epigenetic mechanisms, including histone post-translational modifications and long-range chromatin interactions. CCCTC-binding factor (CTCF) is a multifunctional regulator with a central role in three-dimensional chromatin organization. Although CTCF has been implicated in hematopoietic differentiation and leukemogenesis, its specific function in erythropoiesis remains poorly defined. Here, we investigated the role of CTCF during erythroid differentiation using two complementary models: pluripotent K562 leukemia cells and primary human CD34⁺ hematopoietic stem/progenitor cells, each induced toward the erythroid lineage by distinct stimuli. In both systems, CTCF silencing impaired erythroid differentiation by repression of key erythroid transcription factor genes, including LMO2, KLF1, MYB, and ETS1. This repression was associated with enrichment of repressive histone marks at CTCF-binding sites within their regulatory regions. Moreover, CTCF cooperated with cohesin to establish and stabilize long-range chromatin interactions at these loci. These results provide new insight into how CTCF-dependent chromatin regulation contributes to normal erythroid development and suggest that perturbation of this regulatory axis may have implications for hematopoietic disorders and malignancies. Full article

Heavy metal contamination in drinking water remains a pervasive global challenge with significant consequences for environmental quality and human health. This review synthesizes findings from recent studies examining heavy metal concentrations in different sources of drinking water, including municipal tap water, groundwater, surface water, and bottled/sachet water across various geographical regions. The study used a systematic review of studies published from 2015 to 2024. The result showed a variation in the concentrations of heavy metals from all the sources, with tap water generally exhibiting lower heavy metal levels. Pb, Fe, Mn, and other metals persist in different sources and from many regions with levels above the permissible limits recommended by the World Health Organization (WHO) in some instances, which were sometimes linked to aging distribution systems and other pollution sources. Bottled and sachet water, commonly regarded as safer alternatives, also showed some levels of heavy metals such as Pb, Cd, and Cr, reflecting inconsistent packaging or production oversight. Surface waters display variability with heavy metals pollution, driven by industrial discharge, mining activities, agricultural runoff, and urban wastewater inputs. Groundwater sources, although naturally shielded, frequently contained elevated concentrations of As, Hg, and Ni due to both geological and anthropogenic factors. Pb concentrations were below detection limit in some of the published papers; however, the values reported in this study ranged from ND to 260.0 µg/L (tap water), ND to 0.259 mg/L (surface water), ND to 0.791 mg/L (groundwater), and ND to 123.15 µg/L (bottled water). Arsenic (As) concentrations ranged from ND to 692 µg/L from different sources, with the highest concentration from groundwater. Collectively, these patterns underscore the need for strengthened monitoring frameworks, improved water treatment technologies, and integrated pollution-prevention strategies. Addressing heavy metal contamination in drinking water requires coordinated policy approach and continuous monitoring to reduce human exposure and safeguard global public health. Full article

Background/Objectives: The COVID-19 pandemic posed significant challenges to quality of life, particularly for individuals living with chronic physical and/or mental conditions. Psychological factors such as fear of COVID-19, psychological distress, and resilience may be associated with quality-of-life outcomes during prolonged public health crises. This study aimed to examine quality of life and its psychological correlates among individuals with chronic conditions during the later phases and aftermath of the COVID-19 pandemic crisis. Methods: A cross-sectional study was conducted among 293 adults with chronic physical and/or mental conditions attending the General Hospital of Argolida, Greece. Participants completed validated self-report measures assessing quality of life (MVQOLI), fear of COVID-19 (FCV-19S), depression, anxiety, and stress (DASS-21), and psychological resilience (CD-RISC-25). Descriptive statistics, Spearman correlation analyses, and multivariable regression models were used to examine associations and identify factors associated with quality-of-life domains. Results: Higher levels of fear of COVID-19 and depressive symptoms were significantly associated with poorer quality of life across multiple domains. Depressive symptoms showed consistent negative associations with functional, interpersonal, transcendent, and overall quality-of-life scores. In contrast, psychological resilience was positively associated with interpersonal, transcendent, and overall quality of life. Regression analyses showed that depressive symptoms were negatively associated with overall quality of life, while resilience was independently associated with better quality-of-life outcomes. Conclusions: Psychological distress, particularly depressive symptoms and fear related to COVID-19, was associated with lower quality of life among individuals with chronic conditions during the later phases and aftermath of the COVID-19 crisis. Psychological resilience was positively associated with better quality-of-life outcomes, underscoring its relevance for supporting well-being during and after public health crises. Full article

Sub-15 nm line structures are key building blocks for advanced device prototyping, nanoscale electrodes, and lithography templates such as etch/deposition masks. Although ultrahigh-voltage (≥100 kV) electron-beam lithography (EBL) can more readily achieve extremely small critical dimensions, its tool and infrastructure requirements limit widespread adoption in many laboratories. In contrast, 30 kV field-emission SEM platforms are far more accessible; however, resolution-limit patterning at 30 kV is more sensitive to beam current, exposure dose, and development conditions, motivating the establishment of a reproducible process flow and a well-defined process window. Here, we investigate the resolution limit of isolated lines using a Zeiss Gemini 460 system operated at 30 kV and an in-house pattern generator with 950 k PMMA C2 resist. To demonstrate device-level applicability, we develop a stable lift-off process, and all critical dimensions are evaluated on metal lines after e-beam evaporation and lift-off. By screening beam current and scanning dose to build the dose-to-size relationship, we show that reducing beam current significantly improves the achievable minimum line width. Under 35 pA, using CD ≤ 15 nm as the criterion for sub-15 nm window extraction, the usable dose range is [700, 804.3] µC/cm², corresponding to a dose latitude of ~14.9%. The best performance is obtained at 700 µC/cm², yielding a transferred metal line width of 13.85 nm after lift-off. This work provides a practical resolution-limit process flow and a quantitative process window for performing sub-15 nm patterning on accessible 30 kV platforms, supported by product-level lift-off validation. Full article

To investigate the characteristics and health risks of heavy metal (HM) contamination in soils of typical industrial sites during urban renewal, this study selected Pudong New District, Shanghai, as a case. Seven HMs (Cd, Pb, Cu, Zn, Ni, Hg, and As) were analyzed for their concentrations, ecological risks, spatial patterns, and potential sources. Inverse Distance Weighted (IDW) interpolation was used to assess spatial distribution, Random Forest (RF) regression to predict HM concentrations, and a two-dimensional Monte Carlo simulation to evaluate human health risks. The results showed that all HMs except As exceeded Shanghai background values in surface soils, with varying levels observed in subsoil and saturated layers. The Index of Geoaccumulation (Igeo) and Risk Index (RI) indicated low contamination and moderate ecological risk. Pearson correlation combined with Positive Matrix Factorization (PMF) identified four major sources: traffic emissions dominated by Cd and Zn, combustion-related sources dominated by Pb and Hg, industry-related inputs dominated by Cu and Ni, and a natural source dominated by As. The RF model demonstrated strong predictive accuracy for Cd, Pb, Hg, and As (R² = 0.80–0.94), and predicted values were consistent with observations. Monte Carlo results showed that non-carcinogenic risks for children and adults were within acceptable limits, while carcinogenic risks reached “notable” levels with probabilities of 62.06%, 55.65%, and 22.49% for children, adult females, and adult males, respectively. Cd and As were identified as key contributors. This work provides scientific support for soil pollution prevention and remediation during urban renewal. Full article

Neuroinflammation is a hallmark of multiple sclerosis (MS). MS is marked by glial cell activation, autoreactive T cells, and the release of pro-inflammatory cytokines and free radicals. Current therapeutic strategies aim to modulate the immune response using disease-modifying therapies, to slow disease progression. The specific aims of this study were: (a) to investigate the effect of cannabinoid acids on the release of glial neuroinflammatory mediators, (b) to examine the effect of intraperitoneally administered cannabinoid acids on symptoms of MS, and (c) to evaluate their effects on microglial and astrocyte activation and CD4⁺ T cell infiltration into the spinal cords of MS mice. Exposure of BV2 microglia to cannabinoid acids attenuated lipopolysaccharide (LPS)-induced expression of inducible nitric oxide synthase by 40–90% it also reduced the release of nitric oxide and interleukin-17A. Among the cannabinoid acids tested, cannabidiolic acid (CBDA) significantly increased tumor necrosis factor alpha (TNFα) secretion by up to 40% in LPS-stimulated BV2 cells. Intraperitoneal administration of CBDA also resulted in a twofold increase in TNFα secretion in splenocytes isolated from MS mice, compared to untreated MS controls. This study provides evidence that CBDA significantly reduces neurological scores, while both cannabinoid acids attenuate microgliosis, astrogliosis, and CD4+ T cell migration in lumbar spinal cord sections of MS mice. These compounds cross the blood–brain barrier (BBB) and act directly within the central nervous system. The consistent elevation of TNFα in the presence of CBDA across three experimental models suggests a distinctive immunomodulatory role for CBDA, with potential therapeutic implications in MS. Full article

Cluster of Differentiation 47 (CD47) functions as a key “don’t-eat-me” signal that enables cancer cells to evade macrophage-mediated immune clearance. GV1001, a 16-amino-acid peptide derived from human telomerase reverse transcriptase (hTERT), has been reported to exhibit antitumor and anti-inflammatory properties and to downregulate CD47 expression in human cells. In this study, we investigated whether GV1001 modulated CD47 expression and enhanced antitumor immunity in oral squamous cell carcinoma (OSCC). In vitro, GV1001 significantly reduced CD47 expression in both murine and human OSCC cells in dose- and time-dependent manners, resulting in a marked increase in macrophage-mediated phagocytosis. Mechanistically, GV1001 suppressed CD47 promoter activity and inhibited multiple upstream regulator expression in murine and human OSCC cell lines, while exerting minimal effects on normal human keratinocytes and fibroblasts. In vivo, GV1001 significantly inhibited tumor growth, suppressed CD47 expression, increased macrophage infiltration, and induced tumor cell necrosis and apoptosis in both murine OSCC syngeneic graft model and human OSCC xenograft model. GV1001 administered alone or in combination with cisplatin produced antitumor effects. Collectively, these findings demonstrate that GV1001 functions as a potent immunomodulatory anticancer peptide that downregulates CD47 expression and restores macrophage-mediated tumor clearance, highlighting its potential as a therapeutic strategy for OSCC. Full article

Cyclodextrins (CDs) have gained increasing attention as versatile platforms for enhancing drug delivery to the central nervous system, particularly in overcoming the restrictive properties of the blood–brain barrier (BBB). Owing to their unique cyclic oligosaccharide structure, CDs are capable of forming inclusion complexes with a wide range of therapeutic agents, thereby improving their solubility, stability, and bioavailability. In addition to their role as excipients, growing evidence indicates that CDs can actively modulate biological processes, including membrane fluidity and cholesterol homeostasis, which are critical factors in neurological disorders. This review explores the application of CDs in facilitating drug transport across the BBB through multiple mechanisms, including carrier-mediated transport, receptor-mediated transcytosis, and nanoparticle-based delivery systems. Special emphasis is placed on their use in the treatment of neurodegenerative and neurological diseases, such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, Niemann–Pick type C disease, and other central nervous system disorders. In these contexts, CD-based formulations have demonstrated the ability to enhance brain targeting, reduce pathological protein aggregation, and improve therapeutic outcomes in preclinical models. This review uniquely integrates cyclodextrin’s physicochemical properties with specific blood–brain barrier transport mechanisms, proposing a structure–transport–therapy framework that enables a more predictive understanding of brain-targeted drug delivery. Full article

Background: CD8A-related CD8α deficiency (Immunodeficiency 116) is a rare autosomal recessive primary immunodeficiency disease characterized by absent CD8⁺ T cells and variable sinopulmonary disease. Case Presentation: A seven-year-old boy from a consanguineous family was referred for chronic wet cough and “uncontrolled asthma” despite being prescribed high-dose inhaled corticosteroids and montelukast. He was hospitalized seven times over a two-year period for presumed asthma exacerbations complicated by pneumonia. An examination revealed bilateral crackles without wheezing. Throat culture tested positive for Haemophilus influenzae. CT imaging showed signs of chronic rhinosinusitis (maxillary mucosal thickening) and chronic airway disease with bronchiectatic changes. The patient’s immunoglobulin levels were within normal ranges for his age group. Flow cytometry revealed profound CD8⁺ T-cell lymphopenia (CD8⁺ 0.21%; 11 cells/µL; near-absent after excluding dual-positive cells) with expansion of CD3⁺CD4⁻CD8⁻ T cells (29.5%). CD8A gene sequencing identified a novel homozygous nonsense variant NM_001768.7:c.319C>T (p.Arg107Ter; GRCh38: chr2:86790412G>A), consistent with loss of CD8α and secondary loss of CD8β surface expression. A literature review identified three previously reported symptomatic patients (and two asymptomatic sisters in the first family), all with recurrent respiratory infections and variable structural lung disease. Conclusions: This case highlights CD8A deficiency as a rare mimic of pediatric asthma and expands the genotype spectrum with a truncating CD8A variant. Early lymphocyte immunophenotyping in children with recurrent sinopulmonary infections may prevent delayed diagnosis and progressive airway damage. Full article

Alphaherpesviruses, including Herpes Simplex Virus 1 (HSV-1) and Pseudorabies Virus (PrV), establish lifelong latency in the nervous system and can cause recurrent disease. While latency has classically been attributed to peripheral sensory ganglia, accumulating evidence indicates that the central nervous system (CNS) may also serve as a site of long-term viral persistence and reactivation. Here, we investigated the CNS as a viral reservoir using the attenuated mutant PrV-∆UL21/US3∆kin, which preferentially targets mesiotemporal brain regions. Following intranasal inoculation, mice were analyzed at 11–14, 21, 28, 42, 105, and 190 days post-infection (dpi). To assess the reactivation potential, a subset of animals received cyclophosphamide/dexamethasone at 170 dpi. Viral transcripts were detected by RNAscope™ in situ hybridization and RT-qPCR targeting the lytic gene UL19 encoding the major capsid protein and the latency-associated transcript (LAT). Histopathology included hematoxylin and eosin staining and immunohistochemistry for CD3, Iba1, GFAP, cleaved caspase-3 and viral glycoprotein gB. UL19 RNA signals displayed marked regional and temporal heterogeneity, with prominent detection in mesiotemporal structures. In contrast, LAT RNA levels remained low overall, with a transient peak during the acute phase. RT-qPCR confirmed high UL19 and LAT transcript levels during early infection, while LAT transcription returned to baseline levels thereafter. Histopathology showed a transition from acute necrotizing meningoencephalitis to prolonged low-grade inflammation with glial activation and focal apoptosis. Notably, UL19 RNA signals strongly correlated with T-cell infiltration, particularly at 42 dpi. Together, these findings define regional and temporal patterns of long-term PrV transcriptional activity and associated neuropathology in the murine CNS. Full article

Background/Objectives: Differentiating Cushing’s disease (CD) from adrenocorticotropic hormone (ACTH)-independent Cushing’s syndrome (AICS) remains challenging in patients with equivocal ACTH levels. While dynamic testing is frequently required, baseline hormonal measurements may offer a simpler diagnostic approach. We aim to evaluate the diagnostic value of baseline plasma ACTH, cortisol, and dehydroepiandrosterone sulfate (DHEAS) levels and their derived ratios for differentiation between ACTH-dependent and ACTH-independent Cushing’s syndrome, and to propose a diagnostic algorithm based on these parameters. Methods: This retrospective single-centre study included adult patients with endogenous Cushing’s syndrome aged 18–75 years who were followed at our institution. Patients with ectopic/paraneoplastic Cushing’s syndrome were excluded. The AICS group comprised overt adrenal CS and mild autonomous cortisol secretion cases. Morning baseline plasma ACTH (pg/mL), serum cortisol (µg/dL), and serum DHEAS (µg/dL) levels were measured and ratios calculated: cortisol-to-ACTH ratio (CAR), DHEAS-to-cortisol ratio (DCR), and CAR-to-DHEAS ratio (CAR/D). ROC analysis assessed diagnostic performance with age and sex adjustments. Results: A total of 100 patients were included, comprising 43 patients with CD and 57 with AICS. Plasma ACTH demonstrated high diagnostic accuracy for identifying CD with a cut-off of ≥14.65 pg/mL (sensitivity 100%, specificity 98.25%, AUC 0.998). Serum DHEAS showed strong discriminative power with a cut-off of ≥67.15 µg/dL (sensitivity 88.37%, specificity 91.23%, AUC 0.925), achieving high discriminative power after age–sex adjustment at ≥85.59 µg/dL (sensitivity 100%, specificity 100%, AUC 0.999). CAR showed good performance in identifying CD with a cut-off of ≤0.75 µg/dL per pg/mL (sensitivity 93.02%, specificity 98.25%, AUC 0.980). CAR/D demonstrated high diagnostic power with a cut-off of ≤1.54 (sensitivity 95.35%, specificity 98.25%, AUC 0.974), improving after age–sex adjustment to ≤2.36 (sensitivity 97.87%, specificity 96.23%, AUC 0.992). Conclusions: Baseline plasma ACTH, serum cortisol, and serum DHEAS measurements, along with derived ratios—especially CAR and CAR/D—provide highly accurate differentiation between ACTH-dependent and ACTH-independent Cushing’s syndrome. These widely available measurements may reduce dependence on dynamic testing and improve diagnostic accuracy in patients with equivocal findings. Full article

CdSe-coated electrodes, formed by electrodeposition of CdSe barrier layers on metallic Ti or porous TiO₂ substrates, were characterized by electrochemical impedance spectroscopy in a (photo)cell using aqueous redox electrolytes based on the sulfide/polysulfide or ferro/ferricyanide couples. The influence of electrode material properties, electrolyte contact, thermal annealing, and measurement conditions (illumination, frequency, potential-scan speed) on the shape and features of Mott–Schottky plots was investigated. The obtained information was evaluated on the basis of the ideal Schottky diode model and photocurrent voltammetry data. Deviations from linear diode behavior and uncertainties in the determination of energetic parameters were examined and attributed to the presence of donor density gradients and surface states in the semiconductor electrode, further complicated by chemical corrosion. The origin of the observed non-idealities is inquired into, and specific aspects of the measuring procedure related to the non-stationary character of the interface are discussed. Full article