Search Results (11,016)

The increasing prevalence of childhood obesity has been accompanied by an increase in consumption of ultra-processed foods (UPF), characterized by high energy density and low nutritional quality. Emerging evidence suggests that dietary patterns rich in UPF may contribute to low-grade systemic inflammation and early metabolic dysfunction in children and adolescents. Objective: This systematic review aimed to evaluate the association between UPF consumption and markers of inflammation and metabolic health in pediatric populations. Methods: A systematic literature search was conducted on PubMed in accordance with PRISMA guidelines. Observational and interventional studies evaluating UPF intake or diet-related inflammatory potential in children and adolescents (≤18 years) were included. Outcomes of interest included inflammatory biomarkers (e.g., C-reactive protein, interleukins, tumor necrosis factor-α) and metabolic parameters (e.g., insulin resistance, lipid profile, glucose metabolism). Results: A limited number of studies have directly assessed UPF consumption using the NOVA classification. Overall, these studies suggest a potential association between increased UPF intake and adverse metabolic outcomes, although findings on inflammatory markers remain inconsistent. A larger body of indirect evidence, including studies assessing dietary inflammatory indices and related dietary patterns, consistently supports a link between pro-inflammatory diets and increased inflammation and metabolic dysregulation in pediatric populations. Conclusions: Although direct evidence on UPF consumption remains limited, the available findings, supported by complementary indirect evidence, suggest a plausible relationship between UPF-rich diets, inflammation, and metabolic health in children and adolescents. Further well-designed studies are needed to clarify causality and improve the standardization of dietary assessment methods. Full article

The high incidence of thrombosis in lymphoma is largely due to chronic inflammation and endothelial dysfunction. To elucidate the mechanisms underlying thrombus formation and fibrinolysis, we investigated interactions between circulating endothelial cells and peripheral blood mononuclear cells (MNCs), along with inflammatory signaling pathways, in patients with follicular lymphoma (FL), Hodgkin lymphoma (HL), and diffuse large B-cell lymphoma (DLBCL), independent of the presence of thrombosis, compared to healthy controls by flow cytometry, immunoblotting, and fluorometric assays. We observed increased tissue factor (TF) expression on CD31+ endothelial cells in DLBCL and FL. In DLBCL, inducible nitric oxide synthase expression was elevated in MNCs, while reduced nitrite levels correlated with an advanced clinical stage in patients with thrombosis. In lymphoma, nuclear factor kappa B (NFκB) signaling was activated in MNCs, while signal transducer and activator of transcription 3 (STAT3) activation was increased in DLBCL with thrombosis. Trans-endothelial migration of MNC was enhanced in HL, FL and DLBCL with thrombosis and reduced by inflammatory cytokine tumor necrosis factor alpha (TNF-α) that promoted platelet aggregation like interleukin-6 (IL-6) in HL and FL. Fibrinolytic analyses showed reduced tissue type plasminogen activator in lymphoma, whereas increased urokinase-type plasminogen activator (uPA) was linked to poorer total survival in DLBCL with thrombosis, suggesting a compensatory role in early thrombus resolution. These findings indicate that chronic inflammation promotes endothelial activation, dysregulated fibrinolysis, and increased vascular permeability, contributing to heightened thrombotic risk. This study provides mechanistic insight into lymphoma-associated thrombosis and identifies TF, uPA, and the inflammatory signaling pathways as potential biomarkers and therapeutic targets. Full article

Ultraviolet (UV) irradiation induces complex skin damage, including hyperpigmentation, oxidative stress, and alterations in proteins related to keratinocyte differentiation and epidermal barrier-associated status. This study investigated the multifunctional protective effects of Padina arborescens ethanolic extract (PAEE) against skin damage in melanocytes, keratinocytes, and zebrafish. In alpha-melanocyte-stimulating hormone (α-MSH)-stimulated B16F10 cells, PAEE effectively suppressed the protein kinase A (PKA)/cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) signaling pathway, which was associated with reduced expression of microphthalmia-associated transcription factor (MITF) and tyrosinase, leading to decreased melanin synthesis. PAEE also exhibited photoprotective properties by reducing reactive oxygen species (ROS), inhibiting interleukin-1 beta (IL-1β), and attenuating matrix metalloproteinase-1 (MMP-1) upregulation associated with UVB (ultraviolet B)-induced photodamage in HaCaT keratinocytes. Notably, PAEE restored the UVB-reduced expression of filaggrin and involucrin, representative markers of keratinocyte differentiation and epidermal barrier-associated status, in HaCaT keratinocytes. In zebrafish embryos, PAEE suppressed α-MSH-induced melanin accumulation and UVB-induced ROS generation at non-toxic concentrations. Taken together, these results suggest that PAEE exerts anti-melanogenic and photoprotective effects in cellular and zebrasfish models and may serve as a promising marine-derived ingredient for cosmeceutical applications targeting UVB-related skin damage. Full article

A body of evidence suggests that upregulating O-GlcNAcylation, a reversible post-translational modification of serine and threonine residues on target proteins, is beneficial in neurological diseases. However, this phenomenon is currently underexplored in the pharmacotherapy of epilepsy. Therefore, we aimed to explore the potential effects of combining N-acetylglucosamine (GlcNAc), a precursor for O-GlcNAcylation, and a centrally acting benzodiazepine (diazepam) on oxidative stress, a known driver of epilepsy, and some epileptogenesis-associated genes. Mice (n = 10) were randomly assigned to treatment groups and treated with varied oral doses (100, 200, and 400 mg/kg) of GlcNAc in combination with diazepam (1 mg/kg) for 14 days. Following this, seizure was chemically induced with 70 mg/kg pentylenetetrazol intraperitoneally. Brains of treated mice were excised for antioxidant assays and to determine the expression of genes associated with epileptogenesis: potassium chloride co-transporter (KCC4), interleukin (IL-6), tumour necrosis factor-α (TNF-α), and brain-derived neurotrophic factor (BDNF). Our findings suggest that GlcNAc, when concurrently administered with diazepam, prevents oxidative stress and reduces the gene expression of IL-6, a cytokine associated with neuroinflammation and seizures, whilst increasing the gene expression of KCC4, an ion co-transporter that promotes antiepileptogenesis. Full article

Alcohol-induced liver damage (AILD), characterized by oxidative stress and inflammation, is a major health concern. While black ginseng extract (BGE) exhibits diverse pharmacological activities, its protective effects against AILD and underlying molecular mechanisms remain unclear. This study evaluated the protective effects of BGE against AILD using in vivo, in vitro, and in silico models. In mice, daily oral administration of 25% ethanol (5 g/kg) for 2 weeks induced liver injury. BGE (100–500 mg/kg) significantly reduced serum alanine aminotransferase (AST) and aspartate aminotransferase (ALT)levels while increasing catalase (CAT) and superoxide dismutase (SOD) activities. In ethanol-treated HepG2 cells, BGE inhibited nitric oxide (NO) production and suppressed cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) expression while increasing heme oxygenase-1 (HO-1)expression. Ginsenoside Rh1, quantified at 4.7 mg/g via quadrupole linear ion trap tandem mass spectrometry coupled with UPLC (UPLC-Q-TRAP-MS/MS), was identified as a key bioactive compound. Network pharmacology and molecular docking analyses revealed key inflammatory signaling pathways and core hub genes associated with ginsenoside Rh1. Integrated analyses suggest that ginsenoside Rh1 contributes to the multi-target effects of BGE by modulating inflammatory signaling pathways. Collectively, BGE is a potential therapeutic candidate for the prevention and treatment of AILD, with ginsenoside Rh1 serving as a key bioactive constituent and quality control marker. Full article

The effects of broad-spectrum mycotoxin detoxifiers (BSMDs) on growth performance, liver histopathology, jejunal morphology, and oxidative stress were evaluated in broilers fed diets contaminated with multiple mycotoxins. A total of 800 one-day-old male Ross 308 broilers were randomly assigned to four treatments, with eight replicates of 25 birds each, and reared for 42 days. The treatments included a basal control diet (CON); a multi-mycotoxin-contaminated diet (MMT) containing aflatoxins (25 µg/kg), zearalenone (135 µg/kg), T2 toxin (85 µg/kg), fumonisin (1.90 mg/kg), and deoxynivalenol (0.70 mg/kg); and the MMT diet supplemented with either 1.0 kg/ton BSMD-1 or 1.5 kg/ton BSMD-2. MMT contamination did not affect growth performance, serum malondialdehyde, interleukin-6 levels, liver enzyme activities, or liver lesion scores. Nevertheless, interleukin-10 levels were lower in birds fed the MMT diet (p = 0.03). In birds fed MMT, there was a substantial decrease (p < 0.05) in the height of the jejunal villi, their surface area, and the ratio of their height to the depth of the crypt. While BSMD-supplemented groups displayed values similar to both CON and MMT, MMT birds had higher fatty liver scores than the control group. Overall, multi-mycotoxin contamination impaired gut morphology and immune balance. BSMD supplementation improved intestinal structure, enhanced immune response, and partially mitigated liver alterations. These findings indicate its potential as a dietary intervention to mitigate the detrimental effects of multi-mycotoxin contamination in broilers. 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

Open-heart surgery with cardiopulmonary bypass (CPB) is a high-risk procedure with significant morbidity and mortality. CPB, tissue injury, blood loss, endotoxemia and ischemia–reperfusion injury induce a pronounced systemic inflammatory response, leading to endothelial glycocalyx (EG) damage and vascular endothelial dysfunction. Consequently, immune cells, reactive oxygen species, and enzymes gain free access to vascular endothelial cells, resulting in their dysfunction and enhancing inflammation, vascular permeability, and microvascular impairment. EG degradation is most commonly assessed by measuring the circulating levels of its degradation products. Additionally, CPB triggers an early inflammatory response that is characterized by the secretion of interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor alpha, and IL-18, which play roles in initiating the process of EG injury. EG damage is further propagated by the sustained release of cytokines, inhibiting the regeneration of the glycocalyx layer. Heparanase and matrix metalloproteinases are enzymatic pathways involved in cytokine-mediated EG degradation after cardiac surgery, and the balance between the pro- and anti-inflammatory cytokines determines the magnitude and duration of the inflammatory response and EG impairment, which correlates with adverse clinical outcomes, including myocardial dysfunction, acute lung and kidney injury, neurological complications, and prolonged need for intensive care. Thus, identifying patients with an exaggerated cytokine response could potentially provide more personalized therapy based on the circulating biomarkers of EG shedding, and cytokine-directed preservation of EG represents a promising therapeutic strategy in vascular dysfunction prevention during and after open-heart surgery. In this review, we summarize the current knowledge on cytokine-mediated EG impairment following open-heart surgery with CPB. Full article

Background/Objectives: Dupilumab is a fully human IgG4 monoclonal antibody targeting the interleukin-4 receptor α subunit, inhibiting interleukin-4 and interleukin-13 signalling, and suppressing type 2 inflammation. It is approved for several eosinophilic and type 2 inflammatory diseases, including chronic rhinosinusitis with nasal polyps, asthma, atopic dermatitis, eosinophilic oesophagitis, and, more recently, eosinophilic chronic obstructive pulmonary disease. Although generally well tolerated, dupilumab has been associated with peripheral eosinophilia and, rarely, eosinophil-mediated complications. This study aims to describe cases of eosinophilic granulomatosis with polyangiitis (EGPA) occurring after dupilumab initiation and to review available evidence on this association. Methods: We describe two cases of new-onset EGPA developing after the introduction of dupilumab therapy, analysing clinical features, laboratory findings, management, and outcomes. A narrative review of published case reports and literature addressing dupilumab-associated eosinophilia and EGPA was also performed. Results: Both patients developed EGPA after starting dupilumab, presenting with marked peripheral eosinophilia and systemic manifestations consistent with the disease. Clinical improvement was observed following dupilumab discontinuation and initiation of appropriate immunosuppressive treatment. The literature review identified a small number of similar reports describing EGPA onset or unmasking in temporal association with dupilumab, mainly in patients with underlying type 2 inflammatory disorders. Conclusions: While a causal relationship between dupilumab and EGPA remains unproven, these findings highlight the importance of clinical awareness. Dupilumab remains an effective therapy for severe type 2 inflammatory diseases; careful monitoring may allow early recognition and management of rare eosinophilic complications. Full article

This cross-sectional exploratory study aimed to explore the association between inflammatory biomarkers and multidimensional psychological burden in informal primary caregivers of dependent older adults in an emergency department. We included 78 caregivers and up to 89 controls. Multidimensional psychological burden (perceived stress, depression, anxiety, and caregiver burden) was assessed using standardized instruments. Morning serum levels of cortisol, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive Protein, were measured. Statistical analyses included between-group comparisons (Mann–Whitney U test), correlations (Spearman rank correlation coefficient), and hierarchical block regression adjusted for obesity, diabetes, and hypertension in the caregiver group. Multiplicity was addressed using the False Discovery Rate (FDR) procedure, and the findings were validated through 1000 bootstrap resamples. Caregivers had significantly higher levels of TNF-α compared to controls (p = 0.021), a finding confirmed by bootstrap analysis (95% CI: −2.6730 to −0.2940). IL-6 levels were positively correlated with trait anxiety (p = 0.007) and caregiver burden (p = 0.019). Comorbidity-adjusted hierarchical regression confirmed significant associations between IL-6 levels and trait anxiety and caregiver burden (ΔR² = 0.123, p = 0.007), although these associations did not remain significant after adjustment for FDR. Caregivers showed elevated levels of TNF-α and exploratory associations between IL-6, trait anxiety, and caregiver burden, justifying confirmation in studies with a larger number of participants. Full article

Obesity is characterized by chronic low-grade inflammation and immunometabolic dysfunction. However, the influence of obesity degree on circulating inflammatory mediators and immune-cell–specific molecular pathways remains poorly defined. We aimed to examine the effects of obesity severity on plasma cytokines and adipokines, and on the expression of inflammatory, antioxidant, and mitochondrial genes in peripheral immune cells, with emphasis on gender differences. In this cross-sectional study, 134 adults aged 55–80 years were stratified into overweight, moderate, or severe obesity groups. Plasma cytokine and adipokine levels were quantified with multiplex immunoassays. Gene expression in peripheral blood mononuclear cells and neutrophils was measured by quantitative PCR. Standard hematological parameters were assessed. Two-way analysis of variance and correlation analyses were performed to evaluate associations between obesity severity, gender, circulating biomarkers, and gene expression. Severity of obesity was associated with distinct alterations in circulating inflammatory profiles in a gender-dependent manner. Women exhibited progressive increases in plasma interleukin (IL)-6 with obesity severity, whereas men with severe obesity demonstrated elevated IL-15 and IL-1rα plasma levels. Hematological responses also differed by gender. In contrast, expression of classical inflammatory genes in immune cells was largely unchanged across obesity categories. Women showed higher expression of antioxidant and mitochondrial genes than men, suggesting gender-specific resilience in redox and mitochondrial pathways. Correlations between circulating inflammatory mediators and immune-cell gene expression were generally weak. Obesity severity and gender modulate systemic inflammatory, while immune-cell transcriptional responses are limited, highlighting the importance of gender-specific immunometabolic characterization in obesity research. Full article

Hypersensitivity reactions to iodinated contrast media (ICM) are traditionally categorized as immediate or delayed reactions, involving IgE-mediated pathways, non–IgE-dependent mast cell or complement activation, or T cell–mediated immune mechanisms. However, we observed that some individuals develop systemic inflammatory responses that do not fit these established categories. We describe here a case series of three patients who developed cytokine release syndrome (CRS)-like reactions following iodinated contrast administration, which were initially difficult to distinguish from sepsis and were only recognized after recurrent episodes. Clinical presentation, laboratory findings, cytokine profiles, allergy investigations, and treatment outcomes were reviewed. All patients developed fever, rigors, and hypotension within 5 to 70 h after exposure, accompanied by leukocytosis and markedly elevated inflammatory markers despite negative microbiological investigations. Serum tryptase levels remained within the normal range with no significant rise, while cytokine analyses demonstrated elevations of pro-inflammatory interleukin-6 and other cytokines in patients 1 and 3 where samples were available. Standard corticosteroid premedication did not prevent recurrence, and one patient developed systemic symptoms following intradermal testing. All patients improved with high-dose systemic corticosteroids and supportive care. These findings suggest that ICM may induce a cytokine-mediated inflammatory phenotype distinct from classical hypersensitivity reactions, highlighting the importance of early clinical recognition to guide diagnosis and management. Full article

This study investigated the effects of dietary supplementation with α-mangostin (α-Ma), a bioactive xanthone derived from mangosteen pericarp, on production performance and egg quality in late-phase laying hens. The experiment was conducted using a completely randomized design. In total, 576 healthy 51-week-old Beinong No. 2 laying hens were randomly assigned to 4 dietary treatments (n = 12): a basal diet (CON) or the basal diet supplemented with 80, 120, or 160 mg/kg α-Ma. The experiment lasted for 4 weeks, after which production performance, egg quality, serum biochemical and antioxidant parameters, inflammatory markers, and uterine gene expression were evaluated. Dietary supplementation with α-mangostin, particularly at 120 mg/kg, significantly improved feed efficiency (p < 0.05), as evidenced by a reduced feed-to-egg ratio from week 2 onward, without affecting average daily feed intake or egg production rate. After 4 weeks, hens receiving 120 mg/kg α-Ma exhibited significantly greater egg weight and eggshell strength (p < 0.05). Serum and hepatic antioxidant capacities were significantly enhanced, with increased glutathione peroxidase and catalase activities, elevated total antioxidant capacity, and decreased malondialdehyde levels (p < 0.05). Moreover, α-Ma at 120 mg/kg specifically lowered the concentration of the pro-inflammatory cytokine interleukin-1β in both serum and uterine tissue (p < 0.05). At the molecular level, this dosage significantly upregulated uterine genes essential for eggshell formation (p < 0.05), including calcium transporters (TRPV6, ATP2B2), the matrix protein gene OC-116, and other key genes (LYZ, CA2, SLC4A9, and ATP6V0D2). In conclusion, dietary supplementation with 120 mg/kg α-Ma effectively enhances feed efficiency, strengthens antioxidant and anti-inflammatory defenses, and upregulates uterine genes involved in biomineralization, thereby improving eggshell quality in aging laying hens. These findings support α-Ma as a promising plant-based feed additive for maintaining productivity and egg quality in antibiotic-free layer production systems. Full article

Interleukin-10 (IL-10) is a key immunoregulatory cytokine that suppresses inflammatory gene transcription in myeloid cells through signal transducer and activator of transcription 3 (STAT3). In Alzheimer’s disease and neuroinflammation, microglia express IL10ra and exhibit STAT3 Tyr705 phosphorylation following IL-10 stimulation, indicating IL-10 receptor-dependent STAT3 activation. Recent studies demonstrate that IL-10 induces promoter-selective STAT3-dependent transcriptional regulation in microglia through chromatin-associated mechanisms, whereas gp130-dependent cytokines activate STAT3 to induce transcription of defined target genes, including Socs3 and Ccl5. Following IL-10 receptor activation, STAT3 binds regulatory regions of inflammatory genes, including Il1b, Tnf, Il6, and Nlrp3, with reduced RNA polymerase II and NF-κB binding. IL-10-dependent transcriptional repression involves formation of a nuclear SHIP1–STAT3 complex, localization of histone deacetylase (HDAC)1 and HDAC2 to H3K4me1-enriched enhancer regions, reduced H3K27ac, and decreased chromatin accessibility at regulatory regions of inflammatory genes. IL-10-activated STAT3 induces Socs3, which regulates JAK1 and TYK2 activity and STAT3 phosphorylation. Impairment of IL-10 receptor signaling in microglia is associated with increased inflammatory gene expression, enhanced inflammasome-related transcription, demyelination, and amyloid accumulation. This review focuses on IL-10–STAT3-dependent transcriptional regulation in microglia, including receptor signaling, chromatin-associated mechanisms, and disease-associated gene expression in Alzheimer’s disease and neuroinflammation. Full article

Cutaneous T-cell lymphoma (CTCL) comprises a heterogeneous group of extranodal non-Hodgkin lymphomas. With the publication of the fifth edition of the World Health Organization Classification of Hematolymphoid Tumors, the diagnostic framework for CTCL has shifted from primarily morphologic phenotypes toward an emphasis on molecular drivers. Current research suggests that malignant clones may arise from somatic mutations at the hematopoietic stem cell stage and may follow a continuous hematogenous dissemination model with bidirectional trafficking between the skin and systemic circulation. At the molecular level, genomic instability, often associated with somatic copy-number variations, may promote activation of the janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling pathway through gene-dosage effects. In parallel, chromatin remodeling linked to EZH2 overexpression and reduced special SATB1 expression may support a Th2-polarized program. This phenotype may contribute to epidermal barrier impairment via cytokines such as Interleukins-4 (IL-4) and IL-13, potentially creating conditions permissive for Staphylococcus aureus colonization. Microbial superantigens and exotoxins may further contribute to tumor progression and therapeutic resistance by reinforcing JAK/STAT signaling, particularly STAT3, and reducing CD8+ T-cell–mediated immune surveillance. In the dermis, reprogramming of cancer-associated fibroblasts and polarization of macrophages toward an M2 phenotype may collectively contribute to an immunosuppressive niche. Emerging biomarkers, including CD74, and acquired resistance mechanisms after anti-C-C chemokine receptor 4 therapy further extend the translational relevance of recent pathologic findings. Overall, CTCL evolution appears to be a systemic process shaped by interactions between tumor-intrinsic genetic alterations and the skin microenvironment. Full article