Search Results (11,097)

Eosinophils are multifunctional granulocytes that reside constitutively within mucosal tissues, where they engage in bidirectional communication with the epithelial cells lining the respiratory and gastrointestinal (GI) tracts. Once regarded solely as terminal effectors of the type 2 immunity, eosinophils are now recognized as key regulators of epithelial homeostasis and barrier integrity. Epithelial cells initiate crosstalk by releasing the alarm cytokines such as interleukin (IL)-33, thymic stromal lymphopoietin (TSLP), and IL-25, which drive eosinophil recruitment, activation, and tissue retention. Conversely, eosinophils modulate epithelial function through the release of granule proteins, cytokines, and growth factors with both damaging and reparative consequences. In the airway, this crosstalk underpins the pathogenesis of eosinophilic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), in part via eosinophil-derived mediators that disrupt tight junction integrity and fuel remodeling. In the GI tract, homeostatic eosinophils support villous architecture, epithelial turnover, and goblet cell differentiation through microbiota-driven IL-33 signals and neuropeptide-mediated neuroimmune pathways, whereas dysregulated crosstalk promotes eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD). This review synthesizes recent research to delineate the molecular mechanisms of eosinophil–epithelial crosstalk across mucosal compartments, highlight tissue-specific differences and shared mechanistic themes, and discuss the implications of these findings for targeted therapy. Full article

Objectives: Seawater-immersed burn wounds are highly susceptible to contamination, persistent inflammation, oxidative stress, and delayed healing, while current irrigation solutions remain suboptimal for such acute injuries. This study aimed to evaluate the therapeutic efficacy and underlying mechanisms of plasma-activated water (PAW) as a novel irrigation strategy for these complex wounds. Methods: The antibacterial efficacy of PAW against marine pathogens was first evaluated in vitro. Subsequently, a rat model of seawater-immersed burn injury was established in male Sprague-Dawley (SD) rats to assess the therapeutic effects of PAW irrigation on wound healing, infection control, and underlying biological mechanisms. Results: In vitro, PAW significantly eradicated two major marine pathogens, Vibrio vulnificus and Vibrio parahaemolyticus (p < 0.001). In vivo, PAW markedly accelerated wound closure, achieving complete healing in 23.60 ± 6.50 days vs. 38.67 ± 2.08 days (Normal saline group) and 58.33 ± 10.97 days (Model group) (p < 0.05). PAW significantly reduced bacterial burden, modulated inflammation by decreasing interleukin-6 and increasing interleukin-10, and alleviated oxidative stress, as evidenced by reduced malondialdehyde levels and enhanced superoxide dismutase activity. Histological evaluation demonstrated enhanced re-epithelialization, collagen deposition, and increased expression of vascular endothelial growth factor and platelet endothelial cell adhesion molecule-1. No adverse effects on serum biochemistry or major organ histopathology were observed. Conclusions: PAW may be a safe, promising, and multifunctional irrigation strategy that promotes seawater-immersed burn healing through coordinated antibacterial, anti-inflammatory, antioxidant, and pro-angiogenic effects, highlighting its strong potential for clinical translation. Full article

Background/Objectives: Radon exposure has recently been associated with asthma morbidity, including increased airway inflammation and school absenteeism in children, though limited data on underlying biological mechanisms exist. Interleukin-6 (IL-6), a pleiotropic cytokine implicated in both Type 2-low airway inflammation and radon-related lung carcinogenesis, may represent a key mechanistic link between radon exposure and asthma morbidity. We aimed to evaluate the association between indoor radon exposure and plasma IL-6 levels in children with asthma and whether this relationship differs by allergic sensitization status. Methods: We analyzed baseline data from the School Inner-City Asthma Study, a prospective cohort of children aged 4–13 years with persistent asthma. Monthly indoor radon concentrations at each participant’s residential ZIP Code Tabulation Area were estimated using a validated spatiotemporal prediction model. Plasma IL-6 was measured from baseline blood samples. Multivariable linear mixed-effects models with random intercepts for school were used to assess the association between radon exposure and IL-6, adjusting for demographic, clinical, and socioeconomic covariates. Effect modification by allergic sensitization was evaluated using an interaction term. Results: Among 144 participants, 62.5% were allergen-sensitized. The median home radon concentration was 46.6 Bq/m³ (range 30.7–99.9), and the mean plasma IL-6 was 0.22 pg/mL (SD 0.41). A significant interaction was observed between radon exposure and allergic sensitization status (β-interaction = –0.012; p = 0.014), indicating differential effects by phenotype. Among non-sensitized children, higher radon exposure was associated with increased IL-6 levels (β = 0.0088; p = 0.044), corresponding to a 0.32 pg/mL rise in IL-6 per 37 Bq/m³ increase in radon. No significant association was observed among sensitized children. Conclusions: Indoor radon exposure is associated with higher plasma IL-6 levels in non-sensitized children with asthma, suggesting a potential IL-6–mediated pathway linking radon exposure to asthma morbidity in the Type 2-low phenotype. These findings highlight heterogeneity in environmental asthma responses and support further investigation into radon mitigation as a modifiable factor to improve asthma outcomes. IL-6 may serve as a biomarker to identify children most susceptible to radon-related airway inflammation, guiding personalized mitigation strategies and targeted interventions to improve asthma outcomes. Future studies should incorporate direct home radon measurements, comprehensive endotyping panels, and longitudinal biomarker sampling to validate these findings and elucidate whether IL-6 trans-signaling pathways mediate radon-induced airway injury in non-allergic asthma. Full article

Inflammation at the superior airway level has multiple manifestations, and allergic rhinitis and chronic rhinosinusitis with or without polyps are two of the most frequent and troublesome of them, with innate and adaptive immunity being implicated. Dendritic cells, epithelial cells, neutrophils, macrophages, mucosal mast cells, eosinophils, basophils, innate lymphoid cells (ILCs), and NK cells are the players in innate immunity, while regulatory T (Treg), TH1, TH2, TH17, T follicular helper, and B cells are components of the adaptative immune system. Th9 cells, a subset of T helper cells discovered in 2008 that produce interleukin-9 (IL-9), play a vital role in the adaptive immune response and have advantageous and harmful effects in different diseases due to the induction pattern. We queried international databases for current, up-to-date information regarding the interplay between interleukin 9 (IL-9) and helper T cells (especially Th9 cells), and by other immune cells. Interleukin-9 has multiple immunological functions, acting on various target cells through its specific receptor (IL-9R), such as the following: the regulation of allergic (Th2-type) immune responses; effects on epithelial and mucosal cells, mast cells, and eosinophils; chronic inflammation; and autoimmunity. Thus, there is a further need to translate laboratory findings into clinical practice regarding IL-9. Full article

Fibromyalgia, a syndrome characterized by hyperalgesia and ‘negative emotionality’, and major depressive disorder (MDD) demonstrate substantial overlaps in clinical, neurobiological, and therapeutic domains. Currently, treatment options for fibromyalgia remain limited; however, the epidemiology of this syndrome continues to grow worldwide. The use of animal models is indispensable for developing new treatment strategies for fibromyalgia. Meanwhile, the choice of animal paradigms is limited. Here, we used the ultrasound exposure of emotional stress on CBA, BALB/c, and C57BL/6 mouse strains to model this condition and to identify new molecular targets of fibromyalgia treatment. We exposed young male mice of three common strains to a three-week ultrasound stress (US) comprising emotionally negative and neutral frequencies of 20–25 kHz and 25–45 kHz, resulting in the development of altered pain sensitivity and signs of ‘negative emotionality’. Specifically, mice were studied for timid-like/aggressive behaviors and the tail flick response. Serum levels of corticosterone, cortisol, β-Endorphin, and brain-derived neurotrophic factor (BDNF), as well as brain gene expression of interleukin-33 (Il-33), Bdnf, and its receptor Trkb were investigated. Among the stressed mouse strains, C57BL/6 mice displayed augmented pain sensitivity, allodynia, and suppressed dominant behavior, whereas CBA and BALB/c mice demonstrated opposing changes. Glucocorticoid levels were increased in all stressed groups. Stressed C57BL/6 mice showed downregulated gene and protein expression of functionally inter-related BDNF and IL-33 molecules in the hippocampus, amygdala, and striatum, significantly correlating with behavioral outcomes, as well as lowered blood levels of β-Endorphin and elevated cortisol concentrations. Altogether, our study identified the BDNF/IL-33 regulatory pathway as a molecular correlate of fibromyalgia, and the use of US-exposed young C57BL/6 mice as a potential model that recapitulates this syndrome. Full article

Background/Objectives: Pancreatic adenocarcinoma remains one of the most lethal malignancies, largely due to aggressive biological behavior and limited available insight into biomarker-based prognostic stratification. The aim of our research was to investigate the role of macrophage migration inhibitory factors (MIFs), interleukin-8 (IL-8/CXCL8), and stem cell factors (SCFs) in pancreatic adenocarcinoma. Methods: In this single-center study, sixty hospitalized patients diagnosed with pancreatic adenocarcinoma were prospectively enrolled, and a cross-sectional analysis of baseline cytokine levels was performed. Serum MIF, IL-8/CXCL8, and SCF were assessed in a single analytical run using Luminex xMAP technology. Results: Elevated MIF and IL-8/CXCL8 levels characterized an inflammatory phenotype, associated with leukocytosis, neutrophilia, increased fibrinogen levels, and unequal prevalence of new-onset diabetes. Higher MIF levels were further associated with larger tumor dimension, while IL-8/CXCL8 was associated with increased bilirubin level and recent weight loss (p < 0.05). In contrast, increased SCF predicted a dissemination phenotype as defined by metastasis occurrence (65.4% vs. 28.6%, p = 0.012). SCF demonstrated significant discriminatory ability for metastasis (AUC 0.712, p = 0.013) and remained significantly associated in multivariable analysis. Conclusions: MIF and IL-8/CXCL8 primarily reflect inflammation-driven processes, whereas SCF identifies a dissemination-dominant phenotype, suggesting distinct biological pathways underlying disease progression in pancreatic cancer. Full article

The present study examined the effect of Enterococcus durans cell-free supernatant (CFS) on interleukin (IL) 8, 10 and 1β gene expressions in the intestinal cell line HT-29 treated with Staphylococcus aureus CFS. HT-29 cells were incubated with E. durans CFS or S. aureus CFS, or S. aureus CFS plus E. durans CFS. All concentrations of E. durans CFS did not show cytotoxicity, while the highest treatment (44.9 μg/mL) with S. aureus CFS induced significant cell death. S. aureus CFS did not modify IL-1β gene expression, while E. durans CFS alone or in combination with S. aureus CFS reduced it. Treatment with S. aureus CFS induced greater expression of the IL-8 gene compared to S. aureus CFS plus E. durans CFS. S. aureus CFS alone or in combination with E. durans CFS increased the expression of the IL-10 gene, while E. durans CFS alone did not modify it. These results suggest a potential protective role of the E. durans secretome in mitigating the inflammatory environment in intestinal cells. This treatment could be useful to protect against possible contact with dangerous soluble microbial products present in food. Full article

Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an E3 ubiquitin ligase that plays a crucial role in inflammation, immune responses, and tumor development. It was reported that TRAF6 primarily catalyzes K63-linked polyubiquitination to stabilize substrate proteins, thereby facilitating the malignant phenotype of tumors. Beyond its cytoplasmic roles, TRAF6 undergoes nuclear translocation in response to specific stimuli, where it interacts with chromatin modifiers. TRAF6 acts as a central mediator in key signaling pathways downstream of the Toll-like receptor, interleukin-1 receptor, and tumor necrosis factor receptor superfamilies, including NF-κB activation. TRAF6 exerts diverse oncogenic functions, including promoting cell proliferation, migration, metastasis, immune evasion, and therapy resistance. This involves modulating cellular pathways such as NF-κB and MAPK signaling, which contribute to malignant progression. Aberrant TRAF6 activation contributes to the pathogenesis of multiple malignancies, including colorectal cancer, melanoma, hepatocellular carcinoma, and acute myeloid leukemia, making it a promising therapeutic target for cancer treatment. This review summarizes the structural features, substrate diversity, and multifaceted roles of TRAF6 in cancer, as well as the development of TRAF6-targeting drugs and strategies. We hope this review can provide a comprehensive perspective on TRAF6-targeted therapeutic strategies for cancer. Full article

Mussel foot proteins (Mfps) are renowned for their underwater adhesion, whereas their biotechnological potential for cutaneous wound repair remains largely underexplored. In this study, we identified and characterized a cysteine-rich mussel foot protein, Mfp6-1, from Mytilus coruscus and investigated its therapeutic potential for wound healing. Sequence analysis showed that Mfp6-1 is enriched in cysteine (11.0%) and tyrosine (~16.5%). We successfully expressed recombinant Mfp6-1 (rMfp6-1) in E. coli. Structural prediction based on the mature peptide sequence suggested that rMfp6-1 adopts a relatively compact fold containing several short β-structural elements. In vitro assays demonstrated that rMfp6-1 possesses antioxidant activity in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, and alkylation experiments suggested that cysteine residues contribute importantly to this activity. Dithio-bis-nitrobenzoic acid (DTNB)-based thiol quantification further demonstrated that rMfp6-1 contained abundant accessible free sulfhydryl groups, supporting an important contribution of cysteine-derived thiols to its antioxidant activity. Experiments on a full-thickness mouse wound model showed that rMfp6-1 treatment resulted in significantly faster wound contraction. Morphological analysis further revealed that rMfp6-1 optimizes the healing microenvironment by promoting collagen accumulation and re-epithelialization. Additionally, the treatment was found to trigger vascular endothelial growth factor (VEGF)-mediated angiogenesis, thereby improving the overall quality of the regenerated tissue. Furthermore, rMfp6-1 treatment significantly reduced interleukin-6 (IL-6) expression, suggesting that its antioxidant capacity creates a permissive microenvironment for tissue regeneration by suppressing excessive inflammation. These findings indicate that recombinant rMfp6-1 is a promising bioactive candidate for wound-healing applications. Full article

Glucose oxidase (GOD) is a natural enzyme with antioxidant and antimicrobial properties but its effects on sows remain insufficient. This study investigated the effects of dietary GOD supplementation during gestation on inflammatory response, antioxidant capacity, immune function, and gut microbiota of farrowing sows. Twenty-four primiparous sows were randomly assigned to two groups and fed a basal diet or a basal diet supplemented with GOD (300 mg/kg diet) from gestation day 30 to farrowing. GOD supplementation significantly increased triglyceride, superoxide dismutase, and immunoglobulin M levels (p < 0.05), and significantly decreased alanine aminotransferase and interleukin-6 levels in serum (p < 0.05); significantly reduced placental interleukin-1β, malondialdehyde and tumor necrosis factor-α concentrations and NF-κB gene expression (p < 0.05), and elevated glutathione peroxidase activity and relative mRNA expressions of Nrf2, HO-1, GPX1 and SOD2 (p < 0.05). Moreover, GOD supplementation altered the fecal microbial community structure (p < 0.05), significantly reducing Clostridium, dgaA-11_gut_group, Bacteroides, and Prevotellaceae_NK3B31_group abundance (p < 0.05), while enriching Lachnospira, unclassified_f_Erysipelotrichiaceae, and Anaerostipes (p < 0.05). Collectively, 300 mg/kg glucose oxidase supplementation during mid-to-late gestation improved the health status of farrowing sows by improving nutrient utilization, immune function and antioxidant capacity, and altering fecal microbial structure and relative abundances. Full article

Background/Objectives: Cellular senescence is a stable growth-arrested state accompanied by the senescence-associated secretory phenotype (SASP), a complex inflammatory secretome that contributes to tissue remodeling, chronic inflammation, and age-related disease. Although multiple signaling pathways have been implicated in SASP regulation, the extent to which interleukin-1 (IL-1) signaling is associated with the organization of SASP-associated transcriptional programs remains incompletely defined at the transcriptomic level. Methods: Here, we performed a focused in silico analysis of a publicly available RNA-sequencing dataset (GSE63577) profiling primary human fibroblasts undergoing replicative senescence. Differential expression analysis revealed broad inflammatory remodeling in senescent fibroblasts, including robust upregulation of canonical SASP-associated cytokines, chemokines, and matrix-related factors. Targeted visualization using a curated, literature-defined SASP gene panel confirmed consistent transcriptional activation of key SASP components during replicative senescence. Results: To assess transcriptional associations, we performed correlation-based network analysis centered on IL1A and IL1B. This analysis demonstrated strong transcriptional coupling between IL-1 signaling components, NF-κB-related genes, and SASP-associated transcripts, revealing a highly connected inflammatory module embedded within the senescence transcriptome. Pathway-level integration using curated gene sets further highlighted IL-1 signaling, cytokine signaling, and NF-κB-related pathways as dominant features of senescence-associated transcriptional changes. These patterns were further supported by analysis of an independent fibroblast senescence dataset (GSE41714), demonstrating consistent IL-1-associated and SASP-related transcriptional trends across experimental systems. Conclusions: Together, these findings suggest that IL-1 signaling is consistently associated with a central position within the SASP-associated transcriptional network during replicative senescence in human fibroblasts. Therefore, the present study contributes transcriptomic network-level evidence supporting an association between IL-1 signaling and coordinated SASP-associated inflammatory programs, and highlights its potential relevance for intervention strategies. Full article

Pesticide manufacturing industry wastewater is a complex mixture of potentially harmful components. If not properly treated, discharged effluents may pose serious risks to environment and organisms. In this study, influent and effluent wastewater samples from a pesticide factory were comprehensively non-screened by liquid chromatography high-resolution mass spectrometry, coupled with zebrafish embryo toxicity testing to assess whole effluent toxicity. A total of eight chemical groups were identified, including pesticides, antibiotics, nitrogen compounds, ketones, esters, amines and derivatives, other drugs, and other organic compounds. While wastewater treatment processes reduced most of the analyzed groups of compounds, compounds (e.g., 2-aminophenol, N-Nitrosodipropylamine, and carbamazepine) increased during the treatments. The influent samples were more toxic to zebrafish than the effluent samples in terms of lethality, teratogenic effects, developmental impacts, locomotor behavior, and neurotoxicity. The results showed that locomotor behavior was the most sensitive phenotypic toxicity endpoint, with significantly higher sensitivity than traditional acute lethal or teratogenic endpoints. Through a multi-dimensional assessment approach combining chemical screening, literature-based, risk ranking, and targeted quantification, we identified three predominant pesticide residues in the wastewater samples (both influents and effluents): hexaconazole, fenobucarb and isoprocarb. All three compounds exhibited additive or synergistic toxicity in zebrafish embryos. Exposure to ≥0.08% influent or ≥2% effluent increased inflammation (interleukin-1 beta, IL-1β), oxidative stress (copper/zinc superoxide dismutase, Cu/Zn-Sod), apoptosis (tumor protein p53, p53), and significantly impaired neurodevelopment in zebrafish larvae by altering the expression of sonic hedgehog a (shha), synapsin IIa (syn2a), and glial fibrillary acidic protein (gfap). This study suggests the necessity of incorporating non-apical endpoint (locomotor behavior) into whole effluent toxicity test, as this approach is essential for reducing the environmental risks posed by pesticide factory wastewater. Full article

Pesticide exposure is a plausible but incompletely characterized contributor to kidney injury. This review integrates current clinical, epidemiologic, experimental, and mechanistic evidence on pesticide-related nephrotoxicity, focusing on glyphosate-based herbicides, paraquat, organophosphate insecticides, and atrazine. A structured search of PubMed and Web of Science identified English-language studies published between January 2015 and February 2026. Of 635 records screened, 61 human studies were retained for full-text evaluation, and relevant animal, in vitro, and regulatory sources were additionally reviewed for mechanistic interpretation. Across pesticide classes, the proximal tubule emerged as the most consistent renal target, although downstream pathways differed, including oxidative stress, mitochondrial dysfunction, transporter disruption, endoplasmic reticulum stress, inflammation, apoptosis, ferroptotic signaling, and fibrotic remodeling. Human evidence was strongest for acute kidney injury following severe poisoning, whereas associations between chronic occupational or environmental exposure and chronic kidney disease or end-stage renal disease were more limited and heterogeneous. Biomarkers including kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), β₂-microglobulin, cystatin C, interleukin-18 (IL-18), cytochrome c, and 8-hydroxy-2′-deoxyguanosine (8-OHdG) often detected early tubular stress before abnormalities appeared in conventional renal indices. Overall, pesticide nephrotoxicity is best conceptualized as a spectrum of mechanism-specific tubular injury signatures, supporting a shift toward biomarker-informed early detection, improved hazard identification, and more mechanistically grounded risk assessment. Full article

Background: Acute appendicitis in girls presenting with lower abdominal pain remains a frequent diagnostic dilemma because of the overlap in clinical presentation with gynaecological and non-surgical causes. This study aimed to evaluate the diagnostic performance of IL-6 and CD64 and to compare them with classical inflammatory markers and the Alvarado score. Methods: We conducted a prospective observational diagnostic-accuracy study over a three-year period (December 2022 to December 2025) at the First University Paediatric Surgery Clinic, General Hospital of Thessaloniki “Georgios Gennimatas”. Consecutive girls aged ≤16 years presenting with lower abdominal pain were included. The primary outcome was appendicitis (yes/no), defined by the final clinical diagnosis and, where applicable, intraoperative and/or histopathological confirmation. Diagnostic performance was assessed using ROC curves and AUCs with 95% confidence intervals estimated by the DeLong method. The prespecified primary regression model included the Alvarado score and IL-6; IL-6 was summarised on its original scale and log1p-transformed only for regression analyses to account for right-skewness. Additional multivariable models were exploratory. Results: Of 74 initially assessed cases, one was excluded (appendiceal neuroendocrine tumour, NET G1), yielding a final sample of 73 girls: 37 with appendicitis and 36 without appendicitis. IL-6 was higher in the appendicitis group (median 19.41 vs. 4.10 pg/mL) and showed moderate discrimination (AUC 0.696). CRP showed lower to borderline performance (AUC 0.595), whereas CD64 did not demonstrate useful discrimination (AUC 0.521). The Alvarado score had the highest discriminatory ability (AUC 0.885). In the subset with complete data, adding IL-6 to the Alvarado score did not materially improve discrimination. Conclusions: IL-6 showed moderate diagnostic performance as a standalone biomarker and may be useful as an adjunct, particularly when a clinical score is unavailable or unreliable. CD64 did not add meaningful diagnostic information in this setting. Larger, prespecified studies are required to determine clinically useful cut-offs and to clarify whether IL-6 offers incremental value beyond established clinical assessment. Full article

Inflammation and oxidative stress play important roles in alcohol-induced liver injury. Hyaluronan (HA), a naturally occurring polysaccharide proven to exhibit antioxidant and anti-inflammatory functions, has garnered growing research attention in the field of food in recent years. This study demonstrates that long-term oral administration of HA exerts a protective effect against acute alcohol-induced liver injury (AALI). The findings showed that oral administration of 30, 600, and 1250 kDa HA for 2 and 4 weeks all increased serum and liver HA levels in rats and regulated the composition and abundance of gut microbiota. Meanwhile, oral HA could alleviate the symptoms of liver injury caused by alcohol, including increasing glutathione (GSH) levels, reducing malondialdehyde (MDA) and triglyceride (TG) levels, and decreasing the content of inflammatory factors interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) compared with the AALI model mice. Furthermore, HA could inhibit the increase in reactive oxygen species (ROS) levels in AML12 cells induced by alcohol and improve the survival rate of alcohol-damaged AML12 cells. In conclusion, this study found that oral administration of HA could increase serum and liver HA levels and has a protective effect on AALI, suggesting the application of HA in health foods for hangover relief and liver protection. Full article