Search Results (29,595)

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that represents continuous synovial inflammation, oxidative stress, immune dysregulation, and progressive cartilage degradation and bone erosion. Although disease-modifying antirheumatic drugs (DMARDs), including methotrexate (MTX), have improved clinical outcomes, treatment-limiting adverse effects remain a concern. Increasing evidence suggests that natural bioactive compounds may serve as adjunctive approaches by modulating multiple pathogenic pathways. This review summarizes biomarker-based modulation of inflammatory, oxidative, and immune pathways by plant-derived extracts, nutraceuticals, and biologically derived compounds, with particular emphasis on evidence from adjuvant arthritis (AA). AA is a widely used experimental model that reproduces several inflammatory and oxidative features relevant to RA, including cytokine activation, NF-κB/MAPK signaling, Th17/JAK-STAT3 signaling, redox imbalance, and tissue degeneration. Studies in AA indicate that selected natural compounds, alone or in combination with MTX, can reduce inflammatory cytokines (e.g., IL-1β, IL-6, IL-17A), matrix-remodeling markers (e.g., MMP-9), and oxidative-stress markers (e.g., protein carbonyls and lipid peroxidation) while supporting antioxidant defenses (e.g., HO-1 and CAT). Overall, natural bioactive substances may have potential as adjunctive candidates for further investigation in RA, particularly because of their effects on inflammatory and oxidative pathways. Preclinical studies of MTX combinations have reported additional improvements in selected disease-associated outcomes; however, these findings require confirmation in well-designed clinical studies. This review critically evaluates the preclinical evidence for natural bioactive compounds, with a focus on mechanistic studies in AA and the potential for combination strategies with methotrexate. Full article

Background/Objectives: Cyclophosphamide (CP) can produce acute renal toxicity through overlapping oxidative, inflammatory, and apoptotic processes. Although lycopene is widely studied for antioxidant and anti-inflammatory activity, its renal effects during acute CP exposure remain incompletely defined. We investigated whether a 10-day course of oral lycopene before CP administration altered early biochemical, transcriptional, histological, and apoptosis-related renal responses. Methods: Twenty-eight male CD-1 mice were assigned equally to control, lycopene (20 mg kg⁻¹ day⁻¹), CP (200 mg kg⁻¹ intraperitoneally on day 10), or CP + lycopene groups (n = 7). At 24 h after CP administration, serum BUN and creatinine were measured together with renal TBARS-derived MDA-equivalent values, SOD activity, TNF-α/IL-6/IL-1β mRNA abundance, histopathological injury, and cleaved caspase-3 immunoreactivity. Results: CP increased BUN, creatinine, and renal TBARS-derived MDA-equivalent values; decreased SOD activity; increased all three inflammatory transcripts; worsened tubular and tubulointerstitial injury; and increased cleaved caspase-3 labeling. Compared with CP alone, lycopene pretreatment reduced BUN, renal TNF-α, IL-6, and IL-1β mRNA, tubular and tubulointerstitial damage, and cleaved caspase-3 labeling. Creatinine, renal TBARS-derived MDA-equivalent values, and SOD activity were not significantly different between the CP and CP + lycopene groups. Conclusions: In this prophylactic model (20 mg kg⁻¹ day⁻¹ for 10 days; 24 h assessment), lycopene provided partial early protection against CP-associated renal injury. The response was evident in BUN, inflammatory transcription, tissue injury, and apoptotic labeling, but not in creatinine or the two measured redox indices. The study does not establish pathway causality and does not support extrapolation to post-injury treatment or long-term protection. Full article

Background/Objectives: Polydeoxyribonucleotide (PDRN) has anti-inflammatory and tissue-protective properties associated with activation of the adenosine A_2A receptor (A_2AR). Although hepatoprotective actions of PDRN have previously been described, its potential association with high-mobility group box 1 (HMGB1)-related inflammatory responses and hepatic macrophage accumulation during acute liver injury (ALI) is not fully understood. This study examined whether PDRN affects HMGB1- and monocyte chemoattractant protein-1 (MCP-1)-associated responses together with hepatic macrophage accumulation in ALI. Methods: ALI was induced in ICR mice by carbon tetrachloride (CCl₄) administration. PDRN was administered either alone or together with the selective A_2AR antagonist 3,7-dimethyl-1-propargylxanthine (DMPX). Serum levels of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase were quantified. Histological alterations were evaluated using hematoxylin and eosin staining. Hepatic macrophage accumulation was assessed by F4/80 immunofluorescence staining. Enzyme-linked immunosorbent assays were used to quantify HMGB1, MCP-1, interleukin-10 (IL-10), cyclic adenosine monophosphate (cAMP), and A_2AR. Results: PDRN significantly reduced serum markers of liver injury and attenuated histopathological damage following CCl₄ administration. PDRN treatment also decreased F4/80-positive macrophage accumulation in the hepatic tissue. In addition, PDRN reduced HMGB1 and MCP-1 levels in both the serum and liver tissues while significantly increasing IL-10, cAMP, and A_2AR levels. Conclusions: PDRN attenuated CCl₄-induced ALI and was associated with reduced HMGB1 and MCP-1 levels, decreased hepatic macrophage accumulation, and increased A_2AR/cAMP signaling. These findings suggest that modulation of macrophage-associated inflammatory responses may contribute to the hepatoprotective effects of PDRN. Full article

Polyparasitism is frequently documented in cetaceans; however, the pathological consequences of concurrent multispecies helminth infections and their associated tissue responses remain incompletely understood. This study characterized multispecies helminth infections in two live-stranded dolphins from the Andaman coast of Thailand, a spinner dolphin (Stenella longirostris) and a pantropical spotted dolphin (Stenella attenuata), using integrated postmortem, parasitological, molecular, histopathological, and immunohistochemical approaches. Both dolphins harbored helminths involving multiple organ systems. Pulmonary nematodes were identified as Halocercus delphini, while larval and intestinal cestodes were identified as Clistobothrium sp. and Tetrabothrius sp., respectively. The most prominent pathological alterations occurred in the respiratory tract and included chronic pyogranulomatous bronchopneumonia, airway epithelial injury, fibrosis, and pulmonary congestion associated with Halocercus infection. Additional parasite-associated lesions included chronic enteritis, cholangitis with biliary epithelial injury and ductular reaction, pancreatic inflammation, and localized inflammatory responses surrounding larval cestode cysts in the blubber and testis. Immunohistochemistry demonstrated extensive interleukin-4 (IL-4) immunoreactivity in affected pulmonary and intestinal tissues, whereas interleukin-10 (IL-10) was undetectable. Nitrotyrosine and heat shock protein 70 (HSP70) immunoreactivity were widely distributed across parasite-associated tissues, while caspase-3 immunoreactivity showed tissue-dependent patterns. Collectively, these findings demonstrate that multispecies helminth infections in stranded dolphins were associated with multisystem pathological alterations accompanied by inflammatory, oxidative/nitrosative stress, cellular stress, and apoptotic responses. These findings highlight the potential pathological significance of polyparasitism in stranded dolphins and support consideration of parasite burden and associated tissue responses during cetacean postmortem investigations. Full article

Background and Clinical Significance: Tarui disease, or glycogen storage disease type VII, is a rare autosomal recessive metabolic myopathy caused by muscle phosphofructokinase deficiency. Its manifestations include exercise intolerance, exertional myalgia, muscle cramps, myoglobinuria, rhabdomyolysis, hyperuricemia, and compensated hemolysis. The hematologic phenotype may obscure the underlying metabolic disorder and raise concern for a clonal myeloid neoplasm. Case Presentation: A 23-year-old man was referred for persistent mild thrombocytopenia following evaluation for jaundice and hepatosplenomegaly. He had undergone cholecystectomy at 18 years of age and reported exercise-induced myalgia, muscle cramps, and episodes of dark urine. Laboratory investigations demonstrated mild monocytosis, reticulocytosis, thrombocytopenia, hyperuricemia, elevated lactate dehydrogenase, and predominantly unconjugated hyperbilirubinemia, with a negative direct antiglobulin test. Selected inherited hemolytic disorders, hemoglobinopathies, and paroxysmal nocturnal hemoglobinuria were excluded. Bone marrow examination showed marked erythroid hyperplasia and mild megakaryocytic dysplasia. Testing for JAK2, CALR, and MPL mutations and an extended myeloid next-generation sequencing panel identified no pathogenic variants, and monocytosis resolved during follow-up. Whole-exome sequencing identified a homozygous PFKM missense variant, NM_001354735.1:c.1087A>T, p.(Ile363Phe), classified as a variant of uncertain significance. The patient subsequently developed severe rhabdomyolysis, with a creatine kinase level of 225,000 U/L and recovered after intensive intravenous hydration without renal impairment. Conclusions: Tarui disease should be considered in young patients with compensated hemolysis, hyperuricemia, exertional muscle symptoms, dark urine, or rhabdomyolysis, even when hematologic abnormalities suggest a myeloid disorder. The highly concordant phenotype and homozygous PFKM variant support a clinically probable diagnosis, although pathogenicity remains unconfirmed. Functional and segregation evidence may strengthen causal interpretation and support future variant reclassification. Full article

Background/Objective: Prediabetes is increasingly recognized as a state of chronic, low-grade inflammation that contributes to early β-cell dysfunction, insulin resistance, and progression to type 2 diabetes (T2D). This review synthesizes mechanistic and clinical evidence to characterize the inflammatory landscape of prediabetes, evaluate the consistency of candidate biomarkers, and assess potential for clinical translation. Methods: We conducted a structured narrative review and assessed 22 studies investigating inflammatory and metabolic biomarkers for prediabetes across experimental animal models, human pancreatic islets, and clinical cohorts. Biomarkers included cytokines, oxidative stress indicators, microRNAs, and immune-cell-associated factors. Studies included cross-sectional, longitudinal, and mechanistic designs. Results: Clinical studies generally reported higher CRP and hsCRP. In several cohorts, IL-6 and other inflammatory mediators were increased in individuals with prediabetes. However, inflammatory responses were not uniform across studies. One study reported elevated IL-10 and IL-4 in addition to hsCRP, while TNF-α and IL-6 were not significantly different. Overall, CRP and hsCRP demonstrated the strongest clinical translational evidence, with findings replicated across multiple cohorts and longitudinal evidence linking higher baseline hsCRP or CRP with increased risk of progression to T2D. Other candidates, including IL-6, TNF-α, adiponectin, SFRP4, oxidative stress markers, and microRNAs, remain promising but have more limited or inconsistent evidence for clinical application. Conclusions: Prediabetes is characterized by a multifaceted inflammatory response involving innate and adaptive immune pathways, altered cytokine and microRNA profiles, oxidative stress, and adipose–pancreatic interactions. Although inflammatory biomarkers may enhance conventional metabolic measures for risk stratification, current evidence does not establish any inflammatory marker as a standalone diagnostic test for prediabetes. Full article

MGN-3 (Biobran), a denatured hemicellulose compound derived from rice bran, possesses potent immunomodulatory and antitumor activity; however, its clinical application is constrained by non-specific tissue distribution, rapid systemic elimination, and poor cellular uptake. To overcome these pharmacological limitations, we engineered MGN-3-loaded lipid nanoparticles (MGN-3.LNPs) formulated with bioactive cinnamon and avocado oils to optimize targeted drug delivery against solid carcinoma. Mice bearing subcutaneous Ehrlich Ascites Carcinoma (EAC) solid tumors received free MGN-3, plain lipid nanoparticles (plain LNPs), or MGN-3.LNPs three times weekly from day 8 to day 26 post-inoculation. The administration of MGN-3.LNPs achieved superior tumor volume suppression (95.00%) compared to free MGN-3 (69.00%) and plain LNPs (63.00%) (p < 0.0001). Mechanistically, MGN-3.LNPs effectively inhibited cancer cell proliferation by suppressing Ki-67 expression while promoting expression shifts that strongly suggest the engagement of mitochondrial-mediated apoptotic signaling, including upregulation of tumor protein p53, Caspase-3, Caspase-9, poly(ADP-ribose) polymerase (PARP), and cytosolic cytochrome c (Cyt c), alongside an elevated Bax/Bcl-2 ratio and reduced 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels. Flow cytometric analysis confirmed that MGN-3.LNPs induced marked G0/G1 cell cycle arrest and promoted sub-G1 apoptotic cell accumulation, which was corroborated by Annexin V/propidium iodide (Annexin V/PI) staining and semiquantitative histopathological evaluation. Furthermore, MGN-3.LNPs downregulated the gene expression of proinflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) while restoring redox homeostasis in tumor tissues. Overall, lipidic nanoencapsulation significantly enhances the therapeutic efficacy of MGN-3 against solid tumors through superior nanoscale tissue penetration, prolonged retention, and synergistic lipid–drug bioactivity. Full article

Porphyromonas gingivalis is a keystone periodontal pathogen strongly associated with periodontitis progression. Although testosterone levels have been associated with periodontal health, its direct effects on P. gingivalis virulence remain poorly understood. The aim of this study was to investigate the impact of testosterone exposure on the key virulence characteristics of P. gingivalis strain W50. We found that testosterone significantly increased the growth and biofilm biomass of P. gingivalis W50 after 48 h. Furthermore, testosterone enhanced the extracellular gingipain activity of both lysine and arginine gingipains from P. gingivalis. We also found that IL-1β release from gingival epithelial cells was significantly lowered following infection with testosterone-primed P. gingivalis compared with unprimed W50. At the mRNA level, no differences in pro-IL-1β, IL-8, or CXCL10 gene expression were detected in gingival epithelial cells infected with testosterone-primed P. gingivalis compared with unprimed W50. Finally, testosterone priming significantly enhanced the ability of P. gingivalis to colonize and invade gingival epithelial cells. Overall, these findings indicate that testosterone exposure modulates several virulence-associated phenotypes of P. gingivalis W50 in vitro. The mechanisms underlying these effects and their relevance to periodontal disease in vivo remain to be determined. Full article

Prinsepia utilis Royle seeds are traditionally used in Northwestern Yunnan to relieve skin inflammation and irritation. However, its active constituents and potential molecular mechanisms remain unclear. To investigate the bioactive constituents and anti-inflammatory and skin-soothing effects of P. utilis seed-derived extracts, we characterized their chemical profiles and investigated the potential molecular mechanisms through phytochemical, computational, and complementary biological approaches, as well as in vitro and in vivo tests in this study. The results of this study show that the 75% ethanol eluate (QC04) of P. utilis seeds exhibited the strongest inhibitory effect on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages, with an IC₅₀ value of 239.21 ± 6.70 μg/mL. Subsequently, untargeted metabolomics identified 1039 metabolites, and 20 representative compounds were selected for downstream analysis. Furthermore, network pharmacology analysis identified AKT1, MAPK1, MAPK8, and MAPK14 as core targets, which are mainly involved in the TNF and MAPK signaling pathways. Molecular docking confirmed favorable binding interactions between representative metabolites and these core proteins; meanwhile, a 100 ns molecular dynamics simulation verified the conformational stability of the euscaphic acid–AKT1 complex. Moreover, in the UVB-induced 3D epidermal model (EpiKutis^®), QC04 treatment reduced IL-6 and PGE₂ secretion and downregulated TNF-α and NF-κB p65 expression. In vivo zebrafish assays further demonstrated that QC04 inhibited copper sulfate-induced neutrophil recruitment and histamine-induced vasodilation. Overall, these findings link the metabolites identified in the activity-enriched QC04 fraction with predicted molecular targets and anti-inflammatory and skin-soothing effects, providing experimental evidence for the biological potential of P. utilis seed-derived preparations and supporting further investigation of QC04 as a potential skin-soothing active fraction. Full article

Juvenile colorectal polyps (JP) are the most common polypoid lesions of the colon in children and the leading cause of lower gastrointestinal bleeding in pediatric patients. Although histologically classified as benign hamartomatous lesions, they arise in a context of allergic sensitization and IgE-mediated inflammation, suggesting that the epithelial compartment may play an active role in their pathogenesis. To date, most studies have focused on the immune cell infiltrate, leaving the molecular programs operating within the epithelium largely unexplored. Whole-transcriptome RNA sequencing (RNA-seq) was performed on epithelial cells isolated from pediatric JP (n = 8) and paired tissue circumjacent to polyp (TCP) (n = 7) obtained from children with a history of rectal bleeding and IgE sensitization to food allergens. Differential expression, functional enrichment (GO, KEGG, GSEA), and cross-dataset comparison with TCGA colorectal adenocarcinoma (CRC) was conducted. Candidate genes were validated by RT-qPCR in independent samples, including colorectal cancer (CRC) and inflammatory bowel disease (IBD) tissue. Differential expression analysis identified 3273 differentially expressed genes (2342 upregulated, 931 downregulated in JP vs. TCP), with 220 genes exceeding 32-fold change, including SERPINB3 (log2FC = 12.16), MMP1 (log2FC = 10.19), NMUR2 (log2FC = 10.08) and CHI3L1 (log2FC = 8.87). JP epithelium displayed a coherent type 2 inflammatory signature, encompassing upregulation of the alarmin IL33, eosinophil-attracting chemokines (CCL11, CCL24), IgE receptor subunits (FCER1A, FCER1G), and a coordinately activated leukotriene and prostaglandin biosynthetic program (ALOX5, ALOX5AP, PTGS2). Concurrent alterations in epithelial identity were observed, including downregulation of absorptive enterocyte and intestinal stem cell markers (CDX2, LGR5, ASCL2) alongside upregulation of secretory and regenerative programs, including the ectopic gastric-type mucin MUC5AC. Tight junction dysregulation—notably upregulation of the pore-forming claudin CLDN2 and loss of barrier-sealing claudins (CLDN3, CLDN4, CLDN23)—was consistent with impaired epithelial permeability. Pathway analyses confirmed activation of type 2 immune and extracellular matrix remodeling programs, with concurrent suppression of mitochondrial oxidative phosphorylation. Cross-dataset comparison with TCGA CRC data identified 381 co-upregulated and 87 co-downregulated genes shared between JP and CRC, including SERPINE1, CXCL8, ICAM1, and MMP3, several of which were associated with poorer disease-specific survival in CRC patients. RT-qPCR validation confirmed elevation of CHI3L1 and SERPINE1 in both JP and CRC, while SERPINB4 appeared JP-specific. Epithelial cells from pediatric juvenile colorectal polyps associated with allergic sensitization display a comprehensive type 2 inflammatory transcriptome alongside profound alterations in lineage identity, barrier integrity, and metabolic programming. Partial convergence with CRC-associated gene expression programs—in the absence of histological dysplasia—suggests that chronic allergic inflammation activates conserved epithelial remodeling pathways shared across mucosal tissues. CHI3L1, SERPINE1, and SERPINB4 are candidate biomarkers warranting validation in larger cohorts. Full article

Interleukin-11 (IL-11) is implicated in epithelial dysfunction, fibroblast activation, tissue remodeling, and chronic inflammatory responses; however, the clinical value of circulating IL-11 in airway disease remains uncertain. This single-center retrospective exploratory observational study included 88 adults: 31 with allergic rhinitis, 15 with non-allergic asthma, 22 with allergic asthma associated with allergic rhinitis, and 20 healthy controls. Serum IL-11 concentrations were measured using a quantitative sandwich enzyme-linked immunosorbent assay. Between-group differences were assessed using the Kruskal–Wallis test followed by Holm-adjusted pairwise Mann–Whitney U tests. Associations with disease-specific ordinal clinical categories were evaluated using Spearman rank correlation, with GINA treatment Steps used for asthma phenotypes and ARIA severity categories for allergic rhinitis. Median IL-11 concentrations were 62.01 pg/mL in non-allergic asthma, 78.87 pg/mL in allergic rhinitis, 61.92 pg/mL in allergic asthma associated with allergic rhinitis, and 95.46 pg/mL in healthy controls. The primary global comparison was not statistically significant (H = 5.667, p = 0.129), and no pairwise comparison remained significant after Holm correction. Six measurements (6.8%) were below the assay detection limit; replacing these values with 4.0 pg/mL in a sensitivity analysis did not materially alter the global result (H = 5.671, p = 0.129). Serum IL-11 was not significantly associated with GINA treatment step in non-allergic asthma (rho = −0.170, p = 0.544) or allergic asthma associated with allergic rhinitis (rho = 0.052, p = 0.818), nor with ARIA severity category in allergic rhinitis (rho = 0.046, p = 0.805). In an exploratory analysis adjusted for age, sex, body-mass category, and current smoking status, IL-11 concentrations were lower in each clinical phenotype relative to healthy controls; given the modest group sizes and baseline imbalance, this finding was considered hypothesis-generating. Overall, the primary analysis did not demonstrate significant differences in circulating IL-11 across study groups, and serum IL-11 was not associated with disease-specific ordinal clinical categories. These findings do not support the use of a single serum IL-11 measurement as a stand-alone biomarker of airway disease phenotype or clinical category in this cohort and warrant confirmation in larger, prospectively characterized cohorts. Full article

This study investigates the role of metacognitive awareness in shaping students’ adoption of artificial intelligence (AI) tools for learning within the framework of the Technology Acceptance Model (TAM). Data were collected from 236 students at the University of Ha’il, and structural equation modeling (SEM) was employed to examine the relationships among metacognitive awareness, perceived usefulness (PU), perceived ease of use (PEU), and behavioral intention (BI). The findings indicate that metacognitive awareness has significant positive effects on both PU and PEU. In turn, PU and PEU significantly influence students’ BI to use AI tools for learning, with PU emerging as the stronger predictor. However, metacognitive awareness does not have a significant direct effect on BI. These results suggest that students’ intention to use AI tools is primarily driven by their perceptions of usefulness and ease of use, while metacognitive awareness plays an important role in shaping these perceptions. The study extends the Technology Acceptance Model by positioning metacognitive awareness as an upstream cognitive factor that enhances students’ evaluation of AI technologies in educational contexts. The findings offer practical implications for higher education institutions, emphasizing the importance of developing students’ metacognitive skills to improve their engagement with AI tools. By fostering students’ ability to reflect on and regulate their learning processes, educators can enhance the perceived value and usability of AI technologies, thereby supporting their effective integration into learning environments. Full article

As a traditional Tibetan medicine and health food, the fleshy roots of Sphallerocarpus gracilis were adopted to extract polyphenol powder(PP) in this research. Using a DSS-induced colitis mouse model combined with multi-omics analysis and experimental validation, we explored the protective effects and molecular mechanisms of PP against intestinal inflammation. PP mitigated colitis-related symptoms in a dose-dependent manner, inhibited pro-inflammatory cytokines and dose-dependently reversed elevated IL-10 levels to BC group. Multi-omics data revealed that PP intervention was associated with gut microbiota remodeling, enrichment of Akkermansia muciniphila, restoration of bacterial–fungal homeostasis, and improvement of tryptophan and biotin metabolism. By suppressing HMGB1 and RAGE expression, PP blocked the AGE-RAGE-mediated inflammatory cascade. In addition, PP maintained intestinal mucosal integrity through goblet cell protection, MDA reduction, and the regulation of BAX/Bcl-2, MMP3 and MMP9. Overall, PP relieves UC by regulating gut microecology, host metabolism and the AGE-RAGE pathway, which supports the translational potential of natural polyphenols for inflammatory bowel disease treatment as a gut microecological modulator. Full article

Background: Portulaca oleracea L. (POL) has anti-inflammatory and immunomodulatory activities, but its mechanism against atopic dermatitis (AD) remains incompletely understood. Methods: 2,4-dinitrofluorobenzene (DNFB)-induced AD mice were treated orally with POL or dexamethasone for 14 days. We evaluated skin lesions, scratchizng, serum IgE, histopathology, inflammatory cytokines, skin-barrier genes, JAK/STAT phosphorylation, and fecal metabolites. Results: POL alleviated skin lesions and pruritus, reduced serum IgE concentrations, attenuated epidermal hyperplasia and inflammatory-cell and mast-cell infiltration, and restored keratinocyte architecture. It decreased IL-4, IL-13, and IL-31 expression, increased filaggrin and loricrin expression, and inhibited JAK1, STAT1, and STAT3 phosphorylation. Untargeted metabolomics showed that POL mainly regulated unsaturated fatty acid and steroid hormone biosynthesis and restored levels of anti-inflammatory and antiallergic metabolites, including (±)18-HEPE, docosahexaenoyl ethanolamide, and dehydroepiandrosterone. Conclusions: These findings indicate that POL ameliorates AD by suppressing Th2 inflammation through JAK1/STAT3 signaling, correcting lipid-metabolic disturbances, and restoring skin barrier integrity. Full article

The potential of combining Clostridium butyricum (CB) and glucose oxidase (GOD) in poultry production remains to be systematically evaluated. This study evaluated the effects of dietary CB and GOD, supplied alone or in combination, on ileal antioxidant status, jejunal immune responses, gut epithelial barrier function, and cecal short-chain fatty acid (SCFA) composition in broilers, with the aim of comparing their practical effects rather than investigating synergistic or interactive effects. A total of 192 1-day-old broilers (white-feathered) were randomly distributed among 4 experimental groups, each having 6 replicate pens of 8 chicks. The groups had comparable starting weights (43.53 ± 0.51 g) and an equal male-to-female ratio. The control diet (CON) contained no additives, whereas the other three diets were formulated with CB at an inclusion rate of 400 mg/kg, GOD at the same level, or a mixture of both (400 mg/kg each), corresponding to the CB, GOD, and MIX groups, respectively. This experiment spanned 42 days, comprising an early stage (from day 1 to day 21) and a later stage (from day 22 to day 42). At day 21, the GOD group exhibited a significant elevation in ileal SOD activity relative to the CON group (p < 0.05). Jejunal interleukin-6 (IL-6) levels were significantly decreased in the CB and MIX groups (p < 0.05), while the MIX group also showed a significant decrease in IL-2 and a significant increase in interleukin-10 (IL-10) levels (p < 0.05). The GOD and MIX groups showed a significant elevation of sIgA (p < 0.05), while the CB and GOD groups exhibited marked upregulation of Occludin mRNA (p < 0.05). Butyrate concentrations in the cecum were significantly higher in the CB group than in the CON group (p < 0.05). Likewise, acetate levels were elevated in the MIX group compared with CON (p < 0.05). At day 42, the MIX group exhibited a significant reduction in ileal MDA content compared with the control (p < 0.05). In the jejunum of the MIX group, IL-6 was significantly reduced and IL-10 was significantly elevated (p < 0.05). Additionally, ZO-1 mRNA expression was markedly upregulated in the same group (p < 0.05). Ileal GSH-Px activity was significantly higher only in the CB group (p < 0.05). Overall, combined supplementation with CB and GOD exerted beneficial effects on broiler antioxidant status, immune responses, intestinal barrier-related parameters, and cecal SCFA composition, although the magnitude of these effects varied among endpoints and sampling ages. Full article