Search Results (28,527)

This study investigated the effects of dietary standardized ileal digestible (SID) lysine levels and amylose to amylopectin ratios on the intestinal health of broilers fed an 18.5% crude protein diet from 22 to 42 days of age. A total of 540 healthy male Ross 308 broilers were randomly assigned to nine treatments in a 3 × 3 factorial design consisting of three SID lysine levels (1.00%, 1.20%, and 1.40%) and three AM/AP ratios (0.19, 0.29, and 0.41), with six replicates of 10 birds each. Ileal morphology, intestinal barrier function and inflammation-related gene expression, and the composition of cecal microbiota were evaluated. Significant interactions between lysine level and AM/AP ratio were observed for Occludin, ZO-1, Claudin-1, and TNF-α expression, with the highest expression in the 1.40% lysine + 0.41 AM/AP group and the lowest in the 1.00% lysine + 0.19 AM/AP group. The VH/CD ratio showed a significant interaction, with the highest value in the 1.20% lysine + 0.19 AM/AP group and the lowest in the 1.40% lysine + 0.41 AM/AP group. IL-18 and IL-10 were primarily affected by the main effects of lysine and AM/AP ratio. The expression levels of both IL-10 and IL-18 increased with increasing lysine level and increasing starch AM/AP ratio. Dietary SID lysine level and AM/AP ratio interactively regulate the expression of barrier-related genes, inflammatory status, intestinal morphology, and cecal microbiota, potentially contributing to enhanced intestinal health in broilers. However, because microbial metabolites were not measured, the functional significance of the observed microbiota alterations remains speculative. In broilers fed an 18.5% CP diet, a combination of 1.20% SID lysine with an AM/AP ratio of 0.19 was identified as the optimal strategy for maintaining intestinal morphology from 22 to 42 days of age. Full article

Background/Objectives: Tordylium trachycarpum Boiss. (Apiaceae) is traditionally used in Kurdish ethnomedicine for the management of gastrointestinal disorders; however, its pharmacological efficacy and safety profile remain insufficiently investigated. This study evaluated, for the first time, the gastroprotective activity and associated antioxidant, inflammatory, and apoptotic responses of the methanolic extract of T. trachycarpum using an ethanol-induced gastric ulcer model in Sprague–Dawley rats. Methods: Preliminary phytochemical screening revealed the presence of phenolics, flavonoids, terpenoids, tannins, coumarins, and glycosides. Acute oral toxicity testing demonstrated no signs of toxicity at doses up to 5 g/kg. Gastric ulceration was induced by absolute ethanol, and animals were pretreated with the extract (250 and 500 mg/kg) or omeprazole (20 mg/kg). Results: The extract significantly decreased the gastric lesion area from 258.50 ± 6.38 mm² in the ulcer control group to 143.70 ± 0.76 mm² and 115.50 ± 0.76 mm², corresponding to ulcer inhibition rates of 44.41% and 55.31%. Additionally, the extract increased mucus production, maintained mucosal structure, and raised stomach pH. Biochemical analysis showed a significant increase in antioxidant enzymes [superoxide dismutase (SOD) and catalase (CAT)] and a reduction in malondialdehyde (MDA) levels, indicating attenuation of oxidative stress. In addition, the extract modulated pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-10). Blood-based ELISA analysis demonstrated increased expression of heat shock protein 70 (HSP70) and reduced Bax levels, suggesting anti-apoptotic activity. Conclusions: These findings indicate that T. trachycarpum exerts significant gastroprotective activity through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms, supporting its traditional use and highlighting its potential as a natural therapeutic candidate for the management of gastric ulcers. Full article

Immune checkpoint inhibitors (ICIs) show promise in cancer but have limited efficacy in ovarian cancer. This study compared combinations of the PD-1/PD-L1 inhibitor with anti-LAG-3, anti-TIM-3, or anti-CTLA-4 to identify the most effective regimen by assessing T-cell CD8/CD4 ratios and cytokine production. T cells isolated from ovarian cancer tissues (mean 3.8 × 10⁸ cells) were stimulated and treated with the PD-1/PD-L1 inhibitor alone or combined with anti-LAG-3, anti-TIM-3, or anti-CTLA-4. Flow cytometry measured CD8/CD4 expression; ELISAs quantified TNF-α, IL-6, and IFN-γ. Anti-PD-1 monotherapy produced no significant change in CD8/CD4 ratio (1.36 ± 0.43 vs. 1.41 ± 0.36) or cytokine levels. Combination therapy with PD-1/PD-L1 inhibitor + anti-CTLA-4 induced the largest increase in CD8/CD4 ratio (3.69 ± 1.33, p < 0.001) compared with PD-1/PD-L1 inhibitor alone; increases were smaller for PD-1/PD-L1 inhibitor + anti-LAG-3 (2.11 ± 0.63, p = 0.009) and PD-1/PD-L1 inhibitor + anti-TIM-3 (1.87 ± 0.48, p = 0.026). TNF-α rose significantly only with PD-1/PD-L1 inhibitor + anti-CTLA-4 (106.69 ± 45.42 pg/mL, p = 0.008), not with PD-1/PD-L1 inhibitor + anti-LAG-3 (72.46 ± 31.79 pg/mL, p = 0.231) or PD-1/PD-L1 inhibitor + anti-TIM-3 (82.06 ± 33.63 pg/mL, p = 0.074). IFN-γ increase was greater with PD-1/PD-L1 inhibitor + anti-CTLA-4 than with PD-1/PD-L1 inhibitor + anti-LAG-3 (p = 0.026). In conclusion, dual PD-1/PD-L1 and CTLA-4 blockade induced concomitant increases in T-cell CD8/CD4 proportions and cytokine levels compared to monotherapy or alternative ICI pairings. These descriptive ex vivo observations offer preliminary evidence of altered immune profiles, highlighting this combination as a candidate for further functional validation. Full article

The failure of therapy in muscle invasive bladder cancer (MIBC) is primarily attributed to tumor heterogeneity and therapy resistance. We propose a novel approach targeting interleukin-13 receptor subunit alpha 2 (IL-13Rα2), which is expressed on bladder cancer (BC) cells but absent in normal urothelial cells. We investigated the therapeutic effects of WPD101a immunotoxin (IL-13-DT390) on IL-13Rα2-expressing BC cells in relation to BC cell phenotype and functional characteristics in vitro using both 2-dimensional (2D) and 3-dimensional (3D) models. Cell phenotype and IL-13Rα2 expression were assessed using flow cytometry, immunofluorescence, and Western blot analysis. The biological effects of WPD101a were evaluated by measuring cell viability and proliferation using the MTT, sulforhodamine B (SRB), CellTiter-Glo and Live/Dead assays. Apoptosis was assessed using Annexin V/propidium iodide (PI) staining, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis of CASP genes expression. We found that the reference BC cell lines TCC-SUP, JMSU-1 and UM-UC-3 express IL-13Rα2 at various level in contrast to RT-4, HCV-29 and 5637 cells. Cells expressing IL-13Rα2 were sensitive to WPD101a at lower concentrations in the 2D model (0.1 ng/mL) compared to the 3D model (1.0 ng/mL). IL-13Rα2-negative cells remain resistant to the immunotoxin. WPD101a induces apoptosis in BC cells expressing IL-13Rα2 as confirmed by the presence of apoptotic cells, increase the proportion of cells in the subG1 phase, and by the effector CASP3, CASP7, and initiator CASP8, CASP9 genes expression. This study confirmed receptor-dependent cytotoxic effects of WPD101a and the ability and specificity to inhibit growth and apoptosis induction in MIBC cells expressing IL-13Rα2. Full article

Free amino acids (FAAs) are important low-molecular-weight metabolites involved in osmotic regulation, acid–base balance, and nitrogen metabolism in fish exposed to saline–alkaline environments. To characterize tissue-specific FAA responses in mandarin fish (Siniperca chuatsi), 10 cm juveniles were exposed for 96 h to freshwater control (FW), salinity stress (S, salinity 8), alkalinity stress (A, alkalinity 20 mmol/L), or combined saline–alkaline stress (SA, salinity 8 + alkalinity 20 mmol/L). The contents of 19 FAAs were compared among plasma, muscle, liver, brain, and kidney. FAA profiles showed clear tissue specificity. Total FAA (17) decreased in plasma under all stress treatments, increased in muscle under S and SA but decreased under A, increased in liver and kidney, and decreased under single stress but increased under combined stress in brain. Distinct tissue distribution patterns were observed for functional FAA groups. Under salinity stress, osmoregulation-related FAAs, particularly Ala and Pro, showed higher contents mainly in muscle, liver, and kidney. Under alkalinity stress, kidney showed concurrent increases in multiple FAAs, including Ala, Pro, Glu, Gln, Val, Ile, and Leu, whereas brain was characterized by a high Gln content. Under combined saline–alkaline stress, liver was the main tissue in which multiple functional FAA groups increased simultaneously, kidney maintained elevated levels of several FAAs, and brain showed treatment-specific high levels of Gln and Tau. Redundancy analysis (RDA) indicated weak constrained explanatory power of salinity and alkalinity for the overall FAA profile, whereas tissue-specific differentiation was evident. Glu, Gln, and Pro showed directional consistency with the salinity vector, whereas Val and Leu tended to align with the alkalinity-related ordination direction. Overall, acute saline–alkaline exposure induced a functional and tissue-specific distribution pattern of FAAs rather than a uniform whole-body shift in mandarin fish. Full article

Per- and polyfluoroalkyl substances (PFAS) are persistent, chemically stable compounds widely used in daily life. Perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexanesulfonic acid (PFHxS), and perfluorooctanesulfonic acid (PFOS) were identified as the most relevant PFAS due to their prevalence and toxicity. This study aimed to investigate the immunotoxic mechanisms of a mixture of these PFAS using an in silico approach. Comparative Toxicogenomic Database (CTD), GeneMANIA, CytoHubba (Cytoscape), ToppGene Suite, and Metascape were used for the analysis. A total of 65 immune-related genes were identified as common to all four PFAS, with IFNG, TNF, IL1B, IL6, TYK2, CD3E, CASP8, VAV1, ARHGAP4, and CARD11 emerging as key hub genes. CTD phenotype analysis indicated immune dysregulation, with decreased humoral and adaptive immune responses in humans and tissue-specific modulation of B- and T-cell activity in mice, while no immune-related phenotypes were observed for PFNA. Network analysis identified functional modules associated with apoptotic and immune signaling, endothelial cell migration and angiogenesis, and shared inflammatory and viral response pathways. Disease enrichment analysis associated PFAS with autoimmune disorders (rheumatoid arthritis, asthma), metabolic conditions, and cardiovascular diseases (experimental diabetes, hypertensive disease). These results highlight PFAS involvement in immune modulation, cytokine signaling, and disease susceptibility. Full article

Cross-presentation of exogenous antigens by dendritic cells (DCs) relies on the cytosolic pathway, enabling proteasomal processing and subsequent loading of antigenic peptides onto major histocompatibility complex class I (MHC-I) molecules. Although this pathway is central to CD8⁺ T-cell activation, the molecular mechanisms that regulate intracellular antigen processing and redistribution during cross-presentation remain incompletely defined. In this study, we investigated the contribution of the large-pore channel Pannexin-1 (Panx1) to antigen handling during cross-presentation. Using confocal microscopy and quantitative image analysis in granulocyte–macrophage colony-stimulating factor/interleukin-4 (GM-CSF/IL-4)-derived inflammatory bone marrow-derived dendritic cell (BMDC)-like cellsexposed to ovalbumin (OVA)–Alexa Fluor 488, we observed time-dependent changes in intracellular antigen distribution that were altered upon pharmacological inhibition of Panx1 with the blocking peptide 10Panx1. In parallel, functional assays revealed that Panx1 inhibition significantly reduced SIINFEKL peptide-dependentactivation of B3Z CD8⁺ T-cell hybridomas following pulsing with full-length OVA. Similar effects were observed in the cross-presentation-competent MUTU1940 dendritic cell line. Importantly, Panx1 inhibition did not significantly affect dendritic-cell viability or LPS-induced activation under the experimental conditions tested. In contrast, pharmacological inhibition or genetic deficiency of P2X7 receptor (P2X7) did not produce comparable reductions in cross-presentation, and combined inhibition did not result in additive effects under the experimental conditions tested. Together, these findings provide functional evidence supporting a role for Panx1 in regulating intracellular antigen redistribution associated with cross-presentation. While not establishing direct genetic causality, our data identify Panx1 as a modulatory component influencing antigen-processing events that culminate in CD8⁺ T-cell activation, thereby expanding the current framework of intracellular antigen-processing mechanisms involved in dendritic-cell-mediated cross-presentation. Full article

Background and Objectives: Blood group antigens are well known for their importance in transfusion medicine and transplant compatibility; however, their biological role extends beyond these functions and includes associations with the risk of several diseases. In this study, we investigated the relationship between ABO blood groups and the circulating levels of 73 different molecules. Patients and Methods: Fifty-six healthy donors were enrolled, including 24 individuals with blood group O, 19 with blood group A, and 13 with blood group B. Blood samples were collected and analyzed in a single laboratory using Luminex fluorescent bead-based assay panels to determine the concentrations of 73 circulating molecules. Depending on data distribution, ANOVA or Kruskal–Wallis tests and Student’s t-test or Kolmogorov–Smirnov tests were applied to identify significant differences among groups. Associations were further assessed by binary logistic regression analysis. Results: Subjects with blood group A showed significantly higher circulating levels of IL-1R1, IL-13, IL-23, PDGF-BB, VEGF-A, VEGF-D, soluble VEGF-R2 (KDR), soluble VEGF-R3 (FLT-4), VLA-4, CD141, MMP-1, syndecan-1 (SDC-1), and mannose-binding lectin (MBL) compared with the other blood groups. In contrast, individuals with blood group B exhibited significantly higher levels of IL-22, IL-23, PDGF-BB, CD62P (P-selectin), and amyloid β1–42. Several significant associations were identified by logistic regression analysis. Conclusions: Our findings indicate that ABO blood groups are associated with distinct circulating molecular profiles, supporting the existence of biological differences that may contribute to variations in disease susceptibility among individuals with different blood types. Nevertheless, given the exploratory’s nature and limited sample size of this study, further investigations are required to validate these findings, confirm the observed associations, and clarify their potential clinical implications. Full article

Hyaluronic acid (HA), a major component of the glycome and a non-sulfated glycosaminoglycan, plays a crucial role in regulating stem cell behavior and function, thereby supporting skeletal muscle repair under inflammatory conditions. In this study, we investigated the effects of a mixture of HA fractions with different molecular weights (M-HA; 2–1000 kDa) on the repair capacity and myogenic potential of C2C12 murine myoblasts exposed to inflammatory stimuli. C2C12 cells were cultured, induced to differentiate, and treated with M-HA (1 mg/mL) under either physiological or inflammatory conditions (LPS, 10 µg/mL; IL-1β, 20 ng/mL). M-HA exhibited no cytotoxic effects, even at the highest concentration tested (1.0 mg/mL), and significantly enhanced scratch wound closure. Moreover, M-HA improved the myogenic index at day 5 of differentiation, promoted the expression of myogenic markers, preserved myosin heavy chain (MHC) levels under inflammatory stress, and reduced the expression of autophagy-related genes. Ultrastructural analyses revealed that untreated myotubes displayed swollen mitochondria, disrupted cristae architecture, and numerous autophagic vacuoles, whereas M-HA-treated cells exhibited well-preserved mitochondrial morphology, intact cristae organization, reduced cytoplasmic damage, and maintained myofibrillar structure. Taken together, the functional, molecular, and ultrastructural findings demonstrate that M-HA protects myoblasts from inflammation-induced cellular damage and supports their regenerative capacity. These results underscore the potential of glycomics-based strategies to enhance myogenic differentiation and promote skeletal muscle regeneration in inflammatory microenvironments. Full article

Coordinated responses of intestinal epithelial and immune cells are essential for maintaining barrier integrity and immune homeostasis in dogs, yet our mechanistic understanding of probiotic-derived metabolites remains limited due to reliance on non-canine experimental models, highlighting the need for studies in canine-derived systems. Here, we investigated the effects of metabolites derived from Limosilactobacillus reuteri strain ATCC PTA6127 (Lr6127), delivered as a cell-free supernatant (CFS), on canine epithelial MCA-B1 cells and macrophage-like DH82 cells subjected to lipopolysaccharide (LPS)-induced inflammatory stress. Lr6127 CFS significantly reduced epithelial permeability, decreasing FITC–dextran leakage to 94.9 ± 1.9% (normalized relative to LPS-treated control, which was set as 100%) (p < 0.001), despite no detectable transcriptional changes in tight junction, adherens junction, or mucin genes. Barrier effects were instead associated with changes in markers of cellular stress responses, with heme oxygenase expression decreasing from 0.9 ± 0.1 to 0.7 ± 0.1 (p < 0.05). In DH82 immune cells, Lr6127-derived metabolites altered LPS-induced stress- and inflammation-related gene expression patterns; enhanced anti-apoptotic responses, as reflected by the increased BCL2 expression (1.4 ± 0.1 vs. 1.0 ± 0.0; p < 0.01) and elevated BCL2/BAX ratios (p < 0.01); and reduced expression of pro-inflammatory mediators including IL-6 and CCL2 (p < 0.05–0.001). Proteomic analysis corroborated that Lr6127-derived metabolites reduced the abundance of inflammatory and STAT-associated signaling proteins under LPS challenge, while indicating context-dependent changes in immune-related protein profiles under resting condition. Collectively, these results suggest that Lr6127-derived metabolites improved epithelial barrier function, which was accompanied by coordinated changes in cellular stress-related and inflammatory pathways, highlighting their potential to positively influence host responses. Full article

Objectives: To characterize the one-year functional, anatomical, and molecular responses to intravitreal Ranibizumab in treatment-naïve patients with neovascular age-related macular degeneration (nAMD), and to identify systemic immune and miRNA signatures associated with treatment response. Methods: This prospective longitudinal observational study included 44 treatment-naïve patients with nAMD. Patients received up to four monthly intravitreal Ranibizumab injections, followed by a treat-and-extend regimen. Best-corrected visual acuity using ETDRS letters, central retinal thickness by optical coherence tomography, fluorescein angiography, and OCT angiography were assessed at baseline and 12 months. Peripheral blood samples were collected at both time points to quantify seven circulating cytokines using an IMMULITE chemiluminescent immunoassay and to profile 37 candidate miRNAs by TaqMan OpenArray RT-qPCR from leukocyte-derived RNA. Treatment response was classified using composite anatomical and functional criteria, including intraretinal/subretinal fluid resolution, ≥25% central retinal thickness reduction, and a ≥5 ETDRS letter gain. Results: At one year, patients showed significant central retinal thickness reduction and overall visual stabilization, although good and poor responders differed according to composite response criteria. Statin use was numerically more frequent among poor responders, although this difference was not statistically significant. Soluble IL-2R increased significantly over time in the overall cohort, mainly driven by good responders who showed higher median levels at both visits. IL-8 also increased globally, without significant between-group differences. Among differentially expressed miRNAs, miR-3121 was the only candidate reaching statistical significance and was downregulated in good responders. ROC analysis showed moderate discriminative performance for miR-3121, with an AUC of 0.76. Conclusions: One-year response to Ranibizumab in nAMD may involve systemic immune activation and miRNA regulation. miR-3121 emerges as a candidate biomarker of treatment response, supporting further validation in larger independent cohorts. Full article

This study evaluated the effects of adding zinc oxide nanoparticles (ZnNP), L-arginine (L-Arg), or a combination of both to the diets of growing rabbits to mitigate the physiological and productive consequences of heat stress. Two hundred and eighty 35-day-old New Zealand White rabbits were randomly assigned to four experimental treatments, with 70 rabbits per treatment and seven replicates (10 rabbits/replicate). The control group (Ctr) received the base diet without additives, while the diets of the other groups were fortified with arginine (L-Arg; 3 g/kg), zinc oxide nanoparticles (ZnNP; 40 mg/kg), or a combination of both (Arg-Zn). The results showed that the combined Arg-Zn significantly improved weight gain rate, feed conversion rate, carcass weight, and nutrient digestibility compared to the control group (p < 0.05). At the physiological level, we observed increased serum levels of total antioxidant capacity (T-AOC), glutathione peroxidase (GPx), superoxide dismutase (SOD), immunoglobulin G (IgG), immunoglobulin A (IgA), and triiodothyronine (T3), along with decreased levels of malondialdehyde (MDA), alanine aminotransferase (ALT), and aspartate aminotransferase (AST, p < 0.05) in Arg-Zn-fed rabbits. However, adding the Arg-Zn mixture contributed to a reduction in pathogenic bacteria counts and increased the volatile fatty acid (VFA) levels. At the molecular level, the gene expression of the inflammatory cytokines IL-6 and tumor necrosis factor alpha (TNF-α) decreased; however, the gene expression of claudins-1 (CLDN-1), cationic amino acid transporter-1 (CAT-1), mucin-2 (MUC-2), sodium-glucose co-transporter-1 (SGLT-1), and interferon gamma (IFNγ) increased (p < 0.05) in Arg-Zn-fed rabbits. These results suggest that dietary supplementation with ZnNP and L-Arg may serve as an effective nutritional strategy for improving growth performance, antioxidant status, immune function, and intestinal integrity in rabbits exposed to high ambient temperatures. Full article

Autoimmune myocarditis frequently progresses to inflammatory cardiomyopathy through dysregulated immune–stromal interactions. This study employs single-nuclei RNA-sequencing (snRNA-seq) to profile 46,233 cardiac nuclei from the experimental autoimmune myocarditis (EAM) mouse model at four timepoints: day 0 (healthy), day 14 (inflammation), day 21 (acute inflammation), and day 40 (late cardiac remodelling). Single-nuclei RNA profiling identified 18 transcriptionally distinct cell populations. Global cell–cell communication analysis revealed a dramatic peak of intercellular signalling at day 14 (5907 interactions), with fibroblast subpopulations and macrophages as dominant hubs, followed by partial resolution at day 21 (2264 interactions) and renewed remodelling at day 40 (4862 interactions). Subclustering of the macrophage compartment identified five subpopulations: Mac-TLF, Mac-MHCII, Mac-rMHCII, Mac-ResL, and Classical Monocytes. Tissue-resident macrophages (Mac-TLF, CCR2-) dominated at healthy state (~55%) but were rapidly depleted at day 14, coinciding with a dramatic influx of recruited CCR2⁺ macrophages (Mac-rMHCII), which expanded to over 70% of the compartment and maintained dominance through day 40. At inflammation (day 14), the expanded Mac-rMHCII subpopulation displayed a strongly pro-inflammatory signature (Il1b, Ankrd1, Stat2, Parp14, Apoe), and the overall macrophage compartment was enriched for cytokine response, Fc-gamma receptor, and Notch signalling pathways, while downregulating homeostatic and mitochondrial metabolic programmes, potentially contributing to impaired efferocytosis and cardiomyocyte dysfunction. Macrophage-centred communication networks expanded markedly at day 14 (1047 interactions), with resting fibroblasts (FB-R) as the primary signalling partner, driving pro-inflammatory stromal activation marked by upregulation of Ccl2, Ccl7, and Csf2. Intra-macrophage subcluster communication also intensified at this timepoint (447 interactions). These findings delineate the temporal and functional heterogeneity of cardiac macrophages during EAM progression and identify key immune–stromal interactions driving pathological cardiac remodelling. The coexistence of pro-inflammatory and transitional reparative macrophage subsets highlights the limitations of broad immunosuppression and supports precision strategies targeting CCR2-mediated recruitment, the SPP1 signalling axis, and macrophage–fibroblast crosstalk as therapeutic avenues in myocarditis and its progression. Full article

Introduction: Neuroinflammation is a key feature of both Alzheimer’s disease (AD) and glioblastoma, although it leads to different outcomes in each disorder. In AD, chronic activation of microglia and astrocytes by amyloid-β and tau contributes to neuronal injury and cognitive decline. In glioblastoma, tumor cells exploit inflammatory pathways to create an immunosuppressive microenvironment that supports tumor growth. This review compares the shared and distinct neuroinflammatory mechanisms in AD and glioblastoma and highlights their therapeutic relevance. Materials and Methods: This study was conducted as a narrative review based on a PubMed search performed by three reviewers. English-language articles on AD, glioblastoma, and neuroinflammatory pathways were included, covering original studies, reviews, meta-analyses, and experimental and clinical reports. Keywords included neuroinflammation, microglia, astrocytes, tumor-associated macrophages, inflammasomes, NLRP3, NF-κB, HIF-1α, cytokines, blood–brain barrier, and miRNAs. Due to study heterogeneity, findings were synthesized descriptively. Results: AD and glioblastoma share major neuroinflammatory mechanisms, including microglial and astrocytic activation, cytokine signaling, inflammasome activity, blood–brain barrier dysfunction, hypoxia-related changes, and miRNA regulation. In AD, these pathways promote chronic inflammation, synaptic loss, and neurodegeneration, with NLRP3, NF-κB, and M1-like microglial polarization playing central roles. In glioblastoma, similar pathways are redirected toward tumor progression through tumor-associated macrophages, reactive astrocytes, angiogenesis, immune evasion, and therapy resistance. Key overlapping mediators include IL-1β, TNF-α, NF-κB, HIF-1α, GSK-3β, and selected miRNAs. Conclusions: AD and glioblastoma are connected by common neuroinflammatory pathways, but these processes result in neurodegeneration in AD and tumor support in glioblastoma. Understanding these shared and divergent mechanisms may guide the development of biomarkers and targeted therapies focused on microglia, inflammasomes, cytokines, and immune reprogramming in both diseases. Full article

Propolis is a natural resinous product with a broad spectrum of biological activities, including immunomodulatory and anti-inflammatory effects. Increasing evidence suggests that propolis may influence pathways involved in tissue remodeling and fibrosis; however, comparative studies evaluating different propolis types in endothelial models remain limited. Brain microvascular endothelial cells, as a key component of the blood–brain barrier, constitute a relevant in vitro model for studying anti-inflammatory and neurovascular responses under both physiological and pathological conditions. The aim of this study was to compare the effects of Brazilian green propolis (EEP-BRA) and Polish brown propolis extracts (EEP-PL) on the immunological and fibrotic responses of brain microvascular endothelial cells. Human brain microvascular endothelial cells (hCMEC/D3-BBB) were exposed to propolis extracts (EEP-BRA and EEP-PL) under normoxic and hypoxic conditions to reflect diverse microenvironmental states. The analysis focused on the modulation of release of selected cytokines, including IL-10, IL-4, IL-6, IFN-γ, GM-CSF, TNF-α, IL-2, IL-8, and TGF-β, with particular emphasis on TGF-β as a key regulator of fibrosis. Results: Both propolis extracts significantly modulated cytokine production, although their effects differed depending on the origin of the propolis and oxygen conditions. Under the hypoxia condition followed by IFN-α stimulation, EEP-PL-50 was associated with reduced TNF-α (0.54 vs. 3.61 pg/mL; Hedges g = −6.78; large effect size, p > 0.05) and decreased TGF-β1, IL-8 and TGF-β2/β3. EEP-BRA-50 elicited a distinct profile characterized by increased IL-6 (171.58 vs. 27.63 pg/mL; p < 0.001; g = +6.15) and GM-CSF, while reducing TGF-β1. Both extracts preserved viability > 70% (ISO 10993-5). In conclusion, the results demonstrate that EEP-BRA and EEP-PL exert distinct immunomodulatory effects on brain endothelial cells. These findings highlight the importance of propolis origin in determining its biological activity and support its potential application in modulating inflammation and neurovascular responses. Full article