Search Results (4,332)

Lipopolysaccharide (LPS) impairs the function of ovine follicular granulosa cells (GCs), representing a primary cause of follicular atresia. Selenium (Se), an essential trace element, possesses anti-inflammatory and cytoprotective properties; however, its effects on GC ultrastructure remain largely unknown. In this study, primary ovine GCs were exposed to LPS (10 µg/mL) and treated with sodium selenite (25 nM). Transmission electron microscopy (TEM), JC-1 staining, enzyme-linked immunosorbent assay (ELISA), reactive oxygen species (ROS) detection, flow cytometry, and quantitative real-time PCR (qRT-PCR) were employed to evaluate cellular ultrastructure, mitochondrial membrane potential (ΔΨm), and downstream physiological processes. LPS induced severe mitochondrial pyknosis, cristae loss, and reduced ΔΨm, accompanied by inflammation, oxidative stress, apoptosis, and impaired steroidogenesis. Se intervention markedly ameliorated these ultrastructural injuries, preserving mitochondrial morphology and ΔΨm. Functionally, Se suppressed the release of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β); enhanced the activities of antioxidant enzymes including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) while attenuating ROS accumulation; inhibited apoptosis by upregulating BCL-2 and downregulating BAX and CASPASE-3; and restored E₂ and P₄ secretion via upregulation of STAR and NR5A1. This study provides direct morphological evidence that Se protects ovine GCs from LPS-induced damage by repairing mitochondrial ultrastructure. This structural restoration is central to its integrated anti-inflammatory, antioxidant, anti-apoptotic, and steroidogenic effects. These in vitro findings suggest that Se may serve as a promising nutritional strategy for mitigating inflammation-driven follicular atresia, pending further in vivo validation. Full article

Chronic infected wounds are often characterized by persistent bacterial colonization, biofilm formation, excessive oxidative stress, and prolonged inflammation, which severely impair tissue regeneration. To address these challenges, a multifunctional wound dressing capable of antibacterial activity and microenvironment modulation was developed. In this study, amide-modified hyaluronic acid (HA-ADH) was used as the matrix, and a dynamic coordination network was constructed via Cu²⁺-hydrazide interactions to form an in situ HA-Cu hydrogel. Curcumin-loaded DSPE-PEG2000 micelles were further incorporated to obtain a pH-responsive composite hydrogel (HA-Cu/Cur). The prepared hydrogel exhibited a porous interconnected structure, along with favorable injectability, self-healing capability, tissue adhesiveness, moderate swelling, controllable degradability, and pH-responsive behavior under acidic conditions. In vitro antibacterial assays demonstrated that both HA-Cu and HA-Cu/Cur effectively inhibited the growth and biofilm formation of Escherichia coli and Staphylococcus aureus. The antibacterial activity was associated with disruption of bacterial morphology, depletion of intracellular ATP, and induction of reactive oxygen species, while HA-Cu/Cur showed enhanced performance in antibiofilm activity and oxidative stress-related effects compared with HA-Cu. Cytocompatibility studies revealed that the hydrogel extracts exhibited negligible cytotoxicity toward L929 fibroblasts and RAW 264.7 macrophages, while promoting fibroblast migration and significantly reducing the expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in lipopolysaccharide-stimulated RAW 264.7 cells, with HA-Cu/Cur showing a more pronounced anti-inflammatory effect. In summary, the HA-Cu/Cur hydrogel integrates the antibacterial and pro-healing properties of Cu²⁺ with the antioxidant and anti-inflammatory activities of curcumin. The hydrogel effectively inhibited the growth and biofilm formation of both E. coli and S. aureus, reduced the expression of TNF-α, IL-6, and IL-1β in LPS-stimulated macrophages, and promoted fibroblast migration, demonstrating its potential as a multifunctional wound dressing for the management of infected wounds. Full article

Carrot processing for juice generates substantial pomace residues rich in bioactive compounds, which represent both an environmental challenge and an unexploited resource. This study investigated the protective effects of a polyphenolic extract derived from carrot pomace (CP) against Escherichia coli lipopolysaccharide (LPS)-induced damage. For that, we used IPEC-1 (Intestinal Porcine Epithelial Cells) as an in vitro model of the intestinal epithelium. The total phenolic content of the CP polyphenolic extract (CPE) was 1.017 mg GAE/mL, with flavan-3-ols (epicatechin, catechin, epigallocatechin) accounting for 71.3% of that value. Before being exposed to LPS (10 μg/mL) for 24 h, the cells were pre-treated with CP extract (20.34 µg and 10.17 µg polyphenols/mL of extract corresponding to 1/50 and 1/100 dilution) for 4 h. Epithelial renewal (cell viability, cell proliferation and apoptosis), monolayer/barrier integrity (TEER, FD4 permeability, LDH release), as well as epithelial functionality (synthesis of pro-inflammatory cytokines: TNF-α, IL-1β, IL-6, reactive oxygen species (ROS), nitric oxide (NO) production), MAPK signalling and mitochondrial morphology and function were assessed. The results showed that CP extract had no cytotoxic effects and successfully counteracted LPS-induced loss of cell viability and proliferation. The pre-treatment with CPE at both dilutions significantly reduced LPS-induced apoptosis and cell death. Barrier integrity was preserved with TEER values maintained near baseline: −0.43% and −0.24% for 1/50 and 1/100 dilutions of CPE vs. −53.47% at 72 h for LPS alone, and paracellular FD4 passage was restored to control levels. At the molecular level, CP extract reduced pro-inflammatory cytokine gene expression (IL-6 by 40%, TNF-α by 50–56%) and suppressed LPS-induced MAPK activation by 62.9% and 46.5%, for 1/50 and 1/100 dilutions of CPE, respectively. The pre-treatment of cells with CP extract normalised LPS-induced ROS production and protected mitochondrial morphology and function. These in vitro findings demonstrate that CP extract exerts a protective effect on intestinal epithelial cells, acting through anti-inflammatory, antioxidant and barrier-preserving mechanisms. This supports the hypothesis for valorisation of carrot agro-industrial by-products as functional feed additives for promoting intestinal health. Further in vivo studies are needed to validate this hypothesis and to establish the concentration/rate of inclusion of carrot by-products to achieve the maximal positive effects. Full article

Atherosclerosis is a chronic multifactorial inflammatory vascular disease and the major risk factor for cardiovascular diseases (CVDs), characterized by arterial wall thickening, loss of arterial elasticity and the progressive accumulation of lipids and immune cells, ultimately leading to plaque formation and the development of unstable, rupture-prone plaques. Several studies suggest that gut microbiota might contribute to atherosclerosis, mainly by converting dietary and endogenous molecules into bioactive metabolites, such as trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), and the Gram-negative cell-wall component lipopolysaccharide (LPS). Such metabolites can promote key mechanisms involved in the development and progression of atherosclerotic plaque, and, importantly, plaque vulnerability. Specifically, they can worsen endothelial dysfunction, induce macrophage-driven inflammatory responses, and cause oxidative stress and extracellular matrix degradation. These processes are crucial for thinning of the fibrous cap and destabilization of atherosclerotic plaques. As a result, the risk of plaque rupture and related cardiovascular events increases. In this review, we summarize potential mechanisms by which the gut microbiota and their compounds induce the formation of vulnerable atherosclerotic plaques and discuss findings from experimental models and clinical studies that reveal the crucial role of microbiota–host dynamics in atherosclerosis. In contrast to previous reviews that primarily focused on atherosclerosis development, we specifically highlight the cellular and molecular mechanisms linking gut microbiota to plaque vulnerability and destabilization. We also address future research priorities to define microbiota-driven pathways better and develop targeted therapeutic interventions to reduce plaque vulnerability and cardiovascular risk. Full article

Background/Objective: An obesogenic diet triggers intestinal inflammation and oxidative stress, leading to epithelial barrier dysfunction and increased risk of metabolic disorders. This study investigated the mechanisms by which quercetin protects intestinal integrity in high-fat diet (HFD)–fed mice. Methods: Mice were fed an HFD or a low-fat diet (LFD) with or without 1% quercetin, intestinal gene and protein expression, microRNA levels, permeability, and circulating intestinal biomarkers were assessed. Results: Mice fed an HFD with quercetin (HFDQ) showed a 17% improvement in intestinal barrier integrity with increased expression of tight junction and mucin genes and proteins. The nuclear translocation of the nuclear factor-κB (NF-κB) p65 subunit in the ileum decreased by 34%, whereas its acetylation was reduced by 50–57% throughout the intestine, with downregulation of NF-κB-regulated pro-inflammatory genes and proteins. Quercetin increased the nuclear factor erythroid 2-related factor 2 (NRF2) by ~ 25% across intestinal segments and upregulated antioxidant enzyme genes. It suppressed toll-like receptor 4 (TLR4) by 50% and restored AMP-activated protein kinase (AMPK) and sirtuin 1 to levels comparable to those in LFD mice. Altered microRNAs (miRNA-16, 200b, 122, 34a, and 21) supported these molecular changes. Quercetin also restored short-chain fatty acid receptors and serotonin transporters that were affected by HFD. Plasma lipopolysaccharide (LPS), cluster of differentiation 14, LPS-binding protein, and myeloperoxidase activity decreased by 36, 31, 42, and 37%, while glucagon-like peptide-1 increased by 23%. Conclusions: Quercetin protects epithelial barrier integrity against HFD-induced intestinal inflammation and oxidative stress via the AMPK-mediated NF-κB and NRF2 signaling pathways. Full article

Experimental acute lung injury (ALI) models are widely used to investigate pulmonary inflammation and evaluate therapeutic strategies for acute respiratory distress syndrome (ARDS). Kaempferia marginata is a traditional medicinal plant used to treat fever and has been reported to possess anti-inflammatory properties in lipopolysaccharide (LPS)-activated macrophages. 6β-Acetoxysandaracopimaradien-1α,9α-diol (ASPD), a major isopimarane-type diterpenoid isolated from this plant, has not previously been investigated for its effects on ALI. This study employed an integrated network pharmacology, molecular docking, and experimental validation strategy to investigate the protective effects and potential mechanisms of ASPD against LPS-induced ALI. Network pharmacology analysis identified several inflammation-related hub targets associated with Src, MAPK, and PI3K/Akt signalling. In LPS-stimulated MLE-12 cells, ASPD reduced inflammatory cytokine production and inhibited the phosphorylation of JNK1/2, ERK1/2, p38 MAPK, Akt, and GSK-3β. In mice with LPS-induced ALI, ASPD alleviated histopathological lung injury, pulmonary oedema, and inflammatory cell infiltration while reducing IL-6, TNF-α, and myeloperoxidase activity without apparent toxicity. Immunohistochemical analysis demonstrated reduced Src and ERK1/2 expression in lung tissue. Molecular docking analysis predicted favourable binding affinities between ASPD and selected Src- and MAPK-related signalling proteins. These findings suggest that ASPD attenuates LPS-induced ALI and is associated with alterations in Src-, MAPK-, and Akt/GSK-3β-related signalling. Full article

Chronic inflammation is a key contributor to the pathogenesis of numerous diseases, including cardiovascular, metabolic, and neurodegenerative disorders. Nutraceutical strategies targeting inflammatory pathways are of increasing interest, particularly those based on omega-3 fatty acids. The objective of this study was to evaluate the anti-inflammatory effects of two omega-3-based nutraceutical formulations, Omega 3 Plus and Omega 3 Orange, in primary human monocytes. Primary human monocytes were isolated from peripheral blood of a healthy donor and cultured under standardized conditions. Cells were pre-treated with different concentrations of the test formulations and subsequently stimulated with lipopolysaccharide (LPS, 10 ng/mL) for 24 h. Cell viability was assessed using the AlamarBlue assay. The release of pro-inflammatory mediators, including TNF-α, IL-1β, IL-6, MCP-1, IL-8, and prostaglandin E2 (PGE2), as well as the anti-inflammatory cytokine IL-10, was quantified using ELISA. Both formulations were well tolerated at concentrations up to 2.5%, with no significant cytotoxic effects. LPS stimulation induced a robust increase in inflammatory mediator release. Pre-treatment with Omega 3 Plus and Omega 3 Orange resulted in a significant, dose-dependent inhibition of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6 (up to ~70% reduction). MCP-1 was moderately reduced, whereas IL-8 was only minimally affected. Notably, Omega 3 Orange exhibited a pronounced inhibition of PGE2 production (up to ~95%), while Omega 3 Plus reduced PGE2 levels by approximately 80%. Neither formulation induced IL-10 production in unstimulated cells. These findings demonstrate that both omega-3-based nutraceutical formulations exert potent anti-inflammatory effects in primary human monocytes, primarily through the inhibition of pro-inflammatory cytokines and PGE2. The strong suppression of PGE2 is consistent with a possible modulation of pathways involved in prostaglandin synthesis. These results support the potential application of such formulations in inflammation-associated conditions and warrant further mechanistic and clinical investigation. Full article

The protective effect of arzanol, a natural prenylated phloroglucinol α-pyrone from the Helichrysum microphyllum subsp. tyrrhenicum, was investigated in HaCaT keratinocytes exposed to two inflammatory stimuli: lipopolysaccharide (LPS, 0.5–75 µg/mL), a component of gram-negative bacteria, and polyriboinosinic-polyribocytidylic acid (poly I:C, 0.5–50 µg/mL), a synthetic viral RNA analog. LPS and poly I:C significantly decreased HaCaT cell viability (18–93% reduction in the 5–75 μg/mL LPS range and 25% at 50 μg/mL poly I:C, MTT assay) and increased apoptosis and cell death (NucView 488 and propidium iodide assay) after 3 h and 24 h of exposure. Arzanol (1 h of pre-incubation, 5–25 μM) showed a significant protective effect against LPS and poly I:C-induced damage, preserving cell viability (25% of viability increase at 5 μg/mL LPS concentration, and 30% at 50 μg/mL of poly I:C) and decreasing apoptosis/cell death. Western blot analysis demonstrated the ability of arzanol (5 μM) to reduce the apoptotic protein Bax and the inflammatory cytokine IL-1β levels in HaCaT keratinocytes exposed for 3 h to 5 and 10 μg/mL LPS. Moreover, scratch assay showed the arzanol reparative effect on HaCaT cells. Our results qualified arzanol as a protective drug for dermatological applications in human skin diseases. Full article

Brucellosis remains a major zoonotic disease that affects both public health and animal production worldwide. Conventional live vaccines, including S19, RB51, and A19, are commonly used for disease control; however, concerns regarding their safety and performance under field conditions limit their application. Targeted gene deletion in Brucella abortus S2308 has generated multiple candidate vaccine strains, but their protection relative to conventional vaccines has not yet been clearly established. We synthesized evidence from 15 mouse studies to compare the protective performance of S2308-derived gene-deletion mutants with that of conventional vaccines. The pooled estimate did not show a statistically significant difference in splenic bacterial burden after challenge between mutant and conventional vaccine groups (mean difference [MD] = 0.38, 95% CI: −0.07 to 0.84; p = 0.10), although substantial heterogeneity was observed (I² = 95.38%). Heterogeneity was partially explained by mouse strain, mouse age, the functional categories of deleted genes, number of deletions, and challenge dose. Mutants targeting signal-regulatory genes tended to be associated with lower splenic bacterial loads than those targeting genes involved in lipopolysaccharide (LPS) biosynthesis. Overall, based on post-challenge splenic bacterial burden, current mouse evidence suggests that S2308-derived gene-deletion mutants may reduce bacterial burden to an extent broadly comparable to that achieved by conventional Brucella vaccines in mice. The observed association between signal regulation-related gene deletions and lower splenic bacterial burden should be regarded as exploratory and requires further validation using broader protective endpoints and studies in natural target hosts. Full article

Objective: Icariin (ICA) is an active small molecule extracted from Epimedium, possessing therapeutic potential for inflammatory bone destruction. Small extracellular vesicles (MEVs) derived from bovine milk are safe and efficient drug delivery carriers. We aimed to explore the potential of ICA-loaded bovine milk EVs (ICA-MEVs) to repair inflammatory bone defects in an inflammatory microenvironment and investigated the underlying molecular mechanism, providing new ideas for the treatment of inflammatory bone defects. Methods: We fabricated icariin (ICA)-loaded milk-derived extracellular vesicles (ICA-MEVs) embedded in GelMA hydrogel and systematically evaluated the in vivo repairing efficacy against lipopolysaccharide (LPS)-induced inflammatory calvarial bone defects via micro-CT, HE staining, Masson staining and immunohistochemistry. Subsequent in vitro cellular experiments were carried out to uncover the regulatory mechanism by which ICA-MEVs promotes LPS-inhibited osteoblast proliferation and osteogenic differentiation. Results: ICA-MEVs significantly promoted the repair of inflammatory bone defects, upregulated osteogenic factors such as BMP-2, OCN, and Runx-2, and reduced the levels of IL-1β and TNF-α. ICA-loaded MEVs facilitated the proliferation and osteogenic differentiation of MC3T3-E1 osteoblasts while alleviating cellular inflammatory activation. Mechanistically, ICA-MEVs promoted bone repair by elevating LIM1 expression. Elevated LIM1 bound to the endogenous HIF-1α promoter and triggered subsequent transcriptional activation of HIF-1α. Conclusions: Under inflammatory conditions, ICA-MEVs effectively promoted the proliferation and differentiation of MC3T3-E1 cells and inhibited the expression of inflammatory factors. Mechanistically, ICA-MEVs upregulated HIF-1α transcription and expression by potentiating the LIM1-mediated transcriptional activation of the HIF-1α promoter, thereby facilitating inflammatory bone repair. Although milk-derived EVs exhibited favorable safety profiles in this preclinical study, comprehensive detection of immunogenicity and long-term adverse reactions will be necessary in follow-up research to support clinical transformation. Full article

Background and Objectives: Microscopic colitis (MC) encompasses two chronic inflammatory disorders of the large intestine: collagenous colitis (CC) and lymphocytic colitis (LC). Both conditions are characterised by chronic watery diarrhoea and substantially impaired quality of life. Diagnosis relies on colonoscopy with multiple biopsies, and no reliable non-invasive biomarker currently exists. This exploratory study aimed to investigate circulating fatty acid-binding protein 2 (FABP2), interleukin-10 (IL-10), and lipopolysaccharides (LPSs) as potential biomarkers for MC and to compare their profiles with those in ulcerative colitis (UC). Materials and Methods: Plasma samples were obtained from 45 patients with active CC, 16 patients with active LC, 52 healthy controls, 43 patients with active UC, and 43 patients with inactive UC. Concentrations of FABP2, IL-10, and LPS were measured by enzyme-linked immunosorbent assay (ELISA). Results: Plasma FABP2 concentrations differed significantly across groups (Kruskal–Wallis p = 0.008). CC patients exhibited the highest levels (median 1719.0 pg/mL, IQR 1364.0–2240.0) compared with active UC (median 1272.0 pg/mL, IQR 861.7–1727.5; p = 0.005) and inactive UC (median 1334.0 pg/mL, IQR 854.2–1702.0; p = 0.001), but did not differ significantly from controls (median 1364.5 pg/mL, IQR 982.6–2160.5; p = 0.076) or LC (median 1421.5 pg/mL, IQR 1207.0–2002.2; p = 0.171). IL-10 concentrations also differed across groups (Kruskal–Wallis p = 0.029 after removal of one extreme outlier in active UC). Active UC patients had significantly lower levels (median 2.6 pg/mL, IQR 1.4–4.6) than CC (median 4.0 pg/mL, IQR 3.0–7.2; p = 0.009) and controls (median 4.8 pg/mL, IQR 2.6–7.4; p = 0.005). LPS concentrations showed no overall differences across groups (Kruskal–Wallis p = 0.55), although CC patients had numerically higher levels (median 73.7 pg/mL, IQR 45.6–104.9) compared with controls (median 56.4 pg/mL, IQR 33.7–87.1; p = 0.124). No significant differences were observed between LC and other groups for any biomarker. Conclusions: In this exploratory study, plasma FABP2 and IL-10 showed limited diagnostic accuracy in differentiating CC from UC but failed to distinguish MC from healthy controls. LPS levels were not significantly different among study groups. None of the biomarkers reliably separated LC from other groups, possibly reflecting the small LC sample size. These preliminary findings suggest subtle differences in circulating biomarker profiles between CC and UC that warrant validation in larger cohorts. Full article

Background: Lipopolysaccharide (LPS) functions as a Toll-like receptor 4 (TLR4) agonist that triggers innate immunity; however, structural variations between pathogenic and commensal bacteria distinctly influence its immunostimulatory profile. This study evaluated the immunostimulatory activity of LPS derived from the commensal bacterium Hafnia alvei and explored its potential as an exploratory vaccine adjuvant. Methods: Cytokine induction was evaluated in immune cells across diverse host species, and receptor activation was assessed via reporter assays. To investigate in vivo immunogenicity and preliminary tolerability, H. alvei LPS was formulated into a prototype oil-in-water (O/W) emulsion utilizing ovalbumin (OVA) as a model antigen. Results: LPS from H. alvei strain BA2000346 exhibited immunostimulatory activity comparable to that of Escherichia coli, while inducing greater TNF-α expression than pathogenic Salmonella and Pseudomonas strains. Distinct from E. coli LPS, it demonstrated the capacity to activate both TLR4 and the mannose-recognizing Dectin-2 receptor in reporter systems. This cytokine induction was consistent across various strains and host species. Furthermore, the prototype O/W emulsion formulation enhanced antigen-specific humoral and cellular immune responses while demonstrating preliminary tolerability based on body-weight monitoring and visual clinical observation. Conclusions: H. alvei-derived LPS exhibits TLR4 and Dectin-2 agonist activity in vitro. When synergized with an O/W emulsion delivery system, it provides a preliminary indication of cross-species stimulatory potential and supports further investigation as a hypothesis-generating platform for future vaccine adjuvant development. Full article

Atopic dermatitis (AD) is a chronic inflammatory dermatosis driven by skin barrier impairment and immune dysregulation. This study aimed to investigate the anti-inflammatory and barrier-related effects of the ethanol extract of Bidens bipinnata L. fruits (EEBB) in a calcipotriol (MC903)-induced AD-like dermatitis mouse model and lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. In vivo, repeated topical application of EEBB (60, 180, and 600 μg/day) significantly attenuated MC903-induced AD-like clinical symptoms, skin weight, and erythema index. Notably, EEBB significantly improved skin hydration-related parameters, including relative skin hydration readings and the post-application moisture retention profile, and partially restored filaggrin and loricrin expression in lesional skin, whereas dexamethasone showed limited effects on these hydration-related parameters under the present conditions. Histopathologically, EEBB ameliorated epidermal lesions and reduced inflammatory cell infiltration. Mechanistically, EEBB suppressed the levels of pro-inflammatory (TNF-α, IFN-γ) and Th2 (IL-4, IL-5) cytokines in lesional skin. In vitro, EEBB significantly inhibited the production of nitric oxide (NO) and prostaglandin E₂ (PGE₂), and downregulated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression in RAW 264.7 cells. These effects were associated with inhibited phosphorylation of JNK and p38 MAPK, with no marked effect on ERK phosphorylation under the present conditions. In conclusion, EEBB effectively alleviated AD-like dermatitis, accompanied by improved skin hydration and restoration of barrier-related protein expression, attenuation of local inflammatory responses, and targeted inhibition of the MAPK signaling pathway. Full article

Mastitis remains the most economically damaging disease of dairy production, and recent molecular work has converged on the NLRP3 inflammasome as a key integrative node of its pathogenesis. This narrative review integrates evidence published largely between 2015 and 2026 to show how diverse triggers—Staphylococcus aureus and Escherichia coli, lipopolysaccharide (LPS) and lipoteichoic acid (LTA), non-esterified fatty acids (NEFA), heat stress, environmental xenobiotics including nanoplastics, and microbiota-derived signals—may funnel into a common NLRP3–ASC–caspase-1–GSDMD axis that drives pyroptosis, blood–milk barrier disruption, and clinical disease. The review examines the potential obligatory role of reactive oxygen species (ROS), mitochondrial dysfunction, and selenoprotein-mediated redox control in licensing inflammasome assembly. It further evaluates the emerging gut–mammary and rumen–mammary axes that operate upstream of local epithelial activation. We survey a structurally diverse therapeutic landscape encompassing dietary selenium, probiotics, microbial metabolites, plant-derived nanovesicles, polyphenols, ginsenosides, and small-molecule NLRP3 antagonists, identifying recurring mechanistic motifs that suggest combinatorial regimens may yield additive benefit. Importantly, much of the evidence derives from in vitro and murine models, and we highlight the translational gaps that must be bridged before clinical application in dairy cattle. Finally, we map outstanding research gaps and propose priorities for translational work aimed at sustainable, antibiotic-sparing management of bovine mastitis. Full article

Objective: Neuroinflammation contributes to cognitive impairment across neurodegenerative disorders. Prostaglandins (e.g., PGE₂, PGD₂, PGF₂α) and pro-inflammatory cytokines (TNF-α, IL-1β) are key mediators of lipopolysaccharide (LPS)-induced hippocampal dysfunction. Carvacrol (CRV), a monoterpenic phenol with anti-inflammatory and antioxidant properties, may mitigate these effects, but its impact on hippocampal prostaglandin profiles is not well-defined. Methods: BALB/c mice were randomly assigned to Control (PBS; n = 7), LPS (1 mg/kg, i.p.; n = 10), or LPS + CRV (50 mg/kg, p.o.; n = 7). Body weight was tracked daily for 7 days; rectal temperature was measured once before behavioral testing and euthanasia. Locomotion/anxiety were assessed by the open-field test (OFT; average speed, total distance, freezing, mobility rate) using ToxTrac. Spatial recognition memory was evaluated in the Y-maze novel-arm task (novel-arm entries, duration, total entries, discrimination index [DI]). Hippocampal PGE₂, PGD₂, PGF₂α, TNF-α, and IL-1β were quantified by ELISA. Data were analyzed by one-way ANOVA with Sidak’s post hoc test. Results: OFT measures did not differ among groups (p > 0.05), indicating no confounding locomotor deficits. In the Y-maze, LPS reduced novel-arm entries versus the Control (p = 0.0029), while LPS + CRV showed a nonsignificant increase versus LPS (p = 0.2406). Novel-arm duration differed among groups (p = 0.0033); LPS + CRV spent less time than LPS (p = 0.0128). Critically, DI showed a robust treatment effect (p < 0.0001): LPS markedly impaired DI versus the Control (p < 0.0001), and CRV significantly improved DI versus LPS (p < 0.0001). Biochemically, LPS elevated hippocampal PGE₂ (p < 0.0001) and PGF₂α (p = 0.0040); CRV normalized PGE₂ (p < 0.0001) but not PGF₂α (p = 0.2656). PGD₂ was unchanged. LPS increased TNF-α and IL-1β (both p < 0.0001), and CRV significantly reduced both versus LPS (both p < 0.0001). Conclusions: Acute LPS provokes prostaglandin- and cytokine-driven hippocampal inflammation with associated recognition memory deficits. Carvacrol attenuates cognitive impairment and suppresses hippocampal PGE₂, TNF-α, and IL-1β, supporting a mechanism involving modulation of the prostaglandin–cytokine axis. These findings highlight CRV as a candidate adjunct for inflammation-associated cognitive dysfunction. Full article