Search Results (10,279)

Background and Objectives: A thorough comprehension of the essential molecules and related processes underlying the carcinogenesis, proliferation, and recurrence of acute myeloid leukemia (AML) is crucial. This study aimed to investigate the expression levels, diagnostic and prognostic significance and biological roles of Bcl-2-associated athanogene 4 (BAG4) in AML carcinogenesis. Materials and Methods: Gene expression profiles were analyzed using publicly available datasets, particularly GSE9476 and TCGA, using tools such as GEO2R, GEPIA2, UALCAN and TIMER2.0. The immune infiltration correlation was examined using the GSCA platform, while the function of BAG4 at the single-cell level was analyzed via CancerSEA. Protein–protein and gene–gene interaction networks were constructed using STRING and GeneMANIA, and enrichment analyses were performed using GO, KEGG and DAVID. Expression validation was performed using RT-qPCR in HL-60 (AML) and HaCaT (normal) cells, and ROC curve analysis evaluated the diagnostic accuracy. Results: BAG4 was significantly overexpressed in AML tissues and cell lines compared with healthy controls. High BAG4 expression was associated with poor overall survival and strong diagnostic power (AUC = 0.944). BAG4 was positively associated with immune cell infiltration and negatively associated with CD4+/CD8+ T and NK cells. At the single-cell level, BAG4 was associated with proliferation, invasion, and DNA repair functions. Functional network analysis showed that BAG4 interacted with apoptosis and necroptosis-related genes such as BCL2, BAG3 and TNFRSF1A and was enriched in pathways such as NF-κB, TNF signaling and apoptosis. Conclusions: BAG4 is overexpressed in AML and is associated with adverse clinical outcomes and immune modulation. It may play an important role in leukemogenesis by affecting apoptotic resistance and immune evasion. BAG4 has potential as a diagnostic biomarker and treatment target in AML, but further in vivo and clinical validation is needed. Full article

This study presents data from Reverse Osmosis (RO) and Nanofiltration (NF) spiral-wound polyamide modules tested in a semi-pilot plant with multicomponent mixtures of Volatile Fatty Acids (VFAs) comprising acetic, propionic, butyric, valeric, and hexanoic acids. A robust method combining film theory and dissociation equilibria was developed to estimate interfacial concentrations, enabling accurate analysis of concentration polarization, real rejection, and effective transmembrane driving force. Concentration polarization strongly affects NF membranes, resulting in real rejections up to 20% higher than apparent values, while its effect is negligible for RO membranes. NF rejections show marked sensitivity to pH and VFA feed concentration: at 20 g/L and highest flux, acetic acid real rejection increases from 80% to 91% as pH rises from 6 to 9. At pH 7, rejections decline with feed concentration, with acetic acid dropping from 55% at 20 g/L to 32% at 63 g/L, at the same flux. These changes correlate with the molecular weight of the acids. Conversely, RO rejections are marginally affected by pH and not influenced by concentration due to dominant steric exclusion. Membrane permeabilities remain unaffected by VFAs and align with pure water values. The data analysis framework is effective and applicable across a wide range of conditions and membranes. Full article

Gingival inflammation compromises the integrity of the gingival epithelium and the underlying tissues, highlighting the need for adjuvant therapies with immunomodulatory and healing properties. Casearia sylvestris, a medicinal plant known as guaçatonga, is traditionally used to treat inflammatory lesions. This study aimed to investigate the effects of C. sylvestris on the synthesis of pro- and anti-inflammatory, proteolytic, and antioxidant molecules and on wound healing in epithelial cells. A human telomerase-immortalized gingival keratinocyte cell line (TIGKs) was used, and cells were exposed to Escherichia coli lipopolysaccharide (LPS) in the presence and absence of C. sylvestris extract, its diterpene-concentrated fraction, and its clerodane diterpene casearin J for 24 h and 48 h. Gene expression and protein synthesis were analyzed by RT-qPCR and ELISA, respectively. Nitric oxide (NO) and NF-κB activation were analyzed by Griess reaction and immunofluorescence, respectively. Additionally, cell viability was evaluated by alamarBlue^® assay, and an automated scratch assay was used for wound healing. LPS significantly increased the expression of cytokines (TNF-α, IL-1β, IL-6, IL-8, IL-10, IL-17), proteases (MMP-1 and MMP-13), iNOS as well as NO synthesis, and triggered NF-κB nuclear translocation. It also reduced IL-4 expression, cell viability, and cellular wound repopulation. Treatment with C. sylvestris derivatives significantly abrogated all aforementioned LPS-induced effects by 80–100%. Furthermore, even at higher concentrations, C. sylvestris did not affect cell viability, thus proving the safety of its derivatives. C. sylvestris exerts anti-inflammatory, antiproteolytic, and antioxidant effects on gingival keratinocytes, highlighting its potential as a valuable adjunct in the prevention and treatment of periodontal diseases. Full article

In agricultural practice, in addition to determining the nitrogen (N_f) dose, it is necessary to effectively control its effect on currently grown crops. Meeting these conditions requires not only the use of phosphorus (P) and potassium (K), but also nutrients such as magnesium (Mg) and sulfur (S). This hypothesis was verified in a single-factor field experiment with winter wheat (WW) carried out in the 2015/2016, 2016/2017, and 2017/2018 growing seasons. The experiment consisted of seven variants: absolute control (AC), NP, NPK-MOP (K as Muriate of Potash), NPK-MOP+Ki (Kieserite), NPK-KK (K as Korn–Kali), NPK-KK+Ki, and NPK-KK+Ki+ES (Epsom Salt). The use of K as MOP increased grain yield (GY) by 6.3% compared to NP. In the NPK-KK variant, GY was 13% (+0.84 t ha⁻¹) higher compared to NP. Moreover, GYs in this fertilization variant (FV) were stable over the years (coefficient of variation, CV = 9.4%). In NPK-KK+Ki+ES, the yield increase was the highest and mounted to 17.2% compared to NP, but the variability over the years was also the highest (CV ≈ 20%). The amount of N in grain N (GN) increased progressively from 4% for NPK-MOP to 15% for NPK-KK and 25% for NPK-KK+Ki+ES in comparison to NP. The nitrogen harvest index was highly stable, achieving 72.6 ± 3.1%. All analyzed NUE indices showed a significant response to FVs. The PFP-N_f (partial factor productivity of N_f) indices increased on NPK-MOP by 5.8%, NPK-KK by 12.9%, and NPK-KK+Ki+ES by 17.9% compared to NP. The corresponding N_f recovery of N_f in wheat grain was 47.2%, 55.9%, and 64.4%, but its total recovery by wheat (grain + straw) was 67%, 74.5%, and 87.2%, respectively. In terms of the theoretical and practical value of the tested indexes, two indices, namely, NUP (nitrogen unit productivity) and NUA (nitrogen unit accumulation), proved to be the most useful. From the farmer’s production strategy, FV with K applied in the form of Korn–Kali proved to be the most stable option due to high and stable yield, regardless of weather conditions. The increase in the number of nutritional factors optimizing the action of nitrogen in winter wheat caused the phenomenon known as the “scissors effect”. This phenomenon manifested itself in a progressive increase in nitrogen unit productivity (NUP) combined with a regressive trend in unit nitrogen accumulation (NUA) in the grain versus the balance of soil available Mg (Mg_b). The studies clearly showed that obtaining grain that met the milling requirements was recorded only for NUA above 22 kg N t⁻¹ grain. This was possible only with the most intensive Mg treatment (NPK-KK+Ki and NPK-KK+Ki+ES). The study clearly showed that three of the six FVs fully met the three basic conditions for sustainable crop production: (i) stabilization and even an increase in grain yield; (ii) a decrease in the mass of inorganic N in the soil at harvest, potentially susceptible to leaching; and (iii) stabilization of the soil fertility of P, K, and Mg. Full article

Cholesterol stress profoundly modulates cellular processes, but its underlying mechanisms remain incompletely understood. To investigate cholesterol-responsive networks, we performed integrated transcriptome (RNA-seq) and metabolome (LC-MS) analyses on HeLa cells treated with cholesterol for 6 and 24 h. Through transcriptomic analysis of cholesterol-stressed HeLa cells, we identified stage-specific responses characterized by early-phase stress responses and late-phase immune-metabolic coordination. This revealed 1340 upregulated and 976 downregulated genes after a 6 h cholesterol treatment, including induction and suppression of genes involved in cholesterol efflux and sterol biosynthesis, respectively, transitioning to Nuclear Factor kappa-B (NF-κB) activation and Peroxisome Proliferator-Activated Receptor (PPAR) pathway modulation by 24 h. Co-expression network analysis prioritized functional modules intersecting with differentially expressed genes. We also performed untargeted metabolomics using cells treated with cholesterol for 6 h, which demonstrated extensive remodeling of lipid species. Interestingly, integrated transcriptomic and metabolic analysis uncovered GFPT1-driven Uridine Diphosphate-N-Acetylglucosamine (UDP-GlcNAc) accumulation and increased taurine levels. Validation experiments confirmed GFPT1 upregulation and ANGPTL4 downregulation through RT-qPCR and increased O-GlcNAcylation via Western blot. Importantly, clinical datasets further supported the correlations between GFPT1/ANGPTL4 expression and cholesterol levels in Non-Alcoholic Steatohepatitis (NASH) liver cancer patients. This work establishes a chronological paradigm of cholesterol sensing and identifies GFPT1 and ANGPTL4 as key regulators bridging glycosylation and lipid pathways, providing mechanistic insights into cholesterol-associated metabolic disorders. Full article

Objectives: Saffron, a traditional Chinese medicine, is renowned for its pharmacological effects in promoting blood circulation, resolving blood stasis, regulating menstruation, detoxification, and alleviating mental disturbances. Trans-crocetin, its principal bioactive component, exhibits significant anti-hypoxic activity. The clinical development and therapeutic efficacy of trans-crocetin are limited by its instability, poor solubility, and low bioavailability. Conversion of trans-crocetin into trans-sodium crocetinate (TSC) enhances its solubility, stability, and bioavailability, thereby amplifying its anti-hypoxic potential. Methods: This study integrates network pharmacology with in vivo and in vitro validation to elucidate the molecular targets and mechanisms underlying TSC’s therapeutic effects against high-altitude acute lung injury (HALI), aiming to identify novel treatment strategies. Results: TSC effectively reversed hypoxia-induced biochemical abnormalities, ameliorated lung histopathological damage, and suppressed systemic inflammation and oxidative stress in HALI rats. In vitro, TSC mitigated CoCl₂-induced hypoxia injury in human pulmonary microvascular endothelial cells (HPMECs) by reducing inflammatory cytokines, oxidative stress, and ROS accumulation while restoring mitochondrial membrane potential. Network pharmacology and pathway analysis revealed that TSC primarily targets the EGFR/PI3K/AKT/NF-κB signaling axis. Molecular docking and dynamics simulations demonstrated stable binding interactions between TSC and key components of this pathway. ELISA and RT-qPCR confirmed that TSC significantly downregulated the expression of EGFR, PI3K, AKT, NF-κB, and their associated mRNAs. Conclusions: TSC alleviates high-altitude hypoxia-induced lung injury by inhibiting the EGFR/PI3K/AKT/NF-κB signaling pathway, thereby attenuating inflammatory responses, oxidative stress, and restoring mitochondrial function. These findings highlight TSC as a promising therapeutic agent for HALI. Full article

Tea is one of the most consumed beverages in the world, belonging to the category of compounds known as tannins and flavonoids. One of the polyphenols found in large amounts in green tea leaves (Camellia sinensis) is epigallocatechin-3-O-gallate (EGCG). Though EGCG has shown some pharmacological effects, to date, it has not been utilised as a therapeutic agent. This is attributed to the fact that EGCG lacks adequate stability, and it is known to degrade through epimerization or auto-oxidation processes, especially when it is exposed to light, temperature fluctuations, some pH values, or the presence of oxygen. Consuming green tea with EGCG can alleviate the effects of bone diseases, such as osteoporosis, and support faster bone regeneration in the case of fractures. Therefore, this review focuses on the current state of research, highlighting the effects of EGCG on bone biology, such as enhancing osteoblast differentiation, promoting bone mineralisation, improving bone microarchitecture, and inhibiting osteoclastogenesis through the modulation of the RANK/RANKL/OPG pathway. Additionally, EGCG exerts antioxidant, anti-inflammatory, and dose-dependent effects on bone cells. It also downregulates inflammatory markers (TNF-α, IL-1β, and COX-2) and reduces oxidative stress via the inhibition of reactive oxygen species generation and the activation of protective signalling pathways (e.g., MAPK and NF-κB). Studies in animal models confirm that EGCG supplementation leads to increased bone mass and strength. These findings collectively support the further exploration of EGCG as an adjunct in the treatment and prevention of metabolic bone diseases. The authors aim to present the relationship between EGCG and bone health, highlighting issues for future research and clinical applications. Full article

The developmental processes of microglia follow a general pattern, from immature amoeboid (activated) cells to fully ramified (inactivated) surveilling microglia. However, little is known about the mechanisms controlling the transition of microglia from an activated to an inactivated state during brain development. Due to the complexity of microenvironmentally dynamic changes during neuronal differentiation, interactions between developing nerve cells and microglia might be involved in this process. Extracellular vesicles (EVs) are cell-released particles that serve as mediators of cellular crosstalk and regulation. Using neural progenitor cells (NPCs) and a long-term neuron culture system, we found that EVs derived from NPCs or developing neurons possessed differential capacity on the induction of microglial activation. The exposure of microglia to NPC- or immature neuron (DIV7)-derived EVs resulted in the higher expression of protein and mRNA of multiple inflammatory cytokines (e.g., TNF-α, IL-1β, and IL-6), when compared with mature neuron-derived EVs. Exploration of the intracellular signaling pathways revealed that MAPK signaling, IκBα phosphorylation/degradation, and NF-κB p65 nuclear translocation were strongly induced in microglia treated with NPC- or immature neuron-derived EVs. Using a pharmacological approach, we further demonstrate that Toll-like receptor (TLR) 7-mediated activation of NF-κB and MAPK signaling cascades contribute to EV-elicited microglial activation. Additionally, the application of conditioned media derived from microglia treated with NPC- or immature neuron-derived EVs is found to promote the survival of late-developing dopaminergic neurons. Thus, our results highlight a novel mechanism used by NPCs and developing neurons to modulate the developmental phases and functions of microglia through EV secretion. Full article

Nanoceria is a multifaceted enzyme-like catalyst of ROS-mediated (reactive oxygen species) reactions, which results in its multiple biomedical applications. Biodegradable polysaccharide coatings improve biocompatibility, while the effects of these coatings on the ROS-related activity of nanoceria in cells need thorough studies. Here, we used human embryonic lung fibroblasts to study the effects of maltodextrin and chitosan coatings on cellular oxidative metabolism of nanoceria by examining cell viability, mitochondrial potential, accumulation of nanoparticles in cells, intracellular ROS, expression of NOX4 (NADPH oxidase 4), NRF2 (nuclear factor erythroid 2-related factor 2), NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), and STAT3 (signal transducer and activator of transcription 3) proteins as well as the expression of biomarkers of DNA damage/repair, cell proliferation, and autophagy. Both types of polysaccharide-coated nanoceria were non-toxic up to millimolar concentrations. For maltodextrin-coated nano-CeO₂, in contrast to bare nanoparticles, there was no oxidative DNA damage/repair with moderate activation of NOX4 expression. Like bare nanoceria, maltodextrin-coated nanoparticles demonstrate the proliferative impact and do not activate autophagy. However, maltodextrin-coated nanoparticles have an activating impact on mitochondrial potential and the NF-κB pathway. Chitosan-coated nanoceria causes short-term intracellular oxidative stress, activation of the expression of NOX4, STAT3, and NRF2, oxidative DNA damage, and double-strand breaks accompanied by activation of DNA repair systems. In contrast to maltodextrin-coated nanoparticles, chitosan-coated nanoceria inhibits the NF-κB pathway and activates autophagy. These findings would be useful in the development of advanced nanoceria-based pharmaceuticals and contribute to the understanding of the biochemical properties of nanoceria as a modulator of ROS-dependent signaling pathways. Full article

Konjac glucomannan (KGM) is a natural polysaccharide polymer. It is degraded by gut microbiota-derived β-mannanase into small-molecule nutrients, which exert diverse physiological regulatory effects. As a prebiotic, KGM modulates gut microbiota composition. It selectively fosters the proliferation of beneficial commensals and suppresses potential pathogens, thereby alleviating microbiota-related disorders. Moreover, microbiota fermentation of KGM produces metabolites. Short-chain fatty acids (SCFAs) are particularly notable among these metabolites. They exert multifaceted beneficial effects, including metabolic regulation, intestinal barrier strengthening, and neuroprotective functions. These effects are mediated through inhibition of inflammatory pathways (e.g., NF-κB, MAPK), modulation of lipid metabolism genes (e.g., CD36), and regulation of neurotransmitters (e.g., GABA, 5-HT). This highlights KGM’s therapeutic potential for metabolic, inflammatory, and neurodegenerative diseases. Current clinical use is limited by dose-dependent adverse effects and interindividual response variability, which stem from different microbial communities. This necessitates personalized dosage strategies. Despite these limitations, KGM as a prebiotic polysaccharide exhibits multifaceted bioactivity. Current evidence suggests its potential to synergistically modulate metabolic pathways, gut microbiota composition, immune cell signaling, and neuroendocrine interactions. This highlights its promise for developing novel therapeutic interventions. Full article

Intestinal inflammation involves barrier impairment, immune hyperactivation, and oxidative stress imbalance. Bioactive polysaccharides universally alleviate inflammation via anti-inflammatory, antioxidant, and microbiota-modulating effects, yet exhibit distinct core mechanisms. Elucidating these differences is vital for targeted polysaccharide applications. This research examines distinct regulatory pathways through which diverse bioactive polysaccharides mitigate lipopolysaccharide-triggered intestinal inflammation in male Kunming (KM) mice. This experiment employed Lentinula edodes polysaccharide (LNT), Auricularia auricula polysaccharide (AAP), Cordyceps militaris polysaccharide (CMP), Lycium barbarum polysaccharide (LBP), and Brassica rapa polysaccharide (BRP). The expression levels of biomarkers associated with the TLR4 signaling pathway, oxidative stress, and intestinal barrier function were quantified, along with comprehensive gut microbiota profiling. The results showed that all five polysaccharides alleviated inflammatory responses in mice by inhibiting inflammatory cytokine release, reducing oxidative damage, and modulating gut microbiota, but their modes of action differed: LBP significantly suppressed the TLR-4/MyD88 signaling pathway and its downstream pro-inflammatory cytokine expression, thereby blocking inflammatory signal transduction and reducing oxidative damage; LNT and CMP enhanced the body’s antioxidant capacity by increasing antioxidant enzyme activities and decreasing malondialdehyde (MDA) levels; AAP and BRP enriched Akkermansia (Akk.) within the Verrucomicrobia (Ver.) phylum, upregulating tight junction protein expression to strengthen the intestinal mucosal barrier and indirectly reduce oxidative damage. This research demonstrates that different polysaccharides alleviate inflammation through multi-target synergistic mechanisms: LBP primarily inhibits inflammatory pathways; AAP and BRP focus on intestinal barrier protection and microbiota modulation; and LNT and CMP exert effects via antioxidant enzyme activation. These data support designing polysaccharide blends that leverage complementary inflammatory modulation mechanisms. Full article

In this study, we investigated the effects of dietary supplementation with thermally modified attapulgite on the daily weight gain, serum biochemical indices, and serum metabolites of Simmental fattening cattle. A total of 30 healthy Simmental fattening beef calves of similar age (8 to 9 months old) and body weight (370 ± 10 kg) were randomly divided into two groups, each containing 15 animals. A control group was fed the basal diet, and a treatment group was fed the same basal diet with the addition of 4 g/kg of thermally modified attapulgite. After 75 days of formal experiment, the calves in the two groups were weighed, and blood samples were collected by tail vein blood sampling for determinations of the serum biochemical indices and serum metabolites using liquid chromatography–mass spectrometry (LC-MS) analysis. The results indicated that the addition of thermally modified attapulgite to the diet had no significant effects on the daily weight gain of fattening beef cattle. After feeding with modified attapulgite, the glutathione peroxidase and superoxide dismutase activities in the serum of the experimental group were 55.02% (257.26 U·mL⁻¹ to 165.95 U·mL⁻¹, p < 0.05) and 13.11% (18.98 U·mL⁻¹ to 16.78 U·mL⁻¹, p < 0.05) higher than that in the control group. Compared with the control group, the tumor necrosis factor-alpha content was reduced by 14.50% (31.27 pg·mL⁻¹ to 36.57 pg·mL⁻¹, p < 0.01), and the concentration of interleukin-6 and lipopolysaccharide decreased by 17.00% (34.33 pg·mL⁻¹ to 41.36 pg·mL⁻¹, p < 0.001) and 23.05% (51.34 EU·L⁻¹ to 66.72 EU·L⁻¹, p < 0.001) in the serum of the experimental group. Contrastingly, the thermally modified attapulgite had no significant effects on the levels of serum total protein, albumin, or globulin in Simmental fattening cattle (p > 0.05). Furthermore, the results of serum metabolomic analyses revealed that there were a total of 98 differential metabolites, which were mainly enriched with respect to glycerophospholipid metabolism, Th1 and Th2 cell differentiation, autophagy-other, retrograde endogenous cannabinoid signaling, and the NF-κB signaling pathway. Overall, thermally modified attapulgite was found to effectively increase the activity of antioxidant enzymes, reduce serum inflammatory mediators, may suppress oxidative damage, enhance immunity, and have a positive influence on the health of Simmental fattening beef calves. Full article

The insulin-like growth factor binding protein, acid-labile subunit (IGFALS), plays a crucial role in glucose metabolism and immune regulation, key processes in recovery from surgery. Here, we studied the perioperative serum IGFALS dynamics and explored potential clinical implications. A total of 79 patients undergoing elective cardiac surgery with implementation of cardiopulmonary bypass had their serum isolated at baseline, 24 h, seven days, and three months postoperatively to assess serum concentrations of IGFALS and insulin growth factor 1 (IGF-1). Markers of perioperative injury included troponin I (TnI), high-mobility group box 1 (HMGB-1), and heat shock protein 60 (Hsp-60). Inflammatory status was assessed via interleukin-6 (IL-6) and interleukin-8 (IL-8). Additionally, we measured in vitro cytokine production to viral stimulation of whole blood and monocytes. Surrogates of neuronal distress included neurofilament light chain (NF-L), total tau (τ), phosphorylated tau at threonine 181 (τp181), and amyloid β40 and β42. Renal impairment was defined by RIFLE criteria. Cardiac dysfunction was denoted by serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Serum IGFALS levels declined significantly after surgery and remained depressed even at 3 months. Administration of acetaminophen and acetylsalicylic acid differentiated IGFALS levels at the 24 h postoperatively. Serum IGFALS 24 h post-operatively correlated with production of cytokines by leukocytes after in vitro viral stimulation. Serum amyloid-β1-42 was significantly associated with IGFALS at baseline and 24 h post-surgery Patients discharged home had higher IGFALS levels at 28 days and 3 months than those discharged to healthcare facilities or who died. These findings suggest that IGFALS may serve as a prognostic biomarker for recovery trajectory and postoperative outcomes in cardiac surgery patients. Full article

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder and represents a major public health challenge. With increasing life expectancy, the incidence of AD has also increased, highlighting the need for early diagnosis and improved monitoring. Traditionally, diagnosis has relied on clinical symptoms and neuroimaging; however, the introduction of biomarkers has revolutionized disease assessment. Traditional biomarkers, including the Aβ42/Aβ40 ratio, phosphorylated tau (p-Tau181, p-Tau217, and p-Tau231), total tau (t-tau), and neurofilament light chain (NfL), are fundamental for staging AD progression. Updated guidelines introduced the ATX(N) model, which extends biomarker classification to include additional promising biomarkers, such as SNAP-25, YKL-40, GAP-43, VILIP-1, progranulin (PGRN), TREM2, IGF-1, hFABP, MCP-1, TDP-43, and BDNF. Recent advancements have allowed for the detection of these biomarkers not only in CSF but also in plasma and neuron-derived exosomes, offering less invasive and more accessible diagnostic options. This review explores established and emerging biomarkers and emphasizes their roles in early diagnosis, patient stratification, and precision medicine. Full article

Naturally occurring prostaglandin E₂ (PGE₂) influences cytokine production regulation in bovine neutrophils exposed to Staphylococcus aureus Rosenbach. Here, we employed bovine neutrophils as the primary experimental system, and administered specific inhibitors targeting various receptors, which were subsequently exposed to S. aureus. Cytokine expression levels in dairy cow neutrophils induced by S. aureus via the endogenous PGE₂-EP2/4 receptor pathway were investigated, and its effects on P38, extracellular signal-regulated kinase (ERK), P65 activation, and phagocytic function in Staphylococcus aureus Rosenbach-induced dairy cow neutrophils, were examined. Blocking cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) enzymes substantially decreased PGE₂ production and release in S. aureus-exposed bovine neutrophils. Cytokine output showed significant reduction compared to that in SA113-infected controls. Phosphorylation of P38, ERK, and P65 signaling molecules was depressed in the infected group. Pharmacological interference with EP2/EP4 receptors similarly diminished cytokine secretion and phosphorylation patterns of P38, ERK, and P65, with preserved cellular phagocytic function. During S. aureus infection of bovine neutrophils, COX-2 and mPGES-1 participated in controlling PGE₂ biosynthesis, and internally produced PGE₂ molecules triggered NF-κB and MAPK inflammatory pathways via EP2/EP4 receptor activation, later adjusting the equilibrium between cytokine types that promote or suppress inflammation. This signaling mechanism coordinated inflammatory phases through receptor-mediated processes. Full article