Search Results (5,304)

Voltage-gated Na⁺ channels (Nav) are the molecular determinants of action potential initiation and propagation. Among the nine voltage-gated Na⁺ channel isoforms (Nav1.1–Nav1.9), Nav1.2 and Nav1.6 are of particular interest because of their developmental expression profile throughout the central nervous system (CNS) and their association with channelopathies. Although the α-subunit coded by each of the nine isoforms can sufficiently confer transient Na⁺ currents (I_Na), in vivo these channels are modulated by auxiliary proteins like intracellular fibroblast growth factor (iFGFs) through protein–protein interaction (PPI), and probes developed from iFGF/Nav PPI complexes have been shown to precisely modulate Nav channels. Previous studies identified ZL0177, a peptidomimetic derived from a short peptide sequence at the FGF14/Nav1.6 PPI interface, as a functional modulator of Nav1.6-mediated I_Na⁺. However, the isoform specificity, binding sites, and putative physiological impact of ZL0177 on neuronal excitability remain unexplored. Here, we used automated planar patch-clamp electrophysiology to assess ZL0177’s functional activity in cells stably expressing Nav1.2 or Nav1.6. While ZL0177 was found to suppress I_Na in both Nav1.2- and Nav1.6-expressing cells, ZL0177 elicited functionally divergent effects on channel kinetics that were isoform-specific and supported by differential docking of the compound to AlphaFold structures of the two channel isoforms. Computational modeling predicts that ZL0177 modulates Nav1.2 and Nav1.6 in an isoform-specific manner, eliciting phenotypically divergent effects on action potential discharge. Taken together, these results highlight the potential of PPI derivatives for isoform-specific regulation of Nav channels and the development of therapeutics for channelopathies. Full article

Diabetic cardiomyopathy (DCM) is a serious complication of type 2 diabetes mellitus (T2DM), characterized by cardiac dysfunction, inflammation, and fibrosis. In this study, a T2DM mouse model was established by administering a high-fat diet (60% fat) in combination with streptozotocin injection in male C57BL/6J mice. The mice subsequently underwent an eight-week exercise intervention consisting of swimming training, resistance training, or high-intensity interval training (HIIT). The results showed that all three forms of exercise improved cardiac function and attenuated myocardial hypertrophy in DCM mice. Exercise training further downregulated the expression of pro-inflammatory cytokines, including interleukin-6, tumor necrosis factor-α, nuclear factor κB, and monocyte chemoattractant protein-1, and mitigated myocardial fibrosis by suppressing fibronectin, α-SMA, collagen type I alpha 1 chain, collagen type III alpha 1 chain, and the TGF-β1/Smad signaling pathway. Moreover, exercise inhibited the expression of PANoptosis-related genes and proteins in cardiomyocytes of DCM mice. Notably, HIIT produced the most pronounced improvements across these pathological markers. In addition, all three exercise modalities effectively suppressed the aberrant activation of the cGAS–STING signaling pathway in the myocardium. In conclusion, exercise training exerts beneficial effects against DCM by improving cardiac function and reducing inflammation, PANoptosis, and fibrosis, and HIIT emerged as the most effective strategy. Full article

This study investigated the effects of integrating biofloc with microalgae on growth performance and immune gene expression in red tilapia (Oreochromis sp.). The experiment consisted of four treatments: C (Biofloc), T1 (Chlorella vulgaris and Nannochloropsis sp.; 1:1), T2 (Biofloc + Chlorella vulgaris and Nannochloropsis sp.; 1:1), T3 (Biofloc + Chlorella vulgaris and Nannochloropsis sp.; 2:1) in 500 L plastic tanks for 60 days. T2 and T3 exhibited the lowest ammonia and nitrite levels, respectively. T3 exhibited the highest chlorophyll a and chlorophyll b levels, while T2 showed the highest carotenoid content. T2 showed the highest weight gain (142 ± 0.7 g) and SGR (1.61 ± 0.02) and the lowest FCR (1.79 ± 0.009). T2 exhibited the highest gene expression levels in the intestine, with 7.8-fold upregulation of the cathepsin L (ctsl) gene, 3-fold upregulation of toll-like receptor 7 (tlr7), 6.7-fold upregulation of interleukin-1 b (il-1b), 4.7-fold upregulation of tumor necrosis factor-alpha (tnf-a), and 2.8-fold upregulation of metallothionein (mt). In the head kidney, the mt upregulation was highest in T3 (7.2-fold), while tnf-a and tlr7 upregulations were highest in T2 (5.9-fold and 5-fold, respectively). In the liver, the gene expressions were highest in T3, with 6.4-fold upregulation of mt, 5-fold upregulation of ctsl, 2.7-fold upregulation of tlr7, 3-fold upregulation of il-1b, and 5.4-fold upregulation of tnf-a. These results suggest a synergistic effect of algae and bacteria on immune and antioxidative capacity in red tilapia. Full article

Background/Objectives: Toxoplasma gondii, an obligate intracellular parasite, poses a major global health concern owing to its potential for congenital transmission, particularly during pregnancy. Current pharmacological treatments, including spiramycin and pyrimethamine, exhibit limitations in both efficacy and safety, underscoring the need for novel therapeutic strategies. In this study, we investigated the antiparasitic potential of BthTX-II, an Asp49 phospholipase A₂ (PLA₂) isolated from Bothrops jararacussu venom, in human trophoblast cells (BeWo) and third-trimester human placental explants infected with T. gondii. Methods: In vitro assays were performed using BeWo cells infected with T. gondii tachyzoites and treated with non-cytotoxic concentrations of BthTX-II (3.125, 1.56, and 0.78 µg/mL). An ex vivo model employing third-trimester human placental villous explants was used under similar conditions. Parasite proliferation, adhesion, and invasion were assessed alongside host immune response modulation. Results: Our findings demonstrate that BthTX-II reduces T. gondii proliferation in BeWo cells at all tested non-cytotoxic concentrations. The toxin also significantly impaired parasite adhesion and invasion while modulating host immune response by upregulating interleukin (IL)-6, IL-8, and macrophage migration inhibitory factor (MIF), and downregulating vascular endothelial growth factor—potentially disrupting parasite proliferation. In placental villous explants, BthTX-II (1.56 μg/mL) reduced T. gondii proliferation and modulated IL-8, MIF, and tumour necrosis factor-alpha levels without compromising tissue viability. Conclusions: These findings highlight BthTX-II as a potential candidate in toxoplasmosis treatment. Further investigation should focus on its dual role in limiting parasite development and modulating immune responses at the maternal–fetal interface. Full article

Feeding Allium mongolicum Regel (AMR) could improve lamb growth, immunity, and antioxidant capacity. These effects were supposed to be mediated by the rumen microbiota, as reported in our previous studies, but further verification is required. The purpose of this study was to verify whether changes in serum immunity, antioxidant, and biochemical indicators of meat sheep mediated by AMR are achieved via rumen microbiota regulation. The experiment included two phases. In phase I, twelve 90-day-old male lambs (25 ± 1 kg) were used as rumen fluid donors and consumed a basal diet with 15 g/day AMR for 135 days to induce changes in their rumen microbiota. In phase II, thirty 90-day-old male lambs (23 ± 2 kg) were split into three groups (n = 10 each): the control group (CON) fed the basal diet; the AMR-supplemented group (AMG) fed the basal diet supplemented with 15 g/day of AMR; and the rumen fluid recipient group (RTG) fed the basal diet and received rumen fluid transplantation. The CON and AMG groups received four oral infusions of 250 mL saline, while the RTG group received four oral infusions of 250 mL donor rumen fluid. Phase II lasted for 75 days, and the blood samples were collected on the last day. Rumen fluid transplantation was performed every 15 days, with a total of four infusions of 250 mL each. The results showed that the final body weight and average daily gain (ADG) of the AMG and RTG groups were higher than those of the CON group (p < 0.05), while there were no significant differences between the AMG and RTG groups (p > 0.05). On day 30, the levels of interleukin-10 (IL-10), immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG) in the AMG and RTG groups were increased (p < 0.05), and malondialdehyde (MDA) was significantly decreased (p < 0.05), with no significant differences between the AMG and RTG groups. On day 60, total antioxidant capacity (T-AOC), IgM, IgG, and catalase (CAT) were increased in the AMG and RTG groups, while tumor necrosis factor alpha (TNF-α), low-density lipoprotein cholesterol (LDL-C), and blood urea nitrogen (BUN) were decreased (p < 0.05), and there were no significant differences between the AMG and RTG groups (p > 0.05). High-density lipoprotein cholesterol (HDL-C) in the RTG group was significantly lower than in the CON and AMG groups, while the AMG group had significantly higher HDL-C than the CON group (p < 0.05). Microbial analysis indicated that Mitsuokella, VUNI01, and Caecibacter were positively correlated with IgM; Mitsuokella, CAG 791, Desulfovibrio R, Porcincola, VUNI01, and UBA 7741 were negatively correlated with TNF-α; CAG 791 was positively correlated with T-AOC; VUNI01 was positively correlated with CAT; MDA was negatively correlated with Mitsuokella; Allisonella and UBA 7741 were negatively correlated with HDL-C; and Porcincola, VUNI01, Allisonella, and UBA 7741 were negatively correlated with LDL-C. Therefore, the study indicates that both supplementation with AMR and transplantation of rumen fluid from sheep fed with AMR can enhance the immunity and antioxidant capacity of lambs by increasing the abundance of the aforementioned bacteria. It also verified that the improvement in immunity and antioxidant capacity mediated by Allium mongolicum Regel is driven by the rumen microbiota. Full article

Alcohol Use Disorder (AUD) poses global health challenges, and causes hematological alterations such as macrocytosis and oxidative stress. Disruption of protein structures by alcohol and/or its metabolites may exacerbate AUDs; proteomics can elucidate the underlying biological mechanisms. This study examined the proteins differentially expressed in the cytosol and membrane fractions of erythrocytes obtained from 30 male patients with AUD, comparing them to samples from 15 age- and BMI-matched social drinkers (SDs) and 15 non-drinkers (control). The analysis aimed to identify the molecular differences related to alcohol consumption. The AUD patient subgrouping was based on mean corpuscular volume (MCV), with 16 individuals classified as having a normal MCV and 14 having a high MCV. Proteins were separated via two-dimensional(2D)-gel electrophoresis, digested with trypsin, and identified via Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (TOF) mass spectrometry (MALDI-TOF/TOF). Additionally, levels of malondialdehyde and 4-hydroxyalkenals (MDA + HAE), reduced glutathione (GSH), oxidized glutathione (GSSG), serum carbohydrate-deficient transferrin (%CDT), disialotransferrin (%DST), and sialic acid (SA) were analyzed. The results showed increased MDA + HAE and decreased total thiols in AUD patients, with GSSG elevated and the GSH/GSSG ratio reduced in the AUD MCV-high subgroup. Serum %CDT, %DST, and SA were significantly higher in AUD. Compared to the control profiles, the AUD group exhibited differential protein expression. Few proteins, such as bisphosphoglycerate mutase, were downregulated in AUD versus control and SD, as well as in the MCV-high AUD subgroup. Conversely, endoplasmin and gelsolin were upregulated in AUD relative to control. Cytoskeletal proteins, including spectrin-alpha chain, actin cytoplasmic 2, were overexpressed in the AUD group and MCV-high AUD subgroup. Several proteins, such as 14-3-3 isoforms, alpha-synuclein, translation initiation factors, heat shock proteins, and others, were upregulated in the MCV-high AUD subgroup. Under-expressed proteins in this subgroup include band 3 anion transport protein, bisphosphoglycerate mutase, tropomyosin alpha-3 chain, uroporphyrinogen decarboxylase, and WD repeat-containing protein 1. Our findings highlight the specific changes in protein expression associated with oxidative stress, cytoskeletal alterations, and metabolic dysregulation, specifically in AUD patients with an elevated MCV. Understanding these mechanisms is crucial for developing targeted interventions and identifying biomarkers of alcohol-induced cellular damage. The complex interplay between oxidative stress, membrane composition, and cellular function illustrates how chronic alcohol exposure affects cellular physiology. Full article

Background: Systemic lupus erythematosus (SLE) is an autoimmune disorder associated with premature atherosclerosis and vascular impairment. However, the role of endocan, a biomarker of glycocalyx injury, is not completely clarified in the detection of vascular damage. Therefore, our aim was to investigate serum endocan in comparison with conventional inflammatory markers, arterial stiffness parameters, and carotid ultrasound findings in a cohort of young patients with SLE. Methods: We enrolled 47 clinically active young SLE patients (40 females and 7 males) in the study. Arterial stiffness indicated by augmentation index and pulse wave velocity (PWV) was measured by arteriography. Brachial artery flow-mediated dilatation and common carotid intima-media thickness were detected by ultrasonography. The serum concentrations of endocan, IL-6, MPO, MCP-1, MMP-3, -7, and -9, as well as TNFα, were measured by an enzyme-linked immunosorbent assay (ELISA). Results: We found significant negative correlations between serum endocan and both CH50 and C3. Serum endocan was higher in active SLE patients compared to inactive patients, however, the difference was not statistically significant (241.4 (183–295) vs. 200.3 (167–278) pg/mL; p = 0.313). Serum TNFα and hsCRP significantly correlated with PWV. However, we did not detect significant correlations between vascular diagnostic tests and serum endocan levels. Conclusions: Based on our results, serum endocan is associated with disease activity; however, further studies are needed to clarify the value of serum endocan in the cardiovascular risk estimation of SLE patients. Measurement of serum endocan, as well as the routine assessment of arterial stiffness parameters, should be integrated into the comprehensive management plans of young patients with SLE. Full article

Previous studies revealed that low expression of Selenoprotein S (SELS) could enhance osteogenic differentiation, but the underlying mechanisms remain unclear. In this study, we aimed to elucidate the role of SELS and its transcription-factor-based regulatory mechanism during osteogenic differentiation. In comparison with 12-week-old mice, which represent the stage of stable osteogenic differentiation, 3-week-old mice, representing the active ossification stage, showed significantly higher levels of SELS in the mandible. Transcriptomic analysis revealed that SELS is primarily associated with extracellular matrix organization and collagen biosynthesis during mandibular development. In bone marrow mesenchymal stem cells (BMSCs) with SELS knockdown, SP7 levels were elevated after 7 days of osteogenic induction in vitro. Consistently, immunohistochemical and immunofluorescence staining confirmed increased SP7 expression in the mandibles of 7-week-old Sels knockout mice. Dual-luciferase reporter assays and chromatin immunoprecipitation (ChIP) analysis demonstrated that SP7 directly binds to the heat shock protein 47 (HSP47) promoter and negatively regulates its transcription. Consequently, upregulation of SP7 following SELS knockdown led to downregulation of HSP47 and concurrent upregulation of the SP7 downstream targets, collagen type I alpha 1 chain (COL1A1) and Secreted protein acidic and rich in cysteine (SPARC). SELS expression is upregulated during active osteogenesis. Low expression of SELS regulates osteogenic differentiation in a bidirectional and fine-tuned manner through the SP7–HSP47/COL1A1/SPARC axis. Full article

Rheumatoid arthritis (RA) is an autoimmune disease affecting the synovium. Mitochondrial dysfunction is considered a critical factor in the pathogenesis of RA. The aim of the study was to determine the effect of methotrexate and tofacitinib on mitochondrial function and oxidative stress in an in vitro study on the model synovial cell line SW982. TNF-alpha-stimulated SW982 cells, as well as control untreated cells, were incubated with methotrexate and tofacitinib. A metabolic test was performed to assess mitochondrial function. The oxidative stress generated after the application of the therapeutics was determined by a chromatographic analysis. The results obtained showed an increase in ATP levels (p < 0.0001) and a decrease in proton leak (p < 0.0003) after treatment with tofacitinib. The opposite trend was observed—reduced ATP production (p < 0.0096) and increased levels of proton leak (p < 0.0001)—after treatment with methotrexate. A two-fold increase in 8-ISOPGF2A was measured in comparison to TNF-alpha-stimulated and untreated cells. The dynamics of mitochondrial activity and oxidative stress were monitored in a certified RA model cell line after the administration of two different therapeutics. Methotrexate was found to induce mitochondrial dysfunction and oxidative stress in vitro, while tofacitinib partially improved mitochondrial parameters. Full article

Background/Objectives: No Arabic-language version of the Observable Social Cognition Rating Scale (OSCARS) is available that allows to properly and specifically assess social cognition (SC) in Arabic-speaking populations. This study aimed to examine the preliminary psychometric characteristics of the Arabic translated version of the OSCARS, including factor structure, reliability, concurrent validity, and measurement invariance across sex. Methods: This cross-sectional study has been conducted during February and March 2024 and included 113 chronic, remitted, and clinically stable patients with schizophrenia. Results: The originally proposed two-factor model (Social Cognitive Bias and Social Cognitive Ability) showed acceptable model fit after removal of two items that yielded low factor loadings (items 2 and 3). Total and factor scores showed good internal consistency, with Cronbach’s alpha of 0.85–0.94. Measurement invariance was established across sex groups at the configural, metric, and scalar levels. No significant differences emerged between male and female patients for latent mean scores of the OSCARS. Finally, concurrent validity was supported by appropriate patterns of correlations with functioning, recovery, and emotional intelligence measures. Conclusions: The Arabic OSCARS stands out as a brief, valid, reliable, and comprehensive assessment tool to evaluate SC in Arabic-speaking patients with schizophrenia based on the perspectives of interviewers. Offering this measure to clinicians and researchers who work in Arab settings may close the existing gap in the assessment of SC in schizophrenia. Due to its easy and fast application, the Arabic OSCARS is believed to be highly valuable in clinical and research practices. Full article

Background/Objectives: Human milk provides essential nutrients and immune factors with beneficial impact on term, but especially preterm infants’ development. Therefore, this study focuses on the quantification of differences in the peptidome composition of breast milk from mothers of preterm and term infants, keeping in mind that this could reflect different biological needs of these infants or indicate nutritional gaps for healthy development. Methods: In a prospective observational study, breast milk samples were collected from 10 mothers of preterm infants (29–36 weeks gestational age,) and 13 mothers of term infants (37–41 weeks) at day 4 to 6 postnatally. A non-targeted tandem mass spectrometry approach was employed to analyze the milk peptidome. Results: In total, 4570 peptides were quantified. Adjusting the results for maternal age, weight, and height revealed a significant difference for 130 peptides derived from 19 different proteins between preterm and term milk. Proteins comprised high abundant proteins (e.g., α_S1-casein, κ- casein, or ß-casein), but also proteins that are less prominent in milk but of high functional importance (e.g., Hypoxia-inducible factor 1-alpha, Olfactory receptor 4M1). The differentially abundant peptides included peptides derived from ß-casein, which have already been described as being involved in antimicrobial functions as well as proliferation stimulating. For another 32 peptides, bioactivity was predicted. Conclusions: The current study provides a comprehensive overview on the differences in the milk peptidome at different gestational ages independent from common maternal phenotypes and improved the database for future peptide functionality studies. Full article

Background: The treatment landscape for advanced hepatocellular carcinoma (HCC) has evolved significantly recently; however, access to novel agents remains limited because of high costs. This study aimed to evaluate the systemic treatment patterns and survival outcomes for advanced HCC across different systemic treatment sequences under real-world resource constraints. Methods: This retrospective study was conducted at a tertiary center in Southern Thailand. The medical records of patients (n = 330) with advanced HCC treated with systemic therapy between 2010 and 2024 were reviewed. Outcomes included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Prognostic factors for OS were investigated. Results: First-line therapies included tyrosine kinase inhibitor (TKI; 69.7%), chemotherapy (23.3%), immunotherapy (IO)/targeted therapy (3.6%), dual IO (1.8%), and IO monotherapy (1.5%). The median OS, PFS, and ORR for each cohort were 7.2, 5.2, 10.9, 8.5, and 8.6 months; 3.94, 3.22, 3.48, 6.19, and 2.69 months; and 9.6%, 10.4%, 16.7%, 0%, and 20.0%, respectively. OS improved with increasing lines of therapy (4.5, 12.2, 19.4, and 40.7 months for one to four lines, respectively). Portal vein tumor thrombus, ascites, elevated bilirubin level, high alpha-fetoprotein level, and poor Eastern Cooperative Oncology Group performance status were associated with poor prognosis; multiple treatment lines and overweight status were associated with improved OS. Conclusions: In this large real-world cohort, TKIs remained the mainstay effective treatment option because of limited access to IO-based regimens. Sequential systemic therapy significantly improved survival, emphasizing the importance of preserving treatment eligibility and multidisciplinary team involvement. Chemotherapy could be considered a viable option in resource-limited settings. Full article

Background: Edentulism, or toothlessness, is a significant public health issue with profound implications for physical and systemic health, especially during pregnancy, when hormonal and behavioral changes increase the risk of oral diseases. Indigenous populations are particularly vulnerable due to socioeconomic and cultural factors that limit access to dental care. Methods: This pilot study assessed the oral microbiota of nine women, both pregnant and non-pregnant, aged 18–35 from the Salasaca indigenous community in Ecuador, using 16S rRNA gene sequencing. Samples were collected from dentin, saliva, and oral mucosa, and analyzed for alpha and beta diversity levels, taxonomic composition, and ecological metrics using the DADA2 pipeline and a canonical correspondence analysis. Results: Pregnant participants exhibited significantly lower microbial diversity compared to non-pregnant individuals, with notable differences in species richness and community structure. Dominant phyla included Bacillota, Bacteroidota, and Pseudomonadota. Prevotella sp., Neisseria sp., and Haemophilus sp. were among the prevalent genera, with the canonical correspondence analysis highlighting associations between microbial profiles and variables such as gestational status, marital status, and BMI. Conclusion: The findings suggest that pregnancy influences the oral microbiota composition, potentially predisposing women to dysbiosis and dental pathology. This study highlights the need for targeted oral health strategies during pregnancy and serves as a foundation for larger studies in underserved indigenous populations. Full article

The bidirectional relationship between epilepsy and depression illustrates shared neurobiological mechanisms of neuroinflammation, hypothalamic–pituitary–adrenal axis dysregulation, and glutamatergic dysfunction. Depression is present in 20–55% of people with epilepsy, far greater than in the general population, while depression doubles epilepsy risk 2.5-fold, indicating shared pathophysiology. Neuroinflammatory mediators (interleukin-6, tumor necrosis factor alpha, high-mobility group box 1) establish a vicious cycle: seizures exacerbate inflammation and mood disruption, and stress lowers seizure thresholds. Hippocampal damage and cortisol toxicity also link these disorders, with early life stress imprinting lifelong risk via epigenetic alteration. Genetic studies identify pleiotropic genes (brain-derived neurotrophic factor) that regulate synaptic plasticity, serotonin activity, and immune responses. New treatments target shared pathways: ketamine and AMPAkines normalize glutamate tone; mGluR5 antagonists attenuate hyperexcitability and inflammation; DNA methyltransferase inhibitors reverse aberrant DNA methylation; and probiotics manipulate the gut–brain axis by boosting neuroprotective metabolites like butyrate. Despite challenges—transient effects, precision dosing, and blood–brain barrier penetration—these advances constitute a paradigm shift toward mechanistic repair rather than symptom management. The way forward includes clustered regularly interspaced short palindromic repeats (CRISPR)-based epigenome editing, biomarker-led therapies, and combination approaches (e.g., ketamine and probiotics). Such comorbidity needs to be managed holistically through integrated neuropsychiatry care, offering hope to patients with treatment-refractory symptoms. Full article

Glaesserella parasuis (GPS) is a Gram-negative, pathogenic bacterium that colonizes the upper respiratory tract of piglets and causes Glässer’s disease with peritonitis under stress conditions. The mechanism underlying GPS-induced peritonitis in piglets remains unclear. Baicalin is one of the main active ingredients of Huangqin (Scutellaria baicalensis), which has a significant anti-inflammatory effect on inflammatory diseases. Therefore, this study aimed to elucidate the molecular mechanism by which baicalin alleviates GPS-induced peritonitis in piglets, specifically focusing on the role of the ADAM17/EGFR signaling axis. We investigated the effects of baicalin in vitro using porcine peritoneal mesothelial cells (PPMCs) and in vivo in GPS-infected piglets. Our results showed that baicalin reduced the expression of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) in PPMCs and the peritoneum of piglets after GPS infection. Concurrently, baicalin significantly reduced the upregulation of disintegrin and metalloproteinase 17 (ADAM17), phosphorylated epidermal growth factor receptor (p-EGFR)/EGFR, and phosphorylated extracellular signal-regulated kinase (p-ERK)/ERK induced by GPS infection in PPMCs and the peritoneum of piglets. Crucially, in vitro mechanistic investigations revealed that baicalin can significantly reduce the upregulation of ADAM17, p-EGFR/EGFR, p-ERK/ERK, TNF-α, IL-1β, and IL-6 induced by ADAM17 overexpression in PPMCs. Furthermore, ADAM17 small interfering RNA can significantly reduce the upregulation of ADAM17, p-EGFR/EGFR, p-ERK/ERK, TNF-α, IL-1β, and IL-6 induced by GPS infection in PPMCs. These findings demonstrate that baicalin can inhibit the expression of inflammatory factors TNF-α, IL-1β, and IL-6 through the ADAM17/EGFR axis, and then alleviate the peritonitis caused by GPS in piglets. This provides a theoretical basis for developing novel non-antibiotic strategies, including phytochemical therapeutics and feed additives, for preventing and controlling GPS. Full article