Search Results (263)

Background: Opioid use during pregnancy is linked to preterm birth, fetal growth restriction, and Neonatal Opioid Withdrawal Syndrome. While the placenta is the primary regulator of the uterine environment, the precise molecular mechanisms by which opioids dismantle placental function remain poorly defined. Methods: The transcriptomic landscape of opioid-exposed human placentas from a unique Hawai’i-based cohort was characterized. Results: Transcriptional signatures were defined by genes involved in translational inhibition and metabolic attenuation. Integrative network modeling predicted a prominent stress-signaling hub centered on p38 Mitogen-Activated Protein Kinase and Extracellular Signal-Related Kinase 1/2, paralleling a broad suppression of ribosomal protein transcripts (Ribosomal Protein 27S, -29, and -39). This response was further characterized by the inhibition of the Myelecytomatosis Proto-Oncogene regulatory hub, predicting a loss of mitochondrial phosphate transport through associated genes (via Solute Carrier Family 25A3) and cell-cycle progression (via S-Phase Kinase-Associated Protein 1). Additionally, the genes in this model suggested upregulation of antisense regulatory brakes, such as RAP2C Antisense RNA 1, which might further reinforce this inhibitory state. Conclusion: The findings suggest that prenatal opioid exposure is associated with the disruption of placental homeostasis. This may be coordinated by protein synthesis and bioenergetic flux, as inferred from the modeled eukaryotic Translation Initiation Factor-mediated Integrated Stress Response. These findings establish a localized, clinical baseline of human placental stress, highlighting candidate molecular regulatory nodes to guide future mechanistic studies and biomarker discovery in exposed pregnancies. Full article

Cardiomyopathies are a major category of cardiovascular disease, significantly contributing to global morbidity and mortality. Their pathogenesis involves a complex interplay of genetic and environmental factors, with multiple gene families playing critical roles in disease progression. Among these, the Solute Carrier 12A (SLC12A) family encodes membrane cation-coupled chloride cotransporters (CCCs), which are essential for ion transport and cellular homeostasis. By regulating intracellular chloride and potassium concentrations, SLC12A/CCC transporters may directly influence myocardial electrophysiology, repolarization dynamics, and susceptibility to cardiomyopathies. Dysfunction of potassium-handling cotransporters can disrupt action potential propagation, increasing the risk of arrhythmias, while chloride transport abnormalities exacerbate ischemic injury by impairing cell volume regulation and metabolic responses to hypoxia. This review examines the expression and protein levels of SLC12A/CCCs in cardiac tissue, providing crucial insights into their functional significance for maintaining cardiac ion homeostasis. Understanding the regulatory mechanisms of these transporters could inform therapeutic interventions to restore ion balance and mitigate myocardial dysfunction in affected patients, thereby improving cardiac health. Full article

Enterotoxigenic Escherichia coli K88 (ETEC-K88) is a primary causative agent of post-weaning diarrhea in piglets, yet most in vitro infection models evaluate epithelial injury at a limited number of endpoint time points, failing to capture the temporal dynamics of host–pathogen interactions. Here, we established a time-resolved ETEC-K88 challenge model in IPEC-J2 cells from 0 h to 48 h. The data showed that ETEC-K88 adhesion significantly increased after 4 h and peaked after 24 h, with a critical response transition at 4–8 h characterized by coordinated changes in mRNA expression of tryptophan metabolism, tight junction, aquaporins, and Solute Carrier Transporters (SLC). Additionally, we also evaluated the protective effects of L-tryptophan supplementation in IPEC-J2 with ETEC-K88 infection and found that its addition significantly restored the disrupted gene expression related to tryptophan metabolism, transporter channels, aquaporins, and cell cycle. Finally, two different mouse strains, C57BL/6J and BALB/c mice, were challenged with ETEC-K88 to assess strain- and segment-specific intestinal responses. Although overt diarrhea was not clearly induced in mice, the ETEC-K88 fimbria receptor genes were induced in both mice strains. Additionally, both mice strains exhibited obvious intestinal histomorphological abnormalities and showed the strain- and segment-specific expression of intestinal stem cell marker genes (Lgr5, SOX9), goblet cell marker gene TFF3, and aquaporin genes. In conclusion, we have defined a temporal epithelial response framework for ETEC-K88 infection in IPEC-J2 cells and mice, providing a theoretical basis for developing nutritional strategies against ETEC-associated intestinal dysfunction in pig production. Full article

Elevated ammonia nitrogen significantly reduces the survival rate of Litopenaeus vannamei under low-salinity conditions. Low-salinity culture is widely adopted in shrimp farming but susceptible to ammonia accumulation; however, relevant studies mainly focus on juvenile shrimp under single stress or normal salinity. With the aim of exploring how L. vannamei responds physiologically and molecularly to elevated ammonia nitrogen after low-salinity adaptation, shrimp were gradually acclimated to 5‰ salinity. They were reared at 5‰ for one week before being exposed to high levels of ammonia nitrogen for 96 h. Under these conditions, the shrimp’s hepatopancreas showed antioxidant imbalance and oxidative damage. Elevated blood ammonia, urea nitrogen and uric acid reflected activated synthesis pathways that clear excess ammonia. Transcriptomic and metabolomic profiling at 12, 48, and 96 h revealed 112 DEGs and pronounced alterations in lipids and amino acid derivatives. Integrated gene-metabolite correlation analysis uncovered three core pathways, along with 11 key DEGs and 17 associated metabolites. In the secretion pathway, solute carrier family 4 (anion exchanger),member 2 (slc4a3) was strongly correlated with saquinavir and carnitine. In the metabolism pathway, nicotinamide/nicotinate riboside kinase (nmrk1), chitinase (chia), Gamma-glutamyltranspeptidase (ggt1), UDP-glucose 4-epimerase (gale), and spermine oxidase (smox) were linked to L-pyroglutamic acid, betaine, etc. In the immune pathway, mitogen-activated protein kinase 8/9/10 (bsk) and integrin beta 1 (cd29) were associated with leukotriene E4 and niacin. This study reveals that ammonia stress after low-salinity acclimation induces oxidative stress damage, elevated physiological changes in L. vannamei, and further elucidates the regulatory pathways underlying its response to ammonia nitrogen stress. Full article

Background: The solute carrier family 22 member 23 (Slc22a23), a gene encoding a membrane-orphan transporter, is irreversibly upregulated in the brains of rats following fetal undernutrition. Materials and Method: To identify potential substrates of the SLC22A23 transporter, we analyzed the plasma of both Slc22a23-proficient and deficient rats. Results: We found that the level of lysophosphatidylcholine a C20:4 (LPC(20:4)) in plasma was more than twofold lower in the Slc22a23^−/− rats than in the Slc22a23^+/+ rats. We then conducted a series of animal behavioral tests on Slc22a23-proficient (Slc22a23^+/+) and deficient (Slc22a23^−/−) rats to investigate the effects of LPC(20:4) administration. We observed considerable effects in both Slc22a23^+/+ and Slc22a23^−/− rats, with more pronounced effects in the Slc22a23^+/+ rats. These effects included reductions in total distance travelled in an open field test, reductions in access to the novel objects in a novel object recognition test, reductions in sociability to a familiar rat in a social interaction test, and shorter latencies to the target in the Morris water maze test. Discussion: These findings suggest that LPC(20:4) administration enhances memory acquisition in both Slc22a23^+/+ and Slc22a23^−/− rats, though it appears to be more effective in the Slc22a23^+/+ rats. While the SLC22A23 transporter is likely involved in facilitating the transport of LPC(20:4), other transporters may also play a role in its transport in vivo. Full article

Conventional vaccine adjuvants often lack cell-type specificity and readily trigger excessive systemic inflammation, limiting their clinical application. Immunometabolic signaling centered on the ARF6 (ADP-ribosylation factor 6)-SUCNR1 (Succinate receptor 1) axis governs neutrophil recruitment and subsequent B-cell activation at vaccination sites, offering a promising target to balance adjuvant potency and biosafety. Separately published single-gene data confirm two opposing functions for the two mediators: ARF6 overactivation amplifies local pathological inflammation, whereas succinate-stimulated SUCNR1 drives neutrophil infiltration and humoral immune priming. However, direct paired evidence verifying their bidirectional crosstalk within immunization microenvironments remains limited. This review systematically integrates current research on ARF6 and SUCNR1 immunometabolism to outline a hypothetical dual-regulatory adjuvant strategy: local, transient partial silencing of pathological ARF6 activity via ARF6-targeted ASOs (antisense oligonucleotides) paired with localized succinate delivery to sustain protective SUCNR1 signaling. We summarize the molecular basis of this “one inhibition, one activation” paradigm, alongside ASO chemical modification, myeloid-targeted design, and nanocarrier delivery solutions that resolve the unique ARF6 endocytosis paradox. We further dissect unresolved translational risks, including concentration-dependent succinate inflammatory effects, carrier immunogenicity, and potential impairment of baseline neutrophil migration upon ARF6 suppression. Overall, this work synthesizes fragmented mechanistic data to construct a testable neutrophil-centered adjuvant framework, and highlights outstanding technical and biosafety hurdles that require dedicated preclinical validation to support future adjuvant development. Full article

Identifying physiological changes during the transition period is essential for improving the health and productivity of dairy goats. This study evaluated hematological, biochemical, hormonal, oxidative stress, and molecular alterations in Shami goats during the pre-pregnancy, late pregnancy, and early lactation periods. Eighty clinically healthy goats were examined, and blood samples were analyzed for hematological indices, metabolic and hormonal profiles, oxidative stress biomarkers, and relative expression of genes associated with energy metabolism, antioxidant defense, inflammation, and autophagy. Late pregnancy was characterized by significant (p < 0.05) increases in red blood cell count (RBCs), hemoglobin concentration (Hb), neutrophils, albumin, globulin, urea, insulin-like growth factor-1 (IGF-I), and malondialdehyde (MDA), accompanied by decreased glucose, cholesterol, total protein (TP), antioxidant markers, total leukocyte count, packed cell volume, and monocytes. Early lactation was associated with higher non-esterified fatty acid, triiodothyronine (T3), and thyroxine (T4) levels. Genes involved in lipid mobilization and oxidation, ketogenesis, inflammation, cellular stress, and autophagy; sirtuin 1 (SIRT1), peroxisome proliferator-activated receptor alpha (PPARA), carnitine palmitoyltransferase 1a (CPT1A), 3-hydroxy-3-methylglutaryl-coenzyme a synthase 2 (HMGCS2), cluster of differentiation 36 (CD36), lipase E (LIPE), protein kinase amp-activated catalytic subunit alpha 1 (PRKAA1), solute carrier family 2 member 1 (SLC2A1), haptoglobin (HP), interleukin 6 (IL6), heat shock protein 70 (HSP70), heme oxygenase 1 (HMOX1), beclin 1 (BECN1), and autophagy-related protein 5 (ATG5) were significantly upregulated, whereas antioxidant- and glucose transport-related genes nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase 1 (GPX1), catalase (CAT), thioredoxin (TXN), and solute carrier family 2 member 4 (SLC2A4) were downregulated during the transition period. The results indicate well-orchestrated metabolic and molecular adaptations that can be employed as biological indicators to track the physiological status of Shami goats. These findings fulfilled the study objective and identified potential biomarkers of the transition period in Shami goats. Full article

SLC25A4, solute carrier family 25 member 4, gene is a member of the mitochondrial carrier subfamily within the solute carrier protein family. Pathogenic variants in SLC25A4 are associated with a spectrum of mitochondrial disorders that exhibit variable inheritance patterns and clinical manifestations. Specifically, dominantly inherited variants are typically associated with progressive external ophthalmoplegia with mitochondrial DNA deletions, recessively inherited variants are linked to myopathy and cardiomyopathy, and de novo variants can result in early-onset fatal disease presentations. In this study, we aimed to identify and characterize the disease-causing mutation(s) in a nine-year-old female patient from a consanguineous Saudi family. The patient was asymptomatic until the age of 3 years, when she presented with cardiomyopathy and myopathy. Comprehensive genetic analysis inclusive of whole exome sequencing and segregation analysis using Sanger sequencing identified an SLC25A4 variant (NM_001151.4: exon 2: c.112-1G>C) as the most likely cause of the disease. To assess transcript-level effects, we performed RT-PCR on RNA extracted from the patient’s cultured lymphoblast cell lines (LCLs) and fibroblast cell lines (FCLs). RT-PCR analysis demonstrated that the variant causes aberrant splicing, resulting in a 6 bp in-frame deletion (p.Gln37_Val38del) in the ANT1 protein. Quantitative RT-PCR demonstrated reduced SLC25A4 transcript levels in both FCLs and LCLs. Quantitative PCR analysis of mitochondrial DNA demonstrated a trend toward increased mtDNA copy number in patient-derived FCLs compared with controls, suggesting a possible compensatory response to mitochondrial dysfunction. Furthermore, Seahorse assays revealed marked reductions in both oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) in patient-derived FCLs compared with controls. These findings expand the molecular and functional spectrum of SLC25A4-associated disease and may inform clinical practice, including genetic interventions such as preimplantation genetic diagnosis, premarital genetic screening, targeted genetic counseling, and cascade testing of at-risk family members. Full article

Rs9939609 marker in FTO Alpha-Ketoglutarate-Dependent Dioxygenase (FTO) gene, rs7895307 in Transcription Factor 7-Like 2 (TCF7L2) gene, and rs75493593 in Solute Carrier Family 16 Member 11 (SLC16A11) gene have been associated with anthropometric, metabolic, and clinical variables, but have not been concurrently studied in Mexican children and adolescents with adiposity or mental disorders. In this cross-sectional association study, we genotyped these markers by means of TaqMan real-time polymerase chain reaction in two at-risk pediatric cohorts recruited in Mexico City. Group 1 (n = 175) comprised children and adolescents with overweight/obesity. Group 2 (n = 296) consisted of non-medicated adolescents meeting the Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria for Attention Deficit/Hyperactivity Disorder or a mood disorder. Anthropometric measurements (body mass index —BMI—, waist circumference, body fat percentage), metabolic indices (fasting glucose, lipid profile, Homeostatic Model Assessment for Insulin Resistance), and psychiatric diagnoses were evaluated. In Group 1, the FTO A allele (genotypes AA/AT) was significantly associated with severe obesity according to BMI Z scores (p = 0.004, O.R. 3.33, 95% CI [1.42–7.77]), and it was a predictor of waist circumference (B = 6.16, 95% CI [1.78–10.55], p = 0.006) and muscle percentage (B = 4.21%, 95% CI [0.91–7.51%], p = 0.013) using linear regression models adjusted for age and sex. In Group 2, TCF7L2 AA genotype was associated with increased odds of depression (B = 0.83, p = 0.003, OR = 2.29, 95% CI [1.32–3.96]). While SLC16A11 G allele showed a possible association with insulin resistance or glucose levels, confirmation is needed. These exploratory results highlight the need for larger, well characterized cohort studies to confirm the associations. Full article

High-glucose exposure impairs intestinal metabolic homeostasis and barrier integrity in fish, but the transcriptional responses associated with high-glucose adaptation in fish intestinal epithelial cells remain incompletely understood. This study investigated whether exogenous 5-methylcytosine (5MC) alleviates high-glucose-induced metabolic and epithelial stress in grass carp (Ctenopharyngodon Idella) intestinal epithelial cells and whether these responses are associated with changes in DNA methyltransferase 3 beta (dnmt3b) expression and Caudal type homeobox 1b (cdx1b)/Sodium-glucose cotransporter 1 (sglt1)-related transcriptional responses. As exploratory in silico information, molecular docking predicted candidate complex conformations of DNMT3B with CDX1B and SGLT1, with binding energies of −37.2 and −25.9 kcal/mol, respectively. Functionally, dnmt3b knockdown significantly reduced dnmt3b, Interleukin 6 (il6), and Nuclear factor kappa B (nfκb) expression, while increasing cdx1b, sglt1, Solute carrier family 2 member 3a (slc2a3a), 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4a (pfkfb4a), and Amine oxidase copper containing 1 (aoc1) expression (p < 0.05). CDX2/CDX1B-like immunoreactive protein and SGLT1 protein levels were also increased after dnmt3b knockdown (p < 0.05). Under high-glucose stress, exogenous 5MC exerted concentration-dependent effects. Specifically, 6 mM 5MC significantly reduced residual extracellular glucose, lactate dehydrogenase and diamine oxidase activities, and malondialdehyde content, while increasing glutathione content, cell viability, and cell migration (p < 0.05). These effects remained detectable after replacement with high-glucose medium for an additional 12 h. By contrast, 24 mM 5MC markedly increased lactate dehydrogenase activity and reduced cell viability, suggesting potential cytotoxicity (p < 0.05). S-adenosylmethionine (SAM) levels were significantly lower in the NC and 6 mM groups than in the HG, 12 mM, and 24 mM groups, suggesting changes in SAM-related one-carbon metabolic status rather than direct evidence of altered DNA methylation (p < 0.05). Exogenous 5MC, particularly at 6 mM, alleviated high-glucose-induced metabolic and epithelial stress in grass carp intestinal epithelial cells. These effects were accompanied by changes in several glucose metabolism- and inflammation-related genes. However, the cellular uptake, metabolic fate, DNA incorporation, methylation consequences, and causal roles of these gene-expression changes remain to be further verified. Full article

Neurodegenerative diseases are increasingly recognized as disorders of due to disrupted cellular homeostasis, with mitochondrial dysfunction playing a central and early role in disease progression. This review explores the intricate relationship between mitochondrial function and neuronal health, emphasizing the pivotal role of the solute carrier family 25 (SLC25) transporters in maintaining mitochondrial homeostasis. We provide a comprehensive overview of mitochondrial biology in the central nervous system, including energy metabolism, calcium signaling, redox regulation, organelle interactions and mitochondrial dynamics. We delve into the SLC25 transporter family, highlighting their transport mechanisms, substrates and roles in brain metabolism and neuroprotection. SLC25 on one hand and proteins involved in the regulation of mitochondrial morphology and calcium signaling on the other hand are two sides of the same coin influencing each other. A critical analysis follows, examining how mitochondrial dysfunction contributes to mitochondrial abnormalities in a spectrum of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, ALS and rare mitochondrial encephalopathies. Finally, we assess emerging therapeutic strategies targeting mitochondrial pathways and SLC25 function, including metabolic modulation, gene therapies, antioxidants and pharmacological agents. This review underscores mitochondria and the SLC25 transporters as promising targets for disease-modifying interventions in neurodegeneration and raises key questions about the causality between mitochondrial failure and neuronal death. Full article

Background/Objectives: The gene solute carrier family 52 member 3 (SLC52A3) encodes riboflavin transporter-3, a transmembrane protein essential for riboflavin absorption. Emerging evidence suggests that metabolic transporters may play a role in tumor biology. This study aimed to investigate the expression patterns, prognostic significance, genetic alterations, and functional associations of SLC52A3 in gynecological cancers. Methods: A comprehensive bioinformatic analysis was conducted using multi-omics datasets from The Cancer Genome Atlas (TCGA). Gene expression and survival analyses were performed via GEPIA3. Genetic alterations, including mutations and copy number variations, were assessed using cBioPortal. Immune infiltration correlations were analyzed through TIMER3. Protein–protein interactions and gene enrichment analyses were performed using STRING and GEPIA2, followed by Gene Ontology (GO) and KEGG pathway analyses. Results: SLC52A3 expression was significantly upregulated in ovarian, cervical, and endometrial cancers. Reduced expression of SLC52A3 was associated with poorer overall survival and shorter progression-free interval specifically in endometrial cancer. Genetic alterations in SLC52A3 were not significantly associated with survival outcomes (OS, DFS, and PFS). Functional enrichment analysis indicated that SLC52A3 is involved in biological processes such as cell junction organization and protein localization to the plasma membrane. Additionally, SLC52A3 expression showed positive correlations with genes implicated in tumor progression and metastasis, including NECTIN4, PROM2, TACSTD2, PKP3, SEMA4B, and CD46. Conclusions: These findings suggest that SLC52A3 may serve as a potential prognostic biomarker in endometrial cancer and could play a role in tumor progression pathways. Its functional associations highlight its potential relevance as a therapeutic target, warranting further experimental validation. Full article

Epidemiological and biological evidence indicate a close connection between Alzheimer’s disease (AD) and type-2 diabetes mellitus. Glucose transporter 1 (GLUT1), encoded by the SLC2A1 gene, has a major role in glucose metabolism, the dysregulation of which has been implicated in both diseases. We conducted a case-control association study in a sample of 439 non-diabetic patients with late-onset AD and 304 cognitively healthy, non-diabetic elderly controls to determine the potential risk for developing AD associated with SLC2A1 rs841847 polymorphism. The rs841847 C/C genotype occurrence was higher in the AD group (AD: 60.4%, controls: 50.7%), while the minor T allele-containing genotypes were more frequent among controls (AD: 39.6%, controls: 49.3%). A multivariate logistic regression model adjusted for age, sex, and apolipoprotein E (APOE) ε4 status (ε4 allele carriers versus non-carriers) demonstrated that carriers of the T allele had a significantly reduced risk for AD compared to C/C homozygotes (OR = 0.672; 95% CI: 0.493–0.916; p = 0.012). Although the rs841847 polymorphism has been linked to type-2 diabetes mellitus, the present study investigated this gene variant in AD for the first time. Our findings indicate a moderate protective effect for the rs841847 T allele on the susceptibility to AD. We demonstrated the rs841847 polymorphism as a candidate single nucleotide polymorphism for further examination as a predisposing genetic factor for AD. Full article

Background/Objectives: Calcium–phosphorus metabolism is critical for skeletal development in weaned piglets. This study evaluated the effects of dietary 25-hydroxyvitamin D₃ (25-OH-VD₃) in combination with phytase and probiotics on mineral metabolism, bone development, and related molecular mechanisms in weaned piglets. Methods: Sixty 28-day-old weaned piglets (7.1 ± 1.30 kg) were randomly assigned to four dietary treatments for 31 days (including 3 days of acclimation): CON (basal diet + 50 µg/kg 25-OH-VD₃), HI (CON + 50 mg/kg phytase), CY (CON +10 mg/kg probiotics), HICY (CON + 50 mg/kg phytase + 10 mg/kg probiotics). Apparent calcium digestibility, serum biochemical indices, bone mineral density (BMD), and mRNA and protein expression of calcium–phosphorus transport- and metabolism-related genes in jejunal mucosa and kidney were assessed. Results: Compared with CON, piglets in the HI, CY, and HICY groups showed higher apparent calcium digestibility (p < 0.05). Serum transforming growth factor-β was elevated in CY and HICY (p < 0.05). HI enhanced metatarsal and toe BMD (p < 0.05) and upregulated jejunal solute carrier family 34, member 2 (SLC34A2) and SLC34A3 mRNA expression (p < 0.05). In contrast, HICY reduced mRNA expression of transient receptor potential cation channel subfamily V member 6 and calcium-binding protein D28k, as well as of calcium-binding protein D9k and cytochrome P450 27B1 in the kidney (p < 0.05). Renal calcium-sensing receptor protein abundance increased in CY (p < 0.05). Conclusions: Supplementation of 25-OH-VD₃ with phytase and/or probiotics improved calcium utilization and modulated key transport pathways, contributing to enhanced bone development in weaned piglets. These findings highlight coordinated nutritional regulation of mineral metabolism during early post-weaning growth. Full article

Fish oil (FO) has been shown to confer beneficial effects on hepatic diseases in both humans and animals. This study aimed to investigate whether dietary fish oil (FO) supplementation alleviates deoxynivalenol (DON)-induced liver injury by modulating the ferroptosis signaling pathway in weaned piglets. Twenty-four weaned piglets were allocated to a 2 × 2 factorial design, with the main factors consisting of dietary treatment (5% corn oil or 5% FO supplementation) and DON exposure (basal diet or diet contaminated with 4 mg/kg DON). After 21 days of dietary treatment, piglets were euthanized for collection of blood and liver samples. Dietary FO significantly attenuated DON-induced hepatic structural damage and inflammatory infiltration. Specifically, FO supplementation reduced the activities of aspartate transaminase (AST) and alkaline phosphatase (ALP), as well as the AST/alanine aminotransferase (ALT) ratio following DON exposure. Dietary FO also decreased malondialdehyde (MDA) concentrations in both the liver and serum, lowered hepatic 4-hydroxynonenal (4-HNE) level and Fe²⁺ content, and increased hepatic glutathione (GSH) content. Moreover, dietary FO ameliorated ultrastructural liver damage induced by DON. Furthermore, DON significantly downregulated the mRNA levels of multiple genes associated with iron metabolism and ferroptosis, including heat shock protein beta-1 (HSPB1), acyl-CoA synthetase long chain family member 4 (ACSL4), and arachidonate 15-lipoxygenase (ALOX15), and upregulated the mRNA levels of transferrin (TF), ferritin heavy chain (FTH), solute carrier family 7 member 11 (SLC7A11), and transferrin receptor 1 (TFR1). Dietary FO counteracted these alterations by decreasing the mRNA of SLC7A11, TFR1, FTH, and TF after DON exposure. Finally, FO significantly decreased the protein expression of SLC7A11, iron-responsive element-binding protein 2 (IREB2), and FHT1 and increased the GPX4 protein expression following DON exposure. These findings suggest that FO may ameliorate DON-induced liver injury in weaned piglets, possibly through suppressing the ferroptosis signaling pathway. Full article