PubMed

J Exp Clin Cancer Res. 2025 Jan 17;44(1):17. doi: 10.1186/s13046-025-03280-3.ABSTRACTBACKGROUND: Glioblastoma (GBM) is a lethal brain tumor characterized by the glioma stem cell (GSC) niche. The V-ATPase proton pump has been described as a crucial factor in sustaining GSC viability and tumorigenicity. Here we studied how patients-derived GSCs rely on V-ATPase activity to sustain mitochondrial bioenergetics and cell growth.METHODS: V-ATPase activity in GSC cultures was modulated using Bafilomycin A1 (BafA1) and cell viability and metabolic traits were analyzed using live assays. The GBM patients-derived orthotopic xenografts were used as in vivo models of disease. Cell extracts, proximity-ligation assay and advanced microscopy was used to analyze subcellular presence of proteins. A metabolomic screening was performed using Biocrates p180 kit, whereas transcriptomic analysis was performed using Nanostring panels.RESULTS: Perturbation of V-ATPase activity reduces GSC growth in vitro and in vivo. In GSC there is a pool of V-ATPase that localize in mitochondria. At the functional level, V-ATPase inhibition in GSC induces ROS production, mitochondrial damage, while hindering mitochondrial oxidative phosphorylation and reducing protein synthesis. This metabolic rewiring is accompanied by a higher glycolytic rate and intracellular lactate accumulation, which is not exploited by GSCs for biosynthetic or survival purposes.CONCLUSIONS: V-ATPase activity in GSC is critical for mitochondrial metabolism and cell growth. Targeting V-ATPase activity may be a novel potential vulnerability for glioblastoma treatment.PMID:39825382 | DOI:10.1186/s13046-025-03280-3

BMC Vet Res. 2025 Jan 17;21(1):26. doi: 10.1186/s12917-024-04469-y.ABSTRACTBACKGROUND: The recently identified swine inflammation and necrosis syndrome (SINS) affects tail, ears, teats, coronary bands, claws and heels of affected individuals. The primarily endogenous syndrome is based on vasculitis, thrombosis, and intimal proliferation, involving defence cells, interleukins, chemokines, and acute phase proteins and accompanied by alterations in clinical chemistry, metabolome, and liver transcriptome. The complexity of metabolic alterations and the influence of the boar led to hypothesize a polygenic architecture of SINS. This should be investigated by a transcriptome study. For this purpose, the three to five least affected (SINS-low) and most SINS affected (SINS-high) 3d-old piglets, each of three boars, a relatively SINS stable Duroc boar (DU), a relatively stable Pietrain boar (PI+) and a highly susceptible Pietrain boar (PI-) were selected from 27 litters of mixed semen to minimize environmental effects.RESULTS: A genome-wide expression experiment revealed a huge set of differentially expressed genes that are involved in vasculitis, inflammation and necrosis, keratinization and erythrocyte epitopes. Among them were CRP, GYPA, S100A12, and LIPK. The results confirm and complement previous studies to this topic.CONCLUSIONS: The results confirm the outstanding importance of defence in the context of SINS. At the same time, for the first time, there is evidence for a direct involvement of the keratinisation capacity of the skin and various epitopes of the erythrocyte membrane, which seem to be associated with the severity of SINS. These genes could serve to clarify the pathogenesis of the syndrome and to develop diagnostic tools in future studies.PMID:39825377 | DOI:10.1186/s12917-024-04469-y

BMC Plant Biol. 2025 Jan 18;25(1):72. doi: 10.1186/s12870-025-06101-z.ABSTRACTFlowering is a critical step in the plant life cycle. Angelica sinensis (Oliv.) Diels is a medicinal crop whose root is a well-known herbal medicine used in Asia. Early flowering causes changes in secondary metabolic flow and results in the loss of medicinal quality. Based on untargeted metabolomics studies, quinic acid was identified as a metabolite present in significantly higher concentrations during the early-flowering stage in A. sinensis leaves. This metabolite was subsequently investigated as a potential marker for early bolting in A. sinensis under field conditions. Moreover, quinic acid was found to accelerate flowering in the model plant Arabidopsis thaliana. Importantly, the flowering time was delayed in the quinate dehydrogenase At mutant, and this delay was reversed by quinic acid. Quinic acid upregulated the expression of the GA20OX and GID1 receptors and downregulated the expression of the inhibitor DELLA, thereby affecting the levels of FT and LFY and accelerating plant flowering. Quinic acid also significantly changed the expression of genes such as LOX, JAZ1, MYC2 and MYC3 in the jasmonic acid pathway. The trends of GID1, DELLA (GAI) and LOX2 protein expression were essentially consistent with those at the transcription level. These results suggest that quinic acid may promote plant flowering primarily by regulating the expression of genes and proteins in the gibberellin and jasmonic acid pathways.PMID:39825217 | DOI:10.1186/s12870-025-06101-z

Nat Cancer. 2025 Jan 17. doi: 10.1038/s43018-024-00874-2. Online ahead of print.NO ABSTRACTPMID:39824998 | DOI:10.1038/s43018-024-00874-2

Nat Struct Mol Biol. 2025 Jan 17. doi: 10.1038/s41594-024-01470-9. Online ahead of print.ABSTRACTCholesterol plays a pivotal role in modulating the activity of mechanistic target of rapamycin complex 1 (mTOR1), thereby regulating cell growth and metabolic homeostasis. LYCHOS, a lysosome-localized G-protein-coupled receptor-like protein, emerges as a cholesterol sensor and is capable of transducing the cholesterol signal to affect the mTORC1 function. However, the precise mechanism by which LYCHOS recognizes cholesterol remains unknown. Here, using cryo-electron microscopy, we determined the three-dimensional structural architecture of LYCHOS in complex with cholesterol molecules, revealing a unique arrangement of two sequential structural domains. Through a comprehensive analysis of this structure, we elucidated the specific structural features of these two domains and their collaborative role in the process of cholesterol recognition by LYCHOS.PMID:39824976 | DOI:10.1038/s41594-024-01470-9

Pediatr Res. 2025 Jan 17. doi: 10.1038/s41390-025-03844-1. Online ahead of print.ABSTRACTBACKGROUND: This study examines the influence of prematurity and diabetes (DM) in pregnancy on metabolite patterns at birth, and associations with adiposity development in a prospective cohort.METHODS: Term and preterm (30-36 weeks gestational age [GA]) infants were enrolled and body composition assessments completed through discharge. Targeted metabolomics was used to assess metabolites in cord or infant blood in the first 2 days.RESULTS: Among 91 infants, 62 were preterm and 27 were exposed to DM. In factor analysis, variation in acylcarnitines' and non-essential amino acids differed by GA and DM exposure and were associated with adiposity at term age. DM-group had 1.95-fold increase in t4-OH-pro (p = 0.003) and 2.14-fold increase in taurine (p = 0.004) compared with non-DM group. Preterm infants had 1.77-fold increase in glycerophospholipid PC aa C32:2 versus term group (p < 0.001). Pathway analysis revealed differences across DM and GA groups in pathways associated with citrulline metabolism, amino acid transport/ synthesis, and fatty acid quantity/transport.CONCLUSION: In this cohort of infants, there are unique metabolite signatures associated with DM exposure, prematurity, and adiposity development after birth. These markers may reflect early metabolism changes in the developing infant which relate to known risks of adverse growth and cardiometabolic outcomes in this group.IMPACT: In this study of term and preterm infants, diabetes in pregnancy was associated with unique metabolic signatures at birth, including increased expression of metabolites related to protein synthesis and lipid metabolism. Metabolites related to lipid and protein metabolism were associated with adiposity development at term age, including estimated body fat percent, skin fold thickness measures, and arm circumference measures. Unique signatures of metabolites associated with prematurity and exposure to diabetes in pregnancy may reflect early metabolism changes in the developing infant which relate to known risks of adverse growth and cardiometabolic outcomes in this group.PMID:39824937 | DOI:10.1038/s41390-025-03844-1

Sci Rep. 2025 Jan 17;15(1):2299. doi: 10.1038/s41598-025-86030-x.ABSTRACTChronic kidney disease (CKD) is a global health challenge associated with lifestyle factors such as diet, alcohol, BMI, smoking, sleep, and physical activity. Metabolomics, especially nuclear magnetic resonance(NMR), offers insights into metabolic profiles' role in diseases, but more research is needed on its connection to CKD and lifestyle factors. Therefore, we utilized the latest metabolomics data from the UK Biobank to explore the relationship between plasma metabolites and lifestyle factors, as well as to investigate the associations between various factors, including lifestyle-related metabolites, and the latent phase of CKD onset. The study enrolled approximately 500,000 participants from the UK Biobank (UKB) between 2006 and 2010, excluding 447,163 individuals with missing data for any metabolite in the NMR metabolomics, any biomarker in the blood chemistry (including eGFR, albumin, or cystatin C), any factor required for constructing the lifestyle score, or a baseline diagnosis of CKD. Lifestyle scores (LS) were calculated based on several factors, including diet, alcohol consumption, smoking, BMI, physical activity, and sleep. Each healthy lifestyle component contributed to the overall score, which ranged from 0 to 6. A total of 249 biological metabolites covering multiple categories were determined by the NMR Metabolomics Platform. Random forest algorithms and LASSO regression were employed to identify lifestyle-related metabolites. Subsequently, accelerated failure time models(AFT) were used to assess the relationship between multiple factors, including traditional CKD-related biomarkers (such as eGFR, cystatin C, and albumin) and lifestyle-related metabolites, with the latent phase of incident CKD. Finally, we performed Kaplan-Meier survival curve analysis on the significant variables identified in the AFT model. Over a mean follow-up period of 13.86 years, 2,279 incident chronic kidney disease (CKD) cases were diagnosed. Among the 249 metabolites analyzed, 15 were identified as lifestyle-related, primarily lipid metabolites. Notably, among these metabolites, each 1 mmol/L increase in triglycerides in large LDL particles accelerated the onset of CKD by 24%. Diabetes, hypertension, and smoking were associated with a 56.6%, 31.5% and 22.3% faster onset of CKD, respectively. Additionally, each unit increase in age, BMI, TDI, and cystatin C was linked to a 3.2%, 1.4%, 1.6% and 32.3% faster onset of CKD. In contrast, higher levels of albumin and eGFR slowed the onset of CKD, reducing the speed of progression by 3.0% and 3.9% per unit increase, respectively. Nuclear magnetic resonance metabolomics offers new insights into renal health, though further validation studies are needed in the future.PMID:39824917 | DOI:10.1038/s41598-025-86030-x

Sci Rep. 2025 Jan 17;15(1):2238. doi: 10.1038/s41598-025-86044-5.ABSTRACTThe present study was aimed at revealing the metabolic changes that occurred in the cellular lipid pattern of acute and chronic myeloid leukaemia cells following treatment with cannabidiol (CBD). CBD is a non-psychoactive compound present in Cannabis sativa L., which has shown an antiproliferative action in these type of cancer cells. CBD treatment reduced cell viability and initiated apoptotic and necrotic processes in both cancer cell lines in a time and dose-dependent manner, showing acute myeloid leukaemia (HL-60) cells greater sensitivity than chronic myeloid leukaemia ones (K-562), without differences in the activation of caspases 3/7. Then, control and treated cells of HL-60 and K-562 cell lines were studied through an untargeted lipidomic approach. The treatment was carried out with CBD at a concentration of 10 μM for HL-60 cells and 23 µM CBD for K-562 cells for 48 h. After the extraction of the lipid content from cell lysates, the samples were analysed by UHPLC-QTOF-MS/MS both in the positive and the negative ionization modes. The comprehensive characterization of cellular lipids unveiled several classes significantly affected by CBD treatment. Most of the differences correspond to phospholipids, including cardiolipins (CL), phosphatidylcholines (PC) and phosphosphingolipids (SM), and also triacylglycerols (TG), being many TG species increased after CBD treatment in the acute and chronic models, whereas phospholipids were found to be decreased. The results highlight some important lipid alterations related to CBD treatment, plausibly connected with different metabolic mechanisms involved in the process of cell death by apoptosis in cancer cell lines.PMID:39824876 | DOI:10.1038/s41598-025-86044-5

Ann Allergy Asthma Immunol. 2025 Jan 15:S1081-1206(25)00001-8. doi: 10.1016/j.anai.2024.12.022. Online ahead of print.ABSTRACTBACKGROUND: Allergic rhinitis (AR) is a prevalent chronic inflammatory condition that significantly impacts patient quality of life and poses a substantial public health burden. Recent advancements in metabolomics have facilitated a deeper understanding of the metabolic pathways involved in AR, offering potential for new biomarkers and therapeutic targets.OBJECTIVE: This article aims to conduct a systematic review and meta-analysis of clinical studies summarizing the metabolomic profiles of allergic rhinitis (AR) to gain deeper insights into the metabolic changes and pathological processes underlying AR.METHODS: A comprehensive literature search was conducted across PubMed, Embase, Scopus, and Web of Science databases up to October 2024. A qualitative review of the screened studies was performed, followed by meta-analyses of metabolites reported in at least two studies. High-impact targets, pathways, and their associations were identified using bioinformatic analyses.RESULTS: A total of 21 studies, encompassing 84 metabolites associated with AR, met the inclusion criteria. Seven metabolites consistently exhibited upregulation in AR across multiple studies and were included in the meta-analysis. Pathway enrichment analyses revealed significant involvement of pathways such as "Valine, leucine, and isoleucine biosynthesis" and "Linoleic acid metabolism" in AR pathogenesis. The metabolite-pathway-gene network analysis highlighted key functional connections between metabolites, pathways, and immune response genes.CONCLUSION: This comprehensive analysis indicates that differential metabolites may play pivotal roles in AR pathogenesis, offering potential biomarkers and therapeutic targets. Further studies are necessary to validate these findings and elucidate the complex metabolic pathways involved in AR.PMID:39824455 | DOI:10.1016/j.anai.2024.12.022

Int J Biol Macromol. 2025 Jan 15:139938. doi: 10.1016/j.ijbiomac.2025.139938. Online ahead of print.ABSTRACTResidual feed intake (RFI) is a better indicator of feed efficiency than feed conversion ratio (FCR). It is frequently used to evaluate the efficacy of poultry and livestock feed consumption. Generally, Low RFI (LRFI) is associated with better feed conversion efficiency, whereas high RFI (HRFI) suggests poorer feed conversion efficiency. The study examined the association between microorganisms, tissue and organ functions. The results demonstrated that in contrast to the HRFI group, the LRFI group revealed higher length measurements, the digestive organs' mass, and chest width. The antioxidant indices revealed that the enzymatic activities (catalase and glutathione peroxidase) in the LRFI group were significantly higher than those in the HRFI group. The serum levels of HDLC, AST, and ACTH were identified as potential markers that could affect RFI. The variations between high and low RFI and the function of the liver and cecum microbiota of hens during late laying period were systematically investigated by multiple omics techniques. Through 16S, the most common beneficial microbial population in the gut of LRFI groups, such as Oscillospirales, Ruminococcaceae, and Butyricicoccaceae, has been detected via a microbiome-metabolome association analysis. Through multi-omics analysis, we found that FABP1 and ACSS2 are important regulatory genes affecting RFI. These findings will provide a basis for comprehending the role of gut microbiota in regulating RFI and the molecular mechanism behind the phenotypic changes observed in late-laying hens.PMID:39824417 | DOI:10.1016/j.ijbiomac.2025.139938

Fish Shellfish Immunol. 2025 Jan 15:110128. doi: 10.1016/j.fsi.2025.110128. Online ahead of print.ABSTRACTThe liver-expressed antimicrobial peptide 2 (LEAP2) is gaining recognition for its immune regulatory functions beyond direct antimicrobial activity. In this study, we investigated the role of mudskipper (Boleophthalmus pectinirostris) LEAP2 (BpLEAP2) in enhancing the survival, gut health, and immune resilience against Edwardsiella tarda infection. Pre-oral delivery of BpLEAP2 significantly improved survival rates and mitigated infection-induced damage to the gut, as evidenced by preserved villus length and goblet cell count. Analysis of gut microbial communities using 16S rRNA sequencing revealed that pre-oral delivery of BpLEAP2 increased microbial diversity, evenness, and the abundance of beneficial genera such as Pseudoalteromonas and Shewanella, while reducing pathogenic genera like Pseudorhodobacter. Metabolomic profiling showed that BpLEAP2 altered the gut metabolite composition, significantly increasing levels of bile acids and amino acids, which are known to support gut health and immune responses. Correlation analysis demonstrated strong positive associations between BpLEAP2-induced microbial shifts and increased metabolites involved in amino acid metabolism. These findings suggest that BpLEAP2 promotes intestinal homeostasis by modulating gut microbiota composition and enhancing beneficial metabolite production, ultimately improving gut barrier integrity and conferring resistance against E. tarda infection. This study highlights the potential application of BpLEAP2 in enhancing disease resilience in aquaculture species, offering a promising strategy for sustainable aquaculture practices.PMID:39824300 | DOI:10.1016/j.fsi.2025.110128

Environ Res. 2025 Jan 15:120862. doi: 10.1016/j.envres.2025.120862. Online ahead of print.ABSTRACTMetabolomics measures low molecular weight endogenous metabolites and changes linked to contaminant exposure in biota. Few studies have explored the relationship between metabolomics and contaminants in Arctic wildlife. We analyzed 239 endogenous metabolites and ∼150 persistent organic pollutants (POPs), including total mercury (THg), in the liver of polar bears and their ringed seal prey harvested from low Canadian Arctic (western Hudson Bay; WHB) and high Arctic (HA) locations during 2015-2016. Polar bears from the HA had different metabolomic profiles compared to those from WHB, particularly in several phosphatidylcholines (PCs), with the HA bears having higher concentrations of longer chain PCs. Similarly, HA and WHB ringed seals also had metabolomic profile differences in five PCs related to fat catabolism and transport. The metabolites with the highest impact on discriminating metabolomic profiles between the two species, based on VIP scores, were: tauroursodeoxycholic Acid (TUDCA), histamine, serotonin, lithocholic acid (LCA), and taurolithocholic acid (TLCA). Higher TUDCA levels in polar bears likely reflect their blubber-rich diet, while higher histamine in seal liver may indicate inflammatory responses. Significant correlations were found between liver metabolites and several per- and polyfluoroalkyl substances (PFAS) in both species, including PFOA, PFNA, PFDA, PFEtCHxS, PFOS, and/or PFDS that moderately correlated to PCs. THg in seals and bears was negatively correlated with sarcosine. This study revealed significant correlations and differences in metabolite profiles of polar bears and ringed seals, suggesting that PFAS impacted several pathways related to lipid metabolism, bile acid synthesis, antioxidant defenses, arginine biosynthesis, histidine metabolism, and sphingolipid metabolism, with ringed seals showing greater sensitivity to PFAS. These results indicate that PFAS may influence metabolic processes in Arctic wildlife, although further research is needed to understand the full impact on Arctic wildlife health.PMID:39824276 | DOI:10.1016/j.envres.2025.120862

Mol Cell. 2025 Jan 16;85(2):262-275. doi: 10.1016/j.molcel.2024.12.012. Epub 2025 Jan 16.ABSTRACTCells integrate metabolic information into core molecular processes such as transcription to adapt to environmental changes. Chromatin, the physiological template of the eukaryotic genome, has emerged as a sensor and rheostat for fluctuating intracellular metabolites. In this review, we highlight the growing list of chromatin-associated metabolites that are derived from diverse sources. We discuss recent advances in our understanding of the mechanisms by which metabolic enzyme activities shape the chromatin structure and modifications, how specificity may emerge from their seemingly broad effects, and technologies that facilitate the study of epigenome-metabolome interplay. The recognition that metabolites are immanent components of the chromatin regulatory network has significant implications for the evolution, function, and therapeutic targeting of the epigenome.PMID:39824167 | DOI:10.1016/j.molcel.2024.12.012

Sci Total Environ. 2025 Jan 16;963:178486. doi: 10.1016/j.scitotenv.2025.178486. Online ahead of print.ABSTRACTPinus pinaster Aiton (maritime pine) stands are suffering a generalized deterioration due to different decline episodes throughout all its distribution area. It is well known that external disturbances can alter the plant associated microbiota and metabolome, which ultimately can entail the disruption of the normal growth of the hosts. Notwithstanding, very little is known about the shifts in the microbiota and the metabolome in pine trees affected by decline. The aim of our work was to unravel whether bacterial and fungal communities inhabiting the rhizosphere and root endosphere of P. pinaster trees with symptoms of decline and affected by Matsucoccus feytaudi in the National Park of Sierra Nevada (Granada, Spain) showed alterations in the structure, taxonomical profiles and associative patterns. We also aimed at deciphering potential changes in the rhizosphere and root metabolome. Trees infected by M. feytaudi and healthy individual harbored distinct microbial communities at both compositional and associative patterns. Unhealthy trees were enriched selectively in certain plant growth promoting microorganisms such as several ectomycorrhizal fungi (Clavulina) and Streptomyces, while other beneficial microorganisms (Micromonospora) were more abundant in unaffected pines. The rhizosphere of unhealthy trees was richer in secondary metabolites involved in plant defense than healthy pines, while the opposite trend was detected in root samples. The abundance of certain microorganisms was significantly correlated with several antimicrobial metabolites, thus, being all of them worthy of further isolation and study of their role in forest decline.PMID:39824104 | DOI:10.1016/j.scitotenv.2025.178486

J Hazard Mater. 2025 Jan 14;487:137217. doi: 10.1016/j.jhazmat.2025.137217. Online ahead of print.ABSTRACTTinidazole (TNZ), a common nitroimidazole antibiotic, is pervasive in aquatic ecosystems, posing potential threats to marine organisms. The environmental fate of TNZ, particularly under solar irradiation, and the associated secondary risks are not well characterized. Herein, the photochemical reactivity of TNZ and four other typical nitroimidazoles (i.e., metronidazole, ornidazole, dimetridazole, and secnidazole) were quantified for multiple photoreactive species. The photolysis products of these nitroimidazoles were identified under solar irradiation, from which the reaction pathways were tentatively proposed. Furthermore, the photo-induced toxicity evolution mechanisms of TNZ were investigated by comparing phenotypic, transcriptomic, and metabolomic changes in marine medaka embryos (Oryzias melastigma) after exposure to TNZ and its photo-irradiated mixtures. Our results indicated that the photo-irradiated TNZ enhanced visual toxicity to marine medaka embryos compared to the parent compound. The photolysis mixtures induced embryonic ocular malformation and significantly affected the expression of the associated genes with the initiation/termination of the phototransduction cascade, leading to metabolite changes related to visual impairment. This work reported the first comprehensive assessment of the photolysis-mediated environmental fate and secondary risks of TNZ in seawater. The findings highlighted the necessity of including complex photolysis mixtures under solar irradiation in future chemical risk assessments of marine environments.PMID:39823881 | DOI:10.1016/j.jhazmat.2025.137217

J Hazard Mater. 2025 Jan 13;487:137214. doi: 10.1016/j.jhazmat.2025.137214. Online ahead of print.ABSTRACTThe relationship between fine particulate matter (PM2.5) and cognition has been extensively investigated. However, the causal impact of acute PM2.5 purification on cognition improvement and the underlying biological mechanisms remain relatively opaque. Our double-blinded randomized controlled trial assessed the impact of acute PM2.5 purification on executive function, underpinned by multi-omics approaches including alternative splicing (AS) analysis. A total of 93 participants experienced a two-hour exposure to either reduced and normal PM2.5 levels. We measured the cognition of healthy young adults, collected peripheral blood before and after intervention, and performed multi-omics analysis including transcriptomics, metabolomics, and proteomics. Results indicated that reducing PM2.5 by 1 μg/m3 was associated with a 0.10 % (95 % CI: [0.18 %, 0.01 %]; p = 0.031) improvement in executive function. Notably, we identified 96 AS events without concurrent transcriptional amount alterations. Multi-layered omics analyses revealed disrupted pathways in hypoxia, mitochondrial function and energy metabolism, and immune responses, validated by ELISA and biochemical assay. These findings demonstrated short-term improvements of cognition following PM2.5 purification and provide mechanistic understandings of PM2.5-induced cognition alterations. This study underscores the significance of incorporating AS in the molecular framework of multi-omics research by exploring variable exon splicing, which could enrich multi-omics analysis methodologies and expose to broader audience.PMID:39823879 | DOI:10.1016/j.jhazmat.2025.137214

J Hazard Mater. 2025 Jan 12;487:137195. doi: 10.1016/j.jhazmat.2025.137195. Online ahead of print.ABSTRACTChlorpromazine (CPZ) is an abused sedative that is extensively metabolized in organisms. However, the metabolic pathway of CPZ in aquatic organisms is still unclear. In this study, CPZ metabolites was analyzed in grass carp exposed to CPZ in the raising water using ultrahigh-performance liquid chromatography coupled with quadrupole Orbitrap mass spectrometry (UHPLC-Q-Orbitrap MS). Thirteen CPZ metabolites were identified, including 11 previously reported and 2 newly identified metabolites (M9 and M13), and 5 known metabolites were confirmed using authentic standards. The molecular structures and transformation pathways of CPZ metabolites were putatively deduced, which mainly included oxygenation, demethylation, dechlorination and carboxylation reactions. Quantitative analysis of CPZ and its metabolites were also performed, and CPZ sulfoxide had a higher content as an important characteristic metabolite. In addition, in-silico toxicity prediction reminded that some metabolites possess ecotoxicity and developmental toxicities similar to, or even higher, than CPZ. Moreover, metabolomics results indicated that CPZ exposure could cause metabolic disorder in the endogenous metabolome of grass carp.PMID:39823877 | DOI:10.1016/j.jhazmat.2025.137195

Poult Sci. 2024 Dec 27;104(2):104715. doi: 10.1016/j.psj.2024.104715. Online ahead of print.ABSTRACTOne possible approach to selecting chicks based on quality involves identifying biomarkers in biological samples. Concurrently, understanding the metabolic profile of chicks from different-aged breeders is essential for developing strategies to mitigate the age-related effects on hatchability. This study investigated whether chick quality and breeder age influence the metabolic profile of layer chick meconium. A total of 143 chicks from laying breeder hens, categorized as young, middle-aged or old, were visually assessed for quality, and meconium samples were collected for metabolomic analysis. Sixteen metabolites were found to be associated with good-quality chicks across all breeder ages, with an overall accuracy of 81.94 %. Using metabolite profiles, the accuracy for predicting young-hen-chick quality was 93.2 %, with high sensitivity (92.30 %) and specificity (93.75 %). Four metabolites were associated with poor-quality chicks with an overall accuracy of 77.53 %. Partial least squares discriminant analysis (PLS-DA) revealed enhanced metabolite separation in good-quality chicks, with five metabolites exhibiting high area under the curve (AUC) values (>90 %) in chicks from young hens compared to chicks from hens of other ages, including metabolites related to energy metabolism, hormonal activity, vitamin D synthesis and peptide constitution. Disregarding maternal age, five metabolites varied between good- and poor-quality chicks, but with a low accuracy of 61.26 % for quality discrimination. Chicks from young, middle-aged, and old hens exhibited 12, 11, and 2 metabolites that varied the expression between good and poor qualities, with accuracies for predicting good-quality chicks of 74.46 %, 70.83 %, and 51.06 %, respectively. Certain metabolites with 70 < AUC < 80 % have emerged as potential biomarkers for distinguishing between good- and poor-quality layer chicks. These include metabolites related to energy and growth metabolism, tryptophan and methionine metabolism, antioxidants and some with no known function in embryos. This work identified potential metabolites that can be investigated to mitigate the effects of hen age on hatchability. Additionally, several metabolites have emerged as potential biomarkers for distinguishing between good- and poor-quality chicks, depending on the breeder's age.PMID:39823833 | DOI:10.1016/j.psj.2024.104715

Int Immunopharmacol. 2025 Jan 16;148:114051. doi: 10.1016/j.intimp.2025.114051. Online ahead of print.ABSTRACTOBJECTED: Mal f 1, the first allergen cloned from Malassezia furfur, has been found to have positive IgE reactivity in sera from patients with skin inflammation. In vitro, it has also been shown to induce maturation of dendritic cells and release inflammatory factors. However, its role in skin lipid homeostasis remains largely unexplored.METHODS: A mouse model of skin inflammation was established by intradermal injection of Mal f 1 into the ear. Metabolomic analyses were used to study the potential mechanisms of Mal f 1-induced skin inflammation.RESULTS: Subcutaneous injection of Mal f 1 can successfully induce skin inflammation, including skin thickening, inflammatory cell infiltration and the increase of various inflammatory factors. Mal f 1 caused significant changes in 102 lipid metabolites compared with the control group, which includes metabolites in arachidonic acid metabolism, glycerophospholipid metabolism, linoleic acid metabolism, and cholesterol biosynthesis.CONCLUSIONS: The present study analyze the characteristics of Mal f 1-induced cutaneous inflammation and the associated disorders in skin lipid metabolism, thereby offering valuable insights for future investigations into the pathophysiology, prevention, and treatment strategies for these conditions.PMID:39823796 | DOI:10.1016/j.intimp.2025.114051

Ecotoxicol Environ Saf. 2025 Jan 16;290:117747. doi: 10.1016/j.ecoenv.2025.117747. Online ahead of print.ABSTRACTDichlorvos (DDVP) is an organophosphorus pesticide commonly utilized in agricultural production. Recent epidemiological studies suggest that exposure to DDVP correlates with an increased incidence of liver disease. However, data regarding the hepatotoxicity of DDVP remain limited. Additionally, the regulatory mechanisms underlying DDVP-induced liver injury have not been thoroughly investigated. In this study, we utilized Wistar rats and BRL-3A cells to establish in vivo and in vitro models for examining the effects of DDVP exposure on liver damage. Our findings indicate that DDVP impairs hepatocyte autophagy and increases ROS activity. RNA sequencing and metabolomic analyses revealed that the pathways affected by DDVP exposure in hepatocytes include ABC transporters and amino acid biosynthesis processes. Furthermore, targeting IRGM overexpression through hepatic portal vein injection of adeno-associated virus mitigated DDVP-induced liver injury. These results demonstrate that DDVP exposure induces liver damage in rats through mechanisms that are dependent on ROS and autophagy, at least in part by downregulating IRGM. Our study offers new insights into the molecular mechanisms of liver injury following organophosphate poisoning and suggests that IRGM may represent a novel therapeutic target for DDVP-induced liver injury.PMID:39823667 | DOI:10.1016/j.ecoenv.2025.117747