Mass spectrometry imaging reveals spatial metabolic variation and the crucial role of uridine metabolism in liver injury caused by Schistosoma japonicum

PLoS neglected tropical diseases, Journal Year: 2025, Volume and Issue: 19(2), P. e0012854 - e0012854

Published: Feb. 11, 2025

Schistosomiasis is the second most important parasitic disease worldwide. japonica a unique species endemic to southern China, and schistosomiasis characterized by severe liver injury, inflammation, granuloma, subsequent fibrosis. However, pathological mechanism of this remains unclear. Mass spectrometry imaging (MSI) versatile technique that integrates molecular specificity mass (MS) with spatial information, which could provide an accurate method for observing progression. In study, we used air flow-assisted desorption electrospray ionization (AFADESI-MSI) platform detect wide range metabolites visualize their distribution in tissue mice infected S chistosoma japonicum . negative ion mode analysis, 21 25 different were detected early chronic stages infection, respectively. Thirteen characteristic 3 metabolic pathways related development may be involved chronicity schistosomiasis. There more than 32 40 region-specific changes abundance (including carbohydrates, amino acids, nucleotides, fatty acids) livers at two infection times, also revealed heterogeneous characteristics egg granulomas S. model japonicum, oral treatment praziquantel significantly alleviated disorders, including acid pyrimidine metabolism. Surprisingly, Upase1, key enzyme uridine metabolism, was upregulated 6 weeks after levels negatively correlated multiple lipid-associated metabolites. Further studies vitro supplementation inhibited activation LX-2 cells, restored homeostasis metabolism through peroxisome proliferator-activated receptor γ (PPARγ) pathway, played antifibrotic role. Our findings new insights into mechanisms -induced fibrosis potential targeting therapy.

Language: Английский

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Exploring the causal role of plasma metabolites and metabolite ratios in prostate cancer: a two-sample Mendelian randomization study

Frontiers in Molecular Biosciences, Journal Year: 2025, Volume and Issue: 11

Published: Jan. 6, 2025

Prostate cancer (PCa), the most prevalent malignant neoplasm in males, involves complex biological mechanisms and risk factors, many of which remain unidentified. By employing a novel two-sample Mendelian randomization (MR) approach, this study aims to elucidate causal relationships between circulating metabolome PCa risk, utilizing comprehensive data on genetically determined plasma metabolites metabolite ratios. For MR analysis, we utilized from GWAS Catalog database analyze 1,091 309 ratios relation outcomes within two independent datasets. The inverse variance weighted (IVW) method was primary approach for determining existence relationship, supplemented by additional methods heterogeneity, pleiotropy, cross-validation. false discovery rate (FDR) Bonferroni correction were applied identify significant causative associations. Additionally, reverse Steiger filtering conducted ascertain whether influenced observed levels. Furthermore, metabolic pathway analysis with MetaboAnalyst 6.0 software. In our findings reveal three overlapped (arginine glutamate, phosphate uridine, glycerol mannitol/sorbitol) inversely associated risk. Following FDR (FDR < 0.05), cysteinylglycine disulfide identified as potential reducer whereas Uridine N-acetyl-L-glutamine (NAG) pinpointed factors. Notably, NAG (OR 1.044; 95% CI 1.025-1.063) emerged influence, confirmed stringent (P 0.05/1400). Steiger's directionality test 0.001) proposed direction. revealed association "Glutathione Metabolism" development. This provides insights into effects PCa. could serve candidate biomarkers, contributing elucidation PCa's mechanisms.

Language: Английский

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Mechanism exploration of Wenshen Jianpi Decoction on renoprotection in diabetic nephropathy via transcriptomics and metabolomics

Phytomedicine, Journal Year: 2025, Volume and Issue: 139, P. 156446 - 156446

Published: Jan. 31, 2025

Language: Английский

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Transition of the Coordination Modes in Sodiated Uridine Radicals Revealed by Infrared Multiphoton Dissociation Spectroscopy and Theoretical Calculations

Dalton Transactions, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

The generation of free radicals metal cationized nucleic acids by UVPD is found to be accompanied both transfers radical sites and coordination modes, which revealed IRMPD spectroscopy calculations.

Language: Английский

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Urinary Metabolomics Study of Nucleosides in Rats Following Intraperitoneal Injection of γ-Hydroxybutyric Acid

Analytical Letters, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 15

Published: Feb. 13, 2025

γ-Hydroxybutyric acid (GHB) is a central nervous system depressant with high addiction risk, causing oxidative stress and neurotoxicity. Urinary nucleoside metabolomics studies in single- multiple- administration rats have not been performed. Most levels were higher the single-administered group than multiple-administered group. Multivariate analysis identified cytidine, pseudouridine, uridine, N4-acetylcysteine, adenosine, 5'-deoxy-5'-methylthioadenosine as significant for discrimination principal component (PCA) partial least squares discriminant (PLS-DA). These metabolites performed well receiver operating characteristic (ROC) analysis, suggesting they could be potential biomarkers GHB exposure addiction.

Language: Английский

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5,6-Dihydro-5,6-Epoxymultiplolide A, Cytosporone C, and Uridine Production by Diaporthe hongkongensis, an Endophytic Fungus from Minquartia guianensis

Microorganisms, Journal Year: 2025, Volume and Issue: 13(4), P. 792 - 792

Published: March 31, 2025

Endophytic fungi are valuable sources of bioactive secondary metabolites, with potential applications in pharmaceutical and agricultural fields. This study investigates the metabolic Diaporthe hongkongensis, an endophytic fungus isolated from Minquartia guianensis. To date, no metabolites have been identified this species, highlighting novelty research its contribution to understanding chemical diversity fungi. The was cultivated on parboiled rice under static dark conditions for 28 days, leading isolation following three compounds: 5,6-dihydro-5,6-epoxymultiplolide A (1), cytosporone C (2), uridine (3). Structural identification carried out using nuclear magnetic resonance (NMR) spectroscopy mass spectrometry. results revealed versatility D. as demonstrated by ability produce structurally diverse substances biological relevance. Hence, it describes first marking a significant step profile. known antifungal compound lactone derivative underscores biosynthetic fungus, while nucleoside expands repertoire fungal suggesting possible roles cellular metabolism stress adaptation. These findings highlight role prolific potentially natural products, supporting further exploration their biotechnological applications.

Language: Английский

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Metabolomic profiles of body shapes and their associations with the risk of incident cardiovascular disease in Chinese adults

Nutrition Metabolism and Cardiovascular Diseases, Journal Year: 2025, Volume and Issue: unknown, P. 104031 - 104031

Published: April 1, 2025

Language: Английский

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Epileptic encephalopathy in a young Bengal cat caused by CAD deficiency

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 18, 2025

Abstract Developmental and epileptic encephalopathy type 50 (DEE50) in humans is a severe early-onset neurometabolic disorder caused by biallelic loss-of-function variants the CAD gene encoding key multi-enzymatic protein for de novo pyrimidine nucleotide synthesis. Untreated, condition often fatal, but patients respond to uridine supplementation, which fuels synthesis through CAD-independent salvage pathways. Here, we report novel variant feline 4-month-old Bengal kitten with intractable seizures abnormal behavior. The variant, XP_011279586.1:p.(Ser2015Asn), was predicted affect oligomerization of C-terminal aspartate transcarbamylase (ATCase) domain CAD. Genotyping 110 unaffected cats revealed four additional carriers mutant allele, confirming its presence breed. In CAD-knockout human cell line dependent on uridine, recombinant expression wildtype CAD, not Asn2015 mutant, restored growth without demonstrating that p.Ser2015Asn disrupts function pathogenic. This study facilitates genetic testing affected suggests supplementation could be potential treatment. Furthermore, CAD-deficient might serve as valuable spontaneous large animal model further investigate pathogenic mechanisms this rare humans.

Language: Английский

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Fermented Wheat Germ Ameliorates High-Fat Diet-Induced Maternal Obesity in Rats: Insights from Microbiome and Metabolomics

Journal of Agricultural and Food Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: May 14, 2025

Maternal obesity significantly increases the risk of adverse outcomes for mother and fetus. Fermented wheat germ (FWG) has demonstrated potential to improve metabolic disorders, yet its effects have not been explored in maternal models. This study investigated ameliorating impact FWG rats with obesity, focusing on mechanisms through biochemical, gut microbiome, serum metabolomics analysis. The results that was more effective than reducing body weight gain fat accumulation, improving glycolipid metabolism alleviating inflammation. Specifically, modulated composition microbiota by fostering growth beneficial bacteria (e.g., Corynebacterium) while suppressing genera associated Blautia, Akkermansia, Dorea_A, Faecousia). Furthermore, modified high-fat diet-induced metabolites, primarily affecting pyrimidine amino acid metabolism. These findings suggest may serve as a promising dietary intervention mitigating pregnancy outcomes.

Language: Английский

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DNA methylation regulates growth traits by influencing metabolic pathways in Pacific white shrimp (Litopenaeus vannamei)

BMC Genomics, Journal Year: 2025, Volume and Issue: 26(1)

Published: May 20, 2025

DNA methylation is a critical epigenetic modification that dynamically regulates gene expression associated with economic traits. Pacific white shrimp (Litopenaeus vannamei) one of the most important aquatic species for culturing, and growth trait traits its production. However, research on regulation still at an early stage. This study explored methylome dynamics their associations regulatory mechanism behind using full-subfamily individuals discrepant performance. The methylation-related genes in L. vannamei were identified, showed significantly higher levels slow (SG) group compared to fast-growing (FG) individuals. Whole Genome Bisulfite Sequencing (WGBS) analysis revealed muscles notably decreased SG FG A total 532 differentially methylated promoters 2,067 regions identified. Through integrative transcriptomic data from shrimp, 47 screened out differential (DMGs) (DEGs). Functional enrichment overlapping DEGs/DMGs enriched mainly metabolic pathways, starch sucrose metabolism, linoleic acid ascorbate aldarate pentose glucuronate interconversions. plays role vannamei. level was found be negatively correlated comprehensive analysis, it discovered predominantly affects performance by up-regulating involved such as glucose metabolism amino suggests activity derived cope some unknown internal stress or environmental rather than being allocated growth.

Language: Английский

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