PubMed

Foods. 2025 Apr 8;14(8):1287. doi: 10.3390/foods14081287.ABSTRACTThis study investigated the effects of dietary Antarctic krill meal (AKM) on the physiological metabolism and flavor quality of adult Eriocheir sinensis ovaries during the postharvest temporary rearing. The AKM concentrations tested were 0% (including negative control group and positive control group), 2%, 4%, 6%, and 8%. The results indicate that the E. sinensis ovaries in 8% AKM group produced the highest levels of aroma compounds after thermal processing, including hexanal, heptanal, phenylacetaldehyde, 3-octanone, and 2-methylbutanoic acid ethyl ester. The 8% AKM and negative control group were analyzed by UPLC-MS/MS combined with the nontargeted and widely targeted metabolomics technique. The AKM altered the composition of aroma precursors by adjusting the metabolism of glycerophospholipid, linoleic acid, α-linolenic acid, and amino acid in ovaries. Moreover, lipids composed of polyunsaturated fatty acids (PUFAs) were significantly upregulated (p < 0.05). Dietary supplementation with 8% AKM had the best effect on improving the ovarian flavor quality of E. sinensis. During the postharvest temporary rearing, more aromatic precursors were produced by regulating physiological metabolism. The ovarian flavor was enhanced by lipid oxidation, Maillard reaction, and Strecker degradation during thermal processing.PMID:40282689 | DOI:10.3390/foods14081287

Genes (Basel). 2025 Mar 29;16(4):399. doi: 10.3390/genes16040399.ABSTRACTMetabolic dysfunction-associated steatohepatitis (MASH), a progressive form of fatty liver disease, presents a significant global health challenge. Despite extensive research, fully elucidating its complex pathogenesis and developing accurate non-invasive diagnostic tools remain key goals. Multi-omics approaches, integrating data from transcriptomics, proteomics, metabolomics, and lipidomics, offer a powerful strategy to achieve these aims. This review summarizes key findings from multi-omics studies in MASH, highlighting their contributions to our understanding of disease mechanisms and the development of improved diagnostic models. Transcriptomic studies have revealed widespread gene dysregulation affecting lipid metabolism, inflammation, and fibrosis, while proteomics has identified altered protein expression patterns and potential biomarkers. Metabolomic and lipidomic analyses have further uncovered significant changes in various metabolites and lipid species, including ceramides, sphingomyelins, phospholipids, and bile acids, underscoring the central role of lipid dysregulation in MASH. These multi-omics findings have been leveraged to develop novel diagnostic models, some incorporating machine learning algorithms, with improved accuracy compared to traditional methods. Further research is needed to validate these findings, explore the complex interplay between different omics layers, and translate these discoveries into clinically useful tools for improved MASH diagnosis and prognosis.PMID:40282358 | DOI:10.3390/genes16040399

Genes (Basel). 2025 Mar 27;16(4):383. doi: 10.3390/genes16040383.ABSTRACTBackground/Objectives: Eggshell quality is a critical factor influencing consumer preference and the economic benefits of poultry enterprises, and the uterus is the key site for eggshell synthesis. Yaoshan chicken (YS), an indigenous chicken breed in China, is renowned for its flavorful meat and high-quality eggs. However, its egg production is lower compared to specialized strains. Therefore, the GYR crossbreed was developed by three-line hybridization for YS chicken, which can produce green-shelled eggs with better eggshell thickness and strength than YS chicken (p < 0.01). To explore the molecular mechanisms underlying the differences in eggshell quality between GYR and YS chickens, we conducted an integrated transcriptomic and metabolomic analysis. Methods: Twelve uterus samples (six from GYR and six from YS chickens) were collected during the period of eggshell calcification at 260 days of age. RNA sequencing (RNA-seq) and liquid chromatography-mass spectrometry (LC-MS/MS) were performed to identify differentially expressed genes (DEGs) and differential metabolites (DMs), respectively. Results: A total of 877 DEGs were identified in the GYR group, including 196 upregulated and 681 downregulated genes (|log2 (fold change)| > 1, p-value < 0.05). Additionally, 79 DMs were detected, comprising 50 upregulated and 29 downregulated metabolites (|log₂ (fold change)| > 1, VIP > 1). Notably, the key DEGs (SLCO1B3, SLCO1B1, PTGR1, LGR6, MELTF, CRISP2, GVINP1, and OVSTL), important DMs (prostaglandin-related DMs and biliverdin) and signaling pathways (calcium signaling, neuroactive ligand-receptor interaction, arachidonic acid metabolism, bile secretion, and primary bile acid biosynthesis) were major regulators of the eggshell quality. Furthermore, an integrated transcriptomic and metabolomic analysis revealed two significant gene-metabolite pairs associated with eggshell quality: PTGDS-prostaglandin E2 and PTGS1-prostaglandin E2. Conclusions: This study provides a theoretical foundation for the improved eggshell quality of Yaoshan chicken.PMID:40282343 | DOI:10.3390/genes16040383

Genes (Basel). 2025 Mar 25;16(4):373. doi: 10.3390/genes16040373.ABSTRACTBACKGROUND: Scientific and rational fertilizer management can not only improve the yield and quality of hazelnut (Corylus heterophylla × Corylus avellana) but also reduce the negative impact on the environment.METHODS: Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS) technology was used to reveal the contents of various metabolites in hazelnut seedlings, and differential metabolites were screened by principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA).RESULTS: The results showed that a total of 178 up-regulated differential metabolites (Fold change > 1) and 175 down-regulated differential metabolites (Fold change < 1) were detected in 6 comparison groups (DWF0 vs. DWF4, DWF0 vs. DWF5, DWF0 vs. DWF6, DWF4 vs. DWF5, DWF4 vs. DWF6, DWF5 vs. DWF6). Interestingly, the flavonoid metabolic pathway was dramatically enriched, and it was involved in each fertilization combination. The metabolites of the flavonoid pathway in different fertilized and unfertilized groups were compared and analyzed, which displayed that metabolites tricetin, eriodictyol, garbanzol, apigenin, and biochanin A were significantly up-regulated, while garbanzol and astraglin were significantly down-regulated. More interestingly, the determination of flavonoid content and real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) displayed that the application of trace element water-soluble fertilizer could significantly enhance the flavonoid content and the expression of genes related to the flavonoid biosynthesis pathway, such as phenylalanine ammonia-lyase (PAL) and cinnamate 4-hydroxylase (C4H), with the DWF4 treatment displaying the most significant values.CONCLUSIONS: Overall, the application of trace element water-soluble fertilizer (especially the DWF4 treatment) markedly affected the changes in key metabolites of the flavonoid pathway and the expression levels of key genes, thus promoting the growth and development of the hazelnut, which offers an important starting point for future analysis through genetic engineering.PMID:40282333 | DOI:10.3390/genes16040373

Biology (Basel). 2025 Apr 11;14(4):403. doi: 10.3390/biology14040403.ABSTRACTMetabolomics approaches, such as Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and mass spectrometry (MS), have emerged as powerful tools for studying cardiovascular diseases (CVD), including hypertension. The use of biological fluids, like plasma and serum, has garnered significant interest due to their accessibility and potential in elucidating disease mechanisms. This review aims to summarize the current literature on the application of metabolomics techniques (FTIR, NMR, and MS) in the study of hypertension, focusing on their contributions to understanding disease pathophysiology, biomarker discovery, and therapeutic advancements. A comprehensive analysis of metabolomic studies was performed, with a particular emphasis on the diversity of altered metabolites associated with systolic blood pressure (SBP), diastolic blood pressure (DBP), and sex-related differences. Metabolomics techniques, including FTIR, NMR, and MS, provide comprehensive insights into the biochemical alterations underlying hypertension, such as amino acid and fatty acid metabolism impairment or inflammation and oxidative stress processes. This review underscores their role in advancing biomarker identification, deepening our understanding of disease mechanisms, and supporting the development of targeted therapeutic strategies. The integration of these tools highlights their potential in personalized medicine and their capacity to improve clinical outcomes.PMID:40282268 | DOI:10.3390/biology14040403

Biology (Basel). 2025 Mar 27;14(4):345. doi: 10.3390/biology14040345.ABSTRACTBackground: The accumulation of secondary metabolites in medicinal plants is often influenced by a variety of factors, and rhizosphere microorganisms typically engage in complex interactions with their host plants. Crepis napifera (Franch.) Babc., a regionally significant medicinal plant, contains a diverse array of terpenoids and demonstrates substantial potential for resource development and utilization. Methods: Transcriptome sequencing, metabolomic profiling, and 16S rRNA gene amplicon sequencing were employed to assess the transcriptional expression patterns, metabolic variations, and rhizosphere microbial community composition of C. napifera (Franch.) Babc. roots distributed across various regions. Results: A total of 3679, 8615, and 11,333 differentially expressed genes (DEGs) were identified in the pairwise comparisons between H1 vs. H2, H2 vs. H3, and H1 vs. H3, respectively. Notably, 497 DEGs were consistently detected across all three comparisons. Additionally, Weighted Gene Co-expression Network Analysis (WGCNA) revealed that the expression levels of genes within the turquoise and yellow modules exhibited a significant positive correlation with elevation. In total, 462 differentially expressed metabolites (DEMs) were identified across the same comparisons. Among these compounds, terpenoids, phenolic acids, amino acids and their derivatives, lipids, and alkaloids accounted for 62.98% of the total differential metabolite content. The accumulation patterns of DEMs varied significantly across different regions in the roots of C. napifera (Franch.) Babc. under the three altitude conditions. In response to environmental conditions and the survival strategy of C. napifera (Franch.) Babc. in alpine areas, an investigation into the rhizosphere microbial community was conducted. Four key microbial genera were identified as being correlated with terpenoid biosynthesis and plant nutritional metabolism. Specifically, Pedosphaera, Acidothermus, and Nevskia exhibited terpene biosynthesis capabilities. Additionally, Herbaspirillum, a common microorganism involved in plant nitrogen fixation, respiration, carbon metabolism, and cell wall metabolism, was also enriched in the rhizosphere of C. napifera (Franch.) Babc. These findings suggested that C. napifera (Franch.) Babc. might recruit these microorganisms to enhance its resistance to environmental stress in alpine areas. Conclusions: The accumulation of terpene in C. napifera (Franch.) Babc. across different regions was influenced by transcriptional changes. The rhizosphere microbial communities also changed during this process, showing a recruitment effect that enhances plant growth and offers potential value.PMID:40282210 | DOI:10.3390/biology14040345

Animals (Basel). 2025 Apr 19;15(8):1174. doi: 10.3390/ani15081174.ABSTRACTTemperature is a critical environmental factor that influences the growth, development, metabolism, and overall physiological performance of fish. Eleutheronema tetradactylum is an economically significant fish species; however, its molecular mechanism's response to long-term cold stress is still unclear. In this study, we investigated the physiological responses of the liver in E. tetradactylum exposed to a constant temperature of 18 °C for durations of both 7 and 14 days, utilizing liquid chromatography-mass spectrometry (LC-MS), metabolomics, and conventional biochemical assays. The antioxidant status, liver histology, and metabolite profiles were examined at different time points. Our results revealed that, following sustained cold exposure, the activities of key antioxidant enzymes-superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)-initially increased and then decreased. Additionally, levels of malondialdehyde (MDA), a marker of oxidative damage, significantly elevated after 7 and 14 days of cold stress. Histopathological examination of liver tissues showed varying degrees of vacuolation and nuclear atrophy in hepatocytes, indicating oxidative damage. Metabolomic profiling identified 87 and 116 differentially expressed metabolites in the liver on days 7 and 14, respectively. Pathway enrichment analysis revealed significant alterations in pathways related to carbohydrate digestion and absorption, glutathione metabolism, and glycerolipid metabolism. These findings suggest that mechanisms regulating cell membrane fluidity, energy metabolism, autophagy, and antioxidant defense are crucial for the adaptation of E. tetradactylum to cold stress. Overall, this study provides valuable insights into the molecular and physiological adaptations of E. tetradactylum to low temperature, highlighting the activation of protective antioxidant responses and modifications of metabolic pathways in the liver.PMID:40282008 | DOI:10.3390/ani15081174

Metabolomics. 2025 Apr 26;21(3):58. doi: 10.1007/s11306-025-02257-9.ABSTRACTINTRODUCTION: Mushrooms contain besides proteins a diverse pallet of specialized metabolites bioactive in either beneficial or harmful manner. Therefore, mushrooms have been exploited by humans for centuries for dietary or medical purposes. For example, the edible and medicinal mushrooms Hericium erinaceus and Pleurotus eryngii are grown commercially around the world. In nature, H. erinaceus grows on old or dead tree trunks, and P. eryngii grows on Apiaceae plant roots, whereas in cultivation, they grow on substrates mainly consisting of dry wood chips, straw, and cereals. To make their farming more sustainable, supplements such as olive mill solid waste (OMSW) have been added to support mushroom development. However, so far, the impact of substrate additives on the edible mushroom metabolic content has not been assessed.METHODS: Here, we examined the effect of different proportions of OMSW added to the substrate on the metabolic profiles of the fruiting body (FB) and mycelium of H. erinaceus and P. eryngii mushrooms. The study includes four groups for each mushroom species, mushrooms are grown on 0% OMSW, 33%, 60%, and 80% OMSW, with three biological repeats in each group. We used computational metabolomics strategies including GNPS molecular networking, MS2Query, and the FERMO dashboard, to organize, annotate, and prioritize metabolite features from the untargeted Q-Exactive Plus HR-LC-MS/MS metabolomics data. Following chromatography-based fractionation, the metabolite annotation of four metabolite features was further validated or fine-tuned using 1H-NMR, to resolve structural isomers.RESULTS AND DISCUSSION: Our computational metabolomics strategies showed several annotated metabolite features to be affected by OSMW concentration. In general, the methanolic extracts of H. erinaceus FB and mycelium were more highly enriched with specialized metabolites than those of P. eryngii. Interestingly, OMSW increased several hericenone analogues in the H. erinaceus FB, as well as several erinacerin metabolites from the mycelium. In addition, high concentrations of OMSW decreased the enniatin metabolite abundance. In conclusion, we demonstrate how a change in substrate composition affects the mushroom's specialized metabolome and can induce and alter mushroom metabolite content and diversity. These results highlight the importance of including computational metabolomic strategies to investigate new sustainable growth options for edible mushrooms and other natural foods.PMID:40281221 | DOI:10.1007/s11306-025-02257-9

Cell Death Differ. 2025 Apr 25. doi: 10.1038/s41418-025-01517-4. Online ahead of print.ABSTRACTCells undergoing regulated necrosis systemically communicate with the immune system via the release of protein and non-protein secretomes. Ferroptosis is a recently described iron-dependent type of regulated necrosis driven by massive lipid peroxidation. While membrane rupture occurs during ferroptosis, a comprehensive appraisal of ferroptotic secretomes and their potential biological activity has been lacking. Here, we apply a multi-omics approach to provide an atlas of ferroptosis-induced secretomes and reveal a novel function in macrophage priming. Proteins with assigned DAMP and innate immune system function, such as MIF, heat shock proteins (HSPs), and chaperones, were released from ferroptotic cells. Non-protein secretomes with assigned inflammatory function contained oxylipins as well as TCA- and methionine-cycle metabolites. Interestingly, incubation of bone marrow-derived macrophages (BMDMs) with ferroptotic supernatants induced transcriptional reprogramming consistent with priming. Indeed, exposure to ferroptotic supernatants enhanced LPS-induced cytokine production. These results define a catalog of ferroptosis-induced secretomes and identify a biological activity in macrophage priming with important implications for the fine-tuning of inflammatory processes.PMID:40281125 | DOI:10.1038/s41418-025-01517-4

BMC Genomics. 2025 Apr 25;26(1):407. doi: 10.1186/s12864-025-11611-z.ABSTRACTBACKGROUND: Intramuscular fat (IMF) is a key determinant of meat quality enhancement in pigs. However, its correlation with subcutaneous fat (SCF) deposition presents a challenge. The precise regulation of IMF lipogenesis, without impacting SCF deposition, is a critical issue in the pig industry. To investigate this, our study examined the lipid profiles of longissimus dorsi (LD) muscle and subcutaneous adipose tissue in high IMF (IMFH) and low IMF (IMFL) Chinese Erhualian pigs using lipidomics techniques.RESULTS: We identified 112 differentially abundant lipids (DALs) in the muscle and 101 DALs in the adipose tissue. Notably, 105 specific DALs associated with IMF, including various candidate markers like upregulated lipids of PS (19:2/18:1), TG (14:2/4:0/4:0), PS (17:1/18:2), FA(10:0) + COOH:(s), CL (20:4/18:2/18:2/18:2), and downregulated lipids of FA (20:4), SM (d43:5), TG (38:1/22:6), PC (22:3/20:3), and PC (18:2/24:8), were identified. These specific DALs were implicated in the regulation of linoleic, arachidonic, and alpha-linolenic acid metabolism, and choline metabolism in cancer. We further discovered that the lysophosphlipase 1 (LYPLA1) gene promotes differentiation and lipid deposition of intramuscular pre-adipocytes by affecting the phosphatidylcholine (PC) content.CONCLUSIONS: Our findings identify specific lipids associated with IMF accumulation in both skeletal muscle and subcutaneous adipose depots, thereby offering valuable insights into the lipid composition of porcine IMF and new avenues for targeted IMF deposition.PMID:40281449 | DOI:10.1186/s12864-025-11611-z

Metabolomics. 2025 Apr 26;21(3):57. doi: 10.1007/s11306-025-02253-z.ABSTRACTINTRODUCTION: Cardiovascular disease (CVD) is a significant cause of mortality worldwide. Preventive programs are trying to reduce the burden of the disease. Recent advances in metabolomics profiling open a new avenue for developing complementary CVD evaluation strategies.OBJECTIVES: The aim of the study was to investigate whether a metabolomic profile can provide an additional characterisation of individuals with coronary artery disease (CAD).METHODS: The study included 167 participants with CAD aged 41-79 years. A control group was formed of 166 individuals without CAD, gender- and age-matched to the study group. A total of 188 metabolites were profiled in serum by liquid chromatography-tandem mass spectrometry. After clearing the data, associations between 132 metabolites and CAD presence were analysed using multiple linear regression models.RESULTS: We observed significant differences in serum metabolic profiles between analysed groups on various levels. However, a deeper analysis revealed sphingomyelin 41:1 (SM 41:1) as the main metabolite independently associated with CAD after correction for classical CV risk factors. Its concentration was lower in the CAD group (median 9.79 µmol/L, interquartile range (IQR) 7.92-12.23) compared to control one (median 13.60 µmol/L, IQR 11.30-16.15) (p < 0.001). Further analysis showed that SM 41:1 concentration was inversely correlated with CAD, current smoking, and hypertension; and positively associated with female gender and non-HDL level.CONCLUSIONS: CAD patients present lower plasma concentrations of SM 41:1 than healthy subjects. A better understanding of the biological function of sphingomyelin in CAD patients may help develop therapeutic approaches and risk stratification in this group.PMID:40281287 | DOI:10.1007/s11306-025-02253-z

Sci Rep. 2025 Apr 25;15(1):14569. doi: 10.1038/s41598-025-98992-z.ABSTRACTPlasma amino acids (AAs) have emerged as promising biomarkers for metabolic disorders, yet their causality remains unclear. We aimed to investigate the genetic determinants of AA levels in a cohort of 10,333 individuals and their causal effects on cardiometabolic traits using Mendelian randomization (MR). Plasma levels of 20 AAs were quantified using capillary electrophoresis mass spectrometry. Genome-wide association studies were conducted using BOLT-LMM and heritability estimation via LDSC analysis. Causal effects of AAs on 11 cardiometabolic traits were examined using two-sample MR analyses. We identified 85 locus-metabolite associations across 43 genes for 18 AAs, including 44 novel loci linked to metabolic genes. Heritability for AAs was estimated at 16%. MR analysis demonstrated cystine to positively associate with systolic blood pressure (SBP) (β = 0.056, SE = 0.010), while serine indicated protective effects on SBP (β = - 0.040, SE = 0.011), diastolic BP (β = - 0.044, SE = 0.010), and coronary artery disease (odds ratio 0.888, SE = 0.028). We identified potentially novel genetic loci associated with AA levels and demonstrated robust causal associations between several AAs and cardiometabolic traits. These findings reinforce the importance of AAs as potential biomarkers and therapeutic targets in cardiometabolic health.PMID:40281240 | DOI:10.1038/s41598-025-98992-z

NPJ Biofilms Microbiomes. 2025 Apr 26;11(1):66. doi: 10.1038/s41522-025-00709-7.ABSTRACTWe tested the hypothesis that e-cigarette aerosol is metabolized by the indigenous oral microbiome, leading to structural and functional alterations. We combined untargeted metabolomics of in vitro commensal-rich and pathogen-rich biofilms with metatranscriptomics and fluorescent microscopy and verified the results in human samples. Spectral deconvolution of 4215 peaks identified 969 exposomal and endogenous metabolites that mapped to 23 metabolic pathways. The metabolites clustered by both aerosol characteristics and biofilm composition; and several were verified in human saliva of vapers. E-cigarette exposure upregulated xenobiotic degradation, capsule, peptidoglycan biosynthesis, organic carbon-compound metabolism, antimicrobial resistance, and secretion systems. E-cigarette exposure also altered biofilm architecture characterized by low surface-area to biovolume ratio, high biomass, and diffusion distance. In conclusion, our data suggest that bacterial metabolism of e-cigarette aerosol triggers a quorum-sensing-regulated stress response which mediates the formation of dense, exopolysaccharide-rich biofilms in health-compatible communities and antibiotic resistance and virulence amplification in disease-associated communities.PMID:40280980 | DOI:10.1038/s41522-025-00709-7

Clin Proteomics. 2025 Apr 26;22(1):15. doi: 10.1186/s12014-025-09528-6.ABSTRACTEndometrial cancer (EC), a prevalent and intricate disease, is associated with a poor prognosis among gynecological malignancies. Its incidence rising globally underscores the urgent need for biomarkers detection in both research and clinical settings. Over the past decade, we've witnessed rapid advancements in biological methodologies and techniques. A multitude of omics technologies, encompassing genomic/transcriptomic sequencing and proteomic/metabolomic mass spectrometry, have been extensively employed to analyze both tissue and liquid samples derived from EC patients. The integration of multi-omics data has not only broadened our understanding of the disease but also unearthed valuable biomarkers specific to EC. This review encapsulates the recent progress and future prospects in the application of multi-omics technologies in EC research, emphasizing the potential of multi-omics in uncovering novel biomarkers and enhancing clinical assessments.PMID:40281423 | DOI:10.1186/s12014-025-09528-6

BMC Plant Biol. 2025 Apr 25;25(1):529. doi: 10.1186/s12870-025-06585-9.ABSTRACTBACKGROUND: Kernel color is an important characteristic of foxtail millet (Setaria italica) associated with its market ability, quality, and nutritional value, which is mainly due to the accumulation of carotenoids. Despite its importance, the genetic basis of carotenoid variation in foxtail millet remains largely unexplored. Herein, the molecular mechanisms governing carotenoid accumulation in the kernel of foxtail millet were investigated by an exhaustive methodology encompassing Genome-Wide Association Study (GWAS), Bulk Segregant Analysis sequencing (BSA-seq), and integrated transcriptomic and metabolomic analyses.RESULTS: The total carotenoid content in kernels across 201 foxtail millet germplasms showed a spectrum of variations, which indicated that the kernel color is a quantitative genetic trait controlled by multiple genes. Using GWAS on these germplasms and BSA-seq on an F6 generation Recombinant Inbred Line (RIL) population derived from the GBS (yellow kernel) and NMB (white kernel) cross, we identified genome regions linked with total carotenoid content in foxtail millet kernels. Integrated transcriptomic and metabolomic profiling during grain filling in both yellow and white varieties pinpointed SiPSY1 and SiCCD1 as key genes controlling carotenoid accumulation. Notably, the SNP (G/A) at 364 bp and the Indel (29 bp insertion) at 856 bp within the SiPSY1 promoter predominantly contributed to the variance in promoter activity. These variations markedly affected SiPSY1 expression levels, ultimately determining the phenotypic difference between yellow and white kernels.CONCLUSIONS: These findings provide crucial genetic insights for the molecular mechanisms involved in carotenoid metabolism and lay a solid foundation for millet color breeding in foxtail millet.PMID:40281394 | DOI:10.1186/s12870-025-06585-9

Metabolomics. 2025 Apr 26;21(3):59. doi: 10.1007/s11306-025-02255-x.ABSTRACTINTRODUCTION: The plasma lipidome has emerged as an important indicator for assessing host metabolic and immune status in sepsis. While previous studies have largely examined specific lipid class changes in adults sepsis, comprehensive investigations into plasma lipidomic alterations in pediatric sepsis are limited. This study aimed to characterize the plasma lipidome in pediatric sepsis using a metabolomics-based exploratory approach, providing insights into pathophysiological mechanisms and potential biomarkers.METHODS: A retrospective study was conducted on pediatric patients with sepsis admitted to the pediatric intensive care unit (PICU). Untargeted lipidomics analysis using ultra-performance liquid chromatography coupled with Orbitrap mass spectrometry (UPLC-Orbitrap) was performed to compare metabolomic profiles between non-infected control patients and sepsis patients.RESULTS: Compared to controls, plasma lipid levels in sepsis patients decreased by 33.3%, increased by 20.2%, and remained unchanged in 46.5% of cases. A total of 1,257 differential lipids were identified in sepsis patients, with 24 lipids showing significant associations with pSOFA scores. In the recovery and deterioration subgroups, 186 differential lipids were identified, with triglyceride (TG) representing the highest proportion at 16.4%. Notably, 15 lipids with significant statistical differences were identified as differential lipid species through a comparison of those associated with pSOFA scores and those linked to sepsis prognosis. Fatty acid (FA) levels were significantly elevated in the sepsis group compared to controls, with arachidonic acid (FA(20:4)) showing the most significant increase (P < 0.001).CONCLUSION: Alterations in plasma lipid profiles among children with sepsis reflect disease severity, systemic inflammatory responses, and sepsis prognosis. These findings underscore the prognostic potential of lipidomics and its value in understanding sepsis pathophysiology.PMID:40281388 | DOI:10.1007/s11306-025-02255-x

Adv Sci (Weinh). 2025 Apr 25:e2417355. doi: 10.1002/advs.202417355. Online ahead of print.ABSTRACTMETTL14 dimerizes with METTL3 to install N6-methyladenosine (m6A) on mRNA (m6A writers). Subsequently, m6A readers bind to m6A-marked RNA to influence its metabolism. RNA m6A emerges to critically regulate multiple intracellular processes; however, there is a gap in our understanding of m6A in liver metabolism. Glucose-6-phosphatase catalytic subunit (G6pc) mediates hepatic glucose production (HGP) and serves as the gatekeeper for glycogenolysis and gluconeogenesis; however, G6pc regulation is not fully understood. Here, METTL14 is identified as a posttranscriptional regulator of G6pc. Liver METTL14, METTL3, and m6A-methylated G6pc mRNA are upregulated in mice with diet-induced obesity. Deletion of Mettl14 decreases, whereas overexpression of METTL14 increases, G6pc mRNA m6A in hepatocytes in vitro and in vivo. Five m6A sites are identified, and disruption of them (G6pcΔ 5A) blocks METTL14-induced m6A methylation of G6pcΔ 5A mRNA. METTL14 increases both stability and translation of G6pc but not G6pcΔ 5A mRNA. YTHDF1 and YTHDF3 but not YTHDF2 (m6A readers) bind to m6A-marked G6pc mRNA to increase its synthesis. Deletion of hepatic Mettl14 decreases gluconeogenesis in primary hepatocytes, liver slices, and mice. Hepatocyte-specific restoration of G6pc reverses defective HGP in Mettl14 knockout mice. These results unveil a METTL14/G6pc mRNA m6A/G6pc biosynthesis/HGP axis governing glucose metabolism in health and metabolic disease.PMID:40278833 | DOI:10.1002/advs.202417355

Toxins (Basel). 2025 Apr 3;17(4):178. doi: 10.3390/toxins17040178.ABSTRACTDeoxynivalenol (DON) is a mycotoxin ubiquitously present in the environment. Emerging evidence demonstrated that sulforaphane (SFN) exerts potent protective effects against DON-triggered cytotoxicity through multimodal mechanisms. This study aimed to investigate the protective mechanism of SFN during DON exposure. Untargeted metabolomics of IPEC-J2 cells revealed a total of 399 differential metabolites between the DON and control group and 365 differential metabolites between the SFN + DON and DON group. KEGG enrichment was performed to investigate the potential regulatory pathways. The transcriptome identified a total of 1839 differential expression genes (DEGs) between DON and SFN + DON groups. This result indicated that DON exposure and SFN treatment have a profound impact on cellular metabolism and genes. Integrated analysis of the transcriptome and metabolome showed that spermine was a potential biomarker for SFN treatment. SFN increased spermine abundance by regulating genes in glutathione, beta-alanine, and arginine and proline metabolism pathways. Functional experiments demonstrated that spermine alleviated DON-induced oxidative stress, as evidenced by increased cell viability, reduced ROS levels, restored mitochondrial membrane potential (ΔΨm), and normalized antioxidant enzyme activity. Moreover, spermine significantly decreased the cell apoptosis rate induced by DON, which suggested that spermine significantly alleviated the DON-induced cytotoxicity. Overall, these findings elucidated the protective role of SFN through spermine-related mechanisms against the toxicity of DON.PMID:40278676 | DOI:10.3390/toxins17040178

Toxins (Basel). 2025 Mar 21;17(4):150. doi: 10.3390/toxins17040150.ABSTRACTMembers of the benthic marine dinoflagellate genus Amphidinium produce a variety of bioactive compounds, exhibiting potent cytotoxicity in cell assays. Crude methanolic extracts from three genetically distinct cultured strains of A. eilatiense J.J. Lee were screened for cytotoxicity against three human breast and four lung cancer cell lines to evaluate potential applications in anticancer therapy. A standard tetrazolium cell viability assay demonstrated that the methanolic crude extract (100 µg mL-1) from strain AeSQ181 reduced cell viability by 20-35% in five cancer cell lines. Further bioassay-guided fractionation of these crude extracts yielded non-polar fractions (FNP-5 and FNP-6) with particularly high cytotoxic activity against lung (H1563) and breast (MDA-MB-231) adenocarcinoma cell lines. Untargeted metabolomic analysis of cytotoxic fractions by liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) revealed a much richer chemical diversity profile than previous toxigenicity studies on Amphidinium that exclusively focused on linear and cyclic polyethers and their macrolide analogs as putative cytotoxins. This untargeted metabolomic study showed substantial differences in chemical composition between the biologically active and non-active fractions. Preliminary biological and chemical characterization of these A. eilatiense fractions confirms that this species is a rich source of bioactive natural products with potential applications such as anticancer therapeutics.PMID:40278648 | DOI:10.3390/toxins17040150

Toxics. 2025 Apr 2;13(4):271. doi: 10.3390/toxics13040271.ABSTRACTO3 (ozone) is an environmental pollutant that can exacerbate inflammatory damage and contribute to respiratory diseases. However, the molecular mechanisms and potential targets for intervention in ozone-induced lung inflammatory injury are not yet known. To address this, our study exposed mice to 0.6 ppm and 1.0 ppm of O3 (3 h/d, 14 d), evaluating lung inflammation through histopathological examinations, lung function assessments, and analyses of white blood cells and inflammatory factors in BALF. Furthermore, we employed transcriptomic and non-targeted metabolomic approaches to decipher differentially expressed genes (DEGs) and metabolites in mouse lung tissue from the 1.0 ppm O3 exposure group. A comprehensive integration analysis of these omics data was conducted using Pearson correlation analysis. Finally, our findings show that ozone exposure indeed elicits pulmonary inflammation. Transcriptomic analysis identified 311 differentially expressed genes, predominantly implicated in circadian rhythm, IL-17 signaling pathway, and PPAR signaling. Meanwhile, metabolomic profiling revealed 41 differentially regulated metabolites, mainly associated with riboflavin metabolism, glutathione metabolism, and ABC transporter pathways. Integrated multi-omics analysis through Pearson correlation identified three key components (Pla2g10, O-phosphoethanolamine, and phosphorylcholine) showing significant enrichment in glycerophospholipid metabolism. Collectively, our findings suggest that glycerophospholipid metabolism may serve as potential therapeutic targets and diagnostic biomarkers for ozone-induced pulmonary inflammatory injury.PMID:40278587 | DOI:10.3390/toxics13040271