PubMed

J Biosci Bioeng. 2025 Apr 26:S1389-1723(25)00081-7. doi: 10.1016/j.jbiosc.2025.04.001. Online ahead of print.ABSTRACTJapanese sake is fermented with specific strains of budding yeast Saccharomyces cerevisiae. Sake yeasts can allow the ethanol concentration of sake to exceed 20 % without distillation. While the genetic mutations responsible for these exceptional properties have been investigated, the underlying metabolism has not been fully explored. It is because yeast cells cultured in sake mash are difficult to collect for metabolome analysis. This study aimed to clarify the metabolic differences of K701 sake yeast and the X2180 diploid laboratory strain when cultured under sake fermentation conditions. To find an alternative medium that mimics sake fermentation and is applicable to measurements of intracellular metabolome, we compared three liquid media, including SD2 medium (synthetic dextrose medium containing 2 % glucose), SD20 medium (synthetic dextrose medium containing 20 % glucose and 1.8 % lactic acid) and pseudo-sake medium (a supernatant of saccharified rice supplemented with 1.8 % lactic acid). Culture profile data demonstrated that the pseudo-sake medium successfully reproduced the metabolic traits of K701 observed in sake mash. Targeted metabolome analysis of yeast cells cultured in the pseudo-sake medium revealed that levels of glycolytic metabolites, such as glucose-6-phosphate (G6P), fructose-6-phosphate (F6P), and fructose-1,6-bisphosphate (FBP), were significantly higher with K701. Based on metabolite concentration data, we inferred that K701 cells had a higher ATP regeneration rate. Calculation of differential Gibbs free energy changes revealed that the glucokinase reaction was upregulated in K701. The present study has, for the first time, revealed the metabolism of K701 sake yeast responsible for its exceptional fermentation ability under sake fermentation conditions.PMID:40288942 | DOI:10.1016/j.jbiosc.2025.04.001

Anal Chim Acta. 2025 Jun 22;1356:343979. doi: 10.1016/j.aca.2025.343979. Epub 2025 Apr 4.ABSTRACTBACKGROUND: Mass spectrometry (MS) and nuclear magnetic resonance (NMR) have emerged as pivotal tools in biofluid metabolomics, facilitating investigation of disease mechanisms and biomarker discovery. Despite complementary capabilities, these techniques are rarely combined, although their integration is often beneficial. Typically, different sample preparation approaches are used, and compatibility challenges potentially arise due to the requirement for deuterated buffered solvents in NMR but not MS techniques. Additionally, MS-based approaches necessitate protein removal from samples whilst in NMR proteins can be potentially useful biomarkers. In this study, we developed a blood serum preparation protocol enabling sequential NMR and multi-LC-MS untargeted metabolomics analysis using a single serum aliquot in a research discovery setting.RESULTS: We analysed human serum samples using various untargeted NMR and multi-LC-MS platforms to assess the impact of deuterated solvents and buffers on detected compound-features. Employing multiple LC-MS profiling approaches, we observed no evidence of deuterium incorporation into metabolites following sample preparation with deuterated solvents. Furthermore, we demonstrated that buffers used in NMR were well tolerated by LC-MS. Protein removal, involving both solvent precipitation and molecular weight cut-off (MWCO) filtration, was identified as a primary factor influencing metabolite abundance. Our findings led to the development and validation of a serum sample preparation protocol enabling a combined NMR and multi-LC-MS analysis.SIGNIFICANCE: Using a single clinical serum aliquot for simultaneous untargeted profiling via NMR and multi-LC-MS represents a highly efficient alternative to current methods. This approach reduces sample volume requirements and substantially expands the potential for broader metabolome coverage. Our study offers comprehensive insights into the impact of sample preparation on complex metabolic biofluid profiles, highlighting the compatibility and complementarity of LC-MS and NMR in metabolomics research.PMID:40288864 | DOI:10.1016/j.aca.2025.343979

Anal Chim Acta. 2025 Jun 22;1356:343942. doi: 10.1016/j.aca.2025.343942. Epub 2025 Mar 26.ABSTRACTBACKGROUND: Analyte annotation confidence in untargeted liquid chromatography mass-spectrometry (LC-MS) based chemical analysis can be enhanced by leveraging retention time information. For this, the chromatographic characteristics of the analytical system used should be well characterized. In this study, we measured 604 diverse chemical standards to characterize a dual LC setup consisting of pentabromobenzyl (PBr) and type-C silica hydride (SiH) columns operating in reversed-phase (RP) and aqueous normal-phase (ANP) mode, respectively.RESULTS: ANP and RP separations individually retained 40 % and 64 % of standards in cLogP range from -6.60 to 8.67 and -3.34 to 12.95, respectively. Using both columns, the coverage increased to 79 % of standards with cLogP range from -6.60 to 12.95 (median cLogP = 1.63). Retention selectivity follows the number of basic nitrogen atoms in the molecule on SiH column and polarity (cLogP) on PBr column. Column repeatability and reproducibility were tested in triplicate using a chemically diverse subset of 108 standards. Repeatability of retention times, peak widths and peak areas was 0.3 %, 14 %, 4 % for SiH column and 0.2 %, 12 %, 4 % for PBr column. Similarly, reproducibility was 15 %, 34 %, 30 % for SiH column and 9 %, 18 % and 34 % for PBr column. Predictive RT models were developed based on experimental RT data, achieving R2 values of 0.92 and 0.96, with mean absolute errors of 0.29 min and 0.27 min for SiH and PBr columns, respectively.SIGNIFICANCE: As proof of concept, 129 metabolites were annotated in pooled human serum and plasma by matching standard or predicted RT on one or both columns. The RT models and MS2 spectra of standards are openly available, facilitating uptake of this well-characterized chromatographic system to increase confidence in analyte annotation.PMID:40288861 | DOI:10.1016/j.aca.2025.343942

Free Radic Biol Med. 2025 Apr 25:S0891-5849(25)00252-7. doi: 10.1016/j.freeradbiomed.2025.04.042. Online ahead of print.ABSTRACTOocyte quality is closely linked to metabolic integrity, and age-related metabolic dysregulation is a key factor contributing to oocyte aging. In this study, we utilized non-targeted metabolomics to explore the impact of taurine supplementation on the metabolic profile of postovulatory aging (POA) porcine oocytes. Our analysis revealed that taurine supplementation significantly altered the metabolic landscape, restoring key metabolic pathways associated with energy production, amino acid metabolism, and oxidative stress regulation. Notably, taurine supplementation enhanced mitochondrial function, increased ATP synthesis, and improved the redox balance by upregulating reduced glutathione (GSH) levels and reducing oxidative damage. Metabolomics data also indicated a restoration of critical metabolic intermediates, including those involved in the glutathione synthesis pathway and amino acid metabolism. These findings suggest that taurine can modulate oocyte metabolism, improve cellular energy status, and mitigate oxidative stress, thereby enhancing oocyte quality at the metabolic level.PMID:40288700 | DOI:10.1016/j.freeradbiomed.2025.04.042

J Lipid Res. 2025 Apr 25:100815. doi: 10.1016/j.jlr.2025.100815. Online ahead of print.ABSTRACTThe Estrogen-Related Receptor (ERR) family of nuclear receptors (NRs) serve key roles in coordinating triglyceride (TAG) accumulation with juvenile growth and development. In both insects and mammals, ERR activity promotes TAG storage during the post-embryonic growth phase, with loss-of-function mutations in mouse Esrra and Drosophila melanogaster dERR inducing a lean phenotype. However, the role of insect ERRs in controlling TAG accumulation within adipose tissue remains poorly understood, as nearly all transcriptomic and metabolomic studies have relied on whole animal analyses. Here we address this shortcoming by using tissue-specific approaches to examine the role of dERR in regulating lipid metabolism within the Drosophila larval fat body. We find that dERR autonomously promotes TAG accumulation within fat body cells and regulates expression of genes involved in glycolysis, β-oxidation, and isoprenoid metabolism. As an extension of these results, we not only discovered that dERR mutant fat bodies exhibit decreased expression of known dHNF4 target genes but also found that dHNF4 activity is decreased in dERR mutants. Overall, our findings indicate that dERR plays a multifaceted role in the larval fat body to coordinate lipid storage with carbohydrate metabolism and developmental growth.PMID:40288680 | DOI:10.1016/j.jlr.2025.100815

J Ethnopharmacol. 2025 Apr 25:119884. doi: 10.1016/j.jep.2025.119884. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: The rhizome of Atractylodes macrocephala, called Atractylodes macrocephala Rhizome (AMR), is one of the commonly used traditional Chinese medicines for alleviating constipation induced by spleen-deficiency. However, the specific mechanism responsible for promoting defecation and gastrointestinal transit by AMR remains unclear.AIM OF THE STUDY: To reveal the spleen-invigorating and laxative effects of AMR in spleen-deficiency constipated rats, as well as to explore the underlying mechanism.MATERIALS AND METHODS: The rat model of spleen-deficiency constipation was established through the induction diarrhea, along with irregular exercise and a low-fiber diet pattern. The effects of AMR were then evaluated based on spleen-deficiency and constipation phenotypes. Additionally, an integrated approach combing 16S rRNA gene sequencing with untargeted/targeted metabolomics using ultra performance liquid chromatography-mass spectrometry (UPLC-MS) was employed to elucidate the potential mechanism of AMR in treating spleen-deficiency constipation.RESULTS: The results indicated that AMR, at the dose of 4.32 g crude drug/kg, significantly improved the general characteristics, digestion-absorption function, colonic pathological morphology and levels of neurotransmitters in spleen-deficiency constipated rats. AMR also effectively ameliorated the disturbance in gut microbiota induced by spleen-deficiency constipation, particularly that microbiota associated with constipated phenotypes and bile acid metabolism, including Firmicutes, Bacteroides, norank_f__Erysipelotrichaceae and norank_f__Muribaculaceae. Additionally, plasma and fecal metabolomics revealed that the development of spleen-deficiency constipation was primarily due to perturbed bile acid biosynthesis and metabolism, with AMR prominently ameliorating the abnormal levels of 17 bile acids. Furthermore, western blot analysis confirmed that AMR regulated the abnormal expression of Takeda G protein-coupled receptor 5 (TGR5), a receptor involved in bile acid metabolism.CONCLUSIONS: Our findings provide important insights into the mechanism underlying spleen-deficiency constipation, suggesting that AMR may be a promising candidate for the prevention and treatment of constipation induced by spleen-deficiency.PMID:40288662 | DOI:10.1016/j.jep.2025.119884

Mol Metab. 2025 Apr 25:102157. doi: 10.1016/j.molmet.2025.102157. Online ahead of print.ABSTRACTBACKGROUND: The global prevalence of obesity and type 2 diabetes, particularly among children, is rising, yet the long-term impacts of early-life fecal microbiota transplantation (FMT) on metabolic health remain poorly understood.OBJECTIVE: To investigate how early-life FMT from children to young, sex-matched mice influences metabolic outcomes and adipose tissue function in later, adult life.METHODS: Germ-free mice were colonized with fecal microbiota from either lean children or children with obesity. The impacts on brown adipose tissue (BAT), white adipose tissue (WAT), glucose metabolism, and gut health were analyzed in male and female mice. Microbial communities and metabolite profiles were characterized using sequencing and metabolomics.RESULTS: Male mice receiving FMT from obese donors exhibited marked BAT whitening and impaired amino acid and glucose metabolism. In contrast, female recipients developed hyperglycemia, accompanied by gut barrier dysfunction and WAT impairment. Distinct microbial and metabolite profiles were associated with these phenotypes: Collinsella and trimethylamine in females; and Paraprevotella, Collinsella, Lachnospiraceae NK4A136, Bacteroides, Coprobacillus, and multiple metabolites in males. These phenotypic effects persisted despite changes in host environment and diet.CONCLUSION: Early-life FMT induced long-lasting effects on the metabolic landscape, profoundly affecting adipose tissue function and systemic glucose homeostasis in adulthood. Donor dietary habits correlated with the fecal microbial profiles observed in recipient mice. These findings highlight the critical need for identifying and leveraging beneficial exposures during early development to combat obesity and diabetes.PMID:40288637 | DOI:10.1016/j.molmet.2025.102157

Biochim Biophys Acta Mol Basis Dis. 2025 Apr 25:167873. doi: 10.1016/j.bbadis.2025.167873. Online ahead of print.ABSTRACTINTRODUCTION: Leigh syndrome is often caused by Ndufs4 mutations. The Ndufs4 knockout (KO) mouse model recapitulates key disease features, including systemic inflammation, neurodegeneration, and motor deficits. While dietary interventions such as the ketogenic diet show promise in mitigating mitochondrial dysfunction, conflicting results highlight uncertainties regarding its efficacy. Here, we evaluate the therapeutic potential of a polyunsaturated fatty acid (PUFA)-enriched high-fat diet (HFD) in Ndufs4 KO mice.METHODS: Dietary intervention began at postnatal day 23, with mice receiving either a normal diet (ND) or a HFD enriched with PUFAs. Phenotypic evaluation, including locomotor function, clasping behaviour, and survival, continued until natural death. In a second group of animals, biochemical analyses were conducted after three weeks on the diets, using Western blot to evaluate neurometabolic and inflammatory regulators, flow cytometry to quantify serum inflammation markers, and metabolic profiling to identify alterations in neurometabolism and the neurolipidome.RESULTS: The HFD significantly extended lifespan and improved clasping behaviour in Ndufs4 KO mice but had no effect on locomotor activity or grip strength decline. While whole-brain mTOR (p70S6K1, 4E-BP1) and SIRT1 (PGC1-α, TNF-α) signalling pathways remained unaffected, the diet significantly reduced serum pro-inflammatory markers TNF and IL-6. Furthermore, the PUFA-enriched HFD partially restored disruptions in TCA cycle, ketone body, branched-chain amino acid, and lipid metabolism, indicating potential metabolic reprogramming.CONCLUSION: Dietary interventions, such as a PUFA-enriched HFD, may alleviate systemic inflammation, partially correct metabolic imbalances, and mitigate specific disease phenotypes in Leigh syndrome, warranting further investigation into the underlying mechanisms and broader therapeutic applications.PMID:40288592 | DOI:10.1016/j.bbadis.2025.167873

Am J Clin Nutr. 2025 Apr 25:S0002-9165(25)00239-4. doi: 10.1016/j.ajcnut.2025.04.021. Online ahead of print.ABSTRACTBACKGROUND: Increasing evidence suggests the unique susceptibility of estrogen receptor and progesterone receptor negative (ERPR-) breast cancer to dietary fat amount and type. Dietary n-3 PUFAs, such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), may modulate breast adipose fatty acids and downstream metabolites to counteract pro-carcinogenic signaling in the mammary microenvironment.OBJECTIVE: To determine effects of ∼1 to 5 g/d EPA+DHA over 12 months on breast adipose fatty acid and oxylipin profiles in survivors of ERPR(-) breast cancer, a high-risk molecular subtype.METHODS: We conducted a proof-of-concept 12-month randomized double-blind trial comparing ∼5g/d and ∼1g/d DHA+EPA supplementation in females within 5 years of completing standard therapy for ERPR(-) breast cancer Stages 0-III. Blood and breast adipose tissue specimens were collected every 3 months for fatty acid, oxylipin, and DNA methylation (DNAm) analyses.RESULTS: A total of 51 participants completed the 12-month intervention. Study treatments were generally well-tolerated. While both doses increased n-3 PUFAs from baseline in breast adipose, erythrocytes, and plasma, the 5g/d supplement was more potent with differences of 0.76 (95% CI: 0.56, 0.96), 6.25 (95% CI: 5.02, 7.48), and 5,89 (95% CI: 4.53, 7.25)., respectively. The 5g/d dose also reduced plasma triglycerides from baseline, with change of 27.38 (95% CI: 10.99, 43.78) and 24.58 (95% CI: 9.05, 40,10) at 6 and 12 months, respectively. Breast adipose oxylipins showed dose-dependent increases in DHA and EPA metabolites. Distinct DNAm patterns in adipose tissue after 12 months suggest potential downregulation of aberrant lipid metabolism pathways at the 5g/d dose.CONCLUSIONS: Over 1 year, EPA+DHA dose-dependently increased breast adipose concentrations of these fatty acids and their derivative oxylipin metabolites and produced differential DNAm profiles involved in metabolism-related pathways critical to ERPR(-) breast cancer development. This distinct metabolic and epigenetic modulation of the breast microenvironment is achievable with high-dose n-3 PUFA supplementation.GOV IDENTIFIER: NCT02295059.PMID:40288580 | DOI:10.1016/j.ajcnut.2025.04.021

Food Chem Toxicol. 2025 Apr 25:115475. doi: 10.1016/j.fct.2025.115475. Online ahead of print.ABSTRACTAncient grains, once forgotten due to the dominance of high-yield modern crops, are making a comeback due to concerns over biodiversity loss and global food challenges. This study examines the nutritional composition, safety, and health benefits of Senatore Cappelli, an ancient Italian durum wheat variety (SCW), highlighting its potential as a functional food. Using a multi-method approach, SCW was analyzed across four food chain stages (seeds, flour, pasta, and chaff) for compositional changes, phytochemical content, and safety. The safety of raw material was assessed by determination of biogenic amines, pesticides, mycotoxins and pathogenic microorganisms. The chemical profile detected by NMR spectroscopy revealed the presence of bioactive molecules such as phenolic acids and carotenoids in the case of chaff. The toxicity of ethanolic extracts was evaluated using in vitro assays on murine BV-2 microglial cells and in vivo assays on Caenorhabditis elegans animal model. No cytotoxic effects were detected at concentrations up to 250 ng/mL for chaff extract and 1000 ng/mL for seed, flour, and pasta extracts. Additionally, SCW extracts extended the lifespan of C. elegans, indicating potential anti-aging and health-promoting properties. These results position SCW as a valuable resource for enhancing bioactive compounds, supporting its reintroduction into modern diets and its use in functional food development.PMID:40288518 | DOI:10.1016/j.fct.2025.115475

Food Chem. 2025 Apr 23;485:144498. doi: 10.1016/j.foodchem.2025.144498. Online ahead of print.ABSTRACTThe effect of drying temperature on nutritional metabolite profiles and health benefits in pellicle-free walnut kernels (WKs) remains unclear. This work used widely-targeted metabolomics to identify 1888 metabolites in WKs following three different drying methods. Among these, 697 temperature-sensitive metabolites (TSMs) were identified as key differential nutrition changes induced by drying temperature. Walnut kernels dried by hot-air drying with 80 °C (HD) had much higher antioxidant activity (around 155 %) than the other two drying methods. Based on WGCNA analysis, 249 significantly upregulated antioxidant contribution metabolites (ACMs) were identified as the primary contributors to the improved performance. Network pharmacology further revealed that these metabolites exhibit strong regulatory capabilities against neurological diseases, cardiovascular diseases, and cancer, providing optimal health benefits. A metabolic pathway network was constructed to provide insights into the potential mechanisms underlying the drying process in WKs. This work provides a theoretical basis for enhancing the quality of WKs.PMID:40288341 | DOI:10.1016/j.foodchem.2025.144498

J Hazard Mater. 2025 Apr 18;493:138334. doi: 10.1016/j.jhazmat.2025.138334. Online ahead of print.ABSTRACTThe environmental prevalence of the tire wear-derived emerging pollutant N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q) has increasingly raised public concern. However, knowledge of the adverse effects of 6PPD-Q on soil fauna is scarce. In this study, we elucidated its impact on soil fauna, specifically on the earthworm Eisenia fetida. Our investigation encompassed phenotypic, multi-omics, and microbiota analyses to assess earthworm responses to a gradient of 6PPD-Q contamination (10, 100, 1000, and 5000 μg/kg dw soil). Post-28-day exposure, 6PPD-Q was found to bioaccumulate in earthworms, triggering reactive oxygen species production and consequent oxidative damage to coelomic and intestinal tissues. Transcriptomic and metabolomic profiling revealed several physiological perturbations, including inflammation, immune dysfunction, metabolic imbalances, and genetic toxicity. Moreover, 6PPD-Q perturbed the intestinal microbiota, with high dosages significantly suppressing microbial functions linked to metabolism and information processing (P < 0.05). These alterations were accompanied by increased mortality and weight loss in the earthworms. Specifically, at an environmental concentration of 6PPD-Q (1000 μg/kg), we observed a substantial reduction in survival rate and physiological disruptions. This study provides important insights into the environmental hazards of 6PPD-Q to soil biota and reveals the underlying toxicological mechanisms, underscoring the need for further research to mitigate its ecological footprint.PMID:40288322 | DOI:10.1016/j.jhazmat.2025.138334

Food Chem. 2025 Apr 22;484:144455. doi: 10.1016/j.foodchem.2025.144455. Online ahead of print.ABSTRACTErgot alkaloids (EA) are mycotoxins produced by Claviceps purpurea which commonly infects various cereal species, compromising food safety. This study evaluates the potential of the electronic nose to reliably predict EA contamination in wheat, demonstrating as a proof-of-concept the ability of this technology combined with supervised techniques to distinguish samples contaminated at levels of interest from compliant samples. In particular, the average value of samples correctly classified using PLS-DA was 95.5 %. Furthermore, a volatilomics approach based on HS-SPME/GC-Orbitrap HRMS and chemometrics was successfully applied for the first time to characterize the volatile compound pattern of wheat samples based on the level of EA contamination paying attention to the secondary volatile metabolites. Overall, a high confidence in compound identification was achieved with sub-1 ppm mass accuracy. Unsupervised PCA was used for discrimination purposes, revealing 19 differential compounds (markers), some of which are released during the growth of Claviceps Purpurea fungi.PMID:40288212 | DOI:10.1016/j.foodchem.2025.144455

Sci Total Environ. 2025 Apr 26;979:179518. doi: 10.1016/j.scitotenv.2025.179518. Online ahead of print.ABSTRACTOrganic molecules exuded into water column by marine organisms represent a significant portion of marine dissolved organic matter (DOM) that modulates biochemical interactions. Secreted allelochemicals have been suggested to be involved in regulation of pathogen abundance in seagrass meadows, however, seagrass exometabolome has remained unstudied. We aimed to identify seagrass exometabolites, within and outside meadows, and explore their potential involvement in pathogen suppression under varying environmental conditions. We collected seawater (SW) samples from eelgrass (Zostera marina)-vegetated (V) and non-vegetated (NV) areas across 5 locations spanning 270 km of coastline along the German Baltic Sea. Comparative LC-MS/MS-based untargeted computational metabolomics combined with statistical analyses and machine learning tools were employed to pinpoint (exo)metabolomic signatures of eelgrass leaves. Simultaneously, we measured abiotic parameters and the abundance of three common pathogenic taxa in seawater, and investigated spatiotemporal variations. Here we show the correlation of pathogen biomass and eelgrass pathogen reduction effect with increasing seawater temperature, eutrophication and anthropogenic influences. Exometabolomics studies revealed that eelgrass exudates contributed significantly to overall seawater DOM at molecular level, while SW overlying eelgrass meadows contained many chemical features unique to the eelgrass leaf metabolome. We identified four flavone aglycones as key biomarkers distinguishing SW-V and SW-NV samples. Their drastically increased concentrations correlated with the lowest pathogen biomass, suggesting their role in pathogen regulation. These combined analytical and microbiological approaches indicate that flavones are defensive allelochemicals released into eelgrass meadows upon environmental stress and serve as potential bioindicators of eelgrass' sanitation effect.PMID:40288169 | DOI:10.1016/j.scitotenv.2025.179518

Mol Genet Metab. 2025 Apr 19;145(2):109112. doi: 10.1016/j.ymgme.2025.109112. Online ahead of print.ABSTRACTMucopolysaccharidosis (MPS) types III A and C are inherited neurodegenerative disorders resulting from the lack of a specific enzyme involved in heparan sulfate (HS) catabolism, leading to the accumulation of partially-degraded HS fragments. At present, there are no approved treatments and death is commonly in the second decade of life. Several therapies have undergone pre-clinical evaluation for these conditions, including substrate reduction therapy, with the most studied compound of this class being the isoflavone genistein. However, findings from a Phase III clinical trial demonstrated that high dose oral genistein did not significantly improve neurodevelopmental outcomes in patients with MPS III (Sanfilippo syndrome). Here, we have tested an N-acetylglucosamine analogue, 4-deoxy-N-acetylglucosamine peracetate, as a novel substrate reduction therapy for HS-storing lysosomal storage disorders such as MPS III. Treatment with this compound significantly reduced HS levels in cultured MPS IIIA patient and mouse fibroblasts in a time- and dose-dependent manner. MPS IIIC Drosophila fed 4-deoxy-N-acetylglucosamine peracetate contained significantly less HS relative to those raised on control diets. Likewise, improvements in HS load within the MPS IIIA mouse brain suggests that the compound crossed the blood-brain barrier after oral administration. Although long-term studies are needed, these findings indicate that 4-deoxy-GlcNAc peracetate may be beneficial in slowing the accumulation of HS and may represent a novel substrate reduction therapeutic for MPS III and potentially other HS-storing disorders.PMID:40288156 | DOI:10.1016/j.ymgme.2025.109112

Int J Food Microbiol. 2025 Apr 23;437:111219. doi: 10.1016/j.ijfoodmicro.2025.111219. Online ahead of print.ABSTRACTCarbendazim (CBZ) is a broad-spectrum fungicide commonly used in agriculture, but its residue can contaminate beer ingredients, potentially affecting Saccharomyces cerevisiae and beer quality. In this work, the effect of CBZ on Saccharomyces cerevisiae Saflager S-189 (S-189) and beer quality was investigated. The results demonstrated that S-189 was inhibited at concentrations equal to or exceeding 150 μg/kg of CBZ, reducing its growth rate, cell number, viability, and damaging cell structure. The CBZ disrupted multiple metabolic pathways in S-189, including amino acid biosynthesis, tRNA biosynthesis, and ABC transporters, and negatively affected energy metabolism, antioxidant activity, nutrient transport, and fermentation performance. Compared with the control group, the fermentation degree, alcohol content, and total acidity of beer fermented with 300 μg/kg CBZ-contaminated wort decreased, while the true concentration, pH, turbidity, and alcohol-ester ratio increased. Furthermore, CBZ changed the content of key flavor substances in beer, which affected the flavor quality of beer.PMID:40288109 | DOI:10.1016/j.ijfoodmicro.2025.111219

J Plant Physiol. 2025 Apr 16;309:154494. doi: 10.1016/j.jplph.2025.154494. Online ahead of print.ABSTRACTMetabolomics is a rapidly evolving field focused on the comprehensive identification and quantification of small molecules in biological systems. As the final layer of the biological hierarchy following of the genome, transcriptome and proteome, it presents a dynamic snapshot of phenotype, influenced by genetic, environmental and physiological factors. Whilst the metabolome sits downstream of genes and proteins, there are multiple higher levels-tissues, organs, the entire organism, and interactions with other organisms, which need to be considered in order to fully comprehend organismal biology. Advances in metabolomics continue to expand its applications in plant biology, biotechnology, and natural product discovery unlocking many of nature's most beneficial colors, tastes, nutrients and medicines. Flavonoids and other specialized metabolites are essential for plant defense against oxidative stress and function as key phytonutrients for human health. Recent advancements in gene-editing and metabolic engineering have significantly improved the nutritional value and flavor of crop plants. Here we highlight how advanced metabolic analysis is driving improvements in crops uncovering genes that influence nutrient and flavor profile and plant derived compounds with medicinal potential.PMID:40288107 | DOI:10.1016/j.jplph.2025.154494

Cell Rep. 2025 Apr 25;44(5):115623. doi: 10.1016/j.celrep.2025.115623. Online ahead of print.ABSTRACTTissue-resident macrophages (TRMs) populate throughout various tissues, and their homeostatic metabolism is heavily influenced by these microenvironments. Peroxisomes are organelles that contribute to lipid metabolism. However, the involvement of these organelles in the bioenergetics of TRMs remains undetermined. We conducted a developmental screen of TRMs using a conditional peroxisomal biogenesis factor 5 (Pex5) knockout mouse model that lacks functional peroxisomes in all immune cell subsets. Pulmonary alveolar macrophages (AMs) appeared as the only subset of TRMs that required functional peroxisomes for their development. Pex5 deficiency resulted in reduced AM survival due to increased sensitivity to lipotoxicity, in line with an excess accumulation of ceramides. The absence of peroxisomes had a significant effect on overall mitochondrial fitness and altered their metabolic program, allowing them to engage in glycolysis in addition to oxidative phosphorylation. Our results revealed that AMs have a unique metabolic regulation, where peroxisomes play a central role in their homeostatic development and maintenance.PMID:40287943 | DOI:10.1016/j.celrep.2025.115623

STAR Protoc. 2025 Apr 25;6(2):103794. doi: 10.1016/j.xpro.2025.103794. Online ahead of print.ABSTRACTAnalysis of metabolites provides key insights into brain physiology and function. Due to post-mortem metabolism, both the euthanasia method and dissection time can make a critical difference. Here, we describe a protocol to euthanize rodents by microwave irradiation. This workflow details steps for animal placement, tissue fixation, and post-fixation processing. This protocol enables the rapid halting of metabolic activity for the accurate assessment of the metabolome in situ for analyses such as mass spectrometry and nuclear magnetic resonance. For complete details on the use and execution of this protocol, please refer to Juras et al.1.PMID:40287939 | DOI:10.1016/j.xpro.2025.103794

Diabetol Metab Syndr. 2025 Apr 26;17(1):139. doi: 10.1186/s13098-025-01701-z.ABSTRACTBACKGROUND: This study explores the causal relationships between five major lipids, 249 circulating metabolites, and four diabetic retinopathy (DR) outcomes: overall DR, background DR, severe background DR, and proliferative DR (PDR). We aim to identify plasma proteins that mediate these causal effects, offering insights into potential therapeutic targets.METHODS: We conducted metabolome-wide Mendelian randomization (MR) analyses to assess associations between major lipids, metabolites, and DR outcomes. Multivariable MR (MVMR) and proteome-wide mediated MR (two-step MR) analyses were performed to ensure robust evaluation and identify mediating plasma proteins.RESULTS: Triglycerides were identified as a significant risk factor for DR, mediated by proteins like Dickkopf-3 (DKK3), ST6 N-acetylglucosamine transferase 6 (ST4S6), and Neogenin (NEO1). For background DR, HDL-C, specific VLDL particles, and LDL triglycerides were protective, mediated by proteins like chloride intracellular channel 5 (CLIC5), basal cell adhesion molecule (BCAM), and Ribophorin I (RPN1). Additionally, polyunsaturated fatty acids (PUFAs) and total choline were protective against PDR, mediated by Radical Fringe Gene (RFNG).CONCLUSIONS: This study identifies specific plasma proteins that mediate the effects of lipids and metabolites on DR, establishing a direct molecular link between these biomarkers and disease progression. These findings enhance our understanding of the pathophysiological mechanisms underlying DR and highlight potential targets for therapeutic intervention.PMID:40287778 | DOI:10.1186/s13098-025-01701-z