PubMed

Food Res Int. 2025 Jun;211:116423. doi: 10.1016/j.foodres.2025.116423. Epub 2025 Apr 18.ABSTRACTAs a cutting-edge physical preservation technique, the cellular biological effect of short-term high-intensity static magnetic field (HSMF) on fresh-cut young gingers (FGs) were explored based on metabolome analysis. Results indicated that compared with the 0 mT group, the 15 mT HSMF treatment significantly increased the water content, hardness, brittleness, and contents of total phenols and total flavonoids within FGs, while significantly reduced the weight loss and relative electrolytic leakage (P < 0.05). Furthermore, the 0 mT HSMF treatment caused large losses of volatile terpenes, increases in primary metabolite abundance, and alterations of secondary bioactive component composition within FGs. Compared with the 0 mT group, the HSMF treatments went against the accumulation of primary metabolites, especially amino acids, fatty acids, organic acids. However, the HSMF treatments facilitated the preservation of secondary bioactive metabolites to varying extents. The application of 25 mT and 35 mT HSMF treatments maximally retarded the losses of volatile terpenes while 15 mT HSMF treatment significantly preserved specific terpenoids and phenylpropanoids. These results could be attributed to the suppression of respiration and energy-related pathways, i.e. glycolysis, TCA cycle, pentose phosphate pathway, and purine metabolism, in FGs. These findings may serve as a theoretical foundation and technical reference for the control of FG quality, while also addressing the paucity of research on the cellular biological effects of magnetic fields.PMID:40356113 | DOI:10.1016/j.foodres.2025.116423

Food Res Int. 2025 Jun;211:116393. doi: 10.1016/j.foodres.2025.116393. Epub 2025 Apr 17.ABSTRACTType 2 diabetes mellitus (T2DM) is a complex metabolic disorder characterized by hyperglycemia and insulin resistance. Plantain shell powder (PHP) serves as a high-quality source of dietary fiber, widely utilized in food additives and pharmaceutical applications. In this study, we investigated the hypoglycemic activity and underlying mechanisms of PHP by examining its effects on intestinal microbiota and metabolism in T2DM mice induced by a high-fat diet and streptozotocin (STZ). Our findings indicate that PHP significantly enhances blood glucose homeostasis and insulin sensitivity, reduces organ damage, and regulates blood lipid levels as well as short-chain fatty acid concentrations; notably, higher doses of PHP yielded optimal results. In addition, PHP can regulate the ratio of Bacteroidota to Firmicutes and increase the relative abundance of beneficial bacteria such as Bacteroidales, Muribaculaceae, and Parabacteroides. Furthermore, PHP enhances the enrichment of key metabolic pathways, including α-linolenic acid metabolism, monobactam biosynthesis, and PPAR signaling pathways, thereby promoting the production of beneficial metabolites. Complex interactions exist among these beneficial bacteria and metabolic pathways that are associated with improved metabolic function, regulation of glucose homeostasis, enhancement of insulin sensitivity, and reduction of inflammation. Our study demonstrates that PHP can ameliorate T2DM by reversing alterations in gut microbiota and metabolic profiles caused by T2DM while promoting the regulation of beneficial microbial populations.PMID:40356108 | DOI:10.1016/j.foodres.2025.116393

Food Res Int. 2025 Jun;211:116394. doi: 10.1016/j.foodres.2025.116394. Epub 2025 Apr 18.ABSTRACTThe bioactive compounds present in cocoa, such as polyphenols and methylxanthines, are known for their health benefits. The concentration of these compounds in cocoa beans is influenced by genotype and post-harvest processing. This study utilized a targeted metabolomics approach using UPLC-MS/MS to quantify polyphenols (flavan-3-ols, anthocyanins, flavonols, and phenolic acids) and methylxanthines in fermented and unfermented cocoa beans from 18 genotypes largely cultivated in the Brazilian Amazon region. The major compounds identified were theobromine, (-)-epicatechin, procyanidin C1, procyanidin B2, and caffeine. Fermentation significantly reduced the concentration of most compounds, except for protocatechuic acid, which increased. Principal component analysis revealed that chemical differences between fermented and unfermented cocoa beans are more pronounced than those between genotypes, mainly due to flavan-3-ols and anthocyanins. The concentrations of bioactive compounds varied significantly among the 18 genotypes both before and after fermentation. The fermented beans were grouped into three distinct clusters, the genotype CAB214 exhibited the lowest concentrations of bioactive compounds, while CCN51 had the highest. The observed chemical diversity has important implications for the selection of genotypes aimed at producing chocolate with high levels of bioactive compounds and for formulating products in other industries.PMID:40356107 | DOI:10.1016/j.foodres.2025.116394

Food Res Int. 2025 Jun;211:116379. doi: 10.1016/j.foodres.2025.116379. Epub 2025 Apr 17.ABSTRACTThe aroma components and sensory characteristics of fresh cheese fermented with three novel probiotics (Lacticaseibacillus rhamnosus B6, Limosilactobacillus fermentum B44, and Lacticaseibacillus rhamnosus KF7) were investigated using an omics approach based on HS-SPME-GC-TOFMS. Multi-dimensional and single-dimensional predictive mathematical models were developed to analyze the relationship between sensory scores and characteristic compounds. The results demonstrated that the three probiotics significantly influenced the volatile metabolite composition and sensory properties of fresh cheese. Totally 16 key aroma compounds (OAV ≥ 1) were identified. Based on OAV and (O) PLS-DA, 4, 7, and 4 significantly upregulated key aroma compounds were detected in the B6, B44, and KF7 groups, respectively. The metabolic pathways of these key compounds were reconstructed, revealing their association with fatty acid β-oxidation, aromatic amino acid metabolism, glycolysis, and esterification. L. fermentum B44, L. rhamnosus KF7, and L. rhamnosus B6 promoted the production of favorable key volatiles, altering flavor profiles. The samples of B6, B44, and KF7 groups exhibited distinct flavor characteristics described as "milk odor", "cheese odor", and "lactic odor", respectively, with the B44 sample achieving the highest overall acceptance. A natural logarithm-based partial least squares regression model was optimized, and the suitability of a nonparametric Bayesian Gaussian regression model for fitting sensory scores was confirmed. Among the identified compounds, 1-pentanol emerged as the most likely sensory score marker. This study elucidated the mechanisms underlying the formation of characteristic flavors and metabolites in probiotic fresh cheese and provided a reliable correlation model to support flavor regulation and quality control.PMID:40356103 | DOI:10.1016/j.foodres.2025.116379

Food Res Int. 2025 Jun;211:116373. doi: 10.1016/j.foodres.2025.116373. Epub 2025 Apr 16.ABSTRACTMeizhan Oolong tea is renowned for its rich floral aroma. Understanding the key characteristic aromas of Meizhan Oolong tea and their formation mechanisms during post-harvest processing is help for the further utilization and quality improvement of the Meizhan cultivar. Here, we conducted an integrative analysis of the volatile metabolome and transcriptome during the processing of Meizhan Oolong tea. These results indicate that linalool, phenylacetaldehyde, jasmone, indole, and methyl nonyl ketone contribute to the characteristic aroma of the Meizhan oolong tea, with their accumulation primarily induced by the green-making process. The aroma of Meizhan Oolong tea is regulated by multiple transcription factors, among which CsMYB62 was identified as a hub gene, with its expression level increasing as processing progresses. Through DNA affinity purification sequencing and transcriptome sequencing analysis, 7754 direct target genes of CsMYB62, including those involved in various aspects of aroma formation, were identified. Notably, CsMYB62 can bind to the promoter regions of the CsHDS, CsCM, CsADT, and CsMAO genes, positively regulating the formation of linalool and phenylacetaldehyde. These findings increase our understanding of the regulatory mechanisms involved in the quality of Meizhan Oolong tea during postharvest processing.PMID:40356100 | DOI:10.1016/j.foodres.2025.116373

Food Res Int. 2025 Jun;211:116369. doi: 10.1016/j.foodres.2025.116369. Epub 2025 Apr 17.ABSTRACTPrediabetes represents a pivotal stage in the development and pathogenesis of diabetes, during which notable alterations in the gut microbiota can be observed. Vitamin D (VD) showed anti-diabetic properties, but it is unknown whether the improvement of VD on hyperglycemia is associated with gut microbiota. Thus, our objective was to investigate and verify the effects of VD3 on glucose metabolism in prediabetes, as well as to elucidate the underlying mechanisms. In this study, different concentrations of VD3 were intraperitoneally administered to prediabetic mice induced by high fat diet for 16 weeks. Biochemical analyses, oral glucose tolerance test, 16S rRNA and untargeted metabolomics were used, the mechanism was explored. Then, fecal suspensions collected from the above donors were transplanted into KKay mice for 6 weeks, and the relevant indicators were measured. The results showed that VD3 intervention alleviated glucose metabolism in KKay mice. It increased the protein expression of colon tight junction proteins, alleviated metabolic endotoxemia and inflammation, so that reduced tumor necrosis factor alpha (TNFα) induced toll-like receptor 4/nuclear factor kappa-B (TLR4/NFκB) and improvement of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) insulin signaling pathway. VD3 affected the structure of gut microbiota and metabolites, and functional prediction analysis suggested that VD3 may affect carbohydrate. Besides, the effect of VD3 could be delivered by fecal microbiota transplantation (FMT). Consequently, VD3 ameliorate glucose metabolism by modulating gut microbiota and metabolites in KKay mice, and this ability could be transferred by FMT.PMID:40356099 | DOI:10.1016/j.foodres.2025.116369

Food Res Int. 2025 Jun;211:116363. doi: 10.1016/j.foodres.2025.116363. Epub 2025 Apr 16.ABSTRACTThe natural fermentation of soy sauce presents challenges in process control and raw material residue, limiting its suitability for modern production. This study utilized absolute quantification techniques to investigate inoculation parameters, fermentation performance, biological perturbation, and flavor regulation mechanisms of Staphylococcus carnosus DG06 in Cantonese soy sauce fermentation (CSSF). Results indicated that inoculating S. carnosus DG06 at 6.7 log CFU/g on day 7 significantly enhanced flavor development, particularly esters, alcohols, and ether compounds, while accelerating amino acid production. Although microbial composition and dynamic trends in traditional fermentation (TF) and inoculated fermentation (5IF7) were similar, 5IF7 significantly increased microbial abundance through synergistic interactions among Staphylococcus with Starmerella and Wickerhamiella. Correlation analysis revealed that these interactions promoted flavor production in CSSF. This study provides fermentation parameters of key functional strains for the application of synthetic microbial consortia in intelligent soy sauce brewing.PMID:40356097 | DOI:10.1016/j.foodres.2025.116363

Microb Cell Fact. 2025 May 13;24(1):103. doi: 10.1186/s12934-025-02731-y.ABSTRACTBACKGROUND: The modification of single or multiple genes via metabolic engineering can lead to the dysregulation of central metabolism and affect bacterial growth and metabolite accumulation. Meanwhile, transcription factor engineering can trigger metabolic network reprogramming at the global or systemic level, redirecting metabolic flux toward the synthetic pathways of target metabolites. In this study, we modulated pyrimidine and carbon-nitrogen metabolism in Bacillus subtilis through transcription factor engineering to promote the synthesis of cytidine, a drug intermediate.RESULTS: First, cytidine synthesis was enhanced by knocking out the transcriptional regulator PyrR, which increased the cytidine titer during shake flask fermentation to 0.67 g/L. Second, mutations in the transcriptional regulator catabolite control protein A (CcpA) significantly promoted cytidine synthesis, increasing the shake flask titer to 2.03 g/L. Finally, after culture in a 5 L fermenter, the cytidine titer reached 7.65 g/L, which was 3.77-fold that of shake flask fermentation. Moreover, a cytidine yield and productivity of 0.06 g/g glucose and 0.16 g/L/h, respectively, were achieved. Subsequently, the regulatory mechanisms through which PyrR and CcpA modification affect cytidine biosynthesis were explored through multi-omics analysis. Transcriptome and metabolome analysis revealed that coordinated alterations in carbon, nitrogen, nucleotide, and amino acid metabolism were essential to promote cytidine synthesis. However, the increased cytidine production in recombinant strains was attributed to the enhancement of pyrimidine metabolism, the Phosphotransferase (PTS) system, the tricarboxylic acid (TCA) cycle, the pentose phosphate (PP) pathway, and nitrogen metabolism.CONCLUSIONS: These results indicate that PyrR knockdown can enhance pyrimidine metabolic pathway and promote cytidine synthesis. CcpA mutation can reprogram the central carbon-nitrogen metabolic network, change the metabolic flow to de novo synthesis pathway of pyrimidine nucleoside, increase the supply of cytidine synthesis precursors and promote the accumulation of cytidine. Overall, regulation of engineered carbon and nitrogen metabolic networks is essential for improving the efficiency of microbial cell factories.PMID:40355953 | DOI:10.1186/s12934-025-02731-y

Breast Cancer Res. 2025 May 12;27(1):74. doi: 10.1186/s13058-025-02039-0.ABSTRACTBACKGROUND: In tumors rich in adipose tissue, angiogenesis is a critical factor in promoting cancer cell metastasis. However, the connection between angiogenesis and the mechanisms driving adipose metabolic remodeling in breast cancer (BC) remains insufficiently understood. This research seeks to explore whether and how CPT1A, a crucial rate-limiting enzyme in fatty acid oxidation (FAO), supports angiogenesis through metabolic pathways in BC.METHODS: First, cell functional assays and animal models were employed to elucidate the pro-carcinogenic effects of CPT1A on BC and its role in metabolic alterations. Following this, the reciprocal regulatory relationship between CPT1A and HIF-1α was elucidated using transcriptomic studies, ubiquitination analysis, and dual-luciferase assays. Matrigel tube formation assays, vasculogenic mimicry assays, and chick chorioallantoic membrane (CAM) assays were utilized to evaluate the effect of CPT1A on the pro-angiogenic properties of BC. Subsequently, untargeted metabolomics was employed to identify specific metabolic changes in supernatants with and without CPT1A expression and verified by functional recovery experiments. Finally, the prognostic significance of CPT1A and the vascular marker VEGF in BC tissues was evaluated using tissue microarrays and public databases.RESULTS: CPT1A overexpression significantly enhanced cell proliferation, motility, and angiogenesis via activating the FAO metabolic pathway, as demonstrated by both in vivo and in vitro experiments. Mechanistically, CPT1A regulates the ubiquitination level of hypoxia-inducible factor-1α (HIF-1α), which directly binds to the CPT1A promoter. Mutations at the 63-74 and 434-445 regions significantly reduced CPT1A promoter activity, indicating that these sites are critical for its transcriptional regulation. Ultimately, this interaction creates a reinforcing feedback loop between CPT1A and HIF-1α. Subsequently, this feedback loop alters changes in extracellular L-ascorbic acid (LAA) levels. Interestingly, LAA affects ROS homeostasis through the Nrf2/NQO1 pathway, specifically influencing angiogenesis in BC and HUVECs, while having no significant effect on their proliferation or EMT process. Moreover, increased expression levels of CPT1A and vascular endothelial growth factor (VEGF) were significantly associated with lymph node metastasis and adverse outcomes in BC patients.CONCLUSION: The CPT1A/HIF-1α positive feedback loop critically regulates angiogenesis through activation of the Nrf2/NQO1 pathway, modulated by LAA. These findings highlight CPT1A and VEGF as promising therapeutic targets and prognostic biomarkers for angiogenesis in BC.PMID:40355947 | DOI:10.1186/s13058-025-02039-0

Chin Med. 2025 May 12;20(1):62. doi: 10.1186/s13020-025-01112-2.ABSTRACTMass spectrometry (MS)-based metabolomics has emerged as a transformative tool to unraveling components and their mechanisms in traditional Chinese medicine (TCM). The integration of advanced analytical platforms, such as LC-MS and GC-MS, coupled with metabolomics, has propelled the qualitative and quantitative characterization of TCM's complex components. This review comprehensively examines the applications of MS-based metabolomics in elucidating TCM efficacy, spanning chemical composition analysis, molecular target identification, mechanism-of-action studies, and syndrome differentiation. Recent innovations in functional metabolomics, spatial metabolomics, single-cell metabolomics, and metabolic flux analysis have further expanded TCM research horizons. Artificial intelligence (AI) and bioinformatics integration offer promising avenues for overcoming analytical bottlenecks, enhancing database standardization, and driving interdisciplinary breakthroughs. However, challenges remain, including the need for improved data processing standardization, database expansion, and understanding of metabolite-gene-protein interactions. By addressing these gaps, metabolomics can bridge traditional practices and modern biomedical research, fostering global acceptance of TCM. This review highlights the synergy of advanced MS techniques, computational tools, and TCM's holistic philosophy, presenting a forward-looking perspective on its clinical translation and internationalization.PMID:40355943 | DOI:10.1186/s13020-025-01112-2

Nutr Metab (Lond). 2025 May 12;22(1):41. doi: 10.1186/s12986-025-00936-x.ABSTRACTOBJECTIVE: This study was designed to explore the metabolism features in systemic lupus erythematosus (SLE) and to investigate the role and regulatory mechanism of taurine in the control of CD4+ T cells and the progression of SLE.METHODS: Metabolomic profiles of sera from SLE patients and healthy controls (HCs) were analyzed by mass spectrometry. The therapeutic effects of taurine in vivo were observed in resiquimod (R848) induced mice, and the effects of taurine on various functions of CD4+ T cells were examined by flow cytometry. The effect of mTORC1 agonist MHY1485 on the regulatory capacity of taurine was examined in vitro.RESULTS: Both untargeted metabolomics assays and independent sample validation showed that serum levels of taurine were reduced in SLE patients compared to HCs (P<0.0001), which was inversely correlated with disease activity scores (P<0.05). Taurine supplementation relieved the progression of lupus in R848 induced mice, characterized by a decrease in anti-dsDNA (P<0.01) and proteinuria (P<0.05) and a reduction in the severity of nephritis (P<0.05). And, taurine supplementation improved the differentiation of cell subsets such as Th17 (P<0.001) and Treg cells (P<0.001) in these mice. In vitro, taurine suppressed reactive oxygen species production (P<0.001), proliferation (P<0.0001) and senescence (P<0.0001) of mouse spleen cells. The level of pS6 (P<0.0001) but not AKT in CD4+ T was significantly decreased after taurine treatment, while mTORC1 agonists partially blocked the effect of taurine on CD4+ T cells.CONCLUSION: Taurine may play a therapeutic role by ameliorating CD4+ T cell abnormalities through inhibition of mTORC1 signaling in SLE.PMID:40355931 | DOI:10.1186/s12986-025-00936-x

Nutr Metab (Lond). 2025 May 12;22(1):42. doi: 10.1186/s12986-025-00928-x.ABSTRACTPURPOSE: This study aimed to explore metabolite pathways and identify residual metabolites during the post-neonatal intrahepatic cholestasis caused by citrin deficiency (post-NICCD) phase, while developing a predictive model for failure to thrive (FTT) using selected metabolites.METHOD: A case-control study was conducted from October 2020 to July 2024, including 16 NICCD patients, 31 NICCD-matched controls, 34 post-NICCD patients, and 70 post-NICCD-matched controls. Post-NICCD patients were further stratified into two groups based on growth outcomes. Biomarkers for FTT were identified using Lasso regression and random forest analysis. A non-invasive predictive model was developed, visualized as a nomogram, and internally validated using the enhanced bootstrap method. The model's performance was evaluated with receiver operating characteristic curves and calibration curves. Metabolite concentrations (amino acids, acylcarnitines, organic acids, and free fatty acids) were measured using liquid chromatography or ultra-performance liquid chromatography-tandem mass spectrometry.RESULTS: The biosynthesis of unsaturated fatty acids was identified as the most significantly altered pathway in post-NICCD patients. Twelve residual metabolites altered during both NICCD and post-NICCD phases were identified, including: 2-hydroxyisovaleric acid, alpha-ketoisovaleric acid, C5:1, 3-methyl-2-oxovaleric acid, C18:1OH, C20:4, myristic acid, eicosapentaenoic acid, carnosine, hydroxylysine, phenylpyruvic acid, and 2-methylcitric acid. Lasso regression and random forest analysis identified kynurenine, arginine, alanine, and aspartate as the optimal biomarkers for predicting FTT in post-NICCD patients. The predictive model constructed with these four biomarkers demonstrated an AUC of 0.947.CONCLUSION: While post-NICCD patients recover clinically and biochemically, their metabolic profiles remain incompletely restored. The predictive model based on kynurenine, arginine, alanine, and aspartate provides robust diagnostic performance for detecting FTT in post-NICCD patients.PMID:40355928 | DOI:10.1186/s12986-025-00928-x

Mol Syst Biol. 2025 May 12. doi: 10.1038/s44320-025-00106-4. Online ahead of print.ABSTRACTSolute carrier (SLC) transporters govern most of the chemical exchange across cellular membranes and are integral to metabolic regulation, which in turn is linked to cellular function and identity. Despite their key role, individual functions of the SLC superfamily members were not evaluated systematically. We determined the metabolic and transcriptional profiles upon SLC overexpression in knock-out or wild-type isogenic cell backgrounds for 378 SLCs and 441 SLCs, respectively. Targeted metabolomics provided a fingerprint of 189 intracellular metabolites, while transcriptomics offered insights into cellular programs modulated by SLC expression. Beyond the metabolic profiles of 102 SLCs directly related to their known substrates, we identified putative substrates or metabolic pathway connections for 71 SLCs without previously annotated bona fide substrates, including SLC45A4 as a new polyamine transporter. By comparing the molecular profiles, we identified functionally related SLC groups, including some with distinct impacts on osmolyte balancing and glycosylation. The assessment of functionally related human genes presented here may serve as a blueprint for other systematic studies and supports future investigations into the functional roles of SLCs.PMID:40355754 | DOI:10.1038/s44320-025-00106-4

Nat Methods. 2025 May 12. doi: 10.1038/s41592-025-02660-z. Online ahead of print.ABSTRACTDespite being information rich, the vast majority of untargeted mass spectrometry data are underutilized; most analytes are not used for downstream interpretation or reanalysis after publication. The inability to dive into these rich raw mass spectrometry datasets is due to the limited flexibility and scalability of existing software tools. Here we introduce a new language, the Mass Spectrometry Query Language (MassQL), and an accompanying software ecosystem that addresses these issues by enabling the community to directly query mass spectrometry data with an expressive set of user-defined mass spectrometry patterns. Illustrated by real-world examples, MassQL provides a data-driven definition of chemical diversity by enabling the reanalysis of all public untargeted metabolomics data, empowering scientists across many disciplines to make new discoveries. MassQL has been widely implemented in multiple open-source and commercial mass spectrometry analysis tools, which enhances the ability, interoperability and reproducibility of mining of mass spectrometry data for the research community.PMID:40355727 | DOI:10.1038/s41592-025-02660-z

Rice (N Y). 2025 May 13;18(1):35. doi: 10.1186/s12284-025-00793-5.ABSTRACTEmpirical breeding efforts targeting cold tolerance and ideal plant architecture have significantly improved yield and facilitated the geographic expansion of japonica rice cultivation. However, the genetic drivers and underlying molecular mechanisms of these traits remain insufficiently understood. Here, we identify Plant Height 8 (PH8) as a key gene regulating both plant stature and cold stress response in rice. Genome wide association analysis (GWAS), supported by functional validation, shows that loss of PH8 reduces plant height without affecting other agronomic traits. Notably, we found that PH8 also negatively regulates cold tolerance. A prevalent haplotype, PH8Hap.0, exhibits reduced PH8 expression due to natural variation in its promoter region, resulting in shorter plants and enhanced cold tolerance. Selective sweep and geographic distribution analyses indicate that PH8Hap.0 originated in high-latitude regions and underwent strong directional selection during modern japonica improvement. Functional assays demonstrate that PH8 enhances cold tolerance via improved reactive oxygen species (ROS) scavenging by repressing APX2, an antioxidant gene involved in ROS detoxification. Our findings reveal PH8 as a dual regulator of plant architecture and cold stress adaptation, and highlight PH8Hap.0 as a historically selected allele that contributed to the climatic adaptation and geographical expansion of japonica rice.PMID:40355663 | DOI:10.1186/s12284-025-00793-5

Sci Rep. 2025 May 12;15(1):16474. doi: 10.1038/s41598-025-01509-x.ABSTRACTTinnitus is a prevalent and distressing medical symptom, and no effective pharmacological treatment currently exists. Despite significant advances, tinnitus remains a scientific enigma. To explore the molecular underpinnings of tinnitus, we developed a noise-induced tinnitus model in mice and utilized metabolomics to identify key differences in metabolic pathways. Our results revealed that oxidative stress-related pathways, including glutathione (GSH) metabolism, were significantly enriched in the auditory cortex of mice exhibiting tinnitus-like behavior. To further explore the role of oxidative stress, we examined the involvement of nuclear factor erythroid 2-related factor 2 (Nrf2) in tinnitus by conducting experiments in Nrf2 knockout (Nrf2-KO) mice. While Nrf2-deficient mice did not develop spontaneous tinnitus or hearing loss, they displayed increased susceptibility to prolonged tinnitus-like behavior after noise exposure. This was accompanied by heightened microglial activation, neuroinflammation, and significant alterations in gut microbiota composition, including greater diversity and dysbiosis. Our findings highlight a novel mechanism underlying tinnitus, emphasizing the role of oxidative stress in the auditory cortex and its connection to noise-induced tinnitus. The deficiency of Nrf2 in mice increases their susceptibility to tinnitus, suggesting that Nrf2 may serve as a promising therapeutic target for preventing noise-induced tinnitus.PMID:40355648 | DOI:10.1038/s41598-025-01509-x

Sci Rep. 2025 May 12;15(1):16405. doi: 10.1038/s41598-025-01753-1.ABSTRACTSN-38 (7-ethyl-10-hydroxycamptothecin), the active metabolite of irinotecan, is a crucial anticancer agent frequently studied in drug delivery systems. Irinotecan (CPT-11) is used to treat various solid tumors but is associated with adverse effects such as nausea, vomiting, diarrhea, and steatohepatitis. However, the precise biochemical pathways underlying these side effects remain unclear. To explore SN-38's toxic mechanisms and provide insights for clinical applications of SN-38 delivery systems, we performed untargeted metabolomics to assess metabolic changes in the lungs, heart, stomach, blood, spleen, intestine, liver, and kidneys of SN-38-exposed male mice. Mice were divided into two groups: SN-38 (20 mg/kg/day intraperitoneal) and control (blank solvent). Gas chromatography-mass spectrometry (GC-MS) identified significant metabolic disturbances in all tissues. Specifically, 24, 15, 12, 21, 35, 26, 18, and 28 differential metabolites were detected in the lungs, heart, stomach, blood, spleen, intestine, liver, and kidneys, respectively. KEGG pathway enrichment revealed significant changes in metabolic pathways across these organs, particularly in purine, pyrimidine, amino acid, and glyceric acid metabolism, implicating disruptions in protein synthesis, cellular homeostasis, energy metabolism, and antioxidant defenses. This study is the first to characterize SN-38's multi-organ toxicity using metabolomics.PMID:40355563 | DOI:10.1038/s41598-025-01753-1

EMBO J. 2025 May 12. doi: 10.1038/s44318-025-00450-z. Online ahead of print.NO ABSTRACTPMID:40355557 | DOI:10.1038/s44318-025-00450-z

Nat Commun. 2025 May 12;16(1):4373. doi: 10.1038/s41467-025-59487-7.ABSTRACTMetabolites, lipids, and glycans are fundamental but interconnected classes of biomolecules that form the basis of the metabolic network. These molecules are dynamically channeled through multiple pathways that govern cellular physiology and pathology. Here, we present a framework for the simultaneous spatial analysis of the metabolome, lipidome, and glycome from a single tissue section using mass spectrometry imaging. This workflow integrates a computational platform, the Spatial Augmented Multiomics Interface (Sami), which enables multiomics integration, high-dimensional clustering, spatial anatomical mapping of matched molecular features, and metabolic pathway enrichment. To demonstrate the utility of this approach, we applied Sami to evaluate metabolic diversity across distinct brain regions and to compare wild-type and Ps19 Alzheimer's disease (AD) mouse models. Our findings reveal region-specific metabolic demands in the normal brain and highlight metabolic dysregulation in the Ps19 model, providing insights into the biochemical alterations associated with neurodegeneration.PMID:40355410 | DOI:10.1038/s41467-025-59487-7

Medicine (Baltimore). 2025 May 9;104(19):e42332. doi: 10.1097/MD.0000000000042332.ABSTRACTThis study aimed to investigate the causal relationship between lipidomes and chronic kidney disease (CKD) and identify and quantify the role of immune cells as a potential mediator. Using summary-level data from a genome-wide association study, a 2-sample Mendelian randomization (MR) analysis of genetically predicted lipidomes (7174 cases) and CKD (406,745 cases) was performed. Furthermore, we used 2-step MR to quantitate the proportion of the effect of immune cells traits-mediated lipidomes on CKD. The MR analysis revealed a causal relationship between lipidomes and CKD, with different lipidomes either increasing or decreasing the risk of CKD. Immune cells may serve as intermediaries in the pathway from lipidomes to CKD. Our study indicates that CD33 on basophils accounts for 3.23% of the reduced risk associated with triacylglycerol (53:3) levels in CKD. In conclusion, our study has identified a causal relationship between lipidomes and CKD, as well as the mediating role of CD33 on basophils. However, other risk factors like potential mediators require further investigation. In clinical practice, particular attention should be paid to lipidomic changes, especially triacylglycerol, in patients with CKD.PMID:40355216 | DOI:10.1097/MD.0000000000042332