PubMed
Gut microbiota and metabolites are linked to disease progression in multiple sclerosis
Cell Rep Med. 2025 Mar 27:102055. doi: 10.1016/j.xcrm.2025.102055. Online ahead of print.ABSTRACTProgressive multiple sclerosis (MS) is a neurological disease with limited understanding of the biology associated with transition from relapsing to progressive disease. Intestinal microbes and metabolites are altered in MS, but relation to disease progression is largely unknown. We investigate microbiota and metabolites in subjects with stable MS, those who worsened, and in those with relapsing MS who became progressive over 2 years. We find that Eubacterium hallii, Butyricoccaceae, Blautia, and other short-chain fatty-acid-producing microbes have beneficial associations with worsening of disability, 3T magnetic resonance imaging (MRI) measures, cognition, and quality of life, while Alistipes is detrimentally associated. Global metabolomics identified serum and stool metabolites that are altered in progressive MS and in relapsing subjects who transitioned to progressive disease. Most fecal metabolites associated with disease progression are decreased, suggesting a deficiency of protective factors in the gut. Using a unique MS cohort, our findings identify gut microbiome and metabolite pathways influencing progressive MS.PMID:40185103 | DOI:10.1016/j.xcrm.2025.102055
PM<sub>2.5</sub> exacerbates nasal epithelial barrier damage in allergic rhinitis mice: A crosstalk between gut microbiota and NLRP3 inflammsome
Ecotoxicol Environ Saf. 2025 Apr 3;295:118140. doi: 10.1016/j.ecoenv.2025.118140. Online ahead of print.ABSTRACTNumerous studies have demonstrated a positive correlation between the frequency and severity of allergic rhinitis (AR) with fine particulate matter (PM2.5) exposure, although the exact mechanisms remain poorly understood. This study aimed to investigate the role of gut microbiota disorder and NLRP3 pathway activation in PM2.5-induced nasal epithelial barrier damage in AR mice. The results indicated that PM2.5 could exacerbate rhinitis symptoms and epithelial barrier damage in nasal mucosa. The NLRP3 pathway-related proteins including NLRP3, Caspase-1, GSDMD, and IL-1β were elevated. Additionally, nasal mucosa injury was significantly worsen in AR mice with gut microbiota disorder. Gut Microbiomic studies indicated the Ileibacterium and Alistipes are associated with nasal injury exacerbation. Metabolomic analysis suggested that bile acid metabolism disorder is a potential contributor to aggravate nasal mucosa damage. The correlation analysis revealed that IL-1β was positively associated with Alistipes, Ileibacterium, cholic acid and PC (15:0/15:0). Alistipes was positively correlated with LPE18:2 and negatively correlated with zonula occludens-1 (ZO-1) and Claudin-1 proteins. In summary, gut microbiota disorder may cause abnormal bile acid metabolism and NLRP3 inflammasome activation, which participate in PM2.5 exposure-induced exacerbation of epithelial barrier damage in nasal mucosa. This study supplied a new insight and potential targets for prevention and treatment of AR.PMID:40185032 | DOI:10.1016/j.ecoenv.2025.118140
Effects of hydrothermal treatment and low pH on the fermentation characteristics of polysaccharides based water-soluble Maitake with Lactobacillus acidophilus and L. plantarum
Food Chem. 2025 Mar 22;481:143933. doi: 10.1016/j.foodchem.2025.143933. Online ahead of print.ABSTRACTMaitake (Grifola frondosa) is rich in bioactive polysaccharides and is known for its health benefits. This study investigated the effects of hydrothermal treatment (HT) and low pH conditions on Maitake, revealing their effectiveness in the bioactive polysaccharide extraction and metabolite bioavailability. HT and low pH-induced significant structural changes, with WSP-HT1 showing 99.67 % degradation and yielding 41.46 % β-glucan and 0.43 % α-glucan. Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis demonstrated 45-10 kDa protein transformations, supported by molecular docking and dynamic simulations. FT-IR spectroscopy revealed carbohydrate spectral shifts and increased α-helix random coil association. Treated samples (WSP-LA-pH1, WSP-LA-pH4, WSP-LP-pH1, WSP-LP-pH4) exhibited enhanced optical density, antioxidant activity, fluorescence, and decried surface hydrophobicity. The metabolomic analysis highlighted significant pathway alterations, validated by Principal Component, Partial Least Squares Discriminant, Variable Importance in Projection, and Kyoto Encyclopedia of Genes and Genomes analysis. These findings confirm that hydrothermal treatment and low pH effectively extract active substances, enriching Maitake's medicinal properties.PMID:40184926 | DOI:10.1016/j.foodchem.2025.143933
Analysis of intrinsic effects of compound curing agents on small molecule metabolites and microbial communities in Xuanwei ham based on metabolomics and high-throughput sequencing
Meat Sci. 2025 Apr 2;225:109820. doi: 10.1016/j.meatsci.2025.109820. Online ahead of print.ABSTRACTIn order to reduce the salt content of Xuanwei ham and prevent the fading of the ham section, 18 hind legs of local black pigs were selected. The groups were cured with 6 % salt, 6 % compound curing agent I, and 6 % compound curing agent II, respectively. The differences in small molecule metabolites and microbial communities in Xuanwei ham among the groups were analyzed. The results showed that the compound curing agents promoted the release of many small molecule metabolites. The use of sugar led to the down-regulation of small molecule metabolites such as biogenic amines. Bacteria is the main cause of changes in small molecule metabolites of Xuanwei ham. Aspergillus potentially affect amino acid regulation, Yamadazyma and Debaryomyces promote lipid metabolism, and Staphylococcus promotes lipid oxidation and production of volatile compounds. These findings indicate that the compound curing agents affects small molecule metabolites and microbial communities in Xuamwei ham.PMID:40184916 | DOI:10.1016/j.meatsci.2025.109820
Plasma and urine metabolomics for the identification of diagnostic biomarkers for sulfur mustard-induced lung injury
Int Immunopharmacol. 2025 Apr 3;154:114515. doi: 10.1016/j.intimp.2025.114515. Online ahead of print.ABSTRACTBACKGROUND: Sulfur mustard (SM) is a highly lethal chemical warfare agent that induces severe health complications in exposed individuals. Gaining insights into the metabolic changes caused by SM exposure is essential for understanding its underlying mechanisms and developing effective diagnostic and therapeutic interventions.METHODS: In this investigation, we utilized proton nuclear magnetic resonance (H-NMR) spectroscopy to conduct metabolomic analysis in patients diagnosed with mustard lung disease (MLD) using a non-targeted approach. Metabolite measurements were conducted on plasma and urine samples collected from a total of 54 individuals, including 20 individuals with mild MLD, 20 individuals with moderate MLD, and 14 healthy individuals. Multivariate and univariate analyses were applied to identify metabolites that distinguish between the different groups, and enrichment analysis was performed to unveil the underlying biochemical pathways involved.RESULTS: The obtained metabolic profile had the potential to differentiate moderate from healthy plasma, but not from mild patients using multivariate analysis. Sixteen metabolites from plasma were considered significantly different between the moderate and control groups (VIP > 1 and p < 0.05) that these metabolites involved in fatty acid and amino acid metabolism. Utilizing all 16 metabolites as a combined panel, we were able to distinguish between the moderate and control groups, achieving an area under the curve (AUC) of 0.854. Moreover, 6 and 8 urinary metabolites were detected between mild vs. control and moderate vs. control groups, respectively. Fourteen metabolites exhibited significant fold changes (FC) (FC < 0.66 or FC > 1.5; p < 0.05). These metabolites are involved in amino acid and nicotinate metabolism.CONCLUSION: Our study provides novel insights into the metabolic changes associated with MLD and highlights potential pathways involved in the disease progression. These findings have implications for the development of targeted diagnostic and therapeutic strategies for MLD.PMID:40184812 | DOI:10.1016/j.intimp.2025.114515
Metabolomics analysis of osmotic tolerance enhancement mechanism of wheat gluten peptides on industrial yeast
Food Chem. 2025 Mar 28;482:144092. doi: 10.1016/j.foodchem.2025.144092. Online ahead of print.ABSTRACTPlant-derived wheat gluten peptides have an effective protective ability on industrial yeast against osmotic stress, the enhancement mechanism of osmotic tolerance in yeast by wheat gluten peptides addition was clarified in this study. Results showed that wheat gluten peptides addition increased the intracellular pH and trehalose levels of yeast under osmotic stress, compared to the control. Furthermore, peptides supplementation could regulate the antioxidant defense system and reduce the reactive oxygen species accumulation in yeast, including the increase of intracellular glutathione levels and the activities of antioxidant enzymes catalase and glutathione peroxidase. Metabolomic results indicated that the enhancement mechanism of wheat gluten peptides on yeast osmotic tolerance was related to the promotion of arginine and proline metabolism, pantothenate and coenzyme A biosynthesis, pyrimidine metabolism, and cysteine and methionine metabolism pathways. These results provide new insight into the enhancement mechanism of yeast stress tolerance by plant-derived peptides from a metabolic perspective.PMID:40184741 | DOI:10.1016/j.foodchem.2025.144092
Investigation into the effects of acute heat stress on stress level, meat quality, myofibrillar proteins properties and serum metabolites release of Muscovy ducks (Cairina moschata)
Food Chem. 2025 Mar 28;482:144104. doi: 10.1016/j.foodchem.2025.144104. Online ahead of print.ABSTRACTThis study systematically investigated the effects of acute heat stress (AHS) on Muscovy ducks, focusing on plasma stress indicators, meat quality, myofibrillar proteins (MPs) properties, and serum metabolite profiles. AHS significantly elevated stress level, impairing meat quality, as evidenced by higher L* value, shear force, drip loss, and cooking loss (P < 0.05). It also induced MPs oxidation and aggregation, reflected by elevated carbonyl content, turbidity, zeta potential, and particle size. MPs structural alterations were confirmed by fluorescence quenching and increased exposure of hydrophobic groups. Correlation analysis revealed strong associations between physicochemical changes and MPs oxidation. Metabolomic analysis identified 161 and 105 differential metabolites in the CON vs. LS and CON vs. SS comparisons, respectively, involving 25 metabolic pathways related to energy, amino acids, and fatty acids. These findings provide novel insights into the molecular pathways of AHS-induced meat quality deterioration and reveal potential intervention timing for the poultry industry.PMID:40184737 | DOI:10.1016/j.foodchem.2025.144104
Corrigendum to "Integrating serum pharmacochemistry, network pharmacology, and metabolomics to elucidate the detoxification and effect-adjusting mechanism of Chebulae Fructus-processing on Mongolian medicine Euphorbia pekinensis"[J. Ethnopharmacol. 345...
J Ethnopharmacol. 2025 Apr 3;346:119716. doi: 10.1016/j.jep.2025.119716. Online ahead of print.NO ABSTRACTPMID:40184715 | DOI:10.1016/j.jep.2025.119716
Alterations in fatty acid metabolism in patients with schizophrenia in a multi-omics perspective
Schizophr Res. 2025 Apr 3;279:94-105. doi: 10.1016/j.schres.2025.03.036. Online ahead of print.ABSTRACTBACKGROUND: Recent research has extensively explored the involvement of gut microbes in various fatty acid metabolic processes, elucidating their crucial roles in host energy homeostasis and metabolism. Nevertheless, there remains a dearth of studies examining the comprehensive profile of fatty acid metabolites in schizophrenia and their potential connection to gut microbes.METHOD: Conducting a thorough investigation, this study scrutinized the gut microbiome composition of 63 individuals, consisting of 35 schizophrenia (SZ) patients and 28 demographically matched healthy control (HC) subjects. Feces and serum samples were meticulously collected, with stool samples subjected to 16S rRNA sequencing targeting region V4 and untargeted metabolomics analysis, while serum samples underwent untargeted metabolomics assessment.RESULTS: A total of 21 different genus-level species were identified in the SZ and HC groups. Predictive analysis of gut flora pathways revealed abnormal fatty acid degradation in schizophrenia. Notably, 17 differential fatty acid metabolites were found in feces, whereas 43 were found in serum fatty acid metabolites. A higher proportion of differential fatty acid metabolites were found in serum compared to those in feces. The predominant pathways enriched in fatty acid metabolites included biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, and linoleic acid metabolism. Additionally, a significant correlation was noted between intestinal flora and fatty acids, as well as potential interactions between intestinal flora, fecal fatty acids and serum fatty acids.CONCLUSIONS: Our multi-omics study provides new insights into the pathogenesis of schizophrenia, which may inform the treatment of neurodevelopmental disorders by modifying fatty acid metabolism through modulation of the gut microbiota.PMID:40184646 | DOI:10.1016/j.schres.2025.03.036
Cardiac Slc25a49-Mediated Energy Reprogramming Governs Doxorubicin-Induced Cardiomyopathy through the G6P-AP-1-Sln Axis
Adv Sci (Weinh). 2025 Apr 4:e2502163. doi: 10.1002/advs.202502163. Online ahead of print.ABSTRACTDoxorubicin (Dox), a potent antitumor drug, is linked to cardiac toxicity. Few mechanism-based therapies against cardiotoxicity are available. Dysfunction in mitochondrial energy metabolism contributes to Dox-induced cardiomyopathy. It is aimed at exploring the association between specific mechanism of energy reprogramming and Dox-induced cardiomyopathy. Cardiac-specific ablation of Slc25a49 mice are generated by crossing Slc25a49flox/flox mice with Myh6-Cre mice. Slc25a49HKO mice or SLC25A49KD cardiomyocytes is treated with Dox. Echocardiography, histological analysis, transmission electron microscopy, bulk RNA sequencing, cell bioenergetic profiling, metabolomics test, chromatin immunoprecipitation, and dual-luciferase reporter assay are conducted to delineate the phenotype and elucidate the molecular mechanisms. Specific ablation of Slc25a49 in cardiomyocytes leads to exacerbated Dox-induced cardiomyopathy, characterized by compromised mitochondrial respiration enhanced glycolysis and increased glycolytic metabolite glucose-6-phosphate (G6P) levels, subsequently activating the activator protein-1 (AP-1) complex. The stimulation of the G6P-AP-1 axis intensifies myocardial damage via transcriptionally regulating Sarcolipin (Sln) expression. Strikingly, targeting of this axis with the AP-1 inhibitor T-5224 effectively improves survival and enhances cardiac function in Dox-induced cardiomyopathy. This study provides mechanistic insights into energy reprogramming that permits myocardial dysfunction, and thus provides a proof of concept for antienergy reprogramming therapy for Dox-induced cardiomyopathy through directly modulating G6P-AP-1-Sln axis.PMID:40184586 | DOI:10.1002/advs.202502163
Development of a Single-Cell Spatial Metabolomics Method for the Characterization of Cell-Cell Metabolic Interactions
Anal Chem. 2025 Apr 4. doi: 10.1021/acs.analchem.5c00384. Online ahead of print.ABSTRACTTumor microenvironment (TME) is characterized by complex cellular composition and high molecular heterogeneity. Characterizing the metabolic interactions between different cells in the TME is important for understanding the molecular signatures of tumors and identifying potential metabolic vulnerabilities for tumor treatment. In this research, we develop a single-cell spatial metabolomics method to profile cell-specific metabolic signatures and cell-cell metabolic interactions using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). Different low-molecular-weight metabolites and lipids including glutamate, aspartate, glutamine, taurine, phenylalanine, glutathione, fatty acids, phospholipids, etc. were successfully detected and imaged after optimizing cell culture conductive slides, cell washing, and fixation procedures. Subsequently, we carried out single-cell spatial metabolomics on H460 large-cell lung cancer cells, HT-29 colorectal cancer cells, A549 lung cancer cells, HUH-7 liver cancer cells, and cancer-fibroblasts coculture system. We revealed that the metabolic profiles of both cancer cells and fibroblasts were altered after cell coculture. Glutamate and aspartate significantly increased in fibroblasts after coculture with cancer cells, corresponding to their indispensable roles in the creation of pro-cancer microenvironment. In addition, we discovered that the expressions of fatty acids and phospholipids in tumor cells and fibroblasts were also changed after cell coculture, which is closely related to the competition for energy and nutrient metabolites between different cells. We anticipate this single-cell analysis method to be broadly used in the investigations of diverse cellular models and cell-cell metabolic interactions.PMID:40184576 | DOI:10.1021/acs.analchem.5c00384
Defining the limits of plant chemical space: challenges and estimations
Gigascience. 2025 Jan 6;14:giaf033. doi: 10.1093/gigascience/giaf033.ABSTRACTThe plant kingdom, encompassing nearly 400,000 known species, produces an immense diversity of metabolites, including primary compounds essential for survival and secondary metabolites specialized for ecological interactions. These metabolites constitute a vast and complex phytochemical space with significant potential applications in medicine, agriculture, and biotechnology. However, much of this chemical diversity remains unexplored, as only a fraction of plant species has been studied comprehensively. In this work, we estimate the size of the plant chemical space by leveraging large-scale metabolomics and literature datasets. We begin by examining the known chemical space, which, while containing at most several hundred thousand unique compounds, remains sparsely covered. Using data from over 1,000 plant species, we apply various mass spectrometry-based approaches-a formula prediction model, a de novo prediction model, a combination of library search and de novo prediction, and MS2 clustering-to estimate the number of unique structures. Our methods suggest that the number of unique compounds in the metabolomics dataset alone may already surpass existing estimates of plant chemical diversity. Finally, we project these findings across the entire plant kingdom, estimating that the total plant chemical space likely spans millions, if not more, with most still unexplored.PMID:40184432 | DOI:10.1093/gigascience/giaf033
metLinkR: Facilitating Metaanalysis of Human Metabolomics Data through Automated Linking of Metabolite Identifiers
J Proteome Res. 2025 Apr 4. doi: 10.1021/acs.jproteome.4c01051. Online ahead of print.ABSTRACTMetabolites are referenced in spectral, structural and pathway databases with a diverse array of schemas, including various internal database identifiers and large tables of common name synonyms. Cross-linking metabolite identifiers is a required step for meta-analysis of metabolomic results across studies but made difficult due to the lack of a consensus identifier system. We have implemented metLinkR, an R package that leverages RefMet and RaMP-DB to automate and simplify cross-linking metabolite identifiers across studies and generating common names. MetLinkR accepts as input metabolite common names and identifiers from five different databases (HMDB, KEGG, ChEBI, LIPIDMAPS and PubChem) to exhaustively search for possible overlap in supplied metabolites from input data sets. In an example of 13 metabolomic data sets totaling 10,400 metabolites, metLinkR identified and provided common names for 1377 metabolites in common between at least 2 data sets in less than 18 min and produced standardized names for 74.4% of the input metabolites. In another example comprising five data sets with 3512 metabolites, metLinkR identified 715 metabolites in common between at least two data sets in under 12 min and produced standardized names for 82.3% of the input metabolites. Outputs of MetLInR include output tables and metrics allowing users to readily double check the mappings and to get an overview of chemical classes represented. Overall, MetLinkR provides a streamlined solution for a common task in metabolomic epidemiology and other fields that meta-analyze metabolomic data. The R package, vignette and source code are freely downloadable at https://github.com/ncats/metLinkR.PMID:40184266 | DOI:10.1021/acs.jproteome.4c01051
Integrated metabolomics and spatial transcriptomics of cystic pancreatic cancer precursors reveals dysregulated polyamine metabolism as a biomarker of progression
Clin Cancer Res. 2025 Apr 4. doi: 10.1158/1078-0432.CCR-24-2931. Online ahead of print.ABSTRACTPURPOSE: We conducted metabolomics and spatial cell transcriptomics of intraductal papillary mucinous neoplasms (IPMN), recognized pancreatic cancer precursors, to identify oncometabolites that inform upon risk of malignancy of IPMN.EXPERIMENTAL DESIGN: Untargeted metabolomic analyses were performed on cystic fluid from 125 patients with low-grade dysplasia (LG) or high-grade (HG) dysplasia with/without concurrent PDAC (IPMN/PDAC). Predictive performance of individual metabolites for identifying HG or PDAC/IPMN was determined and compared to CA19-9 performance. Data were intersected with metabolic profiles of resected IPMN tissues and murine Kras;Gnas IPMN cell lines as well as spatial and single-cell transcriptomics of IPMN.RESULTS: A total of 388 metabolites were quantified in cystic fluid of which 69 were differential (p-value <0.05) between cases (HG IPMN + IPMN/PDAC) and patients with LG IPMN. Spermidine and spermine biosynthesis and catabolism was identified as the top perturbed metabolic pathway (FDR-adjusted p-value< 0.0001). Increases in cystic fluid spermidine, n-acetylputrescine, acetylspermidine, diacetylspermidine, diacetylspermine, and acetylcadaverine were associated elevated risk of harboring HG or IPMN/PDAC. An OR-rule comprising CA19-9, n-acetylputrescine, acetylspermidine, and diacetylspermine achieved 54.8% sensitivity for detecting HG and IPMN\PDAC. CA19-9 alone yielded sensitivity of 11.9% (McNemar Test p-value< 0.001). Polyamines were elevated in IPMN\PDAC tissues compared to LG IPMN tissues; spatial and single-cell transcriptomic data revealed transcript levels of polyamine-metabolizing enzymes to be elevated in neoplastic epithelium and tumor-associated macrophages.CONCLUSION: Cystic fluid polyamines offer utility for determining risk of malignancy of IPMN that is complementary to CA19-9, and that has potential to aid in clinical management of patients with IPMN.PMID:40184234 | DOI:10.1158/1078-0432.CCR-24-2931
Integration of Transcriptomics and Metabolomics Reveals Metabolism Dysregulation in HIV-1-Infected Macrophages
Curr Microbiol. 2025 Apr 4;82(5):232. doi: 10.1007/s00284-025-04204-2.ABSTRACTHIV-1 infection leads to metabolic changes in macrophages, yet a comprehensive understanding of its pathogenesis remains limited. To address this, we integrated transcriptomic and metabolomic analyses to uncover intracellular metabolic alterations in HIV-1-infected macrophages. We identified differentially expressed genes (DEGs) using RNA-sequencing, while metabolomic profiling was performed with UHPLC-QE-MS. The integration of transcriptomics and metabolomics was achieved through "Joint Pathway Analysis," and reverse transcription-quantitative PCR (RT-qPCR) was used to validate the identified pathways. Our transcriptomic analysis revealed a total of 890 DEGs, comprising 424 downregulated and 466 upregulated genes in macrophages infected with HIV-1. KEGG enrichment analysis highlighted the biosynthesis of amino acids and glycine, serine, and threonine metabolism as significantly enriched (P < 0.05). RT-qPCR results confirmed the expression of key genes, including PHGDH, PSAT1, PSPH, CBS, CTH, and AOC2, associated with these pathways. From the metabolomic analysis, we identified 60 differential metabolites, with glycerophospholipids representing the majority (51.67%). The integrated analysis revealed significant changes in glycine, serine, and threonine metabolism, glycerophospholipid metabolism, and linoleic acid metabolism in HIV-1-infected macrophages. This study offers an extensive overview of metabolic alterations in HIV-1-infected macrophages, which may enhance our understanding of the pathogenesis and highlight potential therapeutic targets.PMID:40183936 | DOI:10.1007/s00284-025-04204-2
Nuclear magnetic resonance-based lipid metabolite profiles for differentiation of patients with liver cirrhosis with and without hepatocellular carcinoma
J Cancer Res Clin Oncol. 2025 Apr 4;151(4):131. doi: 10.1007/s00432-025-06178-x.ABSTRACTBACKGROUND: Hepatocellular carcinoma is frequently unrecognized in its early stage limiting the access to the first therapeutic steps resulting in a low cure rate. Therefore, an early diagnosis is crucial. In this scenario the analysis of lipidome and metabolome emerged as a promising tool for early detection.AIMS: Aim of the study was to characterize metabolomic profiles as novel markers of early hepatocellular carcinoma.METHODS: Serum basal levels of metabolites, isolated from a cohort of 90 patients (n = 30 early stage; n = 30 advanced stage; n = 30 liver cirrhosis) were analysed using a nuclear magnetic resonance spectroscopy platform. To assess the predictive value of nuclear magnetic resonance profiles, we included the magnetic resonance imaging follow up of control patients with liver cirrhosis.RESULTS: Significant differences were observed in the levels of individual parameters that included total cholesterol, LDL and HDL subclasses, Isoleucine, Valine, Triglycerides, Lactate, Alanine, Albumin, alpha Fetoprotein, Dimethylamine, Glycerol, and total Bilirubin levels in cancer compared to liver cirrhosis (p < 0.05). Furthermore, a significant difference in glycerol levels (p < 0.05) and a decreasing trend in dimethylamine were observed in cirrhotic patients who later developed HCC (16%, n = 5). Retrospective MRI analysis revealed precursor lesions in 3/5 patients, initially not classified as HCC due to their size and hemodynamic features.CONCLUSION: Nuclear magnetic resonance based assessment of lipidomic and metabolomic profiles permit the differentiation of cancer from liver cirrhosis. The data obtained suggests a possible role of lipidomic based serum profiles for early detection.PMID:40183893 | DOI:10.1007/s00432-025-06178-x
Genome-wide insights into the nomenclature, evolution and expression of tobacco TIFY/JAZ genes
Planta. 2025 Apr 4;261(5):103. doi: 10.1007/s00425-025-04676-3.ABSTRACTA systematic nomenclature for tobacco TIFY/JAZ proteins was established via genome-wide analysis, and the gene transcription patterns and potential functions of these proteins were analyzed as well. Intensive studies focused on the plant-specific JAZ regulators of jasmonate (JA) signaling in tobacco due to their critical roles in regulating JA-mediated development, secondary metabolism, and stress responses. JAZs comprise a subfamily of the TIFY proteins, yet the reported TIFY/JAZ regulators of tobacco spp. are tangled in naming confusion, which resulted in nomenclature chaos. Here, we identified 32 TIFY/JAZ proteins via genome-wide analysis of tobacco cultivar TN90 and obtained their homologues in Nicotiana sylvestris and Nicotiana tomentosiformis. By bioinformatic analysis, these TIFY/JAZ regulators were classified into 4 subfamilies (i.e., 21 JAZs, 5 ZIM & ZMLs, 2 TIFY8s, and 4 PPDs) based on their phylogenetic relationship to establish a systematic nomenclature, which indicated gene loss or genomic rearrangement during the formation of common tobacco. Analysis of JA-induced expression revealed that these TIFY/JAZ genes displayed distinct expression patterns in the leaves and roots upon JA treatment. Further microarray and metabolomics assays observed that 5 TIFY/JAZ genes were differentially expressed in the plants with dysfunction of COI1, the receptor protein of JA hormone and that the abundance of a series of primary and secondary metabolites was altered as well. A predicted protein interaction network of tobacco TIFY/JAZ proteins was also constructed, and it indicated that 120 proteins may interact with these regulators. Findings of this work provide valuable information about TIFY/JAZ proteins in regulating JA responses and metabolic processes in tobacco and may contribute greatly to future studies on tobacco TIFY/JAZ proteins.PMID:40183817 | DOI:10.1007/s00425-025-04676-3
Intermittent fasting applied in combination with astaxanthin alleviates D-galactose-induced aging in rats: Comparison in oxidative stress, immune response, and metabolomics
J Food Sci. 2025 Apr;90(4):e70170. doi: 10.1111/1750-3841.70170.ABSTRACTEffective anti-aging strategies involving dietary restriction and antioxidant supplementation are gaining increasing research attention, while the health effects of their combined intervention are rarely reported. In this study, for the first time, we investigated the anti-aging effects and underlying mechanisms of intermittent fasting (IF), astaxanthin (AX), and their combination in D-galactose-induced aging rats. Our results demonstrated that these three treatments effectively inhibited malondialdehyde levels and improved the activity of endogenous antioxidant enzymes in the brain, liver, and serum of aging rats. Simultaneously, the combination of IF and AX had a synergistic effect on the recovery of brain mitochondrial injury as evidenced by permeability transition pore openness, membrane potential, respiratory chain complex enzyme activity, and cortical and hippocampal lesions. Notably, the combination significantly increased the levels of Immunoglobulin M (55.66 ± 3.23%), immunoglobulin G (34.41 ± 2.65%), and IL-2 (23.49 ± 1.78%) compared with the model group. Moreover, AX reduced the accumulation of pro-inflammatory factor IL-6 (23.06 ± 2.02%), while the combination induced more remarkable reduction in the accumulation of IL-1β (35.92 ± 3.06%) in the serum. Considering the serum metabolomics analysis, we hypothesized that IF and AX played a positive role in the regulation of the nervous system, which was associated with the differential metabolites lysope 16:0, N-Acety-L-tyrosine, and L-Alanyl-L-Lysine. This research reveals that the combination therapy provided synergistic anti-aging efficacy by enhancing resistance to oxidative stress, ameliorating mitochondrial dysfunction, and restoring the immune system. These findings might have significant implications for further studies on the exploration of effective anti-aging therapy.PMID:40183702 | DOI:10.1111/1750-3841.70170
Advances in liquid biopsy and virtual biopsy for care of patients with glioma: a narrative review
Expert Rev Anticancer Ther. 2025 Apr 4. doi: 10.1080/14737140.2025.2489629. Online ahead of print.ABSTRACTINTRODUCTION: The World Health Organization's 2021 classification of central nervous system neoplasms incorporated molecular and genetic features for classifying gliomas. Classification of gliomas located in deep-seated structures became a clinical conundrum given the absence of crucial pathological and molecular data. Advances in noninvasive imaging modalities offered virtual biopsy as a novel solution to this problem by identifying surrogate radiomic signatures. Liquid biopsies of blood or cerebrospinal fluid provided another enormous opportunity for identifying genomic, metabolomic and proteomic signatures.AREAS COVERED: We summarize and appraise the current state of evidence with regards to virtual biopsy and liquid biopsy in the care of patients with gliomas. PubMed, Embase and Google Scholar were searched on 7/30/2024 for relevant articles published after the year 2013 in the English language.EXPERT OPINION: A large body of preclinical and preliminary clinical evidence suggests that virtual biopsy is possible with the combined use of multiple novel imaging modalities in conjunction with machine learning and radiomics. Likewise, liquid biopsy in conjunction with focused ultrasound may be a valuable tool to obtain proteomic and genomic data regarding glioma in a minimally invasive manner. These modalities will likely become an integral part of care for patients with glioma in the future.PMID:40183671 | DOI:10.1080/14737140.2025.2489629
Deciphering Metabolic Alterations Associated with Glioma Grading Using Hyperspectral Stimulated Raman Scattering Imaging
Anal Chem. 2025 Apr 4. doi: 10.1021/acs.analchem.4c07042. Online ahead of print.ABSTRACTMetabolic dysregulation is a critical feature of various cancers, including brain tumors. Studying metabolic changes in tumor cells and tissues significantly improves our understanding of tumor development, progression, and treatment response. In this study, we utilize hyperspectral stimulated Raman scattering (SRS) imaging combined with biochemical spectral modeling to identify unique histological and molecular signatures linked to metabolic diversity across different glioma grades, without the need for labeling. By employing rapid label-free SRS histopathology and multivariate curve resolution analysis, we uncover changes in lipid profiles and varying levels of neuron demyelination from low-grade (LG) to high-grade (HG) gliomas. Quantitative analysis of key metabolites using non-negative least-squares regression spectral modeling reveals a significant increase in cellular proteins, DNA, and cholesterol levels, alongside a reduced redox ratio (flavin adenine dinucleotide (FAD)/NADH) in the glioblastoma (GBM, grade IV) tissue compared to pilocytic astrocytoma (PA, grade I) and healthy brain tissues, indicating a shift toward a pro-malignant metabolic state. A neural network diagnostic classifier, trained on 4547 SRS spectra (healthy: 1263; LG: 815; HG: 2469) from 45 patients with PA and GBM, achieves 99.6% accuracy in detecting and grading brain tumors. This study highlights the potential of hyperspectral SRS imaging for rapid, label-free, and spatially resolved analysis of metabolic heterogeneity in human gliomas, paving the way for metabolome-targeted therapeutic strategies in precision brain tumor treatment.PMID:40183640 | DOI:10.1021/acs.analchem.4c07042