PubMed

PLoS One. 2025 Apr 15;20(4):e0321189. doi: 10.1371/journal.pone.0321189. eCollection 2025.ABSTRACTBACKGROUND: The gut microbiota is often altered in chronic liver diseases and hepatocellular carcinoma (HCC), and increasing evidence suggests that it may influence response to cancer immunotherapy. Strategies to modulate the gut microbiome (i.e., fecal microbiota transplant (FMT)) may help to improve efficacy of immune checkpoint inhibitors (ICIs) or even overcome resistance to ICIs. Here, we describe the design and rationale of FAB-HCC, a single-center, single-arm, phase II pilot study to assess safety, feasibility, and efficacy of FMT from patients with HCC who responded to PD-(L)1-based immunotherapy or from healthy donors to patients with HCC who failed to achieve or maintain a response to atezolizumab plus bevacizumab.METHODS: In this single-center, single-arm, phase II pilot study (ClinicalTrials.gov identifier: NCT05750030), we plan to include 12 patients with advanced HCC who failed to achieve or maintain a response to atezolizumab/bevacizumab. Patients will receive a single FMT via colonoscopy from donors with HCC who responded to PD-(L)1-based immunotherapy or from healthy individuals, followed by atezolizumab/bevacizumab every 3 weeks. The primary endpoint is safety, measured by incidence and severity of treatment-related adverse events. The main secondary endpoint is efficacy, as assessed by best radiological response according to RECISTv1.1 and mRECIST. Additional exploratory endpoints include data on the effect of FMT on recipient gut microbiota, as well as metagenomic analysis of stool samples, analyses of circulating immune cells and serum and stool proteomic, metabolomic and lipidomic signatures.DISCUSSION: The results of this study will help to define the potential of FMT as add-on intervention in the systemic treatment of advanced HCC, with the potential to improve efficacy of immunotherapy or even overcome resistance.TRIAL REGISTRATION: EudraCT Number: 2022-000234-42 Clinical trial registry & ID: ClinicalTrials.gov identifier: NCT05750030 (Registration date: 16.01.2023).PMID:40233040 | DOI:10.1371/journal.pone.0321189

Anal Chem. 2025 Apr 15. doi: 10.1021/acs.analchem.5c00074. Online ahead of print.ABSTRACTIn biological membranes, lipids interact with membrane proteins (MPs) and play important roles in allosterically regulating their structure and function. Analyzing lipid-MP interactions is necessary for understanding these regulatory mechanisms; however, there have been few comprehensive and systematic studies to date. To address this, we developed a high-sensitivity, high-throughput platform that integrates lipid-immobilized beads with advanced proteomics to analyze lipid-MP interactions in detail. We prepared six types of lipid-immobilized beads, including sphingomyelin (SM), ceramide (Cer), dihydrosphingomyelin (DHSM), dihydroceramide (DHCer), phosphatidylcholine (PC), and cholesterol (Chol). In addition, we introduced a novel type of beads that immobilized SM and Chol (SM/Chol beads) to mimic lipid rafts. We first demonstrated that SM/Chol beads coprecipitated with Nakanori, a protein that specifically recognizes and binds to SM/Chol complexes, whereas beads immobilized with SM or Chol alone did not coprecipitate. This indicates the effectiveness of SM/Chol beads for the identification of raft-associated proteins. Next, the cell lysates were incubated with the seven types of lipid-immobilized beads and the recovered proteins were analyzed using shotgun proteomics. This approach successfully identified over 7000 lipid-binding proteins. Filtering based on fold-change values and subsequent enrichment analysis revealed distinct binding protein profiles for each lipid, highlighting the functional diversity of lipid-MP interactions and their roles in cellular processes. In summary, our methodology enables an unprecedented large-scale exploration of lipid-MP interactions. This platform provides a versatile tool for examining the lipid-mediated regulation of MPs and offers new insights into the physiological significance of the lipidome and its implications for health and disease.PMID:40233011 | DOI:10.1021/acs.analchem.5c00074

ESC Heart Fail. 2025 Apr 15. doi: 10.1002/ehf2.15285. Online ahead of print.ABSTRACTAIMS: Two general phenotypes of heart failure (HF) are recognized: HF with reduced ejection fraction (HFrEF) and with preserved EF (HFpEF). To develop phenotype-specific approaches to treatment, distinguishing biomarkers are needed. The goal of this study was to utilize quantitative metabolomics on a large, diverse population to replicate and extend existing knowledge of the plasma metabolic signatures in human HF.METHODS: Plasma metabolomics and proteomics was conducted on 787 samples collected by the Penn Medicine BioBank from subjects with HFrEF (n = 219), HFpEF (n = 357) and matched controls (n = 211). A total of 90 metabolites were analysed, comprising 28 amino acids, 8 organic acids and 54 acylcarnitines. Seven hundred thirty-three of these samples also underwent proteomic profiling via the O-Link proteomics panel.RESULTS: Unsaturated forms of medium-/long-chain acylcarnitines were elevated in the HFrEF group. Amino acid derivatives, including 1- and 3-methylhistidine, homocitrulline and symmetric and asymmetric (ADMA) dimethylarginine were elevated in HF, with ADMA elevated uniquely in HFpEF. While the branched-chain amino acids (BCAAs) were minimally changed, short-chain acylcarnitine species indicative of BCAA catabolism were elevated in both HF groups. 3-hydroxybutyrate (3-HBA) and its metabolite, C4-OH carnitine, were uniquely elevated in the HFrEF group. Linear regression models demonstrated a significant correlation between plasma 3-HBA and N-terminal pro-brain natriuretic peptide in both forms of HF, stronger in HFrEF.CONCLUSIONS: These results identify plasma signatures that are shared as well as potentially distinguish HFrEF and HFpEF. Metabolite markers for ketogenic metabolic re-programming were identified as unique signatures in the HFrEF group, possibly related to increased levels of BNP. Our results set the stage for future studies aimed at assessing selected metabolites as relevant biomarkers to guide HF phenotype-specific therapeutics.PMID:40232999 | DOI:10.1002/ehf2.15285

Comput Methods Biomech Biomed Engin. 2025 Apr 15:1-13. doi: 10.1080/10255842.2025.2488501. Online ahead of print.ABSTRACTMass spectrometry (MS) serves as a powerful analytical technique in metabolomics. Traditional MS analysis workflows are heavily reliant on operator experience and are prone to be influenced by complex, high-dimensional MS data. This study introduces a deep learning framework designed to enhance the classification of complex MS data and facilitate biomarker screening. The proposed framework integrates preprocessing, classification, and biomarker selection, addressing challenges in high-dimensional MS analysis. Experimental results demonstrate significant improvements in classification tasks compared to other machine learning approaches. Additionally, the proposed peak-preprocessing module is validated for its potential in biomarker screening, identifying potential biomarkers from high-dimensional data.PMID:40232885 | DOI:10.1080/10255842.2025.2488501

Anal Chem. 2025 Apr 15. doi: 10.1021/acs.analchem.5c00289. Online ahead of print.ABSTRACTOver the past decade, numerous metabolomics techniques have been developed using liquid chromatography-mass spectrometry (LC-MS). These methodologies have yielded significant findings and facilitated the identification of biomarkers. Among these, chemical-tagging methodologies combined with isotope surrogate tags have garnered considerable attention as a leading approach. Chemical-tagging reduces labor and costs by eliminating the need for internal standard preparation. However, the chromatographic deuterium effect (CDE) has persisted as a significant challenge. CDE poses a risk of data misinterpretation in metabolomics due to potential differences in matrix effects. Although the CDE mechanism has been partially elucidated, it has primarily been attributed to differences in hydrophobicity. A detailed understanding of CDE mechanisms would be valuable for designing chemical tags and optimizing liquid chromatography (LC) conditions. Moreover, emphasizing the CDE could aid in the separation and purification of deuterated compounds. In this study, we investigated the mechanistic basis of the CDE. Initially, four chromatography columns with different separation modes─octadecyl, octadecyl with a positively charged surface, biphenyl, and pentafluorophenyl (PFP) groups─were evaluated based on retention differences between 1H- and 2H6-labeled chemically tagged metabolites. Among these, the PFP column demonstrated the most effective reduction of the CDE, suggesting that electronic interactions with fluorine stabilized 2H-labeled metabolites. Further optimization using the PFP column showed its efficacy in reducing the level of CDE in human serum samples. Finally, the optimized approach was successfully applied to global metabolomics analysis of serum from a mouse model of metabolic dysfunction-associated steatohepatitis.PMID:40232871 | DOI:10.1021/acs.analchem.5c00289

Metab Brain Dis. 2025 Apr 15;40(4):184. doi: 10.1007/s11011-025-01604-y.ABSTRACTEarly diagnosis and intervention in children with autism spectrum disorder (ASD) is crucial. At present, diagnosis of ASD is primarily based on subjective tools. Identifying metabolic biomarkers will aid in early diagnosis of ASD complementing the assessment tools. The study aimed to conduct targeted metabolomic analysis and determine the plasma metabolites that can discriminate children with ASD from typically developing children (TD), and to determine the utility of machine learning in classifying ASD children based on the metabotypes. This was a multi-centric, analytical, case-control study conducted between April 2021-April 2023. Fasting plasma samples were obtained from seventy ASD and fifty-eight TD children, aged 2 to 12 years. Samples were quantitively analysed for 52 targeted metabolites (13 amino acids, 37 acylcarnitines, adenosine and 2-deoxyadenosine levels) using tandem mass spectrometry. An in-depth statistical analysis was performed. A total of 26 metabolites (11 amino acids, 14 acyl carnitines and adenosine) were found to be significantly (p < 0.005) different between ASD and TD children. Adenosine and amino acid levels were significantly decreased in ASD children. Among acyl carnitines, short- and long-chain acyl carnitine levels were significantly decreased, while medium-chain acyl carnitine levels were significantly increased in ASD children. Octenoylcarnitine-C8:1 (Cut-off value- 0.025 mmol/L, AUC- 0.683) and adenosine (Cut-off value- 0.025 mmol/L, AUC- 0.673) were found to predict children with ASD at a sensitivity of 55.7% and 57.1%, specificity of 79.3% and 72.4% respectively. Based on the metabolites, machine learning models like Support Vector Machine (SVM) and Random Forest (RF) were able to discriminate ASD from TD children with the classification accuracy score being highest in RF (79.487%, AUC- 0.800). Significant abnormalities in plasma metabolites were observed leading to disturbances in the Krebs cycle, urea cycle and fatty acid oxidation, suggesting mitochondrial dysfunction that may possibly contribute in the pathobiology of ASD. Octenoylcarnitine-C8:1 and Adenosine may serve as potential metabolic biomarkers for ASD.PMID:40232556 | DOI:10.1007/s11011-025-01604-y

Org Biomol Chem. 2025 Apr 15. doi: 10.1039/d5ob00115c. Online ahead of print.ABSTRACTPestalotiopsis sp. (strain IQ-011) produces cuautepestalorin (10), a 7,8-dihydrochromene-oxoisochromane adduct featuring a spiro-polycyclic (6/6/6/6/6/6) ring system. Additionally, it yields its proposed biosynthetic precursors: cytosporin M (1) and oxopestalochromane (11) when cultured under standard conditions (fermentation in solid media). Following an OSMAC approach guided by metabolomic studies (PCA and molecular networks), it was established that the epigenetic modulator DMSO dramatically increases the production of 1 up to 50 times according to feature-based molecular networking (FBMN) analysis, and triggers the production of other derivatives from the epoxyquinol family. Chemo-targeted isolation resulted in the discovery of four new compounds: 19-hydroxycytosporin M (2) and three [4 + 2] cycloaddition products: ent-eutyscoparol J (4), ent-pestaloquinol A (6) and ent-pestaloquinol B (8). The structures of all isolates were established based on spectroscopic, spectrometric, chiroptical, and X-ray diffraction analyses. This study demonstrates the potential of combining metabolomic tools with DMSO as an epigenetic modulator to enhance fungal metabolite diversity and highlights the importance of chiroptical methods for accurate compound identification.PMID:40232401 | DOI:10.1039/d5ob00115c

Biometals. 2025 Apr 15. doi: 10.1007/s10534-025-00684-8. Online ahead of print.ABSTRACTExposure to metal(loid)s and glucose metabolism may influence the progression of gastric precancerous lesions (GPLs) or gastric cancer (GC), but their combined effects remain unclear. Our study aimed to elucidate the combined impact of metal (including metalloid and trace element) exposure and disturbances in glucose metabolism on the progression of GPLs and GC. From a prospective observational cohort of 1829 individuals, their metal(loid) levels and blood metabolism were analysed via inductively coupled plasma‒mass spectrometry and targeted metabolomics gas chromatography‒mass spectrometry, respectively. From healthy normal controls (NC) or GPLs to GC, we observed that the aluminum and arsenic levels decreased, whereas the vanadium, titanium and rubidium levels increased, but the iron, copper, zinc and barium levels initially decreased but then increased; these changes were not obvious from the NC to GPL group. With respect to glucose homeostasis, most metabolites decreased, except for phosphoenolpyruvate (PEP), which increased. Multiple logistic regression analysis revealed that titanium and phosphoenolpyruvate might be risk factors for GPLs, that barium is a protective factor for GC, and that D-glucaric acid might be a protective factor for GPLs and GC. Selenium, vanadium, titanium, succinate, maleate, isocitrate, PEP, and the tricarboxylic acid cycle (TCA) had good predictive potential for GPL and GC. Additionally, metal(loid)s such as arsenic, titanium, barium, aluminum, and vanadium were significantly correlated with multiple glucose metabolites involved in the TCA cycle in the GPL and GC groups. Our findings imply that metal(loid) exposure disrupts glucose metabolism, jointly influencing GPL and GC progression.PMID:40232351 | DOI:10.1007/s10534-025-00684-8

J Agric Food Chem. 2025 Apr 15. doi: 10.1021/acs.jafc.5c03967. Online ahead of print.ABSTRACTMitochondria are pivotal in sustaining skeletal muscle and the systemic metabolic balance. Chlorogenic acid (CA) is a common dietary antioxidant known for its ability to modulate metabolic homeostasis. This study aimed to investigate the impact of CA on high-fat diet (HFD)-induced mitochondrial dysfunction and metabolic disorder in skeletal muscle. C57BL/6J mice fed with a HFD were treated with CA for 12 weeks. The study assessed the overall glycolipid metabolic status, exercise performance, muscle fiber type, and antioxidant capacity of skeletal muscle in HFD-fed mice treated with CA. Results showed that CA reduced fat accumulation, improved exercise capacity, and enhanced mitochondrial performance in HFD-fed mice. Untargeted metabolomics analysis revealed that lactate metabolism and mitochondrial fatty acid oxidation (FAO) responded positively to CA intervention. Molecular mechanisms demonstrated that CA intervention improved mitochondrial biogenesis and function, promoting FAO and oxidative phosphorylation in mitochondria and ultimately reducing fat deposition in skeletal muscle induced by HFD feeding. Mechanistically, CA decreased HFD-induced lactate production and protein lactylation in skeletal muscle, highlighting the importance of the LDHA-lactate axis in mitochondrial function improvement by CA. Therefore, this study provides additional insights supporting the potential of CA as a natural dietary supplement for metabolic syndrome and associated disorders.PMID:40232198 | DOI:10.1021/acs.jafc.5c03967

Epilepsia Open. 2025 Apr 15. doi: 10.1002/epi4.70037. Online ahead of print.ABSTRACTThe intestinal microbiome plays a pivotal role in maintaining host health through its involvement in gastrointestinal, immune, and central nervous system (CNS) functions. Recent evidence underscores the bidirectional communication between the microbiota, the gut, and the brain and the impact of this axis on neurological diseases, including epilepsy. In pediatric patients, alterations in gut microbiota composition-called intestinal dysbiosis-have been linked to seizure susceptibility. Preclinical models revealed that gut dysbiosis may exacerbate seizures, while microbiome-targeted therapies, including fecal microbiota transplantation, pre/pro-biotics, and ketogenic diets, show promise in reducing seizures. Focusing on clinical and preclinical studies, this review examines the role of the gut microbiota in pediatric epilepsy with the aim of exploring its implications for seizure control and management of epilepsy. We also discuss mechanisms that may underlie mutual gut-brain communication and emerging therapeutic strategies targeting the gut microbiome as a novel approach to improve outcomes in pediatric epilepsy. PLAIN LANGUAGE SUMMARY: Reciprocal communication between the brain and the gut appears to be dysfunctional in pediatric epilepsy. The composition of bacteria in the intestine -known as microbiota- and the gastrointestinal functions are altered in children with drug-resistant epilepsy and animal models of pediatric epilepsies. Microbiota-targeted interventions, such as ketogenic diets, pre-/post-biotics administration, and fecal microbiota transplantation, improve both gastrointestinal dysfunctions and seizures in pediatric epilepsy. These findings suggest that the gut and its microbiota represent potential therapeutic targets for reducing drug-resistant seizures in pediatric epilepsy.PMID:40232107 | DOI:10.1002/epi4.70037

Foods. 2025 Mar 19;14(6):1046. doi: 10.3390/foods14061046.ABSTRACTThis study employed ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) combined with multivariate analysis to investigate tissue-specific metabolic profiles in the peel, pulp, and seeds of black wax gourd (Benincasa hispida). A total of 1020 metabolites were identified, including 520 primary metabolites (e.g., amino acids, lipids, and organic acids) and 500 secondary metabolites (e.g., phenolic acids, flavonoids, and alkaloids). Significant metabolic divergence was observed across tissues: 658, 674, and 433 differential metabolites were identified between the peel and the pulp, the peel and the seeds, and the pulp and the seeds, respectively. Unique metabolites such as methyl 5-glucosyloxy-2-hydroxybenzoate and 3,5-di-O-caffeoylquinic acid were exclusive to the peel, while 4-O-(6'-O-glucosyl-imino)-4-hydroxybenzyl alcohol and fertaric acid were specific to the seeds. KEGG pathway enrichment revealed distinct metabolic priorities: flavonoids and phenolic acids dominated in the peel, amino acids and phenylpropanoids in the pulp, and nucleotides and lipids in the seeds. The peel exhibited the highest secondary metabolite abundance (14.27%), whereas the seeds accumulated the most primary metabolites (26.62%), including essential amino acids like L-tryptophan and functional lipids such as linoleic acid. These findings underscore the nutritional and bioactive potential of underutilized by-products (peel and seeds), providing a biochemical foundation for valorizing wax gourd tissues in the food, pharmaceutical, and agricultural industries.PMID:40232096 | DOI:10.3390/foods14061046

Foods. 2025 Mar 18;14(6):1027. doi: 10.3390/foods14061027.ABSTRACTNon-volatile organic acids (NVOAs) are essential to the flavor profile of Baijiu. However, the low levels and diversity of NVOAs in Baijiu make their isolation, annotation, and quantification challenging. In this study, a well-established pipeline combining chemical derivatization, isotope labeling, and high-resolution mass spectrometry with a three-tier annotation process was used to quantify NVOAs in three typical flavor types of Baijiu with high coverage and confidence. The results revealed the annotation of 56, 145, and 1277 NVOAs in Baijiu at tier 1, tier 2, and tier 3 levels, respectively. Among them, a total of 166 high-confidence NVOAs were first reported in Baijiu. Furthermore, multivariate statistical analyses indicated that abundant NVOAs could potentially be used as biomarkers to distinguish between different flavor types of Baijiu. This study provides a powerful tool for the qualification and quantification of NVOAs in Baijiu. The results will greatly expand the understanding of NVOAs in Baijiu.PMID:40232072 | DOI:10.3390/foods14061027

Foods. 2025 Mar 19;14(6):1054. doi: 10.3390/foods14061054.ABSTRACTAs a probiotic strain isolated from Hongqu rice wine (a traditional Chinese fermented food), Limosilactobacillus fermentum FZU501 (designated as Lf) demonstrates exceptional gastric acid and bile salt tolerance, showing potential application as a functional food. The aim of this study was to investigate the protective effect of dietary Lf intervention on alcohol-induced liver injury (ALI) in mice. The results demonstrated that oral administration of Lf effectively ameliorated alcohol-induced lipid metabolism disorders by reducing the serum levels of TC, TG and LDL-C and increasing the serum levels of HDL-C. In addition, oral administration of Lf effectively prevented alcohol-induced liver damage by increasing the hepatic activities of antioxidant enzymes (CAT, SOD, GSH-Px) and alcohol-metabolizing enzymes (ADH and ALDH). Interestingly, 16S amplicon sequencing showed that oral administration of Lf increased the number of Prevotella, Lachnospiraceae_NK4A136_group and Lactobacillus, but decreased the proportion of Faecalibaculum, Adlercreutzia and Alistipes in the intestines of mice that consumed excessive alcohol, which was highly associated with improved liver function. As revealed by liver untargeted metabolomics studies, oral Lf clearly changed liver metabolic profiles, with the signature biomarkers mainly involving purine metabolism, taurine metabolism, tryptophan, alanine, aspartic acid and glutamate metabolism, etc. Additionally, Lf intervention regulated liver gene transcription in over-drinking mice for cholesterol metabolism, bile acid metabolism, fatty acid β-oxidation, alcohol metabolism and oxidative stress. Taken together, the above research results provide solid scientific support for the biological activity of Lf in ameliorating alcohol-induced liver metabolism disorder and intestinal microbiota imbalance.PMID:40232069 | DOI:10.3390/foods14061054

J Proteome Res. 2025 Apr 15. doi: 10.1021/acs.jproteome.5c00166. Online ahead of print.ABSTRACTMaple syrup urine disease (MSUD) is a rare autosomal recessive metabolic disorder causing impaired branched-chain amino acid (BCAA) catabolism and systemic metabolic dysregulation. MSUD has an incidence of approximately 1 in 185,000 U.S. births, with much higher prevalence in the Mennonite communities (up to 1 in 400 live births due to the c.1312T > A p.Tyr438Asn BCKDHA founder mutation). Using a multiomic approach integrating metabolomics, lipidomics, and proteomics, we analyzed blood samples from three patients on a BCAA-restricted diet (MSUDDR), two MSUD patients who received liver transplants (MSUDLT), and six healthy controls. Gene ontology analysis of integrated omics data confirmed systemic metabolic imbalances in MSUD, highlighting increases in glycolysis, oxidative phosphorylation, and purine metabolism. Lipidomic analysis revealed disruptions in sphingolipids and lysophosphatidylcholines, affecting signaling and membrane integrity. Liver transplantation corrected some abnormalities, but key metabolites and proteins remained altered. Proteomic analysis revealed significant alterations in redox homeostasis, energy metabolism, and cytoskeletal organization with partial recovery post-transplantation. Post-translational modifications indicated ongoing oxidative stress and immune activation in the MSUDLT group. Elevated levels of l-isoleucine, l-valine, and their ketoacids persisted post-transplant, correlating with impaired amino acid metabolism, lipid remodeling, and protein folding. These findings provide insights into MSUD-associated metabolic dysfunction and highlight potential therapeutic targets.PMID:40232068 | DOI:10.1021/acs.jproteome.5c00166

Foods. 2025 Mar 17;14(6):1014. doi: 10.3390/foods14061014.ABSTRACTTo investigate the metabolic differences and mechanisms during the fermentation process of coffee-grounds craft beer, HS-SPME-GC/MS untargeted metabolomics technology was used to study the metabolic differences during the fermentation process of coffee-grounds craft beer. Multivariate statistical analysis and pathway analysis were combined to screen for significantly different metabolites with variable weight values of VIP ≥ 1 and p < 0.05. The results indicate that at time points T7, T14, T21, and T28, a total of 183 differential metabolites were detected during the four fermentation days, with 86 metabolites showing significant differences. Its content composition is mainly composed of lipids and lipid-like molecules, organic oxygen compounds, and benzoids, accounting for 63.64% of the total differential metabolites. KEGG enrichment analysis of differentially expressed metabolites showed a total of 35 metabolic pathways. The top 20 metabolic pathways were screened based on the corrected p-value, and the significantly differentially expressed metabolites were mainly enriched in pathways such as protein digestion and absorption, glycosaminoglycan biosynthesis heparan sulfate/heparin, and benzoxazinoid biosynthesis. The different metabolic mechanisms during the fermentation process of coffee-grounds craft beer reveal the quality changes during the fermentation process, providing theoretical basis for improving the quality of coffee-grounds craft beer and having important theoretical and practical significance for improving the quality evaluation system of coffee-grounds craft beer.PMID:40232021 | DOI:10.3390/foods14061014

Foods. 2025 Mar 11;14(6):955. doi: 10.3390/foods14060955.ABSTRACTPrediabetes (pre-DM) is the buffer period before developing overt type 2 diabetes (T2DM), and the search for novel food agents to protect against pre-DM is in high demand. Our team previously reported that the Grifola frondosa (maitake mushroom) polysaccharide F2 reduced insulin resistance in T2DM rats induced by streptozocin (STZ) combined with a high-fat diet (HFD). This study aimed to evaluate the effects of G. frondosa polysaccharide F2 on disordered lipid and glucose metabolism and to investigate its mechanisms in pre-DM mice. F2 (30 and 60 mg/kg/d) was administered (i.g.) for 5 weeks to pre-DM mice. The results showed that F2 decreased the fasting blood glucose and lipid profile index of pre-DM mice (p < 0.05 or 0.0001). An untargeted metabolomics analysis of feces from pre-DM mice showed that F2 reduced the content of conjugated bile acids, including taurochenodeoxycholic acid and taurocholic acid, and increased the free bile acids of lithocholic acid. The results of 16S rDNA sequencing of feces from pre-DM mice showed that bile salt hydrolase (BSH)-producing bacteria, including Bacillus, Bifidobacterium, and Lactococcus, may be the therapy targets of F2 in pre-DM mice. Through the integrated analysis of untargeted metabolomics and 16S rDNA sequencing, it was found that F2 may ameliorate glucose and lipid metabolism disorders by promoting bile acid metabolism while regulating the abundance of BSH-producing bacteria (Lactococcus spp.), suggesting its potential as a functional food ingredient for the prevention of T2DM.PMID:40232013 | DOI:10.3390/foods14060955

Cancer Biol Med. 2025 Apr 15:j.issn.2095-3941.2024.0523. doi: 10.20892/j.issn.2095-3941.2024.0523. Online ahead of print.ABSTRACTOBJECTIVE: Based on multistage metabolomic profiling and Mendelian randomization analyses, the current study identified plasma metabolites that predicted the risk of developing gastric cancer (GC) and determined whether key metabolite levels modified the GC primary prevention effects.METHODS: Plasma metabolites associated with GC risk were identified through a case-control study. Bi-directional two-sample Mendelian randomization analyses were performed to determine potential causal relationships utilizing the Shandong Intervention Trial (SIT), a nested case-control study of the Mass Intervention Trial in Linqu, Shandong province (MITS), China, the UK Biobank, and the FinnGen project.RESULTS: A higher genetic risk score for plasma L-aspartic acid was significantly associated with an increased GC risk in the northern Chinese population (SIT: HR = 1.26 per 1 SD change, 95% CI: 1.07-1.49; MITS: HR = 1.07, 95% CI: 1.00-1.14) and an increased gastric adenocarcinoma risk in FinnGen (OR = 1.68, 95% CI: 1.16-2.45). Genetically predicted plasma L-aspartic acid levels also modified the GC primary prevention effects with the beneficial effect of Helicobacter pylori eradication notably observed among individuals within the top quartile of L-aspartic acid level (P-interaction = 0.098) and the beneficial effect of garlic supplementation only for those within the lowest quartile of L-aspartic acid level (P-interaction = 0.02).CONCLUSIONS: Elevated plasma L-aspartic acid levels significantly increased the risk of developing GC and modified the effects of GC primary prevention. Further studies from other populations are warranted to validate the modification effect of plasma L-aspartic acid levels on GC prevention and to elucidate the underlying mechanisms.PMID:40231997 | DOI:10.20892/j.issn.2095-3941.2024.0523

Foods. 2025 Mar 13;14(6):981. doi: 10.3390/foods14060981.ABSTRACTPostharvest leaf senescence is a pivotal determinant influencing the quality and shelf life of leafy vegetables, exemplified by pak choi (Brassica rapa L. subsp. chinensis). While the regulatory role of gibberellin (GA) in modulating leaf senescence has been documented across diverse plant species, the underlying physiological and molecular mechanisms remain insufficiently characterized. This study, through a combination of transcriptomic and metabolomic analyses, investigated the effect of exogenous GA on postharvest leaf senescence in pak choi. GA treatment alleviated etiolation, maintained chlorophyll levels, reduced conductivity and malondialdehyde content, and delayed the onset of senescence symptoms in postharvest pak choi. Transcriptome profiling indicated that GA suppressed the expression of the senescence-associated genes BraSRGs and BraSAGs. In addition, GA influenced chlorophyll degradation and preserved chlorophyll content by modulating the expression of genes implicated in chlorophyll metabolism, including BraPPH, BraSGR1, BraNYCI, and BraPAO. GA treatment impacted lipid levels and regulated the degradation of membrane phospholipids. Furthermore, exogenous GA treatment disrupted the efficacy of the jasmonic acid signal pathway, primarily through the transcriptional downregulation of key regulatory genes, including BraJAZ10 and BraJAR1. These results provide insights into the role of GA in delaying postharvest leaf senescence and highlight potential targets for improving postharvest management in leafy vegetables.PMID:40231988 | DOI:10.3390/foods14060981

Foods. 2025 Mar 7;14(6):919. doi: 10.3390/foods14060919.ABSTRACTZucchini (Cucurbita pepo subsp. pepo) is a seasonal vegetable (also known as courgette) characterized by health properties due to the content of several bioactive molecules. For this reason, the consumption of zucchini is highly recommended as a part of the Mediterranean diet. The aim of this study was to evaluate the possible influence of a specific compost supply for shifting the characteristics of an integrated agriculture toward a biodynamic standard following Demeter® certified rules. In particular, an approach based on 1H-Nuclear Magnetic Resonance (NMR) spectroscopy and multivariate statistical analysis (MVA) was applied to analyze the differences between the metabolic profiles of the zucchini samples (with the same cultivar, Vitulia), obtained from three different agronomical practices: two focused agricultural systems (compost supplied and integrated), as well as the used benchmark (Demeter biodynamic certified). The obtained results showed that the samples from the plots managed with biofertilizer from compost showed similar behaviour to the samples managed under Demeter biodynamic certification, with higher content of some amino acids, such as arginine, and lower content of sugars than the samples from integrated farming. The concentration of twenty elements was then determined using inductively coupled plasma atomic emission spectroscopy (ICP-AES). The averaged results of the elemental data appear almost parallel to the trend observed with the metabolomics approach. In the present case, the use of a specific compost as a biofertilizer has shown to promote the transition to the quality standards of the Demeter certification, significantly improving the crops' sustainability.PMID:40231901 | DOI:10.3390/foods14060919

Physiol Plant. 2025 Mar-Apr;177(2):e70214. doi: 10.1111/ppl.70214.ABSTRACTThe identification and functional analysis of key stress tolerance-related genes are of paramount importance in elucidating mechanisms regulating plant responses and adaptation to environmental stresses. Significant progress has been achieved in mining stress tolerance-related genes through the integrative analysis of metabolome and other omics data. However, methodologies for the precise identification of secondary metabolites still require further refinement. This study introduces a novel approach for discovering critical stress tolerance-related genes by integrating isolation and identification of drought-responsive secondary metabolites and transcriptome analysis (IISMTA). Using this approach, four drought-responsive metabolites (RMs), namely formononetin, afrormosin, ononin, and wistin, were isolated from Onobrychis viciifolia and further characterized by chromatography, high-resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR) technologies. Only formononetin was identified, while the latter three were undetected in a widely-targeted metabolome analysis, indicating the novelty of our approach. A correlational analysis between proposed biosynthetic pathways of RMs and transcriptome data of drought-stressed vs. non-stressed O. viciifolia seedlings was conducted to identify the genes involved. Among the upregulated genes potentially involved, OvIF7GT, encoding an isoflavone glycosyltransferase, was ectopically expressed in Arabidopsis thaliana to assess its functional role in the biosyntheses of these compounds and plant drought adaptation. Results indicated that OvIF7GT transgenic plants showed increased total flavonoid contents and drought tolerance that was associated with enhanced antioxidant defense and osmoprotection, and reduced oxidative damage. Therefore, the IISMTA developed in this study is a valuable complement to the existing gene and metabolite discovery approaches.PMID:40231838 | DOI:10.1111/ppl.70214