PubMed

Foods. 2025 Mar 31;14(7):1223. doi: 10.3390/foods14071223.ABSTRACTFruit vinegar is typically produced through a two-stage deep liquid fermentation involving alcohol fermentation (Saccharomyces cerevisiae) and acetic acid fermentation (Acetobacter pasteurianus). In order to enhance the flavor and texture of sea buckthorn fruit vinegar, Lactobacillus fermentum was introduced into the alcoholic fermentation stage. At the end of fermentation, the total acid and acetic acid of sea buckthorn (Hippophae rhamnoides L.) fruit vinegar were both enhanced compared with sea buckthorn vinegar brewed through the traditional liquid fermentation method, and in terms of the main active ingredients, the total flavonoid content was slightly enhanced. Non-targeted metabolomics (LC-MS) was used to characterize the characteristic metabolite profiles during the fermentation process. A total of 55 differential metabolites, including organic acids, flavonoids, and amino acids, were identified, and the contents of citric acid, malic acid, and manganic acid, which are the sources of the irritating taste of sea buckthorn berry vinegar, were significantly reduced. In addition, the co-fermentation of Lactobacillus fermentum promoted both glycolysis and the TCA cycle and also led to a significant up-regulation of aromatic metabolites, such as ethyl acetate, ethyl lactate, and ethyl caproate. These results will provide new information on the dynamics of the characterized metabolites during the fermentation of sea buckthorn fruit vinegar.PMID:40238395 | DOI:10.3390/foods14071223

Foods. 2025 Mar 28;14(7):1186. doi: 10.3390/foods14071186.ABSTRACTGamma-aminobutyric acid (GABA) is a nonprotein amino acid, which confers stress resistance to plants. Precise mechanisms underlying GABA accumulation in quinoa (Chenopodium quinoa) subjected to dark and ultrasonic stresses have not been elucidated. We conducted transcriptome and metabolome analyses of quinoa samples exposed to various stress treatments to reveal molecular pathways leading to GABA accumulation. Through the comprehensive integration of metabolome and transcriptome data, an association was revealed between GABA accumulation, 9 differentially expressed metabolites, and 27 differentially expressed genes. Two pathways responsible for GABA synthesis were identified, involving glutamate decarboxylase and aldehyde dehydrogenases, respectively. These enzymes regulate the enrichment of GABA in quinoa under dark and ultrasonic stress conditions. We demonstrated that under ultrasonic stress, proline and alanine increased, whereas glutamate and arginine declined. Phenolic acid, flavonoids, and alkaloid metabolites increased. These findings provide novel insights into the mechanism by which darkness and ultrasound stress enhance GABA, supporting the development of targeted synthetic biology techniques.PMID:40238367 | DOI:10.3390/foods14071186

Foods. 2025 Mar 28;14(7):1193. doi: 10.3390/foods14071193.ABSTRACTEnsuring the authenticity of Mozzarella di Bufala Campana (MdBC), a Protected Designation of Origin (PDO) cheese, is essential for regulatory enforcement and consumer protection. This study evaluates a multi-technology analytical platform developed to detect adulteration due to the addition of non-buffalo milk or non-PDO buffalo milk in PDO dairy buffalo products. Peripheral laboratories use gel electrophoresis combined with polyclonal antipeptide antibodies for initial screening, enabling the detection of foreign caseins, including those originating outside the PDO-designated regions. For more precise identification, Matrix-Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS) differentiates species by detecting proteotypic peptides. In cases requiring confirmation, nano-liquid chromatography coupled to electrospray tandem mass spectrometry (nano-LC-ESI-MS/MS) is used in central state laboratories for the highly sensitive detection of extraneous milk proteins in PDO buffalo MdBC cheese. On the other hand, analysis of the pH 4.6 soluble fraction from buffalo blue cheese identified 2828 buffalo-derived peptides and several bovine specific peptides, confirming milk adulteration. Despite a lower detection extent in the pH 4.6 insoluble fraction following tryptic hydrolysis, the presence of bovine peptides was still sufficient to verify fraud. This integrated proteomic approach, which combines electrophoresis and mass spectrometry technologies, significantly improves milk adulteration detection, providing a robust tool to face increasingly sophisticated fraudulent practices.PMID:40238338 | DOI:10.3390/foods14071193

Foods. 2025 Mar 28;14(7):1181. doi: 10.3390/foods14071181.ABSTRACTAddressing the escalating global burdens of inflammatory bowel disease and antimicrobial resistance demanded innovative food-based approaches to fortify gut health and suppress pathogens. We introduced a novel edible probiotic, Enterococcus faecalis HY0110, isolated from marine Thunnus thynnus. Through comprehensive in vitro, in vivo, and metabolomic analyses, we demonstrated its superior antibacterial effects compared to Lactobacillus rhamnosus GG, along with significantly enhanced antioxidant and free-radical scavenging capacities. Notably, elevated acetic acid production strongly correlated with its antimicrobial efficacy (R ≥ 0.999). HY0110 also exerted antiproliferative effects on HT-29 colorectal cancer cells by attenuating β-catenin and BCL-2 expression while upregulating pro-apoptotic markers P62 and c-PARP. In a DSS-induced colitis model, HY0110 alleviated inflammation, restored gut microbial homeostasis, and enhanced deterministic processes in community assembly dynamics. Furthermore, fermenting Periplaneta americana powder with HY0110 triggered extensive metabolic remodeling, notably a 668.73-fold rise in astragaloside A, plus increases in L-Leucyl-L-Alanine, S-lactoylglutathione, and 16,16-dimethyl prostaglandin A1. These shifts diminished harmful components and amplified essential amino acids and peptides to bolster immune modulation, redox balance, and anti-inflammatory responses. This work established a transformative paradigm for utilizing marine probiotics and novel entomological substrates in functional foods, presenting strategic pathways for precision nutrition and inflammatory disease management.PMID:40238337 | DOI:10.3390/foods14071181

Foods. 2025 Mar 22;14(7):1101. doi: 10.3390/foods14071101.ABSTRACTThe influence of the vineyard location, the yield per vine and the type of alcoholic fermentation on the composition of Merlot wine from two consecutive vintages was investigated in a simultaneous experiment. Grapes from two locations and two crop loads per vine, from controlled and thinned vines, were vinified. At the same time, grapes from control vines were vinified with inoculated and spontaneous alcoholic fermentation. Comparisons of the wine composition were made using a targeted metabolomic approach, microbiological analysis and sensory evaluation. It has been confirmed that the composition of Merlot wine is essentially determined by the location of the vineyard. The analytical marker used to distinguish the two locations was the content of 3-mercaptohexan-1-ol (significantly higher in location B with 38-130%). It has also been shown that the type of alcoholic fermentation has a greater influence on the composition of the wine than the crop load. The analytical marker used for the cluster thinning was the pH of the wine, which increased significantly by 0.03 to 0.08 units with the lower crop load, and for the type of alcoholic fermentation, the concentration of 2-phenethyl acetate, which relates to the sum of acetates and 2-phenylethanol, which increased significantly by 58-299%, 54-218%, and 24-46% in the spontaneously fermented wines. Both the location of the vineyard and spontaneous alcoholic fermentation influenced the significant differences in the sensory characteristics of the wine, while cluster thinning had no such influence. The other influences of the two technical factors on the wine composition depended on the location of the vineyard and the vintage. It can also be concluded that spontaneous alcoholic fermentation reduced the influence of the vintage on the wine composition, while the opposite was the case with cluster thinning.PMID:40238237 | DOI:10.3390/foods14071101

Foods. 2025 Mar 21;14(7):1089. doi: 10.3390/foods14071089.ABSTRACTChannel catfish (Ictalurus punctatus) is a widely consumed freshwater fish known for its nutritional value but is highly prone to spoilage. This study investigated the quality changes of catfish muscle tissue under refrigeration and freezing through physicochemical, metabolomic, and microbial analyses. Results revealed that sensory scores decreased significantly during storage, with frozen samples maintaining similar scores to refrigerated ones after extended periods. Protein degradation and lipid oxidation, indicated by TVB-N and TBARS levels, were more pronounced during prolonged freezing. Metabolomic profiling identified 261 differential metabolites under long-term freezing, including elevated phosphatidylcholines, sphingomyelins, and disrupted amino acid pathways. Shifts in spoilage-associated microbial genera, such as Pseudomonas, and the correlations between microbial genera and specific metabolites, such as Methylobacterium with methylmalonic acid, highlighted microbial-driven spoilage processes. These findings provided a comprehensive understanding of quality deterioration during storage, guiding the development of enhanced preservation strategies for aquatic products.PMID:40238220 | DOI:10.3390/foods14071089

Rheumatology (Oxford). 2025 Apr 16:keaf204. doi: 10.1093/rheumatology/keaf204. Online ahead of print.ABSTRACTOBJECTIVE: NETs involvement in antiphospholipid syndrome (APS) pathogenesis is known, but the role of anti-β2glycoprotein I antibodies (aβ2GPI)-induced NETs in triggering a procoagulant and proinflammatory phenotype in endothelial cells (EC) remains to be evaluated. This study investigated whether NET-aβ2GPI can activate ECs and whether NET-aβ2GPI and NET-PMA have different proteomic profiles.METHODS: Healthy donors (HD) neutrophils were stimulated with APS-aβ2GPI, normal human IgG or PMA. NETs were stained with anti-neutrophil elastase and DAPI, and the ability of aβ2GPI to bind NETs and inhibit DNA degradation was investigated. Following aβ2GPI, NET-aβ2GPI and NET-PMA stimuli, we evaluated EC activation investigating ICAM, VCAM, and TF expression using flow cytometry and RT-qPCR; and EC dysfunction analyzing extracellular microvesicles (EMVs) release via flow cytometry and NanoSight analysis. Mass spectrometry-based proteomics was performed on NET-aβ2GPI and NET-PMA.RESULTS: Unlike normal IgG, aβ2GPI induced NET formation and bound to NETs by colocalizing with the neutrophil elastase signal at 93.6% without preventing NET degradation.Compared with unstimulated EC, NET-aβ2GPI triggered higher mRNA and a robust expression of TF, VCAM and ICAM in EC with a change-fold MFI of 6, 4.2 and 2.3. aβ2GPI induced a significant increase in EMVs compared with untreated samples and those treated with NETs. Fifty-six proteins were identified, 7 resulted upregulated in NET-aβ2GPI and downregulated in PMA-induced ones. GO enrichment analysis revealed that proteins upregulated in NET-aβ2GPI were enriched for ubiquitin protein ligase binding and SLC2A4 translocation to the plasma membrane.CONCLUSION: aβ2GPI-induced NETs can cause EC activation and TF expression.PMID:40238197 | DOI:10.1093/rheumatology/keaf204

Anal Chem. 2025 Apr 16. doi: 10.1021/acs.analchem.4c05480. Online ahead of print.ABSTRACTThe development of spatial multiomics technologies, particularly matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), has revolutionized our ability to map metabolic processes at single-cell resolution. However, the current techniques face challenges in minimizing matrix interferences and achieving comprehensive metabolite detection across multiple ionization modes. In this study, we present a novel dual-modal MSI workflow that leverages the pairing of 1,5-diaminonaphthalene (DAN) and its hydrochloric salt (DAN-HCl) matrices for sequential detection in positive- and negative-ion modes, respectively. This approach significantly enhanced metabolite coverage, spanning both lipid-based and nonlipid small molecules, while eliminating the need for solvent cleaning steps. Applied to a coculture of cholangiocarcinoma (CCLP1) and hepatic stellate (LX2) cells, the workflow revealed significant metabolic distinctions, including differential accumulation of glycerolipids and energy-related metabolites, highlighting the unique metabolic profiles of each cell type. Additionally, several unidentified metabolites were detected, indicating the potential to discover novel metabolic variations. These findings establish our method as a robust tool for single-cell spatial metabolomics with broad applicability in studying complex cellular interactions and advancing both research and clinical applications.PMID:40237634 | DOI:10.1021/acs.analchem.4c05480

CNS Neurosci Ther. 2025 Apr;31(4):e70331. doi: 10.1111/cns.70331.ABSTRACTAIMS: Developing validated treatments for Parkinson's disease (PD) remains a priority for clinicians and researchers. The lack of viable therapies may stem from an incomplete understanding of PD pathogenesis and inadequate therapeutic candidates. The production and transmission of exosomes are gaining recognition in the pathogenesis of neurodegenerative diseases. However, how exosomes affect the pathophysiology of PD has not been well elucidated.METHODS: Here, we investigated the effect of exosomes secreted by rats that were treated with saline or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) in treating healthy or PD model mice, and we evaluated the efficacy of peripheral and intracranial administration of adenine, which is an exosomal metabolite identified through widely targeted metabolomics.RESULTS: We found that exosomes derived from the blood of healthy rats alleviated motor dysfunction, dopaminergic neuron loss in the substantia nigra pars compacta and striatum, oxidative injury, and neuroinflammation. Conversely, exosomes from the blood of PD model rats reproduced the behavioral phenotype and pathology of PD in healthy mice. Additionally, peripheral and intracranial administration of adenine ameliorated the motor coordination disorder and dopaminergic neuron loss, and maintained the homeostasis of oxidative stress and neuroinflammation by activating cAMP/PKA signaling in PD.CONCLUSION: Together, these findings shed light on the mechanism by which exosomes participate in the pathophysiology of PD by transmitting the metabolite adenine and providing potential therapeutic strategies.PMID:40237545 | DOI:10.1111/cns.70331

mSystems. 2025 Apr 16:e0134724. doi: 10.1128/msystems.01347-24. Online ahead of print.ABSTRACTThis study investigated alterations in hematological parameters, gut microbiota composition, and fecal and plasma metabolic profiles among high-altitude residents during reoxygenation periods of 1 week, 1 month, and 4 months to elucidate the effects of reoxygenation on human physiology and metabolism. Exposure to high altitudes alters intestinal flora, plasma and fecal metabolites, disrupting their metabolic balance. Distinct differences in amino acid, lipid, energy, immune, cofactor, and vitamin metabolism pathways were detected between high- and low-altitude populations, with a partial recovery of disparities during reoxygenation. Although the gut microbiota exhibited limited adaptive homeostasis to altitude variations, the abundance of microbial taxa and the expression levels of fecal metabolites during the initial reoxygenation phase, particularly during the first week, were sensitive to the reoxygenated environment. Through 16S rRNA gene sequencing and bioinformatics analysis, operational taxonomic units (OTUs) were annotated at the genus level, revealing that the genera Barnesiella, Parabacteroides, and Megasphaera, along with plasma L-arginine, S1P, and alpha-D-glucose, emerged as potential biomarkers for the first week of reoxygenation among high-altitude populations. Notably, a marked change in oxidative stress levels and an increase in antioxidant capacity were observed in high-altitude residents during early reoxygenation. Tyrosine metabolism, which is jointly regulated by the plasma and fecal metabolites and gut microbiota, plays an important role under high-altitude conditions during initial reoxygenation. Additionally, the plasma metabolites pyridoxine and hypoxanthine and the Rothia genus correlated significantly with high-altitude deacclimatization syndrome scores during the first week of reoxygenation.IMPORTANCEOur research focuses on the prompt activation of tyrosine metabolism in plasma following reoxygenation, along with the regulatory mechanisms employed by the intestinal microbiota and the metabolism of feces to modulate this metabolic process. Notably, in the initial stages of reoxygenation, specific microbial genera such as Barnesiella, Parabacteroides, and Megasphaera, alongside plasma biomarkers including L-arginine, S1P, and alpha-D-glucose, emerge as pivotal players. Additionally, our findings reveal a distinct hematological profile characterized by a decrease in the MCHC and increases in the MCV and RDW-SD during the first week of reoxygenation, and this temporal window marked a crucial juncture in the plasma metabolome. Whereas the first month of reoxygenation signified a pivotal phase in the gut microbiome's adaptation to altered environmental conditions, as evidenced by alterations in alpha diversity.PMID:40237534 | DOI:10.1128/msystems.01347-24

Microbiol Spectr. 2025 Apr 16:e0246624. doi: 10.1128/spectrum.02466-24. Online ahead of print.ABSTRACTCrewed long-term and long-distance missions are the undoubted trends of human space exploration, which require a bioregenerative life support system (BLSS) and its efficient treatment of the highly lignocellulosic organic solid waste under microgravity. Under normal gravity and simulated microgravity effect (mµ-g) created by clinostats, we used the inoculum from the world's longest BLSS experiment "Lunar Palace 365" to ferment and degrade wheat straw. The straw and its lignocellulose contents' weight losses were significantly slowed down by mµ-g. By high-throughput sequencing and metabolomics on the fermentation material, we found that mµ-g largely shrank and fragmented the microbial community's phylogenetic molecular ecological network (pMEN), and enriched many reported antimicrobial metabolites, especially against fungi, the principal lignocellulose degrader (e.g., cyclohexylamine, an antifungal chemical, increased by 188 times). Inspired by the solid-media visualization experiment of Aspergillus nidulans (a representative fungus) which showed a confined hyphal expansion under mµ-g, we proposed a material-convection-based model: the degradation of complex and recalcitrant macromolecules like lignocellulose is a multistep and highly coordinative task for the microbial community, but the mµ-g physically destroyed the material convection in the fermentation material, which confined the diffusion of microbial cells, their metabolic products/substrates, and extracellular enzymes, thus fragmenting the microbial interactions needed for the degradation; the confined diffusion also caused a local resource shortage for next-step degraders, which resulted in a zonal concentration of microbes and thus intensified conflicts manifested in the release of antimicrobial metabolites, especially against fungi.IMPORTANCEThis convection-based model explains the observed phenomena and suggests proper mass-transfer-promoting methods for more "globalized" microbial interactions in such a community-based, highly coordinative, oligotrophic, mixed-phase (physically), and fungi-dominant application scenario under microgravity. The higher lignocellulose degradation efficiency thus achieved would certainly improve the bioregenerative life support system (BLSS) required for long-term space exploration missions. For non-space-exploration scenarios, this model could also serve as an additional illustration of both the biological and physical principles of such multistep bioprocesses.PMID:40237517 | DOI:10.1128/spectrum.02466-24

Microbiol Spectr. 2025 Apr 16:e0019525. doi: 10.1128/spectrum.00195-25. Online ahead of print.ABSTRACTAcinetobacter baumannii commonly causes lower airway colonization and infection and is easily confused. This study aimed to analyze the biological characteristics of carbapenem-resistant A. baumannii (CRAB) ST2 in the lower airway and identify an effective method for distinguishing between A. baumannii colonization and infection. Lower airway CRAB ST2 isolated at the Department of Respiratory and Critical Care Medicine and intensive care unit of our hospital from January 2021 to June 2023 were included, and their whole genome, biofilm-forming ability, bacterial virulence, and metabolome were analyzed. Fifty-six strains of CRAB with ST2 were identified, of which 32 were infection strains and 24 were colonization strains. The virulence and resistance genes, as well as the virulence and biofilm-forming ability, of ST2-type carbapenem-resistant lower airway infecting and colonizing A. baumannii strains were similar. The levels of metabolites were significantly lower in ST2-type carbapenem-resistant lower airway-infecting A. baumannii infection strains than those in the lower airway-colonizing strains. The levels of (S)-(+)-2-(aniline methyl) pyrrolidine, valine, ketoleucine, L-isoleucine, homoserine, N-acetyl-L-aspartate, and 2-aminoethanol-1-phosphate in the lower airway infection strains were significantly lower than those in the lower airway colonization strains. Bacterial virulence tests and biofilm formation ability could not distinguish the same ST of CRAB in the lower airway from the colonization or infection strains; however, metabolomics could. The biosynthesis and degradation pathways of valine, leucine, and isoleucine were downregulated, and changes in their metabolism may be important factors in promoting carbapenem-resistant A. baumanniiCRAB transformation from colonization to infection.IMPORTANCECarbapenem-resistant A. baumannii (CRAB) poses a critical threat in clinical settings, particularly due to challenges in distinguishing airway colonization from active infection, which complicates treatment decisions. This study highlights the limitations of conventional approaches-such as virulence gene profiling, phenotypic virulence assays, and biofilm formation analysis-in differentiating CRAB ST2 strains isolated from lower airway infections versus colonization. By integrating metabolomics, we identified distinct metabolic signatures linked to infection, including significant downregulation of valine, leucine, and isoleucine biosynthesis/degradation pathways and reduced levels of key metabolites (e.g., ketoleucine and L-isoleucine) in infection strains. These findings provide the first evidence that metabolic dysregulation may drive CRAB's transition from colonization to invasive disease. This work advances our understanding of CRAB pathogenicity and offers a novel, metabolism-based strategy to improve diagnostic accuracy, guide targeted therapies, and optimize antimicrobial stewardship in managing CRAB-associated respiratory infections.PMID:40237491 | DOI:10.1128/spectrum.00195-25

Int J Syst Evol Microbiol. 2025 Apr;75(4). doi: 10.1099/ijsem.0.006751.ABSTRACTTwo mesophilic, hydrogenotrophic methanogens, WWM1085 and M. smithii GRAZ-2, were isolated from human faecal samples. WWM1085 was isolated from an individual in the United States and represents a novel species within the genus Methanobrevibacter. M. smithii GRAZ-2 (=DSM 116045) was retrieved from a faecal sample of a European, healthy woman and represents a novel strain within this species. Both Methanobrevibacter representatives form non-flagellated, short rods with variable morphologies and the capacity to form filaments. Both isolates showed the typical fluorescence of F420 and methane production. Compared to M. smithii GRAZ-2, WWM1085 did not accumulate formate when grown with H2 and CO2. The optimal growth conditions were at 35-39 °C and pH 6.5-7.5. Full genome sequencing revealed a genomic difference of WWM1085 to the type strain of M. smithii DSM 861 (=PST), with 93.55% average nucleotide identity (ANI) and major differences in the sequence of its mcrA gene (3.3% difference in nucleotide sequence). Differences in the 16S rRNA gene sequence were very minor, and thus distinction based on this gene marker might not be possible. M. smithii GRAZ-2 was identified as a novel strain within the species Methanobrevibacter smithii (ANI 99.04% to M. smithii DSM 861 [=PST]). Due to the major differences between WWM1085 and M. smithii type strain M. smithii DSM 861 (=PST) in phenotypic, genomic and metabolic features, we propose Methanobrevibacter intestini sp. nov. as a novel species with WWM1085 as the type strain (DSM 116060T = CECT 30992T).PMID:40237437 | DOI:10.1099/ijsem.0.006751

J Extracell Vesicles. 2025 Apr;14(4):e70071. doi: 10.1002/jev2.70071.ABSTRACTTumour-derived small extracellular vesicles (sEV) are critical mediators within the tumour microenvironment (TME) and are known to regulate various metabolic pathways. In metastatic hepatocellular carcinoma (HCC), mass spectrometry protein analysis of HCC-derived sEV (HCC-sEV) identified an upregulation of nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme in maintaining cellular nicotinamide adenine dinucleotide (NAD+) levels. Our study demonstrates that sEV-NAMPT enhances glycolysis, tumorigenesis, and metastasis in HCC. Specifically, sEV-NAMPT activates the NF-κB transcription factor through toll-like receptor 4 (TLR4), leading to elevated SLC27A4 expression. SLC27A4 functions primarily as a long-chain fatty acid transporter and acyl-CoA synthetase. Lipidomic and metabolomic analyses revealed a positive correlation between SLC27A4 and intracellular levels of triacylglycerol (TG) and dihydroxyacetone phosphate (DHAP). Increased TG levels enhance lipolysis via hepatic lipase and facilitate the conversion of glycerol-3-P to DHAP, an intermediate that bridges lipid metabolism and glycolysis. This study uncovers a novel regulatory axis involving sEV-NAMPT and SLC27A4 in glycolysis, independent of traditional fatty acid metabolism pathways. Clinically, targeting sEV-NAMPT with the inhibitor FK866 significantly inhibited tumour growth in various HCC in vivo models, highlighting the potential of sEV-NAMPT as both a biomarker and therapeutic target in HCC.PMID:40237223 | DOI:10.1002/jev2.70071

Curr Pharm Des. 2025 Apr 15. doi: 10.2174/0113816128374077250410042947. Online ahead of print.ABSTRACTBACKGROUND: Simiao Pill (SMP) has been demonstrated to suppress inflammation and modulate immune function, thereby influencing the onset and progression of rheumatoid arthritis (RA). Nonetheless, the specific molecular mechanisms and targets through which SMP mediates metabolic regulation and enhances immune function have yet to be fully elucidated.OBJECTIVE: In this study, we employed an integrated approach combining the analysis of dysregulated metabolites and proteins to identify, screen, and validate the metabolic regulatory targets of SMP in adjuvant-induced arthritis (AIA) rats by using pseudotargeted metabolomics and 4D-DIA quantitative proteomics methodologies.METHODS: An AIA rat model was developed, and SMP was administered to AIA rats. Subsequently, assessments were conducted on paw edema, arthritis scores, histopathological changes and IL-1 β content of inflammatory factors in AIA rats. UHPLC-QTOF-MS/MS was employed to analyze endogenous metabolites in the serum. Metabolic pathway and protein profile were performed on the biomarkers. The protein-lipidphenotype map for the SMP-treated rats was constructed and the primary target closely related to the metabolic regulation of SMP was further screened and verified.RESULTS: Pseudotargeted metabolomics analysis revealed that SMP can mitigate the down-regulation of lipid levels in AIA rats. Pathway enrichment analysis identified arachidonic acid metabolism as the most significantly affected metabolic pathway and SMP was found to substantially ameliorate the dysregulation of this pathway in AIA rats. Subsequent protein profiling led to the identification of five key proteins, with noteworthy obvious corrective effects observed on Ptges3 and Alox15 due to SMP treatment. A comprehensive protein- lipid-phenotypic landscape of SMP-treated rats was analyzed for the specific molecular expressions associated with the arachidonic acid pathway. According to the correlation matrix of dysregulated metabolite/ protein, we found that Ptges3 was ranked as the primary target closely related to the metabolic regulation of SMP, a finding further validated through immunofluorescence staining in rat joint and synovial cells.CONCLUSION: Our study confirmed that SMP exerts an anti-arthritic effect by modulating the arachidonic acid metabolic network via the Ptges3 protein in rat joints and human rheumatoid arthritis synovial fibroblasts. This finding offers a novel mechanistic insight into the pharmacological action of SMP in adjuvant-induced arthritis (AIA) in rats. It informs future research on the therapeutic potential of SMP in rheumatoid arthritis (RA).PMID:40237054 | DOI:10.2174/0113816128374077250410042947

Trends Analyt Chem. 2024 Feb;171:117478. doi: 10.1016/j.trac.2023.117478. Epub 2023 Dec 12.ABSTRACTA literature survey was conducted to identify current practices used by NMR metabolomics investigators when conducting and reporting their metabolomics studies. A total of 463 papers from 2020 and 80 papers from 2010 were selected from PubMed and were manually analyzed by a team of investigators to assess the extent and completeness of the experimental procedures and protocols reported. A significant number of the papers did not report on essential experimental details, incompletely stated which statistical methods were used, improperly applied supervised multivariate statistical analyses, or lacked validation of statistical models. A large diversity of protocols and software were identified, which suggests a lack of consensus and a relatively limited use of commonly agreed upon standards for conducting and reporting NMR metabolomics studies. The overall intent of the survey is to inform and encourage the NMR metabolomics community to develop and adopt best-practices for the field.PMID:40237011 | PMC:PMC11999570 | DOI:10.1016/j.trac.2023.117478

Imeta. 2025 Mar 18;4(2):e70012. doi: 10.1002/imt2.70012. eCollection 2025 Apr.ABSTRACTMaternal health, specifically changes in the gut microbiota, can profoundly impact offspring health; however, our understanding of how gut microbiota alterations during the preconception period influence the offspring remains limited. In this study, we investigated the impact and mechanisms of preconception maternal gut dysbiosis on the development of the enteric nervous system (ENS) in mice. We found that preconception maternal exposure to antibiotics led to the abnormal development of the ENS in offspring, increasing their susceptibility to water avoidance stress at the adult stage. Metagenomic, targeted metabolomic, and transcriptomic analyses revealed that preconception antibiotic exposure disrupted the expression of genes crucial for embryonic ENS development by altering maternal gut microbiota composition. Multi-omics analysis combined with Limosilactobacillus reuteri and propionate gestational supplementation demonstrated that the maternal gut microbiota and metabolites may influence embryonic ENS development via the GPR41-GDNF/RET/SOX10 signaling pathway. Our findings highlight the critical importance of maintaining a healthy maternal gut microbiota before conception to support normal ENS development in offspring.PMID:40236770 | PMC:PMC11995169 | DOI:10.1002/imt2.70012

Trends Analyt Chem. 2024 Nov;180:117918. doi: 10.1016/j.trac.2024.117918. Epub 2024 Aug 19.ABSTRACTCancer is a leading cause of world-wide death and a major subject of clinical studies focused on the identification of new diagnostic tools. An in-depth meta-analysis of 244 clinical metabolomics studies of human serum samples highlights a reproducibility crisis. A total of 2,206 unique metabolites were reported as statistically significant across the 244 studies, but 72% (1,582) of these metabolites were identified by only one study. Further analysis shows a random disparate disagreement in reported directions of metabolite concentration changes when detected by multiple studies. Statistical models revealed that 1,867 of the 2,206 metabolites (85%) are simply statistical noise. Only 3 to 12% of these metabolites reach the threshold of statistical significance for a specific cancer type. Our findings demonstrate the absence of a detectable metabolic response to cancer and provide evidence of a serious need by the metabolomics community to establish widely accepted best practices to improve future outcomes.PMID:40236582 | PMC:PMC11999569 | DOI:10.1016/j.trac.2024.117918

Front Microbiol. 2025 Apr 1;16:1541683. doi: 10.3389/fmicb.2025.1541683. eCollection 2025.ABSTRACTThe gut microbiome has emerged as a potential factor in cancer pathogenesis, but its role in non-functioning pituitary neuroendocrine tumors (NF-PitNETs) remains unclear. This study aimed to elucidate gut microbiome and metabolomic alterations in NF-PitNETs by comparing microbial diversity, pathogenic bacteria, and serum metabolomic profiles between NF-PitNET patients and healthy controls. The gut microbiome was assessed through 16S rRNA sequencing, while serum metabolomics was analyzed using mass spectrometry. Correlation analyses identified potential links between microbial characteristics and metabolic markers. The results revealed that specific pathogenic bacteria, such as Bacteroides, were significantly enriched in NF-PitNET patients. Multi-omics correlations suggested that altered microbiota might contribute to NF-PitNET pathogenesis by modulating host metabolic pathways. These findings highlight the potential role of gut microbiome dysbiosis and its metabolic effects in NF-PitNET development, offering insights into possible therapeutic and diagnostic targets.PMID:40236482 | PMC:PMC11997625 | DOI:10.3389/fmicb.2025.1541683

Front Microbiol. 2025 Apr 1;16:1581166. doi: 10.3389/fmicb.2025.1581166. eCollection 2025.NO ABSTRACTPMID:40236477 | PMC:PMC11998031 | DOI:10.3389/fmicb.2025.1581166