PubMed

Arthritis Res Ther. 2025 Mar 31;27(1):69. doi: 10.1186/s13075-025-03537-4.ABSTRACTBACKGROUND: Osteoarthritis (OA) is associated with abnormal lipid metabolism, wherein elevated levels of phospholipids (PLs) and sphingolipids (SLs) in human and canine synovial fluid (SF) have been observed. The aim of this lipidomic study was to evaluate how closely blood lipid levels reflect changes in SF, building on previous findings.METHODS: Lipids were extracted from knee SF and serum of 44 joint-healthy donors and 58 early (eOA) or late OA (lOA) patients. By electrospray ionization tandem mass spectrometry (ESI-MS/MS), we quantified the extracted lipids and conducted comprehensive statistical analyses.RESULTS: Human SF and serum had similar PL and SL compositions. Quantifying 91 lipid species from 6 major classes revealed OA-related changes in serum, with the lowest levels in healthy controls and elevated levels already in the eOA cohort. Generally, serum PL and SL levels were 3-12 times higher than in SF. Specific PL species were elevated in both SF and serum of eOA and lOA patients compared to healthy controls, while nearly 10% of the PL species measured were higher exclusively in the serum of OA patients.CONCLUSIONS: The significant lipidomic alterations that were detected at an average Outerbridge score of less than 2 suggest that certain serum PLs may serve as indicators for monitoring the early stages of OA even before radiologic detection is possible. With 10% of PL species elevated only in OA serum, our data implicate the existence of a systemic response that parallels the local lipid metabolic response to OA.PMID:40165249 | DOI:10.1186/s13075-025-03537-4

BMC Genomics. 2025 Mar 31;26(1):323. doi: 10.1186/s12864-025-11529-6.ABSTRACTBACKGROUND: Alfalfa (Medicago sativa L.) serves as a vital high-quality forage resource, especially in tropical and subtropical regions where there is a deficiency of protein-rich feed. The red pigmentation of stem of space mutated alfalfa was mainly caused by anthocyanin accumulation. However, investigations into the mechanisms governing anthocyanin biosynthesis in alfalfa stems have been scarce.RESULT: In this study, we conducted combined transcriptome and metabolome analyses on two types of alfalfa stems: space mutation red-stemmed alfalfa and non-space mutation green-stemmed alfalfa (control). Profiling of the anthocyanin metabolome unveiled 45 metabolites linked to anthocyanin biosynthesis, with cyanidin-3-O-glucoside, pelargonidin-3-O-arabinoside, delphinidin-3-O-(6-O-acetyl)-glucoside, and kaempferol-3-O-rutinoside identified as the primary anthocyanins of red-stemmed alfalfa. Transcriptome analysis revealed 72 differentially expressed genes related to anthocyanin biosynthesis pathways, of which 54 genes were highly expressed in red stems, including 12 PALs (phenylalanine ammonia-lyase), 22 4CLs (4-coumaroyl: CoA-ligase), eight CHSs (chalcone synthase), three F3Hs (flavanone 3-hydroxylase), two ANRs (anthocyanidin reductase), three DFRs (dihydroflavonol-4-reductase), three ANSs (anthocyanidin synthase), and one FLS (flavonol synthase) gene. These genes are likely pivotal for anthocyanin biosynthesis in red-stemmed. Co-expression analysis of differentially expressed genes and relative contents of differentially expressed anthocyanin showed that each anthocyanin was closely related to multiple genes, and anthocyanin accumulation process was regulated by multiple genes. The expressions of these genes were significantly positively correlated with the relative contents of cyanidin-3-O-glucoside, pelargonin-3-O-arabinoside, and kaempferol-3-O-rutin.CONCLUSION: Overall, the expression patterns of PAL, 4CL, CHS, F3H, ANR, DFR, ANS, and FLS structural genes in anthocyanin biosynthesis pathway were closely related to the composition and content of anthocyanins. Different anthocyanins' accumulation patterns may result in the different stem colors of alfalfa. These findings provide comprehensive insights into the molecular mechanisms for anthocyanin biosynthesis in red-stemmed alfalfa.PMID:40165085 | DOI:10.1186/s12864-025-11529-6

BMC Plant Biol. 2025 Mar 31;25(1):403. doi: 10.1186/s12870-025-06441-w.ABSTRACTBACKGROUND: Radix Bupleuri is a popular traditional Chinese medicinal plant. Its root contains saikosaponin and volatile oil compounds with antipyretic, anti-inflammatory, and hepatoprotective pharmacological effects. However, there are differences in the content and type of main chemical components in the roots of three Bupleurum species: Bupleurum chinense DC. (Bchi), Bupleurum scorzonerifolium Willd. (Bsco), and Bupleurum marginatum var. stenophyllum (Wolff) Shan et Y.Li (Bmar). The molecular mechanism behind these differences is still unclear. The present study used integrated metabolome and transcriptome analyses to uncover the differences in metabolites and expressed genes among the three Bupleurum species.RESULTS: Metabolomics results revealed that Bmar contained more saikosaponins than Bchi and Bsco. Conversely, Bsco had the highest content of volatile oil monoterpenes but a lower sesquiterpene content than Bchi and Bmar. Transcriptome analysis showed that several genes were highly expressed in Bchi, Bsco, or Bmar, demonstrating the molecular mechanism responsible for the differences in their metabolic components. We combined the metabolomics and transcriptomics data to investigate the relationship between metabolites and genes. The results showed a high correlation between CYP450, UGT, and β-AS genes and 6''-acetyl-saikosaponins A, saikosaponins B1, C, and D. The subcellular localization of the two P450 genes (Bc087391 and Bc036879) in the endoplasmic reticulum suggests that they may be involved in saikosaponin biosynthesis.CONCLUSION: We performed an integrated transcriptome and metabolome analysis to investigate the diversity of the terpenoid biosynthetic pathway in three Bupleurum species. The study provides new insights into the molecular basis of the metabolic differences between the three Bupleurum species. It also serves as a theoretical basis for the clinical application and breeding of Bupleurum resources.PMID:40165079 | DOI:10.1186/s12870-025-06441-w

BMC Infect Dis. 2025 Mar 31;25(1):441. doi: 10.1186/s12879-025-10823-8.ABSTRACTBACKGROUND: Pneumonia Compound Formulation (PCF) is a traditional Chinese medicine (TCM) formula used for the clinical treatment of novel coronavirus pneumonia. However, its efficacy and mechanism of action for community-acquired pneumonia (CAP) are unknown. Therefore, the aim of this study was to evaluate the efficacy of PCF combined with antibiotics in the treatment of CAP and to explore its mechanism based on metabolomics.PATIENTS AND METHODS: This prospective controlled study included 100 CAP patients from June to December 2023. Patients were randomized into an antibiotics-only group (NCM, n = 50) and a combined antibiotics and PCF treatment group (CM, n = 50). Clinical data were collected for all participants. The efficacy of the treatments was assessed by comparing traditional Chinese medicine syndrome scores and clinical parameters before and after treatment. Levels of inflammatory mediators (CRP, IL-6, TNF-α) and immunoglobulins (IgA, IgG, IgM) in the plasma were measured using ELISA. Plasma metabolomics analysis was conducted using ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS).RESULTS: Both the NCM and CM group improved the clinical symptoms of CAP patients, with the CM group showing more significant improvements. Both groups effectively reduced the levels of the inflammatory mediators CRP, but had no significant impact on immunoglobulin levels. CM group using additional PCF significantly altered glycerophospholipid metabolism in patients, primarily characterized by increased levels of phosphatidylinositol, phosphatidylglycerol, and 1-acyl-sn-glycero-3-phosphoethanolamine, and decreased levels of phosphatidylcholine and phosphatidylethanolamine.CONCLUSIONS: PCF is an effective adjunct therapy to antibiotics for the treatment of CAP, enhancing clinical symptom improvement. Its mechanism may involve the regulation of glycerophospholipid metabolism levels in patients, providing a new theoretical basis for the application of PCF in the treatment of CAP.TRIAL REGISTRATION: ChiCTR2400086283 (2024-06-27).PMID:40165069 | DOI:10.1186/s12879-025-10823-8

BMC Plant Biol. 2025 Apr 1;25(1):409. doi: 10.1186/s12870-025-06393-1.ABSTRACTBACKGROUND: Chicory is a unique and nutritious vegetable crop. However, the molecular mechanisms underlying anthocyanin biosynthesis in chicory remain poorly understood. We combined transcriptomics and metabolomics analyses to explore the molecular basis of anthocyanin biosynthesis in red-budded (Z1) and yellow-budded (Z7) chicory.RESULTS: Integrated transcriptomics and metabolomics analyses were performed to investigate the molecular basis of anthocyanin biosynthesis in chicory. A total of 26 key structural genes, including F3'H, DFR, CHS, and ANS, were identified and enriched in pathways such as flavonoid and anthocyanin biosynthesis. Additionally, 29 transcription factors were identified, including 11 MYB, five bHLH, and two WD40 transcription factors, with seven MYB genes upregulated and four genes downregulated, indicating their roles in regulating anthocyanin biosynthesis. Notably, the MYB transcription factor, CI35997, which is homologous to RLL2A in lettuce, was predicted to positively regulate anthocyanin biosynthesis. Other transcription factors, such as AP2/ERF, bZIP, NAC, and Trihelix, have also been implicated. Metabolomics analysis revealed that cyanidin derivatives were the main contributors to the red coloration of chicory buds, with cyanidin-3-O-(6-O-malonyl)-glucoside being the most abundant. Furthermore, a competitive relationship between lignin and anthocyanin biosynthesis was observed, wherein the downregulation of lignin-related genes enhanced anthocyanin accumulation.CONCLUSIONS: This study identified key structural genes and transcription factors that offer molecular-level insights into anthocyanin biosynthesis in chicory. These findings provide valuable guidance for genetic improvement of chicory and other crops with high anthocyanin content.PMID:40165067 | DOI:10.1186/s12870-025-06393-1

BMC Microbiol. 2025 Mar 31;25(1):180. doi: 10.1186/s12866-024-03644-3.ABSTRACTBACKGROUND: Rumen microbial community structure and stability are very important for ruminant health, growth and development, and livestock product yield. Dietary composition and nutritional structure affect microbial diversity and richness. The purpose of this study was to evaluate the effects of different fiber levels of energy feed on the rumen microflora and fermentation function of grazing sheep in salinized sown pasture, to reveal the response of the main microflora of sheep rumen at the phylum and genus levels to different fiber levels of energy feed and to analyze the internal mechanism to provide a reference for the selection of energy feed and the improvement of the production performance of grazing livestock.RESULTS: The fiber level of energy feed affects the rumen fermentation and rumen microbial community structure of grazing sheep. Low-fiber-energy feeds significantly increased the relative abundance of Actinobacteria, while the relative abundances of Cyanobacteria, Ruminococcaceae_UCG_010, Ruminococcaceae_NK4A214_group, and Elusimicrobium significantly decreased, adjusting the relationship between the flora toward cooperation. High-fiber-energy feeds significantly increased the concentration of VFAs, significantly decreased the relative abundances of Proteobacteria, Ruminococcaceae_NK4A214_group and Rikenellaceae_RC9_gut_group, adjusted the relationship between the flora to compete, and promoted the enrichment of metabolic pathways such as "Protein Digestion and Absorption," "Nitrogen Metabolism," "Starch and Sucrose Metabolism," and "Degradation of Other Sugars."CONCLUSIONS: Supplementary feeding of high and low fiber energy feeds reduced the pH value of rumen fluid and the richness and diversity of microorganisms in grazing sheep, reduced the relative abundance of some harmful microorganisms, affected the metabolic activities of some fiber-digesting bacteria, regulated the interaction and competition between bacteria, increased the content of volatile fatty acids (VFAs) and the relative abundance of metabolic-related microorganisms in the supplementary feeding group, and enriched the metabolic-related pathways. However, further understand the mechanism of the effect of fiber level on the rumen of sheep, it is necessary to conduct in-depth analysis using research methods such as transcriptomics, proteomics and metabolomics.PMID:40165064 | DOI:10.1186/s12866-024-03644-3

BMC Microbiol. 2025 Mar 31;25(1):176. doi: 10.1186/s12866-025-03892-x.ABSTRACTBACKGROUND: Congenital hepatic fibrosis (CHF) caused by mutations in the polycystic kidney and hepatic disease 1 (PKHD1) gene is a rare genetic disorder with poorly understood pathogenesis. We hypothesized that integrating gut microbiome and metabolomic analyses could uncover distinct host-microbiome interactions in CHF mice compared to wild-type controls.METHODS: Pkhd1del3-4/del3-4 mice were generated using CRISPR/Cas9 technology. Fecal samples were collected from 11 Pkhd1del3-4/del3-4 mice and 10 littermate wild-type controls. We conducted a combined study using 16 S rDNA sequencing for microbiome analysis and untargeted metabolomics. The gut microbiome and metabolome data were integrated using Data Integration Analysis for Biomarker discovery using Latent cOmponents (DIABLO), which helped identify key microbial and metabolic features associated with CHF.RESULTS: CHF mouse model was successfully established. Our analysis revealed that the genera Mucispirillum, Eisenbergiella, and Oscillibacter were core microbiota in CHF, exhibiting significantly higher abundance in Pkhd1del3-4/del3-4 mice and strong positive correlations among them. Network analysis demonstrated robust associations between the gut microbiome and metabolome. Multi-omics dimension reduction analysis demonstrated that both the microbiome and metabolome could effectively distinguish CHF mice from controls, with area under the curve of 0.883 and 0.982, respectively. A significant positive correlation was observed between the gut microbiome and metabolome, highlighting the intricate relationship between these two components.CONCLUSION: This study identifies distinct metabolic and microbiome profiles in Pkhd1del3-4/del3-4 mice. Multi-omics analysis effectively differentiates CHF mice from controls and identified potential biomarkers. These findings indicate that gut microbiota and metabolites are integral to the pathogenesis of CHF, offering novel insights into the disease mechanism.PMID:40165060 | DOI:10.1186/s12866-025-03892-x

J Sci Food Agric. 2025 Mar 31. doi: 10.1002/jsfa.14250. Online ahead of print.ABSTRACTBACKGROUND: Chinese spicy cabbage (CSC) is a famous traditional fermented vegetable widely consumed in northeast China. However, the differences in characteristics between Liaoning spicy cabbage (LNSC) and Yanbian spicy cabbage (YBSC), as well as the correlation between flavor attributes and microbiota remain unclear. This study clearly delineated the characteristics and correlations of ingredients, aroma characteristics and microbial communities between LNSC and YBSC.RESULTS: Metabolomic analysis revealed distinct compositional differences in both volatile and non-volatile metabolites between LNSC and YBSC. Through relative odor activity value analysis, 17 and 14 key flavor compounds were identified as characteristic components in LNSC and YBSC, respectively. Amplicon sequencing demonstrated significant regional variations in the bacterial community structure of CSC. Spearman correlation analysis demonstrated strong correlations between 20 bacteria and 11 free amino acids, 22 volatile flavor compounds.CONCLUSION: This study systematically compared the quality characteristics between LNSC and YBSC, providing fundamental data for the evaluation of spicy cabbage and fermented food products. © 2025 Society of Chemical Industry.PMID:40164994 | DOI:10.1002/jsfa.14250

Scand J Med Sci Sports. 2025 Apr;35(4):e70044. doi: 10.1111/sms.70044.ABSTRACTEnhancing athletic performance through the manipulation of nutritional intake has ancient roots, with early guidance from "philosophical giants" like Hippocrates, who describes the balance between diet and exercise. Modern sports nutrition emerged in the 20th century, with research identifying carbohydrate (CHO) intake as beneficial for endurance. Studies like Gordon's in the 1920s linked blood glucose levels to marathon performance, while Cade's research in the 1960s on fluid and electrolyte intake led to the founding of Gatorade and the shift toward drinking during exercise to allegedly prevent dehydration and improve sporting performance. Today, sports nutrition is in a "holding pattern" after significant developments in the 1980s, 1990s, and the 2000s. A new era will involve personalized nutrition, but this development will require a game-changing injection of momentum, recognizing that athletes' responses to nutrition interventions vary widely. New technologies will also need to be developed and perfected, including wearables for real-time biometric monitoring (e.g., heart rate variability, glucose, and sweat composition and rate), which offer potential for tailored nutrition (i.e., diet and hydration) strategies. Applications of genetic and multi-omics technologies (like genomics, transcriptomics, metabolomics, proteomics, and epigenomics) are needed to unlock the potential of personalized sports nutrition by analyzing individual responses to factors such as sleep, nutrition, and exercise. The future lies in fast integration of all available data using next-generation bioinformatics and AI to generate personalized recommendations, with an emphasis on empirical evidence rather than solely commercial interests. As technology matures, sports (and exercise) nutrition will continue refining its practices but will need a paradigm shift to deliver precise interventions that may offer athletes the crucial edge needed to maximize performance while promoting short-term and long-term health.PMID:40164953 | DOI:10.1111/sms.70044

Metabolomics. 2025 Mar 31;21(2):47. doi: 10.1007/s11306-025-02245-z.ABSTRACTBACKGROUND: Diabetes mellitus refers to a group of metabolic diseases characterized by chronic hyperglycemia due to multiple etiological factors. As the disease progresses, patients gradually develop microvascular complications, including diabetic nephropathy, diabetic retinopathy, and diabetic neuropathy. However, current clinical methods for detecting these microvascular complications are limitations, thus primary prevention and early diagnosis are of great importance.AIM OF REVIEW: This review summarizes the known blood biomarkers of diabetic microvascular complications, classified according to type of structure, including amino acid metabolism, lipid metabolism, carnitine metabolism, organic acid metabolism, etc., which can be used for the simultaneous typing of diabetes mellitus based on microvascular complications, and to search for the trend of changes to lay the foundation for early diagnosis and understanding of the pathogenesis of diabetic microvascular complications, including oxidative stress, and mitochondrial dysfunction. Searches for the trend of changes to lay the foundation for early diagnosis and understanding of the pathogenesis of diabetic microvascular complications, including oxidative stress, mitochondrial dysfunction.KEY SCIENTIFIC CONCEPTS OF REVIEW: Due to the limitations of diagnostic criteria for diabetic microvascular complications, some patients already have the disease for which they are being tested. Metabolomics reflects the physiological state of an organism by analyzing the small molecules metabolites present in a biological tissue that are related to clinical phenotypes, providing a snapshot of the physiological and pathophysiological metabolic processes occurring within that organism at any given time, thus opening the door for the development of diagnostic biomarkers and precise treatment. In clinical metabolomics, blood is considered a specialized type of connective tissue, which allows it to transport substances throughout the body, connecting different systems together. Also, blood components are probably the most frequently used matrix in metabolomics studies. Therefore, metabolomics is used to analyze blood biomarkers that reflect the course of diabetes and explore the pathways involved in the pathophysiology of the three most common diabetic microvascular complications. Finally, in this review, we discuss the current limitations of metabolomic analysis, and the integrative multi-omics data, including genomics, transcriptomics, and proteomics, required for developing specific biomarkers for diabetic microvascular complications.PMID:40164927 | DOI:10.1007/s11306-025-02245-z

Trop Anim Health Prod. 2025 Apr 1;57(3):148. doi: 10.1007/s11250-025-04400-z.ABSTRACTThis study aimed to investigate the microbial population dynamics and metabolite profiles of Ongole crossbreed cattle (OCC) fed a combination of feed additives using metagenomic and metabolomic analyses. A crossover design was employed, involving four 3-year-old fistulated OCC bulls, each receiving four distinct dietary treatments per experimental period, followed by a washout phase with a basal diet. The treatments consisted of a basal diet (G1) as control, and the addition of feed additives as follows: G2: probiotics (Lactiplantibacillus plantarum); G3: premix; G4: G2 + G3 + amino acids lysine and methionine; and G5: G2 + G3 + amino acids protected with tannin. Rumen fluid was collected for the analysis of microbiome dynamics and metabolite profiles. The bacterial communities in diets G1, G2, G3, and G5 exhibited similar compositions, dominated by Bacteroidota, particularly the genus Prevotella. The G5 diet successfully suppressed the population of archaea, notably Methanosarcinales and Methanobacteriales, which are associated with methane production. A total of 28 significant metabolites (VIP > 1) was identified in rumen fluid, including lipid prenols, phenolic compounds, indoles and derivatives, saturated and unsaturated hydrocarbons, fatty acyls, benzene derivatives, and organooxygen compounds. The volatile compounds profile of rumen fluid showed a marked increase in prenol lipid compounds, especially in the G5 diet. Additionally, Methanosarcinales and Methanobacteriales were negatively correlated with prenol lipid levels. The inclusion of probiotics and protected amino acids alters the microbiome community structure and metabolites, positively affecting ruminant productivity.PMID:40164860 | DOI:10.1007/s11250-025-04400-z

Metabolomics. 2025 Mar 31;21(2):46. doi: 10.1007/s11306-025-02249-9.ABSTRACTINTRODUCTION: The ANGUSTIFOLIA3 (AN3) gene encodes a transcriptional co-activator for cell proliferation in Arabidopsis thaliana leaves. We previously showed that Physcomitrium patens AN3 orthologs promote gametophore shoot formation through arginine metabolism.OBJECTIVES: We analyzed the role of AN3 in Arabidopsis thaliana to understand how seedling growth is regulated by metabolic and physiological modulations.METHODS: We first explored amino acids that affect the seedling growth of an3 mutants. Transcriptome and metabolome analyses were conducted to elucidate the metabolic and physiological roles of AN3 during seedling growth. Lastly, we examined the distribution of reactive oxygen species to corroborate our omics-based findings.RESULTS: Our results indicated that an3 mutants were unable to establish seedlings when grown with leucine, but not arginine. Multi-omics analyses suggested that an3 mutants exhibit a hypoxia-like response. Abnormal oxidative status was confirmed by detecting an altered distribution of reactive oxygen species in the roots of an3 mutants.CONCLUSION: AN3 helps maintain the leucine metabolism and oxidative balance during seedling growth in Arabidopsis thaliana. Future research is necessary to explore the interaction between these processes.PMID:40164829 | DOI:10.1007/s11306-025-02249-9

Exp Mol Med. 2025 Apr 1. doi: 10.1038/s12276-025-01430-3. Online ahead of print.ABSTRACTThe specific function of NR4A1 as a transcriptional regulator in cancer remains unclear. Here we report the biological effect of NR4A1 in suppressing breast cancer (BC) growth. We found that NR4A1 deficiency was correlated with BC progression in the clinic. Genetic deletion of NR4A1 in BC cells significantly promoted cellular proliferation and tumor growth. Moreover, global metabolome screening indicated that the deletion of NR4A1 resulted in tumor lipid remodeling and phospholipid accumulation, which was accompanied by increases in fatty acid and lipid uptake. In addition, NR4A1 knockout induced oxidative stress that aggravated redox balance disruption. Mechanistically, transcriptomic and epigenomic analyses revealed that NR4A1 restrained BC cell proliferation by directly interacting with c-Fos and competitively inhibiting c-Fos binding to the promoter of the target gene PRDX6, which is involved in lipid and redox homeostasis. Notably, we confirmed that the treatment of BC cells with the selective NR4A1 agonist cytosporone B significantly activated the expression of NR4A1, followed by increased interaction between NR4A1 and c-Fos, thereby interfering with c-Fos-mediated transcriptional regulation of BC cell growth. Thus, NR4A1 plays a vital role in reducing the c-Fos-induced activation of downstream signaling cascades in BC, suggesting that agents that activate NR4A1 may be potential therapeutic strategies.PMID:40164686 | DOI:10.1038/s12276-025-01430-3

NPJ Genom Med. 2025 Mar 31;10(1):29. doi: 10.1038/s41525-025-00487-3.ABSTRACTIndividuals affected by a rare disease often experience a long and arduous diagnostic odyssey. Delivery of genetic answers in a timely manner is critical to affected individuals and their families. Multi-omics, a term which usually encompasses genomics, transcriptomics, proteomics, metabolomics and lipidomics, has gained increasing popularity in rare disease research and diagnosis over the past decade. Mass spectrometry (MS) is a technique allowing the study of proteins, metabolites and lipids and their fragments at scale, enabling researchers to effectively determine the presence and abundance of thousands of molecules in a single test, accurately quantify their specific levels, identify potential therapeutic biomarkers, detect differentially expressed proteins in patients with rare diseases, and monitor disease progression and treatment response. In this review, we focus on mass spectrometry (MS)-based omics and survey the literature describing the utility of different MS-based omics and how they have transformed rare disease research and diagnosis.PMID:40164634 | DOI:10.1038/s41525-025-00487-3

Comp Biochem Physiol C Toxicol Pharmacol. 2025 Mar 29:110196. doi: 10.1016/j.cbpc.2025.110196. Online ahead of print.ABSTRACTAlthough recent studies have demonstrated that Marine-fungus-derived citrinin (MFDC) has a significant cytotoxic effect in traditional two-dimensional (2D) monolayer cell culture and animal models, its precise cytotoxic mechanism, particularly in a three-dimensional (3D) cell culture model remains unclear. In this study, a 3D Hepa1-6 cell model based on Matrigel was used to investigate the potential cytotoxic mechanism of MFDC (0-100 μg/mL). The results revealed that, after treatment of 60-100 μg/mL MFDC, the increases of reactive oxygen species (ROS), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in 2D cell model were more significant than those in 3D cell model. In addition, the metabolomic results revealed that the significantly altered metabolic pathways were pyrimidine metabolism and vitamin B6 metabolism, which might be related to the interference of MFDC in the pyrimidine synthesis pathway, as well as the upregulation of pyridoxine 5'phosphate oxidase and pyridoxal kinase activities. This study was the first to compare the cytotoxicology of 2D and Matrigel-based 3D cell models after MFDC induction, and to detect differences in cell metabolites after MFDC induction in 3D cell models, providing a new scientific basis for the use of a 3D cell model and a novel research idea for the cellular damage caused by MFDC.PMID:40164369 | DOI:10.1016/j.cbpc.2025.110196

Behav Brain Res. 2025 Mar 29:115559. doi: 10.1016/j.bbr.2025.115559. Online ahead of print.ABSTRACTObesity is a growing public health concern that significantly impacts cognitive functions, including memory. This research explores how a high-fat diet affects short-term memory, employing the novel object recognition (NOR) test and NMR-based metabolomics to elucidate metabolic alterations in the brain and adipose tissue. The zebrafish were divided into two groups: one receiving a standard diet (SD) and the other a high-fat diet (HFD). Body mass index (BMI) was assessed every two weeks for a period of eight weeks. The NOR test was used to determine the discrimination index (DI) for evaluating the short-term memory of the SD and HFD groups. NMR spectroscopy was employed to investigate the metabolites in brain and adipose tissues, and multivariate data analysis was conducted to discover significant metabolic alterations. The high-fat diet (HFD) resulted in a significant increase in body mass index (BMI) (p < 0.0001) compared to the standard diet (SD) group from week 4 to week 8. A significant reduction in the discrimination index (24.95%) in the HFD group against the SD group suggests a decline in memory performance among HFD subjects. NMR-based metabolomics of adipose tissue revealed that linoleic acid and caprylic acid were consistently found to exhibit increased levels in the HFD group across all assessments, whereas lauric acid, ALA, EPA, and DHA were consistently present at elevated levels in the adipose tissue of the SD group. NMR-based metabolomics of the brain identified GABA, taurine, and histamine as the key metabolites distinguishing the HFD from the SD group in female zebrafish. For male zebrafish brains, taurine, phenylalanine, and tryptophan were identified as the most significant metabolites for differentiating between HFD and SD. These metabolites demonstrated a notable decrease in the HFD group relative to the SD group. The results of this study align with those of previously reported studies in rodents and humans, indicating that memory impairment associated with obesity may stem from neuroinflammation and changes in synaptic plasticity. This research provides insights into the molecular changes in adipose tissue and the brain that occur when individuals receive a high-fat diet (HFD), which may enhance our understanding of the link between obesity and memory impairment, ultimately leading to a better comprehension of the disease.PMID:40164316 | DOI:10.1016/j.bbr.2025.115559

Environ Pollut. 2025 Mar 29:126158. doi: 10.1016/j.envpol.2025.126158. Online ahead of print.ABSTRACTOzone (O3) pollution poses an increasingly serious threat to forest ecosystems. To investigate the effects of O3 exposure on Quercus aliena and elucidate its defense mechanisms, we exposed Q. aliena to O3 and monitored its responses using physiological, transcriptomic, and metabolomic analyses. The results revealed that after 84 days of O3 exposure, the malondialdehyde (MDA) and proline contents in Q. aliena leaves significantly increased, while catalase (CAT) activity and soluble sugar content significantly decreased. Notably, N addition markedly alleviated O3-induced oxidative stress. Integrated transcriptomic and metabolomic analyses revealed that N addition under O3 stress modulated metabolic pathways associated with flavonoid biosynthesis and amino acid metabolism. Specifically, O3 and N treatment increased the levels of rhoifolin, afzelechin, apigenin, luteoloside, kaempferol, and trifolin, while reducing the levels of phloretin, butin, cyanidin, taxifolin, myricetin, 2'-hydroxydaidzein, laricitrin, quercetin, prunin, luteolin, eriodictyol, quercitrin, and dihydromyricetin. Additionally, the co-treatment elevated the concentrations of L-glutamine, arginine, and ornithine, along with the levels of enzymes closely related to their synthesis, such as glnA (Uni0006561, Uni0006562, Uni0077758, Uni0101990), GSH (Uni0086646, Uni0101788), GSS (Uni0037737), and GCLC (Uni0034253). This study elucidates the metabolic alterations in Q. aliena under combined O3 and N treatments, highlighting changes in flavonoid biosynthesis and amino acid metabolism pathways. Using a multi-omics approach, we provide comprehensive insights into the responses of Q. aliena to O3 stress and N addition, offering significant implications for the management and conservation of forest ecosystems under environmental stress.PMID:40164273 | DOI:10.1016/j.envpol.2025.126158

Int J Biol Macromol. 2025 Mar 29:142660. doi: 10.1016/j.ijbiomac.2025.142660. Online ahead of print.ABSTRACTA novel exopolysaccharide AVP-214-1was isolated and purified from the metabolites of a Mariana Trench-derived fungus Aspergillus versicolor SCAU214. AVP-214-1 exhibited a heteropolysaccharide architecture composed of mannose, galactose, and glucose residues. The linear backbone adopted α-(1 → 4)-linked d-galactopyranose and d-glucopyranose units with the following sequence: →[4,6)-α-D-Glcp-(1 → 4)-α-D-Glcp-(1]4 → [4)-α-D-Glcp-(1 → 6)-α-D-Glcp-(1 → 3)-α-D-Glcp-(1]3 → [4,6)-α-D-Glcp-(1 → 4)-α-D-Glcp-(1]2 → [4)-α-D-Glcp-(1]19 → [4)-α-D-Glcp-(1 → 4)-α-D-Galp-(1]2→. Structural complexity arose from two distinct branching motifs: single α-d-glucopyranosyl and an α-D-mannopyranosyl, both attached via C-6 positions of the backbone residues 1,4,6-α-D-Glcp. The molecular weight of AVP-214-1 was determined to be 8277 Da. In functional assays, AVP-214-1 was found to significantly enhance the proliferation of RAW 264.7 macrophage cells and promote the secretion of cytokines, such as IL-6, TNF-α and IL-1β. Metabolomic analysis revealed that AVP-214-1 primarily influences pyrimidine metabolism and amino acid-related metabolic pathways, these metabolic pathways were likely related to immune regulation. These results suggest that AVP-214-1 from a Mariana Trench-derived fungus was a novel immune-stimulating polysaccharide, opening up new avenues for the development of bioactive polysaccharides from deep-sea organisms for potential biotechnological applications.PMID:40164263 | DOI:10.1016/j.ijbiomac.2025.142660

J Affect Disord. 2025 Mar 29:S0165-0327(25)00513-0. doi: 10.1016/j.jad.2025.03.164. Online ahead of print.ABSTRACTOBJECTIVE: Depression affects millions, and current treatments have limitations, necessitating new approaches. Earlier research confirms Hyperforin's ability to reduce anhedonic behaviors in mice and modulate gut microbiota. This study aims to identify specific metabolic changes induced by Hyperforin that could illuminate its impact on gut microbiome metabolism, possibly uncovering novel metabolites for developing antidepressant therapies.METHODS: Following the chronic stress model, untargeted metabolomic analysis of fecal samples was conducted to identify metabolic changes induced by Hyperforin. Bioinformatics tools analyzed the origins of differentially expressed metabolites and their correlation with Akkermansia muciniphila and Muribaculum intestinale. The significant metabolite Carbocysteine was further investigated for its antidepressant effects using behavioral assays in a mouse model of depression. Additionally, the response of the colonic mucus barrier was evaluated using Periodic Acid-Schiff (PAS) staining, scanning electron microscopy (SEM), and enzyme-linked immunosorbent assays (ELISA).RESULTS: Hyperforin significantly altered fecal metabolite profiles in stressed mice, with a notable shift in 239 metabolites mainly associated with co-metabolism pathways and microbiota-specific processes. Among these, Carbocysteine emerged as a key metabolite linked to beneficial bacteria Akkermansia muciniphila and Muribaculum intestinale, with its levels significantly elevated following Hyperforin treatment. Behavioral assessments indicated that Carbocysteine supplementation ameliorated depressive-like behaviors in the chronic restraint stress mouse model. It also enhanced colonic mucus production and integrity.CONCLUSION: Our research highlights Hyperforin's role in modulating gut microbiota metabolism and identifies Carbocysteine as a potential antidepressant. These findings advance our understanding of the gut-brain axis (GBA) in depression and pave the way for developing new therapeutics.PMID:40164238 | DOI:10.1016/j.jad.2025.03.164

Ecotoxicol Environ Saf. 2025 Mar 30;294:118128. doi: 10.1016/j.ecoenv.2025.118128. Online ahead of print.ABSTRACTThe effects of triclosan (TCS) and its transformation product methyl-triclosan (MTCS) on the earthworm Eisenia fetida were investigated using Gas chromatography-mass spectrometry (GC-MS) metabolomics. Earthworms were exposed to 0, 0.25, 1, 4, 16, and 64 µg g-1 of either TCS or MTCS for 14 days in commercial worm bedding. Only MTCS exposure caused any effects on the earthworm metabolites targeted in this study. Succinic acid was elevated relative to the control at concentrations ≥ 0.25 µg g-1 and glucose was elevated at 1 µg g-1. Earthworms exposed to 1 µg g-1 MTCS had the greatest separation from the control using Principal Components Analysis (PCA), while 0.25 and 1 µg g-1 had the largest separation in Discriminant Analysis (DA). Essential amino acids valine, leucine, serine, and phenylalanine had large, standardized coefficients for PCA and DA reflecting their contribution to separation, suggesting that essential amino acid homeostasis was perturbed by MTCS. Malic acid, succinic acid, margaric acid, and glucose were highly correlated (p < 0.01) with Canonical 1 and PC 2, while maltose was correlated with Canonical 2 and PC 7, indicating a strong relationship between these metabolites and the multivariate separation expressed in the canonical variables. Disruption of succinate metabolism by membrane destabilization in mitochondria was hypothesized as a possible mode of action for MTCS.PMID:40164038 | DOI:10.1016/j.ecoenv.2025.118128