PubMed

Fitoterapia. 2025 Feb 21:106449. doi: 10.1016/j.fitote.2025.106449. Online ahead of print.ABSTRACTPaeoniae Radix Alba (PRA) is a traditional Chinese medicine that can be processed with wine to achieve an enhanced effect of promoting blood circulation, thus alleviating blood stasis. However, to date, the changes in the bioactive compounds of PRA before and after wine-processing, as well as the mechanisms of action and the effects on ameliorating blood stasis syndrome (BSS), have not been adequately investigated. Therefore, we systematically elucidated the material basis and mechanisms of action of PRA in the treatment of BSS before and after wine processing by integrating serum pharmacochemistry, network pharmacology, and metabolomics approaches. The wine processing method significantly affected 11 components of PRA, including gallic acid, ethyl gallate, paeoniflorin, and 3-O-methylellagic acid 4-O-β-D-glucopyranoside. Benzoylpaeoniflorin and desbenzoylpaeoniflorin are key serum components of PRA both before and after wine processing. SRC and GAPDH are the central targets through which benzoylpaeoniflorin and desbenzoylpaeoniflorin exert their ameliorative effects on BSS, respectively. The metabolomics results indicated that six metabolic pathways-pyrimidine metabolism, ascorbate and aldarate metabolism, steroid hormone biosynthesis, pentose and glucuronate interconversions, tryptophan metabolism, and lysine degradation-play important roles in the amelioration of BSS by PRA and WPRA. 2'-Deoxycytidine, cortexolone, dihydrocortisol, L-gulonic gamma-lactone, L-uridine, D-ribulose, 4-trimethylammoniobutanoic acid, and indoleacetic acid have been identified as potential biomarkers for the amelioration of BSS by PRA and WPRA. The present study significantly contributes to elucidating the processing mechanism of PRA in "promoting blood circulation to remove blood stasis through wine processing".PMID:39988208 | DOI:10.1016/j.fitote.2025.106449

Int J Biol Macromol. 2025 Feb 21:141356. doi: 10.1016/j.ijbiomac.2025.141356. Online ahead of print.ABSTRACTResistant starch (RS) is a novel type of prebiotic that exerts positive effects on lipid metabolism and intestinal flora. In this study, we investigated the effects of dietary RS on lipid metabolism and the intestinal barrier in largemouth bass (Micropterus salmoides). The experimental fish were fed either a control diet (C), a high-fat diet (H), or H diets supplemented with 0.5 %, 1.5 %, and 3 % RS (HRS0.5, HRS1.5, and HRS3.0). Dietary supplementation with 1.5 % and 3.0 % RS increased the final weight and feed utilization. Moreover, the hepatic crude protein content and the expression of genes related to lipid lipolysis were significantly higher in the HRS1.5 group compared to the H group, whereas hepatic crude lipid content and the expression of genes related to lipid synthesis were considerably lower in the HRS1.5 and HRS3.0 groups than in the H group. Additionally, hepatocyte vacuolation was alleviated in the HRS1.5 and HRS3.0 groups, and the number of liver lipid droplets was significantly decreased. Dietary supplementation with 1.5 % and 3.0 % RS downregulated the expression of pro-inflammatory factors while upregulating the expression of anti-inflammatory factors. Furthermore, analysis of gut microbiota composition revealed that RS supplementation increased the population of beneficial bacteria and short-chain fatty acid (SCFA) contents, decreased the abundance of pathogenic bacteria, and enhanced the diversity and richness of the intestinal flora. Non-targeted metabolomics analysis indicated that the levels of L-arginine and betaine were significantly higher in the HRS1.5 group, while levels of L-methionine and taurocholic acid were notably elevated in the HRS3.0 group. In conclusion, dietary supplementation with 1.5-3.0 % RS improved the balance of intestinal flora, promoted the growth of beneficial bacteria, adjusted the metabolites profile, and increased the SCFA levels. These results suggest that dietary supplementation with 1.5-3.0 % RS can restore the intestinal protective barrier, reduce hepatic lipid accumulation, and regulate lipid metabolism in largemouth bass.PMID:39988156 | DOI:10.1016/j.ijbiomac.2025.141356

Plant Sci. 2025 Feb 21:112439. doi: 10.1016/j.plantsci.2025.112439. Online ahead of print.ABSTRACTRoot exudates impact soil-plant-microbe interactions and play important roles in ecosystem functioning and plant growth. During early plant development the root rhizosphere may change drastically. For maize (Zea mays L.), one of the world's most important crop species, little is known about root exudation patterns during early plant development. We determined abundance and composition of root exudation among maize genotypes from five inbred lines across three early plant development stages (Emergence, V1-2, and V3-4). We characterized the exudates for non-purgeable organic carbon and performed non-targeted metabolomics with high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Across all genotypes, plant development stage had a significant influence on both abundance and composition of exudates. Exudation rates (mg C per cm2 root area d-1) were highest in the emergence stage and logarithmically decreased with plant development. In the emergence stage, the roots released predominantly sugars (most indicative: glucose and fructose) and the metabolite richness was generally higher than in later stages. Secondary compounds (e.g. phenolics, benzoxazinoids, or mucilage) increased significantly in later development stages. Differences in the composition of exudates between genotypes may be related to their respective development strategies, with genotypes accumulating more biomass releasing relatively more compounds related to root establishment (growth and rhizosphere development, e.g. mucilage, fatty and organic acids) and slower developing genotypes relatively more metabolites related to maintenance and defense (e.g. phenolics). Our results shed light onto the early dynamics of maize root exudation and rhizosphere establishment, over a phenotypical spectrum of genotypes.PMID:39988132 | DOI:10.1016/j.plantsci.2025.112439

Cancer Lett. 2025 Feb 21:217583. doi: 10.1016/j.canlet.2025.217583. Online ahead of print.ABSTRACTPancreatic cancer, characterized by its insidious onset, high invasiveness, resistance to chemotherapy, and a grim prognosis, with a five-year survival rate hovering below 10%. The identification of novel therapeutic targets addressing tumor progression is therefore critically important. While perineural invasion (PNI) is recognized as a pathological hallmark and key driver of pancreatic cancer progression, its role in metabolic reprogramming of malignant cells has not been fully elucidated. Using integrated metabolomics approaches, we found perineural invasion in pancreatic cancer significantly enhancing glycolytic flux of pancreatic cancer. Our data delineate a neuroendocrine-paracrine signaling axis in which neurturin secreted by neuronal cells binds to the GFRA2 receptor on pancreatic cancer cells, inducing RET kinase recruitment and subsequent heterodimer assembly. This receptor tyrosine kinase complex phosphorylates hexokinase 2 (HK2) at the evolutionarily conserved Ser122 residue, augmenting its hexokinase activity, ultimately driving aerobic glycolysis flux and fueling pancreatic cancer growth. In vivo experiments corroborate our findings, revealing that neurturin blockade effectively halts pancreatic cancer progression and synergizes with RET inhibitors. Our research underscores neurturin as a promising therapeutic target for the treatment of pancreatic cancer.PMID:39988080 | DOI:10.1016/j.canlet.2025.217583

Mol Metab. 2025 Feb 21:102115. doi: 10.1016/j.molmet.2025.102115. Online ahead of print.ABSTRACTRenalase (Rnls), annotated as an oxidase enzyme, is a GWAS gene associated with Type 1 diabetes (T1D) risk. We previously discovered that Rnls inhibition delays diabetes onset in mouse models of T1D in vivo, and protects pancreatic β cells against autoimmune killing, ER and oxidative stress in vitro. The molecular biochemistry and functions of Rnls are largely uncharted. Here we find that Rnls inhibition defends against loss of β cell mass and islet dysfunction in chronically stressed Akita mice in vivo. We used RNA sequencing, untargeted and targeted metabolomics and metabolic function experiments in a mouse β cell line and human stem cell-derived β cells and discovered a robust and conserved metabolic shift towards glycolysis to counter protein misfolding stress, in vitro. Our work illustrates metabolic functions for Rnls in mammalian cells and suggests an axis by which manipulating intrinsic properties of β cells can rewire metabolism to protect against diabetogenic stress.PMID:39988068 | DOI:10.1016/j.molmet.2025.102115

Sci Total Environ. 2025 Feb 21;968:178888. doi: 10.1016/j.scitotenv.2025.178888. Online ahead of print.ABSTRACTUrbanisation has been considered to promote exotic plant invasion. Ecophysiology predicts phenotypic variation and potential evolution following urbanisation and can be used to evaluate plant invasiveness. However, few studies have included the role of ecophysiological traits for such invasiveness in urban ecosystems. Traditional plant functional traits have been used but have their limitations. Novel approaches such as metabolomics may potentially be useful. The present study explored the invasiveness of the cosmopolitan noxious invasive plant Alternanthera philoxeroides in urban and periurban areas of a megacity city in China using both traditional leaf functional traits and novel leaf metabolome as indicators. We found that traditional leaf functional traits, including specific leaf area, nitrogen concentration, carbon:nitrogen ratio and construction costs, did not differ between urban and periurban A. philoxeroides populations. However, metabolomic profiling showed that the urban populations had an up-regulated expression of zeatin and purine, two cytokinins correlated with plant growth and a down-regulated expression of isoflavonoids, a defensive metabolite for herbivory. Leaf metabolome may, therefore, be sensitive in deciphering the facilitative effects of urbanisation on plant invasion. We also found that the urban populations of A. philoxeroides accumulated more beneficial microbes, which might enhance their invasiveness. Urbanisation likely promotes exotic plants invasion through generation of metabolites, which stimulates growth via modification of the soil microbiome. Our results indicate that leaf metabolome may be used for interpreting plant invasiveness and predicting plant invasion.PMID:39987825 | DOI:10.1016/j.scitotenv.2025.178888

J Hazard Mater. 2025 Feb 20;489:137699. doi: 10.1016/j.jhazmat.2025.137699. Online ahead of print.ABSTRACTHumans are exposed to complex per- and polyfluoroalkyl substances (PFAS) mixtures, yet their neurotoxicity and mechanisms remains unclear. This study exposed male mice to 17 PFAS mixtures at low levels (0.2-20 µg/L) for 49 days via drinking water. Perfluoropentanoic acid (PFPeA), perfluoroheptanoic acid (PFHpA), 6:2 fluorotelomer sulfonic acid (6:2 FTS), and perfluorooctane Sulfonate (PFOS) accumulated in brain tissues, with brain/plasma ratios of 2.03-5.87, 2.94-12.88, 1.90-3.19, and 0.62-0.93, respectively. Electroencephalogram (EEG) results showed significant alterations, including a reduction in beta spectral edge (21.47-13.85 Hz) and an increase in gamma spectral edge (57.64-79.07 Hz). Histopathological analysis revealed necrosis in the hippocampus, contributing to the observed anxiety-like behaviors and memory impairments in exposed mice. Plasma metabolomics highlighted disrupted osmoprotectants, impaired glutamatergic synapse function, and tryptophan metabolism. Brain metabolomics demonstrated suppression of purine metabolism and activation of arachidonic acid metabolism, suggesting involvement in neurotoxic effects. Transcriptomic profiling further identified dysregulation in neuroactive ligand-receptor interactions, cholinergic and GABAergic synapses, and calcium signaling pathways, with oxytocin signaling highlighted as a critical mechanism. This study, for the first time, links PFAS mixture to neurotoxicity via neurotransmitter-related pathways, underscoring the need for public health policies and preventive strategies to mitigate PFAS exposure risks.PMID:39987740 | DOI:10.1016/j.jhazmat.2025.137699

Talanta. 2025 Feb 8;289:127712. doi: 10.1016/j.talanta.2025.127712. Online ahead of print.ABSTRACTThe biological significance of oxidized arachidonoyl-containing glycerophosphocholines, exemplified by the oxidation products of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (oxPAPC), in pathological processes is well-established. However, despite their widespread use in redox lipidomics research, the precise chemical composition of the heterogeneous mixtures of oxPAPC generated in vitro -including the high prevalence of isomers and the oxidation mechanisms involved- remain inadequately understood. To address these knowledge gaps, we developed a multidimensional in-house database from a commercial oxPAPC preparation -employing Liquid Chromatography coupled to Quadrupole Time-of-Flight Mass Spectrometry (LC-QTOF-MS) and Ion Mobility Spectrometry-Mass Spectrometry (IMS-MS). This database includes lipid names, retention times, accurate mass values (m/z), adduct profiles, MS/MS information, as well as collision cross-section (CCS) values. Our investigation elucidated 34 compounds belonging to distinct subsets of oxPAPC products, encompassing truncated, full-length, and cyclized variants. The integration of IMS-MS crucially facilitated: (i) structural insights among regioisomers, exemplified by the 5,6-PEIPC and 11,12-PEIPC epoxy-isoprostane derivatives, (ii) novel Collision Cross Section (CCS) values, and (iii) cleaner MS/MS spectra for elucidating the fragmentation mechanisms involved to yield specific fragment ions. These diagnostic ions were employed to successfully characterize full-length isomers present in human plasma samples from patients with mucormycosis. This comprehensive oxPAPC characterization not only advances the understanding of lipid peroxidation products but also enhances analytical capabilities for in vitro-generated oxidized mixtures. The implementation of this robust database, containing multiple orthogonal (i.e., independent) pieces of information, will serve as a comprehensive resource for the field.PMID:39987613 | DOI:10.1016/j.talanta.2025.127712

Phytomedicine. 2025 Feb 16;139:156531. doi: 10.1016/j.phymed.2025.156531. Online ahead of print.ABSTRACTBACKGROUD: Rheumatoid arthritis (RA) is a prevalent chronic autoimmune disease characterized by symmetric polyarthritis, resulting in pain and swelling in the synovial joints. Flemingia philippinensis, a traditional Chinese medicine, has been shown to be an effective treatment approach for anti-rheumatoid arthritis (RA), which still needs further research in its active ingredient and regulatory mechanisms.PURPOSE: This study aimed at investigate the pharmacodynamic basis and intricate mechanism of action of Flemingia philippinensis (FPTF) in the treatment of RA based on integrated omics technologies.METHODS: UPLC-Q-Orbitrap HRMS was first established to identify the active components of FPTF in blood and network pharmacology was then used to predict the key therapeutic targets and corresponding pathways of FPTF in treatment of RA. To substantiate the pharmacodynamic effects, a collagen-induced arthritis (CIA) animal model was employed to observe the anti-RA effects of FPTF through a series of indicators, including rat body weight, arthritis scoring, paw swelling, histopathological analysis of synovial tissue, and serum inflammatory factors. Subsequently, the potential mechanisms underlying the anti-RA efficacy of FPTF was elucidated by integrating metabolomics analysis with 16S rRNA gene sequencing. Specifically, the RT-qPCR experiment was further conducted to validate the pathways predicted by serum pharmacochemistry, network pharmacology, metabolomics and 16S rRNA gene sequencing.RESULTS: A total of 10 compounds derived from FPTF were identified by serum sample analysis. Utilizing network pharmacology, we identified 117 common targets for FPTF in the treatment of RA. Notably, KEGG analysis highlighted the PI3K/AKT signaling pathway and the IL17 signaling pathway as key pathways associated with the anti-RA effects of FPTF. Pharmacodynamic studies showed that FPTF can significantly alleviate CIA-induced arthritis. Compared with the CIA model group, FPTF treatment significantly improved the expression of mRNA in the PI3K/AKT and IL-17 signaling pathways. Further investigation unveiled a total of 28 differential metabolites in serum samples, among which 21 metabolites were observed to be reversed following FPTF administration. Metabolomic profiling revealed pronounced perturbations in amino acid metabolism, fatty acid metabolism, and glycerophospholipid metabolism pathways in CIA rats, which were partially rectified by FPTF treatment. Additionally, 16S rRNA gene sequencing analysis indicated that FPTF could restore the gut microbiota balance disrupted by RA. RT-qPCR further confirmed that FPTF can modulate key enzymes in metabolic pathway analysis and gut microbiota metabolic pathways.CONCLUSION: This study pioneeringly elucidates the potential pharmacodynamic material basis of FPTF for treatment of RA, detailing the regulated metabolic pathways and key gut microbiota genera involved. The findings provide a comprehensive understanding of mechanisms underlying the effects of FPTF in RA treatment.PMID:39987603 | DOI:10.1016/j.phymed.2025.156531

Phytomedicine. 2025 Feb 14;139:156509. doi: 10.1016/j.phymed.2025.156509. Online ahead of print.ABSTRACTOBJECTIVE: To explore the taste-related quality markers of Qingbanxia, the alum-processed Pinellia ternata tuber.METHODS: Eighteen samples of Banxia and Qingbanxia were analyzed by the Ultra-High Performance Liquid Chromatography coupled with Q-Exactive Orbitrap Mass Spectrometry. Data of all samples were pre-processed by Compound Discoverer 3.3 Software. The discrimination was analyzed by Principal Component Aanalysis, and Orthogonal Partial Least-square Discriminant Analysis. The chemical markers were identified by MS/MS fragments based on the fragment rules. The electronic tongue was utilized to determine the taste traits of Banxia and Qingbanxia. Furthermore, the taste-related material basis was discovered according to correlation analysis and molecular docking.RESULTS: Sixteen potential chemical markers of Banxia and Qingbanxia were identified. Lauryldiethanolamine is a unique bitter component. The taste spectrum of bitterness, sourness and umami changes significantly during the processing of Banxia, with sourness increasing and bitterness and umami decreasing.CONCLUSION: A new approach to explore the taste-related quality markers in alum-processed Banxia was established for the first time based on the Orbitrap MS technology and electronic tongue technology. The bitterness chemical markers were identified for the first time. The mechanism of the sourness of Qingbanxia was clarified. The identification of taste-related quality markers and the generation of comprehensive taste profiles offer an objective and reproducible method for assessing processing efficacy, overcoming the limitations of traditional subjective taste tests. These findings have significant implications for the quality control of Banxia and other traditional Chinese medicine.PMID:39987601 | DOI:10.1016/j.phymed.2025.156509

Biol Reprod. 2025 Feb 23:ioaf038. doi: 10.1093/biolre/ioaf038. Online ahead of print.ABSTRACTThis study investigated differences in uterine and serum metabolome associated with clinical cure failure of metritis in dairy cows. Metritis was diagnosed in lactating Holstein cows from two Florida dairies and defined by the presence of fetid, watery, reddish-brown vaginal discharge from 4 to 12 days postpartum (dpp). Cows with metritis (n = 24) were paired with cows without metritis of similar parity and dpp (n = 24). On the day of metritis diagnosis (day 0), all cows with metritis received antimicrobial therapy. The continued presence of the fetid, watery, reddish-brown discharge on day 5 (n = 16) was defined as clinical cure failure, whereas clinical cure was defined by its absence (n = 8). Metabolome analyses of uterine lavage (days 0 and 5) and serum samples (day 0) were conducted using untargeted gas chromatography time-of-flight mass spectrometry. Normalized data were analyzed using partial least squares-discriminant analysis and ANOVA, adjusting P-values for multiple comparisons. Differences in the uterine metabolome on day 0 associated with clinical cure failure were linked to carbohydrate, amino acid, and lipid metabolism. Greater concentrations of arachidonic acid, ribose, and glutaric acid were associated with clinical cure failure, suggesting a greater degree of tissue lesion and inflammation. No differences in the serum metabolome were associated with cure failure. No differences in uterine metabolome were associated with clinical cure failure on day 5. The findings suggest that clinical cure failure is associated with a greater uterine inflammatory process that did not persist until cure assessment day.PMID:39987553 | DOI:10.1093/biolre/ioaf038

J Biochem Mol Toxicol. 2025 Mar;39(3):e70165. doi: 10.1002/jbt.70165.ABSTRACTThis study aimed to investigate the impact of in vitro low-dose arachidonic acid (AA) addition on enhancing sperm motility in obese infertile men with asthenozoospermia. Semen samples were collected from 115 infertile men, categorized into two BMI groups: 18.5-23.9 kg/m2 and ≥ 28 kg/m2, with all subjects demonstrating a sperm concentration of ≥ 15 × 106/mL. These were further divided into four cohorts based on the percentage of sperm progressive motility (PR): control-normal, control-asthenozoospermia, obese-normal, and obese-asthenozoospermia. Normal PR was classified as ≥ 32%, while asthenozoospermia was characterized by PR < 32%. Metabolomic analysis was employed to quantify seminal plasma metabolites, with differential metabolites identified through statistical evaluation. Additionally, semen samples from 10 infertile men-5 with a body mass index (BMI) of 18.5-23.9 kg/m2 and 5 with a BMI of ≥ 28 kg/m2-underwent further scrutiny. Post-initial semen analysis, 1 mL of semen stock was extracted, treated with 100 pg of AA, incubated at 37°C for 1 h, and reanalyzed to determine the impact on sperm motility. Additionally, 16 Sprague Dawley (SD) rats were split into two groups: control and obese. The control group received a standard diet, while the obese group was subjected to a 45% high-fat diet. After 3 months, the rats were euthanized via cervical dislocation, and their prostate and seminal vesicles were collected for metabolite analysis. A comprehensive analysis of 4635 metabolites in seminal plasma revealed that bile acid secretion emerged as the most significant pathway within the organic systems category, accounting for 0.6% of the total metabolites. Meanwhile, metabolic pathways overwhelmingly dominated the metabolism category, with AA metabolism contributing 4.62%. Notably, 29 metabolites were associated with bile acid secretion, yet no significant differences were observed between the PR ≥ 32% and < 32% groups. In contrast, 214 metabolites were linked to AA metabolism, exhibiting a predominantly downregulated trend, with no upregulated metabolites identified. Within the seminal plasma AA metabolic network, indicators showed a positive association with the induced acrosome reaction, seminal plasma Ca2+ levels, PR, and the proportion of grade A sperm (rapid forward motion, speed ≥ 25 μm/s). Additionally, secretory phospholipase A2 (sPLA2), AA, and cyclooxygenase-1 (COX1) levels demonstrated a negative correlation with anthropometric measurement parameters in the Control-SP group, though this correlation did not reach statistical significance, while a positive correlation was evident in the Obesity-SP group. The concentrations of sPLA2, AA, and COX1 within the AA metabolic network exhibited the following trend: Control-SP-N > Obesity-SP-N > Control-SP-A > Obesity-SP-A. In vitro addition of 100 pg AA significantly enhanced the proportion of grade B sperm (slow-moving, speed < 25 μm/s) while reducing grade C sperm (non-forward-moving) in individuals with a BMI of 18.5-23.9 kg/m2 (p < 0.05). In contrast, for those with a BMI ≥ 28 kg/m2, a marked increase in grade A and grade B sperm and a corresponding reduction in grade C sperm was noted (p < 0.05). Human seminal plasma levels of sPLA2, AA, and COX1 were significantly elevated in the Control-SP group compared to the Obesity-SP group (p < 0.05). However, sPLA2, AA, and COX1 levels in the prostate and seminal vesicle of SD rats did not differ significantly between the Control and Obesity groups (p > 0.05). Distinct metabolic profiles in seminal plasma of infertile men, stratified by BMI, exhibit significant impacts on sperm quality. Low-dose AA, under physiological conditions, maintains sperm integrity and augments fertilization potential. In vitro administration of low-dose AA demonstrates superior effectiveness in enhancing sperm parameters, particularly in obese individuals with asthenozoospermia.PMID:39987515 | DOI:10.1002/jbt.70165

J Basic Microbiol. 2025 Feb 23:e70007. doi: 10.1002/jobm.70007. Online ahead of print.ABSTRACTUnderstanding bacterial genetics and metabolism is vital for developing biopesticides. This study investigates Bacillus subtilis NBAIR-BSWG1, a strain well known for its antagonistic potential. Crude lipopeptides extracted from the strain were evaluated for in vitro activity, showing complete inhibition of Rhizoctonia solani at a concentration of 50 μL/mL potato dextrose agar. To delve deeper into its antagonistic mechanisms, we conducted whole-genome sequencing of NBAIR-BSWG1 using Illumina NextSeq 500. Subsequent analysis with the BlastX diamond tool revealed 19 key biosurfactant genes, including surfactin (srfAA, srfAC, srfAD, srfP), fengycin (ppsE, ppsD, ppsC, ppsB), and putisolvin (dnaK), which were further confirmed by PCR using specific primers. Meanwhile, antiSMASH analysis revealed gene clusters with 100% similarity to those responsible for the synthesis of fengycin, bacilaene, bacillibactin, subtilosin A, and bacilysin, as well as clusters with 82% similarity to surfactin synthesis genes. Additionally, liquid chromatography-mass spectrometry was performed to analyze the cell-free extract produced by NBAIR-BSWG1, revealing the presence of various cyclic lipopeptides, including multiple peaks corresponding to surfactin, iturin, and several novel lipopeptide compounds. This study highlights B. subtilis NBAIR-BSWG1 cyclic lipopeptides as a key to broad-spectrum bio-control and establishes the strain as highly potent.PMID:39987492 | DOI:10.1002/jobm.70007

Metabolomics. 2025 Feb 22;21(2):32. doi: 10.1007/s11306-025-02227-1.ABSTRACTBACKGROUND: Despite the insights that metabolite analysis can provide into the onset, development, and progression of diseases-thus offering new concepts and methodologies for prevention, diagnosis, and treatment-traditional wet lab experiments are often time-consuming and labor-intensive. Consequently, this study aimed to develop a machine learning model named COM-RAN, which is based on a knowledge graph and random forest algorithm, to identify potential associations between metabolites and diseases.METHODS: Firstly, we integrated the known associations between diseases and metabolites. Secondly, we provided a synthesis of the extant data regarding diseases and metabolites, accompanied by supplementary information pertinent to these entities. Thirdly, knowledge graph-based embedded features were used to characterize disease-metabolite associations. Finally, a random forest algorithm was employed to construct a model for identifying potential disease-metabolite associations.RESULTS: The experimental results demonstrated that the proposed model achieved an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.968 in 5-fold cross-validations, while the Area Under the Precision-Recall Curve (AUPR) was 0.901, outperforming the vast majority of existing prediction methods. The case studies corroborated the majority of the novel associations identified by COM-RAN, thereby further demonstrating the reliability of the current method in predicting the potential relationship between metabolites and diseases.CONCLUSION: The COM-RAN model demonstrated promise in predicting associations between diseases and metabolites, suggesting that integrating knowledge graphs with machine learning methodologies can significantly improve the accuracy and reliability of predictions related to disease-associated metabolites.PMID:39987424 | DOI:10.1007/s11306-025-02227-1

Metabolomics. 2025 Feb 22;21(2):33. doi: 10.1007/s11306-025-02231-5.ABSTRACTINTRODUCTION: Extracranial and intracranial tumors are a diverse group of malignant and benign neoplasms, influenced by multiple factors. Given the complex nature of these tumors and usually late or accidental diagnosis, minimally invasive, rapid, early, and accurate diagnostic methods are urgently required. Metabolomics offers promising insights into central nervous system tumors by uncovering distinctive metabolic changes linked to tumor development.OBJECTIVES: This study aimed to elucidate the role of altered metabolites and the associated biological pathways implicated in the development of gliomas and meningiomas.METHODS: The study was conducted on 95 patients with gliomas, 68 patients with meningiomas, and 71 subjects as a control group. The metabolic profiling of gliomas and meningiomas achieved by integrating untargeted metabolomic analysis based on GC-MS and targeted analysis performed using LC-MS/MS represents the first comprehensive study. Three comparisons (gliomas or meningiomas vs. controls as well as gliomas vs. meningiomas) were performed to reveal statistically significant metabolites.RESULTS: Comparative analysis revealed 97, 56, and 27 significant metabolites for gliomas vs. controls, meningiomas vs. controls and gliomas vs. meningiomas comparison, respectively. Moreover, among above mentioned comparisons unique metabolites involved in arginine biosynthesis and metabolism, the Krebs cycle, and lysine degradation pathways were found. Notably, 2-aminoadipic acid has been identified as a metabolite that can be used in distinguishing two tumor types.CONCLUSIONS: Our results provide a deeper understanding of the metabolic changes associated with brain tumor development and progression.PMID:39987409 | DOI:10.1007/s11306-025-02231-5

Arch Dermatol Res. 2025 Feb 22;317(1):460. doi: 10.1007/s00403-025-03942-4.ABSTRACTThis study investigates the causal relationships between plasma metabolites, immune cell phenotypes, and diabetic foot ulcer (DFU). A Mendelian randomization (MR) study was conducted, which included 731 immune cell phenotypes, 1400 metabolites, and DFU. The primary analytical approach was the inverse variance-weighted method. Sensitivity analyses were performed to assess heterogeneity and pleiotropy, and MR analyses in the reverse direction were conducted to examine the possibility of reverse causation. In addition, a mediation analysis was performed to reveal how metabolites mediate the impact of immune cells on DFU. Through MR, reverse MR and sensitivity analysis, the casualty was found in 17 immune cell phenotypes and 18 metabolites. A total of 15 mediating relationships were identified through mediation analysis, including 9 metabolites and 10 immune cell phenotypes. Among them, the highest mediation proportion was citrulline levels mediating CD24+ CD27+ AC (absolute count, B cell panel) to DFU, with a proportion of 11.60%. In conclusion, the study identified causal relationships between 10 immune cell phenotypes mediated by 9 metabolites. These discoveries offered fresh perspectives on the processes behind DFU and laid the groundwork for subsequent studies to create specific treatments for DFU.PMID:39987406 | DOI:10.1007/s00403-025-03942-4

Metabolomics. 2025 Feb 22;21(2):34. doi: 10.1007/s11306-025-02222-6.ABSTRACTMorels are edible fungi growing naturally in the wild and cultivated for food and medicines worldwide. They have been collected and consumed by people since ancient times. In the present study, fruiting bodies of Morchella elata were collected from the field during the years 2020-22 through consecutive field visits. Identification was carried out through a morpho-anatomical and phylogenetic study that confirmed the collected morel species as Morchella elata. The metabolic analysis was conducted using Ultra High-Performance Liquid Chromatography/Mass Spectrometry (UHPLC/MS) and FTICR/orbitrap techniques. The study revealed the presence of 159 organic compounds and 435 peptide sequences in the ascocarp. Different bioactive and significant compounds have been identified in the fruiting bodies of M. elata. This mushroom is highly nutritious, and the presence of these bioactive compounds contributes to its health benefits, making it a potential functional food in nutraceuticals. From the current study, it is concluded that M. elata is an edible, highly nutritive fungus and contains many bioactive contents. It could be used in the screening of bioactive substances useful in the preparation of anticancer drugs.PMID:39987365 | DOI:10.1007/s11306-025-02222-6

Arch Dermatol Res. 2025 Feb 22;317(1):463. doi: 10.1007/s00403-025-03978-6.ABSTRACTPsoriasis is a prevalent inflammatory dermatosis with possible systemic involvement. Metabolomics defines as an extensive study of all low molecular weight metabolites in human body which has recently led to better understanding of the pathogenesis of different disease. To evaluate the targeted lipidomics in sera of patients versus healthy controls. The study included 64 patients with psoriasis and 64 age- and sex-matched healthy controls. All the participants underwent a targeted lipidomics on their sera using Gas Chromatography with flame-ionization detection (GC-FID). The clinical importance of serum level of lipids was also dealt with. Serum level of all tested fatty acids (except for METHYL VACCENATE) in patients was higher than healthy controls, though this difference was significant only for METHYL PALMITATE, METHYL OLEATE and METHYL LINOLEATE (P values: 0.002, 0.001 and 0.001 respectively). Based on our results, the serum levels of METHYL OLEATE, METHYL LINOLEATE, METHYL PALMITATE and METHYL STEARATE could significantly be used for predicting the disease severity (P values: 0.009, < 0.005, 0.02 and 0.001, respectively). METHYL MYRISTOLEATE, METHYL 11-14-17-EICOSATRIENOATE and METHYL LINOLEATE were the fatty acids which their serum levels were significantly predictive of duration of disease (P values: 0.018, < 0.005 and 0.009, respectively). Our findings suggest that circulating specific lipids have different serum levels in psoriasis patients in comparison with healthy controls. We suggest the serum METHYL LINOLEATE as a potential biomarker to evaluate psoriasis severity and prognosis. However, comprehensive, long-term studies are essential for validating its prognostic value.PMID:39987344 | DOI:10.1007/s00403-025-03978-6

Biotechnol Biofuels Bioprod. 2025 Feb 22;18(1):22. doi: 10.1186/s13068-025-02619-4.ABSTRACTBACKGROUND: Lignocellulose is the most abundant renewable bioresource on earth, and its biodegradation and utilization would contribute to the sustainable development of the global environment. Ruminiclostridium papyrosolvens, an anaerobic, mesophilic, and cellulolytic bacterium, produces an enzymatic complex known as the cellulosome. As one of the most highly evolved species among Ruminiclostridium-type species, R. papyrosolvens is particularly relevant for understanding how cellulolytic clostridia modulate their biomass degradation mechanisms in response to diverse carbon sources.RESULTS: Our study investigates the transcriptional responses of Ruminiclostridium papyrosolvens to different carbon sources to understand its lignocellulose utilization. Using RNA-seq, we analyzed gene expression under glucose, cellobiose, xylan, cellulose, and corn stover, identifying distinct metabolic preferences and regulatory responses. We found significant gene expression changes under corn stover compared to other carbon sources, with enrichment in ABC transporters and cell growth pathways. CAZyme gene expression was regulated by TCSs, affecting sugar transporter systems. Metabolic profiling showed R. papyrosolvens produced more complex metabolites during corn stover fermentation, revealing its adaptability to various carbon sources and implications for metabolic engineering.CONCLUSION: This study not only uncovers the intricate response mechanisms of R. papyrosolvens to lignocellulose and its hydrolysates, but it also outlines the strategy for using R. papyrosolvens as a cellulolytic chassis in genetic engineering.PMID:39987219 | DOI:10.1186/s13068-025-02619-4

Microb Cell Fact. 2025 Feb 22;24(1):46. doi: 10.1186/s12934-025-02673-5.ABSTRACTBACKGROUND: Leuconostoc mesenteroides (L. mesenteroides) has known as an electrogenic probiotic bacterium. However, metabolites related to electro-fermentation in ferments of L. mesenteroides are not unveiled.RESULT: Electrogenic L. mesenteroides fermentatively metabolized bovine milk to dense ferments with homogeneous particle-size distribution. A non-targeted metabolomics approach was performed on non-fermented and L. mesenteroides-fermented milk. A total of 917 metabolites were identified and quantified by ultra-high performance liquid chromatography (UHPLC)-tandem mass spectrometry (MS-MS). Thirteen prokaryotic metabolic pathways associated with differentially expressed metabolites (DEMs) were revealed through Koto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Anthranilic acid (AA) and 3-hydroxyanthranilin acid (3-HAA), potentially as electron donors, and quinolinic acid, an electron donor precursor, in the tryptophan kynurenine pathway were significantly increased in the fermented milk. Histidine, arginine, and riboflavin involved in bacterial survival or bioelectricity production were elevated after fermentation.CONCLUSIONS: Results indicate that electrogenic L. mesenteroides can mediate electro-fermentation to transform milk to a new nutritional source which is rich in electron donors reportedly acting as antioxidants.PMID:39987182 | DOI:10.1186/s12934-025-02673-5