PubMed

Mol Nutr Food Res. 2025 Feb 23:e202400539. doi: 10.1002/mnfr.202400539. Online ahead of print.ABSTRACTHoney is known to promote alcohol metabolism effectively. However, the effects of its individual chemical components system on alcohol metabolism and their mechanisms of action have not yet been fully elucidated. We constructed polyphenols and ascorbic acid systems (PAAS) of six different floral kinds of honey by exogenous substances, to investigate their effects on alcohol metabolism in the liver. PAAS consists of 22 kinds of polyphenols (including arbutin and caffeic acid) and ascorbic acid. The results demonstrated that PAAS improved the activity of alcohol dehydrogenase (ADH) and the expression of adh1, but had no significant effect on acetaldehyde dehydrogenase (ALDH) and expression of adh2, which caused a decrease in blood ethanol concentration but no difference in acetaldehyde concentration. Correlation analysis illustrated that arbutin and trans-4-hydroxycinnamic acid in PAAS were important potential substances for promoting alcohol metabolism. In addition, PAAS could also reduce the deleterious effects of alcohol by modulating unsaturated fatty acid biosynthesis, purine metabolism, and other metabolic pathways in the liver. These findings revealed the mechanisms by which PAAS promoted hepatic alcohol metabolism as well as protected the liver and provided a theoretical basis for exploring the mechanisms in honey synergistically promote alcohol metabolism.PMID:39988877 | DOI:10.1002/mnfr.202400539

Environ Sci Technol. 2025 Feb 23. doi: 10.1021/acs.est.4c11413. Online ahead of print.ABSTRACTNanoenabled agriculture technology exhibits potential in reducing arsenic uptake in rice; however, a systematic understanding of the rice-soil-microorganism process of nanomaterials (NMs) is lacking. Soil amendment of metalloid NMs, including SiO2, hydroxyapatite, S0, and Se0 at 10-100 (0.1-5.0 for Se NMs) mg/kg, increased rice biomass by 76.1-135.8% in arsenic-contaminated soil (17.0 mg/kg) and decreased arsenic accumulation in plant tissues by 9.3-78.2%. The beneficial effects were nanoscale-specific and NMs type- and concentration-dependent; 5 mg/kg Se NMs showed the greatest growth promotion and decrease in As accumulation. Mechanistically, (1) Se NMs optimized the soil bacterial community structure, enhancing the abundance of arsM by 104.2% and subsequently increasing arsenic methylation by 276.1% in rhizosphere compared to arsenic-alone treatments; (2) metabolomic analyses showed that Se NMs upregulated the biosynthesis pathway of abscisic acid, jasmonic acid, and glutathione, with subsequent downregulation of the arsenic transporter-related gene expression in roots by 42.2-73.4%, decreasing the formation of iron plaque by 87.6%, and enhancing the arsenic detoxification by 50.0%. Additionally, amendment of metalloid NMs significantly enhanced arsenic-treated rice yield by 66.9-91.4% and grain nutritional quality. This study demonstrates the excellent potential of metalloid NMs for an effective and sustainable strategy to increase food quality and safety.PMID:39988829 | DOI:10.1021/acs.est.4c11413

ACS Appl Mater Interfaces. 2025 Feb 23. doi: 10.1021/acsami.4c21532. Online ahead of print.ABSTRACTSkin trauma often results from pain, swelling, and scarring and can significantly interfere with daily activities. Extracts from the American cockroach, a rapidly reproducing insect, have been recognized for therapeutic properties in wound management. Traditional extraction methods use solvents such as ethanol to obtain the active compounds, but these methods may compromise the intrinsic biological properties of American cockroach extracts. In this study, we investigated the use of nanovesicles isolated from fresh American cockroaches in skin wound treatment and focused on their biological characteristics and therapeutic efficacy. Fresh and dried American cockroach nanovesicles (F-ACNVs and D-ACNVs, respectively) were procured via ultrahigh-speed centrifugation. We found that F-ACNVs exhibited superior cell proliferation-promoting activity. By employing metabolomics, proteomics, and long noncoding RNA (lncRNA) omics, we identified a rich repertoire of metabolites, proteins, and lncRNAs within F-ACNVs. In vitro and in vivo experiments demonstrated that F-ACNVs significantly enhanced the proliferation and migration of human umbilical vein endothelial cells (HUVECs) and human skin keratinocytes (HACATs) as well as the repair of skin mechanical trauma. These effects may be mediated through the activation of angiogenic signaling pathways. Our research introduces a novel therapeutic strategy for treating skin trauma and offers insight into the medicinal potential of insects such as the American cockroach while emphasizing the importance of preserving the intrinsic biological properties of insects for optimal therapeutic outcomes.PMID:39988799 | DOI:10.1021/acsami.4c21532

Clin Exp Dent Res. 2025 Feb;11(1):e70103. doi: 10.1002/cre2.70103.ABSTRACTOBJECTIVE: Cell secretomes represent a promising strategy for periodontal and bone regeneration. The objective of this study was to characterize the secretome of human gingival fibroblasts (GF) from periodontally diseased tissues (GF-perio) using proteomics.MATERIALS AND METHODS: Conditioned media of GF-perio from periodontitis patients (n = 6, 48-h serum-free culture) were subjected to liquid chromatography with tandem mass spectrometry. Global profiles, differentially expressed proteins (DEPs), and functional/gene-set enrichment (FEA) were analyzed using bioinformatics. Selected bone regeneration-related proteins were additionally measured using a multiplex immunoassay. Conditioned media of GF from periodontally healthy subjects were used as a reference.RESULTS: Overall, 1833 proteins were detected in GF-perio secretomes, including several growth factors, cytokines, chemokines, and extracellular matrix proteins important for wound healing and regeneration. Key bone-related cytokines (FGF2, MCP1, GPNMB, MMP2, IL6, IL8) were confirmed by an immunoassay. Compared to the reference group, 127 exclusive proteins and 73 DEPs (p < 0.05) were identified in the GF-perio group. FEA revealed significant enrichment of "exosome" and "cytoplasm" related cellular components in GF-perio secretomes.CONCLUSION: The secretome of GF from periodontally diseased tissues may hold therapeutic potential, with several proteins important for wound healing and regeneration, especially those related to exosome functions.PMID:39988729 | DOI:10.1002/cre2.70103

Eur J Hum Genet. 2025 Feb 23. doi: 10.1038/s41431-025-01815-y. Online ahead of print.ABSTRACTChromatin remodeling is an important system controlling gene expression. CHD3, which is a causative gene of Snijders Blok-Campeau syndrome (SNIBCPS), is a member of the chromodomain helicase DNA-binding (CHD) family related to chromatin remodeling. SNIBCPS is characterized by developmental delay (DD), intellectual disability (ID), macrocephaly, and facial features including a prominent forehead and hypertelorism. Hypersociability/overfriendliness is a notable behavioral feature in patients. Here, we describe five SNIBCPS patients with CHD3 variants from four families, including a sibling pair caused by parental gonosomal mosaicism. We observed two distinct phenotypes in our patients in accordance with previous observations. Phenotype 1: macrocephaly, hypertelorism, overgrowth, DD, and ID; and Phenotype 2: microcephaly, growth retardation, DD, and ID. Phenotype 1 was consistent with the typical SNIBCPS phenotype, while Phenotype 2 was distinct. To understand further the features of the patients with SNIBCPS, we generated chd3-knockout (KO) zebrafish using CRISPR-Cas9 genome editing. No morphological changes were observed in chd3-KO zebrafish. However, behavioral tests showed that chd3-KO zebrafish had strong and sustained interest in others, and were less aggressive toward others, suggesting a recapitulation of the hypersociability/overfriendliness phenotype in patients with SNIBCPS. Metabolomic analysis using whole brains showed changes in metabolites processed by specific mitochondrial enzymes in chd3-KO zebrafish. The administration of metformin, which reportedly ameliorates mitochondrial dysfunction and behavioral abnormalities, attenuated the abnormal behavior of chd3-KO zebrafish. Our study helps delineate the phenotypes of patients with SNIBCPS, provides insights into a characteristic behavior of the disease, and suggests a potential treatment to improve the behavioral symptoms of patients.PMID:39988727 | DOI:10.1038/s41431-025-01815-y

Transl Psychiatry. 2025 Feb 23;15(1):65. doi: 10.1038/s41398-025-03274-x.ABSTRACTAcylcarnitines (ACs) are involved in bioenergetics processes that may play a role in the pathophysiology of depression. Previous genomic evidence identified four ACs potentially linked to depression risk. We carried forward these ACs and tested the association of their circulating levels with Major Depressive Disorder (MDD) diagnosis, overall depression severity and specific symptom profiles. The sample from the Netherlands Study of Depression and Anxiety included participants with current (n = 1035) or remitted (n = 739) MDD and healthy controls (n = 800). Plasma levels of four ACs (short-chain: acetylcarnitine C2 and propionylcarnitine C3; medium-chain: octanoylcarnitine C8 and decanoylcarnitine C10) were measured. Overall depression severity as well as atypical/energy-related (AES), anhedonic and melancholic symptom profiles were derived from the Inventory of Depressive Symptomatology. As compared to healthy controls, subjects with current or remitted MDD presented similarly lower mean C2 levels (Cohen's d = 0.2, p ≤ 1e-4). Higher overall depression severity was significantly associated with higher C3 levels (ß = 0.06, SE = 0.02, p = 1.21e-3). No associations were found for C8 and C10. Focusing on symptom profiles, only higher AES scores were linked to lower C2 (ß = -0.05, SE = 0.02, p = 1.85e-2) and higher C3 (ß = 0.08, SE = 0.02, p = 3.41e-5) levels. Results were confirmed in analyses pooling data with an additional internal replication sample from the same subjects measured at 6-year follow-up (totaling 4141 observations). Small alterations in levels of short-chain acylcarnitine levels were related to the presence and severity of depression, especially for symptoms reflecting altered energy homeostasis. Cellular metabolic dysfunctions may represent a key pathway in depression pathophysiology potentially accessible through AC metabolism.PMID:39988721 | DOI:10.1038/s41398-025-03274-x

Phytochem Anal. 2025 Feb 23. doi: 10.1002/pca.3518. Online ahead of print.ABSTRACTINTRODUCTION: Blood stasis syndrome (BSS) is one of the common syndromes in traditional Chinese medicine. The Chinese medicine compound composed of "Danggui-Guizhi (DG-GZ)"as the core has the effect of reducing blood stasis and promoting blood circulation. However, the difference of efficacy of DG-GZ traditional decoction and dispensing granules in reducing blood stasis are still unclear.OBJECTIVE: Investigation of the difference of decoction and dispensing granules of Danggui (DG) and Guizhi (GZ) in blood stasis syndrome (BSS) in an animal study (Six groups, n = 6).METHODOLOGY: All rats were randomly divided into six groups: control, model, Danggui-Guizhi dispensed granules ( DGK-GZK), Danggui-Guizhi decoction (DG-GZ), Danggui granules-Guizhi decoction (DGK-GZ), and Danggui decoction -Guizhi granules (DG-GZK) groups (n = 6). The blood stasis model was constructed by exposing rats to ice-cold water. Whole blood viscosity (WBV) was used to compare the effects of DG-GZ (4:3 w/w) decoction and dispensing granules in improving BSS. Metabolomics analysis of urine and 16S rRNA gene sequencing were used to investigate metabolic analysis and gut microbiota changes in rats with BSS.RESULTS: The results of WBV showed that DG-GZ and its granules exhibited efficacy against blood stasis, and the effect of DGK-GZK in relieving blood stasis was greater than that of other administration groups. Urine metabolomics demonstrated that DGK-GZK could reverse the abnormal levels of butyrate, citrate, taurine, creatinine, glucose, and other metabolites in BSS rats. DGK-GZK could promote the enrichment of the g__Prevotellaceae_NK3B31_group, g__Ligilactobacillus, and g__Roseburia.CONCLUSIONS: The effect of DGK-GZK intervention in BSS was stronger than that of other compound groups. This study also provides basic experimental data for exploring the difference in efficacy between traditional decoction and dispensing granules.PMID:39988642 | DOI:10.1002/pca.3518

Commun Biol. 2025 Feb 23;8(1):294. doi: 10.1038/s42003-025-07638-3.NO ABSTRACTPMID:39988621 | DOI:10.1038/s42003-025-07638-3

Vascul Pharmacol. 2025 Feb 21:107474. doi: 10.1016/j.vph.2025.107474. Online ahead of print.ABSTRACTGlycosylation is a post-translational modification in which complex, branched carbohydrates (glycans) are covalently attached to proteins or lipids. Asparagine-link protein (N-) glycosylation is among the most common types of glycosylation. This process is essential for many biological and cellular functions, and impaired N-glycosylation has been widely implicated in inflammation and cardiovascular diseases. Different technical approaches have been used to increase the coverage of the N-glycome, revealing a high level of complexity of glycans, regarding their structure and attachment site on a protein. In this context, new insights from genomic studies have revealed a genetic regulation of glycosylation, linking genetic variants to total plasma N-glycosylation and N-glycosylation of immunoglobulin G (IgG). In addition, RNAseq approaches have revealed a degree of transcriptional regulation for the glycoenzymes involved in glycan structure. However, our understanding of the association between cardiovascular risk and glycosylation, determined by a complex overlay of genetic and environmental factors, remains limited. Mostly, plasma N-glycosylation profiling in different human cohorts or experimental investigations of specific enzyme functions in models of atherosclerosis have been reported. Most of the uncovered glycosylation associations with pathological mechanisms revolve around the recruitment of inflammatory cells to the vessel wall and lipoprotein metabolism. This review aims to summarise insights from omics studies into the immune and metabolic regulation of N-glycosylation and its association with cardiovascular and metabolic disease risk and to provide mechanistic insights from experimental models. The combination of emerging techniques for glycomics and glycoproteomics with already achieved omics approaches to map the transcriptomic, epigenomic, and metabolomic profile at single-cell resolution will deepen our understanding of the molecular regulation of glycosylation as well as identify novel biomarkers and targets for cardiovascular disease prevention and treatment.PMID:39988310 | DOI:10.1016/j.vph.2025.107474

Fish Shellfish Immunol. 2025 Feb 21:110224. doi: 10.1016/j.fsi.2025.110224. Online ahead of print.ABSTRACTExcess adiposity impairs immune function and host defense in obese individuals, but studies on this concept in fish remain limited. In aquaculture, rapid growth is often encouraged through intensive farming practices, leading to overfeeding and negatively impacting production. This study aimed to induce obesity in rainbow trout through overfeeding, exploring metabolic abnormalities, immune response alterations, and infection susceptibility via transcriptomic and metabolomic analyses. In the overfed group, fish were fed until they refused to eat, while the control group was fed according to recommended feeding rates for four weeks. Sampling was conducted at weeks 1, 2, and 4 for serological, histopathological, metabolomic, and transcriptomic analyses. After four weeks, mortality rates were compared following Aeromonas salmonicida challenge, and immunological changes assessed one day post-infection. Overfed fish exhibited significant increases in weight gain (WG), body mass index (BMI), elevated AST/ALT levels, hepatocyte hypertrophy, lipid droplet formation, and triglyceride accumulation. At 1, 2, and 4 wpf, the overfed group exhibited distinct metabolic changes, with key alterations in glycolysis/gluconeogenesis, lipid metabolism and amino acid metabolism. KEGG analysis of transcriptomic data revealed a significant decrease in complement and coagulation cascades, including C3, FB, FH, an FI, accompanied by heightened TNF and IL-17 signaling pathways, involving the upregulation of genes such as TNF-α, IL-1β, and IL-6, indicating an enhanced inflammatory response. The overfed group experienced higher mortality post-infection. Excess energy from overfeeding led to hepatic fat accumulation, liver damage, and reduced innate immune responses, particularly in complement activation. These physiological disruptions compromised immune function, highlighting the detrimental effects of overfeeding-induced obesity on fish health. This study offers critical insights into the immunological mechanisms linking obesity to increased disease susceptibility.PMID:39988219 | DOI:10.1016/j.fsi.2025.110224

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