PubMed

Metabolomics. 2025 Jan 25;21(1):20. doi: 10.1007/s11306-024-02219-7.ABSTRACTBACKGROUND: Gestational exposure to non-persistent endocrine-disrupting chemicals (EDCs) may be associated with adverse pregnancy outcomes. While many EDCs affect the endocrine system, their effects on endocrine-related metabolic pathways remain unclear. This study aims to explore the global metabolome changes associated with EDC biomarkers at delivery.METHODS: This study included 75 pregnant individuals who delivered at the University of Cincinnati Hospital from 2014 to 2017. We measured maternal urinary biomarkers of paraben/phenol (12), phthalate (13), and phthalate replacements (4) from the samples collected during the delivery visit. Global serum metabolome profiles were analyzed from maternal blood (n = 72) and newborn (n = 63) cord blood samples collected at delivery. Fifteen of the 29 urinary biomarkers were excluded due to low detection frequency or potential exposures during hospital stay. We assessed metabolome-wide associations between 14 maternal urinary biomarkers and maternal/newborn metabolome profiles. Additionally, performed enrichment analysis to identify potential alterations in metabolic pathways.RESULTS: We observed metabolome-wide associations between maternal urinary concentrations of phthalate metabolites (mono-isobutyl phthalate), phthalate replacements (mono-2-ethyl-5-carboxypentyl terephthalate, mono-2-ethyl-5-hydroxyhexyl terephthalate) and phenols (bisphenol-A, bisphenol-S) and maternal serum metabolome, using q-value < 0.2 as a threshold. Additionally, associations of phthalate metabolites (mono-n-butyl phthalate, monobenzyl phthalate) and phenols (2,5-dichlorophenol, BPA) with the newborn metabolome were noted. Enrichment analyses revealed associations (p-gamma < 0.05) with amino acid, carbohydrate, lipid, glycan, vitamin, and other cofactor metabolism pathways.CONCLUSION: Maternal paraben, phenol, phthalate, and phthalate replacement biomarker concentrations at delivery were associated with maternal and newborn serum global metabolome.PMID:39863779 | DOI:10.1007/s11306-024-02219-7

Int J Colorectal Dis. 2025 Jan 25;40(1):24. doi: 10.1007/s00384-025-04808-x.ABSTRACTPURPOSE: In this study, we investigated the progression of high-grade dysplasia (HGD)/CRC in patients with hereditary colorectal cancer syndromes (HCSS) and concomitant inflammatory bowel diseases (IBDs).METHODS: We described the natural history of a series of patients with confirmed diagnosis of hereditary colorectal cancer syndromes (HCCSs) and concomitant IBDs who were referred to the Hereditary Digestive Tumors Registry at the Fondazione IRCCS Istituto Nazionale dei Tumori of Milan.RESULTS: Between January 1989 and April 2024, among 450 patients with APC-associated polyposis and 1050 patients with Lynch syndrome (LS), we identified six patients with IBDs (five with UC, one with ileal penetrating CD) and concomitant HCCSs (five with LS, one with APC-associated polyposis). Three patients developed CRC (two patients with stage IIA, and one with stage IIIA); in one patient, CRC occurred over a median follow-up of 12 months after IBD diagnosis, while in two, both conditions were diagnosed simultaneously. The median age at initial diagnosis of CRC was 33 years (range 27-41). Five patients (83.3%) underwent surgical procedures (three colonic resections for carcinoma and two for other reasons). Most of them progressed to precancerous or cancerous colonic lesions at a young age. Notably, all patients with CRC had a diagnosis of UC.CONCLUSION: IBD patients with coexistent HCCSs can develop early CRC onset at an advanced stage. These patients should be always referred to tertiary referral centers for strict surveillance programs and early surgical management of advanced colorectal neoplastic lesions. Noninvasive biomarkers of neoplastic changes are advocated to further improve the management of IBD patients with HCCSs.PMID:39863767 | DOI:10.1007/s00384-025-04808-x

Sci Rep. 2025 Jan 25;15(1):3194. doi: 10.1038/s41598-025-87415-8.ABSTRACTMenstrual pain affects women's quality of life and productivity, yet objective molecular markers for its severity have not been established owing to the variability in blood levels and chemical properties of potential markers such as plasma steroid hormones, lipid mediators, and hydrophilic metabolites. To address this, we conducted a metabolomics study using five analytical methods to identify biomarkers that differentiate menstrual pain severity. This study included 20 women, divided into mild (N = 12) and severe (N = 8) pain groups based on their numerical pain rating scale. We developed pretreatment procedures that allowed all analyses from only 100 µL of finger-prick blood collected across the menstrual cycle. Among the 692 quantified metabolites, branched-chain amino acids and specific phosphatidylinositol (PI), especially PI(36:2), were identified as potential biomarkers. Furthermore, the ratio of PI(36:2) to each BCAA or total BCAA effectively discriminated between the severity levels of menstrual pain. These ratios correlated positively with NPRS, indicating high accuracy in pain assessment. This study highlights the potential of small molecular markers to objectively assess menstrual pain severity, aiding evidence-based support and intervention.PMID:39863658 | DOI:10.1038/s41598-025-87415-8

Sci Rep. 2025 Jan 25;15(1):3189. doi: 10.1038/s41598-025-87256-5.ABSTRACTThe characteristics of data produced by omics technologies are pivotal, as they critically influence the feasibility and effectiveness of computational methods applied in downstream analyses, such as data harmonization and differential abundance analyses. Furthermore, variability in these data characteristics across datasets plays a crucial role, leading to diverging outcomes in benchmarking studies, which are essential for guiding the selection of appropriate analysis methods in all omics fields. Additionally, downstream analysis tools are often developed and applied within specific omics communities due to the presumed differences in data characteristics attributed to each omics technology. In this study, we investigate over ten thousand datasets to understand how proteomics, metabolomics, lipidomics, transcriptomics, and microbiome data vary in specific data characteristics. We were able to show patterns of data characteristics specific to the investigated omics types and provide a tool that enables researchers to assess how representative a given omics dataset is for its respective discipline. Moreover, we illustrate how data characteristics can impact analyses at the example of normalization in the presence of sample-dependent proportions of missing values. Given the variability of omics data characteristics, we encourage the systematic inspection of these characteristics in benchmark studies and for downstream analyses to prevent suboptimal method selection and unintended bias.PMID:39863642 | DOI:10.1038/s41598-025-87256-5

Anal Chim Acta. 2025 Feb 22;1340:343581. doi: 10.1016/j.aca.2024.343581. Epub 2024 Dec 22.ABSTRACTBACKGROUND: Normothermic ex situ heart perfusion (ESHP) has emerged as a valid modality for advanced cardiac allograft preservation and conditioning prior to transplantation though myocardial function declines gradually during ESHP thus limiting its potential for expanding the donor pool. Recently, the utilization of dialysis has been shown to preserve myocardial and coronary vasomotor function. Herein, we sought to determine the changes in myocardial metabolism that could support this improvement.RESULTS: Male Yorkshire porcine hearts were subjected to ESHP for 8 h with or without dialysis. Alterations in metabolism were studied with an innovative in vivo solid-phase microextraction (SPME) technology coupled with global metabolite profiling at 15 min, 1.5, 4, and 8 h of perfusion. Bio-SPME sampling was performed by inserting SPME fibres coated with a PAN-based extraction phase containing mixed-mode (C8+benzenesulfonic acid) functionalities into the myocardium to a depth of their entire 8 mm coating or immersing them in the perfusate, followed by a 20-min extraction period for the analytes of interest. Dialyzed hearts demonstrated improved bioenergetics as evidenced by accelerated purine metabolism and less pronounced accumulation of intermediates of fatty acid β/ω-oxidation. Metabolic waste accumulation such as pro-inflammatory lipid mediators (e.g., leukotrienes) was mitigated thereby supporting the process of resolution of inflammation through excretion of specialized pro-resolving mediators (resolvins D1/D2, E2, protecin D1).SIGNIFICANCE: Through implementing the unique analytical pipeline we demonstrated that the addition of dialysis may preserve cardiac metabolism allowing for prolonged ESHP. This strategy has the potential to facilitate high-risk donor organs' reconditioning prior to transplantation.PMID:39863306 | DOI:10.1016/j.aca.2024.343581

Int J Biol Macromol. 2025 Jan 23:140017. doi: 10.1016/j.ijbiomac.2025.140017. Online ahead of print.ABSTRACTThis study investigated the effects of rumen-degradable starch (RDS) on lactation performance, gastrointestinal fermentation, and plasma metabolomics in dairy cows. Six mid-lactation cows, fitted with rumen, duodenum, and ileum cannulas, were used in a duplicated 3 × 3 Latin square design with 28-day periods. The cows were fed a low RDS (LRDS; 62.18 %), medium-RDS (MRDS; 71.25 %), or high-RDS (HRDS; 80.32 %) diet. The results showed that cows fed HRDS had diet a lower milk fat content by 14.77 % (LRDS) and 11.73 % (MRDS), while increased somatic cell count compared to the LRDS and MRDS groups (34.42 and 29.38 %, respectively). Additionally, rumen fluid pH was decreased in the HRDS group than in the MRDS and LRDS groups (7.81 and 7.08 %, respectively), while microbial protein (MCP) concentration was higher in the MRDS group. The HRDS group had lower concentrations of total volatile fatty acids (TVFA) and acetate in the ileal digesta than the LRDS group. The HRDS diet decreased neutral detergent fibre (NDF) digestibility compared with LRDS and MRDS groups (7.68 and 8.50 %, respectively), and reduced plasma concentrations of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), while increasing plasma lipopolysaccharide (LPS) and serum amyloid-A (SAA) levels. Pathway analysis revealed that starch and sucrose metabolism, galactose metabolism, and carbohydrate digestion and absorption were upregulated in the MRDS and HRDS groups. The HRDS diet had a tendency to negatively affect linoleic acid metabolism, glycerophospholipid metabolism, and alpha-linolenic acid metabolism. These findings provide insights into optimising feed efficiency and milk quality by regulating RDS levels in dairy cow diets.PMID:39863231 | DOI:10.1016/j.ijbiomac.2025.140017

J Hepatol. 2025 Jan 23:S0168-8278(25)00022-4. doi: 10.1016/j.jhep.2025.01.015. Online ahead of print.NO ABSTRACTPMID:39863174 | DOI:10.1016/j.jhep.2025.01.015

J Allergy Clin Immunol. 2025 Jan 23:S0091-6749(25)00071-5. doi: 10.1016/j.jaci.2025.01.020. Online ahead of print.ABSTRACTBACKGROUND: Inhibition of IL-4/IL-13 driven inflammation by dupilumab has shown significant clinical benefits in treatment of atopic dermatitis (AD).OBJECTIVE: To assess longitudinal protein and metabolite composition in AD skin during dupilumab treatment.METHODS: Skin tape strip (STS) were collected from lesional/non-lesional skin of 20 AD patients during 16-week dupilumab treatment and from 20 healthy volunteers (HV) followed for 16-weeks. STS extracts were examined by LC-MS proteomic analysis and targeted metabolomics.RESULTS: Approximately 2,500 individual proteins were identified in STS extracts. 490 proteins were present in ≥80% of AD and HV skin samples and differentially expressed in AD skin. 249 proteins were significantly reduced (cluster 1) and 136 were significantly increased (cluster 2) in AD skin (both p<0.0001 compared to HV). Functionally, cluster 1 included proteins involved in epidermal barrier formation, lysosomal enzymes required for lamellae assembly, and oxidative response. Cluster 2 was enriched for markers of epidermal hyperplasia, glycolytic enzymes and actin filament proteins. Significant increase in cluster 1 and significant inhibition in cluster 2 proteins expression was achieved in AD skin by 16-weeks of dupilumab treatment (p<0.0001 for both, compared to baseline) and approached HV skin levels. These improvements were also revealed in differential metabolite changes in STS extracts, including amino acids, nucleotide breakdown products and antioxidants.CONCLUSION: Longitudinal integrated assessment of the skin proteome and metabolome in AD patients treated with dupilumab established significant inhibition of epidermal hyperplasia and improvement in epidermal differentiation. Identified changes were linked to improvements in clinical AD skin assessments, including TEWL and disease severity.CLINICAL IMPLICATIONS: Mass spectrometry analysis identifies molecular improvements in skin protein and metabolite composition in AD patients and their relationship to targeted suppression of IL-4/IL-13 signaling by dupilumab treatment and clinical response.CAPSULE SUMMARY: The study performed longitudinal sampling and analysis of skin samples of AD patients treated by dupilumab and provided evaluation of structural and inflammatory protein components of skin barrier, skin metabolites and their changes on treatment.PMID:39863059 | DOI:10.1016/j.jaci.2025.01.020

J Hazard Mater. 2025 Jan 21;488:137310. doi: 10.1016/j.jhazmat.2025.137310. Online ahead of print.ABSTRACTCigarette smoke (CS), an indoor environmental pollution, is an environmental risk factor for diverse neurological disorders. However, the neurotoxicological effects and mechanisms of CS on Alzheimer's disease (AD) progression remain unclear. We found that CS accelerated the progression of AD, including increasing β-amyloid (Aβ) plaque deposition and exacerbating cognitive decline. Mechanistically, CS exposure increased the levels of NOD-like receptor protein 3 (NLRP3), which impaired autophagic flux in microglia by activating the mammalian target of rapamycin (mTOR) signal. Metabolomics analysis revealed an upregulation of lactate levels and an increase in global protein lysine lactylation in the brain tissue of CS-exposed AD-transgenic mice. Immunoprecipitation-Mass Spectrometry and chromatin immunoprecipitation assays demonstrated that CS elevates H4K12 lactylation (H4K12la) levels, which accumulate at the promoter region of NLRP3, leading to the activation of its transcription. Via inhibiting lactate or NLRP3 activation, oxamate and MCC950 alleviates these CS-induced effects. Therefore, our data suggest that the CS-induced increase in lactate levels triggers NLRP3 transcriptional activation through H4K12la, which subsequently leads to mTOR-mediated autophagy dysfunction in microglia, promoting microglial activation and resulting in Aβ plaque accumulation in AD-transgenic mice. This provides a new mechanism and potential therapeutic target for AD associated with environmental factors.PMID:39862777 | DOI:10.1016/j.jhazmat.2025.137310

Ecotoxicol Environ Saf. 2025 Jan 24;290:117758. doi: 10.1016/j.ecoenv.2025.117758. Online ahead of print.ABSTRACTGlyphosate, a widely used herbicide globally, has prompted concerns regarding its potential health impacts. This study aimed to explore the link between glyphosate exposure and renal function by combining NHANES, a zebrafish model, and metabolomics. A cross-sectional analysis of 2013-2014 NHANES data investigated the relationship between glyphosate exposure and renal function [albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR)]. A subsequent zebrafish experiment was conducted to verify this association. Embryos (0.75 hpf-96 hpf) were exposed to different glyphosate concentrations dissolved in water (0, 30, 60, 90, 120 μg/mL). The underlying mechanism of the association between glyphosate and renal function was explored by the real-time quantitative polymerase chain reaction (RT-qPCR) and non-targeted metabolomics analysis [embryos (0.75 hpf-96 hpf) were exposed to 90 μg/mL glyphosate]. 1170 participants were enrolled in the NHANES study. The NHANES-based study found a positive association between glyphosate and ACR [0.07 (0.01, 0.13)]. Higher urinary glyphosate levels, particularly in the third quartile group, were negatively linked to eGFR [-3.72 (-5.98, -1.46)]. Further zebrafish experiments indicated that zebrafish exposed to 90 μg/mL glyphosate exhibited increased mortality rates, higher fluorescence intensity, up-regulated the havcr1 expression level, and cystic dilatation of the kidney. Non-targeted metabolomics analysis identified differential metabolites (e.g., 5-Hydroxyindole acetic acid) and pathways (e.g., ABC transporters) influenced by glyphosate. Glyphosate exposure is negatively associated with renal function in community adults. The damage to the kidneys caused by glyphosate may be mediated through the regulation of metabolic pathways, and the specific mechanisms require further experimental investigation.PMID:39862699 | DOI:10.1016/j.ecoenv.2025.117758

Ecotoxicol Environ Saf. 2025 Jan 24;290:117763. doi: 10.1016/j.ecoenv.2025.117763. Online ahead of print.ABSTRACTOxytetracycline (OTC), a crop-absorbable antibiotic, poses a health risk to humans through the food chain. Conversely, 24-epibrassinolide (EBL), a plant growth hormone, mitigates the toxic effects of various pollutants on plants. However, the mechanism by which exogenous EBL affects the growth of rape seedlings exposed to OTC remains largely unknown. In this study, we found that environmental OTC concentrations significantly inhibited plant growth and metabolism, whereas exogenous EBL could restore plant growth characteristics. Exogenous EBL significantly decreased reactive oxygen species (ROS) accumulation, alleviating OTC-induced cell membrane lipid peroxidation. This was achieved by increasing the antioxidant capacity and secondary metabolism levels. Notably, our findings suggested that EBL stimulated glutathione S-transferase (GST) and glutathione reductase (GR) activities, enhancing reduced glutathione synthesis and participating in plant OTC detoxification. OTC residues in EBL + OTC-treated seedlings at 21 d were significantly reduced by 29 % compared with OTC alone. Further transcriptomic and metabolomic analyses revealed that the differentially expressed genes and metabolites in the EBL and OTC alone or combined treatment groups were primarily involved in the regulation of phenylpropanoid biosynthesis, glutathione metabolism, and lant hormone signal transduction pathways in response to phytotoxic effects and detoxification mechanisms, as compared to the control group.PMID:39862695 | DOI:10.1016/j.ecoenv.2025.117763

Parasit Vectors. 2025 Jan 25;18(1):27. doi: 10.1186/s13071-024-06654-2.ABSTRACTBACKGROUND: Nippostrongylus brasiliensis-a nematode of rodents-is commonly used as a model to study the immunobiology of parasitic nematodes. It is a member of the Strongylida-a large order of socioeconomically important parasitic nematodes of animals. Lipids are known to play essential roles in nematode biology, influencing cellular membranes, energy storage and/or signalling.METHODS: The present investigation provides a comprehensive, untargeted lipidomic analysis of four developmental stages/sexes (i.e. egg, L3, adult female and adult male stages) of N. brasiliensis utilising liquid chromatography coupled to mass spectrometry.RESULTS: We identified 464 lipid species representing 18 lipid classes and revealed distinct stage-specific changes in lipid composition throughout nematode development. Triacylglycerols (TGs) dominated the lipid profile in the egg stage, suggesting a key role for them in energy storage at this early developmental stage. As N. brasiliensis develops, there was a conspicuous transition toward membrane-associated lipids, including glycerophospholipids (e.g. PE and PC) and ether-linked lipids, particularly in adult stages, indicating a shift toward host adaptation and membrane stabilisation.CONCLUSIONS: We provide a comprehensive insight into the lipid composition and abundance of key free-living and parasitic stages of N. brasiliensis. This study provides lipidomic resources to underpin the detailed exploration of lipid biology in this model parasitic nematode.PMID:39863914 | DOI:10.1186/s13071-024-06654-2

Metabolomics. 2025 Jan 25;21(1):22. doi: 10.1007/s11306-024-02203-1.NO ABSTRACTPMID:39863829 | DOI:10.1007/s11306-024-02203-1

Lupus Sci Med. 2025 Jan 25;12(1):e001401. doi: 10.1136/lupus-2024-001401.ABSTRACTOBJECTIVE: Metabolic reprogramming plays a critical role in modulating the innate and adaptive immune response, but its role in cutaneous autoimmune diseases, such as cutaneous lupus erythematosus (CLE), is less well studied. An improved understanding of the metabolic pathways dysregulated in CLE may lead to novel treatment options, biomarkers and insights into disease pathogenesis. The objective was to compare metabolomic profiles in the skin and sera of CLE and control patients using liquid chromatography-mass spectrometry (LC-MS).METHODS: This was a cross-sectional pilot study comparing metabolomic sera and skin profiles of patients with CLE and normal controls. Patients were recruited from outpatient dermatology clinics at the University of Texas Southwestern and Parkland Health in Dallas, Texas, from January 2019 to October 2020. Skin and serum samples underwent LC-MS analysis. Disease sample metabolite levels were compared with controls, with significance levels adjusted for multiple hypothesis testing.RESULTS: 17 serum samples (9 CLE, 8 control) and 11 skin samples (5 CLE, 6 control) were analysed using LC-MS, yielding 313 known unique metabolic structures from CLE samples. Patients with CLE were found to have 11 metabolites of differential abundance in the skin, but only 2 in the sera. CLE skin showed increased levels of citrulline (log2 fold change (FC)=1.15, p=0.02) and uracil (log2FC=1.79, p=0.04), and downregulation of cyclic ADP ribose (cADPr) (log2FC=0.83, p=0.04), nicotinamide mononucleotide (NMN) (log2FC=0.75, p=0.016) and nicotinamide adenine dinucleotide (NAD+) (log2FC=0.86, p=0.016) versus control skin. CLE sera had increased arabinose (log2FC=1.17, p=0.02) and cystine (log2FC=1.04, p=0.03) compared with control sera.CONCLUSIONS: Metabolites associated with the NAD+ pathway may be dysregulated in the skin of patients with CLE. Available treatments including nicotinamide supplementation and anti-CD38 biologics that can correct these abnormalities can be further investigated in patients with CLE.PMID:39863305 | DOI:10.1136/lupus-2024-001401

Int J Biol Macromol. 2025 Jan 23:140242. doi: 10.1016/j.ijbiomac.2025.140242. Online ahead of print.ABSTRACTIn this study, we successfully integrated the full-length genome of the cyanophage PP into the non-host cyanobacterium Synechococcus elongatus PCC 7942, facilitated by conjugation via Escherichia coli. To address the challenge posed by the toxic open reading frames (ORFs) of PP in E. coli, we first identified and characterized three toxic ORFs. The PP genome was subsequently rearranged, and the expression of these toxic ORFs was controlled using a tandem-induction switch system. The full-length PP genome was then successfully integrated into the genome of S. elongatus PCC 7942. Interestingly, the integration of the PP genome led to a reduction in photosynthesis and carbon fixation in S. elongatus PCC 7942, resembling the effects typically associated with cyanophage infection. Transcriptomic analysis showed that 32 of the 41 ORFs in the PP genome were actively transcribed in S. elongatus PCC 7942, significantly affecting energy metabolism and carbon fixation pathways. These effects were further confirmed by metabolomic analysis.PMID:39863235 | DOI:10.1016/j.ijbiomac.2025.140242

Int J Biol Macromol. 2025 Jan 23:140288. doi: 10.1016/j.ijbiomac.2025.140288. Online ahead of print.ABSTRACTUnderstanding the global transcriptomic and metabolic changes during mulberry growth and development is essential for the enhancing fruit quality and optimizing breeding strategies. By integrating phenotypic, metabolomic, and transcriptomic data across 18 developmental and ripening stages of Da10 mulberry fruit, a global map of gene expression and metabolic changes was generated. Analysis revealed a gradual progression of morphological, metabolic, and transcriptional changes throughout the development and ripening phases. In this study, a new transcriptome transition, which was highly related to stress resistance, was observed after the full ripening stage. Moreover, a novel method was devised by integrating metabolome and phenotypic data to assess fruit quality and determine optimal harvest times early in the supply chain. Phase-specific co-expression networks involved in photosynthesis, quality regulation, and plant immunity were also constructed. Notably, eight flavonoids and six hub genes emerged as potential natural edible coatings or gene-editing targets for mulberry fruit to enhance resistance against biotic and abiotic stress. These findings should facilitate further research on stress resistance, post-harvest management, and sustainable agricultural development.PMID:39863218 | DOI:10.1016/j.ijbiomac.2025.140288

Phytomedicine. 2025 Jan 16;138:156397. doi: 10.1016/j.phymed.2025.156397. Online ahead of print.ABSTRACTBACKGROUND: Huangkui capsule (HKC), a Chinese patent medicine, is clinically used for treating diabetic nephropathy. However, the core disease-specific biomarkers and targets of type 2 diabetic nephropathy (T2DN) and the therapeutic mechanism of HKC are not fully elucidated.PURPOSE: This study aimed to investigate the therapeutic effects and underlying molecular mechanisms of HKC for T2DN.STUDY DESIGN: The db/db mouse model was used to evaluate the efficacy of HKC for T2DN, and the core pathways regulated by HKC were studied to determine its kidney protective mechanism.METHODS: High-throughput UPLC-MS/MS and multivariate analysis were employed to analyze the serum and kidney metabolic profiles of db/db mice, identifying potential core biomarkers of T2DN. Atmospheric pressure matrix-assisted laser desorption/ionization mass spectrometry imaging was used to locate in situ spatial distribution of core biomarkers and drug active ingredients in kidney tissues. Biochemical indicators, histopathology, immunohistochemistry, immunofluorescence, molecular docking, and western blotting were combined to reveal therapeutic effects, pathways, and targets of HKC.RESULTS: HKC substantially improved pathological characteristics, kidney function, oxidative stress, inflammation, and lipid metabolism indicators of T2DN. Twelve core disease-specific biomarker that significantly influenced clustering were identified and its unique spatial distribution information in the kidneys was revealed. 3-dehydrosphinganine, retinyl ester, and 9-cis-retinoic acid (9cRA) could serve as novel disease-specific biomarkers for T2DN. Based on newly discovered biomarkers, quercetin, myricetin, and isorhamnetin were found to act on key enzymes SPT, ALDH1A1, AOX, LRAT, and DGAT1 in retinol and sphingolipid metabolism pathways. Western blotting showed that HKC ameliorated T2DN by targeting these enzymes, upregulating 9cRA and retinyl ester, downregulating 3-dehydrosphinganine, increasing TGF-β signal transduction, inhibiting the expression of the immune fibrosis proteins OX-8, Col-I and α-SMA, inhibiting Th17 cell development and ceramide synthesis, reducing IL-1β, TNF-α, MDA, TC, LDL-C, and TG levels, and increaseing SOD activity.CONCLUSIONS: HKC exerts significant therapeutic effects on T2DN. HKC corrects the metabolic disorder of sphingolipids and retinol, and improves T2DN by regulating the activities of SPT, ALDH1A1, AOX, LRAT, and DGAT1. This study provides valuable ideas and new mechanistic insights for the treatment of T2DN with HKC.PMID:39862790 | DOI:10.1016/j.phymed.2025.156397

Talanta. 2025 Jan 20;287:127603. doi: 10.1016/j.talanta.2025.127603. Online ahead of print.ABSTRACTThere is no consensus in the literature regarding the ideal protocol for obtaining and preparing cell samples for untargeted metabolomics. Nevertheless, the procedures must be carefully evaluated for proper and reliable results for each organism under study. This work proposes a novel protocol for determining intracellular metabolites in Leishmania promastigotes and is fully optimized for application in conjunction with gas chromatography-mass spectrometry platforms. Sample harvesting consisted of stopping metabolic activity by placing the parasite cells in a dry ice bath and removing extracellular interferants with two wash steps using cold PBS. The extraction is carried out with 1.0x108 promastigotes per sample using a mixture of cold 1:1 methanol:water and ultrasound mixing (1 min at 30 % power). Dried extracts were derivatized by oximation (at room temperature for 90 min), followed by silylation (at 40 °C for 30 min). The method developed here can cover a wide range of the Leishmania parasite metabolome, including amino acids and derivatives, organic and fatty acids, carbohydrates and derivatives, and steroids.PMID:39862521 | DOI:10.1016/j.talanta.2025.127603

Sci Total Environ. 2025 Jan 24;964:178604. doi: 10.1016/j.scitotenv.2025.178604. Online ahead of print.ABSTRACTPolyethylene nanoplastics (NPs) are widely diffused in terrestrial environments, including soil ecosystems, but the stress mechanisms in plants are not well understood. This study aimed to investigate the effects of two increasing concentrations of NPs (20 and 200 mg kg-1 of soil) in lettuce. To this aim, high-throughput hyperspectral imaging was combined with metabolomics, covering both primary (using NMR) and secondary metabolism (using LC-HRMS), along with lipidomics profiling (using ion-mobility-LC-HRMS) and plant performance. Hyperspectral imaging highlighted a reduced plant growth pattern. Several vegetative indexes indicated plant toxicity, with 20 mg kg-1 NPs significantly decreasing lettuce density and vegetation health (as indicated by NDVI and plant senescence reflectance indexes). Consistently, photosynthetic activity also decreased. At the biochemical level, metabolomics and lipidomics pointed out a multi-layered broad biochemical reprogramming of primary and secondary metabolism involving a decrease in sterols, sphingolipids, glycolipids, and glycerophospholipids in response to NPs. The reduction in phosphatidylinositol coincided with an accumulation of diacylglycerols (DAG), suggesting the activation of the phospholipase C lipid signaling pathway. Moreover, nanoplastic treatments down-modulated different biosynthetic pathways, particularly those involved in N-containing compounds and phenylpropanoids. Our mechanistic basis of NPs stress in plants will contribute to a better understanding of their environmental impact.PMID:39862496 | DOI:10.1016/j.scitotenv.2025.178604

J Cereb Blood Flow Metab. 2025 Jan 25:271678X251314331. doi: 10.1177/0271678X251314331. Online ahead of print.ABSTRACTCurrent metabolomics technologies can measure hundreds of chemical entities in tissue extracts with good reliability. However, long-recognized requirements to halt enzyme activities during the initial moments of sample preparation are usually overlooked, allowing marked postmortem shifts in levels of labile metabolites representing diverse pathways. In brain many such changes occur in a matter of seconds. These comments overview the concern, contrast representative studies, and specify approaches to consider as standards in the field going forward. Comparison with established metabolite signatures of in vivo brain is an essential validation step when implementing any collection method.PMID:39862175 | DOI:10.1177/0271678X251314331