PubMed

Eur J Med Res. 2025 Apr 26;30(1):332. doi: 10.1186/s40001-025-02609-0.ABSTRACTBACKGROUND: This study aims to identify potential biomarkers in the buffy coat of drug-resistant epilepsy (DRE) patients with mesial temporal lobe epilepsy and to elucidate associated pathways.METHODS: A comprehensive non-targeted metabolomic and Gene Expression Omnibus (GEO) datasets analysis was first performed on buffy coat from DRE patients and non-epilepsy (CON) patients. Potential enriched biomarkers and pathways were integrated with gene expression profiles from GEO datasets to identify robust biomarkers.RESULTS: In the DRE group, there were 15 patients (10 males and 5 females), with an average age of (37.67 ± 15.53) years. In the CON group, there were 10 patients (7 males and 3 females), with an average age of (51.60 ± 18.20) years. A total of 27 potential biomarkers were identified, including 7 down-regulated and 8 up-regulated. Additionally, 9 potential pathways related to DRE were identified. Notably, purine metabolism, tryptophan metabolism and aminoacyl-tRNA metabolism were closely related to DRE. Purine metabolism was up-regulated, while aminoacyl-tRNA and tryptophan metabolism were down-regulated.CONCLUSIONS: The integration of metabolomic data with GEO datasets analysis offers a new strategy to identify robust biomarkers and pathways. The findings obtained from the buffy coat analysis offer potential insights for the diagnosis and treatment of DRE.PMID:40287763 | DOI:10.1186/s40001-025-02609-0

BMC Pregnancy Childbirth. 2025 Apr 26;25(1):506. doi: 10.1186/s12884-025-07626-9.ABSTRACTBACKGROUND: Anemia during pregnancy is associated with various adverse neonatal outcomes. However, the association between maternal anemia during pregnancy and newborn metabolic profiles remains unclear. This study aimed to investigate whether anemia during pregnancy is associated with alterations in neonatal metabolic profiles.METHODS: This prospective observational cohort study included 12,116 pregnant women, with or without gestational anemia, recruited through the Beijing Birth Cohort Study (ChiCTR2200058395), along with their neonates born between July 2021 and October 2022 in Beijing, China.RESULTS: Among the 12,116 participants, 576 pregnant women were diagnosed with anemia (Anemia group), while 11,540 did not have anemia (Control group). The rates of metabolic profile abnormalities were significantly higher in the Anemia group compared to the Control group (P < 0.05): 20.83% vs. 16.1% for the overall metabolic profile, 11.9% vs. 9.25% for amino acid profiles, and 11.11% vs. 8.04% for acylcarnitine profiles. Individual metabolic indicators showed significant differences: alanine and arginine levels significantly decreased, while tyrosine levels significantly increased in the Anemia group. Notably, most acylcarnitines indicators (C0, C2, C4DC + C5-OH, C5DC + C6-OH, C6, C6DC, C10, C10:1, C12, C12:1, C14, C14:1, C14:2, C16, C16:1, C16:1-OH, C18, and C18:1) were significantly reduced in the Anemia group, except for C5, which was elevated. Pathway analysis revealed that these alterations were associated with beta-oxidation of very long-chain fatty acids, oxidation of branched-chain fatty acids, mitochondrial beta-oxidation of long-chain saturated fatty acids, and fatty acid metabolism. All of these pathways were related to fatty acid oxidation. Sensitive analyses in normal birth weight (NBW) and term infants (TI) confirmed these findings and demonstrated their robustness. In addition, in NBW infants and TIs, citrulline and arginine were significantly decreased, which were associated with aspartate metabolism and the urea cycle.CONCLUSIONS: Maternal anemia during pregnancy is significantly associated with alterations in neonatal metabolic profiles, particularly in fatty acid beta-oxidation and related pathways. These findings highlight the potential metabolic consequences of gestational anemia and provide insights into its role in adverse neonatal outcomes and abnormal newborn screening results.PMID:40287617 | DOI:10.1186/s12884-025-07626-9

Sci Rep. 2025 Apr 26;15(1):14688. doi: 10.1038/s41598-025-99606-4.ABSTRACTTo understand the relationship between type 2 diabetes (T2D) and risk for developing cognitive impairment, this study is the first to examine association between metabolites measured at mid-life and cognitive performance assessed later in life (8-10 years) in a T2D-enriched cohort. The discovery set included metabolomics from European Americans (EAs; n = 137) and African Americans (AAs; n = 134) from the Diabetes Heart Study (DHS) and the African American-DHS (AA-DHS). The cognitive testing battery included measures of executive function, memory, attention, language, and global cognition. Ancestry-specific linear regression analyses were performed and a false discovery rate (FDR)-corrected p-value was used to assess significance. Overall, fewer significant metabolites were associated with cognitive performance in AAs (n = 19) as compared to EAs (n = 118) suggesting racial differences. There was a positive association between sphingomyelins and cognitive performance, consistent with prior reports. Novel findings implicated partially characterized metabolites linked to oxidative breakdown of bilirubin to multiple cognitive domains suggesting further exploration of this class of metabolites towards improving pathophysiologic understanding and early intervention. Cross-ancestry replication identified four metabolites that generalized to both populations. Replication was performed among additional study participants, i.e. 421 EAs and 167 AAs, followed by a formal meta-analysis. Replication bolstered the association of multiple metabolites with cognitive function. Among these, cortisol was associated in AAs suggesting a link between stress and risk for reduced cognitive function. Further work is needed to provide insight into the pathophysiologic mechanisms and highlight metabolites for inclusion in risk stratification models of cognitive performance.PMID:40287557 | DOI:10.1038/s41598-025-99606-4

Eur Spine J. 2025 Apr 26. doi: 10.1007/s00586-025-08850-9. Online ahead of print.ABSTRACTOBJECTIVE: The precise mechanisms driving intervertebral disc degeneration (IVDD) development remain unclear, but evidence suggests a significant involvement of inflammatory cytokines and blood metabolites. We aimed to investigate the causal relationships between inflammatory cytokines, IVDD, and blood metabolites using Mendelian randomization (MR) analysis.METHODS: We utilized inflammatory cytokines from a GWAS summary containing 8293 healthy participants, 1400 blood metabolites from the genome-wide association studies (GWAS) Catalog, and IVDD data from the FinnGen repository, all of which are sourced from the largest genome-wide association studies conducted to date. Employing bidirectional MR analyses, we investigated the causal relationships between inflammatory cytokines and IVDD. Additionally, we conducted two mediation analyses, two-step MR and multivariable MR (MVMR), to identify potential mediating metabolites.RESULTS: Four inflammatory cytokines were causally associated with IVDD, while IVDD did not have a significant causal effect on them. In the two-step MR analysis, IFN-γ, IL-1β, IL-6, and TNF-β, along with metabolites N-methyltaurine, Glycosyl-N-behenoyl-sphingadienine (d18:2/22:0), 3-methoxycatechol sulfate (1), 5alpha-androstan-3beta, 17beta-diol monosulfate (2), X-17653, and 1-palmitoleoylglycerol (16:1), were all significantly associated with IVDD (all P < 0.05). MVMR analysis revealed that the associations between IFN-γ and IVDD were mediated by Glycosyl-N-behenoyl-sphingadienine (d18:2/22:0) (5.1%, P = 0.010); IL-1β and IVDD were mediated by 3-methoxycatechol sulfate (1) (8.8%, P = 0.048); IL-6 and IVDD were mediated by X-17653 (- 8.0%, P = 0.007), and 5alpha-androstan-3beta, 17beta-diol monosulfate (2) (5.2%, P = 0.028); TNF-β and IVDD were mediated by 1-palmitoleoylglycerol (16:1) (8.1%, P = 0.011).CONCLUSIONS: The present MR study offers evidence supporting the causal relationships between several specific inflammatory cytokines and IVDD, as well as identifying potential mediating metabolites.PMID:40287509 | DOI:10.1007/s00586-025-08850-9

Nat Commun. 2025 Apr 26;16(1):3945. doi: 10.1038/s41467-025-59356-3.ABSTRACTBreast cancer, particularly triple-negative breast cancer (TNBC), evades the body's immune defences, in part by cultivating an immunosuppressive tumour microenvironment. Here, we show that suppressing local steroidogenesis can augment anti-tumour immunity against TNBC. Through targeted metabolomics of steroids coupled with immunohistochemistry, we profiled the existence of immunosuppressive steroids in TNBC patient tumours and discerned the steroidogenic activity in immune-infiltrating regions. In mouse, genetic inhibition of immune cell steroidogenesis restricted TNBC tumour progression with a significant reduction in immunosuppressive components such as tumour associated macrophages. Steroidogenesis inhibition appears to bolster anti-tumour immune responses in dendritic and T cells by impeding glucocorticoid signalling. Undertaking metabolic modelling of the single-cell transcriptomics and targeted tumour-steroidomics, we pinpointed the predominant steroidogenic cells. Inhibiting steroidogenesis pharmacologically using a identified drug, posaconazole, curtailed tumour expansion in a humanised TNBC mouse model. This investigation paves the way for targeting steroidogenesis and its signalling pathways in breast cancer affected by immune-steroid maladaptation.PMID:40287432 | DOI:10.1038/s41467-025-59356-3

Int Rev Cell Mol Biol. 2025;392:67-100. doi: 10.1016/bs.ircmb.2024.03.009. Epub 2024 May 2.ABSTRACTMetastasis is a lethal disease of cancer, spreading from primary tumors to the bloodstream as circulating tumor cells (CTCs), which disseminate to distant organs at low efficiency for secondary tumor regeneration, thereby contributing to unfavorable patient outcomes. The detection of dynamic CTC alterations can be indicative of cancer progression (residual cancer, aggressiveness, therapy resistance) or regression (therapy response), serving as biomarkers for diagnoses and prognoses. CTC heterogeneity is impacted by both intrinsic oncogenic changes and extrinsic microenvironmental factors (e.g. the immune system and circadian rhythm), altering the genomic/genetic, epigenomic/epigenetic, proteomic, post-translational, and metabolomic landscapes. In addition to homeostatic dynamics, regenerative stemness, and metabolic plasticity, a newly discovered feature of CTCs that influences metastatic outcomes is its intercellular clustering. While the dogma suggests that CTCs play solo as single cells in the circulation, CTCs can orchestrate with other CTCs or white blood cells to form homotypic or heterotypic multi-cellular clusters, with 20-100 times enhanced metastatic potential than single CTCs. CTC clusters promote cell survival and stemness through DNA hypomethylation and signaling pathways activated by clustering-driving proteins (CD44, CD81, ICAM1, Podocalyxin, etc). Heterotypic CTC clusters may protect CTCs from immune cell attacks if not being cleared by cytotoxic immune cells. This chapter mainly focused on CTC biology related to multi-omic features and metastatic outcomes. We speculate that CTCs could guide therapeutic targeting and be targeted specifically by anti-CTC therapeutics to reduce or eliminate cancer and cancer metastasis.PMID:40287221 | DOI:10.1016/bs.ircmb.2024.03.009

Toxicol Appl Pharmacol. 2025 Apr 24:117354. doi: 10.1016/j.taap.2025.117354. Online ahead of print.ABSTRACTTripterygium wilfordii, Hook f. (TW) has been traditionally used in Chinese medicine to treat conditions like rheumatoid arthritis, nephritis, and lupus erythematosus. However, the toxic reactions to the liver pose a huge obstacle to TW's clinical applications. The toxicological mechanisms of TW remain unclear. Male C57BL/6 mice were administered with TW ingredient triptolide (TP) and triptophenolide (TPH) alone or in combination to investigate their individual and synergistic effects on the liver. Elisa tested for LPS in the plasma correlated with liver injury. Metabolomics and 16S rRNA analysis were used to investigate pathological markers associated with intestine function disorder which may contribute to liver injury. The correlation analysis between the differential metabolites and the changing flora was carried out to find the fundamental metabolic molecules, and the results of the correlation analysis were verified by the addition of metabolites in vivo. The concurrent use of TPH and TP cause intestinal bleeding and microbial dysbiosis, then augment level of LPS in the plasma to prompting more severe liver damage induced by TP. Metabolomic analysis and changes in microflora composition proved that the toxic metabolite PCS was significantly related to intestinal barrier damage, and the addition of PCS promoted hepatotoxicity in combination administration. By augmenting PCS, TPH compromises the gut barrier, escalates circulating LPS, and activates the hepatic TLR4/MyD88 pathway, thereby exacerbating TP-induced hepatic injury.PMID:40286878 | DOI:10.1016/j.taap.2025.117354

Comp Biochem Physiol C Toxicol Pharmacol. 2025 Apr 24:110211. doi: 10.1016/j.cbpc.2025.110211. Online ahead of print.ABSTRACTTri-n-butyl phosphate (TnBP) and tricresyl phosphate (TCP), emerging flame retardants and plasticizers, have garnered increasing attention due to their potential risks to ecosystem. A few researches regarding the toxicological mechanisms of TnBP and TCP had been performed, while molecular-level toxic effects of them and metabolic response using microbial models are the lack of relevant investigation. Thus, we investigated the cytotoxicity, oxidative stress response, and metabolic response in E. coli exposed to TnBP and TCP. Exposure to them significantly increased the activities of antioxidant enzymes, indicating activation of the antioxidant defense system. Excessive accumulation of reactive oxygen species (ROS) triggered various biological events, including a reduction in membrane potential (MP), decrease of adenosine triphosphatase (ATPase) activity, and increased malondialdehyde (MDA) content. These findings suggested that oxidative damage compromised membrane proteins function, membrane stability, and intracellular homeostasis. GC-MS and LC-MS-based metabolomics analyses revealed that TnBP and TCP strongly disrupted multiple metabolic pathways, including carbohydrate metabolism, nucleotide metabolism, lipid metabolism, beta-alanine metabolism, pyruvate metabolism and oxidative phosphorylation. These disruptions highlighted the inhibitory effects on molecular functions and metabolic processes. Notably, lipids biomarkers e.g., PC(11:0/16:0), PA(17:1(9Z)/18:2(9Z,12Z)), PE(17:0/14:1(9Z)), and LysoPE(0:0/18:1(11Z)) were significantly altered, verifying that the regulation of lipid-associated metabolite synthesis plays a protective role in maintaining cellular membrane function. In summary, this study enhances our understanding of TnBP and TCP toxicity in E. coli, providing novel insights into their toxicological mechanisms at molecular and network levels. These findings underscore the ecological risks posed by organophosphate flame retardants in aquatic ecosystem.PMID:40286830 | DOI:10.1016/j.cbpc.2025.110211

Cell Rep Med. 2025 Apr 17:102093. doi: 10.1016/j.xcrm.2025.102093. Online ahead of print.ABSTRACTThis study evaluates the efficacy of the postbiotic Probio-Eco in alleviating constipation in humans and mice. A randomized, double-blind, placebo-controlled crossover trial involving 110 adults with chronic constipation (Rome IV criteria) demonstrates that a 3-week Probio-Eco intervention significantly improves constipation symptoms, stool straining, and worry scores. Gut microbiota and metabolomic analyses reveal modulations in specific gut microbiota, succinate, tryptophan derivatives, deoxycholate, propionate, butyrate, and cortisol, correlating with symptom relief. A loperamide-induced mouse model confirms that Probio-Eco and its bioactive components (succinate, 3-indoleacrylic acid, and 5-hydroxytryptophan) alleviate constipation by stimulating mucin-2 secretion, regulating intestinal transport hormones, and promoting anti-inflammatory responses. Multi-omics integration identifies key pathways, including succinate-short-chain fatty acid, tryptophan-5-hydroxytryptophan-serotonin, and tryptophan-3-indoleacrylic acid, driving intestinal homeostasis and motility. These findings highlight the comprehensive efficacy of Probio-Eco and provide robust evidence for its clinical application in constipation management. This study was registered at Chinese Clinical Trial Registry (ChiCTR2100054376).PMID:40286792 | DOI:10.1016/j.xcrm.2025.102093

Phytomedicine. 2025 Apr 16;142:156775. doi: 10.1016/j.phymed.2025.156775. Online ahead of print.ABSTRACTBACKGROUND: Carotid atherosclerosis(CAs) plaques are challenging to reverse. Neixiao-Ruanmai Decoction No 2(NXRMT No 2), a Traditional Chinese Medicine (TCM) decoction, has shown potential in treating CAs. However, while preliminary clinical trials have confirmed the efficacy of NXRMT No 2 in improving CAs, the comparative effectiveness of long-term versus short-term treatment courses remains unclear, and the underlying mechanisms of this decoction are not yet fully understood.METHODS: We conducted clinical trials, animal studies, 16S rRNA sequencing, metabolomics and fecal microbiota transplantation.RESULT: Clinical research results indicate that NXRMT No 2(24 weeks of treatment) reduced total plaque area by 22.02%, maximum plaque thickness by 7.91%, and maximum plaque area by 21.29%. NXRMT No 2 improves patients'serum inflammatory levels, with a 24-week treatment course demonstrated superior efficacy compared to the 12-week treatment. Animal experiments demonstrated that NXRMT No 2 improved CAs progression, modulated the gut microbiota, inhibited the intestinal Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway and activated the expression of intestinal tight junction proteins.CONCLUSION: NXRMT No 2 significantly attenuates CAs progression, with its primary mechanism likely related to modulating the gut microbiota to counteract the TLR4/NF-κB pathway and protect the intestinal barrier. This study provides evidence-based support for the use of NXRMT No 2 in treating CAs, offers guidance on optimal treatment duration for patients, and contributes to the development of traditional Chinese medicine formulations that improve CAs by modulating the gut microbiota-a significant advance in the prevention and treatment of CAs.PMID:40286751 | DOI:10.1016/j.phymed.2025.156775

Phytomedicine. 2025 Mar 26;142:156691. doi: 10.1016/j.phymed.2025.156691. Online ahead of print.ABSTRACTBACKGROUND: Atherosclerosis is the leading cause of cardiovascular disease-related morbidity and mortality. The traditional Chinese medicine Qingre Sanjie Formula (QRSJF), composed of Prunellae Spica, Sargassum, Fritillariae Thunbergii Bulbus, Leonuri Herba, and Forsythiae Fructus, has shown efficacy in treating cardiovascular diseases, although its mechanisms are unclear.PURPOSE: This study aimed to explore the protective effects of QRSJF against atherosclerosis and the mechanisms involved.METHODS: The composition of QRSJF was analyzed using Ultra Performance Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry. An 8-week high-fat diet (HFD)-induced atherosclerosis model was established in ApoE-/- mice. Following model induction, mice received 12 weeks of QRSJF treatment at high- and low doses (3.16 and 1.58 g drug/kg/day, respectively) via oral gavage, while simvastatin (2.6 mg/kg/day) as the positive control. Various techniques, including biochemical assays, vascular ultrasonography, histopathology, untargeted metabolomics, and molecular biology techniques were utilized to evaluate therapeutic effects. The underlying mechanism was investigated in vitro using free fatty acids -induced HepG2 cells.RESULTS: Both low- and high-dose QRSJF effectively attenuated dyslipidemia and decreased serum inflammatory cytokine levels in HFD-fed ApoE-/- mice. In addition, QRSJF alleviated atherosclerotic plaque formation, reduced arterial narrowing, and enhanced plaque stability. Plasma and liver metabolomic analyses further identified that ABC (ATP binding cassette) subfamily transporters and bile acid metabolism as key pathways through which QRSJF ameliorates atherosclerosis. QRSJF also alleviated liver lipid accumulation and increased the expression of liver proteins, including scavenger receptor class B type 1, low-density lipoprotein receptor, ABC subfamily A member 1, cholesterol 7α-hydroxylase (CYP7A1), ABC transporter G5/G8 (ABCG5/G8), bile salt output pump, and liver X receptor alpha (LXR-α). In vitro, QRSJF activated LXR-α expression in HepG2 cells, thereby enhancing the expression of the downstream targets, CYP7A1 and ABCG5/8, and reducing free fatty acid-induced lipid accumulation. Notably, the beneficial effects of QRSJF were abrogated by the LXR-α inhibitor GSK2033.CONCLUSION: QRSJF improves dyslipidemia and reduces atherosclerotic plaque in ApoE-/- mice by activating the LXR-α/ABCG5/G8 pathway. This facilitates cholesterol transport to the liver and promotes bile acid synthesis and cholesterol excretion into the bile and intestine, thereby exerting anti-atherosclerotic effects.PMID:40286749 | DOI:10.1016/j.phymed.2025.156691

Food Chem. 2025 Apr 19;484:144346. doi: 10.1016/j.foodchem.2025.144346. Online ahead of print.ABSTRACTMagnetic field technology is a cutting-edge approach for the physical preservation of foods in recent years. The impact of short-term weak static magnetic field (SWMF) stimulation on the metabolite profiles and metabolic pathways of fresh-cut young ginger (FCYG) was investigated. Results showed that fresh-cut treatment (0 mT) caused large losses of volatile terpenes, increases in primary metabolite abundance, and alterations of secondary bioactive component composition in the FCYG. The 5 mT SWMF treatment better retarded these changes and its metabolite profiles were closest to the control sample. These results could be attributed to the inhibition of the respiration and energy-related pathways, i.e. glycolysis, TCA cycle, pentose phosphate pathway, carbon fixation in photosynthetic organisms, and purine metabolism in the FCYG. The suppression was linked to the significant reduction in the precursors and intermediates of key metabolic pathways. These findings could provide theoretical basis and technical reference for controlling FCYG quality.PMID:40286722 | DOI:10.1016/j.foodchem.2025.144346

Food Chem. 2025 Apr 22;484:144488. doi: 10.1016/j.foodchem.2025.144488. Online ahead of print.ABSTRACTPineapples suffer significant postharvest losses due to browning and quality decay. Chitosan-acetic acid coatings enhance shelf life, yet their metabolic mechanisms remain unclear. This study examined the impact of 1.5 % (m/V) chitosan-acetic acid composite coatings on pineapple storage quality and metabolite profiles under ambient (25 °C) and cold chain (4 °C) conditions via GC-MS analysis. At 25 °C on the 21st day of the study, treated pineapples retained 12.57 % total soluble solids (TSS), compared to 9.28 % in untreated fruits. On day 9, treated fruits at 25 °C showed a notably higher ascorbic acid concentration (73.15 mg/100 g) compared to other groups (p < 0.05), and the ascorbic acid concentration was always at the highest level in the early storage period (9 - 15d). KEGG pathway analysis indicated the coatings maintained postharvest quality by sustaining key indicators (TSS, TA, ascorbic acid), elucidating the mechanism by which chitosan-acetate coating preserves pineapple storage quality.PMID:40286719 | DOI:10.1016/j.foodchem.2025.144488

Food Chem. 2025 Apr 20;484:144428. doi: 10.1016/j.foodchem.2025.144428. Online ahead of print.ABSTRACTEnzyme-mediated production of bioactive compounds has gained significant attention, with carboxylesterase-catalyzed strategy previously showing promise for enriching non-acylated anthocyanin cyanidin-3-diglucoside-5-glucoside (Cy3diG5G). This study investigated the transformation mechanisms underlying the enrichment of Cy3diG5G from red cabbage extracts. The primary pathways involved include deacylation, deglycosylation, and degradation, mediated by carboxylesterase and natural biochemical reactions. Kinetic modeling revealed that the formation of non-acylated anthocyanins, including Cy3diG5G, follows a two-phase piecewise model. During the initial 8 min, carboxylesterase-driven processes dominated, leading to a rapid accumulation of Cy3diG5G. However, as the reaction progressed, intrinsic degradation processes became more pronounced, ultimately stabilizing the Cy3diG5G content. These findings provide deeper insights into anthocyanin accumulation mechanisms and offer valuable guidance for optimizing enzyme-mediated production processes, enabling more efficient and controlled anthocyanin enrichment.PMID:40286714 | DOI:10.1016/j.foodchem.2025.144428

J Hazard Mater. 2025 Apr 23;493:138391. doi: 10.1016/j.jhazmat.2025.138391. Online ahead of print.ABSTRACTRecent studies underscored the toxicity of microplastics (MPs) as vectors for cadmium (Cd) in soil-plant systems, yet the driven potential of soil fauna in real-world environments remains overlooked. This study examined the interactive effects of earthworms and polylactic acid (PLA) MPs (0.5 % w/w) on rhizosphere biochemistry and Cd (2 mg/kg)-induced phytotoxicity in radish. The combined treatment of earthworms and PLA MPs significantly increased the soil available Cd (diethylenetriaminepentaacetic acid -extractable Cd) from 0.79 mg/kg to 1.01 mg/kg compared to the Cd treatment (p < 0.05) and enhanced the bacterial network stability. Cd accumulation in radish was significantly elevated under the combined treatment (roots: 2.04 mg/kg; leaves: 12.31 mg/kg) compared to the Cd treatment (roots: 1.59 mg/kg; leaves: 8.82 mg/kg) (p < 0.05). The combined treatment activated the radish antioxidant system. The combined treatment (roots: 6.08 g; leaves: 1.65 g) significantly reduced radish biomass compared to the Cd treatment (roots: 24.41 g; leaves: 4.45 g) (p < 0.05). Metabolic pathways involving lipid and carbohydrate metabolism, membrane transport, and secondary metabolite biosynthesis were disrupted. Structural equation modeling identified rhizosphere soil properties (pH, SOM, and CEC) as well as Cd and antioxidant systems in the leaf as major contributors to radish growth inhibition.PMID:40286655 | DOI:10.1016/j.jhazmat.2025.138391

Sci Total Environ. 2025 Apr 25;979:179484. doi: 10.1016/j.scitotenv.2025.179484. Online ahead of print.ABSTRACTEnvironmental stressors in the modern world can fundamentally affect human physiology and health. Exposure to stressors like air pollution, heat, and traffic noise has been linked to a pronounced increase in non-communicable diseases. Specifically, aircraft noise has been identified as a risk factor for cardiovascular and metabolic diseases, such as arteriosclerosis, heart failure, stroke, and diabetes. Noise stress leads to neuronal activation with subsequent stress hormone release that ultimately activates the renin-angiotensin-aldosterone system, increases inflammation and oxidative stress thus substantially affecting the cardiovascular system. However, despite the epidemiological evidence of a link between noise stress and metabolic dysfunction, the consequences of exposure at the molecular, metabolic level of the cardiovascular system are largely unknown. Here, we use a murine model system of short-term aircraft noise exposure to show that noise stress profoundly alters heart metabolism. Within 4 days of noise exposure, the heart proteome and metabolome bear the hallmarks of reduced potential for generating ATP from fatty-acid beta-oxidation, the tricarboxylic acid cycle, and the electron transport chain. This is accompanied by the increased expression of glycolytic metabolites, including the end-product, lactate, suggesting a compensatory shift of energy production towards anaerobic glycolysis. Intriguingly, the metabolic shift is reminiscent of what is observed in failing and ischaemic hearts. Mechanistically, we further show that the metabolic rewiring is likely driven by reactive oxygen species (ROS), as we can rescue the phenotype by knocking out NOX-2/gp91phox, a ROS inducer, in mice. Our results suggest that within a short exposure time, the cardiovascular system undergoes a fundamental metabolic shift that bears the hallmarks of cardiovascular disease. These findings underscore the urgent need to comprehend the molecular consequences of environmental stressors, paving the way for targeted interventions to mitigate health risks associated with chronic noise exposure in modern, environments heavily disturbed by noise pollution.PMID:40286622 | DOI:10.1016/j.scitotenv.2025.179484

Environ Int. 2025 Apr 23;199:109495. doi: 10.1016/j.envint.2025.109495. Online ahead of print.ABSTRACTHeat exposure has been identified as a significant contributory factor in the development of cardiovascular diseases, but the biological mechanisms are not yet fully elucidated. We conducted a randomized crossover trial in healthy adults in Shanghai, China. Each subject was alternatively exposed to moderate temperature (22 °C) and elevated temperature (32 °C) in a chamber for 2 h in random order. Blood pressure (BP) and arterial stiffness were measured before and after each exposure session. Genome-wide DNA methylation, untargeted serum proteomics, metabolomics, and 15 targeted serum biomarkers were analyzed. Linear mixed-effects models were used to analyze the data. The pathway enrichment was performed at the ingenuity pathway analysis platform. The network-based xMWAS analysis was further conducted. A total of 30 participants (15 males and 15 females) completed the trial, with an average age of 21.7 ± 1.5 years. Heat exposure was associated with higher pulse wave velocity (4.4 %, 95 % CI: 0.2, 6.8), augmentation index normalized to 75 bpm heart rate (190.7 %, 95 % CI: 19.0, 362.3) and reflection magnitude (35.9 %, 95 % CI: 12.3, 59.5). Exposure to heat was significantly associated with changes in 2 biomarkers on systemic inflammation, 2 on oxidative stress, 1 on coagulation, 2 on lipid metabolism, and 2 on atherosclerotic alterations. Multi-omics analyses indicated heat-induced perturbations in pathways were mostly related to systemic inflammation, oxidative stress, coagulation, and lipid metabolism disorder. Acute heat exposure might impair cardiovascular function and promote multiple adverse biological processes, especially those related to atherosclerosis progression and increase of plaque instability.PMID:40286558 | DOI:10.1016/j.envint.2025.109495

J Chromatogr B Analyt Technol Biomed Life Sci. 2025 Apr 19;1259:124600. doi: 10.1016/j.jchromb.2025.124600. Online ahead of print.ABSTRACTTotal glucosides of paeony (TGP), an active ingredient extracted from the dried root of Paeonia lactiflora Pall., has been approved in China for the treatment of various autoimmune diseases. However, the role and mechanism of TGP in UC have yet to be fully elucidated. This study aims to investigate the regulatory effects and underlying mechanisms of TGP on intestinal homeostasis disruption and immune imbalance in a mouse model of dextran sulfate sodium (DSS)-induced colitis. The results showed that TGP alleviated DSS induced body weight loss, colonic shortening and histopathological changes in mice, and also enhanced the integrity of the intestinal barrier by up-regulating the expression of ZO-1, Occludin and tight junction protein in the colon. The results of 16S and antibiotic cocktail (ABX) experiments showed that TGP alleviated colitis by inhibiting Th17 cell differentiation by correcting intestinal microbial imbalance in UC mice. Mechanism studies showed that TGP inhibited the activation of JAK2/STAT3 signaling pathway in UC mice, and decreased the levels of inflammatory factors in colon supernatant and serum. Importantly, TGP regulates JAK2/STAT3 to inhibit Th17 cell differentiation depending on gut flora. In addition, TGP can also improve the metabolic imbalance in UC mice, especially purine metabolism. In conclusion, TGP promotes the normalization of purine metabolism and relies on gut microbiota to regulate JAK2/STAT3 pathway, inhibit Th17 cell differentiation, and alleviate colitis. Our findings highlight TGP as a promising treatment candidate for ulcerative colitis.PMID:40286482 | DOI:10.1016/j.jchromb.2025.124600

Plant Physiol Biochem. 2025 Apr 17;224:109935. doi: 10.1016/j.plaphy.2025.109935. Online ahead of print.ABSTRACTCotton (Gossypium spp.) originated in tropical and subtropical regions, spreading to higher latitudes through domestication while retaining thermophilic characteristics. Xinjiang, a major cotton-producing area in China, frequently experiences 'late spring cold snaps' due to its location, causing chilling injury during critical sowing periods. Current research on cotton chilling stress primarily focuses on physiological studies such as evaluations of chilling stress and biochemical indices but lacks systematic investigation into the difference among varieties. Phenotypic screening across seed germination, cotyledon, and seedling stages identified upland cotton (Gossypium hirsutum) cultivar, Junmian1 exhibits superior cold tolerance relative to the sensitive genotype C1470. Under chilling stress, Junmian1 protects chloroplasts and other cellular structures in its first true leaf to survive the chilling stress. Weighted gene co-expression network analysis (WGCNA) analysis pinpointed Module Brown as a chilling-tolerance responsive hub, with subsequent validation via virus-induced gene silencing (VIGS) confirming the regulatory roles of GhRBL (Ribulose-bisphosphate carboxylase), GhGI (GIGANTEA), and lncRNA MSTR.1631 in cold tolerance. Additionally, integrated metabolomic and transcriptomic analyses demonstrated that jasmonic acid plays a crucial role in enhancing cotton's chilling tolerance at seedling stage. The primary difference in chilling tolerance between Junmian1 and C1470 is attributed to the signaling efficiency of the jasmonic acid synthesis and metabolism pathways. These findings establish JA metabolic engineering as a viable approach for enhancing cold resilience in early-stage cotton seedlings.PMID:40286456 | DOI:10.1016/j.plaphy.2025.109935

Molecules. 2025 Mar 27;30(7):1490. doi: 10.3390/molecules30071490.ABSTRACTAndrographis paniculata (Burm. f.) and its products have a long history of medicinal use in Asia. A. paniculata products are mainly made from the root extraction of stems, leaves and parts, but there may be differences in the proportion of different parts and different harvest times, which ultimately leads to certain differences in product quality. In this study, the chemical components and non-targeted metabolomics were characterized, and the characteristic compounds in different parts of A. paniculata at various growth stages were analyzed. By utilizing polygonal mass defect filtering, precursor ion lists, and a self-built compound library, a total of 225 components were identified in A. paniculata. Notably, spermidine derivatives and phosphatidylcholines were reported for the first time in this plant species. In total, 41 differential components were identified in different parts of A. paniculata. These findings provide scientific evidence for the selection of quality markers in A. paniculata and its products.PMID:40286081 | DOI:10.3390/molecules30071490