PubMed

Sci Rep. 2026 Apr 10;16(1):11992. doi: 10.1038/s41598-026-39689-9.NO ABSTRACTPMID:41963383 | DOI:10.1038/s41598-026-39689-9

NPJ Sci Food. 2026 Apr 10. doi: 10.1038/s41538-026-00836-1. Online ahead of print.ABSTRACTLingmu tea, produced from Eurya alata Kobuski leaves, is a traditional non-Camellia sinensis tea, yet the chemical basis underlying its quality formation during green tea-type processing remains unclear. This study systematically investigated the effects of processing on sensory quality, chemical composition, and antioxidant capacity of Lingmu tea. Processed tea exhibited a bright orange-yellow infusion, a mellow and umami-dominant taste, and a mature, harmonious aroma characterized by chestnut-like, sweet, woody, and floral notes. Green tea-type processing increased total phenolic content from 183.20 to 224.59 mg/g and total flavonoid content from 87.31 to 120.11 mg/g. Metabolomic analysis revealed significant remodeling of non-volatile metabolites, characterized by flavonoid enrichment and catechin reduction. The major aroma contributors (ROAV > 1), included linalool, 1-octen-3-one, dimethyl sulfide, nonanal, and ethanol, with their dominant contributors differing markedly between fresh leaves and processed tea. Antioxidant capacity was functionally redistributed after processing: DPPH and superoxide anion scavenging activities decreased, whereas total antioxidant capacity increased substantially (from 208.31 to 346.77 μmol/g), while hydroxyl radical scavenging activity showed no significant difference. Overall, this study elucidates the chemical basis of quality formation in Lingmu tea and supports its evaluation, development, and standardization as a functional specialty tea.PMID:41963378 | DOI:10.1038/s41538-026-00836-1

NPJ Sci Food. 2026 Apr 10. doi: 10.1038/s41538-026-00837-0. Online ahead of print.ABSTRACTAuthenticating specialty tea products remains a critical challenge in premium food markets, yet current analytical approaches are constrained by limited reproducibility and susceptibility to instrumental variation. Here, we present a deep learning framework that transforms liquid chromatography-mass spectrometry (LC-MS) metabolomic data into image representations, enabling robust authentication of tea products under real-world analytical conditions. Profiling 274 Tieguanyin tea samples across seasonal harvests (spring and autumn) and processing methods (light-scented and strong-scented), our approach achieved 90.9% (95% confidence interval [CI]: 80.4%-96.0%) classification accuracy-substantially outperforming conventional multivariate and machine learning methods (sPLS-DA: 85.5%; random forest: 87.3%). Critically, when subjected to chromatographic drift-a pervasive source of analytical irreproducibility-our model maintained 78.2% accuracy while traditional methods degraded to 69.1%. This framework addresses fundamental limitations in untargeted metabolomics, offering a generalizable solution for food authentication that extends beyond tea to broader applications in agricultural product verification and systems biology.PMID:41963366 | DOI:10.1038/s41538-026-00837-0

Trends Cell Biol. 2026 Apr 9:S0962-8924(26)00039-5. doi: 10.1016/j.tcb.2026.03.008. Online ahead of print.ABSTRACTFerroptosis is a cell death process defined by the iron-mediated peroxidation of membrane phospholipids that overwhelms the cell's innate antioxidant capabilities. Sitting at the nexus of iron, lipid, reactive oxygen species stress responses, and cellular metabolism, ferroptosis is intricately tied to these pathways. The burgeoning field of cancer metabolism has revealed that cancer cells exhibit changes in ferroptosis-relevant metabolic pathways, thereby opening an important avenue of investigation into whether tumors can have characteristic metabolic alterations that render them exquisitely sensitive to ferroptotic cell death. In this review, we highlight recent findings in the metabolic pathways linking ferroptosis and oncogenesis, as well as implications for future cancer therapeutic strategies.PMID:41963164 | DOI:10.1016/j.tcb.2026.03.008

J Clin Lipidol. 2026 Mar 14:S1933-2874(26)00076-0. doi: 10.1016/j.jacl.2026.03.003. Online ahead of print.ABSTRACTBACKGROUND: Childhood obesity is associated with lifelong metabolic risk, yet depot-specific alterations in adipose tissue metabolism during early life remain poorly understood.OBJECTIVE: This study aimed to characterize the metabolic differences between subcutaneous (sWAT) and visceral (vWAT) white adipose tissue in pediatric obesity using untargeted metabolomics.METHODS: Adipose tissue samples were collected from 12 children with overweight/obesity (OW/OB) and 18 who were of normal weight (NW). Untargeted metabolomics was performed using capillary electrophoresis-mass spectrometry to profile polar metabolites in sWAT and vWAT, and free fatty acids (FFAs) were analyzed using liquid chromatography-mass spectrometry.RESULTS: Comparison of children with OW/OB vs NW revealed pronounced depot-specific heterogeneity. vWAT in children with OW/OB exhibited 24 significantly altered metabolites compared with NW controls. This visceral profile was characterized by elevated ketone bodies (3-hydroxybutyrate and acetoacetic acid), tricarboxylic acid cycle intermediates (citric and pyruvic acids), and long-chain FFAs (palmitic and oleic acids). Concurrently, amino acid imbalances, specifically elevated leucine and arginine but reduced histidine and carnosine, suggested heightened mitochondrial stress and inflammation. In contrast, sWAT from children with OW/OB showed fewer variations (12 metabolites), defined primarily by elevated glutamate, leucine, and short-chain FFAs, reflecting a milder metabolic disruption. Direct comparison between depots revealed that vWAT was enriched in amino acids and carnitine, while sWAT showed relatively higher levels of glycolytic and ketone body intermediates in NW conditions.CONCLUSION: Depot-specific metabolic differences are evident in pediatric obesity. vWAT in children with OW/OB displays a metabolic profile consistent with heightened lipotoxicity and mitochondrial stress, whereas sWAT exhibits fewer, less pronounced metabolic differences.PMID:41963120 | DOI:10.1016/j.jacl.2026.03.003

Food Microbiol. 2026 Sep;138:105088. doi: 10.1016/j.fm.2026.105088. Epub 2026 Mar 18.ABSTRACTDry aging enhances meat quality, yet the interplay between microbial communities and metabolite composition remains insufficiently understood. To address this, we investigated the microbial and metabolomic shifts during low-temperature dry aging of black pig loins to identify key drivers of flavor development. Black pig loins were aged at 2 ± 1 °C temperature and 75 ± 10% humidity for 4 weeks. After the aging process, increased meat elasticity and free amino acid content were associated with significant improvements in quality. Integrated microbial and metabolomic analysis revealed a strong positive correlation between Debaryomyces abundance and key flavor-active metabolites, specifically those derived from amino acid metabolism. This pinpointed Debaryomyces as a primary metabolic driver. To validate these functions, Debaryomyces hansenii strains OFMDh-412 and OFMDh-413, isolated from naturally dry-aged pork, were used as starter cultures. This targeted intervention significantly enhanced flavor development, increased total free amino acid content, and confirmed the role of these strains in flavor formation. In conclusion, this study provided evidence that the targeted application of D. hansenii demonstrated potential as a starter culture for dry-aged pork, enhancing flavor development and meat quality. These findings highlight the significance of microbe-metabolite interactions in flavor development and support the development of innovative dry-aging strategies to produce high-value meat products.PMID:41963061 | DOI:10.1016/j.fm.2026.105088

Food Microbiol. 2026 Sep;138:105072. doi: 10.1016/j.fm.2026.105072. Epub 2026 Mar 16.ABSTRACTTargeted enrichment of tocopherols in fungal fermentation systems remains a significant metabolic engineering challenge. This study presented a novel strategy employing homogentisic acid (HGA) modulation to efficiently enhance tocopherol production in the M. purpureus-fermented coix seed (MFCS) system. Three strategies of exogenous HGA supplementation (Exo-HGA), endogenous HGA accumulation (End-HGA), and the combination of exogenous HGA supplementation and endogenous HGA accumulation (Exo + End-HGA) were systematically investigated. While End-HGA optimally promoted lovastatin, pigment, and biomass, the Exo + End-HGA strategy (supplemented with 250 μg/mL Exo-HGA) achieved superior tocopherol enrichment. The contents of total, α-, and γ-tocopherol reached 225.407, 64.022, and 161.385 μg/mL, respectively, corresponding to a 1.86-fold increase in total tocopherol compared with the control group. A total of 2425 differentially expressed metabolites were identified. The significant accumulation of HGA, concomitant increases in γ-tocotrienol and menatetrenone (VK2), along with a decline in ubiquinone precursors such as 4-hydroxybenzoic acid derivatives, suggested that HGA specifically activated the tocopherol biosynthesis pathway. KEGG pathway analysis further revealed that HGA upregulated the shikimate and methylerythritol phosphate/mevalonate (MEP/MVA) pathways, thereby coordinating the redistribution of carbon flux and repressing competing routes such as phenylpropanoid and alkaloid biosynthesis, ultimately facilitating tocopherol enrichment. This study elucidated the metabolic network underlying HGA-mediated tocopherol enrichment in MFCS, providing a the oretical foundation and potential targets for enhancing tocopherol production through microbial metabolic engineering strategies.PMID:41963045 | DOI:10.1016/j.fm.2026.105072

Food Microbiol. 2026 Sep;138:105066. doi: 10.1016/j.fm.2026.105066. Epub 2026 Feb 24.ABSTRACTSpore-forming Bacillus species, including pathogenic Bacillus cereus and spoilage-associated Bacillus subtilis, are major contributors to foodborne illness and product degradation. Understanding their metabolic behaviour in diverse food matrices is essential for improving risk assessment, spoilage prediction, and fermentation control. This study integrates isothermal microcalorimetry and targeted metabolomics to characterize the metabolic activity of B. cereus and B. subtilis in five nutrient sources: Brain Heart Infusion (BHI) medium, oat drink, milk, pea hydrolysate, and a combined oat-pea matrix. Metabolic heat production was monitored for 24 h at 30 °C. In BHI, B. cereus exhibited a shorter lag phase (mean ± sd: 4.3 h ± 0.8) than B. subtilis (7.9 h ± 1.0) but produced less total heat. Across all food matrices, B. subtilis consistently generated more heat. The oat-pea matrix supported the highest calorimetric growth rates, surpassing oat or pea alone, and showed sugar depletion and accumulation of organic acids, indicating enhanced carbohydrate metabolism. Free amino acid release was matrix- and species-specific: B. subtilis had increased levels in oat, while B. cereus did so in pea. While B. cereus was metabolically active in all matrices, cereulide levels were matrix-dependent: 47.3 ± 1.7 ng/mL in oat, 3.0 ± 0.1 ng/mL in oat-pea, and undetectable in pea. These findings reveal clade-specific and matrix-driven metabolic strategies. This is the first study to combine calorimetry and metabolomics to evaluate Bacillus activity in plant-based and dairy matrices. This approach enhances our understanding of microbial physiology in complex food systems and provides a foundation for developing targeted strategies to improve food safety, stability, and product design.PMID:41963039 | DOI:10.1016/j.fm.2026.105066

J Appl Physiol (1985). 2026 Apr 10. doi: 10.1152/japplphysiol.01072.2025. Online ahead of print.ABSTRACTWe examined the effects of ketone monoester (KME) and carbohydrate (CHO) co-ingestion on exogenous CHO oxidation (via U-13C enriched glucose-fructose drinks), metabolomic responses and exercise capacity. In a randomised crossover design (after 36 h of CHO loading and pre-exercise meal of 12 and 2 g.kg-1, respectively), eight trained male cyclists (V̇O2max; 66 ± 7 mL.kg-1.min-1) ingested 0 g.h-1 (PLA), 120 g.h-1 CHO (CHO), or 120 g.h-1 CHO + 75 g ketone monoester (CHO + KME) during 3 h of cycling at power outputs corresponding to 95 % of lactate threshold (LT) followed by exercise to exhaustion at 150 % LT . Mean blood glucose concentrations during exercise were different between all pairwise comparisons (P<0.05) such that CHO > CHO + KME > PLA (4.9 ± 0.3, 4.4 ± 0.2, 3.7 ± 0.4 mmol.L-1, respectively). Mean exogenous CHO oxidation (1.35 ± 0.15 vs 1.50 ± 0.16 g.min-1, P<0.01) and oxidation efficiency was lower in CHO + KME (67 ± 7 %) compared to CHO (75 ± 6%, P <0.01). Exercise capacity was greater (P<0.05) in CHO (349 ± 189 s) and CHO + KME (319 ± 225 s) compared to PLA (75 ± 105 s), though no differences were evident between CHO and CHO+KME (P>0.05). Ketone monoester ingestion increased abundance of metabolites associated with carbohydrate metabolism (Glucaric acid) and protein turnover (3-Methylhistidine). We conclude that ketone monoester ingestion does not enhance exercise capacity and reduces blood glucose concentrations, exogenous CHO oxidation and oxidation efficiency when compared to CHO alone.PMID:41962970 | DOI:10.1152/japplphysiol.01072.2025

Am J Physiol Renal Physiol. 2026 Apr 10. doi: 10.1152/ajprenal.00431.2025. Online ahead of print.ABSTRACTRecent clinical trials have shown that distal nephron-acting diuretics are effective in managing fluid retention and salt-sensitive hypertension in people with chronic kidney disease (CKD). However, their use may be complicated by diuretic-induced hyponatremia. This study aimed to characterize the metabolomic effects of distal diuretics in people with CKD, including those who develop hyponatremia. Therefore, we analyzed plasma and 24-hour urine samples from a previously completed randomized controlled trial including individuals with CKD (mean eGFR 39 ± 13 ml/min/1.73 m²) treated with amiloride/hydrochlorothiazide (5 mg/50 mg daily) for two weeks. The study included 26 participants in whom we analyzed a set of targeted metabolites. Global untargeted metabolomics was performed in a subcohort of 12 participants including 4 patients who developed hyponatremia (plasma sodium <136 mmol/L) and 8 diuretic-treated controls with stable sodium levels. Distal diuretic therapy decreased plasma glutamine levels and the excretion of several tricarboxylic acid (TCA) cycle-related metabolites. Furthermore, distal diuretics significantly increased urinary ammonium excretion in the absence of hypokalemia or metabolic acidosis. Untargeted metabolomic analysis revealed 988 unique metabolites in the urine. Among those with hyponatremia, we observed a metabolomic signature of oxidative stress, likely due to altered glutamine and carnitine metabolism. These findings suggest that distal diuretics not only act locally in the distal convoluted tubule but also influence proximal tubular metabolism. In conclusion, our results highlight that distal diuretics induce significant metabolic changes in CKD, with urine metabolomics offering valuable insights into the physiological pathways and mechanisms underlying both therapeutic effects and adverse responses.PMID:41962959 | DOI:10.1152/ajprenal.00431.2025

Environ Pollut. 2026 Apr 8:128104. doi: 10.1016/j.envpol.2026.128104. Online ahead of print.ABSTRACTPhragmites australis (P. australis) has potential for wetland phytoremediation through nutrient and heavy metal accumulation; however, the molecular mechanisms underlying its tolerance to lead (Pb) remain poorly understood. This study conducted a pot experiment to investigate physiological, transcriptomic, and metabolomic responses of P. australis to a gradient of Pb concentrations (300, 400, and 500 mg/kg) over three exposure durations (50, 75, and 100 d). The results showed that Pb stress inhibited biomass accumulation in a concentration-dependent manner. The antioxidant system responded dynamically. Peroxidase (POD) activity increased to 1.00-1.29 times that of the control, whereas catalase (CAT) activity and non-enzymatic antioxidants showed temporal and concentration-dependent variations. P. australis preferentially accumulated Pb in roots, with 96-99% of root Pb localized in cell walls, accompanied by significant increases in pectin and lignin contents. Transcriptomic analysis revealed extensive gene expression reprogramming, with differentially expressed genes (DEGs) significantly enriched in pathways related to ribosome function, ABC transporters, and phenylpropanoid and glutathione metabolism. Key functional genes, including those encoding heavy metal ATPases (HMAs) and antioxidant biosynthesis, were specifically upregulated. Metabolomic analysis identified 108 significantly altered metabolites exhibiting concentration-dependent patterns. Under high Pb exposure, pronounced changes were observed in major metabolite categories, including isoprenoids, organic oxygen compounds, and fatty acyls. Integrated multi-omics analysis indicated that Pb detoxification in P. australis primarily relied on root cell wall immobilization and coordinated reprogramming of antioxidant and metabolic pathways. These findings elucidate the mechanisms underlying Pb tolerance in P. australis and provide a scientific basis for assessing its application in the phytoremediation of Pb-contaminated wetlands.PMID:41962819 | DOI:10.1016/j.envpol.2026.128104

Environ Pollut. 2026 Apr 8:128105. doi: 10.1016/j.envpol.2026.128105. Online ahead of print.ABSTRACTEutrophication and chemical pollution often co-occur in coastal ecosystems, where their combined effects impact model sentinel sessile organisms like bivalves. We investigated the interactive effects of the serotonin re-uptake inhibitor fluoxetine (FLX) and hypoxia on metabolic and reproductive processes in the blue mussel Mytilus edulis. Given the central role of serotonin in regulating bivalve metabolism and reproduction, we hypothesized that FLX, alone and combined with hypoxia, will disrupt these functions. Mussels were exposed for three weeks to environmentally relevant FLX concentrations (targets 20 and 200 ng/L, "low" and "high") under normoxia (8.8 mg O2/L) or hypoxia (0.9 mg O2/L). Metabolic and reproductive status were evaluated using histological indicators of tissue condition and gonadal development, supported by biochemical and molecular markers. FLX exposure reduced egg density and promoted digestive gland atrophy. Hypoxia accelerated gonadal development, reduced sperm density and stimulated the electron transport system activity, indicating metabolic compensation for reduced oxygen availability, while energy reserves remained stable. Molecular and metabolite responses to FLX were dependent on concentration and oxygen regime: FLX-induced changes in catecholamine (low FLX) and nucleotide metabolism (high FLX) in normoxia were absent under hypoxia condition. Hypoxia also impacted catecholamine and tricarboxylic acid cycle metabolism, but only at the low FLX concentration. Low FLX reduced mussel β-catenin expression in the gonad, but expression patterns of genes related to gonad development or apoptosis did not consistently align with histological changes, reflecting complex interactions between FLX, oxygen regime, and sex. These findings show that pharmaceutical pollution exerts context-dependent effects through interactions with hypoxia in a habitat-forming marine species.PMID:41962816 | DOI:10.1016/j.envpol.2026.128105

Metabolism. 2026 Apr 8:156602. doi: 10.1016/j.metabol.2026.156602. Online ahead of print.ABSTRACTOBJECTIVE: The basis for protein synthesis is the genetic code. Many of these proteins will affect intermediary metabolites by acting as enzymes, hormones, or by other actions. The aim of the present study was to assess the relationships of a large number of proteins with endogenous metabolites.METHODS: Plasma protein levels were measured by the proximity extension assay (PEA) and metabolites by mass spectrometry. Cross-sectional relationships of 242 proteins and 790 metabolites were evaluated in the EpiHealth and POEM studies using a discovery/validation approach. Genetic instruments identified in UK Biobank for protein levels (n = 1621) and genetics for metabolite levels (n = 777) in SCAPIS and EpiHealth were employed for Mendelian randomization (MR) analysis regarding putative causal associations.RESULTS: In the observational analyses, 20% of the evaluated pairwise protein-metabolite associations were found significant in both the discovery and validation samples. We could however only find support for causal effects in the MR analysis for <0.1% of the pairwise associations, representing 326 unique proteins. The R2 for the relationship between the MR and observational estimates was only 0.05. 37 protein-metabolite relationships that were significant in a congruent fashion in both the observational and MR analyses were identified. A searchable online protein vs metabolite atlas was created for the scientific community to use these results. We also give some examples where metabolites were used to enhance protein findings in cardiovascular epidemiological research.CONCLUSION: This study provides a comprehensive assessment of a large number of protein- metabolite relationships using both observational and MR analyses, highlighting how these results could be used to enhance clinical research.PMID:41962653 | DOI:10.1016/j.metabol.2026.156602

Diabetes Res Clin Pract. 2026 Apr 8:113255. doi: 10.1016/j.diabres.2026.113255. Online ahead of print.ABSTRACTDiabetic foot ulcers (DFUs) are devastating complications of diabetes, defined by impaired healing, high amputation rates, and substantial mortality, with pathogenesis rooted in interconnected metabolic, immune, and vascular dysregulation. Serum metabolomic profiling identifies elevated branched-chain amino acid (BCAA) levels in DFU patients, yet the metabolic mechanisms linking BCAA dysregulation to DFU remain unexplored. This review systematically presents a causal framework: impairment of the BCAA metabolic process (downregulation of BCKDH in skeletal muscle/fat tissue), dysbiosis of the intestinal microbiota leading to systemic accumulation of BCAA, and subsequent activation of the mTORC1/NF-κB signaling cascade. This triggers insulin resistance, mitochondrial dysfunction, and oxidative stress, causing macrophages to polarize to the pro-inflammatory M1 phenotype, disrupting the functions of NK cells and neutrophils, and inhibiting angiogenesis mediated by HIF-1α/VEGF forming a self-perpetuating metabolic-immune-vascular vicious cycle, thereby delaying the wound healing process. This review aims to provide a metabolism-centered framework for understanding the pathogenesis of DFU and for informing future diagnostic and therapeutic research.PMID:41962631 | DOI:10.1016/j.diabres.2026.113255

Chem Biol Interact. 2026 Apr 8:112080. doi: 10.1016/j.cbi.2026.112080. Online ahead of print.ABSTRACTGlutathione (GSH) is an abundant antioxidant which maintains intracellular redox homeostasis by scavenging excess reactive oxygen species to abate oxidative stress. Previous studies have reported lowered GSH synthesis enzyme expression and GSH content in type 2 diabetic (T2D) islets. However, whether impairment to endogenous GSH synthesis and subsequent lowering of GSH content can be implicated in the progressive loss of β cell function in type 2 diabetes, independent of glucolipotoxicity remains unclear. This study sought to determine the impact of endogenous GSH synthesis on β cell function. Glutamate-cysteine ligase catalytic subunit (GCLC) is essential for GSH synthesis. To induce GSH deficiency, GCLC was inhibited in INS-1 (832/13) cells using buthionine sulfoximine (BSO). The 24-hour treatment of INS-1 cells with BSO (250 μM) reduced GSH content to 33% of untreated, however, GSIS was unchanged. INS-1 cells require culture medium which contains 2-Mercaptoethanol (BME) to artificially bolster the cellular redox state. We removed BME from the cell culture medium to determine if further lowering of GSH content altered insulin secretion. The 24-hour treatment of INS-1 cells with BME-free medium containing BSO further reduced GSH levels to 9% of untreated and elicited significantly higher basal insulin secretion. As expected, the concentration of reduced GSH, concentration of oxidized GSH (GSSG), the total GSH pool, redox state of the GSH/GSSG redox couple, and relative redox potential were significantly lower. We find that >90% GSH-deficiency induced basal hyperinsulinemia, independent of significant transcriptomic or metabolomic alteration. These results suggest endogenous GSH synthesis is directly related to β cell function. Additionally, basal hyperinsulinemia is a poorly-understood early change to β cell function in T2D, we provide a useful model for further investigation regarding the control that cellular redox state has over basal hyperinsulinemia.PMID:41962617 | DOI:10.1016/j.cbi.2026.112080

J Ethnopharmacol. 2026 Apr 8:121668. doi: 10.1016/j.jep.2026.121668. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Helicobacter pylori (H. pylori)infection represents the most significant pathogenetic factor for chronic gastritis (CG) and is also the most critical controllable risk factor for the prevention of gastric cancer. Lianpuyin Jiawei Decoction (LPYJWD), a traditional formula originating from Traditional Chinese medicine , has been used to treat H. pylori-induced gastric disorders. Studies have shown that LPYJWD effectively reduce H. pylori-induced gastric mucosal inflammation and improve gastric mucosal damage. However, the potential pharmacological mechanism of LPYJWD requires further elucidation.AIM OF THE STUDY: The present study explored the potential mechanism of LPYJWD in treating H. pylori-induced CG.MATERIALS AND METHODS: The components of LPYJWD entering the bloodstream were identified using UPLC-MS/MS. The H. pylori-induced CG model mice were established by NaHCO3 and suspension of H. pylori bacteria. Network pharmacology, transcriptome, and Metabolomic analyses were integrated to systematically clarify the underlying mechanism of action of LPYJWD against H. pylori-induced CG. Real-time quantitative PCR and Western blot were performed to validate the key mechanisms.RESULTS: LPYJWD was found that 38 potential drug components may exert therapeutic effects. LPYJWD alleviate gastric mucosal inflammation and improve gastric tissue damage of H. pylori-induced CG mice. Metabolomic analysis indicated that LPYJWD affects metabolic pathways, including glycolysis, pentose phosphate, arginine, arachidonic acid, and glycerophospholipid metabolism in gastric mucosal epithelial cells. Network Pharmacology and transcriptome analysis indicated that the LPYJWD may exert therapeutic effects through signaling pathways involving IL-17, TNF, NLRP3, and NF-κB. Further experimental results validated that LPYJWD improves gastric mucosal inflammation through inhibiting the IL-17/NF-κB/NLRP3/ signaling pathway.CONCLUSION: Our findings demonstrated that the potential therapeutic benefits of LPYJWD in ameliorating H. pylori-induced CG by targeting the IL-17 signaling pathway, thereby facilitating a more extensive use of LPYJWD in H. pylori-induced CG.PMID:41962612 | DOI:10.1016/j.jep.2026.121668

J Ethnopharmacol. 2026 Apr 8:121663. doi: 10.1016/j.jep.2026.121663. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Grape seed proanthocyanidin extract (GSPE), derived from Vitis vinifera L., has been used in traditional European and Mediterranean medicine to treat inflammation, vascular diseases, and wounds. Historically employed for "detoxification" and "hard lumps" (possibly tumors), its effects are now attributed to GSPE's antioxidant and antiproliferative properties. Modern studies suggest these mechanisms may underlie its potential anticancer applications, including against bladder cancer.AIM OF THE STUDY: To validate the traditional antitumor claims of grape seeds by investigating grape seed proanthocyanidin extract (GSPE) 's efficacy against bladder cancer (BCa) in vitro and in vivo, with a focus on its metabolic regulatory mechanisms.METHODS: We employed an integrated multi-omics approach combining in vitro assays (including MTT, colony formation, migration, and cell cycle/apoptosis analyses), in vivo orthotopic BCa models, and untargeted metabolomics using ultrahigh-performance liquid chromatography-Q Exactive™ mass spectrometry (UHPLC-Q-Exactive MS). Bioinformatics analysis was performed to examine inosine 5'-monophosphate dehydrogenase 1/2 (IMPDH1/2) expression in BCa tissues and evaluate their prognostic significance. Subsequently, IMPDH1 and IMPDH2 expression levels were quantified by qPCR and Western blot, and their enzymatic activity was assessed in vitro. Molecular docking was then performed to predict potential interactions between GSPE and IMPDH1/2.RESULTS: GSPE exhibited potent dose-dependent anti-tumor effects in BCa cells, suppressing proliferation, colony formation, and migration through induction of G0/G1 arrest and apoptotic cell death. In orthotopic BCa mouse models, GSPE administration achieved 82.66% tumor growth inhibition (p<0.001) without inducing systemic toxicity or bladder irritation, as confirmed by normal serum biochemistry and histopathological analysis. Untargeted metabolomic profiling identified 307 significantly altered metabolites, with purine/pyrimidine metabolism showing the most profound dysregulation. Bioinformatics analysis revealed that elevated IMPDH1/2 expression in BCa tissues correlated with poor patient prognosis. Mechanistically, GSPE both dose-dependently downregulated IMPDH1/2 expression (at mRNA and protein levels), directly inhibited their enzymatic activity, and bound to IMPDH1/2 active sites with high affinity.CONCLUSION: Our findings demonstrate that GSPE serves as a novel IMPDH1/2-targeted therapeutic agent capable of disrupting nucleotide metabolism in BCa through dual inhibition of both enzymatic function and gene expression. While the exact active form(s) in vivo require further pharmacokinetic investigation, the potent anti-tumor efficacy and exceptional safety profile of intravesical GSPE support its significant clinical potential as a phytotherapeutic agent for BCa treatment.PMID:41962611 | DOI:10.1016/j.jep.2026.121663

J Ethnopharmacol. 2026 Apr 8:121667. doi: 10.1016/j.jep.2026.121667. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Enzalutamide resistance is a major clinical bottleneck limiting the therapeutic efficacy of castration-resistant prostate cancer (CRPC). Enzalutamide treatment can exacerbate tumor hypoxia, which is a critical contributor to the development of its resistance. The traditional Chinese formula Guben Qingyuan Herbal Medicine (GBQY), coupled with enzalutamide, has demonstrated potential in delaying enzalutamide resistance. Nevertheless, its interaction with the tumor microenvironment (TME) remains insufficiently investigated.AIM OF THE STUDY: This study aims to explore the anti-tumor role and mechanism of GBQY on CRPC.MATERIALS AND METHODS: Enzalutamide-resistant prostate cancer (PC) cell models and corresponding xenograft models were established to evaluate the therapeutic efficacy of GBQY combined with enzalutamide. A hypoxia-sensitive PC xenograft model was constructed to identify hypoxic tumor cell populations in vivo. The correlation between ATP-citrate lyase (ACLY) and hypoxia-inducible factor (HIF)-1α was predicted via bioinformatics analysis and subsequently validated by chromatin immunoprecipitation (ChIP) assay. The impact of hypoxia and ACLY inhibition/knockdown on PC stem cells (PCSCs) was examined using metabolomics. Additionally, a PCSC xenograft model was used to verify the signaling pathways underlying the therapeutic action of GBQY in combination with enzalutamide.RESULTS: The combinational therapy of GBQY and enzalutamide significantly delayed the occurrence of enzalutamide resistance. This effect was mediated by alleviating tumor hypoxia, accompanied by attenuated expression of cancer stem cell (CSC) markers CD44 and CD133 in tumor tissues. Xenograft-isolated hypoxia tumor cells consisted of a larger proportion of cells exhibiting CSC-like characteristics. Under hypoxic conditions, elevated HIF-1α levels likely functioned as a transcription factor, upregulating ACLY expression. Subsequent ACLY activation induced a specific energy metabolic reprogramming (EMR), characterized by enhanced glucose uptake and pyruvate production. EMR shifted the glycolytic flux towards mitochondrial pyruvate and citrate, thereby accumulating cytosolic acetyl-CoA via ACLY activity. This metabolic phenotype facilitated β-catenin acetylation, triggering the Wnt/β-catenin signaling cascade crucial to enzalutamide resistance in PC.CONCLUSION: These findings provide preclinical evidence supporting the combined application of GBQY and enzalutamide in CRPC treatment. By elucidating the interaction between Traditional Chinese Medicine (TCM) and conventional anti-tumor therapy within TME, this study offers mechanistic insights into resistance modulation and paves the way to optimizing the precision of TCM-based therapeutic strategies in PC management.PMID:41962607 | DOI:10.1016/j.jep.2026.121667

J Chromatogr B Analyt Technol Biomed Life Sci. 2026 Apr 5;1277:125059. doi: 10.1016/j.jchromb.2026.125059. Online ahead of print.ABSTRACTSmall α-ketoacids are important metabolic intermediates that influence metabolic states associated with disease. Measuring α-ketoacid levels and labeling in stable-isotope tracing studies using chromatography coupled to mass spectrometry is sometimes challenging due to their small mass, low cellular abundance, chemical instability, and enzymatic utilization post-quenching. Chemical derivatization is often employed to increase mass-to-charge, improve chromatographic separation in complex samples, and to stabilize α-ketoacids for detection by GC- or LC-MS. Methoximation is one of the most used derivatization strategies to modify α-keto groups present on metabolic α-ketoacids for GC-EI-MS. However, methoxime groups do not significantly increase analyte mass nor contribute to retention on the mid-polar GC columns widely used for metabolic labeling studies. In this study, we evaluate different oximation reagents to improve the selective detection of small α-ketoacid oxime-TBDMS derivatives by GC-EI-MS. We find that oximation using hydroxylamine, ethoxyamine, or O-benzylhydroxylamine offer comparable performance to methoxyamine with distinct effects on column retention and main fragment ion mass-to-charge. We also demonstrate how these approaches may be applied to cell extracts. Our results highlight hydroxylamine or O-benzylhydroxylamine as preferred derivatization reagents to increase alpha-ketoacid mass-to-charge or increase column retention, respectively.PMID:41962351 | DOI:10.1016/j.jchromb.2026.125059

Phytomedicine. 2026 Mar 28;155:158135. doi: 10.1016/j.phymed.2026.158135. Online ahead of print.ABSTRACTBACKGROUND: Semen Persicae, a traditional Chinese medicine, has shown potential in alleviating metabolic dysfunction-associated fatty liver disease (MAFLD). However, the complexity of components limits its clinical application.PURPOSE: To identify the key active component of Semen Persicae responsible for attenuating MAFLD and to elucidate the underlying mechanism.METHODS: The chemical components of Semen Persicae were characterized using mass spectrometry. A high-fat diet-induced MAFLD mouse model and primary liver sinusoidal endothelial cells (LSECs) were employed. Liver histopathology was used to evaluate the efficacy and safety of amygdalin (Amy). Single-cell RNA sequencing (scRNA-seq) and untargeted metabolomics analyses of mouse livers were integrated to preliminarily investigate the mechanism. Scanning electron microscopy (SEM) and assessment of fenestration markers were used to evaluate the fenestrae status of LSECs. Cytoplasmic calcium ion (Ca2+) staining, along with measurements of prostaglandin E2 (PGE2) and inositol triphosphate (IP3) levels, was applied to assess Ca2+ overload in LSECs.RESULTS: Mass spectrometry identified Amy as a major component of Semen Persicae. In a diet-induced MAFLD mouse model, Amy treatment dose-dependently attenuated disease progression, showing therapeutic efficacy comparable to liraglutide, with marked improvements in systemic metabolic parameters and significant reductions in hepatic steatosis and inflammation. Single-cell RNA sequencing identified liver sinusoidal endothelial cells (LSECs) as the most responsive cell population, with Amy markedly reducing the abundance of capillarized LSEC states. Ultrastructural analyses further demonstrated that the reduced fenestration density observed in MAFLD was substantially restored following Amy treatment. Integrated transcriptomic and metabolomic analyses revealed that arachidonic acid metabolism and endoplasmic reticulum Ca²⁺ signaling were prominently affected by Amy. In vitro experiments further confirmed that Amy reduced elevated PGE2 and IP3 levels, thereby suppressing excessive endoplasmic reticulum Ca²⁺ release.CONCLUSION: Amy effectively ameliorates LSECs defenestration by reversing IP3-induced cytoplasmic Ca2+ overload, highlighting its potential as a plant-derived therapeutic candidate for MAFLD.PMID:41962269 | DOI:10.1016/j.phymed.2026.158135