PubMed

Plant Physiol Biochem. 2025 Mar 7;222:109742. doi: 10.1016/j.plaphy.2025.109742. Online ahead of print.ABSTRACTFinger millet (Eleusine coracana Gaertn L.) is an underutilized but nutritionally rich climate resilient food crop that is generally cultivated on marginal lands. Soil salinization is a major abiotic stress that leads to a reduction in growth and yield by affecting various physiological and metabolic processes in plants. The existence of genotypic variation for salt tolerance in finger millet indicates the possibility of crop improvement via plant breeding. The overall objective of the study was to identify metabolic changes associated with improved salt tolerance in finger millet. Understanding tolerance mechanisms plays a pivotal role in the development of elite cultivars. Based on the consensus of several phenotypic data at the germination and seedling stages, we further evaluated two accessions (IE 518 and IE 405) with morphophysiological parameters and metabolomics to dissect the salinity tolerance mechanisms in finger millet. Significant phenotypic separation of IE 518 and IE 405 for salt tolerance was reflected through differences in several physiological processes such as maximum quantum yield of photosystem II (FV/FM), net photosynthesis rate (Pn), shoot Na+ ion accumulation, and oxidative stresses (electrolyte leakage and malondialdehyde content). However, both accessions showed retention of K+ ions, which underscores the role of ion homeostasis in finger millet. Pathway enrichment analysis with the uniquely salt regulated metabolites identified key metabolic pathways such as stress signaling, biotin metabolism, energy metabolism, amino acid biosynthesis, and sugar metabolism in IE 518. An enhanced accumulation of reducing sugars (mannose and melibiose) and amino acids (L-Proline and GABA) in IE 518 under salinity suggests maintaining osmotic balance as a key tolerance mechanism in finger millet.PMID:40088583 | DOI:10.1016/j.plaphy.2025.109742

Int J Food Microbiol. 2025 Mar 12;434:111153. doi: 10.1016/j.ijfoodmicro.2025.111153. Online ahead of print.ABSTRACTSuper-chilling can extend the shelf life of high-oxygen modified atmosphere packaged (MAP) pork from 14 to 56 days compared to conventional chilling storage. The spoilage of raw pork may result from the growth of microorganisms, which ultimately release undesirable metabolites. To investigate this, the microbial and metabolic characteristics of super-chilled MAP pork were determined using 16S rRNA sequencing and untargeted metabolomics based on UHPLC-MS/MS. Dominant spoilage bacteria identified in super-chilled MAP pork (Leuconostoc, Trueperella, Carnobacterium, and Massilia) differ from those in the chilling MAP pork (Brochothrix, Pseudomonas, and Serratia). Metabolomics analysis shows that the different metabolites (DMs) in the super-chilling group contained more lipids and lipid-like molecules, while the DMs in the chilling group contained more organic acids and derivatives. WGCNA reveals that most metabolites in super-chilled MAP pork are correlated to Leuconostoc and Trueperella. According to the KEGG analysis, twenty-nine metabolic pathways were discovered as potential mechanisms underlying the spoilage of super-chilled MAP pork, encompassing lipid, amino acid, and nucleotide metabolism. Random forest analysis identified 63 critical metabolites as spoilage biomarkers, in which 43 metabolites (containing amino acids, lipids, hypoxanthine, xanthine, and nicotinic acid et al.) and 18 metabolites (containing IMP, lactate, and carbohydrate and their phosphorylated products) may be metabolites and substrates of these spoilage bacteria, respectively. This study provides new insights into the changes in microbial and metabolic characteristics that occur during the spoilage of super-chilled MAP pork.PMID:40088522 | DOI:10.1016/j.ijfoodmicro.2025.111153

J Microbiol Immunol Infect. 2025 Mar 8:S1684-1182(25)00045-3. doi: 10.1016/j.jmii.2025.03.002. Online ahead of print.ABSTRACTBACKGROUND/PURPOSE(S): Data regarding the concentrations of tenofovir-diphosphate (TFV-DP) and emtricitabine-triphosphate (FTC-TP) in the Asian population receiving pre-exposure prophylaxis (PrEP) for HIV with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) (TDF/FTC) are limited, and the associations between the frequency of TDF/FTC administration and drug concentration among people receiving on-demand PrEP remain unclear.METHODS: Fifty-seven participants receiving daily TDF/FTC and 113 participants receiving on-demand TDF/FTC were enrolled in this study. The concentrations of TFV-DP and FTC-TP were measured in dried blood spots using liquid chromatography‒mass spectrometry.RESULTS: Thirty-six (62.2 %) daily PrEP users and 38 (33.6 %) on-demand PrEP users achieved TFV-DP concentrations ≥700 fmol/punch. Higher proportions of undetectable FTC-TP were observed in participants whose TFV-DP concentrations were ≤350 fmol/punch, regardless of the frequency of TDF/FTC administration. In participants who used on-demand PrEP, the TFV-DP and FTC-TP concentrations were moderately correlated with the TDF/FTC tablets taken when sampling was performed within 12-24 h after the last dose of TDF/FTC (R = 0.63, p = 0.006 and R = 0.75, p = 0.0005). In addition, on-demand PrEP users who had received 8 tablets within the last 28 days had a median TFV-DP concentration similar to that of those participants who had received 16 tablets (544.6 vs. 556.9 fmol/punch, p > 0.99).CONCLUSIONS: These results underscore the importance of well-controlled sampling times for obtaining reliable TFV-DP and FTC-TP concentrations to estimate the adherence and effectiveness of on-demand PrEP.PMID:40087092 | DOI:10.1016/j.jmii.2025.03.002

J Biosci Bioeng. 2025 Mar 13:S1389-1723(25)00049-0. doi: 10.1016/j.jbiosc.2025.02.007. Online ahead of print.ABSTRACTIn metabolomic studies, sample collection and analysis are typically performed at separate locations, necessitating the transport and storage of samples. However, sample transport and storage conditions are often constrained by the available facilities. Specifically, metabolite levels in biological and food samples can fluctuate due to the activity of endogenous enzymes, depending on the transport and storage conditions. Therefore, in this study, we aimed to achieve metabolite stabilization during storage by sampling human plasma on silica monoliths. Silica monoliths maintained the metabolite samples in a dry state, enabling their transport and storage at high temperatures. Plasmas stored at room temperature and refrigerated were measured using gas chromatography/mass spectrometry (GC/MS), and the fluctuations in metabolites between normal storage and storage on silica monoliths were compared. As a result, fluctuations in several metabolites such as glucose and amino acids were observed during normal storage. However, these were suppressed during storage on silica monoliths. Overall, our findings highlight the efficiency of silica monoliths for sample transport and storage at high temperatures.PMID:40087073 | DOI:10.1016/j.jbiosc.2025.02.007

Nutr Metab Cardiovasc Dis. 2025 Jan 30:103880. doi: 10.1016/j.numecd.2025.103880. Online ahead of print.ABSTRACTBACKGROUND AND AIMS: To assess the associations between serum concentrations of branched-chain amino acids (BCAAs)-valine, leucine, and isoleucine-and different anthropometric markers, including leptin and adiponectin levels, as well as body composition.METHODS AND RESULTS: This cross-sectional study used data from the CoLaus|PsyCoLaus and the OsteoLaus studies in Lausanne, Switzerland. Anthropometric markers included the conicity index (CI), body roundness index (BRI), a body shape index (ABSI), body mass index (BMI), and waist circumference, among others. Grip strength was used as a proxy for muscle mass. Bivariate analysis revealed that most anthropometric markers were positively correlated with BCAA, while adiponectin levels was negatively correlated with BCAA. These correlations were generally stronger in males than in females, with the exceptions of CI, ABSI, and adiponectin. After multivariable analysis, weight and BMI showed the strongest association coefficients with BCAA in males, while in females the strongest associations were found for waist circumference and waist-to-height ratio. No significant associations were found between the ABSI and BCAA levels in males, or between grip strength and BCAA levels in females. Stepwise linear regression identified BMI in males, and waist circumference in females as the anthropometric markers most strongly positively associated with BCAA.CONCLUSION: We observed a significant difference in the association between BCAA levels and anthropometric markers by sex. BMI displayed the strongest positive association with BCAA levels in males while in females, waist circumference exhibited the strongest association.PMID:40087041 | DOI:10.1016/j.numecd.2025.103880

Food Res Int. 2025 Apr;207:116064. doi: 10.1016/j.foodres.2025.116064. Epub 2025 Feb 27.ABSTRACTLipid accumulation and metabolic disorders caused by a high-fat diet (HFD) pose significant threats to human health, and place a substantial burden on individuals and society. In this study, a novel combination comprising three traditional Chinese herbs (lotus leaf, hawthorn, and leaf of Chinese holly) and a probiotic (Bifidobacterium lactis BPL-1) (TCMP) was prepared. Then, its effects on growth performance, fat accumulation, hepatic function and gut microbiota in mice fed a high-fat diet were investigated. According to the results, TCMP significantly reduced adipose tissue fat accumulation, improved hepatic lipid metabolism, and ameliorated glucose homeostasis in HFD-fed mice. Notably, TCMP not only improved the abundance and diversity of gut microbiota and increased the content of beneficial intestinal bacteria related to lipid metabolism (especially Bifidobacterium animalis), but also increased the production of short-chain fatty acids, including2-methylbutyrate, isovaleric acid and isobutyric acid. Additionally, multi-omics (transcriptome and metabolome) analysis revealed that TCMP significantly inhibited the expression of genes involved in the lipid biosynthesis process and modulated the purine and glycerophospholipid metabolism caused by a high-fat diet, thereby achieving the purpose of reducing fat accumulation and regulating lipid metabolism. Taken together, our finding demonstrates the potential of TCMP as a promising therapeutic candidate for combatting obesity and lipid metabolism disorders induced by a high-fat diet.PMID:40086971 | DOI:10.1016/j.foodres.2025.116064

Food Res Int. 2025 Apr;207:116104. doi: 10.1016/j.foodres.2025.116104. Epub 2025 Feb 28.ABSTRACTHoney is a complex matrix that contains a wide range of compounds. This rich composition is influenced by diverse environmental factors, including geographic and botanical origin. Honey has been among the most commonly tampered foods worldwide, with improvements in techniques to do it. Accordingly, there is a recurring need for new techniques and methods to assess the honey's metabolic profiles to distinguish adulterated from non-tampered samples. In this sense, this study aimed to determine the chemical profiles of honey samples from the eleven agroecological zones of the Santa Catarina State (southern Brazil), collected in the 2019-2020 and 2020-2021 harvest seasons through 1D- and 2D-NMR. As a result, a series of metabolites was identified and their concentrations measured in samples. Further, the metabolomic dataset was used for building descriptive models through chemometric techniques, in order to discriminate honey samples according to their geographic and botanical origins and harvest season effect. Twenty-one metabolites were identified, with predominance of glucose and fructose in all samples. Two other carbohydrates (sucrose and maltose) were identified in lower concentrations, in addition to amino acids, organic acids, ketone, alcohol, ester, and alkaloids. No discrepant 1H NMR resonances that could indicate fraud were detected in the spectra. By PCA, it was possible to find clusters with similar geographic origins, i.e., agroecological zones, and botanical origins. In this regard, patterns of composition were detected for honey samples of Eucalyptus spp. and Hovenia dulcis species, which presented acetoin and kynurenate, respectively, in higher concentrations. Taking together, the results allowed demonstrating that NMR spectroscopy coupled to chemometrics is an effective experimental approach to characterize Brazilian honey regarding their geographic origin and season of collection, despite the huge floral diversity available in that country for bee forage.PMID:40086965 | DOI:10.1016/j.foodres.2025.116104

Food Res Int. 2025 Apr;207:116092. doi: 10.1016/j.foodres.2025.116092. Epub 2025 Feb 25.ABSTRACTHigh-fat diets contribute to obesity and metabolic disorders. Ganoderma lucidum is renowned for its abundant bioactive compounds and diverse pharmacological effects. Green tea fermented by G. lucidum (TFG) has been shown to enhance lipid-lowering activity in vitro significantly. Using UPLC-MS/MS and GC-MS/MS, we identified 78 active lipid-lowering compounds in TFG. We explored their potential targets and pathways through network pharmacology, validated by in vivo experiments. In a 4-week trial, 70 mice were randomly assigned to 7 groups: ND (normal diet), HFD (high-fat diet), PC-HFD (HFD with orlistat), NFT1 (HFD with 200 mg/kg/day non-fermented tea), NFT2 (HFD with 400 mg/kg/day NFT), TFG1 (HFD with 200 mg/kg/day TFG), and TFG2 (HFD with 400 mg/kg/day TFG). TFG treatment significantly reduced body weight, hepatic lipid droplets, and epididymal adipocyte size in mice compared to the HFD group. TFG also increased the abundance of lipid-lowering bacteria, such as Lactococcus and Lachnospirales. Liver transcriptomic and fecal metabolomic analyses revealed that TFG reduced triglyceride (TG), diglyceride (DG), monoglyceride (MG), and free fatty acid (FFA) levels and differentially regulated key genes (Dpf3, Atp5k, ND3) involved in the thermogenesis pathway. RT-PCR confirmed that TFG upregulated the mRNA expressions of AMPK, UCP1, PGC1α, and PPARγ in dorsal fat. In conclusion, TFG enhances thermogenesis via the AMPK-PGC1α pathway and increases the abundance of lipid-lowering bacteria, thereby reducing fat accumulation in mice. These findings offer insights into TFG's anti-obesity mechanisms, providing a scientific basis for developing new weight loss methods or products.PMID:40086964 | DOI:10.1016/j.foodres.2025.116092

BMJ Open Ophthalmol. 2025 Mar 13;10(1):e002103. doi: 10.1136/bmjophth-2024-002103.ABSTRACTBACKGROUND: Glaucoma, a leading cause of irreversible blindness worldwide, is characterised by retinal ganglion cell degeneration. Increasing evidence points to metabolic dysfunction, particularly mitochondrial dysfunction, as a contributing factor to glaucomatous neurodegeneration. This systematic review and meta-analysis aimed to identify key metabolic pathways and biomarkers associated with primary open-angle glaucoma (POAG).METHODS: A systematic literature search was conducted to identify studies measuring metabolites in plasma and aqueous humour from patients with POAG using metabolomics techniques. Enrichment analyses for significantly increased metabolites were conducted using MetaboAnalyst. Meta-analyses were performed using random-effects models to calculate effect sizes for metabolites reported in at least three studies.RESULTS: 17 studies involving patients with POAG were included. Pathway analysis revealed significant enrichment of the arginine and proline metabolism pathway in both aqueous humour and plasma. Additionally, the phenylalanine metabolism pathway was enriched in plasma. These pathways are associated with oxidative stress and neurodegeneration, both of which are key factors in POAG pathology. Meta-analysis identified several significantly elevated metabolites, including lysine, glutamine, alanine, histidine, carnitine and creatinine in aqueous humour, as well as methionine in plasma.CONCLUSIONS: This study underscores the central role of metabolic dysfunction in POAG, highlighting specific metabolites and pathways that could serve as biomarkers for early diagnosis and therapeutic intervention. Future research should prioritise longitudinal studies and untargeted metabolomic profiling to further deepen our understanding of metabolic changes and their contributions to glaucoma progression.PROSPERO REGISTRATION NUMBER: CRD42024512098.PMID:40086804 | DOI:10.1136/bmjophth-2024-002103

Environ Pollut. 2025 Mar 12:126050. doi: 10.1016/j.envpol.2025.126050. Online ahead of print.ABSTRACTNanoplastics pollution is a global issue, with the digestive tract being one of the first affected organs, requiring further research on its impact on intestinal health. This study involved orally exposing mice to polystyrene nanoplastics (PS-NPs) at doses of 0.1, 0.5, or 2.5 mg/d for 42 days. The effects on intestinal health were thoroughly assessed via microbiomics, metabolomics, transcriptomics, and molecular biology. Our study demonstrated that the administration of all three doses of PS-NPs resulted in increased colonic permeability, heightened colonic and peripheral inflammation, reduced levels of antimicrobial peptides, and shortened colonic length. These effects may be attributed to a reduction in the abundance of probiotic bacteria, such as Clostridia_UCG-014, Roseburia, and Akkermansia, alongside an increase in the abundance of the pathogenic bacterium Desulfovibrionaceae induced by PS-NPs. Furthermore, we underscored the crucial role of histidine metabolism in PS-NPs-induced colonic injury, characterized by a significant reduction of L-histidine, which is closely related to microbial ecological dysregulation. Corresponding to microbiota deterioration and metabolic dysregulation, transcriptome analysis revealed that PS-NPs may disrupt colonic immune homeostasis by activating the TLR4/MyD88/NF-κB/NLRP3 signaling pathway. In conclusion, this study provided novel insights into the mechanisms by which PS-NPs disrupt intestinal homeostasis through integrated multiomics analysis, revealing critical molecular pathway and providing a scientific basis for future risk assessment of nanoplastics exposure.PMID:40086783 | DOI:10.1016/j.envpol.2025.126050

J Ethnopharmacol. 2025 Mar 12:119617. doi: 10.1016/j.jep.2025.119617. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Danlou Tablet (DLP) was developed from the "Gualou-Xiebai-Baijiu decoction", as documented in the "Synopsis of the Golden Chamber" by Dr. Zhongjing Zhang. It is widely used for clinical treatment of different degrees of coronary heart disease (CHD).AIM: Clinical trials confirmed that DLP can reduce myocardial cell apoptosis and the area of myocardial infarction, as well as protect ischemic myocardium during acute myocardial infarction (AMI). This study aims to explore the potential active components of DLP in the prevention of AMI.MATERIALS AND METHODS: A mouse model of high fat and high cholesterol diets combined with myocardial infarction was used to evaluate the efficacy of DLP. Non-targeted metabolomics and transcriptomics were performed to characterize key candidate metabolic pathways for AMI process. Additionally, a series of arachidonic acid and ARA-related oxylipins were quantitatively analyzed by ultra-high performance liquid chromatogram tandem mass spectrometry. In-sillco molecular docking assays and hypoxia/reoxygenation (H/R)-induced myocardial injury model were performed to investigate the active components of DLP.RESULTS: DLP significantly decreased blood lipid levels and fat/body weight ratios. From a pathological perspective, DLP markedly improved the arrangement and morphology of cardiac myocytes in mice, and reduced myocardial fibrosis, plaque formation, and the ischemia damage. The ARA pathway plays a crucial role in the progression of AMI. The perturbed ARA metabolome was partly restored with treatment of DLP. The generation of 12-HETE mediated by lipoxygenase 12 (ALOX12) was considered as the most distinct metabolite. DLP can significantly inhibit the expression of ALOX12 gene and protein in mouse heart tissues. Further, H/R modeling led to obvious elevation of ALOX12 protein, and mirificin, daidzin, daidzein, and calycosin could significantly reduce the level of ALOX12 in H/R-induced H9c2 myocardial injury model. And these four components can also effectively drop H/R-induced apoptosis by the BCL-2/BAX pathway. Moreover, after ALOX12 protein was silenced in H/R-induced H9c2 cells, mirificin and daidzin resulted in no alterations of apoptotic ratios, while daidzein and calycosin brought obvious decline in apoptotic cells.CONCLUSION: These results indicates that mirificin and daidzin are the main DLP-related active components responsible for alleviating AMI by improving ALOX12 protein expression and the BCL-2/BAX pathway.PMID:40086610 | DOI:10.1016/j.jep.2025.119617

Eur J Pharmacol. 2025 Mar 12:177500. doi: 10.1016/j.ejphar.2025.177500. Online ahead of print.ABSTRACTRoyal jelly acid is a unique unsaturated fatty acid isolated from royal jelly. Recently, royal jelly acid was proposed to have potential therapeutic effects on hyperlipidemia. However, its effect on hyperlipidemia and the underlying molecular mechanism remains unclear. Therefore, in this study, we analyzed the mechanism of anti-hyperlipidemia of royal jelly acid through animal experiments and plasma metabolomics in conjunction with human network pharmacology and molecular docking analyses. We found that royal jelly acid could significantly decrease the serum lipid levels, ameliorate hepatic pathological injury, and reduce the level of oxidative stress in the experimental rats. A total of 41 key metabolites and 10 hub targets played key roles in the exertion of anti-hyperlipidemic effects, including tumor necrosis factor(TNF), insulin(INS) and epidermal growth factor receptor (EGFR). A total of 24 pathways, including tryptophan, citrate cycle, and arachidonic acid metabolisms, were identified as the key pathways involved in royal jelly acid-alleviated hyperlipidemia. The present findings provide new insights into the pathogenesis, diagnosis, and treatment targets of hyperlipidemia as well as contribute to the development and utilization of royal jelly acid related products.PMID:40086581 | DOI:10.1016/j.ejphar.2025.177500

Stem Cell Reports. 2025 Feb 28:102448. doi: 10.1016/j.stemcr.2025.102448. Online ahead of print.ABSTRACTMutations in mitochondrial DNA cause severe multisystem disease frequently associated with muscle weakness. The m.3243A>G mutation is the major cause of mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes (MELAS). Experimental models that recapitulate the disease phenotype in vitro for disease modeling or drug screening are very limited. We have therefore generated hiPSC-derived muscle fibers with variable heteroplasmic mtDNA mutation load without significantly affecting muscle differentiation potential. The cells exhibit physiological characteristics of muscle fibers and show a well-organized myofibrillar structure. In cells carrying the m.3243A>G mutation, the mitochondrial membrane potential and oxygen consumption were reduced in relation to the mutant load. We have shown through proteomic, phosphoproteomic, and metabolomic analyses that the m.3243A>G mutation variably affects the cell phenotype in relation to the mutant load. This variation is reflected by an increase in the NADH/NAD+ ratio, which in turn influences key nutrient-sensing pathways in the myofibers. This model enables a detailed study of the impact of the mutation on cellular bioenergetics and on muscle physiology with the potential to provide a platform for drug screening.PMID:40086445 | DOI:10.1016/j.stemcr.2025.102448

Food Chem. 2025 Mar 6;479:143783. doi: 10.1016/j.foodchem.2025.143783. Online ahead of print.ABSTRACTBanana puree, which serves as a vital intermediate raw material in the production of banana-based products, is prone to browning and aroma loss during the processing stage. This study focuses on elucidating the patterns of browning and aroma loss and investigating the mechanisms behind these phenomena, using Cavendish banana and Pisang Awak banana as subjects. The results showed that Cavendish banana exhibited superior processing suitability in terms of flavor. Through untargeted metabolomics analysis, it was found that the homogenization process affects aroma synthesis and browning pathways, particularly α-linolenic acid metabolism. Targeted metabolomics analysis further identified that the synergistic effect of multiple phenolic substances plays a crucial role in banana browning. Additionally, research indicated that adding 0.5 % cinnamic acid could effectively delay the browning of banana puree and enhance overall flavor quality by inhibiting lipoxygenase activity. This study offers a theoretical foundation for addressing bottleneck issues in the banana processing industry.PMID:40086392 | DOI:10.1016/j.foodchem.2025.143783

J Hazard Mater. 2025 Mar 12;491:137921. doi: 10.1016/j.jhazmat.2025.137921. Online ahead of print.ABSTRACTCadmium (Cd) pollution poses a growing threat to plant growth. Although glutathione (GSH) is recognized for its potential to mitigate Cd-induced stress, its specific effects on alleviating such stress in Pogostemon cablin (patchouli) remain unclear. This study investigated physiological parameters and enzymatic activities across four treatment groups: control (CK), cadmium stress (Cd), glutathione (GSH), and glutathione with cadmium stress (GSH+Cd). Results revealed that chlorophyll a, b, and carotenoid levels in the GSH were approximately 20 % higher than those in the other groups. In contrast, antioxidant enzyme activity in the Cd decreased by about 15 %. Integrated transcriptomic and metabolomic analyses demonstrated that GSH mitigates Cd stress by influencing glycerophospholipid metabolism and flavonoid biosynthesis, with key roles attributed to dgkA1, dgkA2, and CCoAOMT1-4. In conclusion, GSH alleviates Cd stress in P. cablin by enhancing photosynthetic pigment synthesis, reducing reactive oxygen species (ROS) through improved enzymatic activity, and regulating metabolic pathways. These findings provide valuable insights for optimizing the cultivation and management of P. cablin under Cd stress conditions.PMID:40086241 | DOI:10.1016/j.jhazmat.2025.137921

Bioorg Chem. 2025 Mar 9;159:108349. doi: 10.1016/j.bioorg.2025.108349. Online ahead of print.ABSTRACTThe recurrence of drug-resistant and expensive treatment drugs are major causes of the low survival rate of multiple myeloma (MM) patients. Exploring a safe, effective, low-cost and novel drug treatment for MM is a promising strategy to relieve the burden of MM patients. In this study, we found that prodigiosin could inhibit MM cell proliferation and induce MM cell apoptosis, however, it had a lesser cytotoxic effect on normal B cells within the IC50 range of MM cells. In addition, prodigiosin could inhibit the growth of xenograft MM cells in mice. Transcriptomics and targeted amino acid metabolomics confirmed that prodigiosin could regulate amino acid metabolism, and decrease in amino acid utilization by down-regulated aminoacyl tRNA synthetases expression, resulting in slower growth of MM. In conclusion, prodigiosin exerts anticancer effects on MM cells by interfering with the use of amino acids, indicating its potential novel therapeutic application in MM.PMID:40086187 | DOI:10.1016/j.bioorg.2025.108349

Plant Physiol Biochem. 2025 Mar 6;222:109766. doi: 10.1016/j.plaphy.2025.109766. Online ahead of print.ABSTRACTBanana (Musa spp.), a vital tropical fruit and food crop, faces significant challenges from cold and drought stress, which threaten its productivity. Uncovering the overlapping mechanisms of crop responses to abiotic stresses is essential for the development of multi-resistant crop varieties. This study investigates the overlapping response mechanisms of banana to cold and drought stress through integrated metabolomic and transcriptomic analyses. We conducted physiological assessments alongside these analyses to elucidate shared mechanisms. Our results showed that both cold and drought stress disrupted cell membrane stability and reduced relative water content and chlorophyll content in banana leaves. Metabolomic analysis identified 1800 annotated metabolites, with 636 and 405 differentially accumulated metabolites (DAMs) under cold and drought stress, respectively, and flavonoids represented the most abundant metabolite class. Transcriptomic analysis revealed that 5687 differentially expressed genes (DEGs) were induced under both stress conditions, with significant enrichment in pathways related to ascorbic acid, arginine, and proline metabolism. Integrating metabolomic and transcriptomic data highlighted carbohydrate, amino acid, and flavonoid metabolism as the central pathways shared in response to cold and drought stresses. Notably, while these pathways were common, specific structural genes and accumulated metabolites varied between stress types. Additionally, our results suggest that GDP-mannose is the primary ascorbate synthesis route under cold stress, whereas myo-inositol and galacturonic acid pathways dominate under drought stress. These findings enhance our understanding of banana's adaptive responses and provide a foundation for breeding multi-stress-resistant crop varieties in an era of climate change.PMID:40086128 | DOI:10.1016/j.plaphy.2025.109766

J Pharm Biomed Anal. 2025 Mar 8;260:116802. doi: 10.1016/j.jpba.2025.116802. Online ahead of print.ABSTRACTThe focus of this study is to explore the impact of gut microbiota in different states on the blood components of couplet medications (dried toad skin and radix clematidis) and to identify drug metabolites associated with the gut microbiota. By constructing a pseudo-sterile rat model and combining non-targeted metabolomics with plasma pharmacology, we found that the plasma metabolites of couplet medications underwent significant changes in different gut microbiome environments. The GABA and PGE1 levels in the model group and the model+TCM (traditional chinese medicine) group were both significantly lower than those in the normal+TCM group. When the gut microbiota is imbalanced, drug interventions cannot significantly increase the levels of GABA and PGE1. It further confirmed the correlation between the levels of GABA and PGE1 and the gut microbiota. Based on the results of non-targeted metabolomics, we applied network pharmacology and molecular docking to explore the core targets for colorectal cancer treatment based on gut microbiota. In the end, we identified TNF and PPARG as the two core targets. These research findings provide a possibility for clarifying the molecular mechanisms of couplet medications in the treatment of colorectal cancer. It also laid the foundation for further clarifying the molecular mechanisms of Chanling Paste in the treatment of colorectal cancer.PMID:40086049 | DOI:10.1016/j.jpba.2025.116802

Phytomedicine. 2025 Mar 11;140:156639. doi: 10.1016/j.phymed.2025.156639. Online ahead of print.ABSTRACTBACKGROUND: Alcohol-induced liver injury (ALI) poses a significant threat to global human health. The Chinese Yi medicine Liangtoumao (LTM), which originated from the whole plant of Incarvillea arguta Royle (Royle), has been widely used by the Yi ethnic group to prevent and treat ALI and other liver diseases. However, its effectiveness and mechanisms are still under-researched.PURPOSE: The objective of our research is to investigate the chemical composition of LTM aqueous extract, evaluate its potential therapeutic intervention effect on ALI, and explore its mechanisms in rat models.METHODS: The chemical components and constituents of LTM aqueous extract migrating to the blood were analyzed by UPLC-Q-TOF/MS. Sprague-Dawley rats subjected to chronic binge alcohol exposure were utilized to establish chronic ALI models and evaluate the therapeutic effects of LTM aqueous extract. Serum and spatial metabolomics analyses were used to investigate potential mechanisms.RESULTS: A total of 60 chemical components in LTM aqueous extract were identified, with 67 absorbed into the blood, including 29 original compounds and 38 metabolites. Treatment with LTM aqueous extract remarkably alleviated hepatic lesions in livers of ALI rats, improved liver function, reduced oxidative stress and inflammation. Serum metabolomics and hepatic spatial metabolomics identified 30 and 215 differential metabolites, respectively. Metabolic pathways of glyoxylate and dicarboxylate, glycerophospholipid, linoleic acid, taurine and hypotaurine, and cysteine and methionine were closely related to the hepaprotective effects of LTM.CONCLUSION: Our research confirmed significant effects of LTM on ALI prevention and treatment for the first time. Metabolomic findings revealed that LTM significantly influences various aspects of lipid metabolism. This study supports expanded mechanism investigations of LTM and explores its possibility as a potential ALI therapy.PMID:40085992 | DOI:10.1016/j.phymed.2025.156639

Environ Sci Technol. 2025 Mar 14. doi: 10.1021/acs.est.4c10654. Online ahead of print.ABSTRACTPer- and polyfluoroalkyl substances (PFASs) with varying chain lengths, headgroups, and alternative structures are widespread and persistent in soil, yet knowledge of their biological effects and toxic mechanisms on soil microorganisms is limited. This study identified the structure-dependent impacts of PFAS on microbial fatty acid (FA) profiles by integrated field-laboratory investigations. The field investigation uncovered distinct PFAS-FA interaction patterns, varying by PFAS fluorocarbon (FC) chain length and functional group, and FA hydrocarbon (HC) chain length and unsaturation degree. Specifically, long-chain perfluoroalkyl carboxylic acids (PFCAs, FC7-17) increased medium/long-chain FAs (HC ≤ 17) and monounsaturated FAs (MUFAs), while long-chain perfluoroalkyl sulfonic acids (PFSAs, FC6-8) enhanced longer-chain FAs (HC > 17) and MUFAs. Additionally, perfluoroether carboxylic acids (PFECAs) as well as short-chain PFCAs (FC < 7) and PFSAs (FC < 6), which commonly used as alternatives to long-chain PFCAs/PFSAs, were associated with polyunsaturated FAs (PUFAs). The laboratory investigation with Pseudomonas aeruginosa PAO1 validated these FA metabolic disruptions and revealed broader perturbations in phospholipids, acetyl-CoA, and secondary metabolite metabolisms, providing insights into dysregulated membrane synthesis, C/N metabolisms, and bacteria quorum sensing (QS) processes. These findings reveal novel structure-dependent effects of PFASs on microorganisms, highlighting microbial FA profiles as potential metabolic biomarkers for assessing PFAS toxicity and soil health.PMID:40085523 | DOI:10.1021/acs.est.4c10654