PubMed

Front Plant Sci. 2025 Jan 10;15:1523582. doi: 10.3389/fpls.2024.1523582. eCollection 2024.ABSTRACTINTRODUCTION: Melatonin significantly enhances the tolerance of plants to biotic and abiotic stress, and plays an important role in plant resistance to salt stress. However, its role and molecular mechanisms in eggplant salt stress resistance have been rarely reported. In previous studies, we experimentally demonstrated that melatonin can enhance the salt stress resistance of eggplants.METHODS: In this study, we treated salt-stressed eggplant plants with melatonin and a control treatment with water, then conducted physiological and biochemical tests, transcriptomic and metabolomic sequencing, and RT-qPCR validation at different stages after treatment.RESULTS: The results showed that exogenous melatonin can alleviate the adverse effects of salt stress on plants by increasing the activity of antioxidant enzymes, reducing the content of reactive oxygen species in plants, and increasing the content of organic osmoprotectants. Transcriptomic and metabolomic data, as well as combined analysis, indicate that melatonin can activate the metabolic pathways of plant resistance to adverse stress. Compared to the control treatment with water, melatonin can activate the genes of the α-linolenic acid metabolism pathway and promote the accumulation of metabolites in this pathway, with significant effects observed 48 hours after treatment, and significantly activates the expression of genes such as SmePLA2, SmeLOXs and SmeOPR et al. and the accumulation of metabolites such as α-Linolenic acid, (9R,13R)-12-oxophytodienoic acid, 9(S)-HpOTrE and (+)-7-iso-Jasmonic acid. RT-qPCR validated the activating effect of melatonin on the candidate genes of the a-linolenic acid metabolism pathway.DISCUSSION: This study analyzed the molecular mechanism of melatonin in alleviating eggplant salt stress, providing a theoretical foundation for the application of melatonin in enhancing eggplant salt stress resistance in production.PMID:39866315 | PMC:PMC11759302 | DOI:10.3389/fpls.2024.1523582

Front Plant Sci. 2025 Jan 10;15:1471729. doi: 10.3389/fpls.2024.1471729. eCollection 2024.ABSTRACTINTRODUCTION: This study aims to investigate the impact of geographical origin on the metabolite composition and bioactivity of Thesium chinense Turcz. (TCT), a member of the Apiaceae family renowned for its wide range of pharmacological properties, including antioxidant, antimicrobial, and anti-inflammatory effects. In this study, we investigated the whole plants of TCT from different regions in China, aiming to explore the geographical variation of TCT.METHODS: A non-targeted metabolomics approach was employed using ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were utilized to identify and differentiate the metabolite profiles. We investigated the bioactivity, antioxidant activity, total flavonoid content (TFC), and the content of characteristic compounds from TCT sourced from different regions. This aims to further explore the metabolic differences and quality characteristics of TCT from various origins.RESULTS: PCA and PLS-DA analyses indicated that samples from different origins could be clearly distinguished. The analysis revealed 54 differential metabolites, predominantly flavonoids and alkaloids. KEGG pathway analysis indicated significant variations in the biosynthesis pathways of flavonoids and flavanols among the samples. TCT from Anhui province exhibited the highest TFC and strongest antioxidant and anti-inflammatory activities, while samples from Jilin province showed the lowest.DISCUSSION: A strong correlation was observed between metabolite content and geographical origins, suggesting that the bioactivity of TCT is significantly influenced by its provenance. Additionally, the antioxidant and anti-inflammatory activities of TCT were validated, showing a strong predictive relationship with TFC. This research highlights the potential of metabolomics in discerning the subtleties of plant metabolomes, contributing to the advancement of traditional Chinese medicine and its integration into modern healthcare practices.PMID:39866314 | PMC:PMC11760594 | DOI:10.3389/fpls.2024.1471729

Front Plant Sci. 2025 Jan 10;15:1549017. doi: 10.3389/fpls.2024.1549017. eCollection 2024.NO ABSTRACTPMID:39866312 | PMC:PMC11757233 | DOI:10.3389/fpls.2024.1549017

Curr Pharm Des. 2025 Jan 24. doi: 10.2174/0113816128337697250106001808. Online ahead of print.ABSTRACTINTRODUCTION: Fungal endophytes have mutualistic associations with the plant's host, communicating through genetic and metabolic processes. As a result, they gain the ability to generate therapeutically effective metabolites and their derivatives.METHODS: The current study aims to assess antioxidant potential along with the identification of robust metabolites within the crude extract of a potent endophytic fungus Xylaria ellisii isolated from leaf tissues of the Acorus calamus Linn plant.Four endophytic fungi were obtained from leaf tissues of Acorus calamus Linn., and identified morphologically and molecularly as distinct species. Each ethyl acetate extract of the isolated fungi exhibited a unique chemical profile in the HPTLC fingerprint at various wavelengths. The ethyl acetate (EA) extract from the fungal strain ACL-4 (Xylaria ellisii) demonstrated the strongest antioxidant activity among the four fungal endophytes examined, with an EC50 value of 292.64 ± 3.558 μg/mL. Remarkably, fungal endophyte ACL-4 extract exhibited superior antimicrobial activity at the less concentrations compared to ACL-ME extract of leaf crude.RESULTS: The extract of ACL-ME-treated HEK 293T cells exhibited significant toxicity, with an IC50 value of 1481.74 ± 23.772 μg/mL, compared to fungal strain ACL-4-treated HEK 293T cells, which had an IC50 value greater than 2000 μg/mL. Consequently, the crude extract of ACL-4 and ACL-ME along with the standard drug methotrexate exhibited cytotoxic activity against cancer cell line MDA-MB-231 with IC50 concentrations of 146.65 ± 0.394 μg/mL, 528.46 ± 10.912 μg/mL, and 134.11 ± 3.446 μg/mL, respectively. A total of 2,255 compounds were detected through LC-HRMS-based metabolomics in the crude metabolites of Xylaria ellisii, with certain compounds identified in multiple instances. Among this repertoire, 62 robust bioactive compounds were identified through meticulous screening, guided by existing literature. Comparative HPTLC fingerprint analysis, along with antioxidant efficacy assays of ethyl acetate extracts of Xylaria ellisii derived from Acorus calamus leaves and Cassia fistula twigs revealed the host-specific production of bioactive chemicals.CONCLUSION: The top-scoring Keap1 inhibitors derived from Xylaria ellisii, including Pregabalin (-6.083 Kcal/mol), Ferulic acid (-5.434 Kcal/mol), (R)-Piperidine-2-carboxylic acid (-5.31 Kcal/mol), Genipin (-5.197 Kcal/mol), and Brivaracetam (-5.17 Kcal/mol), respectively were considered as Keap 1 inhibitors, potentially mitigate oxidative stress.PMID:39865823 | DOI:10.2174/0113816128337697250106001808

Biotechnol Bioeng. 2025 Jan 26. doi: 10.1002/bit.28935. Online ahead of print.ABSTRACTMicrobes experience dynamic conditions in natural habitats as well as in engineered environments, such as large-scale bioreactors, which exhibit increased mixing times and inhomogeneities. While single perturbations have been studied for several organisms and substrates, the impact of recurring short-term perturbations remains largely unknown. In this study, we investigated the response of Saccharomyces cerevisiae to repetitive gradients of four different sugars: glucose, fructose, sucrose, and maltose. Due to different transport mechanisms and metabolic routes, nonglucose sugars lead to varied intracellular responses. To characterize the impact of the carbon sources and the dynamic substrate gradients, we applied both steady-state and dynamic cultivation conditions, comparing the physiology, intracellular metabolome, and proteome. For maltose, the repeated concentration gradients led to a significant decrease in biomass yield. Under glucose, fructose, and sucrose conditions, S. cerevisiae maintained the biomass yield observed under steady-state conditions. Although the physiology was very similar across the different sugars, the intracellular metabolome and proteome were clearly differentiated. Notably, the concentration of upper glycolytic enzymes decreased for glucose and maltose (up to -60% and -40%, respectively), while an increase was observed for sucrose and fructose when exposed to gradients. Nevertheless, for all sugar gradient conditions, a stable energy charge was maintained, ranging between 0.78 and 0.89. This response to maltose is particularly distinct compared to previous single-substrate pulse experiments or limitation to excess shifts, which led to maltose-accelerated death in earlier studies. At the same time, enzymes of lower glycolysis were elevated. Interestingly, common stress-related proteins (GO term: cellular response to oxidative stress) decreased during dynamic conditions.PMID:39865609 | DOI:10.1002/bit.28935

J Exp Clin Cancer Res. 2025 Jan 27;44(1):26. doi: 10.1186/s13046-025-03295-w.ABSTRACTPURPOSE: Glucose starvation induces the accumulation of disulfides and F-actin collapse in cells with high expression of SLC7A11, a phenomenon termed disulfidptosis. This study aimed to confirm the existence of disulfidptosis in pancreatic ductal adenocarcinoma (PDAC) and elucidate the role of Cancer Susceptibility 8 (CASC8) in this process.METHODS: The existence of disulfidptosis in PDAC was assessed using flow cytometry and F-actin staining. CASC8 expression and its clinical correlations were analyzed using data from The Cancer Genome Atlas (TCGA) and further verified by chromogenic in situ hybridization assay in PDAC tissues. Cells with CASC8 knockdown and overexpression were subjected to cell viability, EdU, transwell assays, and used to establish subcutaneous and orthotopic tumor models. Disulfidptosis was detected by flow cytometry and immunofluorescence assays. RNA sequencing and metabolomics analysis were performed to determine the metabolic pathways which were significantly affected after CASC8 knockdown. We detected the glucose consumption and the NADP+/NADPH ratio to investigate alterations in metabolic profiles. RNA immunoprecipitation combined with fluorescence in situ hybridization assay was used to identify protein-RNA interactions. Protein stability, western blotting and quantitative real-time PCR assays were performed to reveal potential molecular mechanism.RESULTS: Disulfidptosis was observed in PDAC and could be significantly rescued by disulfidptosis inhibitors. CASC8 expression was higher in PDAC samples compared to normal pancreatic tissue. High CASC8 expression correlated with a poor prognosis for patients with PDAC and contributed to cancer progression in vitro and in vivo. Furthermore, CASC8 was associated with disulfidptosis resistance under glucose starvation conditions in PDAC. Mechanistically, CASC8 interacted with c-Myc to enhance the stability of c-Myc protein, leading to the activation of the pentose phosphate pathway, a reduction of the NADP+/NADPH ratio and ultimately inhibiting disulfidptosis under glucose starvation conditions.CONCLUSIONS: This study provides evidence for the existence of disulfidptosis in PDAC and reveals the upregulation of CASC8 in this malignancy. Furthermore, we demonstrate that CASC8 acts as a crucial regulator of the pentose phosphate pathway and disulfidptosis, thereby promoting PDAC progression.PMID:39865281 | DOI:10.1186/s13046-025-03295-w

Biochemistry (Mosc). 2024 Dec;89(12):2133-2142. doi: 10.1134/S0006297924120034.ABSTRACTHypoxia poses a serious challenge for all animals; however, certain animals exhibit a remarkable resilience in the case of prolonged and severe hypoxia. The Siberian wood frog Rana amurensis is a unique amphibian capable of surviving for up to several months at almost complete anoxia. We investigated changes in the metabolome of R. amurensis at the onset of hypoxia (day 1) and within 1 h of reoxygenation after a long-term hypoxia using 1H NMR. We compared our results to the data obtained for animals exposed to 17 days of hypoxia and controls. Despite the differences between the samples analyzed in three different experimental series, we were able to obtain some interesting insights. In most studied vertebrates, succinate accumulates under hypoxic conditions and undergoes rapid conversion upon reoxygenation. We found that reoxygenation caused a decrease in the succinate content in the brain, but not in the liver, where it remained unchanged, suggesting an existence of a mechanism that inhibits succinate conversion. Furthermore, we observed intriguing differences in the behavior of two substances with unknown functions: glycerol and 2,3-butanediol. Glycerol exhibited rapid accumulation during hypoxia and equally rapid processing during reoxygenation. In contrast, 2,3-butanediol required an extended period of time to accumulate, yet persisted after reoxygenation. Overall, our data demonstrate rapid accumulation of most substances during exposure to hypoxia followed by their slower processing upon reoxygenation.PMID:39865027 | DOI:10.1134/S0006297924120034

Comp Biochem Physiol C Toxicol Pharmacol. 2025 Jan 24:110134. doi: 10.1016/j.cbpc.2025.110134. Online ahead of print.ABSTRACTMicroplastics (MPs) are ubiquitous environmental pollutants that have garnered significant attention due to their small particle size, resistance to degradation and large specific surface area, which makes it easy to adsorb various pollutants, particularly heavy metals. Arsenic (As), a common metal poisons, poses significant risks due to its widespread industrial use. When MPs and As co-exist in the environment, they can exert combined toxic effects on organisms, affecting various systems, including the nervous system. However, research on the reproductive damage caused by the co-exposure to MPs and As is limited, and the toxic effects and mechanisms remain unclear. In this study, we investigated the co-exposure of polystyrene microplastics (PSMP) and As on female zebrafish to evaluate the reproductive toxicity and transgenerational effects. The results revealed that the combined exposure exhibited elevated reproductive toxicity, resulting in reduced gonadal indices, abnormal oocyte maturation, and disrupted sex hormone levels, as evidenced by an increased E2/T ratio. Metabolomics analyses revealed that the co-exposure to PSMP and As primarily affected pathways involved in aminoacyl-tRNA biosynthesis, sphingolipid metabolism, linoleic acid metabolism, galactose metabolism, and amino sugar and nucleotide sugar metabolism. These pathways are associated with oxidative stress, lipid synthesis, and sex hormone synthesis. Importantly, the combined exposure group exhibited more pronounced effects on offspring development compared to the alone treatment group, characterized by increased mortality rate, decreased hatching rate, and reduced heart rate. These findings provide evidence that co-exposure to MPs and As damages the reproductive system and adversely affects offspring growth and development.PMID:39864716 | DOI:10.1016/j.cbpc.2025.110134

Environ Pollut. 2025 Jan 24:125692. doi: 10.1016/j.envpol.2025.125692. Online ahead of print.ABSTRACTPNPLA3-I148M genotype is the strongest predictive single-nucleotide polymorphism for liver fat. We examine whether PNPLA3-I148M modifies associations between oxidative gaseous air pollutant exposure (Oxwt) with i) liver fat and ii) multi-omics profiles of miRNAs and metabolites linked to liver fat. Participants were 69 young adults (17-22 years) from the Meta-AIR cohort. Prior-month residential Oxwt exposure (redox-weighted oxidative capacity of nitrogen dioxide and ozone) was spatially interpolated from monitoring stations via inverse-distance-squared weighting. Liver fat fraction was assessed by MRI. Serum miRNAs and metabolites were assayed via NanoString nCounter and LC-HRMS, respectively. Multi-omics factor analysis (MOFA) was used to identify latent factors with shared variance across omics layers. Multivariable linear regression models adjusted for age, sex, body mass index, and genotype with liver fat or MOFA factors as an outcome and examined PNPLA3 (rs738409; CC/CG vs. GG) as a multiplicative interaction term. Overall, a standard deviation difference in Oxwt exposure was associated with 8.9% relative increase in liver fat (p=0.04) and this relationship differed by PNPLA3 genotype (p-value for interaction term: pintx<0.001), whereby relative increases in liver fat for GG and CC/CG participants were 71.8% and 2.4%, respectively. There was no main effect of Oxwt on MOFA Factor 1 expression (p=0.85), but there was an interaction with PNPLA3 genotype (pintx=0.01), whereby marginal slopes were 0.211 and -0.017 for GG and CC/CG participants, respectively. MOFA Factor 1 in turn was associated with liver fat (p=0.006). MOFA Factor 1 miRNAs targeted genes in Fatty Acid Biosynthesis and Metabolism and Lysine Degradation pathways. MOFA Factor 9 was also associated with liver fat and was comprised of branched-chain keto acid and amino acid metabolites. The effects of Oxwt exposure on liver fat is exacerbated in young adults with two PNPLA3 risk alleles, potentially through differential effects on miRNA and/or metabolite profiles.PMID:39864653 | DOI:10.1016/j.envpol.2025.125692

Clin Nutr ESPEN. 2025 Jan 24:S2405-4577(25)00047-6. doi: 10.1016/j.clnesp.2025.01.046. Online ahead of print.ABSTRACTBACKGROUND AND AIMS: Alcohol Use Disorder (AUD) is a psychiatric disorder characterized notably by gut microbial dysbiosis and insufficient dietary fiber intake. This study aims to investigate the effect of dietary fiber placebo-controlled intervention in patients suffering from AUD during a three-week period of alcohol withdrawal, in order to discover microbial-derived metabolites that could be involved in metabolic and behavioral status.METHODS: A randomized, double-blind, placebo-controlled study was performed with 50 AUD patients supplemented with inulin (prebiotic dietary fiber) or maltodextrin (placebo) during 17 days. Fecal microbiota composition, plasma and fecal metabolomics (liquid chromatography coupled to mass spectrometry), blood markers of inflammation and hepatic alterations and psychological assessment (questionnaires) were analyzed before and after the intervention.RESULTS: Fecal metabolomics revealed 14 metabolites significantly modified by inulin versus placebo treatment (increased N8-acetylspermidine and decreased indole-3-butyric acid, 5-amino valeric acid betaine (5-AVAB) and bile acids). 13 plasma metabolites differentiated both treatments (higher levels of long-chain fatty acids, medium-chain acylcarnitines and sphingomyelin species, and reduced 3-methylhistidine by inulin versus placebo). Fecal Lachnoclostridium correlated with 6 of the identified fecal metabolites, whereas plasma lipidic moieties positively correlated with fecal Ruminococcus torques group and Flavonifractor. Interestingly, parameters reflecting liver alterations inversely correlated with sphingomyelin (SM 36:2).CONCLUSIONS: Three weeks of inulin supplementation during alcohol withdrawal leads to specific and different changes in the plasma and fecal metabolome of AUD patients, some of these gut microbiota-related metabolites being correlated with liver function.TRIAL REGISTRATION: NCT03803709, https://clinicaltrials.gov/ct2/show/NCT03803709.PMID:39864520 | DOI:10.1016/j.clnesp.2025.01.046

Behav Brain Res. 2025 Jan 24:115442. doi: 10.1016/j.bbr.2025.115442. Online ahead of print.ABSTRACTNeuropathic pain (NP) is a chronic disease state centred on neuroinflammation with a high prevalence and limited effective treatment options. Peroxisome proliferator-activated receptor α (PPARα) has emerged as a promising target for NP management due to its anti-inflammatory properties. Recent evidence highlights the critical role of the gut microbiome and its metabolites in NP pathogenesis. This study aimed to investigate whether PPARα modulates the development and alleviation of NP by influencing gut microbial communities and serum metabolites. 16S rDNA sequencing and liquid chromatography-mass spectrometry (LC-MS/MS) untargeted metabolomics analyses performed 14 days after the establishment of a chronic constriction injury (CCI) pain model in C57BL/6J mice showed significant changes in gut microbial and metabolite levels in CCI mice. Intraperitoneal injection of the PPARα agonist GW7647 (5mg/kg) significantly attenuated mechanical allodynia and thermal hyperalgesia in CCI mice, whereas injection of the PPARα antagonist GW6471 (20mg/kg) produced the opposite effect. Immunofluorescence analysis revealed that GW7647 effectively suppressed microglial activation. Additionally, PPARα agonist and antagonist treatments markedly altered the composition and abundance of intestinal microbial communities in CCI mice. Further serum LC-MS/MS analysis identified 258 potential serum metabolic biomarkers, many of which correlated with changes in gut microbial composition. These findings demonstrate that PPARα influences serum metabolite profiles by modulating gut microbiota composition, which subsequently affects NP progression. This study provides novel insights into the mechanisms underlying NP and suggests potential therapeutic avenues targeting PPARα and gut microbiota.PMID:39864460 | DOI:10.1016/j.bbr.2025.115442

Comput Biol Chem. 2025 Jan 10;115:108348. doi: 10.1016/j.compbiolchem.2025.108348. Online ahead of print.ABSTRACTThis study aimed to profile metabolites from five Trichoderma strains and assess their cytotoxic and pharmacological activities, particularly targeting oral squamous cell carcinoma (OSCC). UHPLC-TOF-MS analysis revealed the presence of 25 compounds, including heptelidic acid, viridiol isomers, and sorbicillinol from the different Trichoderma extracts. Pharmacokinetic analysis showed moderate permeability and low interaction with P-glycoprotein, suggesting good drug absorption with minimal interference in cellular uptake. ADME-Tox analysis indicated limited inhibition of cytochrome P450 enzymes, low renal clearance, which are favorable for maintaining therapeutic levels. Toxicity predictions revealed some compounds with potential mutagenicity, but low hepatotoxicity and skin sensitization risks. Network pharmacology identified MAPK1 as a key target for oral cancer, and molecular docking and induced fit docking studies demonstrated strong binding affinities of Trichoderma metabolites, including stachyose and harzianol, to MAPK1. In addition, molecular dynamics (MD) simulations confirmed stable interactions. In vitro studies on NIH3T3 and YD-10B cells showed significant cytotoxicity, particularly with extracts CNU-05-001 (IC50:10.15 µg/mL) and CNU-02-009 (10.00 µg/mL) against YD-10B cells. These findings underscore the potential of Trichoderma metabolites in drug discovery, particularly for cancer therapies.PMID:39864356 | DOI:10.1016/j.compbiolchem.2025.108348

Plant Physiol Biochem. 2025 Jan 20;220:109518. doi: 10.1016/j.plaphy.2025.109518. Online ahead of print.ABSTRACTSaline-alkaline stress has caused severe ecological and environmental problems. Castor bean is a potential alkali-tolerant plant, however, its reactive oxygen species (ROS) regulatory mechanisms under alkaline stress remain unclear. This study investigated the physiological, transcriptomic, and metabolomic characteristics of two varieties (ZB8, alkaline-sensitive; JX22, alkaline-resistant) under alkaline stress. Results showed that under alkaline stress, JX22's root length was 1.66-fold greater than ZB8's, while its superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activities were 1.25-, 1.41-, and 1.29-fold higher than ZB8's, respectively. The levels of superoxide anion (O2-) and malondialdehyde (MDA) in JX22 were 0.2- and 0.68-fold of those in ZB8, respectively. Integrated transcriptomic and metabolomic analyses revealed that regarding ROS generation, alkaline stress promoted the upregulation of ACX1 and RBOHD genes in JX22, enabling more efficient ROS signal transduction and subsequent stress response regulation. In terms of ROS signal transduction, alkaline stress induced significant upregulation of protein kinase-encoding genes including CPK4, CPK9, and CPK10 in JX22, which cooperated with RBOHD to regulate ROS production. Concerning ROS scavenging, significant upregulation of SODA, CAT2, and PRXⅡB genes ensured a more efficient enzymatic ROS scavenging system in JX22 under alkaline stress. In contrast, ZB8 could only rely on less efficient non-enzymatic systems, such as carotenoid antioxidants, to mitigate oxidative damage, where genes like CCD7, CYP897B and metabolites including lutein and zeaxanthin played crucial roles. These findings elucidate the ROS response mechanisms of castor bean under alkaline stress, paving new ways for breeding alkaline-resistant varieties.PMID:39864292 | DOI:10.1016/j.plaphy.2025.109518

J Plant Res. 2025 Jan 26. doi: 10.1007/s10265-025-01616-w. Online ahead of print.ABSTRACTBarley (Hordeum vulgare L.) is an important cereal crop used in animal feed, beer brewing, and food production. Waterlogging stress is one of the prominent abiotic stresses that has a significant impact on the yield and quality of barley. Seed germination plays a critical role in the establishment of seedlings and is significantly impacted by the presence of waterlogging stress. However, there is a limited understanding of the regulatory mechanisms of gene expression and metabolic processes in barley during the germination stage under waterlogging stress. This study aimed to investigate the metabolome and transcriptome responses in germinating barley seeds under waterlogging stress. The findings of the study revealed that waterlogging stress sharply decreased seed germination rate and seedling growth. The tolerant genotype (LLZDM) exhibited higher levels of antioxidase activities and lower malondialdehyde (MDA) content in comparison to the sensitive genotype (NN). In addition, waterlogging induced 86 and 85 differentially expressed metabolites (DEMs) in LLZDM and NN, respectively. Concurrently, transcriptome analysis identified 1776 and 839 differentially expressed genes (DEGs) in LLZDM and NN, respectively. Notably, the expression of genes associated with redox reactions, hormone regulation, and other biological processes were altered in response to waterlogging stress. Furthermore, the integrated transcriptomic and metabolomic analyses revealed that the DEGs and DEMs implicated in mitigating waterlogging stress primarily pertained to the regulation of pyruvate metabolism and flavonoid biosynthesis. Moreover, waterlogging might promote flavonoid biosynthesis by regulating 15 flavonoid-related genes and 10 metabolites. The present research provides deeper insights into the overall understanding of waterlogging-tolerant mechanisms in barley during the germination process.PMID:39864038 | DOI:10.1007/s10265-025-01616-w

Cell Commun Signal. 2025 Jan 25;23(1):47. doi: 10.1186/s12964-025-02044-y.ABSTRACTOne hallmark of cancer is the upregulation and dependency on glucose metabolism to fuel macromolecule biosynthesis and rapid proliferation. Despite significant pre-clinical effort to exploit this pathway, additional mechanistic insights are necessary to prioritize the diversity of metabolic adaptations upon acute loss of glucose metabolism. Here, we investigated a potent small molecule inhibitor to Class I glucose transporters, KL-11743, using glycolytic leukemia cell lines and patient-based model systems. Our results reveal that while several metabolic adaptations occur in response to acute glucose uptake inhibition, the most critical is increased mitochondrial oxidative phosphorylation. KL-11743 treatment efficiently blocks the majority of glucose uptake and glycolysis, yet markedly increases mitochondrial respiration via enhanced Complex I function. Compared to partial glucose uptake inhibition, dependency on mitochondrial respiration is less apparent suggesting robust blockage of glucose uptake is essential to create a metabolic vulnerability. When wild-type and oncogenic RAS patient-derived induced pluripotent stem cell acute myeloid leukemia (AML) models were examined, KL-11743 mediated induction of mitochondrial respiration and dependency for survival associated with oncogenic RAS. Furthermore, we examined the therapeutic potential of these observations by treating a cohort of primary AML patient samples with KL-11743 and witnessed similar dependency on mitochondrial respiration for sustained cellular survival. Together, these data highlight conserved adaptations to acute glucose uptake inhibition in diverse leukemic models and AML patient samples, and position mitochondrial respiration as a key determinant of treatment success.PMID:39863913 | DOI:10.1186/s12964-025-02044-y

BMC Plant Biol. 2025 Jan 25;25(1):111. doi: 10.1186/s12870-025-06122-8.ABSTRACTThe homeotic transformation of stamens into pistil-like structures (pistillody) causes cytoplasmic male sterility (CMS). This phenomenon is widely present in plants, and might be induced by intracellular communication (mitochondrial retrograde signaling), but its systemic regulating mechanism is still unclear. In this study, morphological observation showed that the stamens transformed into pistil-like structures, leading to flat and dehiscent pistils, and fruit set decrease in sua-CMS (MS K326, somatic fusion between Nicotiana. tabacum L. K326 and Nicotiana suaveolens). Transcriptome data analysis presented that the expression levels of B-class MADS genes, including pMADS1, GLO1, GLO2, pMADS2.1, pMADS2.2, significantly reduced in the pistil-like structure of sua-CMS. DEGs were enriched in flavonoid and phenylpropanoid biosynthesis pathways. Transcriptome and metabolomics analysis revealed that the expression levels of CHI/CHS (key enzymes regulating flavonoid synthesis), and the contents of flavonoids reduced significantly in the pistil-like structures of sua-CMS. Chemical fluorescence staining assay showed that reactive oxygen species (ROS) levels were higher in the pistil-like structure of sua-CMS. Application of external flavonoids (hesperetin) reduced the frequency of pistillody and ROS levels. These results suggested that the metabolism of flavonoids played important roles in regulating pistillody through ROS in sua-CMS. Our study provides new insights into the regulatory mechanism of pistillody in plants.PMID:39863899 | DOI:10.1186/s12870-025-06122-8

Sci Rep. 2025 Jan 25;15(1):3188. doi: 10.1038/s41598-025-87684-3.ABSTRACTAcute B-lymphoblastic leukemia (B-ALL) is a highly heterogeneous hematologic malignancy, characterized by significant molecular differences among patients as the disease progresses. While the PI3K-Akt signaling pathway and metabolic reprogramming are known to play crucial roles in B-ALL, the interactions between lipid metabolism, immune pathways, and drug resistance remain unclear. In this study, we performed multi-omics analysis on different patient cohorts (newly diagnosed, relapsed, standard-risk, and poor-risk) to investigate the molecular characteristics associated with metabolism, signaling pathways, and immune regulation in B-ALL. Our findings indicate that the PI3K-Akt signaling pathway is significantly enriched across all groups, highlighting its critical role in B-ALL pathogenesis and progression. Furthermore, metabolomic analysis revealed that lipid metabolism, ferroptosis, and glutathione metabolism are closely linked to disease progression. Notably, in relapsed patients, dysregulated lipid metabolism and the activation of antioxidant mechanisms may contribute to treatment resistance. Immune-related pathways, such as the complement system and coagulation cascade, were also significantly enriched in patients with B-ALL. This suggests that these pathways, alongside the PI3K-Akt pathway, play a role in forming the tumor microenvironment, thereby promoting disease progression and relapse. Based on these findings, this study provides novel potential therapeutic targets for the personalized treatment of B-ALL and lays the foundation for further development of PI3K-Akt pathway inhibitors and immunometabolism-targeted therapies.PMID:39863799 | DOI:10.1038/s41598-025-87684-3

Sci Rep. 2025 Jan 25;15(1):3252. doi: 10.1038/s41598-025-87581-9.ABSTRACTThe fungal green synthesis of nanoparticles (NPs) has gained great interest since it is a cost-effective and easy handling method. The process is simple because fungi secrete metabolites and proteins capable of reducing metal salts in aqueous solution, however the mechanism remains largely unknown. The aim of this study was to analyze the secretome of a Trichoderma harzianum strain during the mycobiosynthesis process of zinc and iron nanoparticles. Different profiles of proteins secreted by the fungus grown in the culture media or in the aqueous filtrate were observed through SDS‒PAGE and LC‒MS/MS analysis identifying 99 and 304 proteins, respectively. Particularly, in the aqueous filtrate proteins of metabolic processes and stress response mainly oxidoreductases, were identified. Successfully, ZnO and FeO NPs were synthesized and characterized by transmission electron microscopy, energy dispersive X-ray spectroscopy, dynamic light scattering, thermogravimetric, and FTIR analysis. FTIR revealed organic compounds in nanoparticles acting as probably capping agents. This research is the first report in which a proteomic analysis identifies multiple enzymes involved in the biogenic process of NP biosynthesis from T. harzianum, and its role is clearly demonstrated by the formation of zincite and magnetite nanoparticles.PMID:39863789 | DOI:10.1038/s41598-025-87581-9

Metabolomics. 2025 Jan 25;21(1):21. doi: 10.1007/s11306-025-02224-4.ABSTRACTINTRODUCTION: Preeclampsia (PE) is a common vascular pregnancy disorder affecting maternal and fetal metabolism with severe immediate and long-term consequences in mothers and infants. During pregnancy, metabolites in the maternal circulation pass through the placenta to the fetus. Meconium, a first stool of the neonate, offers a view to maternal and fetoplacental unit metabolism and could add to knowledge on the effects of PE on the fetus and newborn.OBJECTIVES: To compare meconium metabolome of infants from PE and normotensive pregnancies.METHODS: A cohort of preeclamptic parturients and normotensive controls were recruited in Tampere University Hospital during 2019-2022. Meconium was sampled and its metabolome analyzed using liquid chromatography- mass spectrometry in 48 subjects in each group.RESULTS: Differences in abundances of 1263 compounds, of which 19 could be annotated, were detected between the two groups. Several acylcarnitines, androsterone sulfate, three bile acids, amino acid derivatives (phenylacetylglutamine, epsilon-(gamma-glutamyl)lysine and N-(phenylacetyl)glutamic acid), as well as caffeine and paraxanthine were lower in the PE group compared to the control group. Urea and progesterone were higher in the PE group.CONCLUSION: PE is associated with alterations in the meconium metabolome of infants. The differing abundances of several metabolites show alterations in the interaction between the fetoplacental unit and mother in PE, but whether they are a cause or an effect of the disorder remains to be further investigated.PMID:39863780 | DOI:10.1007/s11306-025-02224-4

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