PubMed
Urinary metabolite model to predict the dying process in lung cancer patients
Commun Med (Lond). 2025 Feb 27;5(1):49. doi: 10.1038/s43856-025-00764-3.ABSTRACTBACKGROUND: Accurately recognizing that a person may be dying is central to improving their experience of care at the end-of-life. However, predicting dying is frequently inaccurate and often occurs only hours or a few days before death.METHODS: We performed urinary metabolomics analysis on patients with lung cancer to create a metabolite model to predict dying over the last 30 days of life.RESULTS: Here we show a model, using only 7 metabolites, has excellent accuracy in the Training cohort n = 112 (AUC = 0·85, 0·85, 0·88 and 0·86 on days 5, 10, 20 and 30) and Validation cohort n = 49 (AUC = 0·86, 0·83, 0·90, 0·86 on days 5, 10, 20 and 30). These results are more accurate than existing validated prognostic tools, and uniquely give accurate predictions over a range of time points in the last 30 days of life. Additionally, we present changes in 125 metabolites during the final four weeks of life, with the majority exhibiting statistically significant changes within the last week before death.CONCLUSIONS: These metabolites identified offer insights into previously undocumented pathways involved in or affected by the dying process. They not only imply cancer's influence on the body but also illustrate the dying process. Given the similar dying trajectory observed in individuals with cancer, our findings likely apply to other cancer types. Prognostic tests, based on the metabolites we identified, could aid clinicians in the early recognition of people who may be dying and thereby influence clinical practice and improve the care of dying patients.PMID:40016594 | DOI:10.1038/s43856-025-00764-3
Cerebral salt wasting syndrome as a probable cause of postoperative polyuria in patients with supratentorial Non-midline tumors: A prospective observational study with targeted and quantitative metabolomic approach
Neurosurg Rev. 2025 Feb 28;48(1):274. doi: 10.1007/s10143-025-03425-0.ABSTRACTPolyuria, or excessive fluid loss through the kidneys, is a common issue in neurocritical patients, often resulting from conditions such as fluid volume overload, osmotic diuretics, central diabetes insipidus (CDI), or cerebral salt wasting syndrome (CSWS). Notably, the specific cause of postoperative polyuria within 24 h in patients with tumors located in the supratentorial non-midline region remains poorly understood. To address this gap, we conducted a prospective observational study with 30 patients and found that eight (26.7%) experienced postoperative polyuria. Binary logistic regression analysis of clinical data ruled out fluid volume and osmotic diuretics as the underlying causes of postoperative polyuria, and suggested a very subtle association between tumor size and polyuria (OR = 1.030; p = 0.041). A significant postoperative decrease in serum sodium levels in the polyuria group (p = 0.005) pointed towards CSWS as potential mechanism. Differentiating between CDI and CSWS, both involving neuroendocrine hormone dysregulation, is challenging due to the lack of efficient clinical tests. To overcome this, we developed a novel liquid chromatography-tandem mass spectrometry (LC-MS)-based targeted and quantitative method to measure seven neuroendocrine hormones, including antidiuretic hormone (ADH) related to CDI and six natriuretic peptides associated with CSWS. Elevated levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), and ADH were observed in the polyuria group. Univariate analysis identified ANP, BNP, and ADH as significantly associated with polyuria at a threshold of p < 0.1. Later, multivariate logistic regression further revealed elevated BNP as an independent risk factor for polyuria (OR = 9111.901; p = 0.022). These findings suggest that CSWS may be the primary cause of postoperative polyuria in patients with supratentorial non-midline tumors, as evidenced by the concomitant decrease in serum sodium and increase in natriuretic peptides, particularly BNP.PMID:40016562 | DOI:10.1007/s10143-025-03425-0
Metabolic profiling and gene expression analyses shed light on the cold adaptation mechanisms of Saposhnikovia divaricata (Turcz.) Schischk
Sci Rep. 2025 Feb 27;15(1):7070. doi: 10.1038/s41598-025-91094-w.ABSTRACTThe northeastern region of China experiences a distinctly cold climate influenced by the Siberian High during the winter months, thus resulting in severe cold weather conditions. Snow cover is prevalent and can persist for several months. This prolonged exposure to low temperatures necessitates specific adaptations in terms of agriculture and plant life, particularly for perennial herbs. Saposhnikovia divaricate (Turcz.) Schischk (SD) is a widely distributed perennial herb in the northeastern and northern provinces of China. However, there is limited documentation on the molecular mechanism through which this plant adapts to cold stress. Therefore, we elucidated the SD response to cold stress by transcriptome and metabolome analysis. Cold stress induced chlorosis and wilting in plants, thus leading to added function of antioxidant enzymes and higher levels of malondialdehyde, proline, soluble sugars. Notably, the differentially expressed genes (DEGs) were primarily related with sugar metabolism, ROS sweep, flavonoid and terpenoid biosynthesis, plant hormone signalling pathways, lipid metabolism, and transcription factors. Additionally, the differentially expressed metabolites (DEMs) mainly included lipids, flavonoids, terpenoid compounds, sugar-related metabolites, alkaloids and other metabolites. Furthermore, integrated analysis revealed coexpression patterns between carbohydrate metabolism-related genes and genes reference flavonoid and terpenoid biosynthesis, along with their corresponding metabolites. Finally, the qPCR results revealed notable over-expression levels of stress-related genes, including those participated in plant hormone signalling pathways (PP2C and AUX), flavonoid biosynthesis (CH3), antioxidant enzymes (AOX and CAT), and sugar-related metabolite metabolism (TPS, SPS, and SS). In conclusion, our findings suggest that cold stress strongly affects plant hormone signalling pathways, ROS scavenging mechanisms, unsaturated fatty acid synthesis and flavonoid and terpenoid biosynthesis in SD. These discoveries provide valuable insights into the impact of cold climates on herbaceous plants.PMID:40016325 | DOI:10.1038/s41598-025-91094-w
The association between metabolite concentrations and wellbeing in adults
Sci Rep. 2025 Feb 27;15(1):6997. doi: 10.1038/s41598-025-91558-z.ABSTRACTThe biological complexity of wellbeing is studied from various perspectives, including genetics and epigenetics. However, there is a knowledge gap concerning other layers, such as metabolomics, which is dynamic and changes throughout life. This study explores the association between metabolites and wellbeing in a sample (N = 4748) drawn from the Netherlands Twin Register. A latent factor score for wellbeing was constructed based on: Quality of Life, Life Satisfaction, and Subjective Happiness. A total of 231 blood metabolites were analyzed using 1HNMR technique. Linear regression models were performed for each metabolite, while correcting for family clustering, relevant covariates, and multiple testing. None of the metabolites were significantly associated with wellbeing after multiple testing correction. Despite the lack of significant findings, the 34 metabolites with the lowest p-value (0.25) pointed to the same metabolic pathway: endogenous lipid metabolism. This pathway has previously been linked to wellbeing in a GWAS and associated with related phenotypes in other metabolomic studies. In conclusion, this study confirms the biological complexity of wellbeing and speculates on a potential role of lipids. Further research is needed to confirm these hypotheses.PMID:40016293 | DOI:10.1038/s41598-025-91558-z
Domesticated rice alters the rhizosphere microbiome, reducing nitrogen fixation and increasing nitrous oxide emissions
Nat Commun. 2025 Feb 27;16(1):2038. doi: 10.1038/s41467-025-57213-x.ABSTRACTCrop domestication has revolutionized food production but increased agriculture's reliance on fertilizers and pesticides. We investigate differences in the rhizosphere microbiome functions of wild and domesticated rice, focusing on nitrogen (N) cycling genes. Shotgun metagenomics and real-time PCR reveal a higher abundance of N-fixing genes in the wild rice rhizosphere microbiomes. Validation through transplanting rhizosphere microbiome suspensions shows the highest nitrogenase activity in soils with wild rice suspensions, regardless of planted rice type. Domesticated rice, however, exhibits an increased number of genes associated with nitrous oxide (N2O) production. Measurements of N2O emissions in soils with wild and domesticated rice are significantly higher in soil with domesticated rice compared to wild rice. Comparative root metabolomics between wild and domesticated rice further show that wild rice root exudates positively correlate with the frequency and abundance of microbial N-fixing genes, as indicated by metagenomic and qPCR, respectively. To confirm, we add wild and domesticated rice root metabolites to black soil, and qPCR shows that wild rice exudates maximize microbial N-fixing gene abundances and nitrogenase activity. Collectively, these findings suggest that rice domestication negatively impacts N-fixing bacteria and enriches bacteria that produce the greenhouse gas N2O, highlighting the environmental trade-offs associated with crop domestication.PMID:40016229 | DOI:10.1038/s41467-025-57213-x
p85β acts as a transcription cofactor and cooperates with BCLAF1 in the nucleus
Nat Commun. 2025 Feb 27;16(1):2042. doi: 10.1038/s41467-025-56532-3.ABSTRACTp85β is a regulatory subunit of the phosphoinositide 3-kinase (PI3K). Emerging evidence suggests that p85β goes beyond its role in the PI3K and is functional in the nucleus. In this study, we discover that nuclear p85β is enriched at gene loci and regulates gene transcription and that this regulatory role contributes to the oncogenic potential of nuclear p85β. A multi-omics approach reveals the physical interaction and functional cooperativity between nuclear p85β and a transcription factor BCLAF1. We observe genome-wide co-occupancy of p85β and BCLAF1 at gene targets associated with transcriptional responses. Intriguingly, the targetome includes BCLAF1 of which transcription is activated by p85β and BCLAF1, indicating a positive autoregulation. While BCLAF1 recruits p85β to BCLAF1 loci, p85β facilitates the assembly of BCLAF1, the scaffold protein TRIM28 and the zinc finger transcription factor ZNF263, which together act in concert to activate BCLAF1 transcription. Collectively, this study provides functional evidence and mechanistic basis to support a role of nuclear p85β in modulating gene transcription.PMID:40016211 | DOI:10.1038/s41467-025-56532-3
Comparative Metabolomics of Clostridium acetobutylicum ATCC824 and its Engineered Strain, C. acetobutylicum DG1
J Microbiol Biotechnol. 2025 Feb 25;35:e2407028. doi: 10.4014/jmb.2407.07028.ABSTRACTClostridium acetobutylicum, a strict gram-positive anaerobe, plays a pivotal role in biotechnological applications, particularly in the biosynthesis of 1,3-propanediol, a critical biofuel component and monomer for bioplastic production. This study introduces C. acetobutylicum DG1, a metabolically engineered strain designed to enhance the 1,3-propanediol pathway. Despite its development, comprehensive metabolic comparisons between the parent and modified strains remain unexplored. Our research addresses this gap by employing gas chromatography coupled with time-of-flight mass spectrometry to delineate the global metabolite landscapes of both strains. Through multivariate statistical analysis such as principal component analysis and hierarchical clustering analysis, we discovered pronounced disparities in their metabolite profiles across the acidogenic and solventogenic phases. Detailed metabolomics investigations underscored significant divergences in amino acid metabolism, fatty acid metabolism, and the tricarboxylic acid cycle. These findings shed light on the metabolic alterations induced by genetic engineering in C. acetobutylicum, offering novel insights into microbial metabolism that could guide future biotechnological innovations.PMID:40016151 | DOI:10.4014/jmb.2407.07028
Age, sex, and mitochondrial-haplotype influence gut microbiome composition and metabolites in a genetically diverse rat model
Aging (Albany NY). 2025 Feb 27;null. doi: 10.18632/aging.206211. Online ahead of print.ABSTRACTWe evaluated the impact of sex and mitochondrial-haplotype on the age-related changes in the fecal gut microbiome of the genetically heterogeneous rodent model, the OKC-HETB/W rat. The age-related changes in the microbiome differed markedly between male and female rats. Five microbial species changed significantly with age in male rats compared to nine microbial species in female rats. Only three of these microbes changed with age in both male and female rats. The mitochondrial-haplotype of the rats also affected how aging altered the microbiome. Interestingly, most of the microbial species that changed significantly with age were mitochondrial-haplotype and sex specific, i.e., changing in one sex and not the other. We also discovered that sex and mitochondrial-haplotype significantly affected the age-related variations in content of fecal short-chain fatty acids and plasma metabolites that influence or are regulated by the microbiome, e.g., tryptophan derived metabolites and bile acids. This study demonstrates that the host's sex plays a significant role in how the gut microbiome evolves with age, even within a genetically diverse background. Importantly, this is the first study to show that the mitochondrial-haplotype of a host impacts the age-related changes in the microbiome.PMID:40015964 | DOI:10.18632/aging.206211
An in-depth analysis of the effects of excessive acetochlor exposure on chicken liver health
Pestic Biochem Physiol. 2025 Mar;208:106280. doi: 10.1016/j.pestbp.2024.106280. Epub 2024 Dec 27.ABSTRACTAcetochlor, a commonly used herbicide, poses significant risks to ecosystem and organism health through contamination of the food chain. Despite its widespread use, there is a lack of comprehensive studies on its toxicological effects on avian species. This study investigates the impact of environmental acetochlor exposure on chicken liver health using metabolomics analysis and histopathological techniques. Microscopic examination revealed autophagy-like structures and endoplasmic reticulum (ER) expansion, with significant effects observed at higher exposure levels. Biochemical analysis and metabolomics also demonstrated acetochlor-induced ferroptosis, highlighting disruptions in liver function. Further, in vitro studies revealed that acetochlor stimulates autophagy, which regulates ferroptosis via ferritin degradation, mediated through the ER-CaMKII pathway. These findings emphasize the importance of understanding the molecular mechanisms involved in acetochlor toxicity, particularly the role of the Ca2+/CaMKII pathway, ER stress, and autophagy in ferroptosis. The study contributes to a deeper understanding of how environmental contaminants affect avian species, providing critical insights for better herbicide risk assessment, pollution control, and sustainable agricultural practices.PMID:40015872 | DOI:10.1016/j.pestbp.2024.106280
Fe<sub>2</sub>O<sub>3</sub> nanoparticles enhance soybean resistance to root rot by modulating metabolic pathways and defense response
Pestic Biochem Physiol. 2025 Mar;208:106252. doi: 10.1016/j.pestbp.2024.106252. Epub 2024 Dec 12.ABSTRACTFour doses of Fe2O3 NPs suspension (10, 50, 100, and 500 mg/L) and one dose of EDTA-FeNa2 solution (10 mg/L) were foliar applied to two soybean (Glycine max) varieties (ND12 and C103) with Fusarium oxysporum. Notably, soybean disease indices were significantly reduced following foliar application of Fe2O3 NPs. At 50 mg/L Fe2O3 NPs, disease indices were reduced by 60.29 % and 43.75 % in ND12 and C103, respectively; these values were significantly better than EDTA-FeNa2, which reduced disease indices by 22.02-28.10 % compared to infected control. Furthermore, root biomass increased by 54.28 % and 42.95 %; chlorophyll a increased by 31.03 % and 43.78 %; SOD activity increased by 40.82 % and 45.59 %; and GmPAL expression increased by 16.64 and 7.23-fold with 50 mg/L Fe2O3 NPs on ND12 and C103, respectively, compared to the infected control. Importantly, the control efficiency of Fe2O3 NPs was 3-6 times higher than that of EDTA-FeNa2. Metabolomic analysis indicated that 50 mg/L Fe2O3 NPs significantly increased the metabolite content of TCA biomolecules in both soybeans; for example, citric acid increased by 102.06 % and 29.88 % compared to the infected control. The results suggest that Fe2O3 NPs mitigate root rot through multiple mechanisms, including augmentation of antioxidant enzyme activity to mitigate disease-induced oxidative stress, activation of relevant defense genes to enhance resistance, and increased levels of TCA and amino acid metabolites to provide energy for soybean response. These findings underscore the significant potential of Fe2O3 NPs in disease suppression for an environmentally friendly sustainable agriculture.PMID:40015848 | DOI:10.1016/j.pestbp.2024.106252
Role of Bacillus atrophaeus B1 in gut on nicotine tolerance of the fall armyworm
Pestic Biochem Physiol. 2025 Mar;208:106248. doi: 10.1016/j.pestbp.2024.106248. Epub 2024 Dec 10.ABSTRACTThe fall armyworm (FAW), Spodoptera frugiperda is one of the most destructive polyphagous herbivores. Some detoxification genes have been proved to be involved in the adaptability to host plants in FAW, while the role of its gut microbiota on the responses of host switches, and their ability to adapt to new host plants remain poorly understood. Herein, we isolated five strains of nicotine-degrading bacteria from the gut of S. frugiperda larvae, among which Bacillus atrophaeus B1 exhibited the highest nicotine tolerance. This strain showed a minimum inhibitory concentration (MIC) value of 2 g/L and a nicotine degradation rate of 46.36 %. We sequenced the complete genome of B. atrophaeus B1 and 15 candidate genes were identified maybe related to nicotine degradation, among which GE003027, GE002849, GE002602, GE000220 and GE002708 had significantly higher expression when exposed to nicotine. Non-targeted metabolomics revealed 98 differentially accumulated metabolites (DAMs) under nicotine stress, which were 72 metabolites upregulated and 26 metabolites downregulated, and the pathways most affected involved xenobiotic biodegradation and metabolism, energy metabolism, and amino acid metabolism. B. atrophaeus B1 may accumulate 2-ketoglutaric acid and γ-aminobutyric acid during degradation of nicotine, which is non-toxic to S. frugiperda, and participated in the tricarboxylic acid (TCA) cycle. Additionally, 2-ketoglutaric acid and γ-aminobutyric acid were detected both in B. atrophaeus B1 and S. frugiperda treated with nicotine. Antibiotic treatment deprived most of the gut bacteria, followed by a decrease in tolerance of S. frugiperda to nicotine, and the nicotine degradation rate was significantly increased as expected after reinfection with B. atrophaeus B1. These findings provide new insights into the bacterial metabolism of nicotine degradation and offer a theoretical basis for understanding the rapid adaptability of S. frugiperda to various host plants.PMID:40015844 | DOI:10.1016/j.pestbp.2024.106248
Nanoconfined in-situ sampling and extracting switching needle device construction for highly enrichment of polar metabolites in human urine
Anal Chim Acta. 2025 Apr 1;1345:343738. doi: 10.1016/j.aca.2025.343738. Epub 2025 Jan 30.ABSTRACTUrine, as a non-invasive sampling specimen, offers significant advantages for the diagnosis and treatment of diseases. However, as a water-based matrix, most metabolites in urine are high polarity, which limits the ultrafast extraction and high enrichment of these polar metabolites from urine. Though solvent-based extraction method has demonstrated considerable benefits in extraction rates, the necessity for selecting water-immiscible solvents restricts the extraction of highly polar metabolites. Consequently, there is a pressing need for a rapid extraction method that achieves a high enrichment factor specifically targeting highly polar metabolites in urine. (90) RESULTS: This study is the first attempt to use water-soluble solvent to extract highly polar metabolites from urine. Firstly, a needle device capable of switching between sampling and extracting modes was constructed by utilizing carbon nanofibers/carbon fibers (CNFs/CFs) filled with the needle tip. Under the effect of nanoconfinement, the needle can achieve in-situ ultrafast extraction employing a methanol/water mixture as the nanoconfined extraction solvent. Additionally, the nanodistribution of the extracted solvent within the nanoconfined space enhances the exaction rate and efficiency. By coupling this method with HILIC-LC/MS detection protocol, 33 highly polar metabolites from human urine were simultaneously quantified within 3 min. Following systematic validation, the established method was successfully applied to urine target metabolomics analysis for hepatocellular carcinoma, the potential diagnosis biomarkers were screened out using multiple data processing methods. (130) SIGNIFICANCE: In conclusion, the home-made nanoconfinement effect based in-situ sampling and extracting (NISE) switching needle device demonstrates strong advantages in the highly enrichment and ultrafast analysis of highly polar metabolites in an aqueous matrix, providing a promising tool for clinical disease diagnosis and screening. (44).PMID:40015780 | DOI:10.1016/j.aca.2025.343738
A critical analysis of Adaptive Box-Cox transformation for skewed distributed data management: Metabolomics of Spanish and Argentinian truffles as a case study
Anal Chim Acta. 2025 Apr 1;1345:343704. doi: 10.1016/j.aca.2025.343704. Epub 2025 Jan 28.ABSTRACTBACKGROUND: Metabolic variations retrieved in metabolomic data are considered a benchmark for detecting biomatrix variability. Therefore, identifying target metabolites is crucial to keep track of any substrate modification and preserve it from any undesired alteration. Unfortunately, such a task can be negatively affected by detecting false positives, often triggered by complicated data distributions. In this work, we undertook an investigation of the metabolic profile of Spanish and Argentine truffles using a robust methodology. The issue of skewed data distributions has been effectively addressed through a normalization preprocessing, enhancing biomarker identification and samples classification.RESULTS: A data normality-improved parametric test (ANOVA) was employed to define the target metabolites, which significantly vary between two regions of origin: Spain and Argentina. Specifically, Adaptive Box-Cox transformation was employed to improve the ANOVA test's performance so that data distributions were fitted to a Gaussian variable. Using the Bonferroni-Holm method for false discovery rate correction, we demonstrated the effectiveness of this transformation for the case under investigation. Results were compared with two non-parametric tests (Kruskall-Wallis and Permutation test), selected as a reference methodology, to provide a better understanding of non-normal distributions often encountered in metabolomic data analysis. 17 metabolites out of the 57 investigated metabolites exhibited notable variability across the two geographical regions. The validity of this methodology was supported through the discrimination of samples belonging to different groups. In this regard, both univariate and multivariate statistical models were tested through Monte Carlo simulations and yielded consistent results.SIGNIFICANCE: Data analysis outcomes are sensitive to variables distributions. The present study shows an effective tool to increase data normality, thereby enhancing the statistical power for biomarker discovery and improving models' classification performances. These results find justification from the current knowledge within the field of food sciences, enabling their application in advancing research in the truffle analysis domain.PMID:40015769 | DOI:10.1016/j.aca.2025.343704
Methionine cycle inhibition disrupts antioxidant metabolism and reduces glioblastoma cell survival
J Biol Chem. 2025 Feb 25:108349. doi: 10.1016/j.jbc.2025.108349. Online ahead of print.ABSTRACTGlioblastoma (GBM) is a highly aggressive primary malignant adult brain tumor that inevitably recurs with a fatal prognosis. This is due in part to metabolic reprogramming that allows tumors to evade treatment. Therefore, we must uncover the pathways mediating these adaptations to develop novel and effective treatments. We searched for genes that are essential in GBM cells as measured by a whole-genome pan-cancer CRISPR screen available from DepMap and identified the methionine metabolism genes MAT2A and AHCY. We conducted genetic knockdown, evaluated mitochondrial respiration, and performed targeted metabolomics to study the function of these genes in GBM. We demonstrate that MAT2A or AHCY knockdown induces oxidative stress, hinders cellular respiration, and reduces the survival of GBM cells. Furthermore, selective MAT2a or AHCY inhibition reduces GBM cell viability, impairs oxidative metabolism, and shifts the cellular metabolic profile towards oxidative stress and cell death. Mechanistically, MAT2a and AHCY regulate spare respiratory capacity, the redox buffer cystathionine, lipid and amino acid metabolism, and prevent oxidative damage in GBM cells. Our results point to the methionine metabolic pathway as a novel vulnerability point in GBM. Significance We demonstrated that methionine metabolism maintains antioxidant production to facilitate pro-tumorigenic ROS signaling and GBM tumor cell survival. Importantly, targeting this pathway in GBM has the potential to reduce tumor growth and improve survival in patients.PMID:40015640 | DOI:10.1016/j.jbc.2025.108349
The 2-methylcitrate cycle and the glyoxylate shunt in Pseudomonas aeruginosa are linked through enzymatic redundancy
J Biol Chem. 2025 Feb 25:108355. doi: 10.1016/j.jbc.2025.108355. Online ahead of print.ABSTRACTThe 2-methylcitrate cycle (2-MCC) and the glyoxylate cycle are central metabolic pathways in Pseudomonas aeruginosa, enabling the organism to utilize organic acids such as propionate and acetate during infection. Here, we show that these cycles are linked through enzymatic redundancy, with isocitrate lyase (AceA) exhibiting secondary 2-methylisocitrate lyase (2-MICL) activity. Furthermore, we use a combination of structural analyses, enzyme kinetics, metabolomics, and targeted mutation of PrpBPa to demonstrate that whereas loss of PrpB function impairs growth on propionate, the promiscuous 2-MICL activity of AceA compensates for this by mitigating the accumulation of toxic 2-MCC intermediates. Our findings suggest that simultaneous inhibition of PrpB and AceA could present a robust antimicrobial strategy to target P. aeruginosa in propionate-rich environments, such as the cystic fibrosis airways. Our results emphasize the importance of understanding pathway interconnections in the development of novel antimicrobial agents.PMID:40015638 | DOI:10.1016/j.jbc.2025.108355
Environmental basis for early onset breast cancer
Reprod Toxicol. 2025 Feb 25:108866. doi: 10.1016/j.reprotox.2025.108866. Online ahead of print.ABSTRACTPregnancy provokes a heightened amino acid requirement, especially in the third trimester. Alterations to late pregnancy amino acid metabolism have been associated with environmental breast carcinogen exposures, including DDT and PFAS. This project examined whether maternal serum amino acids in late pregnancy are associated with subsequent breast cancer risk. Archival third trimester serum samples from 172 women who were later diagnosed with breast cancer were compared to samples from 351 women without known breast cancer. A prospective metabolome-wide association study (MWAS) for breast cancer cases showed that associated amino acid pathways included lysine, arginine, proline, aspartate, asparagine, alanine, tyrosine, tryptophan, histidine and branched-chain amino acids. Lower mean concentrations of individual amino acids, including histidine, threonine, lysine and proline, were associated with increased risk of breast cancer, and network analyses showed that these amino acids were negatively associated with protective breast cancer risk factors. Prospective MWAS for breast cancer cases diagnosed within 15years of sample collection showed pathway associations for tryptophan, histidine, lysine and methionine and cysteine pathways. Nutrient stresses caused by low amino acid levels impair immunosurveillance and activate oncogenic mechanisms of cell survival, thereby providing mechanisms by which environmental exposures in late pregnancy can contribute to breast cancer risk.PMID:40015485 | DOI:10.1016/j.reprotox.2025.108866
Molecular networking guided metabolomics for mapping the secondary metabolome of six Melaleuca species and their digestive enzymes' inhibitory potential
Fitoterapia. 2025 Feb 25:106457. doi: 10.1016/j.fitote.2025.106457. Online ahead of print.ABSTRACTMelaleuca, a member of the Myrtaceae family, comprises around 300 species that are originally endemic to Australia and Southeast Asia and are cultivated as ornamental plants in Egypt. Melaleuca species are recognized as profound producers of a wide array of secondary metabolites and are valued for their essential oils which are widely used in the pharmaceutical and cosmetic industries. Yet their secondary metabolome is not fully explored. A metabolomics approach compromising UPLC-HRMS/MS coupled with feature-based molecular networking (FBMN) was employed to glean a holistic overview of the secondary metabolome of six Melaleuca species cultivated in Egypt. Additionally, the extracts were screened for the in vitro inhibition of the digestive enzymes (i.e., α-amylase and pancreatic lipase). The FBMNs allowed for the annotation of 195 metabolites, belonging to diverse chemical classes, such as phenolics and phenyl propanoids (i.e., hydrolyzable tannins, phenolic acids, chromones, flavonoids, stilbenes, and lignans), terpenoids (i.e., megastigmanes, monoterpenes, and triterpenes), and other miscellaneous compounds. Among the annotated features only 15 % were previously reported to occur in the genus Melaleuca, and 11 metabolites were proposed as potentially new natural products. The adopted protocol highlighted the profound capability of Melaleuca plants to produce secondary metabolites of various chemical classes holding the potential to exhibit beneficial biological activities. For instance, the studied extracts diminished the activity of both the α-amylase and pancreatic lipase enzymes. Such findings propose the Melaleuca species as potential candidates for the development of plant-derived products for obesity management.PMID:40015378 | DOI:10.1016/j.fitote.2025.106457
Clinical translation of metabolomics markers in endometrial carcinoma
J Obstet Gynaecol Res. 2025 Mar;51(3):e16246. doi: 10.1111/jog.16246.ABSTRACTOBJECTIVE: This comprehensive review highlights the current research on metabolomics and the metabolic pathways involved in endometrial cancer (EC), offering potential non-invasive biomarkers for EC.METHODS: The data was extracted from published manuscripts between 2015 and 2024 using the reputed search engine "Pubmed." All gathered data were organized into a single table, facilitating a comparison with earlier findings.RESULTS: The results of this study revealed most metabolites identified in previous metabolomic research on EC are associated with lipid, glucose, and amino acid metabolism.CONCLUSION: Therefore, understanding these metabolic pathway alterations in EC is crucial for improving diagnosis, prognosis, and treatments by specially targeting these metabolic pathways.PMID:40015330 | DOI:10.1111/jog.16246
Human Untargeted Metabolomics in High-Throughput Gut Microbiome Research: Ethanol vs Methanol
Anal Chem. 2025 Feb 27. doi: 10.1021/acs.analchem.4c05142. Online ahead of print.ABSTRACTUntargeted metabolomics is frequently performed on human fecal samples in conjunction with sequencing to unravel the gut microbiome functionality. As sample collection efforts are rapidly expanding, with individuals often collecting specimens at home, metabolomics experiments should adapt to accommodate the safety and needs of bulk off-site collections and improve high throughput. Here, we show that a 95% ethanol, safe to be shipped and handled, extraction part of the Matrix Method pipeline recovers comparable amounts of metabolites as a validated 50% methanol extraction, preserving metabolic profile differences between investigated subjects. Additionally, we show that the fecal metabolome remains relatively stable when stored in 95% ethanol for up to 1 week at room temperature. Finally, we suggest a metabolomics data analysis workflow based on robust centered log ratio transformation, which removes the variance introduced by possible different sample weights and concentrations, allowing for reliable and integration-ready untargeted metabolomics experiments in gut microbiome research.PMID:40015251 | DOI:10.1021/acs.analchem.4c05142
Integrated transcriptomic and metabolomic analysis reveals the causes of mass mortality in juvenile pearl oysters (Pinctada maxima)
Comp Biochem Physiol Part D Genomics Proteomics. 2025 Feb 23;55:101454. doi: 10.1016/j.cbd.2025.101454. Online ahead of print.ABSTRACTPinctada maxima is a pearl oyster species producing large, high-quality marine pearls. However, juvenile mortality (shell length < 5 cm) in this species adversely affects commercial pearl production. Understanding the molecular mechanism and genes related to mass mortality will help mitigate this problem. Therefore, the present study investigated the transcriptomic and metabolic differences between pearl oysters during high mortality (HM) and after this period (PD) to shed light on the causes of juvenile mass mortality. Initial analysis of biochemical parameters revealed that protease, α-amylase, and catalase activities in the hepatopancreatic tissues of pearl oysters at the HM stage were significantly lower than at the PD stage. Conversely, glutathione and lysozyme contents, and superoxide dismutase, acid phosphatase, alkaline phosphatase activities were notably higher at the HM stage than at the PD stage. Metabolomic analysis identified 98 metabolites in the adductor muscle significantly different between the two stages, which enriched glycerophospholipid metabolism, glutathione metabolism, arachidonic acid metabolism, oxidative phosphorylation, and neuroactive ligand-receptor interaction pathways. Transcriptome analysis identified 677 differentially expressed genes in the adductor muscle between these stages, which enriched neuroactive ligand-receptor interaction, glutathione metabolism, and ECM-receptor interaction pathways. Finally, an integrated analysis of the metabolome and transcriptome suggested that pearl oysters at the HM stage experience oxidative stress, activate immune-related genes, and exacerbate the low energy status. These findings on the causes of mass mortality lay a theoretical foundation for improving the survival rate of juveniles and advancing the industrialization of P. maxima.PMID:40015133 | DOI:10.1016/j.cbd.2025.101454