PubMed
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
A comprehensive metabolomic and lipidomic study of olanzapine in the treatment of first-episode schizophrenia
Asian J Psychiatr. 2025 Feb 19;105:104387. doi: 10.1016/j.ajp.2025.104387. Online ahead of print.ABSTRACTBACKGROUND: Despite advances in research, critical gaps remain in understanding the molecular mechanisms of antipsychotic medications such as olanzapine. This study investigated the molecular pathways by which olanzapine exerts its therapeutic effects and causes metabolic side effects by analyzing changes in the serum metabolic and lipid profiles of patients with first-episode schizophrenia.METHODS: Clinical symptoms were assessed using the Positive and Negative Symptom Scale (PANSS) in 43 patients with first-episode schizophrenia. Body mass index (BMI) and fasting glucose (GLU) and tetraplex lipids levels were measured before and after treatment. Changes in patient serum metabolic and lipid profiles before and after treatment were examined. Correlation analysis was used to identify differential metabolites and lipid molecules that were significantly associated with changes in clinical symptoms and metabolic side-effect indicators.RESULTS: After 8 weeks of olanzapine treatment, there was a significant decrease in all PANSS scores and a significant increase in BMI and GLU, total cholesterol, and low-density lipoprotein cholesterol levels in patients with first-episode schizophrenia. Metabolomic and lipidomic analyses identified 70 metabolites and 67 lipids in the serum that changed significantly after treatment. Correlation analysis revealed that the clinical symptom changes in the patients before and after treatment were significantly associated with 11 metabolites (most related to inflammation and oxidative stress), while the metabolic side-effect indicators were significantly associated with 14 lipid molecules.CONCLUSIONS: Olanzapine may improve psychotic symptoms by modulating inflammation and oxidative stress-related metabolites; however, olanzapine may also cause metabolic disturbances by affecting lipid metabolic pathways.PMID:40015078 | DOI:10.1016/j.ajp.2025.104387
Revealing the key antioxidant compounds and potential action mechanisms of Bauhinina championii honey based on non-targeted metabolomics, mineralogical analysis and physicochemical characterization
Food Chem. 2025 Feb 19;477:143456. doi: 10.1016/j.foodchem.2025.143456. Online ahead of print.ABSTRACTBauhinia championii (BC) honey, highly regarded for its functional properties, is popular among consumers and holds significant economic potential, particularly in the food and health industries. However, limited knowledge of the bioactivities, especially its outstanding antioxidant activity, hampers the development of functional products. This study comprehensively compared BC honey's physicochemical properties, elemental composition, metabolic profile, and antioxidant properties with five other honeys. Results revealed that BC honey had a darker color, higher electrical conductivity (335.67 ± 6.81 μS cm-1), and higher levels of minerals and flavonoids. It exhibited stronger radical scavenging activity, with DPPH (96.49 % ± 0.38) and ABTS (2.1593 mM ± 0.014) values. Multivariate analysis suggested that its superior antioxidant properties are likely due to high flavonoid content, particularly 7-O-methylchrysin. This study offers insights into BC honey's antioxidant characteristics and supports its use in functional products.PMID:40015020 | DOI:10.1016/j.foodchem.2025.143456
New insights into ovarian regression-related mitochondrial dysfunction in the late-laying period
Poult Sci. 2025 Feb 22;104(4):104938. doi: 10.1016/j.psj.2025.104938. Online ahead of print.ABSTRACTDuck egg production sharply decreases during the late-laying period, which likely stems from an ovarian mechanism. However, the molecular mechanisms underlying ovarian regression during the late-laying period remain unclear. In this study, egg-laying (LLP) and ceased-laying (CLP) ducks at 72 weeks of age were selected to explore the potential mechanism of ovarian regression. Proteomic analysis demonstrated the importance of mitochondrial function in ovarian regression. Notably, metabolomic analysis showed that CLP ducks disturbed TCA cycle, as exhibited by the lower fumarate content. The ovarian expression of protein markers for mitochondrial biogenesis (PGC-1α and TFAM) and function (SIRT1 and SIRT3) were suppressed in CLP ducks. CLP ducks had significantly increased MDA levels and reduced SOD, CAT, GSH-Px, and T-AOC activities, inducing excessive oxidative stress. Interestingly, ACSL4, a key regulator of ferroptosis, was associated with the mitochondrial envelope and membrane function during ovarian regression. CLP ducks showed significantly reduced GSH levels and increased Fe2+ content, as well as decreased the expression of ferroptosis-related proteins (GPX4 and SLC7A11) and antioxidant-related proteins (COX2, CAT, SOD1, and SOD2). Collectively, our findings suggest that ovarian regression-mediated mitochondrial dysfunction contributes to oxidative stress-induced ferroptosis in ducks that have ceased laying.PMID:40014974 | DOI:10.1016/j.psj.2025.104938
Bridging the gap between research and decision making: A European survey to enhance cooperation in wastewater-based epidemiology (WBE) for illicit drugs
Public Health. 2025 Feb 26;241:158-163. doi: 10.1016/j.puhe.2025.02.009. Online ahead of print.ABSTRACTOBJECTIVES: Illicit drug use presents a significant challenge to global health and public safety, requiring innovative and effective monitoring strategies. This study aimed to evaluate the current landscape of wastewater-based epidemiology (WBE) for monitoring illicit drugs in Europe, focusing on collaboration, current practices, and barriers, while identifying opportunities for improvement.STUDY DESIGN: Cross-sectional survey-based study.METHODS: Coordinated by the Sewage Analysis CORe Group Europe (SCORE) and the European Union Drugs Agency (EUDA), two surveys were conducted in 2023 targeting researchers and stakeholders using WBE for illicit drugs. Data were analysed to identify trends, gaps, and opportunities for improving WBE implementation.RESULTS: The findings indicate a robust research infrastructure and diverse analytical methods among European institutions. Two-thirds of the participating countries reported using WBE data to inform policy. However, challenges persist, particularly in securing funding and coordination, as well as generating national estimates from multiple locations and addressing specific local policy needs.CONCLUSIONS: WBE has proven to be a valuable tool for monitoring illicit drug trends and informing drug policies. To unlock its full potential, sustained funding, methodological standardization, and enhanced cooperation are essential. This study provides critical insights into the European WBE landscape, offering a roadmap for strengthening the integration of actionable WBE data into public health and policy frameworks.PMID:40014941 | DOI:10.1016/j.puhe.2025.02.009
Two-photon polymerization of miniaturized 3D scaffolds optimized for studies on glioblastoma multiforme in spaceflight-like microgravity conditions
Biofabrication. 2025 Feb 27. doi: 10.1088/1758-5090/adbb21. Online ahead of print.ABSTRACTThe obtainment of innovative models recalling complex tumour architectures and activities in vitro is a challenging drive in the understanding of pathology molecular bases, yet a crucial passage to the identification of targets for advanced oncotherapy. Cell environment recapitulation by 3D scaffolding and gravitational unloading of cell cultures represent powerful means in tumour biomimicry process, but their simultaneous adoption has consistently been explored only in the latest decade. Here, an unprecedented bioengineering approach capitalizing on spaceflight biology practice is proposed for modelling of glioblastoma multiforme, a highly aggressive neoplasm that affects the central nervous system and that has poorly effective pharmacological and radiological countermeasures. Tumour modelling was pursued by the original implementation of two-photon polymerization in fast prototyping of 3D scaffolds on flexible substrates for U87-MG glioma cell culture, and by the exposure of cell-laden scaffolds to simulated microgravity (s-µg). Realistic spaceflight conditions were applied to collect preliminary information suitable to testing of U87-MG cell-laden scaffold in low Earth orbit. Response of glioma cells anchored to 3D scaffolds was investigated by microscopy, quantitative reverse transcription-polymerase chain reaction and proteomic analyses, revealing synergic regulatory effects of cell scaffolding and s-µg on markers of tumour cell growth, metabolism and invasiveness.PMID:40014921 | DOI:10.1088/1758-5090/adbb21
Molecular networking: An efficient tool for discovering and identifying natural products
J Pharm Biomed Anal. 2025 Feb 11;259:116741. doi: 10.1016/j.jpba.2025.116741. Online ahead of print.ABSTRACTNatural products (NPs), play a crucial role in drug development. However, the discovery of NPs is accidental, and conventional identification methods lack accuracy. To overcome these challenges, an increasing number of researchers are directing their attention to Molecular networking (MN). MN based on secondary mass spectrometry has become an important tool for the separation, purification and structural identification of NPs. However, most new tools are not well known. This review started with the most basic MN tool and explains it from the principle, workflow, and application. Then introduce the principles and workflows of the remaining eight new types of MN tools. The reliability of various MNs is mainly verified based on the application of phytochemistry and metabolomics. Subsequently, the principles and applications of 12 structural annotation tools are introduced. For the first time, the scope of 9 kinds of MN tools is compared horizontally, and 12 kinds of structured annotation tools are classified from the type of compound structure suitable for identification. The advantages and disadvantages of various tools are summarized, and make suggestions for future application directions and the development of computing tools in this review. MN tools are expected to enhance the efficiency of the discovery and identification in NPs.PMID:40014895 | DOI:10.1016/j.jpba.2025.116741
Integrating 16S rDNA sequencing analysis and targeted metabolomics to explore the mechanism of Xiexin Tang in treating atherosclerosis mice induced by high-fat diet
J Pharm Biomed Anal. 2025 Feb 25;259:116760. doi: 10.1016/j.jpba.2025.116760. Online ahead of print.ABSTRACTXiexin Tang (XXT) is a classic Chinese medicine formula that can be used to treat Atherosclerosis (AS). This study aimed to investigate the mechanism by which XXT regulated AS lipid levels. Firstly, the mixture components of XXT were analyzed by High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Then, the AS model based on Apolipoprotein E knockout (ApoE-/-) mice was established. Cytokines related to lipid metabolism and bile acid metabolism were detected by Quantitative Real-time PCR (qRT-PCR). 16S rDNA gene sequencing was performed to analyze differential bacterial populations, and the mechanism of XXT regulation of bile acids affecting lipid metabolism was further explored by targeted metabolomics. Further, antibiotic-treated mice were used to investigate the role of gut microbiota in the anti-AS effect of XXT. The results showed that XXT attenuated the lipid levels and reversed the abnormal elevation of cytokines, such as hepatic lipid metabolism and inflammatory reaction in AS mice. XXT also repaired the gut barrier damage and reversed gut microbiota disorders in AS mice. Furthermore, the metabolic levels of bile acids were reshaped by XXT. Whereas, in the absence of gut microbiota, XXT failed to attenuate lipid levels and inhibit the expression of cytokines related to inflammation and bile acid metabolism in AS mice and failed to play a role in ultimately treating AS. In conclusion, XXT could effectively inhibit the inflammatory reaction and lipid accumulation in AS mice, and this effect was closely related to its remodeling of gut microbiota to regulate bile acid metabolism.PMID:40014894 | DOI:10.1016/j.jpba.2025.116760