PubMed

Histochem Cell Biol. 2025 Apr 14;163(1):44. doi: 10.1007/s00418-025-02372-7.ABSTRACTPeroxisomes have gained increasing attention and are now considered vital players in normal physiological functions. To gain further insight into how peroxisomal defects influence cellular functions, we developed BV-2 microglial models featuring CRISPR/Cas9 gene-edited mutations in peroxisomal Acox1 or Abcd1 and Abcd2 genes. The Acox1-/- BV-2 cell line we generated lacks acyl-CoA oxidase 1, the key enzyme that initiates peroxisomal β-oxidation. In contrast, the double mutant Abcd1/d2-/- BV-2 cell line carries mutations in the genes encoding the membranous ABC transporters ABCD1 and ABCD2, which are responsible for transporting fatty acyl-thioesters inside peroxisome. Here, for the first time, we used analytical fractionation to compare these three genotypes. Through flow cytometry, we observed an increase in cell granularity in these mutant cells, which could be associated with alterations in peroxisome distribution and mitochondrial dynamics. Additionally, the analysis of organelle markers in microglial cells, employing differential centrifugation, exhibited an enrichment of peroxisomes particularly in both L and P fractions of these BV-2 cell line models. The use of an isopycnic Nycodenz density gradient showed that peroxisomes sedimented with a median density of 1.18 g/ml. Notably, our results revealed no significant differences in the distribution profiles of organelles when comparing microglial BV-2 Wt cells with deficient Acox1‒/‒ or Abcd1/d2-/‒ BV-2 cells, which lack peroxisomal fatty acid beta-oxidation. Our study is the first to report on the fractionation of brain-derived microglial cells, laying valuable groundwork for future proteomic and/or metabolomic analyses of peroxisome fractions.PMID:40229507 | DOI:10.1007/s00418-025-02372-7

Sci Rep. 2025 Apr 14;15(1):12782. doi: 10.1038/s41598-025-97641-9.ABSTRACTCholangiocarcinoma (CCA) has high recurrence rates that severely limit long-term survival. Effective tools for accurate recurrence monitoring and diagnosis remain lacking. Metabolic reprogramming, a key driver of CCA growth and recurrence, is underutilized in cancer screening and management. This study aimed to identify metabolite-based biomarkers to evaluate recurrence severity, enhance disease management, and elucidate the molecular mechanisms underlying CCA recurrence. A comprehensive, non-targeted serum metabolomics analysis using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was conducted. Support Vector Machine (SVM) modeling was employed to develop a predictive framework based on metabolite biomarkers. The analysis revealed significant alterations in metabolomics and lipidomics across CCA recurrence subtypes. Notably, changes in metabolites such as amino acids, lipid-derived carnitines, and glycerophospholipids were associated with cancer progression through enhanced energy production and lipid remodeling. The SVM-constructed metabolite-based predictive model demonstrated predictive accuracy comparable to current clinical diagnostic standards. These findings provide novel insights into the metabolic mechanisms underlying CCA recurrence, addressing critical clinical challenges. By advancing early diagnostic approaches, particularly for preoperative detection, this study offers a reliable method for predicting recurrence in CCA patients. This enables effective treatment planning and supports the development of personalized therapeutic strategies, ultimately improving patient outcomes.PMID:40229491 | DOI:10.1038/s41598-025-97641-9

EMBO Rep. 2025 Apr 14. doi: 10.1038/s44319-025-00447-z. Online ahead of print.ABSTRACTGroup A Streptococcus (GAS) causes various human diseases linked to virulome expression predominantly regulated by the two-component system (TCS), CovR/S. Here, we demonstrate that asparagine (Asn) presence in a minimal chemically defined medium increases virulence gene expression in a CovR-dependent fashion. It also decreases the transcription of asparagine synthetase (AsnA), the ABC transporter responsible for Asn uptake (GlnPQ), and that of the hemolysin toxins responsible for scavenging Asn from the host. Metabolomics data show that Asn availability increases intracellular ADP/ATP ratio, which enhances phosphatase activity in structurally related CovS sensors and is probably responsible for the Asn-mediated decrease in CovR phosphorylation. Mutants deficient in AsnA, GlnPQ, asparaginase, (AsnB) activities are attenuated in a mouse model of human GAS invasive soft tissue infection. The similarity between the mechanisms of Asn-mediated regulation of GAS virulence and tumor growth suggests that, as in cancer, components maintaining Asn homeostasis could be targeted for anti-GAS treatments.PMID:40229432 | DOI:10.1038/s44319-025-00447-z

Nat Commun. 2025 Apr 14;16(1):3465. doi: 10.1038/s41467-025-58459-1.ABSTRACTWhile it has been suggested that alterations in the composition of gut microbial metabolites may play a causative role in the pathophysiology of autism spectrum disorder (ASD), it is not known how gut microbial metabolites are associated with ASD-specific brain alterations. In this cross-sectional, case-control observational study, (i) fecal metabolomics, (ii) task-based functional magnetic resonance imaging (fMRI), and (iii) behavioral assessments were obtained from 43 ASD and 41 neurotypical (NT) children, aged 8-17. The fMRI tasks used socio-emotional and sensory paradigms that commonly reveal strong evoked brain differences in ASD participants. Our results show that fecal levels of specific tryptophan-related metabolites, including kynurenate, were significantly lower in ASD compared to NT, and were associated with: 1) alterations in insular and cingulate cortical activity previously implicated in ASD; and 2) ASD severity and symptoms (e.g., ADOS scores, disgust propensity, and sensory sensitivities). Moreover, activity in the mid-insula and mid-cingulate significantly mediated relationships between the microbial tryptophan metabolites (indolelactate and tryptophan betaine) and ASD severity and disgust sensitivity. Thus, we identify associations between gut microbial tryptophan metabolites, ASD symptoms, and brain activity in humans, particularly in brain regions associated with interoceptive processing.PMID:40229237 | DOI:10.1038/s41467-025-58459-1

BMJ Open. 2025 Apr 14;15(4):e102029. doi: 10.1136/bmjopen-2025-102029.ABSTRACTINTRODUCTION: Myocardial protection against ischaemia-reperfusion injury is a key determinant of heart function and outcome following cardiac surgery in children. However, myocardial injury still occurs routinely following aortic cross-clamping, as demonstrated by the ubiquitous rise in circulating troponin. del Nido cardioplegia was designed to protect the immature myocardium and is widely used in the USA but has not previously been available in the UK, where St. Thomas' blood cardioplegia is most common. The del Nido versus St. Thomas' blood cardioplegia in the young (DESTINY) trial will evaluate whether one solution is better than the other at improving myocardial protection by reducing myocardial injury, shortening ischaemic time and improving clinical outcomes.METHODS AND ANALYSIS: The DESTINY trial is a multicentre, patient-blinded and assessor-blinded, parallel-group, individually randomised controlled trial recruiting up to 220 children undergoing surgery for congenital heart disease. Participants will be randomised in a 1:1 ratio to either del Nido cardioplegia or St. Thomas' blood cardioplegia, with follow-up until 30 days following surgery. The primary outcome is area under the time-concentration curve for plasma high-sensitivity troponin I in the first 24 hours after aortic cross-clamp release. Secondary outcome measures include the incidence of low cardiac output syndrome and Vasoactive-Inotropic Score in the first 48 hours, total aortic cross-clamp time, duration of mechanical ventilation and lengths of stay in the paediatric intensive care unit and the hospital.ETHICS AND DISSEMINATION: The trial was approved by the West Midlands-Coventry and Warwickshire National Health Service Research Ethics Committee (21/WM/0149) on 30 June 2021. Findings will be disseminated to the academic community through peer-reviewed publications and presentation at national and international meetings. Parents will be informed of the results through a newsletter in conjunction with a national charity.TRIAL REGISTRATION NUMBER: ISRCTN13638147; Pre-results.PMID:40228861 | DOI:10.1136/bmjopen-2025-102029

J Med Chem. 2025 Apr 14. doi: 10.1021/acs.jmedchem.5c00614. Online ahead of print.ABSTRACTTo discover new antimalarials, a screen of the Janssen Jumpstarter library against Plasmodium falciparum uncovered the N-acetamide indole hit class. The structure-activity relationship of this chemotype was defined and culminated in the optimized frontrunner analog WJM664, which exhibited potent asexual stage activity and high metabolic stability. Resistant selection and whole-genome sequencing revealed mutations in PfATP4, which was validated as the target by showing that analogs exhibited reduced potency against parasites with resistance-conferring mutations in PfATP4, a metabolomic signature similar to that of the PfATP4 inhibitor KAE609, and inhibition of Na+-dependent ATPase activity consistent with on-target inhibition of PfATP4. WJM664 inhibited gamete development and blocked parasite transmission to mosquitoes but exhibited low efficacy in aPlasmodium berghei mouse model, which was attributed to ATP4 species differentiation and its moderate systemic exposure. Optimization of these attributes is required for N-acetamide indoles to be pursued for development as a curative and transmission-blocking therapy.PMID:40228810 | DOI:10.1021/acs.jmedchem.5c00614

Pharmacol Res. 2025 Apr 12:107736. doi: 10.1016/j.phrs.2025.107736. Online ahead of print.ABSTRACTSex-related differences in asparagine metabolism are associated with cancer prognosis. However, the effect of exogenous asparagine on colorectal cancer (CRC) growth in men and women remain unclear. This study aims to understand the relationship between exogenous asparagine supplementation and 17β-estradiol levels and to elucidate mechanisms underlying sex-dependent signaling during CRC development. We administered asparagine intraperitoneally to tumor-bearing immunodeficient male and female Rag2/Il2RG (R2G2) mice. Asparagine supplementation caused a significant increase in tumor asparagine levels in both the tumor-bearing male and female R2G2 mice but increased serum estradiol levels and suppressed tumor growth in female R2G2 mice only. Additionally, we combined transcriptome, metabolome and immunochemical analyses and found that intraperitoneal asparagine treatment induced sex-dependent intra-tumoral metabolic changes to asparagine, aspartate, glutamine and glutamate levels in CRC cells. We observed that in females, exogenous asparagine exerts a negative feed-back effect on de novo asparagine synthesis and is associated with the activation of a sub-population of macrophages that may secrete 17β-estradiol via an aromatase or cytochrome P450 family 19 (CYP19)-dependent mechanism, resulting in improved tumor-specific survival. Conversely, in male mice, asparagine treatment augments tumor growth and is related to decreased numbers of macrophages, reduction in CYP19-mediated 17β-estradiol secretion leading to worsened tumor-specific survival. Overall, our results reveal a novel and sex-specific role for exogenous asparagine during cancer progression and underscores the importance of understanding mechanisms that control asparagine biosynthesis.PMID:40228761 | DOI:10.1016/j.phrs.2025.107736

Neurobiol Learn Mem. 2025 Apr 12:108053. doi: 10.1016/j.nlm.2025.108053. Online ahead of print.ABSTRACTPrevious reports have shown an association between a Western high-fat diet (HFD) and poor cognitive performance. So far, there are no reports of whether a mild HFD can affect rabbit learning and hippocampal metabolic profile. This study was designed to explore whether feeding a mild HFD (5 % lard and 5 % soy oil) for 20 weeks affected eyeblink discrimination and discrimination reversal learning and hippocampal metabolic profiles. After 20 weeks on the HFD or a normal control diet, all rabbits received one day of adaptation, 20 daily sessions of two-tone discrimination (1-kHz CS + followed by air puff and 8-kHz CS- not followed by air puff), a rest day, and then 40 daily sessions of discrimination reversal (8-kHz CS + and 1-kHz CS-). Compared to rabbits fed a regular chow diet, rabbits fed a mild HFD showed better discrimination evidenced by higher responding to CS+, lower responding to CS-, and a larger discrimination index (CS+ - CS-). Widely targeted metabolomics analysis identified 1805 metabolites in the hippocampus, and significant HFD-induced changes in 162 and 165 differential metabolites in males and females, respectively. These included glycerophospholipids and fatty acyls. KEGG enrichment analysis showed glycerophospholipid metabolism (ko00564) was significantly enriched in the HFD group notably lysophosphatidylethanolamine and lysophosphatidylcholine. In summary, our data show a long-term mild HFD facilitated discrimination learning in rabbits without inducing a metabolic syndrome, and altered the hippocampal metabolic profile, which may affect neuronal cell membrane lipids and behavioral performance.PMID:40228735 | DOI:10.1016/j.nlm.2025.108053

Environ Pollut. 2025 Apr 12:126239. doi: 10.1016/j.envpol.2025.126239. Online ahead of print.ABSTRACTPersistent organic pollutants (POPs) are associated with many adverse health effects in humans, including cancers, immune, reproductive, neurological disorders and metabolic diseases. These chemicals are known to accumulate in fatty tissues, from which they can be released in other tissue compartments of living organisms, in particular, upon weight loss. This dynamic distribution of POPs remains, however poorly investigated. In this study, a xenografted POP-contaminated adipose tissue (AT) model was used to assess 1) their concentrations in the ATs, the liver and the brain and 2) their associated effects by transcriptomics, metabolomics and lipidomics approaches. In the ATs, the liver and the brain of mice grafted with POP-contaminated fat pad, most of POPs were detected 3 days and 21 days after the graft with the highest concentrations in the ATs and the lowest concentrations in the brain. Conversely, per- and polyfluoroalkyl substances presented a distinct profile as they persist in the liver but not in the ATs or in the brain. In the AT of POP-exposed mice, the most dysregulated pathways were related to mitochondrial functions, endobiotic (carbohydrate, lipid, amino acid) and xenobiotic metabolism and inflammatory response. In the liver of grafted mice, many pathways related to mitochondrial functions and metabolism were dysregulated. These results support that realistic mixture of POPs that accumulate in AT and liver induces a systemic metabolic dysfunction which may represent the mechanisms by which the POPs can promote metabolic diseases such as obesity, type 2 diabetes and cardiovascular diseases.PMID:40228731 | DOI:10.1016/j.envpol.2025.126239

J Clin Anesth. 2025 Apr 13;103:111833. doi: 10.1016/j.jclinane.2025.111833. Online ahead of print.ABSTRACTOBJECTIVE: To elucidate the role of gut microbiota and their metabolites, including short-chain fatty acids (SCFAs) and targeted metabolomics, in the development of postoperative delirium (POD) in elderly patients.DESIGN: Prospective nested case-control study.SETTING: A Chinese tertiary hospital.PARTICIPANTS: Elderly patients underwent elective orthopedic surgery.METHODS: Participants were assessed for POD using the 3-min Diagnostic Confusion Assessment Method (3D-CAM). Biological samples, including feces and plasma, were collected. A 1:1 propensity score matching (PSM) was conducted to match POD cases with non-POD cases. 16S ribosomal RNA (rRNA) sequencing and metabolomics analyses were performed on the matched case series. Predictive models were developed using logistic regression analysis, incorporating bacterial genera and metabolites that exhibited significant differences between the two groups as predictors.RESULTS: Among 234 patients who were followed up, 41 were diagnosed with POD. A total of 39 cases were matched for both the POD and control groups using PSM. No significant differences were found in the α-diversity and β-diversity of preoperative gut microbiota between the two groups. However, specific bacterial genera, including Romboutsia, Bacteroides faecalis, Blautia mucilaginosa, and Eggerthella lenta, exhibited significant differences. The risk of POD was associated with higher postoperative plasma levels of propionic acid, histidine, aspartate, and ornithine. Logistic regression and receiver operating characteristic curve analyses revealed that indicators derived from the gut microbiota and metabolites could predict POD, with an area under the curve of 0.8413 (95 % confidence interval (CI): 0.7393-0.9434).CONCLUSION: This study identified four preoperative bacterial genera and four postoperative plasma metabolites associated with an increased risk of POD in elderly orthopedic patients, suggesting the potential of gut microbiota and metabolite profiles as biomarkers for improving risk prediction and guiding interventions.PMID:40228374 | DOI:10.1016/j.jclinane.2025.111833

Environ Sci Technol. 2025 Apr 14. doi: 10.1021/acs.est.4c12870. Online ahead of print.ABSTRACTThe gastrointestinal tract (GIT) is crucial in the absorption and metabolism of xenobiotics, including phthalates─widespread environmental contaminants associated with various health risks. Estimating human exposure to phthalates via biomonitoring is challenging due to their complex metabolic pathways, resulting in a mass-balance gap between internal and external exposure. The relative contributions of the GIT and liver to phthalate metabolism remain underexplored. This study investigated the metabolism of three representative phthalate diesters─dibutyl phthalate (DBP), di(2-ethylhexyl)phthalate (DEHP), and diethyl phthalate (DEP) in GIT. We first incubated these diesters in simulated stomach and small intestine fluids to identify the primary enzyme responsible for their hydrolysis. The kinetics were further investigated under varying pH conditions (4.0, 5.0, 6.0, 7.0 or 7.5) to mimic the small intestine environment. Next, using a refined human physiologically based toxicokinetic model, we quantified the relative contributions of preabsorption intestinal versus postabsorption hepatic biotransformation to the body burden of phthalates. Our results suggested that DBP and DEHP were extensively metabolized (>90%) in the GIT by lipase, with comparatively lower hepatic involvement, while DEP underwent minimal preadsorption metabolism (13%) in the GIT, highlighting the influence of structure-dependent differences on metabolic rates. This study emphasized the importance of incorporating both intestinal and hepatic metabolism into toxicokinetic analyses. The findings demonstrate the GIT's critical role in limiting phthalate bioavailability, underscoring the need to account for the intestinal first-pass effect in toxicokinetic models to enhance predictions of phthalate pharmacokinetics and health impacts.PMID:40228148 | DOI:10.1021/acs.est.4c12870

Cancer Commun (Lond). 2025 Apr 14. doi: 10.1002/cac2.70023. Online ahead of print.ABSTRACTBACKGROUND: Hepatocellular carcinoma (HCC) is a deadly malignancy known for its ability to evade immune surveillance. NOP2/Sun RNA methyltransferase family member 2 (NSUN2), an RNA methyltransferase involved in carcinogenesis, has been associated with immune evasion and energy metabolism reprogramming. This study aimed to examine the molecular mechanisms underlying the involvement of NSUN2 in immune evasion and metabolic reprogramming of HCC.METHODS: Single-cell transcriptomic sequencing was applied to examine cellular composition changes, particularly immune cell dynamics, in HCC and adjacent normal tissues. Bulk RNA-seq and proteomics identified key genes and proteins. Methylation sequencing and methylated RNA immunoprecipitation (MeRIP) were carried out to characterize the role of NSUN2 in 5-methylcytosine (m5C) modification of sterol O-acyltransferase 2 (SOAT2). Clinical samples from 30 HCC patients were analyzed using reverse transcription-quantitative polymerase chain reaction and Western blotting. Gene expression was manipulated using CRISPR/Cas9 and lentiviral vectors. In vitro co-culture models and metabolomics were used to study HCC cell-T cell interactions, energy metabolism, and immune evasion. Tumor growth in an orthotopic mouse model was monitored by bioluminescence imaging, with subsequent measurements of tumor weight, volume, and immunohistochemical staining.RESULTS: Single-cell transcriptomic analysis identified a marked increase in malignant cells in HCC tissues. Cell communication analysis indicated that tumor cells might promote cancer progression by evading immune clearance. Multi-omics analyses identified NSUN2 as a key regulator in HCC development. MeRIP confirmed that NSUN2 facilitated the m5C modification of SOAT2. Analysis of human HCC tissue samples demonstrated pronounced upregulation of NSUN2 and SOAT2, along with elevated m5C levels in HCC tissues. In vitro experiments uncovered that NSUN2 augmented the reprogramming of energy metabolism and repressed the activity and cytotoxicity of CD8+ T cells, contributing to immune evasion. In vivo studies further substantiated the role of NSUN2 in fostering immune evasion and tumor formation of HCC by modulating the m5C modification of SOAT2.CONCLUSIONS: The findings highlight the critical role of NSUN2 in driving HCC progression through the regulation of m5C modification on SOAT2. These findings present potential molecular markers for HCC diagnosis and therapeutic targets for its treatment.PMID:40227950 | DOI:10.1002/cac2.70023

Cancers (Basel). 2025 Mar 29;17(7):1150. doi: 10.3390/cancers17071150.ABSTRACTINTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is insidious, with only 15-20% of those diagnosed suitable for surgical resection as it is either too advanced and has invaded local structures or has already spread to distant sites. The associated tumor microenvironment provides a protective shield which limits the efficacy of chemotherapeutic agents, but also impairs the delivery of nutrients required for the PDAC cells. To compensate for this, metabolic adaptions occur to provide alternative sources of fuel. The aim of this study is to explore metabolomic differences between participants with resectable PDAC compared to healthy volunteers (HV). The objectives were to use nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) to determine if resectable PDAC induces sufficient metabolic adaptations and variations which could be used to discriminate between the two groups.METHODS: Plasma samples were collected from fasted individuals with resectable PDAC (n = 23, median age 68 [IQR 56-75], 69.6% male) and HV (n = 24, median age 63 [IQR 58-71], 54.2% male). Samples were analyzed using NMR and the Biocrates MxP Quant 500 kit at University Hospital Southampton.RESULTS: NMR spectroscopy identified six independent metabolites that significantly discriminated between the PDAC and HV groups, including elevated plasma concentrations of 3-hydroxybutyrate and citrate, with decreased amounts of glutamine and histidine. MS analysis identified 84 metabolites with a significant difference between the PDAC and HV cohorts. The metabolites with a fold change (FC) > 1.5 in the PDAC population were conjugated bile acids (taurocholic acid, glycocholic acid, and glycochenodexoycholic acid).DISCUSSION: In conclusion, using metabolomics, biochemical differences between resectable PDAC and HV were detected. These differences indicate metabolic plasticity and utilization of alternative fuel sources.PMID:40227642 | DOI:10.3390/cancers17071150

Antioxidants (Basel). 2025 Mar 17;14(3):349. doi: 10.3390/antiox14030349.ABSTRACTSeed aging has adverse effects on agricultural production, mainly because seed vigor is inhibited. Spermidine can improve seed vitality and germination ability to a certain extent and is essential for plant growth and plant response to stress. This study explored how spermidine counteracted aging effects on sorghum seed germination through antioxidant metabolism regulation. Aged seeds showed decreased vigor due to heightened reactive oxygen species (ROS) and diminished antioxidants. Applying spermidine notably enhanced aged seeds' germination and vigor by boosting antioxidant enzyme activity and curbing ROS. Integrated transcriptomic, proteomic, and metabolomic analyses demonstrated that the majority of differentially expressed genes following exogenous spermidine treatment in aged sorghum seeds were significantly enriched in pathways related to glutathione metabolism, phenylpropanoid, and flavonoid biosynthesis, resulting in increased expression of genes encoding peroxidase, chalcone synthase, and glutathione s-transferase. Exogenous spermidine facilitated the synthesis of peroxidases and glutathione transferases. Analysis of flavonoid pathway intermediates showed a notable increase in antioxidant metabolites like isoquercitrin, underscoring their role in oxidative stress resistance. This multi-omics strategy underscores Spd's role in boosting aged seeds' antioxidants, highlighting the molecular basis of seed aging and Spd's rejuvenating impact.PMID:40227429 | DOI:10.3390/antiox14030349

Antioxidants (Basel). 2025 Feb 28;14(3):296. doi: 10.3390/antiox14030296.ABSTRACTThis study employed multi-omics analysis to systematically evaluate the toxic effects of intraperitoneal injection of MC-LR on GIFT tilapia. The results showed that 96 h post injection, serum levels of aspartate GOT, GPT, LYZ, T-AOC, and SOD significantly decreased (p < 0.05). In contrast, hepatic levels of CAT and MDA significantly increased. The 16S rDNA sequencing method revealed a significant reduction in the α diversity of the intestinal microbiota. At the phylum level, the relative abundances of Firmicutes and Bacteroidota significantly decreased; at the genus level, several genera, including Bacteroides and Pseudomonas, also exhibited significant changes. Functional prediction indicated that the affected pathways were primarily related to metabolism and disease. Additionally, targeted metabolomics analysis showed a significant decrease in the levels of several SCFAs, such as butyric acid. Correlation analysis further elucidated the complex interactions between the intestinal microbiota, biochemical indicators, and SCFA metabolism. Overall, the study demonstrated that MC-LR induced oxidative stress and liver damage and led to intestinal microbiota imbalance and metabolic dysfunction in GIFT tilapia.PMID:40227293 | DOI:10.3390/antiox14030296

Astrobiology. 2025 Apr 14. doi: 10.1089/ast.2024.0068. Online ahead of print.ABSTRACTA primary aim of current and future space exploration missions is the detection and identification of chemical and biological indicators of life, namely biomarkers, on Mars. The Mars Sample Return NASA-ESA program will bring to Earth samples of martian soil, acquired from up to 7 cm depth. The ESA Rosalind Franklin rover will search for signs of life in the subsurface (down to a depth of 2 meters), given the highly radioactive conditions on Mars' surface, which are not ideal for life as we know it and for the preservation of its traces. In the frame of the Lichens and Fungi Experiment, small fragments of Antarctic sandstones colonized by cryptoendolithic microbial communities were exposed to space and simulated martian conditions in low Earth orbit for 18 months, aboard the EXPOSE-E payload. Through the use of Raman and infrared spectroscopies, as well as a metabolomic approach, we aimed to detect organic compounds in a quartz mineral matrix. The results show that pigments, such as melanin, carotenoids, and chlorophyll, lipids, and amino acids, maintained their stability within minerals under simulated martian conditions in space, which makes them ideal biomarkers for the exploration of putative life on Mars.PMID:40227267 | DOI:10.1089/ast.2024.0068

Antioxidants (Basel). 2025 Feb 28;14(3):298. doi: 10.3390/antiox14030298.ABSTRACTLichens are an important source of diverse and unique secondary metabolites with recognized biological activities through experimental and computational procedures. The objective of this study is to investigate the metabolomic profile of the ethanolic extract of the Antarctic lichen Gondwania regalis and evaluate its antioxidant and antidiabetic activities with in vitro, in silico, and molecular dynamics simulations. Twenty-one compounds were tentatively identified for the first time using UHPLC/ESI/QToF/MS in negative mode. For antioxidant activity, the DPPH assay showed an IC50 value of 2246.149 µg/mL; the total phenolic content was 31.9 mg GAE/g, the ORAC assay was 13.463 µmol Trolox/g, and the FRAP assay revealed 6.802 µmol Trolox/g. Regarding antidiabetic activity, enzyme inhibition yielded IC50 values of 326.4513 µg/mL for pancreatic lipase, 19.49 µg/mL for α-glucosidase, and 585.216 µg/mL for α-amylase. Molecular docking identified sekikaic acid as the most promising compound, with strong binding affinities to catalytic sites, while molecular dynamics confirmed its stability and interactions. Toxicological and pharmacokinetic analyses supported its drug-like potential without significant risks. These findings suggest that the ethanolic extract of Gondwania regalis is a promising source of bioactive compounds for developing natural antioxidant and antidiabetic therapies.PMID:40227259 | DOI:10.3390/antiox14030298

Antioxidants (Basel). 2025 Feb 28;14(3):292. doi: 10.3390/antiox14030292.ABSTRACTThis study aimed to characterize the metabolomic profile of monofloral honey from Eucryphia cordifolia (ulmo) and evaluate the potential transfer of bioactive compounds from the plant parts, including the leaves and flowers, to the honey. Using UHPLC/Q-TOF-MS analysis, various flavonoids and phenolic acids were identified and quantified in extracts from the leaves, flowers, and honey from E. cordifolia. Given their rich polyphenolic composition, E. cordifolia leaves were included in this study to assess their potential contribution to the antioxidant properties and chemical markers of ulmo honey. Additionally, the polyphenolic compounds in honey samples were quantified. Chromatographic analysis via UHPLC-MS/MS revealed that ulmo honey contains phenolic acids such as gallic, syringic, ferulic, chlorogenic, caffeic, and coumaric acid, as well as flavonoids including pinocembrin, quercetin, luteolin, kaempferol, epicatechin, apigenin, and isorhamnetin. The results indicate that pinocembrin and gallic acid are the main chemical markers of ulmo honey, while isorhamnetin could complement its characterization as a complementary marker. UHPLC/Q-TOF-MS analysis was also utilized to compare the compounds present in the honey with those found in the plant parts (leaves and flowers), respectively. A total of 10 shared compounds were identified, 9 of which were preliminarily identified, while 1 remains unknown. Notably, dihydroquercetin 3-O-rhamnoside, quercetin 3-O-rhamnoside, cyanidin 3-(p-coumaroyl)-glucoside, and eupatorin were detected in ulmo honey for the first time. Along with gallic acid, pinocembrin, and isorhamnetin, these compounds could contribute to a characteristic fingerprint for identifying the botanical origin of the honey. Overall, these findings provide valuable insights into the chemical composition of ulmo honey and its potential application as a functional product with antioxidant properties.PMID:40227239 | DOI:10.3390/antiox14030292

Nucleic Acids Res. 2025 Apr 10;53(7):gkaf280. doi: 10.1093/nar/gkaf280.ABSTRACTNuclear actin mediates enhancer-dependent transcriptional regulation at compartment level, playing critical roles in 3D genome organization. In β-actin depleted cells, H3K27 acetylation is enhanced, directly affecting enhancer-dependent transcriptional regulation and gene expression changes during compartment-switching. Here, we report these mechanisms are influenced by the long non-coding RNA (lncRNA) Meg3. Bulk RNA-seq analysis and qPCR on wild-type (WT), heterozygous (HET), and β-actin knockout (KO) mouse embryonic fibroblasts (MEFs) show that β-actin depletion significantly alters expression of several lncRNAs, including Meg3. Results from ChIRP-seq, ChIRP-MS, and fRIP-qPCR revealed that in β-actin KO cells, Meg3 becomes enriched and binds to H3K27 acetylation marks within gene regulatory regions. By integrating RNA-seq, H3K27 acetylation ChIP-seq, ATAC-seq, and HiC-seq data through activity by contact (ABC) analysis, we discovered Meg3 binding disrupts promoter-enhancer interactions in β-actin KO cells. These results, combined with metabolomics in WT, HET, and β-actin KO MEFs, show Meg3 binding to regulatory regions at sites of increased H3K27 acetylation impairs the expression of genes involved in the synthesis of chondroitin, heparan, dermatan sulfate, and phospholipases. We propose that in β-actin KO cells Meg3 binds to H3K27 acetylation levels. This interferes with promoter-enhancer interactions, disrupts genome organization, and downregulates gene expression and key metabolic pathways.PMID:40226914 | DOI:10.1093/nar/gkaf280

Nutr Res Pract. 2025 Apr;19(2):273-291. doi: 10.4162/nrp.2025.19.2.273. Epub 2025 Mar 19.ABSTRACTBACKGROUND/OBJECTIVES: This study aimed to use plasma metabolites to identify clusters of breast cancer survivors and to compare their dietary characteristics and health-related factors across the clusters using unsupervised machine learning.SUBJECTS/METHODS: A total of 419 breast cancer survivors were included in this cross-sectional study. We considered 30 plasma metabolites, quantified by high-throughput nuclear magnetic resonance metabolomics. Clusters were obtained based on metabolites using 4 different unsupervised clustering methods: k-means (KM), partitioning around medoids (PAM), self-organizing maps (SOM), and hierarchical agglomerative clustering (HAC). The t-test, χ2 test, and Fisher's exact test were used to compare sociodemographic, lifestyle, clinical, and dietary characteristics across the clusters. P-values were adjusted through a false discovery rate (FDR).RESULTS: Two clusters were identified using the 4 methods. Participants in cluster 2 had lower concentrations of apolipoprotein A1 and large high-density lipoprotein (HDL) particles and smaller HDL particle sizes, but higher concentrations of chylomicrons and extremely large very-low-density-lipoprotein (VLDL) particles and glycoprotein acetyls, a higher ratio of monounsaturated fatty acids to total fatty acids, and larger VLDL particle sizes compared with cluster 1. Body mass index was significantly higher in cluster 2 compared with cluster 1 (FDR adjusted-P KM < 0.001; P PAM = 0.001; P SOM < 0.001; and P HAC = 0.043).CONCLUSION: The breast cancer survivors clustered on the basis of plasma metabolites had distinct characteristics. Further prospective studies are needed to investigate the associations between metabolites, obesity, dietary factors, and breast cancer prognosis.PMID:40226766 | PMC:PMC11982688 | DOI:10.4162/nrp.2025.19.2.273