PubMed

Metabolites. 2025 Mar 21;15(4):213. doi: 10.3390/metabo15040213.ABSTRACTBackground/Objectives: Currently, the diagnosis of autism spectrum disorder (ASD) relies on behavioral observations, frequently causing delays in early identification. Prognostic markers are essential for customizing therapy and monitoring progress. However, there are currently no recognized biomarkers for ASD. The current systematic review aims to analyze studies on the intestinal metabolome in children (both autistic and non-autistic) to identify potential metabolites for diagnostic and prognostic purposes. Methods: We searched Medline, Scopus, Embase, and Web of Science for relevant publications. Results: We identified 11 studies examining the gut metabolome that distinguished between autistic and non-autistic children. These studies also revealed connections between gut metabolites, developmental scores, and symptoms. The substances identified were associated with metabolic pathways such as amino acids, vitamins, lipids, oxidative stress, glycans, xenobiotics, and nucleotides. Conclusions: These findings suggest metabolic changes that may be linked to the causes or development of autism. Although these observations came from a few reports, only high-quality studies were included in this review. Further research is essential to confirm the identified substances as biomarkers.PMID:40278342 | DOI:10.3390/metabo15040213

J Pers Med. 2025 Mar 24;15(4):124. doi: 10.3390/jpm15040124.ABSTRACTBackground: Hepatobiliary liver cancers (HBLCs) represent the sixth most common neoplasm in the world. Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) constitute the main HBLC types, with alarming epidemiological projections. Methods: In recent decades, alterations in gut microbiota, with mutual implications on the gut-liver axis and gut-biliary axis permeability status, have been massively investigated and proposed as HBLC pathogenetic deus ex machina. Results: In the HCC setting, elevated intestinal levels of Escherichia coli and other Gram-negative bacteria have been demonstrated, resulting in a close association with increased lipopolysaccharide (LPS) serum levels and, consequently, chronic systemic inflammation. In contrast, the intestinal microbiota of HCC individuals feature reduced levels of Lactobacillus spp., Bifidobacterium spp., and Enterococcus spp. In the CC setting, evidence has revealed an increased expression of Lactobacillus spp., with enhanced levels of Actynomices spp. and Alloscardovia spp. Besides impaired strains/species representation, gut-derived metabolites, including bile acids (BAs), short-chain fatty acids (SCFAs), and oxidative-stress-derived products, configure a network severely impacting the progression of HBLC. Conclusions: In the era of Precision Medicine, the clarification of microbiota composition and functioning in HCC and CC settings can contribute to the identification of individual signatures, potentially providing novel diagnostic markers, therapeutic approaches, and prognostic/predictive tools.PMID:40278303 | DOI:10.3390/jpm15040124

J Xenobiot. 2025 Mar 26;15(2):48. doi: 10.3390/jox15020048.ABSTRACTDuckweeds are a family of small floating macrophytes (the Lemnaceae) that inhabit quiet freshwaters worldwide. They have long been employed to determine toxicity to higher plants in the aquatic environment, and standardized national and international protocols have been developed for this purpose using two representative species. While these protocols, which assess the growth of the leaf-like fronds of the tested duckweed, are indeed suitable and still frequently used for detecting the toxicity of water-borne substances to aquatic higher plant life, they are cumbersome and lengthy, determine endpoints rather than depict toxicity timelines, and provide no information as to the mechanisms involved in the indicated toxicity. Progress has been made in downscaling, shortening and improving the standardized assay procedures, and the use of alternative duckweed species, protocols and endpoints for detecting toxicity has been explored. Biomarkers of toxic effect have long been determined concomitantly with testing for toxicity itself, and their potential for the assessment of toxicity has recently been greatly expanded by transcriptomic, proteomic and metabolomic techniques complemented by FITR spectroscopy, transformation and genotoxicity and timescale toxicity testing. Improved modern biomarker analysis can help to both better understand the mechanisms underlying toxicity and facilitate the identification of unknown toxins.PMID:40278153 | DOI:10.3390/jox15020048

J Fungi (Basel). 2025 Apr 19;11(4):325. doi: 10.3390/jof11040325.ABSTRACTRecent studies highlight the potential of Saccharomyces species as probiotics due to their ability to modulate microbial interactions and reduce cariogenic activity, yet the underlying metabolic mechanisms remain unclear. This study investigates the cross-kingdom metabolic effects of Saccharomyces boulardii and Saccharomyces cerevisiae on the metabolic processes of Streptococcus mutans and Candida albicans using a metabolomics-based approach. Untargeted LC-MS/MS analysis was conducted to assess metabolites in a planktonic model, followed by metabolomic profiling and pathway analysis to identify key metabolic alterations. The results revealed that S. boulardii and S. cerevisiae demonstrated metabolic regulatory effects on S. mutans and C. albicans. Specifically, S. boulardii down-regulated 262 metabolites and up-regulated 168, while S. cerevisiae down-regulated 265 metabolites and up-regulated 168. Both yeast species down-regulated carbohydrate and amino acid metabolism in S. mutans and C. albicans, resulting in reduced biomolecule synthesis and a less acidic environment. S. boulardii and S. cerevisiae also up-regulated certain metabolic processes, including purine metabolism, suggesting a compensatory mechanism for nucleotide synthesis. Notably, dual regulatory effects were observed, where specific metabolites were simultaneously up-regulated and down-regulated, indicating complex metabolic crosstalk. These findings suggest that both S. boulardii and S. cerevisiae modulate microbial metabolism through a shared mechanism, offering potentials for dental caries prevention.PMID:40278145 | DOI:10.3390/jof11040325

J Fungi (Basel). 2025 Apr 18;11(4):323. doi: 10.3390/jof11040323.ABSTRACTPhlebopus portentosus is an edible and medicinal ectomycorrhizal mushroom with delicious and high nutritional value. However, the mechanism of secondary metabolite biosynthesis in P. portentosus is still unclear. In this study, the genomics, metabolomics, and transcriptomics were integrated to reveal the biosynthesis mechanism of secondary metabolites in P. portentosus under different cultivation conditions. The 31.4 Mb genome of P. portentosus YAF023 with 15 scaffolds was assembled by Illumina and Nanopore sequencing and annotated, and 206 cytochrome P450s, 201 carbohydrate-active enzymes, 186 transcription factors, 18 terpene synthases (TPSs), and 5 polyketide synthases (PKSs) were identified. Multi-omics analysis showed that PpPKS1 is probably involved in the biosynthesis of Ethyl orsellinate; PpPKS2 and PpPKS5 are probably involved in the synthesis of 6-Methylsalicylic acid and Cytochalasin Z5, respectively; PpTRI5 was involved in the tetracyclic sesquiterpene β-type trichodiene compounds; and PpSTCs was involved in the synthesis of β-copaene analogs or derivatives. Co-expression network analysis and binding site prediction of the promoter regions suggested that PpHOX4 and PpHSF1 regulated the gene expression of PpPKS1, and Ppzf-C2H2 32 and PpHSF5 regulated the gene expression of PpSTCs 8, and PpSTCs 3, respectively. This study will provide an important foundation for further development and utilization of secondary metabolites of P. portentosus.PMID:40278143 | DOI:10.3390/jof11040323

J Fungi (Basel). 2025 Apr 10;11(4):302. doi: 10.3390/jof11040302.ABSTRACTPersistent fungal pathogens remain a threat to global food security as these pathogens continue to infect crops despite different mitigating strategies. Traditionally, synthetic fungicides are used to combat these threats, but their environmental and health impacts have spurred interest in a more sustainable, eco-friendly approach. Endolichenic fungi (ELF) are a relatively underexplored group of microorganisms found thriving inside the lichen thalli. They are seen as promising alternatives for developing sustainable plant disease management strategies. Hence, in this study, a total of forty ELF isolates from two fruticose lichen hosts-Ramalina and Usnea, were tested and compared for their antagonistic activities against three economically important filamentous fungal pathogens-Colletotrichum gloeosporioides, Cladosporium cladosporioides, and Fusarium oxysporum. The results of the dual culture assay showed that all ELF isolates successfully reduced the growth of the three filamentous fungal pathogens with varying degrees, and with direct contact inhibition as the predominant trait among the endolichenic fungi. Comparing the antagonistic activities between the different endolichenic fungi from the two lichen hosts, ELF isolates from Ramalina generally demonstrated a higher percentage inhibition of growth of the test fungi as compared to ELF isolates from Usnea. This study underscores the importance of endolichenic fungi as an efficient biocontrol agent.PMID:40278123 | DOI:10.3390/jof11040302

J Fungi (Basel). 2025 Apr 2;11(4):279. doi: 10.3390/jof11040279.ABSTRACTThe human gastrointestinal tract harbors a vast array of microorganisms, which play essential roles in maintaining metabolic balance and immune function. While bacteria dominate the gut microbiome, fungi represent a much smaller, often overlooked fraction. Despite their relatively low abundance, fungi may significantly influence both health and disease. Advances in next-generation sequencing, metagenomics, metatranscriptomics, metaproteomics, metabolomics, and computational biology have provided novel opportunities to study the gut mycobiome, shedding light on its composition, functional genes, and metabolite interactions. Emerging evidence links fungal dysbiosis to various diseases, including inflammatory bowel disease, colorectal cancer, metabolic disorders, and neurological conditions. The gut mycobiome also presents a promising avenue for precision medicine, particularly in biomarker discovery, disease diagnostics, and targeted therapeutics. Nonetheless, significant challenges remain in effectively integrating gut mycobiome knowledge into clinical practice. This review examines gut fungal microbiota, highlighting analytical methods, associations with human diseases, and its potential role in precision medicine. It also discusses pathways for clinical translation, particularly in diagnosis and treatment, while addressing key barriers to implementation.PMID:40278100 | DOI:10.3390/jof11040279

Ginekol Pol. 2025 Apr 25. doi: 10.5603/gpl.101741. Online ahead of print.ABSTRACTOBJECTIVES: In this pilot study the proton Nuclear Magnetic Resonance (¹H NMR)-based metabolomics was applied to explore the serum metabolomes of the patients with high-grade serous ovarian carcinoma (HGSOC) and the patients with benign gynaecological disease and to identify the characteristic biomarkers.MATERIAL AND METHODS: We analyzed serum samples from 17 HGSOC patients and 14 control patients with benign gynecological conditions. Serum metabolites were profiled using 1H NMR spectroscopy, and multivariate data analyses, including Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA), were performed to identify discriminating metabolites.RESULTS: The multivariate analysis revealed the lower levels of the lipid compounds, choline, branched-chain amino acids, 3-hydroxybutyrate (3HB), acetoacetate, and the higher level of lactate in the sera of the HGSOC patients compared to the control group.CONCLUSIONS: NMR-based metabolomic analysis can serve as a supporting method for the detection of ovarian cancer and may be useful as an adjunct to molecular diagnostics.PMID:40278006 | DOI:10.5603/gpl.101741

Cells. 2025 Apr 9;14(8):565. doi: 10.3390/cells14080565.ABSTRACTBackground: Vitiligo is featured by the manifestation of white maculae and primarily results from inflammatory/immune-selective aggression to melanocytes. The trigger mechanism leading to the activation of resident immune cells in the skin still lacks a molecular description. There is growing evidence linking altered mitochondrial metabolism to vitiligo, suggesting that an underlying metabolic defect may enable a direct activation of the immune system. Recent evidence demonstrated the association of vitiligo with disorders related to systemic metabolism, including insulin resistance (IR) and lipid disarrangements. However, IR, defined as a cellular defect in the insulin-mediated control of glucose metabolism, and its possible role in vitiligo pathogenesis has not been proven yet. Methods: In this study, we compared the Ins/IGF-1 intracellular signaling of dermal and epidermal cells isolated from non-lesional vitiligo skin to that belonging to cells obtained from healthy donors. Results: We demonstrated that due to the intensified glucose uptake, S6, and insulin receptor substrate 1 (IRS1) chronic phosphorylation, their inducibilities were downsized, a condition that coincides with the definition of insulin resistance at the cellular level. Correspondingly, the mitogenic and metabolic activities normally provoked by Ins/IGF-1 exposure resulted in significantly compromised vitiligo cells (p ≤ 0.05). Besides all the vitiligo-derived skin cells manifesting an energetic disequilibrium consisting of a low ATP, catabolic processes activation, and chronic oxidative stress, the functional consequences of this state appear amplified in the keratinocyte lineage. Conclusion: The presented data argue for insulin and IGF-1 resistance collocating dysfunctional glucose metabolism in the mechanisms of vitiligo pathogenesis. In vitiligo keratinocytes, the intrinsic impairment of intracellular metabolic activities, particularly when associated with stimulation with Ins/IGF-1, converges into an aberrant pro-inflammatory phenotype that may initiate immune cell recruitment.PMID:40277891 | DOI:10.3390/cells14080565

Protein Sci. 2025 May;34(5):e70144. doi: 10.1002/pro.70144.ABSTRACTAberrant levels of the cysteine protease Calpain-2 have been linked to neurodegeneration, inflammation, and cancer, yet our understanding of this protease and its substrates remains limited. Systematic studies to identify Calpain-2 substrates have been largely confined to peptide libraries or in vitro studies, which fail to represent physiological cellular conditions and physiologically relevant substrates. To identify existing and novel Calpain-2 substrates, we used a genetic approach to knockout Calpain-2 in the THP-1 human monocyte-like cells, followed by proteomic and N-terminomic/TAILS mass spectrometry approaches to identify Calpain-2 substrates. We identified 51 substrates that may be cleaved directly by Calpain-2 or indirectly by downstream proteases. The direct cleavage of selected substrates by Calpain-2 was confirmed using in vitro assays. Finally, metabolomics analysis identified a role for Calpain-2 in the regulation of pyrimidine and glutathione metabolism. Our unbiased and quantitative mass spectrometry analytical pipeline provides new evidence on the physiological functions of Calpain-2 and its newly identified substrates in THP-1 cells.PMID:40277457 | DOI:10.1002/pro.70144

Microbiol Spectr. 2025 Apr 25:e0165324. doi: 10.1128/spectrum.01653-24. Online ahead of print.ABSTRACTPodophyllotoxin (PPT), an extract from the traditional medicinal plant Dysosma, offers anti-viral and anti-cancer benefits, though its use is limited by toxicity. The mechanisms of PPT's inherent pulmonary toxicity remain elusive. This study leverages the novel "Toxicological Evidence Chain" theory to explore the potential involvement of the "gut-lung axis" in PPT-induced pulmonary toxicity. In this study, we examined injury phenotypes in rats, evaluated pulmonary pathological changes, measured pro-inflammatory factors, and conducted comprehensive analyses of both pulmonary and gut microbiomes and metabolomics. Our findings indicate that exposure to PPT leads to significant pulmonary damage in these animals. The PPT group exhibited significantly elevated levels of total protein, albumin, alkaline phosphatase, and lactate dehydrogenase in bronchoalveolar lavage fluid, accompanied by marked upregulation of interleukin (IL)-18, tumor necrosis factor-alpha, IL-6, and IL-1β expression in lung tissue. Furthermore, 16S rRNA gene sequencing analysis revealed significant increases of Akkermansia, Escherichia-Shigella, and Bacteroides in both intestinal contents and lung tissue of PPT-treated animals, concomitant with notable elevations in short-chain fatty acids (SCFAs) such as isobutyric acid and isovaleric acid, and reductions in acetic acid, propionic acid, and butyric acid. The increased abundance of Akkermansia and Escherichia-Shigella may enhance pulmonary inflammatory factors through effects on intestinal barrier integrity and direct immune stimulation, while elevated Bacteroides may alter SCFA production, exacerbating pulmonary inflammation under PPT treatment, suggesting a potential role in the manifestation of PPT-induced pulmonary toxicity. This study offers new insights into the mechanisms of PPT-induced pulmonary toxicity, highlights the role of the gut-lung axis, and provides avenues for therapeutic intervention.IMPORTANCE: PPT, derived from the medicinal plant Dysosma, is known for its anti-cancer and anti-viral properties but limited by severe pulmonary toxicity. This study illuminates the gut-lung microbiota axis's role in mediating this toxicity, revealing how specific microbial and metabolic alterations contribute to lung damage. By uncovering these mechanisms, our research opens avenues for interventions that could mitigate PPT's side effects, potentially enhancing its safety and widening its therapeutic use.PMID:40277406 | DOI:10.1128/spectrum.01653-24

Biomed Chromatogr. 2025 Jun;39(6):e70093. doi: 10.1002/bmc.70093.ABSTRACTCorydalis yanhusuo W.T.Wang (YHS) is a commonly used traditional Chinese medicine, often prescribed for treating a variety of pains. In recent years, there has been a gradual increase in the number of reports to liver injury caused by YHS and its preparations, but the exact type and mechanism of hepatotoxicity are still unclear. In the present study, we demonstrated that YHS could induce idiosyncratic drug-induced liver injury (IDILI) in the inflammatory activation models. A total of 459 differential genes and 25 differential metabolites were identified by transcriptomics and metabolomics, which were significantly enriched in the TNF and NF-κB signaling pathways as well as glycerophospholipid metabolism, sphingolipid metabolism, and arachidonic acid metabolism. In addition, YHS significantly increased the levels of TNF-α, IL-1β, and IL-6. Therefore, we believe that the mechanism of toxicity may be related to the TNF and NF-κB signaling pathways, with glycerophospholipid metabolism, sphingolipid metabolism, and arachidonic acid metabolism also playing important roles. It provides a reference for the safe and rational use of YHS in clinical practice and contributes to the precise prevention and control of the risk of liver toxicity associated with YHS.PMID:40277353 | DOI:10.1002/bmc.70093

Food Funct. 2025 Apr 25. doi: 10.1039/d4fo05713a. Online ahead of print.ABSTRACTBreast milk (BM), as an optimal food, provides the newborn with a variety of minor compounds relevant for health and wellbeing. Endogenous steroids, also minor constituents, are mainly secreted in BM as conjugated metabolites. Recent research has revealed the relevance of steroid conjugates in many physiological processes. Thus, their presence in BM appears to be very intriguing, especially in relation to breastfeeding. The objective of our study was to profile conjugated steroid metabolites present in BM in relation to the lactation stage, and to promote further evaluation of their importance in breastfeeding. For this purpose, we developed and used a direct UHPLC-MS/MS metabolomics approach capable to detect more than 60 conjugated metabolites (mono-sulfated, mono-glucuronylated, bis-sulfated and sulfate-glucuronylated) from all steroid families. We compared the occurrence of these metabolites in samples collected from breastfeeding mothers and stratified by lactation stages: colostrum, transitional and mature milk. Our results showed that many biologically relevant conjugated steroids are secreted in BM. Their concentrations were highest in colostrum, decreased remarkably in transitional and were much lower in mature milk, with some exceptions. The profile of metabolites also differed considerably between lactation stages. The approximate daily secretion in BM indicated that infants are exposed to significant oral doses of steroid conjugates during the first week of lactation. The supply of these metabolites in BM declined and became constant after the second week postpartum. Overall, our data provide a foundation for further investigation on the physiological relevance of BM secreted steroid metabolites in relation to both mother and child.PMID:40277187 | DOI:10.1039/d4fo05713a

Xenobiotica. 2025 Apr 25:1-10. doi: 10.1080/00498254.2025.2497047. Online ahead of print.ABSTRACT1. Feature-based molecular networking (FBMN), an advanced metabolomics tool leveraging MS/MS spectral similarity, was applied to update metabolite characterization of fenbendazole (FBZ), a veterinary antiparasitic agent with emerging anticancer potential in humans. Despite its therapeutic promise, FBZ's human metabolic pathways remain poorly understood.2. In this study, FBMN was utilised for the comprehensive in vitro profiling of FBZ metabolites across species, employing high-resolution liquid chromatography-mass spectrometry (LC-HRMS) with data-dependant MS2 acquisition.3. Nine metabolites, including two novel sulfate-conjugated forms (M2 sulfate and M7 sulfate), were identified and structurally characterised through integrated FBMN analysis. Oxidative metabolites (M1-M4) were found to be more abundant in rat liver microsomes, whereas monkey hepatocytes exhibited higher levels of most metabolites. Notably, hydrolysed FBZ (M5) dominated human samples, accounting for the largest proportion in both liver microsomes and hepatocytes, suggesting species-specific enzymatic activity.4. The application of FBMN provided an enhanced, systematic approach for metabolite identification and inter-species comparison, revealing critical metabolic differences that support FBZ biotransformation. These findings offer novel insights into FBZ's metabolic pathways, supporting its safety and efficacy assessment for potential human therapeutic applications.PMID:40277129 | DOI:10.1080/00498254.2025.2497047

Environ Sci Technol. 2025 Apr 25. doi: 10.1021/acs.est.5c00681. Online ahead of print.ABSTRACT1,2-Bis (2,4,6-tribromophenoxy) ethane (BTBPE) has been increasingly detected in environmental and biota samples, primarily accumulating in the liver. However, the mechanism underlying BTBPE-induced metabolic dysregulation remains unclear. In this study, molecular docking and microscale thermophoresis assays indicated that BTBPE binds to zebrafish liver X receptor α (LXRα). Subsequently, zebrafish embryos were exposed to BTBPE, an LXR antagonist (GSK2033), or coexposed to BTBPE with an LXR agonist (GW3965) for 120 h postfertilization (hpf). The results showed that BTBPE induced reduction in body weight and lipid levels, likely via inhibition of the LXR signaling pathway. Exposure of adult female zebrafish to environmentally relevant concentrations of BTBPE (0.01-10 μg/L) for 28 days induced developmental toxicity, evidenced by decreases in body weight, growth rate, and fat accumulation. Metabolomic analysis revealed that BTBPE-induced alterations in liver metabolites were primarily associated with LXR-mediated lipid metabolic pathways such as glycerophospholipid metabolism and primary bile acid biosynthesis. Additionally, BTBPE impaired the physical barrier and induced inflammation, resulting in gut microbiota dysbiosis, which is potentially linked to LXR activation. These effects were validated through the alterations of multiple biomarkers at various levels. Overall, our results suggest that BTBPE disrupts lipid metabolism and gut function via the LXR-mediated pathway.PMID:40277015 | DOI:10.1021/acs.est.5c00681

ACS Agric Sci Technol. 2025 Mar 7;5(4):593-602. doi: 10.1021/acsagscitech.4c00722. eCollection 2025 Apr 21.ABSTRACTThe pattern of plant responses, particularly on the seeds/grains metabolite profile, after generational exposure to contaminants is not well documented. Seeds from wheat cultivated in soil amended with PFOS at 0 and 25 mg/kg in the first generation were grown in clean soil to produce daughter plants and seeds in the second generation and assigned treatment combinations of 0-0 mg/kg PFOS and 25-0 mg/kg PFOS. Plant stress and responses including growth and biomass production, chlorophyll content, lipid peroxidation, and enzyme activity were measured over a short exposure period (21 days growth period). Biomass yields, elemental concentration, and grain metabolites were also measured after a long exposure period (92 days growth period). The daughter plants exhibited decreased chlorophyll content and lipid peroxidation in a short exposure period. The elemental concentrations were mostly not affected except for changes in microelements, except B, in the grains. In the metabolomics analysis, grains harvested from plants previously exposed to PFOS (i.e., 25-0 mg/kg PFOS) showed increased abundances of sucrose, linolenic acid, tryptophan, inositol-4-monophosphate, and ferulic acid, perhaps in response to adaptation to former stress. The current findings seem to suggest that one-generation exposure to PFOS does not cause detrimental effects on the next generation after the cessation of exposure. The results provide insights into the effects of generational exposure of plants to PFOS.PMID:40276683 | PMC:PMC12015812 | DOI:10.1021/acsagscitech.4c00722

Front Cell Dev Biol. 2025 Apr 10;13:1543636. doi: 10.3389/fcell.2025.1543636. eCollection 2025.ABSTRACTBACKGROUND: Doxorubicin (DOX) is a widely used chemotherapeutic agent known for its efficacy against various cancers, but its clinical application is often limited by its cardiotoxic effects. The exact mechanisms of DOX-induced cardiotoxicity remain unclear, requiring further investigation. Early diagnosis is essential to enhance the quality of life and prognosis for patients with malignancies. This study aims to identify biomarkers and therapeutic targets for DOX cardiotoxicity.METHODS: Heart tissue samples from 20 DOX-treated cardiotoxic mice and 19 normal controls were analyzed using liquid chromatography-mass spectrometry (LC-MS). Multivariate statistical analysis identified differential metabolites. Key metabolites were assessed using a random forest algorithm, and ROC curves evaluated diagnostic value. H9C2 rat cardiomyoblast cells were cultured to investigate the protective effects of these metabolites.RESULTS: Among 291 metabolites, significant differences emerged between cardiotoxic and normal mice. Five metabolites-4-hydroxy-valeric acid, 2-methylbutanoic acid, traumatic acid, PI (18:2 (9Z, 12Z)/0:0), and MIPC (t18:0/24:0 (2OH))-showed diagnostic potential. ROC analysis indicated excellent value for 4-hydroxy-valeric acid and PI (18:2 (9Z, 12Z)/0:0) and high discriminatory power for 2-methylbutanoic acid (AUC = 0. 99). Pathway analysis highlighted glycosylphosphatidylinositol-anchor biosynthesis, unsaturated fatty acids biosynthesis, pantothenate and CoA pathways, among others, associated with DOX-induced cardiotoxicity. In addition, we found that the differential metabolite Cer (d18:0/12:0) can improve DOX-induced myocardial cell damage and inhibit apoptosis-related protein expression at the cellular level.CONCLUSION: Heart tissue metabolomics with LC-MS identified critical metabolites and pathways associated with DOX cardiotoxicity, suggesting biomarkers for early diagnosis and potential therapeutic targets to mitigate DOX-related cardiotoxicity and improve clinical outcomes.PMID:40276655 | PMC:PMC12018317 | DOI:10.3389/fcell.2025.1543636

Front Pharmacol. 2025 Apr 10;16:1559584. doi: 10.3389/fphar.2025.1559584. eCollection 2025.ABSTRACTIntroduction: Aging is associated with significant metabolic alterations that contribute to cellular senescence and age-related functional decline. As individuals age, an increased prevalence of oral diseases and a gradual decline in oral functions are observed. However, the metabolic shifts underlying oral mucosal aging remain unexplored. Methods: We initially conducted histological analyses on the tongues from young (4-week-old), adult (4-month-old) and old (20-month-old) C57BL/6 mice to identify age-related alterations in the tongue mucosa. Subsequently, metabolomics analysis was performed to characterize metabolic profiles of mouse tongues across these age groups and identify metabolic biomarkers of oral mucosal aging. Then we validate the anti-senescence effect of carnosine and investigate its underlying mechanisms using a tert-butyl hydroperoxide (tBHP)-induced cellular senescence model in vitro. Finally, metabolomics analyses of human saliva and blood were conducted to explore associations between carnosine levels and systemic aging. Results: Compared to young and adult mice, we observed epithelial atrophy and an accumulation of senescent cells in the tongue mucosa of old mice. After that, we found significant differences in the metabolic profiles among the young, adult, and old mouse tongues. Carnosine was identified as a potential biomarker of oral mucosal aging, as its levels declined significantly with age. Consistently, carnosine synthase 1 (CARNS1) activity decreased, and carnosinase 2 (CNDP2) activity increased with age in the tongue mucosa. Furthermore, carnosine protected oral epithelial cells from tBHP-induced cellular senescence by reducing oxidative stress, mitigating DNA damage, and downregulating Nrf2/HO-1 pathway. In humans, salivary and blood carnosine levels also declined with age and were significantly associated with age-related diseases. Discussion: Our findings reveal dynamic metabolic reprogramming during natural oral mucosal aging and highlight the dual role of carnosine as both an aging biomarker and a therapeutic target for combating age-related mucosal degeneration. These insights support the development of novel carnosine-based interventions to preserve oral mucosal function, prevent age-related oral diseases, and improve oral health in the aging population, thereby advancing healthy aging.PMID:40276606 | PMC:PMC12018427 | DOI:10.3389/fphar.2025.1559584

Front Endocrinol (Lausanne). 2025 Apr 10;16:1518043. doi: 10.3389/fendo.2025.1518043. eCollection 2025.ABSTRACTOBJECTIVE: To identify potential diagnostic metabolic biomarkers for pregnancy loss (PL) by performing untargeted metabolomics analysis.METHODS: The present study performed untargeted metabolomics analysis on plasma samples from PL patients (n=70) and control subjects (n=122) using liquid chromatography‒mass spectrometry (LC‒MS). Metabolic profiles were evaluated using orthogonal partial least squares discriminant analysis (OPLS-DA), and pathway enrichment analysis was conducted via the KEGG database. LASSO regression was employed to identify significant metabolites, and their diagnostic performance was evaluated through receiver operating characteristic (ROC) curves. Pearson correlation analysis was used to explore the relationships between differentially abundant metabolites and clinical parameters.RESULTS: In total, 359 metabolites were identified, 57 of which were significantly altered between the control and PL group through OPLS-DA. Differential metabolites were significantly enriched in caffeine metabolism, tryptophan metabolism, and riboflavin metabolism pathways. Key metabolites, such as testosterone glucuronide, 6-hydroxymelatonin, and (S)-leucic acid, exhibited strong diagnostic potential, with AUC values of 0.991, 0.936 and 0.952, respectively, and the combined AUC was 0.993. Furthermore, Pearson correlation analysis revealed a significant negative correlation between the waist‒to‒hip ratio (WHR) and the abundance of testosterone glucuronide (r = -0.291, p = 0.0146), and a significant positive correlation between WHR and (S)-leucic acid (r = 0.248, p = 0.0381) in the PL group.CONCLUSION: We identified a panel of plasma metabolites with significant diagnostic potential for PL. These biomarkers may facilitate early, noninvasive diagnosis and offer insights into metabolic dysregulation associated with pregnancy loss.PMID:40276553 | PMC:PMC12018233 | DOI:10.3389/fendo.2025.1518043

Front Nutr. 2025 Apr 10;12:1541162. doi: 10.3389/fnut.2025.1541162. eCollection 2025.ABSTRACTThe fruiting bodies of Ganoderma lucidum are renowned for their therapeutic properties, primarily due to their triterpenoid content. Variability in G. lucidum strains may influence the composition and abundance of triterpenoids. In this study, we explored the triterpenoid superiority in a newly developed G. lucidum strain (GL_V2) obtained through mutation breeding, and compared it to a widely cultivated strain (GL_V1). GL_V2 exhibited a 1.4-fold increase in total triterpenoid content and higher DPPH radical scavenging activity compared to GL_V1, while polysaccharide levels remained consistent. Using UPLC-Q-Orbitrap-MS and chemometric analyses, we identified 589 metabolites, including 86 triterpenoids. Multivariate statistical analyses revealed clear differences in overall metabolite profiles and triterpenoid compositions between the two strains. OPLS-DA identified 56 triterpenoids as key distinguishing markers with VIP values above 1.0. Notably, GL_V2 exhibited increased levels of seven ganoderic acids, two ganoderiols, three ganolucidic acids, and two ganosporelactones, while GL_V1 showed higher concentrations of six lucidenic acids. These results highlight the superior triterpenoid composition of GL_V2 and its potential for developing more potent G. lucidum-derived products. This study offers valuable insights into varietal differences in triterpenoid profiles and their implications for the cultivation and therapeutic use of G. lucidum. Additionally, the findings of this study suggest that GL_V2 holds significant potential for the development of more effective nutraceutical and pharmaceutical products derived from G. lucidum.PMID:40276533 | PMC:PMC12018227 | DOI:10.3389/fnut.2025.1541162