PubMed

Microbiol Spectr. 2025 Mar 25:e0237724. doi: 10.1128/spectrum.02377-24. Online ahead of print.ABSTRACTMusic intervention is gaining recognition as a cost-effective therapeutic for improving human health. Despite its growing application, the mechanisms through which music exerts beneficial health effects remain largely unexplored. Here, we show that music can exert beneficial effects in mice through modulating gut microbiome composition. Adult mice were exposed to ambient noise, Mozart's Flute Quartet in D Major, K. 285, or white noise over a three-week period. Afterward, we observed treatment-specific changes in the community of gut commensal bacteria in these animals. Upon subsequent challenge with the bacterial pathogen Salmonella typhimurium, control groups exhibited significant weight loss and increased Salmonella colonization, whereas the Mozart-treated group did not. 16S ribosomal RNA gene sequencing revealed that the Mozart group showed a significant increase in Lactobacillus salivarius, a probiotic known for its antibacterial properties. Further experiments confirmed that L. salivarius mitigated Salmonella infection in mice and that L. salivarius acidified local environments in in vitro culture, thus inhibiting Salmonella growth. Additionally, mice exposed to Mozart consumed more food but showed similar body weight compared to the control groups. Behavioral assessments, including open field and object location tests, revealed that Mozart-treated mice were more active, less anxious, and exhibited enhanced spatial memory. Finally, Mozart exposure was shown to significantly boost colonization of administered L. salivarius and alter gut metabolite profiles. These findings suggest that music exposure fosters healthier gut microbiota, enhancing resistance to bacterial infections and highlighting the potential of music therapy as a novel strategy to combat drug-resistant pathogen infections.IMPORTANCE: Music therapy is increasingly recognized as a low-cost approach to improving health, but how it works remains unclear. Our study demonstrates that music can positively influence health by altering the gut microbiome. In a mouse model, exposure to Mozart's Flute Quartet in D Major enhanced the gut microbiota, specifically increasing levels of the beneficial bacterium Lactobacillus salivarius. This probiotic protected mice from Salmonella infection by creating an acidic environment that inhibited pathogen growth. Mozart-treated mice also showed reduced anxiety, better spatial memory, and higher food intake without weight gain, suggesting the benefits of music exposure. These findings reveal a novel link between music, gut health, and disease resistance, suggesting that music therapy could be a promising strategy for enhancing gut microbiota and combating infections, including those caused by drug-resistant bacteria.PMID:40130867 | DOI:10.1128/spectrum.02377-24

Anal Chem. 2025 Mar 25. doi: 10.1021/acs.analchem.5c00606. Online ahead of print.ABSTRACTMultiomics analysis at the single-cell level is essential for both fundamental research and clinical applications, with proteomics and metabolomics being particularly crucial for providing insights into cellular states and functions. The state of the art flow cytometry has shown great potential in identifying cellular proteins, while emerging metabolite mass spectrometry cytometry techniques address metabolite detection. Herein, we propose a tandem platform that integrates fluorescence flow cytometry with electrospray ionization mass spectrometry for one-step single-cell analysis of protein and metabolites. An algorithm was established to correlate multidimensional information in individual cells, with additional data processing modules designed to ensure accuracy and facilitate further analysis. The tandem cytometry platform demonstrated efficacy in profiling breast cancer cells, particularly under hypoxic conditions, revealing metabolic shifts with decreased glutathione and increased l-glutamine levels, indicative of hypoxia-inducible factor activity. This platform introduces a powerful analytical capability that promises to elevate the precision of cell-based diagnostics and therapeutic strategies.PMID:40130787 | DOI:10.1021/acs.analchem.5c00606

J Sci Food Agric. 2025 Mar 25. doi: 10.1002/jsfa.14237. Online ahead of print.ABSTRACTBACKGROUND: Sweet potato (Ipomoea batatas (L.) Lam.) with high yield and diverse nutrients, is the third most important food crop in the world. Manganese (Mn) is an essential cofactor that plays a critical role in the development and maturation of the crop. However, the molecular mechanism underlying the sweet potato response to Mn remains unclear.RESULTS: In this study, Mn treatment increased the depth of yellow color in sweet potato, augmented sugar and carotenoid accumulation in storage roots, accompanied with a decline in plant hormones. Especially, Mn-treated storage roots displayed more than a 200% increase in β-carotene content compared to the control, while the abscisic acid (ABA) content was reduced by at least 50%. An integrated metabolomic and transcriptomic analysis suggested that Mn application regulated transcriptional and metabolic profiles of carotenoid biosynthesis, soluble sugar, carbon fixation in photosynthetic organisms and biosynthesis of amino acids. Further study revealed that Mn treatment stimulated β-carotene accumulation in storage roots by up-regulation of the transcripts of GGPPS, ZIDS, LCYB and OR, along with down-regulation of CCD1 and CCD4. Moreover, Mn application reduced ABA content through preventing the expression of NCED1.CONCLUSION: Our results indicated that Mn, emerging as an agrochemical candidate, will meet agricultural challenges by not only enriching the flesh coloration but also augmenting the nutritional value of sweet potatoes. © 2025 Society of Chemical Industry.PMID:40130642 | DOI:10.1002/jsfa.14237

Food Funct. 2025 Mar 25. doi: 10.1039/d4fo04519j. Online ahead of print.ABSTRACTPhlorizin is a dihydrochalcone with various biological activities. To elucidate the mechanism of mitigating high glucose-induced metabolic disorders by phlorizin, the integrated approach combining metabolomics and gene expression profiling was used. The results demonstrated that phlorizin effectively mitigated the impact of high glucose on various growth indicators of C. elegans, as well as decreased lipofuscin, ROS, glucose and triglyceride levels. Metabolomics analysis revealed that phlorizin significantly affected the metabolic pathways of carbohydrates, lipids, and amino acids in C. elegans, indicating its potential role in maintaining energy homeostasis. Gene expression analysis indicated that phlorizin reversed the downregulation of IIS, mTOR and lipid metabolism pathways and promoted the nuclear translocation of DAF-16. In the C. elegans mutant BQ1, the effect of phlorizin on lowering glucose and triglyceride levels was eliminated, meaning that AKT-1 was found to be a key target protein for phlorizin's hypoglycemic and lipid-lowering effects. Molecular docking results also indicated a strong interaction between phlorizin and AKT-1 protein. In summary, phlorizin alleviated metabolic disorders and gene expression imbalances induced by high glucose, and AKT-1 was first found as the key target protein for phlorizin achieving hypoglycemic and hypolipidemic effects.PMID:40130478 | DOI:10.1039/d4fo04519j

J Proteome Res. 2025 Mar 25. doi: 10.1021/acs.jproteome.4c00507. Online ahead of print.ABSTRACTMetabolic perturbations of the gut microbiome have been implicated in the pathogenesis of multiple human diseases, including type-2 diabetes (T2D). However, our understanding of the global metabolic alterations of the gut microbiota in T2D and their functional roles remains limited. To address this, we conducted a high-coverage metabolomics profiling analysis of serum samples from 1282 Chinese individuals with and without T2D. Among the 220 detected microbiota-associated compounds detected, 111 were significantly altered, forming a highly interactive regulatory network associated with T2D development. Pathway enrichment and correlation analyses revealed aberrant metabolic pathways, primarily including the activation of pyrimidine metabolism, unsaturated fatty acid biosynthesis, and diverse amino acid metabolisms such as Tryptophan metabolism, Lysine metabolism, and Branched-chain amino acid biosynthesis. A microbiota-dependent biomarker panel, comprising pipecolinic acid, methoxysalicylic acid, N-acetylhistamine, and 3-hydroxybutyrylcarnitine, was defined and validated with satisfactory sensitivity (>78%) for large-scale, population-based T2D screening. The functional role of a gut microbial product, N-acetylhistamine, was further elucidated in T2D progression through its inhibition of adenosine monophosphate-activated protein kinase phosphorylation. Overall, this study expands our understanding of gut microbiota-driven metabolic dysregulation in T2D and suggests that monitoring these metabolic changes could facilitate the diagnosis and treatment of T2D.PMID:40130449 | DOI:10.1021/acs.jproteome.4c00507

Cancer Med. 2025 Mar;14(6):e70808. doi: 10.1002/cam4.70808.ABSTRACTBACKGROUND: Differentiated thyroid cancer (DTC) is the primary subtype of thyroid cancer. Timely diagnosis and intervention are crucial for improving prognosis and survival. However, the effectiveness of existing serum markers is limited, necessitating the discovery of new biomarkers.METHODS: This study utilized liquid chromatography-tandem mass spectrometry to analyze tryptophan metabolic profiles in serum samples from 105 DTC patients and 50 healthy controls. Independent predictors of DTC were identified through univariate intergroup comparisons and multivariate logistic regression analysis, leading to the development and validation of a new diagnostic model.RESULTS: Significant differences were observed in 11 tryptophan metabolites between DTC patients and controls. Logistic regression identified nicotinamide, 3-hydroxyanthranilic acid, 5-hydroxytryptophan, melatonin, and indole-3-propionic acid as independent predictors. The nomogram prediction model was established based on these five metabolites, and according to the Hosmer-Lemeshow test, the model showed good fit. The five-metabolite diagnostic model demonstrated 84.8% sensitivity, 90.0% specificity, and an area under the ROC curve of 0.932. Decision curve analysis indicated that the model had significant advantages over serum thyroglobulin.DISCUSSION: Tryptophan metabolism exhibits distinct changes in DTC patients, with specific metabolites serving as early diagnostic markers. The five-metabolite panel demonstrates potential for improving early detection and management of DTC.PMID:40130383 | DOI:10.1002/cam4.70808

Front Physiol. 2025 Mar 10;16:1577465. doi: 10.3389/fphys.2025.1577465. eCollection 2025.NO ABSTRACTPMID:40130192 | PMC:PMC11931043 | DOI:10.3389/fphys.2025.1577465

Front Bioinform. 2025 Mar 10;5:1513790. doi: 10.3389/fbinf.2025.1513790. eCollection 2025.ABSTRACTBACKGROUND: Parkinson's disease is a complex, age-related, neurodegenerative disease associated with dopamine deficiency and both motor and nonmotor deficits. Therapeutic pathways remain challenging in Parkinson's disease due to the low accuracy of early diagnosis, the difficulty in monitoring disease progression, and the limited availability of treatment options.OBJECTIVES: Few data are present to identify urinary biomarkers for various ailments, potentially aiding in the diagnosis and tracking of illness progression in individuals with Parkinson's disease. Thus, the analysis of urinary metabolomic biomarkers (UMB) for early and mid-stage idiopathic Parkinson's disease (IPD) is the main goal of this systematic review.METHODS: For this study, six electronic databases were searched for articles published up to 23 February 2024: PubMed, Ovid Medline, Embase, Scopus, Science Direct, and Cochrane. 5,377 articles were found and 40 articles were screened as per the eligibility criteria. Out of these, 7 controlled studies were selected for this review. Genetic profiling for gene function and biomarker interactions between urinary biomarkers was conducted using the STRING and Cytoscape database.RESULTS: A total of 40 metabolites were identified to be related to the early and mid-stage of the disease pathology out of which three metabolites, acetyl phenylalanine (a subtype of phenylalanine), tyrosine and kynurenine were common and most significant in three studies. These metabolites cause impaired dopamine synthesis along with mitochondrial disturbances and brain energy metabolic disturbances which are considered responsible for neurodegenerative disorders. Furoglycine, Cortisol, Hydroxyphenylacetic acid, Glycine, Tiglyglycine, Aminobutyric acid, Hydroxyprogesterone, Phenylacetylglutamine, and Dihydrocortisol were also found commonly dysregulated in two of the total 7 studies. 158 genes were found which are responsible for the occurrence of PD and metabolic regulation of the corresponding biomarkers from our study.CONCLUSION: The current review identified acetyl phenylalanine (a subtype of phenylalanine), tyrosine and kynurenine as potential urinary metabolomic biomarkers for diagnosing PD and identifying disease progression.PMID:40130009 | PMC:PMC11931117 | DOI:10.3389/fbinf.2025.1513790

Food Sci Nutr. 2025 Mar 24;13(4):e70075. doi: 10.1002/fsn3.70075. eCollection 2025 Apr.ABSTRACTAlthough Psidium cattleianum (strawberry guava, Myrtaceae) is known for its anti-inflammatory, antioxidant, antimicrobial, and antidiabetic properties, its phytochemical profile and associated bioactivities remain largely underexplored. This study employed UHPLC-QTOF-HRMS for untargeted phenolic profiling of leaf and fruit extracts from P. cattleianum, followed by semi-quantification of phenolic subclasses and multivariate data analysis. Four hundred sixty-nine metabolites, including various phenolic subclasses-predominantly flavonoids and phenolic acids were- identified and annotated. Using HEK-293 cells stably transfected with TRPA1 or TRPV1 cation channels, it was found that both leaf and fruit extracts activate and rapidly desensitize TRPA1 in a concentration-dependent manner (EC50 18 and 30 μg/mL; IC50 60 and 47 μg/mL, respectively). Additionally, molecular docking analysis provided deeper insights into the interactions between P. cattleianum phytochemicals and the TRPA1 cation channel, identifying theaflavin 3,3'-O-digallate as the phenolic compound with the highest affinity (S score of -9.27 Kcal/mol). Interestingly, except for theaflavin 3,3'-O-digallate, compounds enriched in the leaf extract exhibited weaker binding interactions and lower S scores (approximately -7 Kcal/mol) compared to those enriched in the fruit extract. Also, a 100 ns molecular dynamics study of theaflavin 3,3'-O-digallate with TRAP1 demonstrated high binding stability of the complex. Overall, this study offers valuable insights into the phytochemical characteristics of P. cattleianum extracts and reveals their mechanism of action through affinity for the TRPA1 cation channel-receptors.PMID:40129993 | PMC:PMC11931593 | DOI:10.1002/fsn3.70075

Front Immunol. 2025 Mar 10;16:1530098. doi: 10.3389/fimmu.2025.1530098. eCollection 2025.ABSTRACTINTRODUCTION: Cordyceps militaris extract (CME) and cordycepin (CPN) are biomolecules with a wide range of biological activities, including anti-inflammatory, antioxidant and anti-tumour effects. The research objective wasto investigate the influences of CME and cordycepin CPN on colonic morphology, microbiota composition and colonic metabolomics in lipopolysaccharide (LPS)-challenged piglets.METHODS: Twenty-four weaned castrated piglets were randomly divided into four groups: control group (fed basal diets), LPS group (fed basal diets), CPN-LPS group (basal diets + 60 mg/kg cordycepin), and CME-LPS group (basal diets + 60 mg/kg C. militarisextract). On the 21st day, the LPS, CPN-LPS, and CME-LPS groups received an injection of 100 μg/kg BW LPS, while the control group was given sterile saline.RESULTS: The findings demonstrated that CPN or CME attenuated intestinal morphology damage with LPS-challenged piglets. CPN and CME alleviated intestinal microbiota dysbiosis and metabolic disorders under LPS-challenged by enriching serum protein levels, regulating of inflammatory cytokine secretion and altering colonic microbial composition. Colonic microbiota analysis that the CPN improved the relative abundance of Acidobacteriota and inhibited Faecalibacterium, CME promoted the relative abundance of Prevotella and Lachnospiraceae NK4A136group. Meanwhile, the alleviation of colonic damage is achieved through modulation of metabolic pathways linked to tryptophan metabolism, biosynthesis of amino acids and butanoate metabolism.DISCUSSION: Conclusively, our preliminary findings reveal that CPN or CME could serve as a beneficial dietary supplement to alleviate gut diseases in weaning piglets.PMID:40129987 | PMC:PMC11931037 | DOI:10.3389/fimmu.2025.1530098

Front Immunol. 2025 Mar 10;16:1475160. doi: 10.3389/fimmu.2025.1475160. eCollection 2025.ABSTRACTINTRODUCTION: Lipid profiles change in human immunodeficiency virus (HIV) infection and correlate with inflammation. Lipidomic alterations are impacted by multiple non-HIV-related behavioral risk factors; thus, use of animal models in which these behavioral factors are controlled may inform on the specific lipid changes induced by simian immunodeficiency virus (SIV) infection and/or antiretroviral therapy (ART).METHODS: Using ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy, we assessed and compared (ANOVA) longitudinal lipid changes in naïve and ART-treated SIV-infected pigtailed macaques (PTMs). Key parameters of infection (IL-6, TNFa, D-dimer, CRP and CD4+ T cell counts) were correlated (Spearman) with lipid concentrations at critical time points of infection and treatment.RESULTS: Sphingomyelins (SM) and lactosylceramides (LCER) increased during acute infection, returning to baseline during chronic infection; Hexosylceramides (HCER) increased throughout infection, being normalized with prolonged ART; Phosphatidylinositols (PI) and lysophosphatidylcholines (LPC) decreased with SIV infection and did not return to normal with ART; Phosphatidylethanolamines (PE), lysophosphatidylethanolamines (LPE) and phosphatidylcholines (PC) were unchanged by SIV infection, yet significantly decreased throughout ART. Specific lipid species (SLS) were also substantially modified by SIV and/or ART in most lipid classes. In conclusion, using a metabolically controlled model, we identified specific lipidomics signatures of SIV infection and/or ART, some of which were similar to people living with HIV (PWH). Many SLS were identical to those involved in development of organ dysfunctions encountered in virally suppressed individuals. Lipid changes also correlated with markers of disease progression, inflammation and coagulation.DISCUSSION: Our data suggest that lipidomic profile alterations contribute to residual systemic inflammation and comorbidities seen in HIV/SIV infections and therefore may be used as biomarkers of SIV/HIV comorbidities. Further exploration into the benefits of interventions targeting dyslipidemia is needed for the prevention HIV-related comorbidities.PMID:40129985 | PMC:PMC11931036 | DOI:10.3389/fimmu.2025.1475160

Front Pharmacol. 2025 Mar 10;16:1503785. doi: 10.3389/fphar.2025.1503785. eCollection 2025.ABSTRACTIntroduction: Polygonatum cyrtonema Hua (PC) is an essential herbal medicine in China, known for improving muscle quality and enhancing physical function; its active ingredients are polysaccharides (PCPs). A previous study revealed the anti-atrophy effects of PCPs in cachectic mice. However, whether the effects of PCPs on anti-atrophy are associated with gut microenvironment remain elusive. This research endeavored to assess the medicinal efficacy of PCPs in alleviating muscle atrophy and fat lipolysis and explore the potential mechanisms. Methods: A cancer cachexia model was induced by male C57BL/6 mice bearing Lewis lung tumor cells and chemotherapy. The pharmacodynamics of PCPs (32 and 64 mg/kg/day) was investigated through measurements of tumor-free body weight, gastrocnemius muscle weight, soleus muscle weight, epididymal fat weight, tissue histology analysis, and pro-inflammatory cytokines. Immunohistochemistry and Western blotting assays were further used to confirm the effects of PCPs. 16S rRNA sequencing, LC-MS and GC-MS-based metabolomics were used to analyze the gut microbiota composition and metabolite alterations. Additionally, the agonist of free fatty acid receptor 2 (FFAR2)-a crucial short-chain fatty acid (SCFA) signaling molecule-was used to investigate the role of gut microbiota metabolites, specifically SCFAs, in the treatment of cancer cachexia, with comparisons to PCPs. Results: This study demonstrated that PCPs significantly mitigated body weight loss, restored muscle fiber atrophy and mitochondrial disorder, alleviated adipose tissue wasting, strengthened the intestinal barrier integrity, and decreased the intestinal inflammation in chemotherapy-induced cachexia. Furthermore, the reversal of specific bacterial taxa including Klebsiella, Akkermansia, norank_f__Desulfovibrionaceae, Enterococcus, NK4A214_group, Eubacterium_fissicatena_group, Eubacterium_nodatum_group, Erysipelatoclostridium, Lactobacillus, Monoglobus, Ruminococcus, Odoribacter, and Enterorhabdus, along with alterations in metabolites such as amino acids (AAs), eicosanoids, lactic acid and (SCFAs), contributed to the therapeutic effects of PCPs. Conclusion: Our findings suggest that PCPs can be used as prebiotic drugs targeting the microbiome-metabolomics axis in cancer patients undergoing chemotherapy.PMID:40129936 | PMC:PMC11931129 | DOI:10.3389/fphar.2025.1503785

Front Neurol. 2025 Mar 10;16:1535136. doi: 10.3389/fneur.2025.1535136. eCollection 2025.ABSTRACTPostherpetic neuralgia (PHN), a representative type of neuropathic pain, has attracted much research on its diagnosis and therapy at the molecular level. Interestingly, this study based on the brain-gut axis provided a novel point of view to interpret the mechanism of PHN. Past neuroanatomical and neuroimaging studies of pain suggest that the prefrontal cortex, anterior cingulate cortex, amygdala, and other regions of the brain may play crucial roles in the descending inhibition of PHN. Dominant bacterial species in patients with PHN, such as Lactobacillus, generate short-chain fatty acids, including butyrate. Evidence indicates that disturbance of some metabolites (such as butyrate) is closely related to the development of hyperalgesia. In addition, tryptophan and 5-HT in the intestinal tract act as neurotransmitters that regulate the descending transmission of neuropathic pain signals. Concurrently, the enteric nervous system establishes close connections with the central nervous system through the vagus nerve and other pathways. This review aims to investigate and elucidate the molecular mechanisms associated with PHN, focusing on the interplay among PHN, the gut microbiota, and relevant metabolites while scrutinizing its pathogenesis.PMID:40129863 | PMC:PMC11932021 | DOI:10.3389/fneur.2025.1535136

Front Neurosci. 2025 Mar 10;19:1498981. doi: 10.3389/fnins.2025.1498981. eCollection 2025.ABSTRACTMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), Gulf War Syndrome (GWS), and Fibromyalgia (FM) are complex, chronic illnesses with overlapping clinical features. Symptoms that are reported across these conditions include post-exertional malaise (PEM), fatigue, and pain, yet the etiology of these illnesses remains largely unknown. Diagnosis is challenging in patients with these conditions as definitive biomarkers are lacking; patients are required to meet clinical criteria and often undergo lengthy testing to exclude other conditions, a process that is often prolonged, costly, and burdensome for patients. The identification of reliable validated biomarkers could facilitate earlier and more accurate diagnosis and drive the development of targeted pharmacological therapies that might address the underlying pathophysiology of these diseases. Major driving forces for biomarker identification are the advancing fields of metabolomics and proteomics that allow for comprehensive characterization of metabolites and proteins in biological specimens. Recent technological developments in these areas enable high-throughput analysis of thousands of metabolites and proteins from a variety of biological samples and model systems, that provides a powerful approach to unraveling the metabolic phenotypes associated with these complex diseases. Emerging evidence suggests that ME/CFS, GWS, and FM are all characterized by disturbances in metabolic pathways, particularly those related to energy production, lipid metabolism, and oxidative stress. Altered levels of key metabolites in these pathways have been reported in studies highlighting potential common biochemical abnormalities. The precise mechanisms driving altered metabolic pathways in ME/CFS, GWS, and FM remain to be elucidated; however, the elevated oxidative stress observed across these illnesses may contribute to symptoms and offer a potential target for therapeutic intervention. Investigating the mechanisms, and their role in the disease process, could provide insights into disease pathogenesis and reveal novel treatment targets. As such, comprehensive metabolomic and proteomic analyses are crucial for advancing the understanding of these conditions in-order to identify both common, and unique, metabolic alterations that could serve as diagnostic markers or therapeutic targets.PMID:40129725 | PMC:PMC11931034 | DOI:10.3389/fnins.2025.1498981

J Mol Cell Cardiol Plus. 2025 Mar 1;11:100290. doi: 10.1016/j.jmccpl.2025.100290. eCollection 2025 Mar.ABSTRACTHeart failure (HF) remains a major cause of morbidity and mortality worldwide and represents a major challenge for diagnosis, prognosis and treatment due to its heterogeneity. Traditional biomarkers such as BNP and NT-proBNP are valuable but insufficient to capture the complexity of HF, especially phenotypes such as HF with preserved ejection fraction (HFpEF). Recent advances in multi-omics technology and novel biomarkers such as cell-free DNA (cfDNA), microRNAs (miRNAs), ST2 and galectin-3 offer transformative potential for HF management. This review explores the integration of these innovative biomarkers into clinical practice and highlights their benefits, such as improved diagnostic accuracy, enhanced risk stratification and non-invasive monitoring capabilities. By leveraging multi-omics approaches, including lipidomics and metabolomics, clinicians can uncover new pathways, refine the classification of HF phenotypes, and develop personalized therapeutic strategies tailored to individual patient profiles. Remarkable advances in proteomics and metabolomics have identified biomarkers associated with key HF mechanisms such as mitochondrial dysfunction, inflammation and fibrosis, paving the way for targeted therapies and early interventions. Despite the promising results, significant challenges remain in translating these findings into routine care, including high costs, technical limitations and the need for large-scale validation studies. This report argues for an integrative, multi-omics-based model to overcome these obstacles and emphasizes the importance of collaboration between researchers, clinicians and policy makers. By linking innovative science with practical applications, multi-omics approaches have the potential to redefine HF management and lead to better patient outcomes and more sustainable healthcare systems.PMID:40129519 | PMC:PMC11930597 | DOI:10.1016/j.jmccpl.2025.100290

Environ Sci Technol. 2025 Mar 25. doi: 10.1021/acs.est.4c10717. Online ahead of print.ABSTRACTPregnancy is a potential critical window to air pollution exposure for long-term maternal metabolic effects. However, little is known about potential early metabolic mechanisms linking air pollution to maternal metabolic health. We included 544 pregnant Mexican women with both ambient PM2.5 levels during pregnancy and untargeted serum metabolomics to examine associations between pregnancy PM2.5 exposure (overall and monthly) and postpartum metabolites, implementing FDR-adjusted robust linear regression controlling for covariates. Pathway enrichment analyses (in Reactome and MetaboAnalyst) and effect modification by fetal sex and folic acid supplementation were also evaluated. Higher PM2.5 exposure levels throughout pregnancy were associated with higher bile acids and amino acids, dysregulated glycerophospholipids, or lower fatty acyl levels (FDR < 0.05), among other metabolites. Potential critical windows of susceptibility to monthly PM2.5 on metabolites were observed in early to midpregnancy (FDR < 0.005). Main findings were consistent by strata of fetal sex and folic acid supplementation. Metabolic pathways corresponding to positive PM2.5-metabolite associations indicated enriched bile acid, dietary lipid, and transmembrane transport metabolism, whereas for negative PM2.5-metabolite associations, we identified altered pathways involving adipogenesis, incretin peptide hormone, GLP-1, PPAR-alpha, and fatty acid receptors (FDR < 0.05). PM2.5 exposures during pregnancy, especially in early gestation, altered maternal postpartum lipids as well as amino acid metabolism.PMID:40129413 | DOI:10.1021/acs.est.4c10717

J Proteome Res. 2025 Mar 25. doi: 10.1021/acs.jproteome.5c00017. Online ahead of print.ABSTRACTHuman cytomegalovirus (HCMV) is the leading cause of congenital infections resulting in severe morbidity and mortality among newborns worldwide. Currently, the most significant prognostic factor of congenital cytomegalovirus (cCMV) infection is the time of maternal infection, with a more severe clinical phenotype if the mother's first outbreak occurs during the first trimester of pregnancy. Nonetheless, the pathogenesis of cCMV infection has still to be completely characterized. In particular, little is known about the metabolic response triggered by HCMV in congenitally infected newborns. As such, urinary metabolic profiling by 1H nuclear magnetic resonance (NMR) might represent a promising tool to be exploited in the context of cCMV. This study aims to investigate the impact of HCMV infection on the urine metabolome in a population of congenitally infected newborns and uninfected controls by 1H NMR spectroscopy combined with multivariate statistical analysis. The 1H NMR spectra of patients (n = 35) and controls (n = 15) allowed the identification of an overall amount of 55 metabolites. Principal Component Analysis (PCA) and clustering correctly assigned 49 out of 50 newborns into the infected and control groups. Partial Least-Squares-Discriminant Analysis (PLS-DA) revealed that newborns with cCMV resulted in having increased betaine, citrate, 3-hydroxybutyrate, 4-hydroxybutyrate, acetoacetate, formate, glycolate, lactate, succinate, and threonine levels in the urine. On the other hand, healthy controls showed increased 4-aminohippurate, creatine, creatinine, fumarate, mannitol, taurine, and dimethylamine levels. These results showed a clear difference in metabolomic fingerprint between newborns with cCMV infection and healthy controls. Thus, metabolomics can be considered a new, promising diagnostic and prognostic tool in the clinical management of cCMV patients.PMID:40129280 | DOI:10.1021/acs.jproteome.5c00017

Biomed Chromatogr. 2025 May;39(5):e70026. doi: 10.1002/bmc.70026.ABSTRACTHoneybran-fried Cimicifuga Rhizoma (HBCR) is often used to treat prolonged diarrhea and prolapse of the anus, uterine prolapse, and gastric ptosis caused by spleen qi deficiency and the inability to elevate qi, and thus the lowering of middle qi. Rats were divided randomly into four groups. Fecal samples of rats in each group were subjected to metabolomics analysis. We identified the chemical components of HBCR using liquid chromatography-tandem mass spectrometry. We predicted the potential active components and key targets of HBCR using network pharmacology to construct a "drug-potential active ingredient-target-disease" network. The key targets screened by network pharmacology and differential metabolites screened by metabolomics analysis were subjected to combined pathway analysis. Pharmacodynamic indices showed that HBCR had a good therapeutic effect upon IBS-D. Metabolomics analysis revealed 26 differential metabolites in the treatment of IBS-D by HBCR. A total of 69 chemical components were identified, and 32 potential active components and 296 key targets were screened. Combination of metabolomics analysis and network pharmacology for joint pathway analysis revealed that the therapeutic effect of HBCR may be affected by the metabolism of linoleic acid, retinol, arachidonic acid, and tryptophan. HBCR had significant therapeutic effects in rats with IBS-D.PMID:40129176 | DOI:10.1002/bmc.70026

Int Wound J. 2025 Apr;22(4):e70158. doi: 10.1111/iwj.70158.ABSTRACTMass spectrometry is increasingly utilised in medicine to identify and quantify small biomarkers for diagnostic and prognostic purposes. Conventional mass spectrometry, however, requires time-consuming sample preparation, hindering its clinical application. Direct sampling mass spectrometry, which allows for direct analysis of patient samples with minimal preparation, offers potential for clinical use. This systematic review examines the utility of direct sampling mass spectrometry for the assessment of external wounds and explores its translational applications in wound care. Out of 2 930 screened abstracts, six studies were included employing various direct sampling mass spectrometry technologies. These studies focused on burn wounds (n = 3), pressure ulcers (n = 2), and acute surgical wounds (n = 1). Both targeted and untargeted molecular profiling methods were used to examine biomarkers related to inflammatory and healing processes, including various proteins, lipid species, and other metabolites. Direct sampling mass spectrometry was found to complement conventional methods such as histology, providing additional insights into the spatial localisation and accumulation of metabolites within wounds. Additionally, imaging techniques equipped with this technology can spatially map wound surfaces and reveal dynamic changes in wounds as they age or progress through different healing processes, with specific metabolite and protein accumulations potentially aiding in prognostication.PMID:40129114 | DOI:10.1111/iwj.70158

Aging Cell. 2025 Mar 24:e14465. doi: 10.1111/acel.14465. Online ahead of print.ABSTRACTCaloric restriction is associated with slow aging in model organisms. Additionally, some drugs have also been shown to slow aging in rodents. To better understand metabolic mechanisms that are involved in increased lifespan, we analyzed metabolomic differences in six organs of 12-month-old mice using five interventions leading to extended longevity, specifically caloric restriction, 17-α estradiol, and caloric restriction mimetics rapamycin, canagliflozin, and acarbose. These interventions generally have a stronger effect in males than in females. Using Jonckheere's trend test to associate increased average lifespans with metabolic changes for each sex, we found sexual dimorphism in metabolism of plasma, liver, gastrocnemius muscle, kidney, and inguinal fat. Plasma showed the strongest trend of differentially expressed compounds, highlighting potential benefits of plasma in tracking healthy aging. Using chemical set enrichment analysis, we found that the majority of these affected compounds were lipids, particularly in male tissues, in addition to significant differences in trends for amino acids, which were particularly apparent in the kidney. We also found strong metabolomic effects in adipose tissues. Inguinal fat exhibited surprising increases in neutral lipids with polyunsaturated side chains in male mice. In female mice, gonadal fat showed trends proportional to lifespan extension effect across multiple lipid classes, particularly phospholipids. Interestingly, for most tissues, we found similar changes induced by lifespan-extending interventions to metabolomic differences between untreated 12-month-old mice and 4-month-old mice. This finding implies that lifespan-extending treatments tend to reverse metabolic phenotypes to a biologically younger stage.PMID:40129070 | DOI:10.1111/acel.14465