PubMed

FASEB J. 2025 Mar 31;39(6):e70457. doi: 10.1096/fj.202403239R.ABSTRACTDietary prebiotics pectin and resistant starch type-4 (RS-4) promote satiety and alter gut microbiota; however, the underlying neurohormonal mechanisms of satiety remain poorly understood. We determined the effects of pectin, RS-4, and their combination on energy balance and gut microbiota composition, and assessed whether the gut hormones peptide YY (PYY) and cholecystokinin (CCK) play a role in fiber-induced satiety. High-fat diet -induced obese male rats (n = 7-8/group) were fed either control, pectin, RS-4, or a combination of pectin and RS-4 diet. We found that pectin, RS-4, and their combination decreased food intake. Pectin alone, or combined with RS-4, shifted substrate utilization towards fat and reduced gains in weight and adiposity. Pectin alone or combined with RS-4 enhanced the expression and plasma concentrations of PYY and CCK. Importantly, systemic blockade of PYY-Y2 and CCK-1 receptors attenuated the hypophagic effects of pectin, and CCK-1 receptor blockade partly attenuated the hypophagia from RS-4. The prebiotics significantly altered fecal β-diversity metrics, suggestive of improvements in gut microbiota composition. Pectin and RS-4 alone, or in combination, were associated with increased relative abundance of phylum Bacteroidota, decreased Firmicutes, and increased concentrations of amino acids and biogenic amines in feces. Collectively, these findings suggest that dietary pectin and RS-4 improved energy balance and gut microbiota composition, and importantly, demonstrated that the satiety effects of these diets were mediated, in part, via enhanced endogenous PYY and CCK signaling.PMID:40085424 | DOI:10.1096/fj.202403239R

Geroscience. 2025 Mar 14. doi: 10.1007/s11357-025-01599-5. Online ahead of print.ABSTRACTAging is a major risk factor for disease, and developing effective pharmaceutical interventions to improve healthspan and promote longevity has become a high priority for society. One of the molecular pathways related to longevity in various model organisms revolves around lowering AKT1 levels. This prompted our in silico drug screen for small molecules capable of mimicking the transcriptional effects of AKT1 knockdown. We found topoisomerase inhibitors as a top candidate longevity-drug class. Evaluating multiple compounds from this class in C. elegans revealed that the topoisomerase inhibitor amonafide has the greatest benefit on healthspan and lifespan. Intriguingly, the longevity effect of amonafide was not solely dependent on DAF-16/FOXO, the canonical pathway for lifespan extension via AKT1 inhibition. We performed RNA-seq on amonafide-treated worms and revealed a more youthful transcriptional signature, including the activation of diverse molecular and cellular defense pathways. We found the mitochondrial unfolded protein response (UPRmt) regulator afts-1 to be crucial for both improved healthspan and extended lifespan upon amonafide treatment. Moreover, healthspan was partially dependent on the immune response transcription factor zip-2 and the integrated stress response transcription factor atf-4. We further examined the potential of amonafide in age-related disease. Treating a C. elegans model for Parkinson's disease with amonafide improved mobility. In conclusion, we identified amonafide as a novel geroprotector, which activates mitochondrial-, pathogen-, and xenobiotic-associated defense responses that-though more studies are needed-may serve as a candidate for Parkinson's disease therapy.PMID:40085390 | DOI:10.1007/s11357-025-01599-5

Curr Microbiol. 2025 Mar 14;82(5):193. doi: 10.1007/s00284-025-04165-6.ABSTRACTThe genome of Streptomyces sp. SM1P was sequenced to give a contig of 7,561,428 bp (71.7% G + C content) and 24 putative secondary metabolite biosynthetic gene clusters (BGCs). Eight of the BGCs showed high similarity (≥ 80%), three have moderate similarity (between 50 and 79%), and eleven showed low similarity (less than 50%) to known BGCs. The strain was cultivated in 7 different media prepared in 3 different solvents and the secondary metabolites were extracted with ethyl acetate to give 21 different extracts. All extracts showed antimicrobial and cytotoxic activities, with extracts from the ISP1/NaCl and ISP4/ASW cultures were the most active against bacteria and brine shrimp nauplii, respectively. The extract of the ISP2/NaCl culture, which gave a high number of spots on TLC, was also active against Plasmodium berghei. Untargeted metabolomic analysis of the ISP1/NaCl, ISP2/NaCl, and ISP4/ASW extracts using gas chromatography-mass spectrometry (GC-MS) and comparisons of the data against the National Institute of Standards and Technology 20 Mass Spectral Library showed variations between their secondary metabolites. Principal Component Analysis of the m/z values showed a correlation between ISP1/NaCl and ISP2/NaCl but not with ISP4/ASW. Metabolomic analysis of ISP2/NaCl extract using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) and comparisons of the data with those in the GNPS database and others indicated the presence of a lankamycin derivative (an antibiotic) and a cyclosporin derivative (an immunosuppressant). However, many other metabolites did not have a match. The results showed that Streptomyces sp. SM1P has potential as a producer of new secondary metabolites, particularly those with antimicrobial and antitumor activities.PMID:40085245 | DOI:10.1007/s00284-025-04165-6

Curr Opin Hematol. 2025 Mar 12. doi: 10.1097/MOH.0000000000000863. Online ahead of print.ABSTRACTPURPOSE OF REVIEW: This review focuses on recent advances in the understanding of red blood cell (RBC) metabolism as a function of hypoxia and oxidant stress. In particular, we will focus on RBC metabolic alterations during storage in the blood bank, a medically relevant model of erythrocyte responses to energy and redox stress.RECENT FINDINGS: Recent studies on over 13 000 healthy blood donors, as part of the Recipient Epidemiology and Donor Evaluation Study (REDS) III and IV-P RBC omics, and 525 diversity outbred mice have highlighted the impact on RBC metabolism of biological factors (age, BMI), genetics (sex, polymorphisms) and exposure (dietary, professional or recreational habits, drugs that are not grounds for blood donor deferral).SUMMARY: We review RBC metabolism from basic biochemistry to storage biology, briefly discussing the impact of inborn errors of metabolism and genetic factors on RBC metabolism, as a window on systems metabolic health. Expanding on the concept of clinical chemistry towards clinical metabolomics, monitoring metabolism at scale in large populations (e.g., millions of blood donors) may thus provide insights into population health as a complementary tool to genetic screening and standard clinical measurements.PMID:40085132 | DOI:10.1097/MOH.0000000000000863

J Agric Food Chem. 2025 Mar 14. doi: 10.1021/acs.jafc.4c12660. Online ahead of print.ABSTRACTDeveloping effective therapies for type 2 diabetes mellitus (T2DM) remains a critical global health priority. This study explored the novel antidiabetic potential of MCPS-3, a polysaccharide derived from Momordica charantia L., and its underlying mechanisms in a high-fat diet and streptozotocin-induced T2DM mouse model. Our results indicated that MCPS-3 treatment significantly reduced serum glucose levels, improved glucose tolerance, and enhanced insulin sensitivity, alongside increased glycogen storage and improved liver enzyme activities. It also alleviated diabetes-induced damage in the pancreas, liver, and kidneys and improved serum lipid profiles by lowering triglycerides and LDL-C while increasing HDL-C levels. Mechanistic studies revealed that MCPS-3 activated the IRS1/PI3K/AKT and AMPK pathways, essential for glucose and lipid regulation. Importantly, MCPS-3 treatment restored gut microbial balance by increasing microbial diversity and shifting the composition of harmful and beneficial bacteria. Metabolomic analysis further identified changes in 46 metabolites, implicating pathways related to steroid and lipid metabolism. These findings underscore the multifaceted nature of MCPS-3's antidiabetic effects, including its role as a modulator of gut microbiota and metabolic pathways, and support its potential as a therapeutic agent for improving metabolic health in T2DM.PMID:40085053 | DOI:10.1021/acs.jafc.4c12660

Anal Chem. 2025 Mar 14. doi: 10.1021/acs.analchem.4c06520. Online ahead of print.ABSTRACTMass spectrometry imaging (MSI) is a technique that uncovers the contextual distribution of biomolecules in tissue. This involves collecting large data sets with information-rich mass spectra in each pixel. To streamline image processing and interpretation, the MSI community has developed toolboxes for image preprocessing, segmentation, statistical analysis, and visualization. These generally require data to be input as imzML files, an Extensible Markup Language file with vocabulary for mass spectrometry and imaging-specific parameters. While commercial systems (e.g., MALDI) come with proprietary file converters, to our knowledge, no open-access user-friendly converters exist for continuously acquired imaging data (e.g., nano-DESI, DESI). Here, we present imzML Writer, an easy-to-use Python application with a graphical user interface to convert data from vendor format into pixel-aligned imzML files. We package this application with imzML Scout, allowing visualization of the resulting file(s) and batch export of ion images across a range of image and data formats (e.g., PNG, TIF, CSV). To demonstrate the utility of files generated by imzML Writer, we processed nano-DESI data with popular tools such as Cardinal MSI and METASPACE. Overall, this work provides a simple open-access tool for emerging MSI modality users to access advanced MSI processing tools reliant on imzML format. ImzML Writer is available as a distributable Python package via pip or as a standalone program for Mac and PC at https://github.com/VIU-Metabolomics/imzML_Writer.PMID:40084954 | DOI:10.1021/acs.analchem.4c06520

Allergy. 2025 Mar 14. doi: 10.1111/all.16526. Online ahead of print.ABSTRACTAn estimated 10% of coronavirus disease (COVID-19) survivors suffer from persisting symptoms referred to as long COVID (LC), a condition for which approved treatment options are still lacking. This systematic review (PROSPERO: CRD42024499281) aimed to explore the pathophysiological mechanisms underlying LC and potential treatable traits across symptom-based phenotypes. We included studies with primary data, written in English, focusing on omics analyses of human samples from LC patients with persistent symptoms of at least 3 months. Our search in PubMed and Embase, conducted on January 8, 2024, identified 642 studies, of which 29 met the inclusion criteria after full-text assessment. The risk of bias was evaluated using the Joanna Briggs Institute appraisal tool. The synthesis of omics data, including genomics, transcriptomics, proteomics, metabolomics, and metagenomics, revealed common findings associated with fatigue, cardiovascular, pulmonary, neurological, and gastrointestinal phenotypes. Key findings included mitochondrial dysfunction, dysregulated microRNAs associated with pulmonary dysfunction, tissue impairment, blood-brain barrier disruption, coagulopathy, vascular dysfunction, microbiome disturbances, microbial-derived metabolite production and persistent inflammation. Limitations include cross-study heterogeneity and variability in sampling methods. Our review emphasizes the complexity of LC and the need for further longitudinal omics-integrated studies to advance the development of biomarkers and targeted treatments.PMID:40084919 | DOI:10.1111/all.16526

Microbiol Spectr. 2025 Mar 14:e0177224. doi: 10.1128/spectrum.01772-24. Online ahead of print.ABSTRACTPulmonary tuberculosis (PTB) and diabetes mellitus (DM) are prevalent chronic diseases with substantial implications for human health. DM patients are more susceptible to PTB, which exacerbates diabetes-related complications. However, the complex molecular mechanisms underlying the enhanced susceptibility of DM patients to PTB infection remain poorly understood. In this study, α- and β-diversity of gut microbiota was significantly reduced in PTB patients and PTB-DM patients. The abundances of families Lachnospiraceae and Ruminococcaceae in the the Firmicutes phylum were reduced in PTB patients and further diminished in PTB-DM patients. On the other hand, untargeted metabolomics in frozen serum and stool samples indicated that phenylalanine, tyrosine, and tryptophan biosynthesis, metabolites of arginine, proline, tryptophan, and histidine were consistently altered in PTB patients and PTB-DM patients, with significant upregulation of most metabolites. Amino acids like serine, proline, and histidine were both remarkably elevated in PTB and PTB-DM patients. The correlation network analysis reveals the relationships between the shared microbial biomarkers and the shared metabolic pathways. This research contributes to the exploration of pivotal diagnostic biomarkers for both patients with PTB and PTB accompanied by diabetes. Specifically, shared reductions were identified in the genera g-Roseburia, g-Ruminococcaceae_UCG.013, g-Ruminococcaceae_NK4A214, g-Lachnospiraceae_unclassified, and g-Firmicutes_unclassified in addition to notable regulation of amino acids, like glycine, serine, and histidine in patients with PTB and PTB-DM. Our study expands the comprehension of the intricate connections linking gut microbiota, fecal metabolites, and serum metabolites in PTB and PTB-DM patients.IMPORTANCE: This study expands the understanding of the complex links between gut microbiota, fecal metabolites, and serum metabolites in patients with PTB and PTB-DM through multi-omics techniques. It is helpful for us to understand the complex molecular mechanism of increased susceptibility to PTB infection in diabetic patients.PMID:40084872 | DOI:10.1128/spectrum.01772-24

mSystems. 2025 Mar 14:e0114824. doi: 10.1128/msystems.01148-24. Online ahead of print.ABSTRACTThe development and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) in children are closely related to alterations of gut microbiota. This study aims to investigate changes in the gut microbiota signature and microbial metabolites in children with MASLD. We collected fecal samples from children and adolescents aged 6-16 years, and the presence of MASLD was diagnosed by ultrasound. We performed 16S ribosomal DNA sequencing and targeted metabolomics in 36 and 25 subjects, consisting of healthy controls, children with obesity, and children with MASLD. The α-diversity was significantly lower in children with obesity and MASLD compared with healthy controls. Linear discriminant analysis of effect size analysis identified Anaerostipes and A. hadrus as the top biomarkers differentiating the obesity group from the MASLD group. In MASLD patients with high alanine aminotransferase values (≥50 U/L for boys and 44 U/L for girls), we observed a decrease in the gut microbiota health index. MASLD patients with high shear wave elastography (E) values (≥6.2 kPa) showed an increased abundance of Ruminococcus torques, which was positively correlated with the levels of deoxycholic acid (DCA) and E values. Importantly, the mediation analysis identified positive associations between R. torques and clinical indicators of MASLD that were mediated by DCA. Overall, our study suggests that gut microbiota and metabolites are significantly altered in children with MASLD, and targeting R. torques may offer potential benefits for disease management.IMPORTANCEThis study investigated alterations in the gut microbiota signature and microbial metabolites in children with metabolic dysfunction-associated steatotic liver disease (MASLD). We found that an increased abundance of Ruminococcus torques was associated with increased levels of deoxycholic acid and the progression of MASLD, suggesting that R. torques may serve as a novel clinical target in pediatric MASLD.PMID:40084870 | DOI:10.1128/msystems.01148-24

Org Lett. 2025 Mar 14. doi: 10.1021/acs.orglett.5c00231. Online ahead of print.ABSTRACTA combination of genomic and metabolomic analyses paired with molecular networking was applied to a collection of Paenibacillus spp. to identify the producers of a little-studied class of lipopeptides known as paenilipoheptins. Mass spectrometry and NMR spectroscopy allowed revision of the structure of previously reported paenilipoheptin A and elucidation of the structure of novel paenilipoheptin B.PMID:40084850 | DOI:10.1021/acs.orglett.5c00231

Pest Manag Sci. 2025 Mar 14. doi: 10.1002/ps.8770. Online ahead of print.ABSTRACTBACKGROUND: Maize is a critically important world staple food, yet its productivity is exposed to a notorious invasive pest of the fall armyworm (Spodoptera frugiperda). To discern the transgenerational effects and potential pest control efficacy, we evaluated chlorantraniliprole, azadirachtin, and uniconazole on S. frugiperda development, reproduction, metabolome, and larval transcriptome.RESULTS: Exposure to chlorantraniliprole, azadirachtin, and uniconazole has impacted S. frugiperda larval development, pupation, fecundity, and longevity. Biochemical analysis of the specific enzyme activities [acetylcholinesterase (AChE), carboxylesterase (CarE), glutathione-S-transferase (GST), and cytochrome P450 (P450)] showed a very high magnitude of activity changes. Chlorantraniliprole and azadirachtin had prominent influences on the expression of common genes involved in DNA replication, oxidative phosphorylation, digestion, immune reaction, and the endocrine system, as shown by RNA sequencing. In contrast, uniconazole affected gene regulation only marginally. Besides, the pesticides significantly affected the maize plants by altering their metabolome and transcriptome profiles and dramatically enhanced plant mortality, especially after chlorantraniliprole and azadirachtin treatments. RNA sequencing of maize plants treated with chlorantraniliprole, azadirachtin, and uniconazole revealed significant gene expression changes, providing insights into the plant's adaptive responses and potential alterations in insect-plant interactions.CONCLUSION: These results indicate complex, transgenerational effects of S. frugiperda itself and maize plants. These findings underline the potential of integrating these compounds into bio-intensive pest management strategies against S. frugiperda, with implications for enhancing maize protection. © 2025 Society of Chemical Industry.PMID:40084608 | DOI:10.1002/ps.8770

Front Chem. 2025 Feb 27;13:1544876. doi: 10.3389/fchem.2025.1544876. eCollection 2025.ABSTRACTOxidative stress-induced damage is a significant contributor to the impairment of Leydig cells in the testes, potentially diminishing the secretion of testosterone and other androgens, thereby resulting in testosterone deficiency. Salidroside, the principal bioactive constituent derived from Rhodiola, exhibits potent antioxidant properties. This study aims to investigate the underlying mechanisms by which salidroside enhances testosterone secretion. The study investigated the oxidative damage in TM3 cells induced by H2O2 and demonstrated that salidroside significantly decreased the levels of ROS and MDA, while increasing the levels of testosterone, SOD, GSH. These changes effectively ameliorated oxidative stress, mitigated oxidative damage, protected TM3 cells, and enhanced testosterone secretion. Additionally, UPLC-QE-Orbitrap-MS was employed to analyze the metabolomics of TM3 cells, identifying 28 distinct metabolites and associated metabolic pathways. Key metabolic pathways identified include Arginine biosynthesis, Alanine, aspartate and glutamate metabolism, Citrate cycle (TCA cycle), Phenylalanine metabolism, Pyruvate metabolism. Utilizing network pharmacology, the core targets of salidroside in enhancing testosterone secretion were further investigated, revealing the involvement of AMACR, CYP3A4, ECHS1, HSD17B10, MPO, and TYR. This discovery was confirmed by dry-wet analysis. To sum up, salidroside can reduce the level of oxidative stress and promote testosterone secretion through multiple metabolic pathways and multiple targets. In a word, salidroside may provide a new strategy for preventing and treating testosterone deficiency.PMID:40084278 | PMC:PMC11904911 | DOI:10.3389/fchem.2025.1544876

Bio Protoc. 2025 Mar 5;15(5):e5196. doi: 10.21769/BioProtoc.5196. eCollection 2025 Mar 5.ABSTRACTMany small molecules require derivatization to increase their volatility and to be amenable to gas chromatographic (GC) separation. Derivatization is usually time-consuming, and typical batch-wise procedures increase sample variability. Sequential automation of derivatization via robotic liquid handling enables the overlapping of sample preparation and analysis, maximizing time efficiency and minimizing variability. Herein, a protocol for the fully automated, two-stage derivatization of human blood-based samples in line with GC-[Orbitrap] mass spectrometry (MS)-based metabolomics is described. The protocol delivers a sample-to-sample runtime of 31 min, being suitable for better throughput routine metabolomic analysis. Key features • Direct and rapid methoximation on vial followed by silylation of metabolites in various blood matrices. • Measure ~40 samples per 24 h, identifying > 70 metabolites. • Quantitative reproducibility of routinely measured metabolites with coefficients of variation (CVs) < 30%. • Requires a Thermo ScientificTM TriPlusTM RSH (or comparable) autosampler equipped with incubator/agitator, cooled drawer, and automatic tool change (ATC) station equipped with liquid handling tools. Graphical overview Workflow for profiling metabolites in human blood using automated derivatization.PMID:40084079 | PMC:PMC11896771 | DOI:10.21769/BioProtoc.5196

Bio Protoc. 2025 Mar 5;15(5):e5237. doi: 10.21769/BioProtoc.5237. eCollection 2025 Mar 5.ABSTRACTCapturing produced, consumed, or exchanged metabolites (metabolomics) and the result of gene expression (transcriptomics) require the extraction of metabolites and RNA. Multi-omics approaches and, notably, the combination of metabolomics and transcriptomic analyses are required for understanding the functional changes and adaptation of microorganisms to different physico-chemical and environmental conditions. A protocol was developed to extract total RNA and metabolites from less than 6 mg of a kind of phototrophic biofilm: oxygenic photogranules. These granules are aggregates of several hundred micrometers up to several millimeters. They harbor heterotrophic bacteria and phototrophs. After a common step for cell disruption by bead-beating, a part of the volume was recovered for RNA extraction, and the other half was used for the methanol- and dichloromethane-based extraction of metabolites. The solvents enabled the separation of two phases (aqueous and lipid) containing hydrophilic and lipophilic metabolites, respectively. The 1H nuclear magnetic resonance (NMR) analysis of these extracts produced spectra that contained over a hundred signals with a signal-to-noise ratio higher than 10. The quality of the spectra enabled the identification of dozens of metabolites per sample. Total RNA was purified using a commercially available kit, yielding sufficient concentration and quality for metatranscriptomic analysis. This novel method enables the co-extraction of RNA and metabolites from the same sample, as opposed to the parallel extraction from two samples. Using the same sample for both extractions is particularly advantageous when working with inherently heterogeneous complex biofilm. In heterogeneous systems, differences between samples may be substantial. The co-extraction will enable a holistic analysis of the metabolomics and metatranscriptomics data generated, minimizing experimental biases, including technical variations and, notably, biological variability. As a result, it will ensure more robust multi-omics analyses, particularly by improving the correlation between metabolic changes and transcript modifications. Key features • Co-extraction of metabolites and total RNA from 6 mg of dry biomass of phototrophic biofilms, notably oxygenic photogranules. • Biphasic metabolome extraction for the characterization of hydrophilic and lipophilic metabolites using 1H NMR. • Total RNA extraction with sufficient quality and quantity for analysis of (meta)transcriptome. Graphical overview Metabolomic and RNA co-extraction from oxygenic photogranules.PMID:40084078 | PMC:PMC11896772 | DOI:10.21769/BioProtoc.5237

Theranostics. 2025 Feb 10;15(7):3035-3054. doi: 10.7150/thno.102822. eCollection 2025.ABSTRACTNasopharyngeal carcinoma (NPC) is a heterogeneous cancer with variable therapeutic responses, highlighting the need to better understand the molecular factors influencing treatment outcomes. This study aims to explore spatially metabolic and gene expression alterations in NPC patients with different therapeutic responses and PD-1 expression levels. Methods: This study employs spatial metabolomics (SM) and spatial transcriptomics (ST) to investigate significant alterations in metabolic pathways and metabolites in NPC patients exhibiting therapeutic sensitivity or elevated programmed death 1 (PD-1) expression. The spatial distribution of various cell types within the TME and their complex interactions were also investigated. Identified prognostic targets were validated using public datasets from TCGA, and further substantiated by in vitro functional analyses. Results: SM analysis revealed substantial reprogramming in lipid metabolism, branched-chain amino acid (BCAA) metabolism, and glutamine metabolism, which were closely associated with therapeutic response and PD-1 expression. ST analysis highlighted the critical role of interactions between precursor T cells and malignant epithelial cells in modulating therapeutic response in NPC. Notably, six key genes involved in BCAA metabolism (IL4I1, OXCT1, BCAT2, DLD, ALDH1B1, HADH) were identified in distinguishing patients with therapeutic sensitivity from those with therapeutic resistance. Functional validation of DLD and IL4I1 revealed that gene silencing significantly inhibited NPC cell proliferation, colony formation, wound healing, and invasion. Silencing DLD or IL4I1 induced cell cycle arrest. Reduction in α-Ketomethylvaleric acid (KMV) levels was demonstrated upon IL4I1 silencing. Immunohistochemical analysis further confirmed that high expression of these six genes was significantly associated with poor prognosis in NPC patients, a trend corroborated by data from the TCGA head and neck cancer cohort. Conclusions: This study highlights the pivotal roles of key molecular players in therapeutic response in NPC, providing compelling evidence for their potential application as prognostic biomarkers and therapeutic targets, thereby contributing to precision oncology strategies aimed at improving patient outcomes.PMID:40083932 | PMC:PMC11898293 | DOI:10.7150/thno.102822

Front Nutr. 2025 Feb 27;12:1500600. doi: 10.3389/fnut.2025.1500600. eCollection 2025.ABSTRACTNutritional programming is a manipulation of fetal and neonatal development through maternal feeding. In humans and pigs, maternal yeast supplementation was demonstrated as a promising approach to positively to modulate newborns' health. This study aimed to investigate the effects of Saccharomyces cerevisiae var. boulardii CNCM I-1079 (SB) supplementation in pregnant and lactating bitches on the newborns' early growth rate (EGR, between birth and 2 days of life), metabolic profiles, and the association between both of them. A total of 17 female dogs and their 81 puppies were included. From day 28 of gestation until the end of the study, bitches were divided into two groups, one of which received orally 1.3 × 109 colony forming units of live yeast per day. Puppies from mothers receiving the live yeast were defined as the SB group (n = 40) and the others were defined as the placebo group (n = 4 1). For each puppy, EGR was calculated, and blood and urine samples were collected at D2 for metabolome analysis using liquid chromatography-mass spectrometry (LCMS). Puppies from the SB group presented higher EGR compared with the placebo group (12% vs. 7%; p = 0.049). According to the Sparse Partial Least Squares Discriminant Analysis (sPLS-DA), both urine and serum metabolome profiles were significantly different between the two groups with a total of 29 discriminating metabolites in urine and serum. Fourteen of them were implicated in the nitrogen metabolism pathway including, gamma-aminobutyrate, 3-methyl-l-histidine and xanthosine (less abundant in SB compared with placebo group, all p < 0.05), adenine, aspartate and proline (more abundant in SB compared with placebo group, all p < 0.05). Metabolic pathways pointed to proline synthesis, a crucial component in collagen synthesis and osteoarticular system development. Urinary proline abundance was positively correlated with EGR (r = 0.45; p < 0.001). These findings highlight the potential benefits of maternal supplementation with SB promoting early neonatal growth, essential for the neonatal survival, through nitrogen metabolism orientation.PMID:40083890 | PMC:PMC11903263 | DOI:10.3389/fnut.2025.1500600

Mol Clin Oncol. 2025 Feb 20;22(4):35. doi: 10.3892/mco.2025.2830. eCollection 2025 Apr.ABSTRACTAn overview of metabolomics in cancer research, focusing on the identification of biomarkers, pharmacological targets and therapeutic agents, is provided in the present review. The fundamentals of metabolomics, the role of metabolites in cancer emergence and the methods used in metabolomic analysis, are reviewed. The applications of metabolomics in cancer therapy and diagnostics, as well as the challenges encountered in metabolomic research, are discussed. Finally, the potential clinical uses of metabolomics in cancer research and its future possibilities are explored, emphasising the importance of non-invasive diagnostic and monitoring techniques. The present review highlights the significance of metabolite-based metabolomics as a specialised tool for illuminating disease processes and identifying treatment potentials. The malfunctioning of metabolomic pathways and metabolite accumulation or depletion is caused by metabolomics abnormalities. Metabolite signatures close to a subject's phenotypic informative dimension can be used to monitor therapies and disease prediction diagnosis and prognosis. Non-invasive diagnostic and monitoring techniques with high specificity and selectivity are urgently needed. Metabolite-based metabolomics is a specialised metabolic biomarker and pathway-analysis technique, illuminating the putative processes of numerous human illnesses and determining treatment potentials. Locating biochemical pathway modifications that are early warning signs of pathological malfunction and illness is possible by identifying functional biomarkers linked to phenotypic variance. Scientists generated numerous metabolomics profiles to disclose the underlying processes and metabolomics networks for therapeutic target research in biomedicine. The metabolomic analysis of the potential utility of metabolites as biomarkers for clinical events is summarised in the present review. The significance of metabolite-based metabolomics as a specialised tool for illuminating disease processes and identifying treatment potentials is highlighted.PMID:40083862 | PMC:PMC11905217 | DOI:10.3892/mco.2025.2830

Food Chem X. 2025 Feb 14;26:102284. doi: 10.1016/j.fochx.2025.102284. eCollection 2025 Feb.ABSTRACTIn this study volatile and non-volatile flavour metabolites were systematically measured in prawn, scallop, squid, barramundi, salmon, snapper, and tuna using headspace solid-phase microextraction gas chromatography-mass spectrometry for volatile compounds, liquid chromatography-mass spectrometry for non-volatile taste metabolites, and inductively coupled plasma mass spectrometry for elemental analysis. The data indicated that a core group of flavour compounds were commonly present across seafood species, contributing to fundamental seafood flavour. Orthogonal partial least squares-discriminant analysis identified unique odourants, tastants, and elements that differentiate individual species. These findings provide valuable insights for understanding differences in the flavour between key seafood species and in formulating more realistic plant-based seafood flavours.PMID:40083856 | PMC:PMC11905853 | DOI:10.1016/j.fochx.2025.102284

Front Cardiovasc Med. 2025 Feb 27;12:1529921. doi: 10.3389/fcvm.2025.1529921. eCollection 2025.ABSTRACTINTRODUCTION: Mutations in the sarcomere protein, particularly in cardiac myosin binding protein C gene (MyBPC3), were the most frequent genetic cause of hypertrophic cardiomyopathy (HCM). The pathogenic MyBPC3 P459fs mutation has been reported in HCM patients. However, there was limited knowledge of the structure-function relationships and potential pathways in clinical HCM with MyBPC3 P459fs mutation.METHODS: We used multi-omics approaches and super-resolution imaging to explore the effects of MyBPC3 P459fs mutation on humans and cells. HCM patients carrying MyBPC3 P459fs mutation (MyBPC3-P459fs HCMs) and healthy controls (HCs) were evaluated for myocardial function using both conventional and advanced echocardiography. In parallel, H9C2 myocardial cells infected with either MyBPC3 P459fs mutation (P459fs cells) or its wild type (WT cells) were investigated for myocardial fiber formation and the potential pathways behind this using super-resolution imaging and metabolomics and proteomics.RESULTS: First, conventional and advanced echocardiography showed that MyBPC3-P459fs HCMs exhibited left ventricular diastolic and systolic dysfunction. Subsequently, super-resolution imaging indicated that P459fs cells formed fewer and shorter myocardial fibers in the cytoplasm compared to WT cells. Moreover, our metabolomic and proteomic data suggested several key components of mitochondrial membrane integrity, myocardial remodeling, myocardial energy metabolism, oxidative stress, inflammation, and actin binding capacity were significantly altered in response to P459fs mutation.CONCLUSIONS: This investigation indicated myocardial dysfunction and myocardial fiber disarray in clinical HCMs with MyBPC3 P459fs mutation and added potential pathways underlying this. These findings provided a link between the observed structural and functional disorders in MyBPC3 P459fs mutation and its onset of HCM pathogenesis and might have a significant translational contribution to effective treatment in HCM patients with MyBPC3 P459fs mutation.PMID:40083819 | PMC:PMC11903464 | DOI:10.3389/fcvm.2025.1529921

Front Microbiol. 2025 Feb 27;16:1576969. doi: 10.3389/fmicb.2025.1576969. eCollection 2025.ABSTRACT[This corrects the article DOI: 10.3389/fmicb.2025.1452423.].PMID:40083791 | PMC:PMC11903761 | DOI:10.3389/fmicb.2025.1576969