Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Higher Serum Monolaurin Is Associated with a Lower Risk of COVID-19: Results from a Prospective Observational Cohort Study

Thu, 27/03/2025 - 11:00
Int J Mol Sci. 2025 Mar 10;26(6):2452. doi: 10.3390/ijms26062452.ABSTRACTThe COVID-19 pandemic has stimulated the search for effective preventive and therapeutic agents. In recent years, many studies have considered the effects of different nutrients. This study aimed to investigate the association between serum monolaurin levels and the risk of developing COVID-19 among healthcare workers. In this prospective observational cohort study, 2712 healthcare workers from the University Hospital "Maggiore della Carità" in Novara, Italy were enrolled. Participants underwent blood sampling and were followed up for six months to evaluate the protective role of serum monolaurin against COVID-19 infection. Monolaurin levels were quantified using targeted metabolomic analysis. The study cohort consisted of 1000 individuals with a mean age of 46.4 years, predominantly female. Higher serum monolaurin concentrations were significantly associated with a lower risk of SARS-CoV-2 infection at both 3- and 6-month follow-ups. The optimal cut-off value for serum monolaurin, which provides protective efficacy, was identified as 0.45 µg/mL. Higher serum monolaurin levels appear to be associated with a reduced risk of COVID-19, suggesting its potential as a protective dietary supplement against SARS-CoV-2 infection. This study contributes to the growing body of evidence supporting the role of dietary factors in the management and prevention of infectious diseases and highlights the potential of targeted metabolomics in identifying prophylactic biomarkers.PMID:40141096 | DOI:10.3390/ijms26062452

Regulatory Mechanisms of Yili Horses During an 80 km Race Based on Transcriptomics and Metabolomics Analyses

Thu, 27/03/2025 - 11:00
Int J Mol Sci. 2025 Mar 8;26(6):2426. doi: 10.3390/ijms26062426.ABSTRACTEquine endurance exercise induces physiological changes that alter metabolism and molecular pathways to maintain balance after intense physical activity. However, the specific regulatory mechanisms remain under debate. Identifying differentially expressed genes (DEGs) and differential metabolites (DMs) associated with equine endurance is essential for elucidating these regulatory mechanisms. This study collected blood samples from six Yili horses before and after an 80 km race and conducted transcriptomics and metabolomics analyses, yielding 722 DEGs and 256 DMs. These DEGs were primarily enriched in pathways related to amino acid biosynthesis, cellular senescence, and lipid metabolism/atherosclerosis. The DMs were predominantly enriched in fatty acid biosynthesis and the biosynthesis of unsaturated fatty acids. The integrative transcriptomics and metabolomics analyses of DEGs and DMs highlight functional changes during the endurance race. The findings offer a holistic understanding of the regulatory mechanisms underlying equine endurance and a solid foundation for formulating training programs to optimize horse performance in endurance racing.PMID:40141070 | DOI:10.3390/ijms26062426

Multi-Omics Association Analysis of DOF Transcription Factors Involved in the Drought Resistance of Wheat Induced by <em>Strigolactone</em>

Thu, 27/03/2025 - 11:00
Int J Mol Sci. 2025 Mar 7;26(6):2396. doi: 10.3390/ijms26062396.ABSTRACTDrought is one of the main adverse factors affecting the growth and development of wheat. The molecular regulation pathway of Strigolactone (SLs or SL),which induces drought resistance in wheat, needs to be further clarified. In this study, SL and Tis (Strigolactone inhibitor) were sprayed on leaves to clarify the changes in wheat drought resistance and their effect on antioxidant enzyme activity, photosynthesis and other metabolic processes. However, 20 kinds of DOF transcription factors were identified by transcriptome metabolome association analysis, and they were highly enriched on chromosome 2. Moreover, the proline, glycosides, indoleacetic acid, betaine, etc., in wheat are the key factors affecting the change in the drought resistance of wheat. The study initially revealed the mechanism of the involvement of DOF in the SL regulation pathway and revealed its impact on different metabolites of wheat, thus providing a theoretical reference for the subsequent molecular verification and breeding of excellent drought-resistant varieties.PMID:40141041 | DOI:10.3390/ijms26062396

Hypertrophic Cardiomyopathy-Associated CRYAB<sup>R123W</sup> Activates Calcineurin, Reduces Calcium Sequestration, and Alters the CRYAB Interactome and the Proteomic Response to Pathological Hypertrophy

Thu, 27/03/2025 - 11:00
Int J Mol Sci. 2025 Mar 7;26(6):2383. doi: 10.3390/ijms26062383.ABSTRACTHypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular condition in the world, affecting around 1 in 500 people. HCM is characterized by ventricular wall thickening, decreased ventricular chamber volume, and diastolic dysfunction. Inherited HCM is most commonly caused by sarcomere gene mutations; however, approximately 50% of patients do not present with a known mutation, highlighting the need for further research into additional pathological mutations. The alpha-B crystallin (CRYAB) mutation CRYABR123W was previously identified as a novel sarcomere-independent mutation causing HCM associated with pathological NFAT signaling in the setting of pressure overload. We generated stable H9C2 cell lines expressing FLAG-tagged wild-type and mutant CRYAB, which demonstrated that CRYABR123W increases calcineurin activity. Using AlphaFold to predict structural and interaction changes, we generated a model where CRYABR123W uniquely binds to the autoinhibitory domain of calcineurin. Co-immunoprecipitation using the CRYAB FLAG tag followed by mass spectrometry showed novel and distinct changes in the protein interaction patterns of CRYABR123W. Finally, mouse heart extracts from our wild-type CRYAB and CRYABR123W models with and without pressure overload caused by transverse aortic constriction (TAC) were used in global proteomic and phosphoproteomic mass spectrometry analysis, which showed dysregulation in cytoskeletal, metabolomic, cardiac, and immune function. Our data illustrate how CRYABR123W drives calcineurin activation and exhibits distinct changes in protein interaction and cellular pathways during the development of HCM and pathological cardiac hypertrophy.PMID:40141027 | DOI:10.3390/ijms26062383

Association of circulating metabolic biomarkers with risk of lung cancer: a population-based prospective cohort study

Thu, 27/03/2025 - 11:00
BMC Med. 2025 Mar 26;23(1):176. doi: 10.1186/s12916-025-03993-4.ABSTRACTBACKGROUND: There is emerging evidence that metabolites might be associated with risk of lung cancer, but their relationships have not been fully characterized. We aimed to investigate the association between circulating metabolic biomarkers and lung cancer risk and the potential underlying pathways.METHODS: Nuclear magnetic resonance metabolomic profiling was conducted on baseline plasma samples from 91,472 UK Biobank participants without cancer and pregnancy. Multivariate Cox regression models were employed to assess the hazard ratios (HRs) of 164 metabolic biomarkers (including metabolites and lipoprotein subfractions) and 9 metabolic biomarker principal components (PCs) for lung cancer, after adjusting for covariates and false discovery rate (FDR). Pathway analysis was conducted to investigate the potential metabolic pathways.RESULTS: During a median follow-up of 11.0 years, 702 participants developed lung cancer. A total of 109 metabolic biomarkers (30 metabolites and 79 lipoprotein subfractions) were associated with the risk of lung cancer. Glycoprotein acetyls demonstrated a positive association with lung cancer risk [HR = 1.13 (95%CI: 1.04, 1.22)]. Negative associations with lung cancer were found for albumin [0.78 (95%CI: 0.72, 0.83)], acetate [0.91 (95%CI: 0.85, 0.97)], valine [0.90 (95%CI: 0.83, 0.98)], alanine [0.88 (95%CI: 0.82, 0.95)], glucose [0.91 (95%CI: 0.85, 0.99)], citrate [0.91 (95%CI: 0.85, 0.99)], omega-3 fatty acids [0.83 (95%CI: 0.77, 0.90)], linoleic acid [0.83 (95%CI: 0.77, 0.89)], etc. Nine PCs represented over 90% of the total variances, and among those with statistically significant estimates, PC1 [0.85 (95%CI: 0.80, 0.92)], PC2 [0.88 (95%CI: 0.82, 0.95)], and PC9 [0.87 (95%CI: 0.80, 0.93)] were negatively associated with lung cancer risk, whereas PC7 [1.08 (95%CI: 1.00, 1.16)] and PC8 [1.16 (95%CI: 1.08, 1.26)] showed positive associations with lung cancer risk. The pathway analysis showed that the "linoleic acid metabolism" was statistically significant after the FDR adjustment (p value 0.0496).CONCLUSIONS: Glycoprotein acetyls had a positive association with lung cancer risk while other metabolites and lipoprotein subfractions showed negative associations. Certain metabolites and lipoprotein subfractions might be independent risk factors for lung cancer. Our findings shed new light on the etiology of lung cancer and might aid the selection of high-risk individuals for lung cancer screening.PMID:40140895 | DOI:10.1186/s12916-025-03993-4

Metabolic modelling reveals the aging-associated decline of host-microbiome metabolic interactions in mice

Thu, 27/03/2025 - 11:00
Nat Microbiol. 2025 Mar 26. doi: 10.1038/s41564-025-01959-z. Online ahead of print.ABSTRACTAging is accompanied by considerable changes in the gut microbiome, yet the molecular mechanisms driving aging and the role of the microbiome remain unclear. Here we combined metagenomics, transcriptomics and metabolomics from aging mice with metabolic modelling to characterize host-microbiome interactions during aging. Reconstructing integrated metabolic models of host and 181 mouse gut microorganisms, we show a complex dependency of host metabolism on known and previously undescribed microbial interactions. We observed a pronounced reduction in metabolic activity within the aging microbiome accompanied by reduced beneficial interactions between bacterial species. These changes coincided with increased systemic inflammation and the downregulation of essential host pathways, particularly in nucleotide metabolism, predicted to rely on the microbiota and critical for preserving intestinal barrier function, cellular replication and homeostasis. Our results elucidate microbiome-host interactions that potentially influence host aging processes. These pathways could serve as future targets for the development of microbiome-based anti-aging therapies.PMID:40140706 | DOI:10.1038/s41564-025-01959-z

Baseline gut microbiome and metabolites are correlated with changes in alcohol consumption in participants in a randomized Zonisamide clinical trial

Thu, 27/03/2025 - 11:00
Sci Rep. 2025 Mar 26;15(1):10486. doi: 10.1038/s41598-025-92313-0.ABSTRACTDevelopment and severity of alcohol use disorder (AUD) has been linked to variations in gut microbiota and their associated metabolites in both animal and human studies. However, the involvement of the gut microbiome in alcohol consumption of individuals with AUD undergoing treatment remains unclear. To address this, stool samples (n = 32) were collected at screening (baseline) and trial completion from a double-blind, placebo-controlled trial of zonisamide in individuals with AUD. Alcohol consumption was measured both at baseline and endpoint of 16-week trial period. Fecal microbiome was analyzed via 16 S rRNA sequencing and metabolome via untargeted LC-MS. Both sex (p = 0.003) and psychotropic medication usage (p = 0.025) are associated with baseline microbiome composition. The relative abundance of 11 genera at baseline was correlated with percent drinking reduction (p.adj < 0.1). Overall microbiome community structure at baseline differed between high and low reducers of alcohol drinking (67-100% and 0-33% drinking reduction, respectively; p = 0.034). A positive relationship between baseline fecal GABA levels and percent drinking reduction (R = 0.43, p.adj < 0.07) was identified by microbiome function prediction and confirmed by ELISA and metabolomics. Metabolomics analysis also found 3-hydroxykynurenine, a neurotoxic intermediate metabolite of tryptophan, was negatively correlated with drinking reduction (p.adj = 0.047), and was over-represented in low reducers. These findings highlight importance of baseline microbiome and amino acid metabolites in drinking reduction in AUD participants undergoing zonisamide treatment. It may hold significant value as a predictive tool in clinical settings to better personalize intervention and improve reduction in alcohol consumption in future.PMID:40140641 | DOI:10.1038/s41598-025-92313-0

Resolving multi-image spatial lipidomic responses to inhaled toxicants by machine learning

Thu, 27/03/2025 - 11:00
Nat Commun. 2025 Mar 26;16(1):2954. doi: 10.1038/s41467-025-58135-4.ABSTRACTRegional responses to inhaled toxicants are essential to understand the pathogenesis of lung disease under exposure to air pollution. We evaluate the effect of combined allergen sensitization and ozone exposure on eliciting spatial differences in lipid distribution in the mouse lung that may contribute to ozone-induced exacerbations in asthma. We demonstrate the ability to normalize and segment high resolution mass spectrometry imaging data by applying established machine learning algorithms. Interestingly, our segmented regions overlap with histologically validated lung regions, enabling regional analysis across biological replicates. Our data reveal differences in the abundance of spatially distinct lipids, support the potential role of lipid saturation in healthy lung function, and highlight sex differences in regional lung lipid distribution following ozone exposure. Our study provides a framework for future mass spectrometry imaging experiments capable of relative quantification across biological replicates and expansion to multiple sample types, including human tissue.PMID:40140638 | DOI:10.1038/s41467-025-58135-4

Longitudinal fecal microbiota and volatile metabolomics preceding necrotizing enterocolitis in preterm infants: a case-control study

Thu, 27/03/2025 - 11:00
Sci Rep. 2025 Mar 26;15(1):10419. doi: 10.1038/s41598-025-94692-w.ABSTRACTAlterations in fecal microbiota and volatile organic compound (VOC) profiles of preterm infants have been demonstrated before onset of necrotizing enterocolitis (NEC). However, NEC-specific signatures need to be identified before potential application as predictive biomarker in clinical practice. A prospective multicenter case-control study was conducted to identify preclinical fecal microbiota and VOC profiles of infants that developed NEC. Microbiota analysis (PCR-based IS-pro technique) and VOC analysis (gas chromatography-mass spectrometry) were performed on fecal samples collected up to three days before clinical NEC onset. In 112 infants (56 NEC, 56 matched controls), sufficient number fecal samples were collected for either microbiota or VOC analysis. Prior to NEC onset, Clostridium perfringens (p = 0.023, unadjusted) was more present in infants with NEC, versus controls. VOC analysis showed a clear distinction between fecal profiles of NEC cases and controls (area under the curve = 0.82). Fourteen unique VOC features contributed to this discrimination. Fecal microbiota and VOC profiles may serve as early indicators of NEC, and allow for increased understanding of pathophysiological mechanisms of NEC, but larger validation cohorts are needed before an overarching NEC-specific predictive microbiota-based biomarker can be implemented.PMID:40140438 | DOI:10.1038/s41598-025-94692-w

Last Decade Insights in Exploiting Marine Microorganisms as Sources of New Bioactive Natural Products

Wed, 26/03/2025 - 11:00
Mar Drugs. 2025 Mar 7;23(3):116. doi: 10.3390/md23030116.ABSTRACTMarine microorganisms have emerged as prolific sources of bioactive natural products, offering a large chemical diversity and a broad spectrum of biological activities. Over the past decade, significant progress has been made in discovering and characterizing these compounds, pushed by technological innovations in genomics, metabolomics, and bioinformatics. Furthermore, innovative isolation and cultivation approaches have improved the isolation of rare and difficult-to-culture marine microbes, leading to the identification of novel secondary metabolites. Advances in synthetic biology and metabolic engineering have further optimized natural product yields and the generation of novel compounds with improved bioactive properties. This review highlights key developments in the exploitation of marine bacteria, fungi, and microalgae for the discovery of novel natural products with potential applications in diverse fields, underscoring the immense potential of marine microorganisms in the growing Blue Economy sector.PMID:40137302 | DOI:10.3390/md23030116

Investigating the Mechanism of Action of Ipomoea pes-caprae in the Treatment of Rheumatoid Arthritis Based on Serum Metabolomics and Network Pharmacology

Wed, 26/03/2025 - 11:00
Mar Drugs. 2025 Mar 7;23(3):114. doi: 10.3390/md23030114.ABSTRACTIpomoea pes-caprae (L.) Sweet (Convolvulaceae) is a commonly used marine Chinese medicine in the coastal areas of southern China. Traditionally, it has been used in the treatment of rheumatoid arthritis (RA). However, the mechanism of action against RA remains unclear. This study aimed to explore the mechanism of action of Ipomoea pes-caprae water extract (IPE) in the treatment of RA through serum metabolomics and network pharmacology. Rat models of RA with wind-dampness cold bi-syndrome (WCM) and wind-dampness heat bi-syndrome (WHM) were established to evaluate the therapeutic effect of IPE against RA. Ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) technology was used to analyze the absorbed components of IPE in the plasma of the two models. Serum metabolomics was employed to identify potential biomarkers and metabolic pathways of IPE in the treatment of RA. The key targets and related pathways of RA were screened using network pharmacology and validated using molecular docking. The biomarker-pathway-target network was mapped via the combination of metabolomics and network pharmacology. A total of 10 chemical constituents were identified from WHM rat plasma, and eight chemical constituents were identified from WCM rat plasma. Serum metabolomics research identified 20 endogenous potential biomarkers, and 10 major metabolic pathways closely related to WHM and WCM. Network pharmacology analysis yielded 65 overlapping targets, with the core targets being ALB, AKT1, EGFR, and CASP3. Molecular docking showed that the four absorbed components in plasma had a strong binding activity with ALB and AKT1. Combining metabolomics and network pharmacology, two major biomarkers and two major pathways were identified. IPE can effectively relieve the symptoms of RA, and the potential mechanism of IPE in treating RA has been preliminarily elucidated. These results can provide a scientific basis for further drug research and development, as well as clinical application.PMID:40137300 | DOI:10.3390/md23030114

Whole-Genome Sequencing of <em>Flammulina filiformis</em> and Multi-Omics Analysis in Response to Low Temperature

Wed, 26/03/2025 - 11:00
J Fungi (Basel). 2025 Mar 17;11(3):229. doi: 10.3390/jof11030229.ABSTRACTThe growth of Flammulina filiformis is strongly dependent on low-temperature cues for the initiation of primordia formation. To obtain a comprehensive understanding of the molecular mechanisms that govern the mycelial response to cold stress, de novo genome sequencing of the F. filiformis monokaryon and multi-omics data (transcriptome and metabolome) analyses of the mycelia, primordia, and fruiting bodies were conducted in the present study. Genome sequencing based on PacBio HiFi and Hi-C resulted in a 36.3 Mb genome sequence that mapped to 12 chromosomes, comprising 11,886 protein-coding genes. A total of 25 cold-responsive (COR) genes and 520 cold-adapted enzymes were identified in the genome. Multi-omics analyses showed that the pathways related to carbohydrate metabolism in the mycelia under low temperature (10 °C) were significantly enriched. Further examination of the expression profiles of carbohydrate-active enzymes (CAZymes) involved in carbohydrate metabolism revealed that out of 515 CAZyme genes in F. filiformis, 58 were specifically upregulated in mycelia under low-temperature conditions. By contrast, the expression levels of these genes in primordia and fruiting bodies reverted to those prior to low-temperature exposure. These indicate that CAZyme genes are important for the low-temperature adaptation of F. filiformis. This research contributes to the targeted breeding of F. filiformis.PMID:40137266 | DOI:10.3390/jof11030229

Adaptative Divergence of Cryptococcus neoformans: Phenetic and Metabolomic Profiles Reveal Distinct Pathways of Virulence and Resistance in Clinical vs. Environmental Isolates

Wed, 26/03/2025 - 11:00
J Fungi (Basel). 2025 Mar 12;11(3):215. doi: 10.3390/jof11030215.ABSTRACTCryptococcus neoformans is a life-threatening fungal pathogen that primarily affects immunocompromised individuals. While antiretroviral therapy has reduced incidence in developed nations, fluconazole-resistant strains and virulent environmental isolates continue to pose challenges, especially because they have many mechanisms of adaptability, supporting their survival. This study explores the phenetic and metabolomic adaptations of C. neoformans in clinical and environmental contexts to understand the factors influencing pathogenicity and resistance.METHODS: An in silico observational study was conducted with 16 C. neoformans isolates (6 clinical, 9 environmental, and 1 reference) from the NCBI database. Molecular phenetic analysis used MEGA version 11.0.13 and focused on efflux pump protein sequences. Molecular phenetic relationships were assessed via the UPGMA clustering method with 1000 bootstrap replicates. The enzymatic profiling of glycolytic pathways was conducted with dbCAN, and metabolomic pathway enrichment analysis was performed in MetaboAnalyst 6.0 using the KEGG pathway database.RESULTS: Molecular phenetic analysis revealed distinct clustering patterns among isolates, reflecting adaptations associated with clinical and environmental niches. Clinical isolates demonstrated enriched sulfur metabolism and glutathione pathways, likely adaptations to oxidative stress in host environments, while environmental isolates favored methane and glyoxylate pathways, suggesting adaptations for survival in carbon-rich environments.CONCLUSION: Significant phenetic and metabolomic distinctions between isolates reveal adaptive strategies for enhancing virulence and antifungal resistance, highlighting potential therapeutic targets.PMID:40137253 | DOI:10.3390/jof11030215

Decoding the Tissue-Specific Profiles of Bioactive Compounds in Helvella leucopus Using Combined Transcriptomic and Metabolomic Approaches

Wed, 26/03/2025 - 11:00
J Fungi (Basel). 2025 Mar 6;11(3):205. doi: 10.3390/jof11030205.ABSTRACTHelvella leucopus, an endangered wild edible fungus, is renowned for its distinct health benefits and nutritional profile, with notable differences in the bioactive and nutritional properties between its cap and stipe. To investigate the molecular basis of these tissue-specific variations, we conducted integrative transcriptomic and metabolomic analyses. Metabolomic profiling showed that the cap is particularly rich in bioactive compounds, including sterols and alkaloids, while the stipe is abundant in essential nutrients, such as glycerophospholipids and amino acids. Transcriptomic analysis revealed a higher expression of genes involved in sterol biosynthesis (ERG1, ERG3, ERG6) and energy metabolism (PGK1, ENO1, PYK1) in the cap, suggesting a more active metabolic profile in this tissue. Pathway enrichment analysis highlighted tissue-specific metabolic pathways, including riboflavin metabolism, pantothenate and CoA biosynthesis, and terpenoid backbone biosynthesis, as key contributors to the unique functional properties of the cap and stipe. A detailed biosynthetic pathway network further illustrated how these pathways contribute to the production of crucial bioactive and nutritional compounds, such as sterols, alkaloids, linoleic acid derivatives, glycerophospholipids, and amino acids, in each tissue. These findings provide significant insights into the molecular mechanisms behind the health-promoting properties of the cap and the nutritional richness of the stipe, offering a theoretical foundation for utilizing H. leucopus in functional food development and broadening our understanding of bioactive and nutritional distribution in edible fungi.PMID:40137243 | DOI:10.3390/jof11030205

Integrated Multi-Omics Analysis to Investigate the Molecular Mechanisms Underlying the Response of <em>Auricularia heimuer</em> to High-Temperature Stress

Wed, 26/03/2025 - 11:00
J Fungi (Basel). 2025 Feb 20;11(3):167. doi: 10.3390/jof11030167.ABSTRACTHigh-temperature stress is a key factor that reduces the yields of edible fungi. Auricularia heimuer (A. heimuer) is a nutrient-rich edible fungus that is widely cultivated in China. In this study, we analyzed the physiological, transcriptomic, and metabolomic results of A. heimuer (variety "Hei29") under high-temperature stress. Our findings revealed that high temperatures (30 °C and 35 °C) significantly reduced hyphal growth, increased malondialdehyde content and antioxidant enzyme activity, and enhanced the accumulation of secondary metabolites, such as phenolic compounds and flavonoids. A total of 15 candidate genes potentially responsive to high-temperature stress were identified through transcriptomic analysis, including those involved in regulating antioxidant defense, heat shock response, sugar metabolism, amino acid metabolism, and accumulating secondary metabolites. Metabolomic analysis identified three candidate metabolites potentially responsive to high-temperature stress, including kinetin, flavonoids, and caffeic acid, as well as several metabolic pathways, including nucleotide metabolism, ABC transporters, and cofactor biosynthesis. These mechanisms help mitigate oxidative damage to cellular structures and energy deficits caused by elevated temperatures, enabling the fungus to maintain cellular stability, metabolic function, and growth under heat stress. This study is the first to explore the molecular mechanism of A. heimuer in response to high-temperature stress. The results provide valuable insights into the molecular mechanisms of heat stress tolerance in A. heimuer, highlighting potential targets for developing heat-tolerant strains for industrial application.PMID:40137205 | DOI:10.3390/jof11030167

Correction: Badillo-Sanchez et al. Human Archaeological Dentin as Source of Polar and Less Polar Metabolites for Untargeted Metabolomic Research: The Case of Yersinia pestis. Metabolites 2023, 13, 588

Wed, 26/03/2025 - 11:00
Metabolites. 2025 Mar 11;15(3):187. doi: 10.3390/metabo15030187.ABSTRACTOne contributor's name was missing in the original version of the authorship of the paper [...].PMID:40137177 | DOI:10.3390/metabo15030187

Diet-Induced Proteomic and Metabolomic Signatures in Chronic Kidney Disease: A Precision Nutrition Approach

Wed, 26/03/2025 - 11:00
Metabolites. 2025 Mar 20;15(3):211. doi: 10.3390/metabo15030211.ABSTRACTBackground: Diet is a key modifiable factor that can either support renal health or accelerate the onset and progression of chronic kidney disease (CKD). Recent advances in multiomics, particularly proteomics and metabolomics, significantly enhanced our understanding of the molecular mechanisms linking diet to CKD risk. Proteomics offers a comprehensive analysis of protein expression, structure, and interactions, revealing how dietary components regulate cellular processes and signaling pathways. Meanwhile, metabolomics provides a detailed profile of low-molecular-weight compounds, including endogenous metabolites and diet-derived molecules, offering insights into the metabolic states that influence kidney function. Methods: We have conducted a narrative review of key papers from databases such as PubMed, Scopus, and Web of Science to explore the potential of proteomic and metabolomic analysis in identifying molecular signatures associated with diet in human and animal biological samples, such as blood plasma, urine, and in kidney tissues. These signatures help elucidate how specific foods, food groups, and overall dietary patterns may either contribute to or mitigate CKD risk. Results: Recent studies the impact of high-fat diets on protein expression involved in energy metabolism, inflammation, and fibrosis, identifying early biomarkers of kidney injury. Metabolic, including disruptions in in fatty acid metabolism, glucose regulation, and amino acid pathways, have been recognized as key indicators of CKD risk. Additionally, several studies explore specific metabolites found in biological fluids and renal tissue in response to protein-rich foods, assessing their potential roles in a progressive loss of kidney function. Emerging evidence also suggests that dietary interventions targeting the gut microbiota may help alleviate inflammation, oxidative stress, and toxin accumulation in chronic kidney disease. Notably, recent findings highlight metabolomic signatures linked to beneficial shifts in gut microbial metabolism, particularly in the context of prebiotic supplementation. Conclusions: By integrating proteomics and metabolomics, future research can refine precision nutrition strategies, helping mitigate CKD progression. Expanding large-scale studies and clinical trials will be essential in translating these molecular insights into actionable dietary guidelines.PMID:40137175 | DOI:10.3390/metabo15030211

A Pilot Study: Maternal Undernutrition Programs Energy Metabolism and Alters Metabolic Profile and Morphological Characteristics of Skeletal Muscle in Postnatal Beef Cattle

Wed, 26/03/2025 - 11:00
Metabolites. 2025 Mar 19;15(3):209. doi: 10.3390/metabo15030209.ABSTRACTObjectives: This study investigated the long-term effects of maternal undernutrition on overall muscle metabolism, growth performance, and muscle characteristics in postnatal offspring of Wagyu (Japanese Black) cattle. Methods: Wagyu cows were divided into nutrient-adequate (control, CNT; n = 4, 120% of requirements) and nutrient-restricted groups (NR; n = 4; 60% of requirements), and treated from day 35 of gestation until parturition. Diets were delivered on the basis of crude protein requirements, meeting 100% and 80% of dry matter requirements in CNT and NR groups, respectively. All offspring were provided with the same diet from birth to 300 days of age (d). Longissimus thoracis muscle (LM) samples were collected from the postnatal offspring. Results: The NR offspring had lower birth body weight, but their body weight caught up before weaning. These offspring showed enhanced efficiency in nutrient utilization during the post-weaning growth period. Comprehensive analyses of metabolites and transcripts revealed the accumulation of proteinogenic amino acid, asparagine, in NR offspring LM at 300 d, while the abundance of nicotinamide adenine dinucleotide (NADH) and succinate were reduced. These changes were accompanied by decreased gene expression of nicotinamide phosphoribosyltransferase (NAMPT), NADH: ubiquinone oxidoreductase subunit A12 (NDUFA12), and NADH dehydrogenase subunit 5 (ND5), which are essential for mitochondrial energy production. Additionally, NR offspring LM exhibited decreased abundance of neurotransmitter, along with a higher proportion of slow-oxidative myofibers and a lower proportion of fast-oxidative myofibers at 300 d. Conclusions: Offspring from nutrient-restricted cows might suppress muscle energy production, primarily in the mitochondria, and conserve energy expenditure for muscle protein synthesis. These findings suggest that maternal undernutrition programs a thrifty metabolism in offspring muscle, with long-term effects.PMID:40137173 | DOI:10.3390/metabo15030209

Metabolomics in Parkinson's Disease and Correlation with Disease State

Wed, 26/03/2025 - 11:00
Metabolites. 2025 Mar 18;15(3):208. doi: 10.3390/metabo15030208.ABSTRACTChanges in the level of metabolites, small molecules that are intermediates produced by metabolism or catabolism, are associated with developing diseases. Metabolite signatures in body fluids such as plasma, cerebrospinal fluid, urine, and saliva are associated with Parkinson's disease. Here, we discuss alteration of metabolites in the TCA cycle, pentose phosphate pathway, kynurenic network, and redox system. We also summarize the efforts of many research groups to differentiate between metabolite profiles that characterize PD motor progression and dyskinesia, gait and balance, and non-motor symptoms such as depression and cognitive decline. Understanding how changes in metabolites lead to progression in PD may allow for the identification of individuals at the earliest stage of the disease and the development of new therapeutic strategies.PMID:40137172 | DOI:10.3390/metabo15030208

Effect of Antifreeze Glycopeptides on the Quality and Microstructure of Frozen Lamb Meatballs

Wed, 26/03/2025 - 11:00
Metabolites. 2025 Mar 13;15(3):202. doi: 10.3390/metabo15030202.ABSTRACTThis study explored the protective effects of antifreeze glycopeptide and alginate on the quality of -18 °C frozen lamb meatballs across various storage periods.METHODS: Measurements of volatile salt nitrogen (TVB-N), thiobarbituric acid (TBARS), water retention, water distribution, microstructure, and metabolite changes were taken in the lamb meatballs.RESULTS: The results showed that the addition of antifreeze glycopeptides (AFGs) significantly preserved the quality characteristics of lamb meatballs. In particular, the 0.30% antifreeze glycopeptide demonstrated the strongest protective effect on water retention and metabolites during freezing. The ice crystal area within the microstructure of lamb meatballs with added antifreeze glycopeptides was markedly reduced compared to the others after 14 days of freezing (p < 0.05). Additionally, AFGs lessened the lipid oxidation reaction and prolonged the oxidation time of lamb after 28 days of freezing.CONCLUSION: In summary, AFGs beneficially affected the quality of frozen lamb meatballs and are a potential, safe, and efficient cryoprotectant.PMID:40137166 | DOI:10.3390/metabo15030202

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