PubMed

Sci China Life Sci. 2025 Apr 7. doi: 10.1007/s11427-024-2882-x. Online ahead of print.ABSTRACTMetabolites in skeletal muscles play an important role in their growth, development, immunity and other physiological activities. However, the genetic basis of metabolites in skeletal muscle remains poorly understood. Here, we identified 247 candidate divergent regions containing 905 protein-coding genes closely related to metabolic pathways, including lysine degradation and fatty acid biosynthesis. We then profiled 3,060 metabolites in 246 skeletal muscle samples from F2 segregating population generated by mallard×Pekin duck crosses using metabolomic approaches. We identified 2,044 significant metabolome-based GWAS signals and 21 candidate genes potentially modulating metabolite contents in skeletal muscle. Among them, the levels of 2-aminoadipic acid in skeletal muscle were significantly correlated with body weight and intramuscular fat content, determined by a 939-bp CR1 LINE insertion in AADAT. We further found that the CR1 LINE insertion most possibly led to a splice mutation in AADAT, resulting in the downregulation of the lysine degradation pathway in skeletal muscle. Moreover, intramuscular fat content and fatty acids biosynthesis pathway was significantly increased in individuals with CR1 LINE insertion. This study enhances our understanding of the genetic basis of skeletal muscle metabolic traits and promotes the efficient utilization of metabolite traits in the genetic improvement of animals.PMID:40208415 | DOI:10.1007/s11427-024-2882-x

Clin Exp Med. 2025 Apr 10;25(1):111. doi: 10.1007/s10238-025-01605-2.ABSTRACTMetabolic abnormalities have been identified in various solid tumors and hematologic diseases, with reprogramming of central carbon metabolism occurring to promote disease progression. However, the metabolic profile of central carbon in acute myeloid leukemia (AML) remains unknown. We employed targeted metabolomics to analyze the alterations in central carbon metabolites present in the blood of acute myeloid leukemia (AML) patients. Models constructed using orthogonal partial least squares discriminant analysis (OPLS-DA) were utilized to evaluate intergroup differences in metabolite levels. Furthermore, a public database facilitated the kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. Additionally, metabolites exhibiting significant differences were selected, and their effects on the proliferation and drug resistance of human myeloid leukemia cell lines were validated in vitro using CCK-8 analysis, MTT assays, and flow cytometry. Our results indicated that 27 targeted metabolites were up-regulated and eight targeted metabolites were down-regulated in the AML group. These metabolites were primarily enriched in pathways related to the biosynthesis of cofactors, glyoxylate and dicarboxylate metabolism, glucagon signaling, 2-oxocarboxylic acid metabolism, biosynthesis of amino acids, the citrate cycle (TCA cycle), and central carbon metabolism in cancer. Notably, significant changes were observed in malic acid, alpha-ketoisovaleric acid, and glucuronic acid. In vitro experiments demonstrated that exogenous glucuronic acid can promote the growth and drug resistance of human AML cells. In conclusion, this study reveals alterations in central carbon metabolites in the blood of AML patients and identifies metabolites that may play a role in AML development and drug resistance.PMID:40208363 | DOI:10.1007/s10238-025-01605-2

J Cosmet Dermatol. 2025 Apr;24(4):e70168. doi: 10.1111/jocd.70168.ABSTRACTBACKGROUND: Pollutant particles can penetrate and accumulate in skin, leading to excessive oxidative stress, inflammation, and skin disorders. Reduced glutathione (GSH) is considered as "the master antioxidant" and major detoxification agent.AIMS: To characterize the metabolomic changes of skin keratinocytes under the pollutant benzo[a]pyrene (BaP) challenge and investigate the interventional effects of glutathione amino acid precursors (GAP).METHODS: Normal human epidermal keratinocytes (NHEKs) were challenged with BaP with or without GAP treatment. GSH/GSSG levels were measured by UPLC-MS/MS. Non-targeted metabolome analysis was conducted with UPLC-QTOF mass spectrometry. Transcriptomics analysis was performed using RNA-seq. DNA damage biomarker γ-H2AX was analyzed by western blot. Reconstructed pigmented skin equivalent models (pLSE) were used for evaluating phenotypical changes.RESULTS: One micromolar BaP exposure induced widespread metabolic reprogramming in in vitro NHEKs with over-represented differential metabolites in pathways including purine and pyrimidine nucleotide metabolism, xenobiotic metabolism, methylation, and RNA modification, etc. GAP co-treatment improved GSH/GSSG ratio, reduced reactive BaP metabolites, and partially reversed BaP induced metabolic and transcriptomic alterations. Western blotting further confirmed that GAP treated samples showed reduced γ-H2AX staining. In pLSE models, GAP treatment significantly ameliorated BaP induced skin darkness and hyperpigmentation.CONCLUSIONS: In summary, GAP shows in vitro protective effects against BaP by maintaining GSH homeostasis, helping metabolic detoxification, reducing DNA damage, and is effective in preventing hyperpigmentation of skin models under pollution challenge.PMID:40208244 | DOI:10.1111/jocd.70168

Expert Rev Proteomics. 2025 Apr 10. doi: 10.1080/14789450.2025.2491357. Online ahead of print.ABSTRACTINTRODUCTION: A holistic view on biological systems is today a reality with the application of multi-omic technologies. These technologies allow the profiling of genome, epigenome, transcriptome, proteome, metabolome as well as newly emerging 'omes.' While the multiple layers of data accumulate, their integration and reconciliation in a single system map is a cumbersome exercise that faces many challenges. Application to human health and disease requires large sample size, robust methodologies and high-quality standards.AREAS COVERED: We review the different methods used to integrate multi-omics, as recent ones including artificial intelligence. With proteomics as an anchor technology, we then present selected applications of its data combination with other omics' layers in clinical research, mainly covering literature from the last five years in the Scopus and/or PubMed databases.EXPERT OPINION: Multi-omics is powerful to comprehensively type molecular layers and link them to phenotype. Yet, technologies and data are very diverse and still strategies and methodologies to properly integrate these modalities are needed.PMID:40207843 | DOI:10.1080/14789450.2025.2491357

Biomed Chromatogr. 2025 May;39(5):e70085. doi: 10.1002/bmc.70085.ABSTRACTChinese yam (Dioscorea opposita Thunb. cv. Tiegun) has been utilized in traditional medicine and as a food source for centuries. However, the metabolite profiles and antioxidant activities of yam by-product peel have not been studied sufficiently. Thus, to effectively identify the active metabolites in yam peel, we employed a UHPLC-MS/MS-based widely targeted metabolomics on Chinese yam peel from loessial soil (LPCY) and sandy soil (SPCY). A total of 1054 metabolites were identified, comprising 379 primary metabolites, 528 secondary metabolites, and 147 other compounds. Notably, multivariate analyses revealed the presence of 143 differentially accumulated metabolites (DAMs) between SPCY and LPCY. Linoleic acid metabolism, phenylpropanoid biosynthesis, plant hormone signal transduction, pyruvate metabolism, and sphingolipid metabolism were the main differentially regulated pathways. The DPPH, ABTS, and FRAP assays demonstrated that the antioxidant activities of LPCY were significantly higher than those of SPCY. Correlation analysis revealed that most DAMs, including phenolic acids, lipids, organic acids, and amino acids, exhibited significant positive correlations with antioxidant activities (r ≥ 0.7, p < 0.05). These results indicate that loessial soil promotes the accumulation of antioxidant-active compounds. Overall, this study suggests that yam peels hold significant potential as a rich natural source of bioactive substances.PMID:40207649 | DOI:10.1002/bmc.70085

Ecology. 2025 Apr;106(4):e70069. doi: 10.1002/ecy.70069.ABSTRACTSeminal hypotheses in ecology and evolution postulate that stronger and more specialized biotic interactions contribute to higher species diversity at lower elevations and latitudes. Plant-chemical defenses mediate biotic interactions between plants and their natural enemies and provide a highly dimensional trait space in which chemically mediated niches may facilitate plant species coexistence. However, the role of chemically mediated biotic interactions in shaping plant communities remains largely untested across large-scale ecological gradients. Here, we used ecological metabolomics to quantify the chemical dissimilarity of foliar metabolomes among 473 tree species in 16 tropical tree communities along an elevational gradient in the Bolivian Andes. We predicted that tree species diversity would be higher in communities and climates where co-occurring tree species are more chemically dissimilar and exhibit faster evolution of secondary metabolites (lower chemical phylogenetic signal). Further, we predicted that these relationships should be especially pronounced for secondary metabolites known to include antiherbivore and antimicrobial defenses relative to primary metabolites. Using structural equation models, we quantified the direct effects of rarefied median chemical dissimilarity and chemical phylogenetic signal on tree species diversity, as well as the indirect effects of climate. We found that chemical dissimilarity among tree species with respect to all metabolites and secondary metabolites had positive direct effects on tree species diversity, and that climate (higher temperature and precipitation, and lower temperature seasonality) had positive indirect effects on species diversity by increasing chemical dissimilarity. In contrast, chemical dissimilarity of primary metabolites was unrelated to species diversity and climate. Chemical phylogenetic signal of all metabolite classes had negative direct effects on tree species diversity, indicating faster evolution of metabolites in more diverse communities. Climate had a direct effect on species diversity but did not indirectly affect diversity through chemical phylogenetic signal. Our results support the hypothesis that chemically mediated biotic interactions shape elevational diversity gradients by imposing stronger selection for chemical divergence in more diverse communities and maintaining higher chemical dissimilarity among species in warmer, wetter, and more stable climates. Our study also illustrates the promise of ecological metabolomics in the study of biogeography, community ecology, and complex species interactions in high-diversity ecosystems.PMID:40207495 | DOI:10.1002/ecy.70069

Biomed Chromatogr. 2025 May;39(5):e70083. doi: 10.1002/bmc.70083.ABSTRACTDa-Huang-Zhe-Chong Pills (DHZCPs) have demonstrated efficacy in treating uterine fibroids (UFs), but the mechanisms underlying their action remain unclear. In this study, untargeted serum metabolomic analysis was employed to investigate the therapeutic effects of DHZCP in a rat model of UFs utilizing advanced ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) and pattern recognition. Histopathological examination through H&E staining revealed significant improvements in uterine morphology following DHZCP administration. The levels of four serum hormones, that is, estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and progesterone (PROG), tended to shift toward normal in the DHZCP-treated group compared with the model group. Our metabolomic profiling identified 20 distinct endogenous metabolites that were differentially expressed between UF and normal rats, with DHZCP treatment significantly normalizing 16 of these metabolic markers. Comprehensive pathway analysis highlighted three major metabolic pathways affected by DHZCP intervention: tryptophan metabolism, riboflavin metabolism, and arginine-proline metabolism. Notably, spearman correlation analysis indicated that tryptophan, lysoPC (18:1/0:0), uric acid, and serotonin were strongly positively correlated with serum levels of both E2 and PROG. Additionally, riboflavin, indoleacetic acid, and indole-3-propionic acid were positively correlated with E2 levels. Our findings suggest that DHZCP may exert therapeutic effects primarily through the modulation of tryptophan and riboflavin metabolism, providing a solid foundation for its clinical application.PMID:40207468 | DOI:10.1002/bmc.70083

Mov Disord. 2025 Apr 10. doi: 10.1002/mds.30189. Online ahead of print.ABSTRACTBACKGROUND: The immune system likely plays a role in the pathogenesis of spinocerebellar ataxia type 3 (SCA3). Peripheral blood leukocytes are indicative of the immune status in neurodegenerative diseases. However, alterations in the characteristics of peripheral blood leukocytes at different stages of SCA3 and their potential roles in disease progression remain unclear.OBJECTIVES: The goal was to identify leukocyte profiles alterations at different stages of SCA3 and analyze their correlation with disease severity.METHODS: This cross-sectional study included 150 total ATXN3 expansion carriers (20 pre-ataxic and 130 ataxic) and 113 healthy controls. Differences in leukocyte profiles were analyzed, and correlations with clinical characteristics were assessed using Spearman and partial correlation. Logistic regression and receiver operating characteristic curve identified independent factors associated with disease severity. Mediation analysis evaluated the effect of lymphocyte counts on the relationship between disease duration and SARA scores.RESULTS: Alterations in neutrophil, lymphocyte, eosinophil, and basophil counts were observed across ATXN3 expansion carriers, including those in pre-ataxic and ataxic stages, compared with healthy controls. Lymphocyte counts negatively correlated with SARA and International Cooperative Ataxia Rating Scale scores, particularly in speech function. Leukocyte, monocyte, and basophil counts were also negatively associated with ataxia scales scores or sub-item scores. Lymphocyte counts distinguished disease severities, and partially mediated the effect of disease duration on ataxia scale scores in ataxic SCA3.CONCLUSIONS: Leukocyte profiles alterations at different stages of SCA3 may be closely linked to disease progression and severity. Lymphocyte counts may serve as valuable indicators of disease severity. © 2025 International Parkinson and Movement Disorder Society.PMID:40207410 | DOI:10.1002/mds.30189

Alzheimers Dement. 2025 Apr;21(4):e14604. doi: 10.1002/alz.14604.ABSTRACTIndividuals with Down syndrome (DS) are highly susceptible to Alzheimer's disease (AD). The integration of genomics, transcriptomics, epigenomics, proteomics, and metabolomics enables unprecedented understanding of DS-AD, offering a detailed picture of this complex issue. The vast -omics data also present challenges that reflect the complexity of genetic information flow. These studies nonetheless reveal critical mechanisms behind AD risk, including unique observations in DS that differ from those seen in the general population and familial dominant AD. In addition, the correlations between the AD polygenic risk score and proteins related to female infertility and autoimmune thyroiditis corroborate clinical observations. Metabolomic data reveal disrupted metabolic networks, offering prospects for a dynamic score to create specialized nutritional interventions. By adopting a multidimensional perspective with integrated reductionism, the evolving landscape presents an opportunity to identify promising directions for developing precision strategies to mitigate the impact of AD in the DS population. HIGHLIGHTS: Individuals with Down syndrome (DS) are highly susceptible to Alzheimer's disease (AD). DS-AD is characterized by its polygenic nature, extending beyond chromosome 21 with significant contributions from various chromosomes. DS-AD also presents unique features that differ from those observed in the general population and familial dominant AD. Our review consolidates key findings from genomics, transcriptomics, epigenomics, proteomics, and metabolomics, providing a comprehensive view of the molecular mechanisms underlying DS-AD. We highlight promising research directions to further elucidate the pathogenesis of DS-AD.PMID:40207399 | DOI:10.1002/alz.14604

J Cachexia Sarcopenia Muscle. 2025 Apr;16(2):e13749. doi: 10.1002/jcsm.13749.ABSTRACTBACKGROUND: Age-related primary sarcopenia and end-stage renal disease (ESRD)-related muscle wasting are discrete entities; however, both manifest as a decline in skeletal muscle mass and strength. The etiological pathways differ, with aging factors implicated in sarcopenia and a combination of uremic factors, including haemodialysis, contributing to ESRD-related muscle wasting. Understanding these molecular nuances is imperative for targeted interventions, and the integration of proteomic and metabolomic data elucidate these intricate processes.METHODS: We generated detailed clinical data and multi-omics data (plasma proteomics and metabolomics) for 78 participants to characterise sarcopenia (n = 28; mean age, 72.6 ± 7.0 years) or ESRD (n = 22; 61.6 ± 5.5 years) compared with controls (n = 28; 69.3 ± 5.7 years). Muscle mass was measured using bioelectrical impedance analysis and handgrip strength. Five-times sit-to-stand test performance was measured for all participants. Sarcopenia was diagnosed in accordance with the 2019 Consensus Guidelines from the Asian Working Group for Sarcopenia. An abundance of 234 metabolites and 722 protein groups was quantified in all plasma samples using liquid chromatography with tandem mass spectrometry.RESULTS: Muscle mass, handgrip strength and lower limb muscle function significantly lower in the sarcopenia group and the ESRD group compared with those in the control group. Metabolomics revealed altered metabolites, highlighting exclusive differences in ESRD-related muscle wasting. Metabolite set enrichment analysis revealed the involvement of numerous metabolic intermediates associated with urea cycle, amino acid metabolism and nucleic acid metabolism. Catecholamines, including epinephrine, dopamine and serotonin, are significantly elevated in the plasma of patients within the ESRD group. Proteomics data exhibited a clearer distinction among the three groups compared with the metabolomics data, particularly in distinguishing the control group from the sarcopenia group. The ciliary neurotrophic factor receptor was top-ranked in terms of the variable importance of projection scores. Plasma AHNAK protein levels was higher in the sarcopenia group but was lower in the ESRD group. Proteomic set enrichment analysis revealed enrichment of several pathways related to sarcopenia, such as hemopexin, defence response and cell differentiation, in sarcopenia group. Multi-omic integration analysis revealed associations between relevant metabolites, including catecholamines, and a group of annotated proteins in extracellular exosomes.CONCLUSIONS: We identified distinct multi-omic signatures in individuals with ESRD or sarcopenia, providing new insights into the mechanisms underlying ESRD-related muscle wasting, which differ from primary sarcopenia. These findings may support interventions for context-dependent muscle loss and contribute to the development of targeted treatments and preventive strategies for muscle wasting.PMID:40207397 | DOI:10.1002/jcsm.13749

Org Lett. 2025 Apr 10. doi: 10.1021/acs.orglett.5c00953. Online ahead of print.ABSTRACTLauicyclone A (1), a new skeletal diterpenoid characterized by an unprecedented carbon skeleton, represents the first reported natural product featuring a complex tricyclo[4.3.1]decane framework. Along with Lauicyclones B-E (2-5), all five compounds were isolated from Croton laui. Comprehensive spectroscopic analyses, quantum-chemical calculations, and X-ray diffractions were used to identify their structures. The antitumor mechanism of compound 1 was investigated using 1H NMR-based metabolomics.PMID:40207356 | DOI:10.1021/acs.orglett.5c00953

Food Chem X. 2025 Feb 4;26:102264. doi: 10.1016/j.fochx.2025.102264. eCollection 2025 Feb.ABSTRACTRipening is a key process driving the transformation of non-volatiles in Keemun congou black tea (KCBT), affecting its flavour profile and health functions. In this study, taste was quantitatively evaluated by using sensory and biomimetic electrodes and by employing metabolomic techniques. The results revealed that the content of polyphenols was greatly affected by ripening, catechins and flavonoids reduced by 63.5 % and 9.2 %, respectively, and theaflavins increased by 14.6 %, thereby attenuating the bitterness and astringency of the tea infusion while enhancing its sweetness and mellowness. Experiments regarding the inhibition of α-amylase and α-glucosidase activity and scavenging of 2,2-diphenyl-1-picrylhydrazyl radical revealed that ripening triggered the cascade reaction of polyphenols to form catechin polymers and flavonoid glycosides, thereby changing the dual biological functions of hypoglycaemia and free radical scavenging in vitro. Our study confirms the key role of ripening in enhancing the taste quality and potential health functional activities of KCBT.PMID:40207296 | PMC:PMC11979434 | DOI:10.1016/j.fochx.2025.102264

Med Genet. 2025 Apr 8;37(2):137-146. doi: 10.1515/medgen-2025-2009. eCollection 2025 Jun.ABSTRACTHuman induced pluripotent stem cell (hiPSC)-based disease modelling has significantly advanced the field of cardiogenetics, providing a precise, patient-specific platform for studying genetic causes of heart diseases. Coupled with genome editing technologies such as CRISPR/Cas, hiPSC-based models not only allow the creation of isogenic lines to study mutation-specific cardiac phenotypes, but also enable the targeted modulation of gene expression to explore the effects of genetic and epigenetic deficits at the cellular and molecular level. hiPSC-based models of heart disease range from two-dimensional cultures of hiPSC-derived cardiovascular cell types, such as various cardiomyocyte subtypes, endothelial cells, pericytes, vascular smooth muscle cells, cardiac fibroblasts, immune cells, etc., to cardiac tissue cultures including organoids, microtissues, engineered heart tissues, and microphysiological systems. These models are further enhanced by multi-omics approaches, integrating genomic, transcriptomic, epigenomic, proteomic, and metabolomic data to provide a comprehensive view of disease mechanisms. In particular, advances in cardiovascular tissue engineering enable the development of more physiologically relevant systems that recapitulate native heart architecture and function, allowing for more accurate modelling of cardiac disease, drug screening, and toxicity testing, with the overall goal of personalised medical approaches, where therapies can be tailored to individual genetic profiles. Despite significant progress, challenges remain in the maturation of hiPSC-derived cardiomyocytes and the complexity of reproducing adult heart conditions. Here, we provide a concise update on the most advanced methods of hiPSC-based disease modelling in cardiogenetics, with a focus on genome editing and cardiac tissue engineering.PMID:40207041 | PMC:PMC11976404 | DOI:10.1515/medgen-2025-2009

Front Nutr. 2025 Mar 26;12:1549913. doi: 10.3389/fnut.2025.1549913. eCollection 2025.ABSTRACTBACKGROUND: Propolis, a natural mixture rich in bioactive compounds, has shown the potential to relieve exercise-induced fatigue. However, the underlying mechanism remains unclear. This study aimed to explore the anti-fatigue effects of ethanol extract of propolis (EEP) and its potential mechanisms.METHODS: Male C57BL/6 mice aged 6-8 weeks were subjected to swim training with or without EEP supplementation (400 mg/kg.bw) for 3 weeks, followed by a exhaustive swimming test to simulate exercise-induced fatigue. The exhaustion time and fatigue-related biochemical indices were measured to assess the anti-fatigue effects. The anti-fatigue mechanism of EEP was further investigated using untargeted serum metabolomics and 16S rRNA gene sequencing of the gut microbiota.RESULTS: The results showed that supplementation with EEP significantly increased the exhaustive swimming time of the mice by 27.64%, with no significant effects on body weight, food intake, or viscera and muscle index among the 3 groups. Biochemical analysis indicated that EEP effectively alleviated fatigue-related biochemical indices caused by excessive exercise, including liver glycogen (LG), muscle glycogen (MG), blood lactate (BLA), blood urea nitrogen (BUN), lactate dehydrogenase (LDH), interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), superoxide dismutase (SOD), total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA). Serum metabolomics analysis revealed that EEP reversed the levels of 6 key metabolites (Gamma-Aminobutyric acid, pipecolic acid, L-isoleucine, sucrose, succinic acid, and L-carnitine), which are involved in 7 metabolic pathways related to energy metabolism, amino acid metabolism, and carbohydrate metabolism. 16S rRNA sequencing analysis of the cecal contents showed that EEP altered the composition and structure of the gut microbiota, increasing the abundance of butyrate-producing bacteria and reducing the abundance of harmful bacteria. Correlation analysis revealed that specific bacterial genera were closely related to certain differential metabolites and biochemical indices.CONCLUSION: Our study showed that EEP significantly increased exercise endurance in mice and exerted anti-fatigue effects by modulating key metabolites and the gut microbiota.PMID:40206950 | PMC:PMC11980171 | DOI:10.3389/fnut.2025.1549913

Front Vet Sci. 2025 Mar 26;12:1569196. doi: 10.3389/fvets.2025.1569196. eCollection 2025.ABSTRACTINTRODUCTION: Tibetan pigs, native to the Qinghai-Tibet Plateau, have adapted over millennia to extreme conditions such as low oxygen, harsh cold, and high UV radiation, impacting their muscle characteristics and digestive tract microbiota. The quality of pork from Tibetan pigs (TP) and black pigs (BP) is influenced by various factors, including genetics, diet, and environmental adaptation. However, the specific influence of digestive tract microbiota metabolites on muscle traits remains poorly understood. Our goal was to correlate omic variations with meat quality traits and identify potential biomarkers predictive of superior meat quality, elucidate the regulatory effects of digestive tract microbial metabolites on Tibetan pig muscle characteristics, and reveal the genetic and nutritional mechanisms that promote adaptation to extreme environmental conditions.METHODS: This analysis encompassed metabolomic profiling of the entire digestive tract-including the stomach, jejunum, cecum, colon, and rectum-as well as histological, amino acid, fatty acid composition, and transcriptomic assessments of the longissimus dorsi muscle tissues to investigate how digestive tract microbial metabolites influence muscle adaptation to high altitudes.RESULTS: Analyses revealed that Tibetan pig muscles contain smaller, more oxidative fibers enriched with flavor-enhancing amino acids. This was accompanied by a more favorable n-6/n-3 fatty acid ratio. Distinct patterns of microbial metabolites were observed in the digestive tract, influencing protein digestion and purine metabolism, and correlating with muscle glycine levels. Transcriptomic data showed varied gene expression in metabolic pathways related to salivary and pancreatic secretion, as well as carbohydrate and fatty acid metabolism. Integrated multi-omics approaches linked stomach metabolism, particularly through bile secretion pathways influenced by acetylcholine, to muscle functionality, highlighting the important role played by the ATP1B4 gene in enabling muscle physiology in Tibetan pigs.DISCUSSION: This study highlights the importance of targeted dietary interventions in improving meat quality for specific pig breeds. It also provides a theoretical foundation for precision agriculture strategies aimed at enhancing the meat quality of both TP and BP pigs.PMID:40206253 | PMC:PMC11979216 | DOI:10.3389/fvets.2025.1569196

ISME Commun. 2025 Mar 18;5(1):ycaf047. doi: 10.1093/ismeco/ycaf047. eCollection 2025 Jan.ABSTRACTPhages can reshape the metabolic network of hosts to support specific requirements for replication during infection. However, metabolomic profiling of phage-elicited host global metabolic alterations and the linkage of phage-encoded auxiliary metabolic genes to these alterations are understudied. In this study, the dynamics of intracellular metabolites of Dinoroseobacter shibae DFL12, a member of marine environmentally and biogeochemically relevant Roseobacter clade, in response to four distinct lytic roseophage infections were investigated. Metabolomic profiling indicated that roseophage infections significantly altered host metabolism in a phage-specific manner. Pathway enrichment analyses showed that the central carbon pathway and DNA, amino acid, and coenzyme metabolism were commonly altered by roseophages, revealing a central role of these pathways in phage replication. Furthermore, clear infection stage-specific host responses were observed, corresponding to different metabolic demands of phage replication in the early and late infection stages. Interestingly, the content of host vitamin B1, which is the essential nutrient provided by D. shibae to its symbiotic microalgae, increased in the early infection stage for most roseophages, implying that phage infection may impact the symbiosis of D. shibae with microalgae. Finally, combined metabolomic and phage genomics analyses showed that roseophages adopt different strategies to expand the host pyrimidine pool (recycling or de novo synthesis of pyrimidine nucleotides), and this difference was likely related to variation in the GC content between phage and host genomes. Collectively, these results highlight the potential importance of phage-specific and infection stage-specific host metabolic reprogramming in marine phage-host interactions, bacteria-microalgae symbiosis, and biogeochemical cycles.PMID:40206216 | PMC:PMC11981692 | DOI:10.1093/ismeco/ycaf047

Front Pharmacol. 2025 Mar 26;16:1554479. doi: 10.3389/fphar.2025.1554479. eCollection 2025.ABSTRACTINTRODUCTION: Ovarian function decline results in reduced estrogen levels, leading to endocrine disorders, oxidative stress damage, and excessive activation of inflammatory factors, all of which contribute to the development of premenstrual syndrome (PMS). Kunxinning Granules (KXN) has been clinically approved for PMS treatment, but its bioactive ingredients and mechanism of action remain unclear. This study aimed to investigate the active metabolites and molecular mechanism of KXN in treating PMS rats, laying a foundation for the clinical development of PMS treatment.METHODS: An ovariectomized (OVX) rat model was established to evaluate the efficacy of KXN in treating PMS. Molecular network (MN) analysis, combined with UPLC/Q-TOF-MS, identified prototype compounds in the samples and constructed a chemical classification map based on their structures. A network analysis and proteomics were conducted to predict potential pathways through which KXN regulates PMS. Quantitative metabolomics assays were used to confirm these potential pathways. Additionally, target prediction and binding enzyme activity detection elucidated the key active metabolites and mechanisms of action in KXN.RESULTS: KXN exhibited significant effectiveness in supplementing estrogen deficiency and uterine atrophy in the OVX model. We identified 16 absorbed metabolites as the potential pharmacological ingredients of KXN in vivo. The steroid hormone biosynthesis pathway, a crucial pathway of KXN in PMS, played a key role in KXN's effectiveness. KXN improved hormonal metabolic disorders by regulating this pathway. The main metabolites in KXN, including astragaloside IV, icariin and baohuoside I increased estradiol levels by enhancing the activity of CYP19A1, the representative enzyme in hormone biosynthesis pathway.DISCUSSION: This study shows that KXN could relieve anxiety, depression, and osteoporosis in PMS. This pharmacological effect is exerted through steroid hormone synthesis to address estrogen deficiency. The findings provide valuable insights into the underlying mechanisms and support its clinical application.PMID:40206089 | PMC:PMC11979375 | DOI:10.3389/fphar.2025.1554479

Front Pharmacol. 2025 Mar 26;16:1498358. doi: 10.3389/fphar.2025.1498358. eCollection 2025.ABSTRACTINTRODUCTION: Sheep placenta extract (SPE) is a representative traditional medicinal substance that exhibits multiple experimentally validated physiological properties, including anti-aging effects, wound healing acceleration, antioxidant activity, and anti-inflammatory mechanisms. However, the mechanism by which SPE influences the delay of aging is still not yet clear.METHODS: Exploring the effects of sheep placenta extract on D-gal induced senescence in a mouse model of aging by macrogenomics and metabolomics.RESULTS: In the serum of aging mice treated with SPE, the levels of antioxidant function such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) were notably higher compared to those in the blank group, whereas malondialdehyde (MDA) levels decreased. We revealed that SPE alleviated the changes in gut microbiota caused by aging in mice, with a significant decrease in the Firmicutes/Bacteroidetes (F/B) ratio in the gut. Furthermore, Akkermansia muciniphila (A. muciniphila), which is known for its regulating immune response and potential anti-aging effects, showed a significant increase of 1177.94%. The analysis of UHPLC-QE-MS combined with orthogonal partial least squares discriminant analysis (OPLS-DA) screening of differential metabolites in mouse serum metabolic profiles revealed a significant upregulation of cis-5,8,11,14,17-eicosapentaenoic acid (EPA) and triptolide in serum metabolites, following SPE treatment, which are commonly believed to have immunosuppressive, anti-inflammatory, anti-proliferative, and anti-tumor effects.DISCUSSION: The role of SPE in ameliorating aging may be associated with the increased abundance of A. muciniphila in the gut microbiota and the accumulation of two metabolites, EPA and triptolide, in the serum.PMID:40206069 | PMC:PMC11979192 | DOI:10.3389/fphar.2025.1498358

Front Pharmacol. 2025 Mar 21;16:1549834. doi: 10.3389/fphar.2025.1549834. eCollection 2025.ABSTRACTINTRODUCTION: Chinemys reevesii (Gray) species-sourced Testudinis Carapax et Plastrum (TCP) is an animal-based traditional Chinese medical material, and its decoction or extract possesses multiple pharmacological effects. However, other species-sourced substitutes are sometimes used in the market, potentially impairing the quality and effectiveness of TCP medications. To address this issue, it is very necessary to develop applicable approaches that can accurately differentiate genuine TCP from its counterfeit counterparts.METHODS: In this study, liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based metabolomic and lipidomic analyses were performed to comprehensively detect water-soluble metabolites and organic-soluble lipids in water decoctions of genuine TCP and its substitutes, such as Trachemys scripta elegans (Wied)- and Ocadia sinensis (Gray)-sourced tortoise shells. Differential analyses based on fold change (FC), principal component analysis (PCA), and Orthogonal partial least squares-discriminant analysis (OPLS-DA) were performed to assess the differences among TCP decoctions from different origins, as well as between decoctions of TCP samples and the two substitutes. Further, Kyoto Encyclopedia of Genes and Genomes (KEGG) database-based pathway enrichment analysis was performed for differential metabolites and lipids among them. Besides, LC-MS/MS-based absolute quantitative method was used to quantify the amino acid-relevant metabolites in decoctions of TCP and substituted tortoise shell samples.RESULTS: All told, 1117 water-soluble metabolites (including amino acids, organic acids, nucleotides and their metabolites or derivatives, etc.) and 574 organic-soluble lipids (including glycerolipids, sphingolipids, glycerophospholipids, fatty acids, and sterol lipids) were detected in decoctions of TCP and two substitutes. Comparative analyses revealed that there were significantly differential metabolites and lipids among TCP decoctions from different origins, as well as between decoctions of TCP samples and the two substitutes. Of particular interest, the content of N-methyl-4-aminobutyric acid was lower in the substituted samples than TCP samples. Furthermore, the content of 27 amino acids, 22 amino acid derivatives, and 18 small peptides in the decoctions of TCP and two substitutes were absolutely quantified, constituting up to tens of milligrams per 10 g of tortoise shell.DISCUSSION: In conclusion, our study provides comprehensive metabolomic and lipidomic information of TCP decoction. However, the current results represent preliminary data, and further extensive research is required to validate these findings.PMID:40206067 | PMC:PMC11980632 | DOI:10.3389/fphar.2025.1549834

Front Pharmacol. 2025 Mar 26;16:1526653. doi: 10.3389/fphar.2025.1526653. eCollection 2025.ABSTRACTBACKGROUND: Chronic heart failure (CHF) is one of the leading causes of high mortality worldwide. It is characterized by pathological hypertrophy and poses a major threat to human health. Aconiti Lateralis Radix Praeparata is widely used in ancient China to treat CHF. However, the pathology is obscured, necessitating further exploration.METHODS: Prospective targets were predicted by network analysis. A transverse aortic constriction (TAC) mice model was subsequently constructed to determine the effects of aqueous extract of Aconiti Lateralis Radix Praeparata (AEA) on CHF. The echocardiography was performed to investigate cardiac function. Histopathological analysis of cardiac tissue was conducted to assess myocardial fibrosis. Nontargeted metabolomics was performed to analyze serum metabolites. The phosphorylation level of PI3K and AKT, and downstream targets such as Bnip3, p62, Atg5, and LC3II were measured by Western blotting. In vitro, norepinephrine (NE) was used to stimulate cardiac hypertrophy. Parameters such as reactive oxygen species levels, mitochondrial membrane potential, ATP concentration, and CK/MB content were detected in H9c2 cells.RESULTS: AEA significantly alleviated CHF. Network analysis indicated the participation of AKT in CHF, and was modulated by Aconiti Lateralis Radix Praeparata. In vivo, AEA administration effectively ameliorated cardiac performance, evidenced by the elevation of ejection fraction. Histopathological analysis displayed a diminishment of collagen fiber. Metabolomics analysis showed that several metabolites such as tetrahydroxycorticosterone, decylubiquinone and taurocholic acid were increased in the TAC mice serum. Additionally, the phosphorylation levels of PI3K and AKT, and expression levels of Drp1, Opa1, Bnip3, p62, Atg5 and LC3II were altered in TAC group. In vitro, NE stimulation increased the cell surface area and deteriorated mitochondrial functions in H9c2 cells. However, AEA administration partially reversed such results, and the mechanism was associated with mitophagy.CONCLUSION: This study revealed that AEA improved cardiac function via the PI3K/AKT/Bnip3 pathway.PMID:40206063 | PMC:PMC11979612 | DOI:10.3389/fphar.2025.1526653