PubMed

Chin Med J (Engl). 2025 May 13. doi: 10.1097/CM9.0000000000003532. Online ahead of print.NO ABSTRACTPMID:40364489 | DOI:10.1097/CM9.0000000000003532

Plants (Basel). 2025 May 4;14(9):1387. doi: 10.3390/plants14091387.ABSTRACTIris dichotoma Pall., renowned for its high ornamental value, is frequently cultivated in flowerbeds and courtyards, endowing garden landscapes with unique allure. Dark-hued flowers are widely regarded as more aesthetically appealing. This study utilized the petals of two distinct Iris dichotoma Pall. phenotypes as research materials to investigate the underlying mechanism of flower color formation. The purple-flowered Iris dichotoma Pall. was designated as Group P, and the white-flowered one as Group W. A comprehensive integrative analysis of the transcriptome and metabolome of the two petal types was carried out. Metabolomic analysis revealed that the contents of several anthocyanin derivatives, including delphinidin, petunidin, malvidin, peonidin, and procyanidin, were significantly higher in purple petals compared to white petals, with delphinidin exhibiting the highest content. The transcriptomic analysis detected 6731 differentially expressed genes (DEGs) between the white and purple petal types. Specifically, 3596 genes showed higher expression levels in purple petals, while 3135 genes exhibited lower expression levels in purple petals compared to white petals. Ten phenylalanine ammonia-lyase (PAL) genes, two chalcone synthase (CHS) genes, one anthocyanidin reductase (ANR) gene, one 4-coumarate-CoA ligase (4CL) gene, one dihydroflavonol 4-reductase (DFR) gene, one flavanone 3'-hydroxylase (F3'H) gene, and one flavonol synthase (FLS) gene were identified; they all had purple petals displaying higher expression levels than white petals. This research uncovers the potential formation mechanism of anthocyanins in the two Iris dichotoma Pall. types, thereby furnishing a theoretical foundation for floral breeding endeavors.PMID:40364416 | DOI:10.3390/plants14091387

Plants (Basel). 2025 May 3;14(9):1381. doi: 10.3390/plants14091381.ABSTRACTPeonies are globally renowned ornamental plants, and distant hybridization is a key method for breeding new varieties, though it often faces cross-incompatibility challenges. The metabolic mechanisms underlying the crossing barrier between tree peony (Paeonia sect. Moutan) and herbaceous peony (P. lactiflora) remain unclear. To identify key metabolites involved in cross-incompatibility, we performed a cross between P. ostii 'Fengdanbai' (female parent) and P. lactiflora 'Red Sara' (male parent) and analyzed metabolites in the stigma 12 h after pollination using UPLC-MS. We identified 1242 differential metabolites, with 433 up-regulated and 809 down-regulated, including sugars, nucleotides, amino acids, lipids, organic acids, benzenoids, flavonoids, and alkaloids. Most differential metabolites were down-regulated in hybrid stigmas, potentially affecting pollen germination and pollen tube growth. Cross-pollinated stigma exhibited lower levels of high-energy nutrients (such as amino acids, nucleotides, and tricarboxylic acid cycle metabolites) compared to self-pollinated stigma, which suggests that energy deficiency is a contributing factor to the crossing barrier. Additionally, cross-pollination significantly impacted KEGG pathways such as nucleotide metabolism, purine metabolism, and vitamin B6 metabolism, with most metabolites in these pathways being down-regulated. These findings provide new insights into the metabolic basis of cross-incompatibility between tree and herbaceous peonies, offering a foundation for overcoming hybridization barriers in peony breeding.PMID:40364410 | DOI:10.3390/plants14091381

Plants (Basel). 2025 May 1;14(9):1377. doi: 10.3390/plants14091377.ABSTRACTThis study aimed to examine wild-growing Hypericum perforatum L. tea (Hyperici herba) collected from Rtanj Mountain (Serbia). This research includes the following approaches: phytochemical and antioxidant characterization of H. perforatum infusion tea to determine its realistic composition (What do we consume when drinking the tea?), as well as a detailed examination of methanol(ic) extracts as the optimal extraction system. Due to the broad spectrum of both polar and nonpolar metabolites, 80% methanolic and pure methanol extracts were prepared for ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC Q-ToF) characterization through untargeted metabolomics analysis. Given the high diversity of compounds identified, the 80% methanolic extract was selected for further antioxidant examination and bioautographic characterization, including an antimicrobial activity assessment. UHPLC Q-ToF analysis identified 35 phenolics in the methanolic extract, compared to 25 metabolites in the infusion tea. The main differences were observed in flavonol/flavan-3-ol aglycones, xantones, and coumestans, which are more nonpolar compounds found only in the methanol(ic) system. Notably, specific H. perforatum metabolites were entirely absent in the infusion tea. Specifically, pseudohypericin, pseudoprotohypricin, and adhyperfirin were detected in the pure methanol extract, whereas hyperfirin was present in both methanol(ic) extracts. Additionally, eight furano-polycyclic polyprenylated acilphloroglucinols (FPPAPs) were identified in the methanol(ic) extracts as possible products of the thermal degradation and/or oxidation of hypericin/hyperforin. Both the infusion tea and methanolic extracts exhibited excellent antioxidant properties, with variations depending on the applied assay. High-performance thin-layer chromatography (HPTLC) analysis also confirmed the presence of a wide spectrum of phytochemical classes. Bioautography confirmed a promising activity of methanolic extracts against both Staphylococcus aureus and Klebsiella pneumoniae.PMID:40364406 | DOI:10.3390/plants14091377

Plants (Basel). 2025 May 1;14(9):1376. doi: 10.3390/plants14091376.ABSTRACTGibberella root rot (GRR), caused by Fusarium graminearum, is one of the major threats to maize production. However, the mechanism underlying maize's response to GRR is not fully understood. Multi-omics study incorporating metabolomics reveals insights into maize-pathogen interactions. Using metabolomics and mass spectrometry imaging (MSI), maize inbred lines with GRR resistance (W438) and susceptibility (335M) were deployed to characterize specific metabolites associated with GRR. Analysis of significantly altered metabolites suggested that glycerophospholipid metabolism was highly associated with GRR resistance or susceptibility. Furthermore, the distinct accumulation of lysophosphatidylethanolamine (lysoPE) and lysophosphatidylcholine (lysoPC) from glycerophospholipid metabolism, along with the significant up-regulation of phospholipase (PLA) gene in the susceptible line, suggested that high levels of lysoPC and lysoPE contributed to GRR susceptibility. Meanwhile, genes encoding lysophospholipase (LPLA), the detoxification enzymes of lysoPC, were significantly activated in both genotypes. However, the significantly higher expression of LPLAs in the resistant line corresponded to a significant increase in the content of non-toxic sn-glycero-3-phosphocholine, whereas this increase was not observed in the susceptible line. MSI analysis revealed the involvement of other potential phospholipids in GRR susceptibility. Taken together, maintaining an appropriate concentration of lysophospholipids is crucial for their role in the signaling pathway that triggers GRR resistance without causing damage to maize roots.PMID:40364405 | DOI:10.3390/plants14091376

Plants (Basel). 2025 Apr 30;14(9):1355. doi: 10.3390/plants14091355.ABSTRACTPlant-phyllosphere feedback (PPF) is an ecological process in which phyllosphere microbiota, originating from plant litter, are transmitted via aerosols and subsequently influence the growth of conspecific or heterospecific plants. However, the cross-species generality of this mechanism and its role in invasive plant success remain to be fully elucidated. This study systematically examined PPF effects using three invasive/native congeneric plant pairs from distinct families (Phytolaccaceae, Asteraceae, and Amaranthaceae) in Jiangxi Province, China. Key findings include the following: (1) Wide conspecific negative feedback across families, with four of six species exhibiting 6.2-12.7% biomass reduction under their own litter treatments (p < 0.05). (2) Comparable feedback intensity between invasive and native species, as indicated by average pairwise indices (invasive I = -0.05 vs. native I = -0.04; p = 0.15). Notably, the invasive species Phytolacca americana uniquely showed a positive biomass response (+7.1%), though underlying mechanisms (phytochemical or microbial) were not investigated. (3) Lack of correlation between PPF strength and plant functional traits or phylogenetic distance, as indicated by Mantel tests (p > 0.8), in contrast to the trait/phylogeny associations commonly observed in soil feedback systems. This study provided the first evidence of PPF universality across multiple plant families-previously documented only within Asteraceae-and highlights the potential microbial-mediated advantages in plant invasions. Future research should integrate spatiotemporal metagenomic and metabolomic approaches to decipher the dynamic pathogen/microbe networks and their phytochemical interactions.PMID:40364394 | DOI:10.3390/plants14091355

Molecules. 2025 May 1;30(9):2023. doi: 10.3390/molecules30092023.ABSTRACTDrosophila melanogaster is broadly used to model host-pathogen interactions. Entomopathogenic nematodes are excellent research tools for dissecting the molecular and functional basis of parasitism and the host's anti-parasitic response. In this work, we used discovery metabolomics to explore the differences in the metabolome composition of wild type D. melanogaster larvae that were infected with symbiotic nematodes (Steinernema carpocapsae carrying Xenorhabdus nematophila mutualistic bacteria) or axenic nematodes (S. carpocapsae lacking their bacterial partners). Benefiting from their high separation power, sensitivity, and compatibility with low amounts of the starting metabolome, we leveraged microanalytical capillary electrophoresis electrospray ionization mass spectrometry (CE-ESI-MS) to profile the small (<500 Da) polar portion of the metabolome among these experimental treatments. We detected and quantified 122 different small molecules, of which 50 were identified with high confidence. Supervised multivariate analysis revealed that the infection was paralleled with changes in amino acid biosynthesis (arginine, phenylalanine, tryptophan, and tyrosine), metabolism (alanine, arginine, aspartate, glutamate, glycine, proline, serine, and threonine), and classical signalling (aspartate, γ-aminobutyrate, glutamate, and pyridoxine). This study demonstrates the ability of high-sensitivity CE-ESI-MS to uncover metabolic perturbations during infection. The results from the metadata may facilitate the design of targeted studies to explore small biomolecules and their functions during host-pathogen interaction.PMID:40363828 | DOI:10.3390/molecules30092023

Molecules. 2025 Apr 30;30(9):2020. doi: 10.3390/molecules30092020.ABSTRACTThe discovery of bioactive natural products is often challenged by the complexity of isolating and characterizing active compounds within diverse mixtures. Previously, we introduced a 1H NMR-based weighted gene correlation network analysis (WGCNA) approach to identify spectral features linked to growth inhibitory activity of Piper (Piperaceae) leaf extracts against model plant, fungal, and bacterial organisms. This method enabled us to prioritize specific spectral features linked to bioactivity, offering a targeted approach to natural product discovery. In this study, we validate the predictive capacity of the WGCNA by isolating the compounds responsible for the bioactivity-associated resonances and confirming their antifungal efficacy. Using growth inhibition assays, we verified that the isolated compounds, including three novel antifungal agents, exhibited significant bioactivity. Notably, one of these compounds contains a rare imidazolium heterocyclic motif, marking a new structural class in Piper. These findings substantiate the 1H NMR-based WGCNA as a reliable tool for identifying structural types associated with biological activity, streamlining the process of discovering bioactive natural products in complex extracts.PMID:40363825 | DOI:10.3390/molecules30092020

Molecules. 2025 Apr 30;30(9):2003. doi: 10.3390/molecules30092003.ABSTRACTAge-related skeletal muscle atrophy is a major health concern in the elderly, contributing to reduced mobility, increased risk of falls, and metabolic dysfunction. The senescence-accelerated prone 8 (SAMP8) mouse model, known for its rapid aging and early cognitive decline, serves as an essential model for studying age-related muscle degeneration. While previous studies have shown that exercise attenuates muscle atrophy by promoting regeneration and improving strength, the underlying metabolic mechanisms remain poorly understood. This study used the SAMP8 model to evaluate the effects of exercise on muscle atrophy and associated metabolic changes. Our results show that exercise promoted muscle growth by reducing body weight, increasing skeletal muscle mass, and decreasing fat accumulation. Furthermore, exercise improved grip strength, muscle tone, and muscle fiber cross-sectional area, thereby preserving muscle functionality. NMR-based metabolomic analysis identified key metabolic pathways modulated by exercise, including glycine, serine, and threonine metabolism; alanine, aspartate, and glutamate metabolism; pyruvate metabolism; and taurine and hypotaurine metabolism. These findings underscore the therapeutic potential of exercise in combating age-related muscle wasting and elucidate the metabolic pathways underlying its benefits.PMID:40363810 | DOI:10.3390/molecules30092003

Molecules. 2025 Apr 29;30(9):1980. doi: 10.3390/molecules30091980.ABSTRACTNatural polysaccharides (NPs), as a class of bioactive macromolecules with multitarget synergistic regulatory potential, exhibit significant advantages in diabetes intervention. This review systematically summarizes the core hypoglycemic mechanisms of NPs, covering structure-activity relationships, integration of the gut microbiota-metabolism-immunity axis, and regulation of key signaling pathways. Studies demonstrate that the molecular weight, branch complexity, and chemical modifications of NPs mediate their hypoglycemic activity by influencing bioavailability and target specificity. NPs improve glucose metabolism through multiple pathways: activating insulin signaling, improving insulin resistance (IR), enhancing glycogen synthesis, inhibiting gluconeogenesis, and regulating gut microbiota homeostasis. Additionally, NPs protect pancreatic β-cell function via the nuclear factor E2-related factor 2 (Nrf2)/Antioxidant Response Element (ARE) antioxidant pathway and Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) anti-inflammatory pathway. Clinical application of NPs still requires overcoming challenges such as resolving complex structure-activity relationships and dynamically integrating cross-organ signaling. Future research should focus on integrating multi-omics technologies (e.g., metagenomics, metabolomics) and organoid models to decipher the cross-organ synergistic action networks of NPs, and promote their translation from basic research to clinical applications.PMID:40363788 | DOI:10.3390/molecules30091980

Molecules. 2025 Apr 25;30(9):1923. doi: 10.3390/molecules30091923.ABSTRACTPolygonati Rhizoma, widely used as a traditional functional food and herbal medicine, is well known for its health-promoting activities after the process of "nine cycles of steaming-drying". Based on UPLC-MS/MS, 1369 secondary metabolites were identified in P. cyrtonema rhizomes, mainly alkaloids, amino acids and derivatives, flavonoids, organic acids, phenolic acids, and saccharides. The P. cyrtonema rhizomes were rich in xylose, arabinose, glucose, sorbose, mannose, galactose, rhamnose, inositol, fucose, sedoheptulose, phosphorylated monosaccharides, sugar acid, and sugar alcohols. Particularly, 23 types of modifications were detected for amino acids, while the most frequent modifications were acetylation, methylation (nono-, di-, and tri-), cyclo-, homo-, and hydroxylation. Based on the metabolic profile, samples from the third cycle (Tre-3) and the sixth cycle (Tre-6) were firstly clustered together due to similar metabolites and then grouped with samples from the ninth cycle (Tre-9). Differentially accumulated metabolites were mainly enriched in "Metabolic pathways", "Biosynthesis of cofactors", "Biosynthesis of secondary metabolites", "Flavonoid biosynthesis", "Purine metabolism", "ABC transporters", "Biosynthesis of amino acids", and "Nucleotide metabolism" pathways. During repeated steaming-drying processes, 39 metabolites occurred, including alkaloids, amino acids and derivatives, flavonoids, lignans and coumarins, lipids, nucleotides and derivatives, organic acids, phenolic acids, and terpenoids. This research will provide a critical scientific basis for postharvest processing of P. cyrtonema rhizomes.PMID:40363730 | DOI:10.3390/molecules30091923

Polymers (Basel). 2025 Apr 27;17(9):1190. doi: 10.3390/polym17091190.ABSTRACTPolyhydroxyalkanoates (PHAs), as biosynthetic and biodegradable polymers, serve as alternatives to petroleum-based plastics, yet face critical cost barriers in large-scale production. While magnetic field (MF) stimulation enhances microbial activity, the optimal MF parameters and metabolic mechanisms for PHA biosynthesis remain unexplored. This study optimized magnetic field parameters to increase PHA biosynthesis in Haloferax mediterranei. A custom-engineered electromagnetic system identified 110 mT of static magnetic field (SMF) as the optimal level for biosynthesis, reaching 77.97 mg/(L·h) PHA volumetric productivity. A pulsed magnetic field caused oxidative stress and impaired substrate uptake despite increasing PHA synthesis. Prolonged SMF exposure (72 h) maximized PHA productivity, while 48 h of exposure attained 90% efficiency. Metabolomics revealed that SMF-driven carbon flux redirection via regulated butanoate metabolism led to a 2.10-fold increase in (R)-3-hydroxybutanoyl-CoA), while downregulating acetoacetate (0.51-fold) and suppressing PHA degradation (0.15-fold). This study pioneers the first application of metabolomics in archaea to decode SMF-induced metabolic rewiring in Haloferax mediterranei. Our findings establish SMF as a scalable bioenhancement tool, offering sustainable solutions for the circular bioeconomy.PMID:40362974 | DOI:10.3390/polym17091190

Nutrients. 2025 May 6;17(9):1597. doi: 10.3390/nu17091597.ABSTRACTBackground: Neurodegenerative diseases (NDDs) are multifactorial disorders frequently associated with gut dysbiosis, oxidative stress, and inflammation; however, the pathophysiological mechanisms remain poorly understood. Methods: Using untargeted mass spectrometry-based metabolomics and 16S sequencing of human stool, we investigated bacterial and metabolic dyshomeostasis in the gut microbiome associated with early disease stages across three NDDs-amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD)-and healthy controls (HC). Results: We discovered a previously unrecognized link between a microbial-derived metabolite with an unknown role in human physiology, 2,3-dihydroxypropane-1-sulfonate (DHPS), and gut dysbiosis in NDDs. DHPS was downregulated in AD, ALS, and PD, while bacteria involved in DHPS metabolism, Eubacterium and Desulfovibrio, were increased in all disease cohorts. Additionally, select taxa within the Clostridia class had strong negative correlations to DHPS, suggesting a potential role in DHPS metabolism. A catabolic product of DHPS is hydrogen sulfide, and when in excess, it is known to promote inflammation, oxidative stress, mitochondrial damage, and gut dysbiosis, known hallmarks of NDDs. Conclusions: These findings suggest that cryptic sulfur metabolism via DHPS is a potential missing link in our current understanding of gut dysbiosis associated with NDD onset and progression. As this was a hypothesis generating study, more work is needed to elucidate the role of DHPS in gut dysbiosis and neurodegenerative diseases.PMID:40362907 | DOI:10.3390/nu17091597

Nutrients. 2025 May 5;17(9):1585. doi: 10.3390/nu17091585.ABSTRACTBackground: Metabolic-dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disorder globally. Probiotic supplementation has shown promise in its prevention and treatment. Although Weissella viridescens, a lactic acid bacterium with immunomodulatory effects, has antibacterial and anti-inflammatory activities, there is a lack of direct evidence for its role in alleviating MASLD. This study aimed to investigate the protective effects of W. viridescens strain Wv2365, isolated from healthy human feces, in a high-fat diet (HFD)-induced rat model of MASLD. Methods: Rats were randomly assigned to a normal chow diet (NC), high-fat diet (HFD), and HFD supplemented with W. viridescens Wv2365 (Wv2365) groups. All groups were fed their respective diets for 8 weeks. During this period, the NC and HFD groups received a daily oral gavage of PBS, while the Wv2365 group received a daily oral gavage of Wv2365. Results: Wv2365 supplementation significantly reduced HFD-induced body weight gain, improved NAFLD activity scores, alleviated hepatic injury, and restored lipid metabolism. A liver transcriptomic analysis revealed the downregulation of inflammation-related pathways, along with decreased serum levels of TNF-α, IL-1β, IL-6, MCP-1, and LPS. Wv2365 also activated the Nrf2/HO-1 antioxidant pathway, enhanced hepatic antioxidant enzyme activities and reduced malondialdehyde levels. A gut microbiota analysis showed the enrichment of beneficial genera, including Butyricicoccus, Akkermansia, and Blautia. Serum metabolomic profiling revealed increased levels of metabolites including indole-3-propionic acid, indoleacrylic acid, and glycolithocholic acid. Conclusions: Wv2365 attenuates hepatic injury, oxidative stress, and inflammation in a rat model of high-fat-diet-induced MASLD, supporting its potential as a probiotic candidate for the modulation of MASLD.PMID:40362894 | DOI:10.3390/nu17091585

Nutrients. 2025 May 4;17(9):1582. doi: 10.3390/nu17091582.ABSTRACTBACKGROUND: The global rise in ultra-processed food (UPF) consumption and the persistent burden of mental disorders have raised growing public health concerns. Emerging evidence suggests that unfavorable dietary patterns, particularly with high UPF intake, contribute to the development of mental disorders.OBJECTIVE: To assess the associations of UPF-related metabolic signatures and mental disorders.METHODS: In this population-based cohort study of 30,059 participants from the UK Biobank, we first identified a plasma metabolic signature associated with UPF intake leveraging nuclear magnetic resonance metabolomics. We then applied Cox and logistic regression models to investigate the associations of both UPF consumption and its metabolic signature with incident mental disorders and specific psychological symptoms, respectively.RESULTS: Higher UPF intake was significantly associated with increased risks of overall mental disorder (hazard ratio per 10% increment [95% confidence interval]: 1.04 [1.02, 1.06]), depressive disorder (1.14 [1.08, 1.20]), anxiety disorder (1.12 [1.06, 1.18]), and substance use disorder (1.06 [1.01, 1.11]), as well as several psychological symptoms including suicidal ideation (odds ratios [95% confidence interval]: 1.12 [1.03, 1.16]) and anxiety feeling (1.05 [1.01, 1.09]). Similarly, the UPF-related metabolic signature was independently associated with elevated risks of these mental health outcomes and partially mediated the associations between UPF intake and mental disorders.CONCLUSIONS: These findings highlighted the potential metabolic pathways underlying the neuropsychiatric risks of UPF consumption and underscored the importance of dietary quality in mental health.PMID:40362891 | DOI:10.3390/nu17091582

Nutrients. 2025 Apr 30;17(9):1549. doi: 10.3390/nu17091549.ABSTRACTBackground: Diet-derived advanced glycation end products (dAGEs) are closely associated with obesity and metabolic disorders. This study investigates the therapeutic potential of myriocin (Myr), a sphingolipid synthesis inhibitor, in counteracting dAGE-induced obesity and its underlying mechanisms. Methods: Male C57BL/6J wild-type mice were randomly assigned to receive either a low-AGE diet or a high-AGE diet with or without the administration of myriocin for a duration of 24 weeks. At the end of the experimental period, blood samples, whole livers, and adipose tissues were harvested for subsequent biochemical, histological, and molecular analyses. Results: Using a 24-week high-AGE diet mouse model, we demonstrate that Myr significantly reduces body weight gain (by 76%) and adipose tissue accumulation, while alleviating hepatic steatosis. Myr improves glucose homeostasis by lowering fasting blood glucose (a 44.5% reduction), enhancing oral glucose tolerance, and restoring hepatic glycolysis/gluconeogenesis balance via upregulating glucokinase and suppressing G6pc. Notably, Myr reduces serum LDL-C, TG, and TC levels by 52.3%, 51.8%, and 48.8%, respectively, and ameliorates liver dysfunction as evidenced by normalized ALT/AST activities. Metabolomics reveal Myr reshapes amino acid, carbohydrate, and lipid metabolism pathways. Mechanistically, Myr suppresses lipogenesis by downregulating Srebp1, Fasn, and Acc, while activating AMPK-PGC1α signaling to enhance mitochondrial biogenesis (a 2.1-fold increase in mtDNA) and thermogenesis via Ucp1 upregulation in brown and white adipose tissues. Conclusions: Our findings unveil Myr as a novel dual regulator of lipid and glucose metabolism through AMPK-PGC1α-mediated mitochondrial activation, providing the first evidence of sphingolipid inhibition as a therapeutic strategy against dAGE-induced metabolic syndrome. This study establishes a multifaceted mechanism involving hepatic lipid regulation, adipose browning, and systemic metabolic reprogramming, advancing potential clinical applications for obesity-related disorders.PMID:40362857 | DOI:10.3390/nu17091549

Nutrients. 2025 Apr 30;17(9):1542. doi: 10.3390/nu17091542.ABSTRACTBACKGROUND: During aging, protein nutrition has a bidirectional role in regulating healthy lifespan by modulating body metabolism and neurological function. However, the current "low-high" hypothesis on the dynamics of protein requirements is mainly based on male animal models, and its applicability to female physiology (e.g., estrogen fluctuations) is unclear. The present study aims to fill the gap in the study of protein demand dynamics in female naturally aging mice and to investigate the effects of different protein levels on the health status of female C57BL/6J mice at different stages of aging.METHODS: In this study, four dietary interventions (high protein, HP; low protein, LP; model test, MT; and control, C) were evaluated by constructing a C57BL/6J female mouse model at three ages, 9 M (9 months), 16 M (16 months), and 20 M (20 months), which are approximately equivalent to 34, 65, and 78 years of age in humans, respectively, to determine the effects on naturally aging mice. The effects of the interventions were quantitatively described by behavioral, neuropathological, oxidative, and inflammatory indices and NMR metabolomics using Principal Component Analysis to construct a comprehensive quantitative scoring method.RESULTS: The comprehensive quantitative scores Fsum was highest in the HP group, lowest in the LP group, and in between in the MT group. The HP intervention showed the most significant improvement in the aged group (20 M) mice, with a 35.2% reduction in avoidance latency (p < 0.01) and a 32.9% increase in pyramidal cell density in the hippocampal CA1 region (p < 0.05), while the LP intervention led to a cognitive decline in the mice, with an avoidance latency that was prolonged by 15.2% (p < 0.05). Metabolomics analysis revealed that mouse samples of all ages showed age-dependent metabolic re-adaptation: the 9 M group may reflect gut microbial metabolism rather than direct host TCA cycle activity, suggesting an indirect association with energy metabolism; an enhanced degradation of branched-chain amino acids (BCAAs) was seen in the middle-aged group (16 M); and amino acid biosynthesis was predominant in the old group (20 M).CONCLUSIONS: Female mice have sustained neuromotor benefits to high-protein diets at different aging stages, and the dynamics of their protein requirements differ significantly from those of males. The study reveals the critical role of gender factors in protein nutritional strategies and provides an experimental basis for precise protein supplementation in older women.PMID:40362850 | DOI:10.3390/nu17091542

Nutrients. 2025 Apr 27;17(9):1471. doi: 10.3390/nu17091471.ABSTRACTBackground: Higher circulating branched-chain amino acids (BCAAs) are linked to cardiometabolic and neurological diseases. While diet is the primary BCAA source, its impact on circulating levels remains unclear. This study examined the association between dietary intake and circulating BCAA concentrations in a large population-based sample. Methods: Data from 2159 participants (58.2% women, mean age 53.4 ± 8.6 years) were analyzed. Dietary intake was assessed using a questionnaire covering 91 individual food items, 9 nutrient categories, and 3 dietary patterns. BCAA concentrations were measured via LC-MS. All analyses were stratified by gender. Results: Circulating BCAA levels were higher in men than in women. BCAA levels were negatively associated with vegetables (standardized β = -0.029, p = 0.088; -0.051, p = 0.003; -0.038, p = 0.043 for leucine, isoleucine, and valine, respectively), dairy (-0.037, p = 0.029; -0.063, p < 0.001; -0.041, p = 0.028), and fruit (-0.031, p = 0.084; -0.039, p = 0.030; -0.041, p = 0.034), and a positive trend was observed for meat and meat-derived products, but the associations did not reach statistical significance. Vegetal protein, total carbohydrates, and monosaccharides showed a significant negative association with circulating BCAAs levels. Participants who complied with "dairy ≥ 3/day", "meat ≤ 5/week", or "at least three guidelines" had lower circulating BCAA levels. Conclusions: Circulating BCAA levels were negatively associated with dairy, vegetables, fruits, plant protein, carbohydrates, non-digestible fiber, calcium, and iron. While circulating BCAA levels were linked to meat consumption and adherence to dietary guidelines, the association was not linear. Differences were observed between men and women, which may be attributed to variations in dietary intake and preferences.PMID:40362780 | DOI:10.3390/nu17091471

Nutrients. 2025 Apr 24;17(9):1424. doi: 10.3390/nu17091424.ABSTRACTBackground/Objectives: Alginate and its oligosaccharides (AOS) are widely used in the food industry all over the world. However, how they are fermented by the human gut microbiota has not been fully elucidated. Here, we aim to explore the structure-property relationships of the fermentation of these carbohydrates by the human gut microbiota. Methods: High-performance liquid chromatography, 16S rRNA gene amplicon high-throughput sequencing, whole genome sequencing, and metabolome analysis were used to study the fermentation of alginate and AOS by the human gut microbiota. Results and Conclusions: Low-molecular-weight alginate and AOS were more fermentable than alginate. Moreover, fermentation of AOS with a molecular weight (Mw) of 0.8 kDa produced higher amounts of acetate and butyrate than that with a Mw of 0.3 kDa. B. xylanisolvens was a keystone species responsible for the fermentation. Additionally, each B. xylanisolvens strain was characterized with a unique capability for AOS fermentation. Specifically, B. xylanisolvens P19-10, a bacterium isolated from healthy human colon, exhibited the best fermentation capacity. Genomic analysis suggested that B. xylanisolvens P19-10 was armed with a plethora of carbohydrate-active enzymes. Additionally, the polysaccharide lyase family 6_1 was identified as a candidate enzyme responsible for the utilization of AOS. Moreover, fermentation of AOS by B. xylanisolvens P19-10 was associated with significant changes in bacterial metabolites and metabolic pathways. Future perspectives: Our study provides novel mechanistic insights into the fermentation of alginate and AOS by human gut microbiota, which has applications for the development of new carbohydrate-based nutraceuticals and foods.PMID:40362733 | DOI:10.3390/nu17091424

Nutrients. 2025 Apr 23;17(9):1418. doi: 10.3390/nu17091418.ABSTRACTBACKGROUND: Celastrol, a pentacyclic triterpenoid active component isolated from the root bark of the traditional medicinal plant Tripterygium wilfordii, displays significant anti-inflammatory, antioxidant, and immunomodulatory properties. However, its clinical application remains limited due to inadequate bioavailability.METHODS: Regarding these issues, we innovatively developed a novel peanut cultivar (cel-peanut) enriched with celastrol through distant hybridization combined with metabolomics screening. Guided by the research concept of "natural anti-inflammatory diets for metabolic disease management", we established a high-fat diet-induced ApoE-/- atherosclerotic mouse model to systematically evaluate the anti-atherosclerosis effects and mechanisms of cel-peanut.RESULTS: Our results revealed that cel-peanut significantly reduced serum levels of triglycerides (TGs) and increased high-density lipoprotein cholesterol (HDL-C). Concurrently, cel-peanut markedly decreased the atherosclerotic lesion area and enhanced collagen content within plaques. Mechanistic investigations demonstrated that cel-peanut reduced serum malondialdehyde (MDA) levels and suppressed the concentration of pro-inflammatory cytokine IL-6 in atherosclerotic lesions. Furthermore, cel-peanut promoted intestinal health by modulating the composition and functionality of gut microbiota, thereby attenuating atherosclerosis progression.CONCLUSIONS: Overall, these findings indicate that cel-peanut exerts therapeutic effects against atherosclerosis through its anti-inflammatory, antioxidant, and gut microbiota-modulating properties. This study proposes a novel nutritional intervention strategy for atherosclerosis and provides a promising adjuvant strategy for clinical atherosclerosis treatment.PMID:40362727 | DOI:10.3390/nu17091418