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

A panomics-driven framework for the improvement of major food legume crops: advances, challenges, and future prospects

Mon, 12/05/2025 - 12:00
Hortic Res. 2025 Mar 18;12(7):uhaf091. doi: 10.1093/hr/uhaf091. eCollection 2025 Jul.ABSTRACTFood legume crops, including common bean, faba bean, mungbean, cowpea, chickpea, and pea, have long served as vital sources of energy, protein, and minerals worldwide, both as grains and vegetables. Advancements in high-throughput phenotyping, next-generation sequencing, transcriptomics, proteomics, and metabolomics have significantly expanded genomic resources for food legumes, ushering research into the panomics era. Despite their nutritional and agronomic importance, food legumes still face constraints in yield potential and genetic improvement due to limited genomic resources, complex inheritance patterns, and insufficient exploration of key traits, such as quality and stress resistance. This highlights the need for continued efforts to comprehensively dissect the phenome, genome, and regulome of these crops. This review summarizes recent advances in technological innovations and multi-omics applications in food legumes research and improvement. Given the critical role of germplasm resources and the challenges in applying phenomics to food legumes-such as complex trait architecture and limited standardized methodologies-we first address these foundational areas. We then discuss recent gene discoveries associated with yield stability, seed composition, and stress tolerance and their potential as breeding targets. Considering the growing role of genetic engineering, we provide an update on gene-editing applications in legumes, particularly CRISPR-based approaches for trait enhancement. We advocate for integrating chemical and biochemical signatures of cells ('molecular phenomics') with genetic mapping to accelerate gene discovery. We anticipate that combining panomics approaches with advanced breeding technologies will accelerate genetic gains in food legumes, enhancing their productivity, resilience, and contribution to sustainable global food security.PMID:40352287 | PMC:PMC12064956 | DOI:10.1093/hr/uhaf091

Polymicrobial detection and salivary metabolomics of children with early childhood caries

Mon, 12/05/2025 - 12:00
PeerJ. 2025 May 6;13:e19399. doi: 10.7717/peerj.19399. eCollection 2025.ABSTRACTBACKGROUND: Early childhood caries (ECC) has been proposed to be associated with various microorganisms and metabolites. This study aims to compare the prevalence of specific microbial species and salivary metabolomics profile in children with and without ECC, and to explore the correlation between salivary metabolites and targeted microbes.METHOD: Five ml of unstimulated saliva was collected from 32 ECC and 22 caries-free children. Clinical indexed were recorded and questionnaires regarding oral health and dietary habits were obtained from the guardians. The presence of eight specific microbial species were examined using species-specific quantitative PCR (qPCR). Untargeted metabolomics was analyzed to identify key differential metabolites and pathways. Correlations among clinical, microbial, and metabolomic data were further explored.RESULTS: The prevalence of Scardovia wiggsiae (90.6%, P < 0.001), Streptococcus mutans (43.8%, P = 0.006), Streptococcus sobrinus (62.5%, P < 0.001), Ligilactobacillus salivarius (93.6%, P = 0.01) and Candida albicans (56.3%, P < 0.001) were significantly higher in the ECC group. The prevalence of ECC was higher in children with two targeted species present compared with children with one targeted species. Histidine metabolism and branched-chain amino acids degradation were activated in ECC group, while glyoxylate and dicarboxylate metabolism, purine and pyrimidine metabolism were inhibited. Histidine and glutathione metabolism was activated with enrichment of targeted microbial species, while linoleic acid metabolism and biotin metabolism was inhibited. The duration of each toothbrushing was a significant risk factor for ECC experience.CONCLUSION: The prevalence of Scardovia wiggsiae, Streptococcus mutans, Streptococcus sobrinus and Candida albicans is higher in ECC children compared to caries-free children. Oral habits and salivary metabolites also vary between ECC and caries-free children.PMID:40352277 | PMC:PMC12063607 | DOI:10.7717/peerj.19399

Allelopathic effects and composition of aqueous extracts from different parts of <em>Galinsoga parviflora</em> Cav. on <em>Medicago sativa</em> L. and <em>Avena sativa</em> L

Mon, 12/05/2025 - 12:00
PeerJ. 2025 May 8;13:e19378. doi: 10.7717/peerj.19378. eCollection 2025.ABSTRACTBACKGROUND: Galinsoga parviflora Cav. is a high-risk invasive plant that seriously threatens the development of grasslands in southern China. However, the allelopathic effects on Medicago sativa L. and Avena sativa L., which are widely cultivated forages around the world, have not been reported.METHODS: To explore the allelopathic mechanism of G. parviflora, the allelopathic effects of aqueous extracts from different parts of G. parviflora on M. sativa and A. sativa were investigated. The germination rate (GR), germination potential (GP), seedling height, fresh weight, and chlorophyll content of M. sativa and A. sativa seedlings were measured to elucidate the allelopathy of G. parviflora on the two forages. Based on the five indicators, synthetical allelopathic effects (SAE) of extracts was also calculated. In addition, the allelopathic components of the extracts in G. parviflora were quantitatively revealed by untargeted metabolomics detection. Furthermore, two key allelopathic substances, 1,4-cyclohexanedicarboxylic acid (CHDA) and trehalose, were selected to explore the inhibitory effect on two notorious weed species in China, such as gramineous Digitaria sanguinalis L. and broad-leaved Amaranthus retroflexus L.RESULT: (1) The inhibitory effects of aqueous extracts from different parts of G. parviflora on recipient plants were different, the root was the weakest, and the whole plants was the strongest, with the values of synthetical allelopathic effects (SAE) on M. sativa at the highest concentration being -0.12 and -0.40, respectively. (2) Compared with A. sativa, M. sativa was generally more susceptible to the extracts. (3) The differences in the content of CHDA or trehalose might be a reason why extracts from different parts of G. parviflora exhibited different allelopathic effects. (4) The herbicidal activity test of key allelopathic substances found that CHDA has a strong inhibitory effect on the germination of D. sanguinalis and almost does not affect M. sativa and A. sativa. Thus, this discovery not only revealed allelopathic effects and components in different parts of G. parviflora, but provided scientific evidence for weed control based on natural plant extracts in the future.PMID:40352272 | PMC:PMC12066104 | DOI:10.7717/peerj.19378

Umbilical cord mesenchymal stem cell-derived secretome as a potential treatment for systemic lupus erythematosus: A double-blind randomized controlled trial

Mon, 12/05/2025 - 12:00
Narra J. 2025 Apr;5(1):e1799. doi: 10.52225/narra.v5i1.1799. Epub 2025 Mar 3.ABSTRACTUmbilical cord mesenchymal stem cell-derived (UCMSC-derived) secretome is anti- apoptotic, anti-inflammatory, antifibrotic, angiogenic, and tissue-regenerating. Thus, it may treat systemic lupus erythematosus (SLE). The aim of this study was to investigate the impact of the UCMSC-derived secretome on SLE patients' disease activity, using Mexican systemic lupus erythematosus disease activity index (MEX-SLEDAI) score, complement (C3 and C4) levels, tumor necrosis factor-alpha (TNF-α), anti-double-stranded DNA (anti-dsDNA), and interleukin-6 (IL-6) levels. This double-blind randomized controlled trial investigated the efficacy and safety of UCMSC-derived secretome in SLE patients with moderate disease activity. A total of 29 female patients were randomized into two groups to receive weekly 1.5 cc intramuscular injections of UCMSC-derived secretome or placebo (0.9% NaCl) for six weeks. Disease activity was assessed using the MEX-SLEDAI score, C3 and C4 levels, pro-inflammatory cytokines (IL- 6 and TNF-α), and anti-dsDNA antibodies at baseline, Day 22, and Day 43. Results showed a significant reduction in MEX-SLEDAI scores in the secretome group compared to the placebo group (p < 0.05). Complement C3 levels significantly increased in the secretome group on Day 43, indicating improved immune homeostasis, while C4 levels did not show significant differences between groups. IL-6 and TNF-α levels showed decreasing trends in the secretome group. Anti-dsDNA levels exhibited a decreasing trend in the secretome group, though not statistically significant. Importantly, no severe adverse events were observed, underscoring the safety of the intervention. UCMSC-derived secretome demonstrated immunomodulatory and anti-inflammatory effects, reducing disease activity in SLE patients. These findings suggest its potential as a safe and effective adjunct therapy for SLE, although further studies with larger sample sizes and extended follow-up periods are needed to validate these results.PMID:40352183 | PMC:PMC12059846 | DOI:10.52225/narra.v5i1.1799

Analysis of specialist doctors' behavior towards SGLT2 inhibitors prescription in Indonesia: A qualitative study

Mon, 12/05/2025 - 12:00
Narra J. 2025 Apr;5(1):e2089. doi: 10.52225/narra.v5i1.2089. Epub 2025 Mar 19.ABSTRACTSodium-glucose cotransporter-2 inhibitors (SGLT2is) have a broad range of clinical indications and are recommended by various guidelines for the management of diabetes, heart failure, and chronic kidney disease. However, prescribing rates for these agents are suboptimal towards various intended indications in many countries, including Indonesia. The aim of this study was to analyze the prescribing practices of SGLT2is among endocrinologists, cardiologists, and nephrologists in Indonesia. A qualitative method was utilized to provide a comprehensive understanding of this phenomenon. Semi-structured online interviews were performed with 18 participants, comprising seven specialized doctors as primary informants; eight key informants representing pharmacies, governmental bodies, and pharmaceutical marketing representatives; and three patients as supplementary informants. Furthermore, closed observations of two specialist doctors were undertaken as an additional data collection method. Informants were recruited using criterion and snowball sampling methods. The Theoretical Domains Framework was used as an interview guide; all interviews were audio visual-recorded, transcribed verbatim, and subsequently analyzed for thematic content with NVivo version 12. Seven themes emerged concerning the prescribing behavior of SGLT2is: socioeconomic status, therapeutic rationality, utilization barriers, utilization optimization, the urge to prescribe, therapeutic expectations and targets, and aspects of the health system and ethical considerations. Most informants possessed favorable perspectives regarding using SGLT2is when prescribed appropriately, yet specific elements necessitate enhancement to refine therapeutic justification, including initiatives to incorporate SGLT2is into the national formulary.PMID:40352173 | PMC:PMC12059814 | DOI:10.52225/narra.v5i1.2089

Effect of in ovo-fed amino acids on muscle and liver metabolome of broiler chickens at 24 h post-hatch

Mon, 12/05/2025 - 12:00
Front Physiol. 2025 Apr 25;16:1542426. doi: 10.3389/fphys.2025.1542426. eCollection 2025.ABSTRACTIn ovo administration of amino acids has been shown to alleviate the adverse effects of heat stress on broiler chickens during the finisher phase. However, their specific influence on thermogenic organs in the early post-hatch period is not fully understood. Therefore, the aim of the present study was to explore and investigate the effects of in ovo-fed amino acids on amino acid metabolism in the liver and muscle of one-day-old broiler chicks. To achieve this, breast muscle and liver samples were taken from six randomly selected chicks per experimental group and subjected to a targeted metabolomic analysis. The experimental groups included a control group injected with 52 µL of sterile diluent/egg (CTRL), a group injected with 3.0 mg of L-Met + 2.0 mg of L-Cys/egg (T1), and a group injected with 0.4 mg of L-Leu + 1.6 mg of L-Met + 1.6 mg of L-Cys/egg (T2). The Sparse Partial Least Square - Discriminant Analysis (sPLS-DA) showed that T1 and T2 had very similar metabolomic profiles. Consequently, data from T1 and T2 were merged into a single group (Injected) for statistical analysis. Compared to CTRL, multiple pathways were significantly enriched in the muscle and liver of the Injected group. These enriched pathways included those involved in the metabolism of cysteine and methionine (FDR = 0.01), glutathione (FDR < 0.001), histidine (FDR = 0.01), taurine (FDR = 0.01), glycine, serine, and threonine (FDR = 0.01) as well as the pathway of arginine biosynthesis (FDR = 0.03). Moreover, only four muscle metabolites: homocysteine (r = -0.63, P = 0.03), S-Adenosyl-homocysteine (r = -0.62, P = 0.03), phosphocholine (r = 0.50, P = 0.01), and betaine (r = 0.52, P = 0.004), as well as four liver metabolites: phenyl pyruvic acid (r = 0.55, P = 0.02), dimethylglycine (r = 0.55, P = 0.03), phenylalanine (r = 0.50, P = 0.02), and alpha-aminobutyric acid (r = -0.53, P = 0.02) were significantly correlated with the rectal temperature of sampled chicks, suggesting a role of these metabolites in thermoregulation. In conclusion, the in ovo feeding of amino acids on embryonic day 18 was associated with the enrichment of pathways directly or indirectly involved in the response of the antioxidant defense system to oxidative stress in the liver and muscle tissues.PMID:40352141 | PMC:PMC12061718 | DOI:10.3389/fphys.2025.1542426

Application of Metabolomics and the Discovery of Potential Serum Biomarkers for Diuretic Resistance in Heart Failure

Mon, 12/05/2025 - 12:00
Rev Cardiovasc Med. 2025 Apr 22;26(4):27001. doi: 10.31083/RCM27001. eCollection 2025 Apr.ABSTRACTBACKGROUND: Diuretic resistance (DR) is characterized by insufficient fluid and sodium excretion enhancement despite maximum loop diuretic doses, indicating a phenotype of refractory heart failure (HF). Recently, metabolomics has emerged as a crucial tool for diagnosing and understanding the pathogenesis of various diseases. This study aimed to differentiate diuretic-resistant patients from non-resistant HF to identify biomarkers linked to the emergence of DR.METHODS: Serum samples from HF patients, both with and without DR, were subjected to non-targeted metabolomic analysis using liquid chromatography-tandem mass spectrometry. Metabolite variations between groups were identified using principal component analysis and orthogonal partial least-square discriminant analysis. Metabolic pathways were assessed through the Kyoto Encyclopedia of Genes and Genomes database enrichment analysis, and potential biomarkers were determined using receiver operating characteristic curves (ROCs).RESULTS: In total, 192 metabolites exhibited significant differences across the two sample groups. Among these, up-regulation was observed in 164 metabolites, while 28 metabolites were down-regulated. A total of 28 pathways involving neuroactive ligand-receptor interaction and amino acid biosynthesis were affected. The top five metabolites identified by ROC analysis as potential DR biomarkers were hydroxykynurenine, perillic acid, adrenic acid, 5-acetamidovalerate, and adipic acid.CONCLUSIONS: Significant differences in metabolite profiles were observed between the diuretic-resistant and non-diuretic-resistant groups among patients with HF. The top five differentially expressed endogenous metabolites were hydroxykynurenine, perillic acid, adrenic acid, 5-acetamidovalerate, and adipic acid. The metabolic primary pathways implicated in DR were noted as amino acid, energy, and nucleotide metabolism.CLINICAL TRIAL REGISTRATION: This study was registered with the China Clinical Trials Registry (https://www.chictr.org.cn/hvshowproject.html?id=197183&v=1.7, ChiCTR2100053587).PMID:40351663 | PMC:PMC12059756 | DOI:10.31083/RCM27001

Patients with periodontitis exhibit persistent dysbiosis of the gut microbiota and distinct serum metabolome

Mon, 12/05/2025 - 12:00
J Oral Microbiol. 2025 May 8;17(1):2499284. doi: 10.1080/20002297.2025.2499284. eCollection 2025.ABSTRACTOBJECTIVES: Animal studies suggest that periodontopathic bacteria induce gut dysbiosis and related pathology, possibly connecting periodontitis to non-oral diseases. However, the effects on the gut ecosystem in periodontitis patients are not fully understood.METHODS: We conducted a comprehensive analysis of the salivary and gut microbiota using 16S rRNA sequencing in periodontitis patients before and after treatment, comparing them to healthy participants. Serum metabolites were also analyzed.RESULTS: Periodontitis patients showed high alpha diversity in both salivary and gut microbiota with a strong correlation. Significant differences were also observed in the gut microbiota composition between patients before treatment and healthy participants, irrespective of the ectopic colonization of periodontitis-associated bacteria in the gut. Co-abundance group analysis demonstrated that the gut microbiota of healthy participants was enriched with short-chain fatty acid producers. Changes in the gut microbiota coincided with alterations in the serum metabolite profile. While periodontal therapy improved salivary microbiota, it did not significantly affect gut microbiota.CONCLUSIONS: Gut dysbiosis of periodontitis patients may impact systemic metabolite profiles. Given that periodontal therapy alone did not substantially improve the gut microbiota, adjunctive strategies targeting the gut microbiome may be effective in reducing the risk of periodontitis-associated diseases.PMID:40351551 | PMC:PMC12064113 | DOI:10.1080/20002297.2025.2499284

Early potential metabolic biomarkers of T1 stage lung adenocarcinoma based on serum metabolomics

Mon, 12/05/2025 - 12:00
Front Mol Biosci. 2025 Apr 25;12:1544774. doi: 10.3389/fmolb.2025.1544774. eCollection 2025.ABSTRACTBACKGROUND: This study aims to investigate serum metabolite changes in patients with early-stage (T1) lung adenocarcinoma, identify potential diagnostic biomarkers, and establish an early warning mechanism for T1 stage lung adenocarcinoma.METHODS: The study included two groups: a lung adenocarcinoma group and a healthy control group. Serum samples underwent non-targeted metabolomics analysis. Total ion chromatograms (TIC) were generated to assess system stability. Chromatographic data were analyzed using multivariate statistical methods, including principal component analysis (PCA) for dimensionality reduction. Partial least squares discriminant analysis (PLS-DA) further validated PCA findings. Variables with VIP scores >1.0 in the PLS-DA model were selected, combined with ANOVA and T-tests (P < 0.05), to identify differentially expressed metabolites. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the diagnostic performance of selected metabolites.RESULTS: Serum metabolites significantly differed between the lung adenocarcinoma group and the healthy control group. Multivariate statistical analysis and ROC curve evaluation identified four potential diagnostic biomarkers: Cortisol, 3-Oxo-OPC4-CoA, PE-NMe(14:1(9Z)/14:1(9Z)), and Ceramide (d18:1/9Z-18:1), with AUC values of 0.930, 0.895, 0.890, and 0.795, respectively.CONCLUSION: Cortisol,3-Oxo-OPC4-CoA,PE-NMe(14:1(9Z)/14:1(9Z)), and Ceramide (d18:1/9Z-18:1) exhibit significantly altered metabolic levels in T1 stage lung adenocarcinoma patients and can serve as metabolic biomarkers. These markers may enhance the sensitivity and specificity of early diagnosis, facilitating improved detection of T1 stage lung adenocarcinoma.PMID:40351532 | PMC:PMC12061714 | DOI:10.3389/fmolb.2025.1544774

Effect of freeze-pressure regulated extraction technology on the physicochemical properties and pharmacological activities of guizhi extract

Mon, 12/05/2025 - 12:00
Front Chem. 2025 Apr 25;13:1581429. doi: 10.3389/fchem.2025.1581429. eCollection 2025.ABSTRACTExtraction is the core process for obtaining bioactive compounds from medicinal plants. Enhancing the extraction efficiency of aromatic herbs has become a critical challenge. This study introduced a novel freeze-pressure regulated extraction (FE) technique to improve the extraction efficiency of Gui Zhi (GZ). Compared to traditional methods, FE yielded a significantly lower pH of 4.74, a higher zeta potential of -13.93 mV, and a smaller average particle size of 304.57 nm. Scanning electron microscopy (SEM) and mercury intrusion porosimetry (MIP) confirmed that FE creates larger pores and an expanded surface area, facilitating more effective compound release. HPLC analysis indicated that FE increased the cinnamaldehyde content from 348.53 to 370.20 μg/g. UPLC-MS analysis further demonstrated that FE is more effective for extracting volatile and phenolic compounds. Furthermore, the therapeutic effect of GZ extract on a wind-cold syndrome model was investigated. FE significantly alleviated symptoms and restored lung tissue integrity, through the regulation of the citric acid cycle and thiamine metabolism pathways. The findings not only support the application of FE technology in herbal extraction but also offer novel approaches for the efficient utilization of herbs like GZ in modern medicine.PMID:40351525 | PMC:PMC12061963 | DOI:10.3389/fchem.2025.1581429

Metabonomic analysis reveals correlations between mycotoxins and secondary metabolites in <em>Penicillium expansum</em> cultures via time-of-flight mass spectrometry

Mon, 12/05/2025 - 12:00
Food Chem X. 2025 Apr 16;27:102475. doi: 10.1016/j.fochx.2025.102475. eCollection 2025 Apr.ABSTRACTPenicillium expansum is a major postharvest pathogen causing fruit decay and mycotoxin contamination. This study investigated the mycotoxin production and metabolic profiles of 91 P. expansum strains using metabolomic analysis. Six mycotoxins were identified, with patulin (PAT) and chaetoglobosin A being particularly prevalent at 77.56 and 45.58 mg·kg-1 respectively. Untargeted metabolomics profiled 506 metabolites, revealing a decrease in major metabolites during cultivation due to fungal assimilation. Comparative analysis between high- and low-PAT samples showed distinct metabolic signatures in organic acids, benzenoids, organoheterocyclic metabolites, which are linked to mycotoxin production pathways. These differential metabolites were used to build discriminant models, with random forest model achieving 98 % accuracy in distinguishing high- and low-PAT samples. Metabolites, mainly 3, 4-dihydroxybenzoic acid and 4-ketopimelic acid, were explored as potential biomarkers for PAT contamination diagnosis. This research enhances the understanding of P. expansum's metabolic diversity and supports improved fruit quality and safety control.PMID:40351499 | PMC:PMC12063009 | DOI:10.1016/j.fochx.2025.102475

Exploring seasonal differences in taste and nonvolatiles of Lu'an Guapian tea and perceptual interactions between odorants and EGCG via multi-sensory analysis and metabolomics

Mon, 12/05/2025 - 12:00
Food Chem X. 2025 Apr 24;27:102497. doi: 10.1016/j.fochx.2025.102497. eCollection 2025 Apr.ABSTRACTLu'an Guapian (LAGP) tea, a traditional Chinese green tea exclusively produced from mature leaves without buds or stems, is known for its mellow taste and distinct appearance. Subjective (sensory evaluation) and objective assessment (colorimeter and E-tongue) were conducted to provide a deeper insight into the differences between LAGP made from summer and autumn leaves and spring leaves. A total of 52 key differential metabolites were screened by metabolomics. Catechins and flavonoids, especially flavonol glycosides, exhibited significant seasonal variation. Pathway enrichment analysis indicated that flavonoid biosynthesis was the key factor that caused the quality changes of LAGP tea in different seasons. Additionally, preliminary explorations revealed that appropriate addition of odorants, especially hexanal (12.0-14.4 μg/L) and (Z)-3-hexen-1-ol (4.88-5.85 μg/L), could effectively mask the bitterness of EGCG and improve sensory acceptability. These findings provide theoretical insights into the seasonal effects of LAGP tea and guide the optimization of optimization of summer-autumn tea production.PMID:40351498 | PMC:PMC12063033 | DOI:10.1016/j.fochx.2025.102497

Study on the correlation between microbial community succession and main flavor substances in the mashes of Tanggou liquor

Mon, 12/05/2025 - 12:00
Food Chem X. 2025 Apr 24;27:102486. doi: 10.1016/j.fochx.2025.102486. eCollection 2025 Apr.ABSTRACTThis study employed integrated omics to investigate microbial dynamics and flavor development in Tanggou wine fermentation. High-throughput sequencing identified 182 bacterial and 82 fungal OTUs, with late-stage DLD samples exhibiting peak diversity, including 49 unique bacteria and 14 fungi. Lactobacillus dominated bacterial communities at 99.14-99.85%, creating acidic conditions that enhanced lactic acid synthesis and ester stability. Kazachstania prevailed in fungal communities at 73.28-97.72%, mediating β-glucosidase-driven terpene liberation. Metabolomics revealed a 12.7-fold increase in tricarboxylic acids during DLD phase, while GC-IMS detected 77 volatiles dominated by esters, notably ethylhexanoate and phenylethanol. Four strong-flavor Baijiu signature esters peaked in DLD base liquor through stage-specific accumulation. Microbial network analysis demonstrated Lactobacillus-Kazachstania synergy in ethyl lactate production, while thermophilic actinomycetes modulated ethyl hexanoate/pyrazine ratios via lipase activity. These findings highlight microbial consortium engineering as an effective strategy for flavor optimization in traditional liquor manufacturing.PMID:40351497 | PMC:PMC12063030 | DOI:10.1016/j.fochx.2025.102486

The Immune Regulation of Melanin From <em>Gallus gallus domesticus</em> Brisson Against Cyclophosphamide-Induced Immunosuppression

Mon, 12/05/2025 - 12:00
Food Sci Nutr. 2025 May 9;13(5):e70253. doi: 10.1002/fsn3.70253. eCollection 2025 May.ABSTRACTBlack-bone silky fowl (Gallus gallus domesticus Brisson), medicinal food homology, utilizes to enhance human immunity. However, it remains unclear whether Black-bone silky fowl melanin (BSFM), one of its bioactive components, could affect immune function. The purpose of this study is to examine the immunoregulatory effect and the underlying mechanism of BSFM in the cyclophosphamide-induced immunosuppressive mice model. The findings revealed that BSFM could significantly increase white blood cells (WBC) in peripheral blood; upregulate the expression of IL-4, TNF-α, and M-CSF in the plasma; and reduce tissue damage. Mechanistically, proteomics has revealed that BSFM therapy substantially affected the quantity of 29 proteins (Mtatp6, Cst3, Pglyrp1, Igkc, and other targets), which mostly participate in the phosphatidylcholine catabolic process, positive regulation of type IIa hypersensitivity, lipid catabolic process, and neutrophil chemotaxis. Metabolomics indicated that BSFM reduced the levels of Octanoylglucuronide, Gly-Gly, and N-alpha-acetyl-ornithine and modulated arginine biosynthesis. Furthermore, BSFM treatment modified the composition of gut microbiota and increased the relative abundance of Prevotella, S24-7, Olsenella, Lactococcus, hgcl-clade, Parasutterella, and Acetobacter. A significant correlation modified the composition of gut microbiota among inflammation-associated parameters, gut microbiota, and various metabolites (DMs) through Pearson correlation analysis. These findings suggest that BSFM holds promise in enhancing the human immune system and may serve as a complementary therapy in conventional chemotherapy.PMID:40351363 | PMC:PMC12064410 | DOI:10.1002/fsn3.70253

The Potential Mechanisms of Althaea rosea (Linn.) Cavan. Flower in Alleviating Tetrodotoxin Poisoning: An Integrated Metabolomics, Network Pharmacology and Experimental Validation

Mon, 12/05/2025 - 12:00
Drug Des Devel Ther. 2025 May 5;19:3657-3680. doi: 10.2147/DDDT.S505270. eCollection 2025.ABSTRACTPURPOSE: Tetrodotoxin (TTX) poisoning manifests rapidly and severely, and there are currently no clinically effective treatments. Althaea rosea (Linn.) Cavan. flower, documented in the "National Compendium of Chinese Herbal Medicines", is traditionally recognized and clinically applied for its potential to mitigate tetrodotoxin (TTX) poisoning. This study aims to explores the pharmacodynamic components and mechanisms of the ethyl acetate extract of Althaea rosea flower (EAEAR) in a TTX-induced rat model.METHODS: Ultra-performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap-HRMS) was used to identify active components in EAEAR. Metabolomics combined with network pharmacology was used to explore the mechanisms underlying the mitigating effects of EAEAR in TTX-intoxicated rats. Experimental validation was performed on key targets of the pathway through Western blotting or enzyme-linked immunosorbent assay. And differential metabolites in key pathways were further validated using ultra-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UPLC-QqQ-MS/MS).RESULTS: A total of 35 active components were identified in EAEAR, 12 core components and 15 core targets were screened in network pharmacology, and metabolomics revealed 15 different metabolites. The arginine and proline metabolism pathway and the arginine biosynthesis pathway were identified as critical pathways for EAEAR's effect in alleviating TTX poisoning. Validation results indicated that EAEAR treatment led to significant alterations (P <0.05) in six key targets (MAOA, AOC1, ALDH7A1, NAGS, NOS2, and NOS3) and three differential metabolites (GABA, Pro, and NAG) in TTX-intoxicated rats.CONCLUSION: EAEAR alleviates TTX poisoning symptoms by modulating targets and metabolites in the arginine and proline metabolism pathways and the arginine biosynthesis pathway. This study provides a theoretical basis for further exploration of its therapeutic potential and mechanisms against TTX poisoning.PMID:40351347 | PMC:PMC12063623 | DOI:10.2147/DDDT.S505270

<em>Asparagopsis taxiformis</em> mitigates ruminant methane emissions via microbial modulation and inhibition of methyl-coenzyme M reductase

Mon, 12/05/2025 - 12:00
Front Microbiol. 2025 Apr 25;16:1586456. doi: 10.3389/fmicb.2025.1586456. eCollection 2025.ABSTRACTINTRODUCTION: Asparagopsis taxiformis (A. taxiformis) has shown great potential to mitigate methane (CH4) emissions in recent years. This study aims to evaluate the impact of A. taxiformis on methane emissions and to fill the knowledge gap regarding its mechanisms of action in affecting CH4 metabolism and rumen fermentation.METHODS: The experimental design consisted of a control group (CON) and test groups supplemented with 2% (Low), 5% (Mid), and 10% (High) of dried and freeze-dried treatment A. taxiformis, respectively, for 48 h of in vitro rumen fermentation. The optimal combination strategy for mitigating CH4 emissions was confirmed by analyzing nutrient degradation, CH4 production and rumen fermentation parameters, and the mechanism of action was analyzed by metagenomic and metabolomic approaches.RESULTS AND DISCUSSION: The results showed that freeze-dried treatment had better potential to mitigate CH4 emissions than dried treatment, and supplementation of freeze-dried treatments at Low, Mid, and High groups significantly reduced CH4 production by 32.44%, 98.53%, and 99.33%, respectively. However, the High group exhibited a huge negative impact on rumen fermentation. Therefore, subsequent analyses focused on the Low and Mid groups to explore the underlying mechanisms. Metagenomics analyses showed that supplementation of freeze-dried treatment with the Mid-level supplementation significantly increased the relative abundance of propionate-producing bacteria such as Prevotella, Ruminobacter, and Succinivibrio, while inhibited acetate-producing bacteria such as Ruminococcus, altered the pattern of volatile fatty acid (VFA) synthesis in the rumen, and reduced H2 availability for methanogenesis and promoted propionate production, indirectly alleviating CH4 production. Moreover, by suppressing the relative abundance of Methanobrevibacter, CH4 production in the rumen was directly suppressed. Furthermore, KEGG pathway analysis showed that A. taxiformis significantly inhibited the abundance of K00399, methyl-coenzyme M reductase alpha subunit, which directly inhibited CH4 synthesis. Metabolomics analysis of A. taxiformis supplementation significantly enriched ketoglutarate, malate, isocitrate, and melatonin, which may have reduced the release of rumen fermented H2, thereby mitigating CH4 emissions. In summary, freeze-dried treatment A. taxiformis at the 5% supplementation level achieved the optimal balance between CH4 mitigation and rumen fermentation efficiency.PMID:40351315 | PMC:PMC12061954 | DOI:10.3389/fmicb.2025.1586456

Comprehensive analysis of gut microbiota and fecal metabolites in patients with autism spectrum disorder

Mon, 12/05/2025 - 12:00
Front Microbiol. 2025 Apr 25;16:1557174. doi: 10.3389/fmicb.2025.1557174. eCollection 2025.ABSTRACTINTRODUCTION: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and the presence of restricted, repetitive behaviors or interests. Studies have revealed that gut microbiota and their metabolism play important roles in ASD, and become the underlying mechanisms of ASD.METHODS: In this study, we performed long-read 16S rRNA sequencing and untargeted metabolomics to comprehensively characterize the profiles of gut microbiota and fecal metabolites in 34 ASD patients and 18 healthy controls. The associations between gut microbiota, fecal metabolites and clinical symptoms were analyzed to screen related biomarkers for ASD.RESULTS: The results showed the similarity of the overall microbial richness and diversity between ASD patients and controls, however, some specific bacterial taxa exhibited significant differences, including Klebsiella and Escherichia-Shigella at genera level, and Clostridium-sporogenes, Escherichia-coli-O157H7 and Bacteroides-ovatus at species level. The fecal metabolomics validated that a lot of metabolites had significantly differential levels, including a series of organic acids, amino acids and dopamine.DISCUSSION: The associations of gut microbiota and fecal metabolites might shed new light on the pathogenesis of ASD and help us to understand the importance of gut microbiota as potential biomarkers and therapeutic targets in the development of ASD.PMID:40351314 | PMC:PMC12062028 | DOI:10.3389/fmicb.2025.1557174

The Influence of Bisphenol A on Parsley: A Biochemical and Metabolomics Integrative Perspective

Mon, 12/05/2025 - 12:00
Physiol Plant. 2025 May-Jun;177(3):e70262. doi: 10.1111/ppl.70262.ABSTRACTBisphenol A (BPA), a widely used industrial chemical, poses environmental concerns due to its persistence and potential effects on plant systems. This study examines the impact of three BPA exposure levels on parsley plants, focusing on physiological, biochemical, and metabolomic responses. BPA exposure significantly shaped the plant's defense mechanisms, mainly through increased phenolic (up to 16.81%) and flavonoid (up to 37.94%) accumulation compared to the control group, which, in turn, enhanced antioxidant activity [up to 34% in 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 51% in cupric reducing antioxidant capacity (CUPRAC)]. A moderate correlation between phenolic content and radical scavenging ability [R: 0.61 for DPPH and R: 0.44 for 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS)] highlights phenolics' role in mitigating BPA-induced oxidative stress. Low BPA concentrations stimulated gas exchange and photosynthesis, while higher levels (≥3 mg/L) disrupted these processes, causing physiological damage, especially in stomatal conductance (gs) and photochemical efficiency (Fv/Fo). Metabolomic profiling revealed concentration-dependent shifts in secondary metabolism, lipid biosynthesis, and stress-response pathways. At higher BPA levels, plants elicited defense mechanisms, such as flavonoids (rhamnetin, luteolin-7-O-β-D-glucronide, and quercetin-7-O-glucoside) and anthocyanin pathways, to tackle oxidative stress, though these systems became overwhelmed. Our findings show that while parsley can initially adapt to low BPA exposure, higher concentrations compromise its physiological and metabolic balance, threatening plant health and productivity.PMID:40351267 | DOI:10.1111/ppl.70262

Oral Delivery of Ellagic Acid Encapsulated in Milk Exosomes: Sex-Based Differences in Bioavailability, Urolithin Production, and Gut Microbiota Modulation

Mon, 12/05/2025 - 12:00
Mol Nutr Food Res. 2025 May 12:e70104. doi: 10.1002/mnfr.70104. Online ahead of print.ABSTRACTMilk exosomes (EXOs) enhance polyphenols' bioavailability, but their potential for oral administration remains underexplored. Ellagic acid (EA) is poorly bioavailable. We investigate whether EA encapsulated in EXOs (EXO-EA) consumed orally improves EA bioavailability and (or) modulates gut microbiota. For 2 weeks, BALB/c mice received EXO, non-encapsulated EA (NEA), or EXO-EA (0.27 mg EA/kg bw) orally. Targeted and untargeted metabolomics (UPLC-qTOF-MS), fecal SCFAs (GC-MS), and gut microbiota (PacBio 16S-sequencing) were performed. Additionally, EA plasma and brain kinetics were evaluated in rats following intravenous administration of EXO-EA and NEA. Unlike NEA, EXO-EA quadrupled EA plasma levels in Sprague-Dawley rats and enabled brain detection. However, oral EXO-EA in mice failed to deliver EA systemically due to gastrointestinal instability, confirmed by in vitro digestion. Sex-dependent EXO-EA metabolomic effects were observed. Also, in males only, EXO-EA increased fecal urolithin A and SCFAs and enriched the microbiota with Christensenellaceae R7, Ruminococcus species, and Clostridium fusiformis, among others. In females, both EXO-EA and NEA enriched the microbiota with bifidobacteria, including Bifidobacterium pseudolongum. Oral EXO-EA impacted plasma metabolome, modulated gut microbiota, and increased urolithin A and SCFA production sex-dependently. However, gastrointestinal instability, limited EA encapsulation, and low dose administered prevented systemic delivery.PMID:40351018 | DOI:10.1002/mnfr.70104

Tibetan Tea Alleviates the Intestinal Dysfunction in Sleep-Deprived Mice Through Regulating Oxidative Stress and Inflammation-Related Intestinal Metabolisms

Mon, 12/05/2025 - 12:00
Mol Nutr Food Res. 2025 May 11:e70098. doi: 10.1002/mnfr.70098. Online ahead of print.ABSTRACTSleep deprivation (SD) disrupts intestinal homeostasis through excessive reactive oxygen species (ROS) accumulation. Tibetan tea is a potential dietary intervention for inflammation, it's effect on SD-induced intestinal inflammation remains unclear. This study investigates the alleviating effects of Tibetan tea water-soluble extract (TTE) on intestinal dysfunction in SD mice. After TTE supplementation, the physiological activity, inflammatory cytokines, and oxidative stress levels were assessed in SD-induced intestinal dysfunction mice. SD increased ROS levels and pro-inflammatory cytokines in plasma and small intestine, causing intestinal injury characterized by reduced goblet cells, decreased Mucin2 (MUC2) expression, and impaired tight junction proteins. Conversely, TTE reversed these disorders and improved mucosal injury in the small intestine. Furthermore, TTE modulated gut microbiota by enriching probiotics linked to SCFA production and restored SD-induced metabolic disturbances in the small intestine and systemic circulation, particularly affecting tricarboxylic acid (TCA) cycle, urea cycle, and TAG-related metabolites. Overall, TTE remarkably ameliorated SD-induced intestinal dysfunction through reducing ROS, restoring intestinal barrier function, and regulating the gut microbiome, which suggested that Tibetan tea could contribute to the treatment of intestinal inflammation.PMID:40350986 | DOI:10.1002/mnfr.70098

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