PubMed

Food Chem. 2025 Feb 19;477:143456. doi: 10.1016/j.foodchem.2025.143456. Online ahead of print.ABSTRACTBauhinia championii (BC) honey, highly regarded for its functional properties, is popular among consumers and holds significant economic potential, particularly in the food and health industries. However, limited knowledge of the bioactivities, especially its outstanding antioxidant activity, hampers the development of functional products. This study comprehensively compared BC honey's physicochemical properties, elemental composition, metabolic profile, and antioxidant properties with five other honeys. Results revealed that BC honey had a darker color, higher electrical conductivity (335.67 ± 6.81 μS cm-1), and higher levels of minerals and flavonoids. It exhibited stronger radical scavenging activity, with DPPH (96.49 % ± 0.38) and ABTS (2.1593 mM ± 0.014) values. Multivariate analysis suggested that its superior antioxidant properties are likely due to high flavonoid content, particularly 7-O-methylchrysin. This study offers insights into BC honey's antioxidant characteristics and supports its use in functional products.PMID:40015020 | DOI:10.1016/j.foodchem.2025.143456

Poult Sci. 2025 Feb 22;104(4):104938. doi: 10.1016/j.psj.2025.104938. Online ahead of print.ABSTRACTDuck egg production sharply decreases during the late-laying period, which likely stems from an ovarian mechanism. However, the molecular mechanisms underlying ovarian regression during the late-laying period remain unclear. In this study, egg-laying (LLP) and ceased-laying (CLP) ducks at 72 weeks of age were selected to explore the potential mechanism of ovarian regression. Proteomic analysis demonstrated the importance of mitochondrial function in ovarian regression. Notably, metabolomic analysis showed that CLP ducks disturbed TCA cycle, as exhibited by the lower fumarate content. The ovarian expression of protein markers for mitochondrial biogenesis (PGC-1α and TFAM) and function (SIRT1 and SIRT3) were suppressed in CLP ducks. CLP ducks had significantly increased MDA levels and reduced SOD, CAT, GSH-Px, and T-AOC activities, inducing excessive oxidative stress. Interestingly, ACSL4, a key regulator of ferroptosis, was associated with the mitochondrial envelope and membrane function during ovarian regression. CLP ducks showed significantly reduced GSH levels and increased Fe2+ content, as well as decreased the expression of ferroptosis-related proteins (GPX4 and SLC7A11) and antioxidant-related proteins (COX2, CAT, SOD1, and SOD2). Collectively, our findings suggest that ovarian regression-mediated mitochondrial dysfunction contributes to oxidative stress-induced ferroptosis in ducks that have ceased laying.PMID:40014974 | DOI:10.1016/j.psj.2025.104938

Public Health. 2025 Feb 26;241:158-163. doi: 10.1016/j.puhe.2025.02.009. Online ahead of print.ABSTRACTOBJECTIVES: Illicit drug use presents a significant challenge to global health and public safety, requiring innovative and effective monitoring strategies. This study aimed to evaluate the current landscape of wastewater-based epidemiology (WBE) for monitoring illicit drugs in Europe, focusing on collaboration, current practices, and barriers, while identifying opportunities for improvement.STUDY DESIGN: Cross-sectional survey-based study.METHODS: Coordinated by the Sewage Analysis CORe Group Europe (SCORE) and the European Union Drugs Agency (EUDA), two surveys were conducted in 2023 targeting researchers and stakeholders using WBE for illicit drugs. Data were analysed to identify trends, gaps, and opportunities for improving WBE implementation.RESULTS: The findings indicate a robust research infrastructure and diverse analytical methods among European institutions. Two-thirds of the participating countries reported using WBE data to inform policy. However, challenges persist, particularly in securing funding and coordination, as well as generating national estimates from multiple locations and addressing specific local policy needs.CONCLUSIONS: WBE has proven to be a valuable tool for monitoring illicit drug trends and informing drug policies. To unlock its full potential, sustained funding, methodological standardization, and enhanced cooperation are essential. This study provides critical insights into the European WBE landscape, offering a roadmap for strengthening the integration of actionable WBE data into public health and policy frameworks.PMID:40014941 | DOI:10.1016/j.puhe.2025.02.009

Biofabrication. 2025 Feb 27. doi: 10.1088/1758-5090/adbb21. Online ahead of print.ABSTRACTThe obtainment of innovative models recalling complex tumour architectures and activities in vitro is a challenging drive in the understanding of pathology molecular bases, yet a crucial passage to the identification of targets for advanced oncotherapy. Cell environment recapitulation by 3D scaffolding and gravitational unloading of cell cultures represent powerful means in tumour biomimicry process, but their simultaneous adoption has consistently been explored only in the latest decade. Here, an unprecedented bioengineering approach capitalizing on spaceflight biology practice is proposed for modelling of glioblastoma multiforme, a highly aggressive neoplasm that affects the central nervous system and that has poorly effective pharmacological and radiological countermeasures. Tumour modelling was pursued by the original implementation of two-photon polymerization in fast prototyping of 3D scaffolds on flexible substrates for U87-MG glioma cell culture, and by the exposure of cell-laden scaffolds to simulated microgravity (s-µg). Realistic spaceflight conditions were applied to collect preliminary information suitable to testing of U87-MG cell-laden scaffold in low Earth orbit. Response of glioma cells anchored to 3D scaffolds was investigated by microscopy, quantitative reverse transcription-polymerase chain reaction and proteomic analyses, revealing synergic regulatory effects of cell scaffolding and s-µg on markers of tumour cell growth, metabolism and invasiveness.PMID:40014921 | DOI:10.1088/1758-5090/adbb21

J Pharm Biomed Anal. 2025 Feb 11;259:116741. doi: 10.1016/j.jpba.2025.116741. Online ahead of print.ABSTRACTNatural products (NPs), play a crucial role in drug development. However, the discovery of NPs is accidental, and conventional identification methods lack accuracy. To overcome these challenges, an increasing number of researchers are directing their attention to Molecular networking (MN). MN based on secondary mass spectrometry has become an important tool for the separation, purification and structural identification of NPs. However, most new tools are not well known. This review started with the most basic MN tool and explains it from the principle, workflow, and application. Then introduce the principles and workflows of the remaining eight new types of MN tools. The reliability of various MNs is mainly verified based on the application of phytochemistry and metabolomics. Subsequently, the principles and applications of 12 structural annotation tools are introduced. For the first time, the scope of 9 kinds of MN tools is compared horizontally, and 12 kinds of structured annotation tools are classified from the type of compound structure suitable for identification. The advantages and disadvantages of various tools are summarized, and make suggestions for future application directions and the development of computing tools in this review. MN tools are expected to enhance the efficiency of the discovery and identification in NPs.PMID:40014895 | DOI:10.1016/j.jpba.2025.116741

J Pharm Biomed Anal. 2025 Feb 25;259:116760. doi: 10.1016/j.jpba.2025.116760. Online ahead of print.ABSTRACTXiexin Tang (XXT) is a classic Chinese medicine formula that can be used to treat Atherosclerosis (AS). This study aimed to investigate the mechanism by which XXT regulated AS lipid levels. Firstly, the mixture components of XXT were analyzed by High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Then, the AS model based on Apolipoprotein E knockout (ApoE-/-) mice was established. Cytokines related to lipid metabolism and bile acid metabolism were detected by Quantitative Real-time PCR (qRT-PCR). 16S rDNA gene sequencing was performed to analyze differential bacterial populations, and the mechanism of XXT regulation of bile acids affecting lipid metabolism was further explored by targeted metabolomics. Further, antibiotic-treated mice were used to investigate the role of gut microbiota in the anti-AS effect of XXT. The results showed that XXT attenuated the lipid levels and reversed the abnormal elevation of cytokines, such as hepatic lipid metabolism and inflammatory reaction in AS mice. XXT also repaired the gut barrier damage and reversed gut microbiota disorders in AS mice. Furthermore, the metabolic levels of bile acids were reshaped by XXT. Whereas, in the absence of gut microbiota, XXT failed to attenuate lipid levels and inhibit the expression of cytokines related to inflammation and bile acid metabolism in AS mice and failed to play a role in ultimately treating AS. In conclusion, XXT could effectively inhibit the inflammatory reaction and lipid accumulation in AS mice, and this effect was closely related to its remodeling of gut microbiota to regulate bile acid metabolism.PMID:40014894 | DOI:10.1016/j.jpba.2025.116760

PLoS One. 2025 Feb 27;20(2):e0319779. doi: 10.1371/journal.pone.0319779. eCollection 2025.ABSTRACTChronic stress and orthodontic treatment have been revealed to trigger systemic stress responses in rats. This study aimed to investigate the effects of restraint stress and orthodontic treatment on the intestinal epithelial structure, barrier function, flora, and metabolism in rats. Twenty 8-week-old male Wistar rats were randomly divided into four groups: sham-stressed non-orthodontic (CC), sham-stressed orthodontic (CO), stressed non-orthodontic (SC), and stressed orthodontic (SO). The stress intervention involved subjecting the rats to restraint stress for 21 days, while the orthodontic intervention consisted of maxillary first molar traction from days 8 to 21. Histological and immunohistochemical staining were used to observe the epithelial structure and barrier function of the colon. The intestinal flora and metabolite alterations were investigated by 16S rRNA high-throughput sequencing and untargeted metabolomics sequencing. Colonic epithelial tissue disruption, mucus cells reduction, and a decreased expression of intestinal tight junction proteins were observed in the CO, SC, and SO groups. Lactobacillus spp. abundance was significantly lower in the CO group than in the CC group. Prevotella spp. abundance was significantly lower in the SC and SO groups than in the CC and CO groups. The differential metabolite enrichment pathways between each inter-group comparison might all be related to amino acid biosynthesis, protein digestion and absorption, and cofactor biosynthesis. Both restraint stress and orthodontic treatment may adversely affect the colonic epithelial structure and barrier function of rats. The intestinal flora structure and types of metabolites were also affected cumulatively.PMID:40014578 | DOI:10.1371/journal.pone.0319779

Proc Natl Acad Sci U S A. 2025 Mar 4;122(9):e2425526122. doi: 10.1073/pnas.2425526122. Epub 2025 Feb 27.ABSTRACTMimicking metabolic pathways on electrodes enables in vivo metabolite monitoring for decoding metabolism. Conventional in vivo sensors cannot accommodate underlying complex reactions involving multiple enzymes and cofactors, addressing only a fraction of enzymatic reactions for few metabolites. We devised a single-wall-carbon-nanotube-electrode architecture supporting tandem metabolic pathway-like reactions linkable to oxidoreductase-based electrochemical analysis, making a vast majority of metabolites detectable in vivo. This architecture robustly integrates cofactors, self-mediates reactions at maximum enzyme capacity, and facilitates metabolite intermediation/detection and interference inactivation through multifunctional enzymatic use. Accordingly, we developed sensors targeting 12 metabolites, with 100-fold-enhanced signal-to-noise ratio and days-long stability. Leveraging these sensors, we monitored trace endogenous metabolites in sweat/saliva for noninvasive health monitoring, and a bacterial metabolite in the brain, marking a key milestone for unraveling gut microbiota-brain axis dynamics.PMID:40014569 | DOI:10.1073/pnas.2425526122

Cell Rep. 2025 Feb 26;44(3):115357. doi: 10.1016/j.celrep.2025.115357. Online ahead of print.ABSTRACTDespite advances in cancer treatment, the development of effective therapies remains an urgent unmet need. Here, we investigate the potential of bacteria-derived metabolites as a therapeutic alternative for the treatment of cancer. We detect 3-hydroxydodecanedioic acid in the serum of tumor-bearing mice treated with serum from mice previously supplemented with a mix of Clostridiales bacteria. Further, 3-hydroxydodecanoic acid, an intermediate derivative between dodecanoic and 3-hydroxydodecanedioic acids, exhibits a strong anti-tumor response via GPR84 receptor signaling and enhances CD8+ T cell infiltration and cytotoxicity within tumor tissue in multiple cancer models. Metabolomics analysis of colorectal cancer patient serum reveals an inverse correlation between the abundance of these metabolites and advanced disease stages. Our findings provide a strong rationale for 3-hydroxydodecanoic acid and the GPR84 receptor to be considered as promising therapeutic targets for cancer treatment.PMID:40014452 | DOI:10.1016/j.celrep.2025.115357

J Agric Food Chem. 2025 Feb 27. doi: 10.1021/acs.jafc.4c12157. Online ahead of print.ABSTRACTThis study investigated the effects of 2,4-epibrassinolide (EBR) residues on Dendrobium officinale quality. The residues decreased from 0.164 to 0.238 mg/kg (2 h) to 0.014-0.071 mg/kg (35 d) in the stems with 0.02-0.05 mg/L EBR applications. Polysaccharide, mannose, and glucose content were increased in the stems and leaves, reaching a maximum of 61% in dried stems on 35 d. The increase in content may result from the significant upregulation of enzyme activities, including UGP, SUS, and SPS. Further analysis by nontargeted metabolomics revealed 5 upregulated (UDP-l-rhamnose, mannose-6-phosphate, GDP-mannose, chitobiose, and N-acetyl-galactosamine-6-phosphate) and 13 downregulated metabolites associated with polysaccharide and monosaccharide growth in the 0.02-0.05 mg/L EBR treatments. These differential metabolites regulate the biosynthesis of polysaccharides mainly through key metabolic pathways, such as glucose and fructose metabolism. These results provide a reference for the regulatory mechanisms governing the quality indicators of Dendrobium officinale after EBR application.PMID:40014423 | DOI:10.1021/acs.jafc.4c12157

Anal Bioanal Chem. 2025 Feb 27. doi: 10.1007/s00216-025-05790-7. Online ahead of print.ABSTRACTIn this study, we developed a customized high-resolution mass spectrometry metabolomics workflow integrating the dual sugar test employing lactulose and mannitol as test probes for intestinal permeability assessment with untargeted screening of small molecules. Urine samples were collected from patients with major depression and healthy controls as part of a clinical study at the psychiatric department. Using a dual injection/dual chromatography setup, the test probes were quantified by hydrophilic interaction liquid chromatography (HILIC) in a targeted assay, while drugs and their metabolites were profiled in an untargeted manner by reversed-phase separation. Rigorous method development and validation allowed for selective separation of sugar isomers and consequently accurate quantification of lactulose and mannitol in urine. Internal standardization with compound specific stable isotope-labeled standards enabled excellent analytical figures of merit such as high recoveries, precision (< 5%), and working range (5 orders of magnitude). Within one analytical run, intestinal permeability was assessed together with drugs and their metabolites, allowing to screen for confounding drugs and patient compliance to the therapeutic scheme.PMID:40014070 | DOI:10.1007/s00216-025-05790-7

Physiol Genomics. 2025 Feb 27. doi: 10.1152/physiolgenomics.00055.2024. Online ahead of print.ABSTRACTThe majority of exercise physiology research has been conducted in males, resulting in a skewed biological representation of how exercise impacts the physiological system. Extrapolating male-centric physiological findings to females is not universally appropriate and may even be detrimental. Thus, addressing this imbalance and taking into consideration sex as a biological variable is mandatory for optimization of precision exercise interventions and/or regimens. Our present analysis focused on establishing multiomic profiles in young, exercise-naïve males (n=23) and females (n=17) at rest and following acute exercise. Sex differences were characterized at baseline and following exercise using skeletal muscle and extracellular vesicle transcriptomics, whole blood methylomics, and serum metabolomics. Sex-by-time analysis of the acute exercise response revealed notable overlap, as well as divergent molecular responses between males and females. An exploratory comparison of two combined exercise regimens (high-intensity: HITT and traditional: TRAD) was then performed using singular value decomposition, revealing latent data structures that suggest a complex dose-by-sex interaction response to exercise. These findings lay the groundwork for an understanding of key differences in responses to acute exercise exposure between sexes. This may be leveraged in designing optimal training strategies, understanding common and divergent molecular interplay guiding exercise responses, and elucidating the role of sex hormones and/or other sex-specific attributes in responses to acute and chronic exercise.PMID:40014011 | DOI:10.1152/physiolgenomics.00055.2024

Adv Sci (Weinh). 2025 Feb 27:e2413819. doi: 10.1002/advs.202413819. Online ahead of print.ABSTRACTWorldwide, donkeys (Equus asinus) are valued for their meat and milk, and in China also for the medical value of their skin. Physiological characteristics are key to the donkey's adaptability, including their digestive, respiratory, and reproductive systems, which enable them to survive and work in a variety of environments. However, the understanding of donkey physiological characteristics at the cellular level remains poor. Thus, single-cell transcriptome sequencing is used to construct a detailed transcriptional atlas based on 20 tissues from the Dezhou donkey (in total 84 cell types and 275 050 high quality cells) to perform an in-depth investigation of molecular physiology. Cross-species and cross-tissue comparative analyses reveal SOX10 to be an evolutionally conserved regulon in oligodendrocytes and illuminate the distinctive transcriptional patterns of donkey sebocytes. Moreover, through multispecies skin metabolomics, highly abundant, species-specific metabolites in donkey skin are identified, such as arachidonic acid and gamma-glutamylcysteine, and the pivotal role of sebocytes in donkey skin metabolism is highlighted. In summary, this work offers new insights into the unique metabolic patterns of donkey skin and provides a valuable resource for the conservation of donkey germplasm and the advancement of selective breeding programs.PMID:40013957 | DOI:10.1002/advs.202413819

Adv Sci (Weinh). 2025 Feb 27:e2416453. doi: 10.1002/advs.202416453. Online ahead of print.ABSTRACTRisk stratification using multi-omics data deepens understanding of immunometabolism in successfully treated people with HIV (PWH) is inadequately explained. A personalized medicine approach integrating blood cell transcriptomics, plasma proteomics, and metabolomics is employed to identify the mechanisms of immunometabolic complications in prolonged treated PWH from the COCOMO cohort. Among the PWHs, 44% of PWH are at risk of experiencing immunometabolic complications identified using the network-based patient stratification method. Utilizing advanced machine learning techniques and a Bayesian classifier, five plasma protein biomarkers; Tubulin Folding Cofactor B (TBCB), Gamma-Glutamylcyclotransferase (GGCT), Taxilin Alpha (TXLNA), Pyridoxal Phosphate Binding Protein (PLPBP) and Large Tumor Suppressor Kinase 1 (LATS1) are identified as highly differentially abundant between healthy control (HC)-like and immunometabolically at-risk PWHs (all FDR<10-10). The personalized metabolic models predict metabolic perturbations, revealing disruptions in central carbon metabolic fluxes and host tryptophan metabolism in at-risk phenotype. Functional assays in primary cells and cortical forebrain organoids (FBOs) further validate this. Metabolic perturbations lead to persistent monocyte activation, thereby impairing their functions ex vivo. Furthermore, the chronic inflammatory plasma microenvironment contributes to synaptic dysregulation in FBOs. The endogenous plasma inflammatory microenvironment is responsible for chronic inflammation in treated immunometabolically complicated at-risk PWH who have a higher risk of cardiovascular and neuropsychiatric disorders.PMID:40013867 | DOI:10.1002/advs.202416453

mSystems. 2025 Feb 27:e0018625. doi: 10.1128/msystems.00186-25. Online ahead of print.ABSTRACTDuring infection, Histoplasma capsulatum yeasts interact with a variety of phagocytic cells, where macrophages represent an important niche for long-term intracellular fungal survival and replication. In the phagosomes of macrophages, a hostile environment where most microorganisms are killed, Histoplasma not only survives but overcomes several biological challenges and proliferates intracellularly. To better understand the characteristics of intracellular Histoplasma and the phagosomal environment, a metabolomic platform was used to analyze Histoplasma yeasts cultured on different carbon sources and yeasts extracted from macrophages, identifying metabolites associated with pathogenesis. Metabolomic results of in vitro-grown yeasts were further characterized with available transcriptomic data, informing underlying gene expression patterns in response to contrasting milieus. These approaches revealed that Histoplasma yeasts, unlike many other yeasts, do not ferment sugars to ethanol, and, when cultivated on glycolytic versus gluconeogenic carbon sources, produce distinct metabolomes with altered intracellular amino acid, lipid, and sugar contents. Furthermore, analysis of Histoplasma-inoculated media illustrated that Histoplasma secretes mannitol and anthranilates. Lastly, a comparison of the metabolomes derived from in vitro cultivation versus intracellular growth highlighted leucine and cysteine/cystine as amino acids, which may serve as sources of carbon, nitrogen, and sulfur to yeasts within macrophages. These results detail metabolites linked to Histoplasma metabolism during macrophage infection, identifying potential candidates to target for novel histoplasmosis therapeutics.IMPORTANCEIntracellular pathogens reside within host cells, surviving against innate immune responses while exploiting host resources to proliferate. Understanding the mechanisms that underlie their survival and proliferation is critical for developing novel treatments and therapeutics for the diseases these pathogens cause. While Histoplasma is a unique example of a true intra-phagosomal pathogen, insights into its pathogenesis may still inform the study of other intracellular pathogens.PMID:40013825 | DOI:10.1128/msystems.00186-25

New Phytol. 2025 Feb 27. doi: 10.1111/nph.20434. Online ahead of print.ABSTRACTThe increased positive impact of plant diversity on ecosystem functioning is often attributed to the accumulation of mutualists and dilution of antagonists in diverse plant communities. While increased plant diversity alters traits related to resource acquisition, it remains unclear whether it reduces defence allocation, whether this reduction differs between roots and leaves, or varies among species. To answer these questions, we assessed the effect of plant species richness, plant species identity and their interaction on the expression of 23 physical and chemical leaf and fine root defence traits of 16 plant species in a 19-yr-old biodiversity experiment. Only leaf mass per area, leaf and root dry matter content and root nitrogen, traits associated with both, resource acquisition and defence, responded consistently to species richness. However, species richness promoted a decoupling of these defences in leaves and fine roots, possibly in response to resource limitations in diverse communities. Species-specific responses were rare and related to chemical defence and mutualist collaboration, likely responding to species-specific antagonists' dilution and mutualists' accumulation. Overall, our study suggests that resource limitation in diverse communities might mediate the relationship between plant defence traits and antagonist dilution.PMID:40013369 | DOI:10.1111/nph.20434

Front Endocrinol (Lausanne). 2025 Feb 12;16:1522756. doi: 10.3389/fendo.2025.1522756. eCollection 2025.ABSTRACTBACKGROUND: Cardiovascular Disease (CVD) is the leading cause of global mortality, with its incidence rate rising year by year due to the prevalence of metabolic diseases. Existing primary and secondary prevention strategies for cardiovascular disease have limitations in identifying some high-risk groups, and 1.5-level prevention aims to achieve more precise intervention by early identification of subclinical target organ damage. This study introduces oral (tongue coating) microbiota as metabolic markers for the first time, in combination with multiple metabolic factors, to explore their potential in assessing subclinical target organ damage and optimizing cardiovascular risk stratification, in order to provide a new path for the early identification and intervention of CVD.METHODS: This study is a prospective cohort study aimed at assessing the association between tongue coating microbiota characteristics and multiple metabolic factors with subclinical target organ damage, and identifying high-risk groups suitable for cardiovascular 1.5-level prevention. The study will be conducted in Suzhou City, Jiangsu Province, China, planning to include 5000-6000 eligible subjects, with inclusion criteria of age ≥18 years, excluding individuals with a history of CVD and other serious diseases. Baseline assessment includes demographic information, lifestyle (including dietary patterns), medical history, physical examination, and collection of tongue coating microbiota samples. Subjects will be followed up every 2 years, with the primary outcome being the first occurrence of coronary heart disease and stroke, and the secondary outcome being subclinical target organ damage.DISCUSSION: This study focuses on cardiovascular 1.5-level prevention strategy, combining metabolic factors with tongue coating microbiota characteristics, aiming to optimize the risk assessment system for subclinical target organ damage. This approach can not only fill the gap in traditional risk assessment but also provide new ideas for the early identification and intervention of CVD. In the future, the feasibility and effectiveness of this strategy will be verified through multicenter studies, and it is expected to be promoted to a wider medical system, significantly improving the health management level of high-risk groups for CVD.TRIAL REGISTRATION NUMBER: http://itmctr.ccebtcm.org.cn, identifier ITMCTR2024000616.PMID:40013311 | PMC:PMC11860102 | DOI:10.3389/fendo.2025.1522756

J Inflamm Res. 2025 Feb 22;18:2629-2646. doi: 10.2147/JIR.S495784. eCollection 2025.ABSTRACTBACKGROUND: Acute myocardial infarction (AMI) is a critical cardiovascular event characterized by sudden coronary blood flow interruption, leading to myocardial ischemia and necrosis. Despite advances in acute therapeutic measures, understanding the metabolic damage related to AMI, particularly through specific protein expressions, remains limited. This study utilized Olink cardiovascular metabolomics technology to explore cardiovascular metabolism-related protein biomarkers associated with AMI, aiming to address the clinical need for early diagnosis and targeted therapy.METHODS: This study utilized Olink cardiovascular metabolomics technology to analyze 92 cardiovascular metabolism-related proteins in coronary blood samples from 20 AMI patients and 10 healthy controls. Differentially expressed proteins were identified using statistical t-tests, followed by functional enrichment analysis (GO and KEGG) and protein-protein interaction network construction. Five core proteins were validated in plasma samples from an additional 125 AMI patients and 120 healthy controls via enzyme-linked immunosorbent assay. To evaluate diagnostic performance, receiver operating characteristic curves were generated using GEO-related datasets, and Mendelian randomization analysis was employed to investigate the causal relationship between core proteins and AMI risk.RESULTS: The study identified 32 proteins with significantly altered expression levels between AMI patients and healthy controls. Among these, five core proteins-PCOLCE, FCN2, REG1A, DEFA1, and CRTAC1-were significantly associated with key biological processes such as metabolism, collagen formation, and the PI3K/AKT signaling pathway. These proteins showed strong correlations with clinical indicators, including BMI, LVEF, NT-proBNP, CK-MB, and cTnT. FCN2 and DEFA1 were further validated as having a causal relationship with AMI risk, indicating their potential as diagnostic biomarkers.CONCLUSION: The identified core proteins PCOLCE, FCN2, REG1A, DEFA1, and CRTAC1 are potential biomarkers for the early diagnosis and risk assessment of AMI. These findings suggest that these proteins could serve as targets for future therapeutic interventions aimed at mitigating cardiovascular metabolic damage in AMI.PMID:40013238 | PMC:PMC11863793 | DOI:10.2147/JIR.S495784

Front Microbiol. 2025 Feb 12;16:1522075. doi: 10.3389/fmicb.2025.1522075. eCollection 2025.ABSTRACTBACKGROUND: Despite the extensive research conducted on heat responses of Lentinula edodes heterokaryotic cells, the responses of the two sexually compatible monokaryons to heat stress (HS) remain largely unknown.METHODS: To bridge this gap, we examined the nucleus-specific (SP3 and SP30) heat resistant mechanisms using an integrated physiological, metabolomic and transcriptomic approach.RESULTS: The results showed that HS elicited the boost of ROS and hampered mycelium growth for both monokaryons. Metabolome and transcriptome analysis demonstrated that the two sexually compatible monokaryons responded differently to HS. For SP3, the differentially expressed genes (DEGs) were significantly enriched in Mitogen-Activated Protein Kinase (MAPK) signaling, cell cycle and sugar metabolism, whereas those DEGs for SP30 were enriched in glyoxylate and dicarboxylate metabolism, and protein processing. The differentially accumulated metabolites (DAMs) of both strains were enriched in the glycerophospholipid metabolism, alpha-linolenic acid metabolism, biosynthesis of cofactors, etc, but were regulated differently in each strain. The enriched KEGG pathways for SP3 tend to be downregulated, whereas those in SP30 exhibited a contrary trend. The genes in MAPK signaling pathway were associated with the glycerophospholipid metabolism in SP3, but not in SP30. Omics-integration analysis revealed distinguishing regulatory networks and identified completely different hub genes for the two strains.DISCUSSION: Our findings revealed, for the first time, the different heat-resistance mechanisms of the two compatible nuclei and provided candidate metabolites, responsive genes and regulatory pathways for further experimental validation.PMID:40012783 | PMC:PMC11861359 | DOI:10.3389/fmicb.2025.1522075

Front Microbiol. 2025 Feb 10;16:1511885. doi: 10.3389/fmicb.2025.1511885. eCollection 2025.ABSTRACTINTRODUCTION: The gut microbiota and bile acids (BAs) have emerged as factors involved in the development of non-alcoholic fatty liver disease (NAFLD). Xiaohua Funing decoction (XFD) is a traditional Chinese medicine formula used for the treatment of NAFLD. Previous studies have indicated that XFD protects liver function, but the underlying mechanism remains unclear.METHODS: In this study, a Wistar rat model of NAFLD (Mod) was established via a high-fat diet. The effects of obeticholic acid (OCA) and XFD on Mod rats were subsequently evaluated. Wistar rats in the control (Con) group were fed a standard diet. There were eight rats in each group, and the treatment lasted for 12 weeks. Furthermore, metagenomic sequencing and BA metabolomic analyses were performed.RESULTS: Compared to the Con group, the Mod group presented significant differences in body and liver weights; serum total cholesterol (TC) and triglyceride (TG) levels; and liver TG, TC, and bile salt hydrolase levels (p < 0.05 or p < 0.01). Importantly, OCA and XFD administration normalized these indicators (p < 0.05 or p < 0.01). Pathology of the liver and white fat steatosis was observed in the Mod group, but steatosis was significantly alleviated in the OCA and XFD groups (p < 0.05 or p < 0.01). The abundances of Bacteroidales_bacterium, Prevotella_sp., bacterium_0.1xD8-71, and unclassified_g_Turicibacter in the Mod group were significantly different from those in the Con group (p < 0.05 or p < 0.01), whereas the abundance of Bacteroidales_bacterium was greater in the XFD group. A total of 17, 24, and 24 differentially abundant BAs were detected in the feces, liver, and serum samples from the Mod and Con groups, respectively (p < 0.05 or p < 0.01). In the feces, liver, and serum, XFD normalized the levels of 16, 23, and 14 BAs, respectively, including glycochenodeoxycholic acid, deoxycholic acid, murideoxycholic acid, lithocholic acid, 23-nordeoxycholic acid, and 3β-ursodeoxycholic acid. In addition, glycochenodeoxycholic acid was identified as a potential biomarker of NAFLD.DISCUSSION: In summary, our experiments revealed that XFD regulates the gut microbiota and BAs, providing beneficial effects on liver lipid accumulation in NAFLD.PMID:40012777 | PMC:PMC11863611 | DOI:10.3389/fmicb.2025.1511885