PubMed

J Pharm Biomed Anal. 2025 Mar 4;260:116790. doi: 10.1016/j.jpba.2025.116790. Online ahead of print.ABSTRACTHeart failure (HF) is a major complication in patients with end-stage renal disease (ESRD) and is the leading cause of death in this high-risk population. Sacubitril/Valsartan is an angiotensin receptor-neprilysin inhibitor (ARNI) that has been shown to improve treatment outcomes in patients with ESRD accompanied by HF. Unfortunately, in clinical practice, some patients who received sacubitril/valsartan treatment not only did not show a good therapeutic effect, but also got worse with the passage of time. To explore potential biomarkers for predicting the clinical efficacy of sacubitril/valsartan, serum samples were prospectively collected upon admission and again collected after sacubitril/valsartan treatment was completed. Patients were divided into good response group (GR) and poor response group (PR). At the same time, samples before treatment were divided into GR group and PR group by sample tracing and matching, and metabolomics analysis was conducted. In the end, a total of 9 different metabolites were identified between patients in the early GR and PR groups. In order to find more effective biomarkers, two algorithms, random forest (RF) and support vector machine (SVM), were used for metabolite selection and performance evaluation, and three kinds of Lysophosphatidylcholine (LysoPC) metabolites showed good predictive effect, and the expression of the enzyme phospholipase A2 group IVA (PLA2G4A), associated with this metabolite was significantly elevated in the PR group. The disordered metabolism may reduce the sensitivity of patients to sacubitril/valsartan treatment, and PLA2G4A targeted inhibitors may be a promising therapeutic strategy to improve the sensitivity of patients with ESRD and HF to sacubitril/valsartan treatment.PMID:40058083 | DOI:10.1016/j.jpba.2025.116790

Redox Biol. 2025 Feb 28;81:103546. doi: 10.1016/j.redox.2025.103546. Online ahead of print.ABSTRACTBACKGROUND: High-altitude exposure has been associated with an increased risk of hyperuricemia (HU) and gout, though the underlying mechanisms remain poorly understood.METHODS: We conducted a comprehensive analysis of the serum metabolome and phenome in both discovery and validation cohorts of Han Chinese individuals who underwent long-term moderate-altitude exposure (∼12 months), as well as in an independent cohort consisting of local Han Chinese and Tibetans residing in Nyingchi (>5 years). Beta-Alanine intervention was applied in hypoxanthine and potassium oxonate-induced in vitro and in vivo experiments.RESULTS: Individuals exposed to moderate altitude exhibited elevated serum urate and an increase in overall medium-chain fatty acids (MCFAs), coupled with a decrease in overall amino acids (AAs) and short-chain fatty acids (SCFAs). Rmcorr correlation analysis revealed a significant negative association between Beta-Alanine and serum urate, whereas nonanoic acid was in versa, potentially driving lower serum urate in long-term exposed residents. Both in vitro and in vivo experiments demonstrated that Beta-Alanine inhibited xanthine oxidase (XOD) and reversed the HU phenotype in human hepatocytes and mice induced by hypoxanthine (HX) and potassium oxonate (PO), with a urate-lowering effect in mice. Hepatic pathology and transcriptome analysis of HU mice treated with Beta-Alanine indicated that the mechanisms involved the inhibition of XOD, amelioration of the inflammation phenotype in hepatocytes, and promotion of renal urate excretion. Furthermore, the 10-fold cross-validation random forest classification (RFC) predictive modeling based on selected metabolites and phenotypes achieved an area under receiver operating characteristic (ROC) curve (AUC) value of 0.93 (95 % confidence interval (CI): 0.85-1.00) and 0.79 (95 % CI: 0.59-0.98) for distinguishing individuals with high risk of asymptomatic HU (AHU) in the training dataset and validation dataset, respectively.CONCLUSIONS: This study reveals serum urate and metabolome altered in moderate-altitude exposed individuals and Beta-Alanine intervention could ameliorate hyperuricemia. Our findings suggest that targeting the circulating metabolome may pave novel avenues to counter diseases associated with HU.PMID:40058067 | DOI:10.1016/j.redox.2025.103546

Redox Biol. 2025 Mar 5;81:103580. doi: 10.1016/j.redox.2025.103580. Online ahead of print.ABSTRACTDespite the increasing recognition of the interplay between depression and cardiovascular disease (CVD), the precise mechanisms by which depression contributes to the pathogenesis of cardiovascular disease remain inadequately understood. The involvement of gut microbiota and their metabolites to health and disease susceptibility has been gaining increasing attention. In this study, it was found that depression exacerbated cardiac injury, impaired cardiac function (EF%: P < 0.01; FS%: P < 0.05), hindered long-term survival (P < 0.01), and intensified adverse cardiac remodeling (WGA: P < 0.01; MASSON: P < 0.0001) after myocardial ischemia/reperfusion (MI/R) in mice. Then we found that mice receiving microbiota transplants from chronic social defeat stress (CSDS) mice exhibited worse cardiac function (EF%: P < 0.01; FS%: P < 0.01) than those receiving microbiota transplants from non-CSDS mice after MI/R injury. Moreover, impaired tryptophan metabolism due to alterations in gut microbiota composition and structure was observed in the CSDS mice. Mechanistically, we analyzed the metabolomics of fecal and serum samples from CSDS mice and identified indole-3-propionic acid (IPA) as a protective agent for cardiomyocytes against ferroptosis after MI/R via NRF2/System xc-/GPX4 axis, played a role in mediating the detrimental influence of depression on MI/R. Our findings provide new insights into the role of the gut microbiota and IPA in depression and CVD, forming the basis of intervention strategies aimed at mitigating the deterioration of cardiac function following MI/R in patients experiencing depression.PMID:40058066 | DOI:10.1016/j.redox.2025.103580

ISME J. 2025 Mar 9:wraf047. doi: 10.1093/ismejo/wraf047. Online ahead of print.ABSTRACTMarine planktonic Radiolaria harboring symbiotic microalgae are ubiquitous in the oceans and abundant in oligotrophic areas. In these low-nutrient environments, they are among the most important primary producers. Systematic studies of radiolarian biology are limited because Radiolaria are non-culturable and prone to damage during sampling. To obtain insight into the mechanistic basis of radiolarian photosymbiosis we address here the metabolic contributions of the partners to the performance of the holobiont. Therefore, we describe the metabolic inventory of two highly abundant photosymbiotic Radiolaria - colony-forming Collodaria and single-celled Acantharia and compare their metabolomes to metabolomes of respective free-living algae. Most of the metabolites detected in the symbiosis are not present in the free-living algae, suggesting a significant transformation of symbionts' metabolites by the host. The metabolites identified in both the holobiont and the free-living algae encompass molecules of primary metabolism and a number of osmolytes, including dimethylsulfoniopropionate. Mass spectrometry imaging revealed the presence of dimethylsulfoniopropionate in both the symbionts and host cells, indicating that the algae provide osmolytic protection to the host. Furthermore, our findings suggest a possible dependence of Collodaria on symbiotic vitamin B3. Distinctive differences in phospholipid composition between free-living and symbiotic stages indicate that the algal cell membrane may undergo rearrangement in the symbiosis. Our results demonstrate a strong interdependence and rewiring of the algal metabolism underlying Radiolaria-microalgae photosymbioses.PMID:40057976 | DOI:10.1093/ismejo/wraf047

Mol Cancer. 2025 Mar 8;24(1):71. doi: 10.1186/s12943-025-02269-y.ABSTRACTEpigenomic modifications-such as DNA methylation, histone acetylation, and histone methylation-and their implications in tumorigenesis, progression, and treatment have emerged as a pivotal field in cancer research. Tumors undergo metabolic reprogramming to sustain proliferation and metastasis in nutrient-deficient conditions, while suppressing anti-tumor immunity in the tumor microenvironment (TME). Concurrently, immune cells within the immunosuppressive TME undergo metabolic adaptations, leading to alterations in their immune function. The complicated interplay between metabolites and epigenomic modulation has spotlighted the significance of epigenomic regulation in tumor immunometabolism. In this review, characteristics of the epigenomic modification associated with tumors are systematically summarized alongside with their regulatory roles in tumor metabolic reprogramming and immunometabolism. Classical and emerging approaches are delineated to broaden the boundaries of research on the crosstalk research on the crosstalk between tumor immunometabolism and epigenomics. Furthermore, we discuss potential therapeutic strategies that target tumor immunometabolism to modulate epigenomic modifications, highlighting the burgeoning synergy between metabolic therapies and immunotherapy as a promising avenue for cancer treatment.PMID:40057791 | DOI:10.1186/s12943-025-02269-y

Chin Med. 2025 Mar 8;20(1):33. doi: 10.1186/s13020-025-01085-2.ABSTRACTBACKGROUND: Shi Zheng (SZ, syndrome of dampness) is a major syndrome type in traditional Chinese Medicine (TCM), the ambiguity of its pathomechanism and the lack of blood diagnostic indicators have limited the understanding of the development of SZ.PURPOSE: To explore the pathological mechanism of SZ and establish a symptom-centered diagnosis and treatment model.METHODS: We recruited 250 participants, including healthy individuals and patients diagnosed with SZ. Serum metabolomics and proteomics analyses were performed to screen common pathways. Along with the biological significance of common pathways, a common pathway-symptom correlation diagram was constructed to elucidate the pathological mechanism underlying the occurrence and development of SZ. The enrichment score and correlations with SZ main symptom was used to screen the key common pathways. The key common pathways related to differential metabolites and proteins were used to establish a multi-index diagnostic model and protein therapy target group.RESULTS: Joint metabolomics and proteomics analyses revealed 18 common pathways associated with symptoms. Six key pathways, such as pathogenic Escherichia coli infection, rheumatoid arthritis, PPAR signaling pathway, bile secretion, GnRH signaling pathway, and fat digestion and absorption were correlated with the main symptoms of SZ. These symptoms included greasy/thick/slippery tongue coating, heavy head, heavy body, heavy limbs, heavy joints, greasy hair, sticky mouth, sticky stool, and damp scrotum. Moreover, seven differential metabolites related to the key pathways were identified: LysoPA (20:3(5Z,8Z,11Z)/0:0), prostaglandin E2, leukotriene B4, lithocholate 3-O-glucuronide, 3-hydroxyquinine, lithocholic acid glycine conjugate, and PA(18:0/22:6(5Z,8E,10Z,13Z,15E,19Z)-2OH(7S, 17S)), and the combined diagnostic value of the seven indicators was the highest (discovery cohort: AUC = 0.90; validation cohort: AUC = 0.99). There were 23 differential proteins related to the key pathways, and six protein targets were identified, including RHOA, TNFSF13, PRKCD, APOA2, ATP1A1, and FABP1.CONCLUSION: The combined analysis of metabolomics and proteomics established a symptom-centered diagnosis and treatment model of Shi Zheng.PMID:40057776 | DOI:10.1186/s13020-025-01085-2

Microb Cell Fact. 2025 Mar 8;24(1):57. doi: 10.1186/s12934-025-02645-9.ABSTRACTMethicillin-resistant Staphylococcus aureus (MRSA) is a significant pathogen associated with healthcare-related infections that are often challenging to treat. Conditions such as, skin and soft tissue infections, bloodstream infections, and pneumonia highlight the critical need for effective therapeutic strategies. Careful use of antibiotics under medical supervision is essential to prevent the further emergence of MRSA. Recent studies have documented the antibacterial efficacy of certain endophytic fungi extracts against MRSA, suggesting their potential as a source of novel treatments. This study investigates the metabolomic profiling of the endophytic fungus Aspergillus sp. SH1 using liquid chromatography-high-resolution electrospray ionization mass spectrometry (LC-HR-ESI-MS) and evaluates the anti-MRSA potential of the fungal extract. The metabolomic analysis identified 27 compounds (1-27) with diverse chemical natures, including polyketides, alkaloids, cyclic tripeptides, polypropionate derivatives, and sesquiterpenes. The fungal extract exhibited potent anti-MRSA activity, with an IC50 value of 9.8 µg/mL, compared to ciprofloxacin (IC50 = 25.7 µg/mL). To support these findings, in silico studies were performed to model the binding interactions of the identified compounds with key MRSA-related targets, including Toll-like receptor 2 (TLR2), von Willebrand factor (VWF), tumor necrosis factor (TNF), and penicillin-binding protein 2a (PBP2a). Compounds 2, 9, 15, 16, 20, 22, and 25 demonstrated enhanced binding affinities, suggesting their potential as lead molecules for developing new antibacterial agents targeting MRSA. In conclusion, this study highlights the promising anti-MRSA potential of Aspergillus sp. SH1 extract, providing a foundation for further exploration of its bioactive compounds in combating resistant bacterial infections.PMID:40057756 | DOI:10.1186/s12934-025-02645-9

Sci Rep. 2025 Mar 8;15(1):8103. doi: 10.1038/s41598-025-92756-5.ABSTRACTTinospora cordifolia has been used for thousands of years to treat various health conditions, including neurodegenerative diseases. The study aimed to elucidate the mechanism of action and protein targets of T. cordifolia in the context of Alzheimer's disease through untargeted metabolomics and network pharmacology. LC-MS/MS analysis resulted in 1186 metabolites, including known bioactive compounds such as liquiritin, Plastoquinone 3, and Shoyuflavone A, to name a few. The network pharmacology analysis highlighted the metabolite-protein interaction with the enrichment of 591 human proteins, including neurotransmitter receptors and other regulatory proteins. Pathway analysis highlighted the enrichment of cAMP, mTOR, MAPK, and PI3K-Akt signaling pathways along with cholinergic, dopaminergic, serotonergic, glutamatergic synapse, and apoptosis. The docking results suggest that T. cordifolia metabolites could interact with key Alzheimer's disease targets BACE1 and MAO-B, suggesting its role in neuroprotection. These findings provide insights into the biochemical pathways underlying T. cordifolia's therapeutic effects and provides a foundation for future exploration of T. cordifolia in the context of translational research.PMID:40057579 | DOI:10.1038/s41598-025-92756-5

Nat Commun. 2025 Mar 8;16(1):2338. doi: 10.1038/s41467-025-57299-3.ABSTRACTDuring mitochondrial damage, information is relayed between the mitochondria and nucleus to coordinate precise responses to preserve cellular health. One such pathway is the mitochondrial integrated stress response (mtISR), which is known to be activated by mitochondrial DNA (mtDNA) damage. However, the causal molecular signals responsible for activation of the mtISR remain mostly unknown. A gene often associated with mtDNA mutations/deletions is Polg1, which encodes the mitochondrial DNA Polymerase γ (PolG). Here, we describe an inducible, tissue specific model of PolG mutation, which in muscle specific animals leads to rapid development of mitochondrial dysfunction and muscular degeneration in male animals from ~5 months of age. Detailed molecular profiling demonstrated robust activation of the mtISR in muscles from these animals. This was accompanied by striking alterations to enzymes in the mitochondrial folate cycle that was likely driven by a specific depletion in the folate cycle metabolite 5,10 methenyl-THF, strongly implying imbalanced folate intermediates as a previously unrecognised pathology linking the mtISR and mitochondrial disease.PMID:40057508 | DOI:10.1038/s41467-025-57299-3

Hepatobiliary Pancreat Dis Int. 2025 Feb 27:S1499-3872(25)00051-7. doi: 10.1016/j.hbpd.2025.02.004. Online ahead of print.ABSTRACTBACKGROUND: Recent studies suggest an association between the expansion of Prevotella copri and the disease severity in children with metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to investigate the causative role and molecular mechanisms of P. copri in pediatric MASLD.METHODS: C57BL/6 J mice aged 3 weeks were fed a high-fat diet (HFD) and orally administered with P. copri for 5 weeks. We assessed the key features of MASLD and the gut microbiota profile. By untargeted metabolomics on mouse fecal samples and the supernatant from P. copri culture, we identified P. copri-derived metabolite and tested its effects in vitro.RESULTS: In HFD-fed mice, administration of P. copri significantly promoted liver steatosis. Genes associated with inflammation and fibrosis were significantly upregulated in the livers from the HFD + P. copri group compared with those in the livers from the HFD group. In addition, P. copri reduced gut microbial diversity, increased the proportion of Firmicutes and decreased Bacteroidota. Importantly, 5-aminopentanoic acid (5-AVA) was significantly enriched in both mouse feces from the HFD + P. copri group and the culture supernatant of P. copri. In vitro, 5-AVA aggravated palmitic acid-induced lipid accumulation in HepG2 cells and primary mouse hepatocytes. Mechanistically, P. copri-produced 5-AVA exacerbated hepatic steatosis by promoting lipogenesis and fatty acid uptake, while also reducing hepatic very-low-density lipoprotein export.CONCLUSIONS: Our findings demonstrated that P. copri promotes liver steatosis in HFD-fed juvenile mice through its metabolite 5-AVA, suggesting its potential as a therapeutic target for the management of pediatric MASLD.PMID:40057459 | DOI:10.1016/j.hbpd.2025.02.004

J Allergy Clin Immunol. 2025 Mar 6:S0091-6749(25)00261-1. doi: 10.1016/j.jaci.2025.02.030. Online ahead of print.ABSTRACTBACKGROUND: The first year of life represents a dynamic immune development period that impacts the risk of developing respiratory-related diseases, including asthma, recurrent infections, and eczema. However, the role of immune-mediating proteins in childhood respiratory diseases is not well characterized in early life.METHODS: We applied weighted gene correlation network analysis (WGCNA) to derive modules of highly correlated proteins during early life immune development using plasma samples collected from children at age 1 year (N=294) in the Vitamin D Antenatal Asthma Reduction Trial (VDAART). Using regression analysis, we evaluated relationships between protein modules at age 1 and respiratory-related diseases by age 6. We integrated protein modules with additional 'omics and social, demographic, and environmental data for further characterization.RESULTS: Our analysis identified four protein modules at age 1 year associated with incidence of childhood asthma and/or recurrent wheeze (Padj range: 0.02-0.03), respiratory infections (Padj range: 6.3x10-9-2.9x10-6), and eczema (Padj=0.01) by age 6 years; associations between modules and clinical outcomes were temporally sensitive and were not recapitulated using protein profiles at age 6 years. Age 1 modules were associated with environmental factors (Padj range: 2.8x10-10-0.03) and alteration in metabolomic pathways (Padj range: 2.8x10-6-0.04). No genome-wide SNPs were identified for any protein module.CONCLUSION: These findings suggested protein profiles as early as age 1 year predicted development of respiratory-related diseases by age 6. In the future, applying network approaches to study protein profiles may represent a new strategy to identify children susceptible to respiratory-related diseases in the first year of life.PMID:40057284 | DOI:10.1016/j.jaci.2025.02.030

Neuropharmacology. 2025 Mar 6:110405. doi: 10.1016/j.neuropharm.2025.110405. Online ahead of print.ABSTRACTChronic pain due to lumbar disc herniation (LDH) significantly impairs quality of life and is often accompanied by emotional disturbances, such as anxiety and depression. Despite the recognition of these comorbidities, the underlying neural mechanisms remain unclear. This study investigates the role of neurotransmitter imbalances and key regulatory molecules in LDH-induced chronic pain and related emotional disturbances, with a focus on synaptic plasticity in the amygdala. A rat model of LDH was developed using male Sprague-Dawley rats. Behavioral assessments were conducted to evaluate pain hypersensitivity, anxiety, and depression-like behaviors. Cerebrospinal fluid (CSF) metabolomics and amygdala transcriptomics were employed to analyze neurotransmitter profiles and gene expression. In vitro experiments were conducted to explore the role of PRKCG in synaptic plasticity. Behavioral tests showed significant pain hypersensitivity and anxiety- and depression-like behaviour in LDH rats. Metabolomic analysis revealed altered levels of glutamate and γ-aminobutyric acid (GABA) in the CSF, indicating neurotransmitter imbalances. Transcriptomic profiling identified changes in genes related to synaptic plasticity, including PRKCG. PRKCG knockdown led to reduced CAMKII phosphorylation and GRIA1 expression, supporting its role in modulating synaptic plasticity. This study provides evidence that neurotransmitter imbalances and alterations in synaptic plasticity within the amygdala may contribute to the persistence of chronic pain and associated emotional disturbances in LDH. PRKCG may represent a novel therapeutic target for treating both chronic pain and related emotional disturbances.PMID:40057176 | DOI:10.1016/j.neuropharm.2025.110405

Eur J Pharmacol. 2025 Mar 6:177480. doi: 10.1016/j.ejphar.2025.177480. Online ahead of print.ABSTRACTMultidrug-resistant (MDR) Pseudomonas aeruginosa (PSA), recently reclassified by the World Health Organization (WHO) as a high-priority antimicrobial-resistant pathogen, continues to impose a substantial global health burden due to escalating resistance and stagnant therapeutic innovation. Colistin retains critical clinical utility against MDR P. aeruginosa infections; however, its dose-limiting nephrotoxicity and neurotoxicity necessitate strategies to optimise therapeutic indices. This study investigated the molecular mechanism underlying the synergistic activity of aspirin in potentiating colistin efficacy against MDR P. aeruginosa. In vitro analyses revealed marked synergistic bactericidal activity (FIC index ≤0.5), with metabolomic profiling demonstrating suppression of key metabolic pathways integral to bacterial membrane biogenesis, including glycerophospholipid metabolism and fatty acid biosynthesis. Ultrastructural imaging confirmed irreversible disruption of membrane integrity via combined treatment. In a rat model of P. aeruginosa-induced pneumonia, colistin-aspirin co-administration demonstrated superior efficacy to monotherapy, significantly reducing pulmonary bacterial load (3 to 4-log CFU/g reduction vs colistin alone; p<0.01), attenuating histopathological injury, and suppressing pro-inflammatory cytokine levels (IL-6, IL-8, TNF-α) by 30-47%. Critically, this synergy enabled a reduction of colistin dosing to one-sixteenth while maintaining bactericidal potency. These findings provide mechanistic insights into aspirin-mediated colistin sensitisation and evidence supporting combinatorial regimens to circumvent colistin toxicity barriers. This work establishes a rational foundation for clinical translation of repurposed aspirin-colistin therapy against MDR P. aeruginosa infections.PMID:40057155 | DOI:10.1016/j.ejphar.2025.177480

Int J Biol Macromol. 2025 Mar 6:141809. doi: 10.1016/j.ijbiomac.2025.141809. Online ahead of print.ABSTRACTThe European sweet cherry (Prunus avium) is highly valued for its superior quality, delectable taste, and robust stress resistance, leading to its extensive cultivation in the world. However, the previous incomplete genome assemblies have impeded its evolution and genetic regulation studies. In this study, we generated a Telomere-to-Telomere gap-free genome assembly of P. avium cv. Tieton, using advanced sequencing technologies. The assembled genome comprises eight pseudochromosomes with a genome size of 342.23 Mb and a contig N50 of 40.66 Mb. Comparative genomic analysis identified several unique stress resistance-related genes, possibly associated with the species' environmental adaptation. The integrative analyses of genomics, transcriptomes and metabolomes identified some key structural genes and metabolites crucial to flavonoid biosynthesis of sweet cherry. Our analyses revealed that 85 flavonoid metabolites, which are highly differentially accumulated among five tissues (flesh, stem, leaf, bud, and seed) of cherry. Interestingly, eight abundant flavonoids (Narcissoside, Typhaneoside, Myricetin 3-0-galactoside, Diosmin, Neohesperidin, Liquiritin apioside, 5,6,7-Trimethoxyflavone and Oroxin B) were highly accumulated in cherry flesh tissues. The gene-metabolite correlation analysis revealed that seven genes (HTC8, HTC6, CYP75B1_9, CYP75B1_10, 4CL1, DFR1, and FLS1) significantly regulated flavonoid accumulation in cherry flesh. Additionally, some structural genes (4CL6, PAL3, CYP75A2, F3H1, CYP75B1_8, and CYP75B1_10) were identified in the flavonoid biosynthetic pathway and were highly expressed, aligning with high flavonoid metabolite content in cherry flesh. These identified genes and metabolites are likely pivotal in conferring sweet cherry's stress resistance and high-quality traits. These findings offer deep insights into the mechanisms of genomic evolution and flavonoid biosynthesis, which also lay a solid foundation for further function genomics studies and breeding improvement in cherry.PMID:40057088 | DOI:10.1016/j.ijbiomac.2025.141809

Int J Biol Macromol. 2025 Mar 6:141827. doi: 10.1016/j.ijbiomac.2025.141827. Online ahead of print.ABSTRACTHibernation poses significant physiological challenges to the animals, making it an excellent model for investigating the impacts of extreme environment changes on animal health. This study explored the gut microbiota and host metabolism in hibernating snakes using 16S rRNA gene sequencing and untargeted metabolomics. Ten king ratsnakes were divided into active and hibernating groups, and their gut microbial compositions and serum metabolomic profiles were analyzed. Results demonstrated a significant reduction in gut microbial diversity during hibernation, with the abundance of Cetobacterium increasing dramatically from 5.57 % to 49.56 %, establishing it as the predominant genus in hibernating snakes. Metabolomic analysis revealed significant alterations in lipid and amino acid metabolism, with 69 metabolites downregulated during hibernation. Correlation analyses identified Cetobacterium as a central hub in the correction networks, influencing numerous gut microorganisms and showing a strong association with host metabolic depression. In addition to the recognized ability to produce vitamin B12 and short-chain fatty acids, this study further confirmed the robust antioxidant ability of snake-derived Cetobacterium somerae strains. These findings highlight the potential role of Cetobacterium in the physiological adaptation of snakes during hibernation and provide a foundation for exploring its applications in reptilian health management.PMID:40057061 | DOI:10.1016/j.ijbiomac.2025.141827

J Thromb Haemost. 2025 Mar 6:S1538-7836(25)00126-6. doi: 10.1016/j.jtha.2025.02.027. Online ahead of print.ABSTRACTBACKGROUND: 2-Methoxybenzoic acid (2MOA) is a natural compound with potential salicylate-like effects; however, its impact on arterial thrombosis remains unclear. This study aims to investigate the effects of 2MOA on thrombogenesis and its underlying mechanisms.METHODS: FeCl3-induced carotid artery injury and laser-induced cremaster artery injury thrombosis assays were utilized to explore the effect of 2MOA on thrombogenesis in vivo. Various ex vivo platelet function assays were conducted to evaluate the impacts of 2MOA on platelet activity. In addition, untargeted metabolomics analysis was performed to identify the alterations in intraplatelet metabolites following 2MOA treatment.RESULTS: We found that 2MOA significantly ameliorated thrombosis in a dose-dependent manner, without affecting the normal hemostasis in C57BL/6J mice. 2MOA suppressed platelet reactivity as indicated by decreased spreading, retraction, and aggregation in both mouse and human platelets. Metabolomics analysis revealed significantly alterations in purine metabolism following 2MOA treatment, which increased cyclic guanosine monophosphate (cGMP) production in platelets. Mechanistically, 2MOA inhibited the activity of carbonic anhydrase, leading to elevated intra-platelet cGMP level, and subsequent suppression of cytosolic phospholipase A2 phosphorylation.CONCLUSION: Our study illustrates that 2MOA efficaciously inhibits platelet reactivity and alleviates thrombogenesis via suppressing carbonic anhydrase activity, which should be a promising reagent in the prevention and treatment of arterial thrombotic events.PMID:40056982 | DOI:10.1016/j.jtha.2025.02.027

Sci Total Environ. 2025 Mar 7;971:179045. doi: 10.1016/j.scitotenv.2025.179045. Online ahead of print.ABSTRACTThis study employed a combined approach of untargeted UHPLC-HRMS and targeted GC-MS analyses to investigate the effects of different cultivation media on the growth and bromoform production of Asparagopsis taxiformis tetrasporophytes. Growth performance and metabolic profiles were analyzed under various nutrient conditions, including PES, F/2, Walne, and a control medium. Significant variations in growth rates and metabolic compositions were observed across the media. Multivariate analyses revealed distinct clustering patterns, with PES and F/2 forming separate clusters from Walne and the control, indicating substantial differences in metabolic makeup. The PES medium, with its optimized micronutrient ratios, supported the highest growth rates and unique metabolic signatures, while F/2, though slightly less effective, offered a more cost-effective alternative for large-scale cultivation. Significant metabolic pathways were upregulated under PES, suggesting optimal conditions for A. taxiformis growth and metabolic activity. Targeted GC-MS analysis revealed that tetrasporophytes grown in PES exhibited significantly higher bromoform levels-up to 12,695 μg/g-compared to gametophytes and other seaweeds. This underscores the superior growth performance and bromoform production in PES, while highlighting the importance of considering both performance and cost in cultivation strategies aimed at methane mitigation.PMID:40056866 | DOI:10.1016/j.scitotenv.2025.179045

Eur J Med Chem. 2025 Mar 4;289:117476. doi: 10.1016/j.ejmech.2025.117476. Online ahead of print.ABSTRACTThe NLRP3 inflammasome is crucial for immune responses. However, its overactivation can lead to severe inflammatory diseases, underscoring its importance as a target for therapeutic intervention. Although numerous inhibitors targeting NLRP3 exist, regulating its degradation offers an alternative and promising strategy to suppress its activation. The degradation of NLRP3 is primarily mediated by the proteasomal and autophagic pathways. The review not only elaborates on the traditional concepts of ubiquitination and NLRP3 degradation but also investigates the important roles of indirect regulatory modifications, such as phosphorylation, acetylation, ubiquitin-like modifications, and palmitoylation-key post-translational modifications (PTMs) that influence NLRP3 degradation. Additionally, we also discuss the potential targets that may affect NLRP3 degradation during the proteasomal and autophagic pathways. By unraveling these complex regulatory mechanisms, the review aims to enhance the understanding of NLRP3 regulation and its implications for developing therapeutic strategies to combat inflammatory diseases.PMID:40056798 | DOI:10.1016/j.ejmech.2025.117476

Microbiol Res. 2025 Mar 4;296:128135. doi: 10.1016/j.micres.2025.128135. Online ahead of print.ABSTRACTWalnut (Juglans sigillata), an economically significant ecotype of the Juglans genus in the Juglandaceae family, is cultivated mainly in southwest China, a region prone to seasonal drought. Drought significantly reduced both the yield and quality of walnuts in this area. Arbuscular mycorrhizal fungi (AMF) are symbiotic fungi that colonize plant roots and play crucial roles in enhancing plant drought resistance. This study investigated the effects of AMF on the alleviation of drought stress. Compared to non-inoculated drought-stressed plants, AMF inoculation improved plant growth, increased photosynthetic capacity, enhanced reactive oxygen species (ROS) scavenging ability, and significantly activities of superoxide Dismutase, peroxidase, and catalase were significantly increased by 19.90 %, 18.43 %, and 8.39 %, respectively. malondialdehyde, Superoxide anion, and Hydrogen peroxide levels decreased by 18.39 %, 20.75 %, and 21.44 %, respectively, and soluble sugar and proline concentrations also significantly increased (P < 0.05), helping to maintain the osmotic balance. In addition, transcriptome results showed that ATP-binding cassette transporter related to drought resistance were significantly enriched in plants inoculated with AMF, and genes related to growth, such as IAA and CKT synthesis, transcription factors (BZIP, WRKY, and GTE), and related antioxidant enzymes. The mitogen-activated protein kinases pathway-related genes were upregulated in the inoculated drought treatment group, whereas pinobanksin and homoeriodictyol were upregulated in the inoculated drought treatment group, both of which provide support for drought resistance. In summary, AMF alleviated drought stress and promoted Juglans sigillata growth by modulating key physiological, biochemical, and molecular mechanisms involved in drought resistance. This study offers important theoretical insights that support the application of AMF in sustainable agricultural practices.PMID:40056711 | DOI:10.1016/j.micres.2025.128135

Talanta. 2025 Mar 4;291:127891. doi: 10.1016/j.talanta.2025.127891. Online ahead of print.ABSTRACTDiabetic liver injury (DLI) is a significant complication of diabetes mellitus, leading to severe liver dysfunction and non-alcoholic fatty liver disease (NAFLD). Understanding the metabolic alterations and reprogramming in DLI is critical for identifying therapeutic targets. Despite the prevalence of DLI, its underlying metabolic mechanisms remain poorly understood, and effective treatments are lacking. In this study, we employed a multimodal mass spectrometry imaging approach, combining air-flow-assisted desorption electrospray ionization (AFADESI-MSI) with matrix-assisted laser desorption ionization (MALDI-MSI) to achieve a comprehensive spatial analysis of metabolic changes in DLI model rats, focusing on the potential therapeutic effects of ferulic acid, a compound known for its antioxidant and anti-inflammatory properties. This approach allowed for the wide-coverage and high-resolution visualization of over 200 metabolites in the liver tissues of DLI model rats. The study involved comparing metabolic profiles between control, DLI, and ferulic acid-treated groups, with ferulic acid administered at a dosage of 50 mg/kg daily for 20 weeks. The analysis revealed significant metabolic reprogramming in DLI, characterized by alterations in glucose, lipid, bile acid, and nucleotide metabolism. Specifically, we identified over 100 metabolites with heterogeneous distributions across liver sections, highlighting region-specific metabolic impairments. Ferulic acid treatment notably reversed many of these metabolic disturbances, particularly in glucose and lipid metabolism, suggesting its potential to restore metabolic homeostasis in DLI. This study provides critical insights into the metabolic underpinnings of DLI and demonstrates the therapeutic potential of ferulic acid in modulating these pathways. The findings underscore the utility of AFADESI- and MALDI-MSI in studying liver diseases and suggest that the metabolites identified could serve as novel biomarkers for DLI diagnosis and treatment.PMID:40056655 | DOI:10.1016/j.talanta.2025.127891