PubMed

J Ethnopharmacol. 2024 Nov 15:119112. doi: 10.1016/j.jep.2024.119112. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Epilepsy (EP) is one of the most prevalent chronic neurological disorders in children, characterised by a prolonged course and a propensity for recurrence. Banxia Baizhu Tianma Decoction (BBTD), a traditional Chinese medicine formula, is commonly employed in the clinical management of EP and has demonstrated satisfactory therapeutic effects.AIM OF THE STUDY: This study aimed to evaluate the anti-epileptic effects of BBTD and to explore its molecular mechanisms.MATERIALS AND METHODS: EP rat model was induced by pentylenetetrazol (PTZ) and treated with BBTD. Parameters such as seizure grade and duration were recorded to evaluate the improvement of BBTD on epileptic behavior. Nissl staining was used to observe the pathological changes in the cerebral motor cortex. The expression levels of the Bax and Bcl-2 in the motor cortex were measured by western blot analysis to assess neuronal damage and apoptosis. The therapeutic action of BBTD was evaluated by examining the levels of neurotransmitters γ-aminobutyric acid (GABA) and glutamate (Glu) in the brain tissue of EP rats, along with assessments of neuronal damage and apoptosis. Non-targeted metabolomics techniques were employed to conduct a comprehensive analysis of serum and urine metabolites, and network analysis of metabolite-related targets was performed to enhance understanding of the anti-epileptic effects and mechanisms of BBTD.RESULTS: After BBTD treatment, the EP model rats exhibited reduced seizure severity and shortened seizure duration. Moreover, BBTD mitigated PTZ-induced neuronal damage, as evidenced by a significant increase in the number of Nissl bodies in the motor cortex following treatment. At the same time, BBTD inhibited neuronal apoptosis, as demonstrated by the up-regulation of the anti-apoptotic protein Bcl-2 and down-regulation of the pro-apoptotic protein Bax in the brain tissue of treated rats. In addition, BBTD reversed the decreased levels of GABA and the increased levels of Glu in the brain tissue of the model group. Metabolomics analyses suggested that BBTD treatment for EP may be closely associated with alterations in urinary metabolites related to vitamin B6 and pyrimidine metabolism, as well as serum metabolites involved in purine metabolism, glycerophospholipid metabolism and vitamin B6 metabolism. Finally, network analysis of metabolite targets indicated that dopamine and alpha-linolenic acid metabolites may play significant roles in the therapeutic effects of BBTD on EP.CONCLUSION: BBTD demonstrated anti-epileptic effects in PTZ-induced seizure rats by regulating neurotransmitter balance, reducing neuronal damage and inhibiting apoptosis, suggesting its potential for the development of novel AEDs. This is the first time that UHPLC-MS-based urine and serum metabolomics have been used to elucidate the anti-epileptic mechanism of BBTD, providing insights into the underlying mechanisms of BBTD's action.PMID:39551285 | DOI:10.1016/j.jep.2024.119112

Microbes Infect. 2024 Nov 15:105438. doi: 10.1016/j.micinf.2024.105438. Online ahead of print.ABSTRACTThe fungal disease chytridiomycosis (causative agent Batrachochytrium dendrobatidis [Bd]) is a primary contributor to amphibian species declines. The morphological and physiological reorganisation that occurs during amphibian metamorphosis likely increases the vulnerability of metamorphs to Bd. To address this, we exposed pro-metamorphic tadpoles of Fleay's barred frog (Mixophyes fleayi) to Bd and sampled skin and liver sections from control and exposed animals throughout metamorphosis (Gosner stages 40, 42 and 45). We used an untargeted metabolomics approach to assess the metabolic impacts of Bd infection during the critical metamorphic stages, extracting metabolites from sampled tissues and analysing them via Nuclear Magnetic Resonance spectrometry. Most exposed animals became moribund at Gosner stage 45, while a subset seemingly cleared their infections. Metabolite abundance varied throughout development, with Gosner stage 45 samples distinct from previous stages. Clinically infected animals at Gosner stage 45 exhibited profound metabolic dysregulation (e.g., upregulation of amino acid biosynthesis and degradation) in comparison to uninfected groups (negative controls and 'cleared' animals). Despite showing parallels with previous metabolomic analyses of Bd-infected adult frogs, we identified variations in our results that could be attributed to the dramatic changes that characterise metamorphosis and may be driving the heightened vulnerability observed in metamorphic amphibians.PMID:39551241 | DOI:10.1016/j.micinf.2024.105438

J Dairy Sci. 2024 Nov 15:S0022-0302(24)01298-0. doi: 10.3168/jds.2024-25632. Online ahead of print.ABSTRACTLacticaseibacillus rhamnosus Probio-M9 (Probio-M9), a probiotic strain sourced from healthy breast milk, is recognized for its resilience to gastric and bile acids, along with its potential health benefits for infants. Its unique origin may influence its metabolic properties and effectiveness, garnering increasing interest within the scientific community in recent years. However, research on its efficacy as a starter culture for milk fermentation and the associated metabolic shifts remains limited. This study aimed to track the dynamic metabolomic changes of Probio-M9 during the fermentation process. We utilized Probio-M9 as the sole inoculant for milk fermentation, collecting samples at 1.5 to 3-h intervals to monitor the fermentation progression. Moreover, the metabolomics changes of the fermented milk were investigated after a 28-d storage period to evaluate post-storage stability. Metabolite profiles were generated using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MSE). A total of 34 representative differential metabolites were identified, primarily comprising peptides and saccharides, followed by acids, amino acids, alcohols, aldehydes, ketones, and intermediate metabolites. Notably, substantial alterations in metabolite levels were observed between 10.5 to 12 h into the fermentation process. Functional metabolites like syringaldehyde, leucic acid, and gentianose accumulated toward the end of fermentation, while peptides emerged as the main differential metabolites after the 28-d storage period. The study offers novel insights into the metabolic dynamics of Probio-M9 during fermentation and storage, which may inform the optimization of Probio-M9 fermented milk production processes. However, it is important to note that the focus of this study on a single starter strain may limit the generalizability of these findings.PMID:39551178 | DOI:10.3168/jds.2024-25632

Ecotoxicol Environ Saf. 2024 Nov 16;288:117348. doi: 10.1016/j.ecoenv.2024.117348. Online ahead of print.ABSTRACTCyanobacterial blooms and aquatic macrophytes can affect the health, physiology, and behavior of freshwater fish. Changes in food intake can be a key indicator of stress in teleost fish, while changes in metabolite abundance in the gut can indicate a shift in metabolic priorities, including response to environmental stressors. Here, we exposed stone moroko (Pseudorasbora parva) to the cyanobacterium Microcystis aeruginosa and/or the macrophyte Ottelia acuminata and analyzed changes in fish health, appetite regulation, and intestinal metabolome after 96-h exposures. We found that O. acuminata treatment didn't change the tested indicators, while exposure to M. aeruginosa increased concentrations of appetite-inhibiting factors, such as CART and GLP-1, and decreased concentrations of stimulatory factors like orexin. Exploration of the metabolome following exposure revealed that the appetite-inhibiting influence of M. aeruginosa was positively correlated with key metabolites of lipid, amino acid, and cholesterol metabolism, especially those associated with bile acid synthesis and secretion. Further, the presence of O. acuminata decreased the adverse effects of M. aeruginosa among neuro-endocrine regulatory factors, which could be explained by altered regulation of intestinal amino acid metabolites. The deeper mechanism by which O. acuminata moderates the harmful effects of M. aeruginosa remains to be identified.PMID:39550875 | DOI:10.1016/j.ecoenv.2024.117348

Talanta. 2024 Nov 12;284:127211. doi: 10.1016/j.talanta.2024.127211. Online ahead of print.ABSTRACTCarotid artery stenosis is mainly produced due to the progressive accumulation of atherosclerotic plaque in the vascular wall. The atherosclerotic plaque is characterized by the accumulation of lipids, low density proteins, expression of chemokines and adhesion molecules, and migration of monocytes and lymphocytes into the plaque. Its rupture can produce stroke, but embolic propensity depends principally on the composition and vulnerability of plaque rather than the severity of stenosis. It is important, then, to ascertain which patients with carotid artery stenosis have a greater risk of developing neurological symptomatology. Here, we present a metabolomic study by using nuclear magnetic resonance (NMR) spectroscopy in atheroma plaque and serum samples from patients with recently symptomatic and asymptomatic carotid stenosis to search for metabolites that could be used as biomarkers associated with plaque vulnerability and subsequent risk of rupture. Thirty-eight atheromatous plaque samples (24 asymptomatic patients and 14 symptomatic) and 70 serum samples (43 asymptomatic and 27 symptomatic) were studied by NMR spectroscopy. The data were analysed using multivariate statistics (PLS-DA) to determine a model to discriminate between symptomatic and asymptomatic samples (atheroma plaques and sera). The calculated PLS-DA models showed a 100 % sensitivity and a 96.6 % specificity for the cross validation to discriminate between symptomatic and asymptomatic plaques, and 88.37 % sensitivity and 77.78 % specificity when serum samples were analysed. According to the results of our multivariate and univariate analysis, the most discriminative metabolites for plaque vulnerability were threonine in serum samples, and glutamate in plaque samples. Also, an analysis of the main metabolic pathways involved in plaque vulnerability revealed that d-glutamine and d-glutamate metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis were the most affected pathways in plaque and serum, respectively.PMID:39550810 | DOI:10.1016/j.talanta.2024.127211

Sci Rep. 2024 Nov 16;14(1):28270. doi: 10.1038/s41598-024-79481-1.ABSTRACTThe understanding of the role played by extracellular vesicles (EVs) in different tissues has improved significantly in the last years, but remains limited concerning the conjunctiva, a complex eye tissue whose role is pivotal for corneal protection. Here, we conducted a comparative study to isolate and characterize EVs from human conjunctival epithelial (IM-HConEpiC) and human conjunctival mesenchymal stromal cell (Conj-MSCs) secretomes using different isolation methods: differential ultracentrifugation (UC), and a combination of ultrafiltration (UF) with precipitation or size exclusion chromatography (SEC). EVs were characterized by total protein content, size, morphology, and expression of protein markers. EV functional effect was tested in an in vitro oxidative stress model. We successfully recovered EVs with the three methods, although significantly higher yields were obtained with UF-precipitation. Dynamic light scattering analysis confirmed the presence of nano-sized particles, being UC-isolated EVs larger than those isolated by UF-precipitation and UF-SEC. Atomic Force Microscopy showed EVs with a slightly ellipsoidal morphology. EVs enriched with UF-precipitation method were further analyzed, confirming the expression of Alix, CD63, TSG101, and Syntenin-1 by Western blotting and showing that Conj-MSC-derived EVs significantly reduced oxidative stress on IM-HConEpiC. Therefore, we conclude that UF-precipitation is the most efficient method for conjunctival EV enrichment.PMID:39550477 | DOI:10.1038/s41598-024-79481-1

Cancer Cell Int. 2024 Nov 16;24(1):381. doi: 10.1186/s12935-024-03573-1.ABSTRACTBACKGROUND: Despite advancements in therapeutic approaches, including taxane-based chemotherapy and androgen receptor-targeting agents, metastatic castration-resistant prostate cancer (mCRPC) remains an incurable tumor, highlighting the need for novel strategies that can target the complexities of this disease and bypass the development of drug resistance mechanisms. We previously demonstrated the synergistic antitumor interaction of valproic acid (VPA), an antiepileptic agent with histone deacetylase inhibitory activity, with the lipid-lowering drug simvastatin (SIM). This combination sensitizes mCRPC cells to docetaxel treatment both in vitro and in vivo by targeting the cancer stem cell compartment via mevalonate pathway/YAP axis modulation.METHODS: Here, using a combined proteomic and metabolomic/lipidomic approach, we characterized tumor samples derived from 22Rv1 mCRPC cell-xenografted mice treated with or without VPA/SIM and performed an in-depth bioinformatics analysis.RESULTS: We confirmed the specific impact of VPA/SIM on the Hippo-YAP signaling pathway, which is functionally related to the modulation of cancer-related extracellular matrix biology and metabolic reprogramming, providing further insights into the molecular mechanism of the antitumor effects of VPA/SIM.CONCLUSIONS: In this study, we present an in-depth exploration of the potential to repurpose two generic, safe drugs for mCRPC treatment, valproic acid (VPA) and simvastatin (SIM), which already show antitumor efficacy in combination, primarily affecting the cancer stem cell compartment via MVP/YAP axis modulation. Bioinformatics analysis of the LC‒MS/MS and 1H‒NMR metabolomics/lipidomics results confirmed the specific impact of VPA/SIM on Hippo-YAP.PMID:39550583 | DOI:10.1186/s12935-024-03573-1

Virol J. 2024 Nov 16;21(1):295. doi: 10.1186/s12985-024-02571-z.ABSTRACTMounting evidence suggests that the gut-heart axis is critical in the pathogenesis of cardiovascular diseases. The gut serves as the primary pathway through which Coxsackievirus B3 (CVB3) infects its host, leading to acute viral myocarditis (AVMC). However, little is known about the role of gut microflora and its metabolites in the development of AVMC. The AVMC model was established by intraperitoneal injection of CVB3 in mice. Then, 16S ribosomal RNA (16S rRNA) gene sequencing and ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) untargeted metabolomics profiling were performed to analyze the microflora composition and metabolic profile of colonic contents. Compared to the Control mice, the AVMC mice displayed a significant reduction in gut microflora richness and diversity, as revealed by an increased abundance of Proteobacteria and a decreased abundance of Cyanobacteria and Desulfobacterota. LEfSe analysis indicated that the main genera differing between the two groups were Escherichia-Shigella, Lactobacillus, Clostridium_sensu_stricto_1, Prevotellaceae_UCG-001, and Odoribacter. Based on the criterion of OPLS-DA VIP ≥ 1.0 and p-value < 0.05, a total of 198 differential metabolites (DMs) were identified in the gut, including 79 upregulated and 119 downregulated metabolites, of which lipids and lipid-like molecules accounted for the largest proportion. Notably, both altered gut bacterial taxa and metabolites were significantly enriched in the Lipid metabolism pathway, with Traumatic acid (TA), Alpha-Linolenic acid (ALA), Eicosapentaenoic acid (EPA), and Docosahexaenoic acid (DHA) being the key DMs in the pathway. Additionally, significant positive correlations (|r| > 0.80 and p < 0.05) were found between TA levels and Anaerotruncus and Bilophila abundance, between EPA levels and Clostridium_sensu_stricto_1 abundance, and between DHA levels and Escherichia-Shigella abundance, respectively. CVB3 infection leads to notable alterations in gut microflora composition and its metabolic profile, which may participate in AVMC development. Our findings provide important clues for future in-depth studies on AVMC etiology.PMID:39550578 | DOI:10.1186/s12985-024-02571-z

BMC Cardiovasc Disord. 2024 Nov 16;24(1):654. doi: 10.1186/s12872-024-04306-y.ABSTRACTBACKGROUND: The spontaneous echo contrast (SEC) in patients with atrial fibrillation (AF) indicates a prethrombic state that ultimately progresses into thrombus formation. A comprehensive understanding of specific plasma metabolomics characteristics may protect AF patients from thrombus, particularly in the early stage.OBJECTIVES: Through the investigation of metabolic pathways, we endeavor to uncover the metabolomic characteristics associated with SEC states, and to examine the differential metabolites by which may exert their influence on thrombotic states.METHODS: Patients with AF were enrolled, and the participants were divided into three groups based on the results of the echocardiogram: non-SEC, low-SEC and high-SEC group. Samples were collected and subjected to non-targeted metabolomics analysis. The analytical process included data quality control, metabolite difference analysis, component analysis, Kegg cluster analysis, etc. RESULTS: Our metabolic phenotype revealed a clear differential metabolic pattern between the SEC and non-SEC. Specifically, we identified 35 and 142 significantly differential metabolites in venous and atrial plasma, respectively, suggesting that SEC may be involved in pervasive metabolic dysregulation and that the degree of metabolic dysregulation in atrial plasma is more severe than that in venous blood.CONCLUSION: Patients with SEC have a significantly different metabolic pattern compared to those without SEC. Our work promoted the understanding of mechanism of the occurrence and development of SEC, facilitated the screening of the target metabolites for its therapeutic intervention, and provided evidence for the prevention and treatment of SEC or thrombosis in AF. Our work also provided new directions for subsequent research in related fields. In conclusion, our study not only provides a theoretical basis for understanding the occurrence and development of SEC in AF, but also provides recommendations for the daily diet of AF patients with SEC, such as a balanced intake of essential amino acids, avoiding excessive intake of benzoic acid, and intake of appropriate inositol.CLINICAL TRIAL NUMBER: Not applicable.PMID:39550544 | DOI:10.1186/s12872-024-04306-y

Cell Death Differ. 2024 Nov 16. doi: 10.1038/s41418-024-01410-6. Online ahead of print.ABSTRACTAcyl-CoA binding protein (ACBP), also known as diazepam-binding inhibitor (DBI), is an extracellular checkpoint of autophagy. Here, we report that patients with histologically confirmed metabolic-associated steatohepatitis (MASH) or liver fibrosis exhibit elevated levels of circulating ACBP/DBI protein as compared to non-affected controls. Plasma ACBP/DBI strongly correlated with the NAFLD and FIB4 scores in patients, and these correlations were independent of age and body mass index. We studied the capacity of a monoclonal antibody (mAb) neutralizing mouse ACBP/DBI to combat active liver disease in several mouse models, in which steatohepatitis had been induced by four different protocols, namely, (i) methionine/choline-deficient diet, (ii) Western style diet (WD) alone, (iii) WD combined with the hepatotoxic agent CCl4, and (iv) a combination of CCl4 injections and oral ethanol challenge. Injections of anti-ACBP/DBI mAb attenuated histological, enzymological, metabolomic and transcriptomic signs of liver damage in these four models, hence halting or reducing the progression of non-alcoholic and alcoholic liver disease. Steatosis, inflammation, ballooning and fibrosis responded to ACBP/DBI inhibition at the preclinical level. Altogether, these findings support a causal role of ACBP/DBI in MASH and liver fibrosis, as well as the possibility to therapeutically target ACBP/DBI.PMID:39550516 | DOI:10.1038/s41418-024-01410-6

Sci Rep. 2024 Nov 16;14(1):28312. doi: 10.1038/s41598-024-79598-3.ABSTRACTThe remobilization of stored assimilates from stems to seeds plays a pivotal role in augmenting barley yield, particularly under water stress conditions. This study examines the molecular mechanisms underlying stem reserve utilization by conducting a comparative analysis of the proteome and metabolome across three barley contrasting genotypes: Yousef, Morocco, and PBYT17. Evaluations were performed at 21 and 28 days after anthesis (DAA) under both water stress and control conditions. The results indicate that the Yousef genotype exhibits superior remobilization of stem reserves, thereby demonstrating its potential to thrive even in adverse environmental conditions. Utilizing advanced quantitative proteomics and targeted metabolomics, this investigation identified a significant number of metabolites and proteins exhibiting differential accumulation across the genotypes. Specifically, 17 metabolites and 1580 proteins were catalogued, highlighting the intricate biochemical responses to water stress. Noteworthy enzymes such as sucrose synthase, inositol monophosphatase 3, and galactokinase were found to be closely associated with remobilization efficiency. In the drought-tolerant genotype, these enzymes maintained stable levels, in stark contrast to the decline observed in the susceptible genotype. This stability is crucial for promoting seed development through ascorbic acid synthesis and for mitigating oxidative stress, which is exacerbated by drought conditions. The elevated levels of certain metabolites, including glucose 6-phosphate, and UDP-glucose, in the drought-tolerant genotype suggest a robust mechanism for maintaining signalling molecules for carbon availability, which is then instrumental in regulating plant growth and seed size development. The findings from this study strongly imply that the drought-tolerant genotype, through enhanced antioxidant capacity, can effectively produce energy-rich storage compounds, thereby optimizing carbon allocation under water stress. Such insights are invaluable for future breeding strategies aimed at improving barley resilience in the face of climate variability.PMID:39550394 | DOI:10.1038/s41598-024-79598-3

Nat Commun. 2024 Nov 16;15(1):9947. doi: 10.1038/s41467-024-54181-6.ABSTRACTAberrant Ras homologous (Rho) GTPase signalling is a major driver of cancer metastasis, and GTPase-activating proteins (GAPs), the negative regulators of RhoGTPases, are considered promising targets for suppressing metastasis, yet drug discovery efforts have remained elusive. Here, we report the identification and characterization of adhibin, a synthetic allosteric inhibitor of RhoGAP class-IX myosins that abrogates ATPase and motor function, suppressing RhoGTPase-mediated modes of cancer cell metastasis. In human and murine adenocarcinoma and melanoma cell models, including three-dimensional spheroid cultures, we reveal anti-migratory and anti-adhesive properties of adhibin that originate from local disturbances in RhoA/ROCK-regulated signalling, affecting actin-dynamics and actomyosin-based cell-contractility. Adhibin blocks membrane protrusion formation, disturbs remodelling of cell-matrix adhesions, affects contractile ring formation, and disrupts epithelial junction stability; processes severely impairing single/collective cell migration and cytokinesis. Combined with the non-toxic, non-pathological signatures of adhibin validated in organoids, mouse and Drosophila models, this mechanism of action provides the basis for developing anti-metastatic cancer therapies.PMID:39550360 | DOI:10.1038/s41467-024-54181-6

Behav Brain Res. 2024 Nov 14:115339. doi: 10.1016/j.bbr.2024.115339. Online ahead of print.ABSTRACTBACKGROUND: Exercise is acknowledged for its beneficial effects on brain health; however, the intricate underlying molecular mechanisms remain poorly understood.AIMS: This study aimed to explore aerobic exercise-induced metabolic alterations in the brain.METHODS: We conducted an eight-week treadmill running exercise program in two-month-old male C57/BL6J mice. Body weight, serum lipid, glucose levels, and spatial cognition were measured. Spatial metabolomic analysis was performed to compare the metabolomic profiles across different brain regions. Immunohistochemical methods were used to compare the expression of carnitine palmitoyltransferase 1c (CPT1c).RESULTS: Exercise induced significant changes in the analysed metabolomic profiles. There were 904 differentially expressed metabolites (DEMs) detected in the whole brain section. Notable alterations in lipid profiles were observed, and among the 292 lipids detected, there were 74 (25.34%), 85 (29.11%), and 78 (26.71%) lipids differentially expressed in the hippocampus, thalamus, and hypothalamus of the Exe group, respectively. Lipid metabolism related pathways and enzymes were also altered, with L-carnitine and CPT1c upregulated in the three regions (p<0.05), and epinephrine levels decreased in the hippocampus (p<0.05). Furthermore, the vitamin B6 metabolism pathway was altered in the hypothalamus.CONCLUSIONS: This study highlighted the significant changes in lipid metabolism induced by involuntary exercise in the brains of young male mice. Exercise also altered epinephrine levels and the vitamin B12 metabolic pathway in specific brain regions, which indicated the multifaceted effects of exercise on the brain.PMID:39549874 | DOI:10.1016/j.bbr.2024.115339

Microbiol Res. 2024 Oct 28;290:127942. doi: 10.1016/j.micres.2024.127942. Online ahead of print.ABSTRACTMetabolites of plant and microbial origin have a great influence on plant-microbe interactions. Members from Bacillus subtilis are known to produce a plethora of metabolites that shape plant responses towards biotic and abiotic stresses. Similarly, endophyte B. subtilis L1-21 efficiently controls the Huanglongbing (HLB) causing pathogen: Candidatus Liberibacter asiaticus (CLas). However, the molecular mechanisms are highly elusive. Herein, our study highlights the critical role of endophyte L1-21 in planta-produced surfactin in its colonization in citrus plants and regulation of plant-microbe interactions by comparing three gene knockout mutants △srfAA-L1-21, △sfp-L1-21, and △pel-L1-21. All three mutants exhibited reduced pathogen control and colonization efficiency compared to wild-type (WT) L1-21, but knockout mutant deficient of surfactin △srfAA-L1-21 was significantly impaired in the abovementioned functions as compared to △sfp-L1-21 and △pel-L1-21. Further, △srfAA-L1-21 could not activate various metabolic pathways in citrus as WT-L1-21. Integrated metabolomic-transcriptomic analysis reveals that important secondary metabolites such as flavonoids, volatile organic compounds, and lignins were highly accumulated in citrus plants treated with WT-L1-21 as compared to △srfAA-L1-21, highlighting the role of surfactin as an elicitor of the defense system in citrus-HLB pathosystem. Interestingly, auxin-related metabolites and transcripts were also downregulated in △srfAA-L1-21 compared to WT-L1-21 showing that surfactin might also influence plant-microbe interactions through metabolic reprogramming. Further, higher enrichment of Bacilli with WT-L1-21 might corresponds to surfactin-mediated regulation of community-related behavior in Bacilli. To the best of our knowledge, this is the first study reporting the role of surfactin from Bacillus endophyte in metabolic reprogramming in citrus-HLB pathosystem and mounting defense response against CLas pathogen.PMID:39549644 | DOI:10.1016/j.micres.2024.127942

Ecotoxicol Environ Saf. 2024 Nov 15;288:117323. doi: 10.1016/j.ecoenv.2024.117323. Online ahead of print.ABSTRACTBenzo[a]pyrene (BaP), a major harmful component in PM2.5, is widely present in automobile emissions and atmospheric pollution. BaP exposure directly targets the lungs, often resulting in acute lung injury (ALI). However, comprehensive metabolic and transcriptomic profiles related to BaP-induced ALI remain unexplored. To simulate BaP-induced lung injury, we performed intratracheal instillation of BaP. To investigate how BaP exposure affects lung transcriptome and metabolic profiles, we used RNA sequencing and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). We aimed to understand the underlying mechanisms of BaP-induced lung damage. Metabolomics analyses indicated that in BaP-exposed animals, most fatty acids, carbohydrates, and steroids were significantly reduced, whereas most amino acids and organic acids remained unchanged. Analysis of transcriptomics data showed that fatty acid synthesis decreased and fatty acid oxidation increased, suggesting that lipid breakdown occurs after BaP exposure. Additionally, there were increases in oxidative stress system activity and decreases in immune system function. Finally, BaP altered mitochondrial, lipid, immune system, and fatty acid pathways, as indicated by pathway enrichment analyses. These results show that BaP substantially affects metabolic and inflammatory responses, enhancing the broader understanding of the underlying mechanisms of ALI after BaP exposure.PMID:39549570 | DOI:10.1016/j.ecoenv.2024.117323

Comput Biol Med. 2024 Nov 14;184:109393. doi: 10.1016/j.compbiomed.2024.109393. Online ahead of print.ABSTRACTSerum metabolome analysis is essential for identifying disease biomarkers and predicting patient outcomes in precision medicine. Thus, this study aims to compare Ultra-High Performance Liquid Chromatography-High-Resolution Mass Spectrometry (UHPLC-HRMS) with Fourier Transform Infrared (FTIR) spectroscopy in acquiring the serum metabolome of critically ill patients, associated with invasive mechanical ventilation (IMV), and predicting death. Three groups of 8 patients were considered. Group A did not require IMV and survived hospitalization, while Groups B and C required IMV. Group C patients died a median of 5 days after sample harvest. Good prediction models were achieved when comparing groups A to B and B to C using both platforms' data, with UHPLC-HRMS showing 8-17 % higher accuracies (≥83 %). However, developing predictive models using metabolite sets was not feasible when comparing unbalanced populations, i.e., Groups A and B combined to Group C. Alternatively, FTIR-spectroscopy enabled the development of a model with 83 % accuracy. Overall, UHPLC-HRMS data yields more robust prediction models when comparing homogenous populations, potentially enhancing understanding of metabolic mechanisms and improving patient therapy adjustments. FTIR-spectroscopy is more suitable for unbalanced populations. Its simplicity, speed, cost-effectiveness, and high-throughput operation make it ideal for large-scale studies and clinical translation in complex populations.PMID:39549530 | DOI:10.1016/j.compbiomed.2024.109393

Food Chem. 2024 Nov 12;465(Pt 1):141998. doi: 10.1016/j.foodchem.2024.141998. Online ahead of print.ABSTRACTDietary polysaccharides affect the intestinal microorganisms and their metabolites in the host. Clarifying the relationship among polysaccharides, intestinal microflora, and their metabolites is helpful to formulate dietary nutrition intervention strategies. Thus, we explored the regulatory effects of fucoidan on the human gut microbiota and its metabolites. After 48 h of fermentation, fucoidan significantly reduced the pH value in the broth, accompanied by an increase in total short-chain fatty acids, acetic acid, and propanoic acid contents. Fucoidan significantly reduced the relative abundance of Escherichia_shigella and Blebsiella and increased the relative abundance of Bifidobacterium and Lactobacillus. Concurrently, fucoidan altered the composition of intestinal microbial metabolites. These results indicate that fucoidan can regulate the metabolism of the intestinal flora and host, which may contribute to the intestinal health of the host.PMID:39549519 | DOI:10.1016/j.foodchem.2024.141998

Food Chem. 2024 Nov 9;465(Pt 1):141950. doi: 10.1016/j.foodchem.2024.141950. Online ahead of print.ABSTRACTProvence rosé wines have gained global popularity, making them vulnerable to fraud. This study aimed to identify specific chemical markers to detect counterfeit Provence rosé wines. An untargeted LC-MS-based metabolomics analysis was performed on a set of 30 wines classified as "Provence," "Non-Provence," and "Provence imitations." Using the Molnotator workflow, 1300 potential metabolites were generated, and five key chemomarkers were selected through a machine learning pipeline. Further targeted analysis and bioinformatics using in silico MS/MS fragmentation systems confidently annotated three specific chemomarkers for "Provence" rosé: acuminoside, tetrahydroxydimethoxyflavone, and 5'-methoxycastavinol. A composite score using a PLS model combining the 3 chemomarkers effectively distinguished authentic wines, with high accuracy (sensitivity 83.3 %, specificity 100 %, accuracy 93.3 %).PMID:39549510 | DOI:10.1016/j.foodchem.2024.141950

Tuberculosis (Edinb). 2024 Nov 13;149:102577. doi: 10.1016/j.tube.2024.102577. Online ahead of print.ABSTRACTBACKGROUND: Pulmonary tuberculosis (PTB) is the main cause of infection-related mortality and the most common infectious disease that develops resistance to antibiotics. Gut microbiota and their associated metabolites are assumed to induce and influence the development of PTB. However, the alterations of gut microbiota and metabolites in TB patients is currently unclear.METHODS: Fecal samples were collected from 13 PTB patients, 13 LTBI patients, and 13 healthy controls (HC). 16S rRNA sequencing and metabolomics were used to analyze the changes in the intestinal microbiota and the composition of fecal metabolites in groups.RESULTS: Our findings indicated that the α-diversity of the gut microbiota in patients with PTB and LTBI decreases compared to HC, and at the phylum level, the relative abundance of Firmicutes decreases and the relative abundance of Bacteroides increases. And six genera were notably enriched in PTB patients and four in LTBI patients. Metabolomic analysis showed alterations in metabolite levels, such as short-chain fatty acids and amino acids.CONCLUSIONS: we comprehensively explored the changes in the gut microbes and fecal metabolites in patients with PTB and LTBI from the perspective of the gut microbiota, which may provide potential diagnostic biomarkers and therapeutic targets for TB diagnosis and treatment.PMID:39549509 | DOI:10.1016/j.tube.2024.102577

J Plant Physiol. 2024 Nov 9;303:154379. doi: 10.1016/j.jplph.2024.154379. Online ahead of print.ABSTRACTThe plant metabolome is considered an important interface between the genome and its phenome, where it plays a significant role in regulating plant growth in response to various environmental cues. A wide array of specialized metabolites is produced by plants, which are essential for mediating environmental interactions and their adaptation. Notably, enhanced accumulation of these specialized metabolites, particularly plant secondary metabolites (PSMs), is a part of the chemical defense response that is directly linked to improved stress tolerance. Therefore, exploring the genetic diversity underlying the immense variation of the secondary metabolite pool could unravel the adaptation mechanisms in plants against different environmental stresses. The post-genomic profiling platforms have enabled the exploration of the link between metabolic diversity and important agronomic traits. The current review focuses on the major achievements and future challenges associated with plant secondary metabolite (PSM) research in graminaceous crops using advanced omics approaches. Given this, we briefly summarize different strategies adopted to explore the genetic diversity and evolution of PSMs in cereal crops. Further, we have discussed the recent technological advancements to integrate multi-omics approaches linking the metabolome diversity with the genome, transcriptome, and proteome of these crops under stress. Combining these data with phenomics (the omics of phenotypes) provides a holistic view of how plants respond to stress. Next, we outlined the genetic manipulation studies performed so far in cereals to engineer secondary metabolic pathways for enhanced stress tolerance. In summary, our review provides new insight into developing genetic and genomic trends in exploring the secondary metabolite diversity in graminaceous crops and discusses how this information can be utilized in designing strategies to generate future stress-resilient crops.PMID:39549316 | DOI:10.1016/j.jplph.2024.154379