PubMed

Metabolites. 2024 Dec 6;14(12):686. doi: 10.3390/metabo14120686.ABSTRACTVitamin D deficiency is one of the most common metabolic disorders in the European population. A low level of 25-OH vitamin D3 is related to an elevated risk of myocardial infarction (MI). The aim of our study was to examine the relationship between calcidiol and calcitriol serum concentration and left ventricular ejection fraction early after interventional treatment for acute coronary syndrome. A total of 80 patients diagnosed with MI, who underwent primary percutaneous coronary intervention, were included in the study. Blood samples for calcidiol, calcitriol, and vitamin D-binding protein were obtained 24 h after primary PCI and were measured using an enzyme-linked immunosorbent assay. Only 9% of patients had a proper level of 25-OHD3 in the serum (30-80 ng/mL). A total of 16% of patients revealed a suboptimal concentration of 25-OHD3 (20-30 ng/mL), and in 75% of patients, the concentration of 25-OHD3 was lower than 20 ng/mL. Moreover, patients with left ventricle ejection fraction of <40% had significantly lower concentrations of calcidiol and calcitriol. A low calcitriol serum concentration affects post-MI left ventricle ejection fraction early after myocardial infarction onset. It seems that 1.25(OH)D3 may contribute to acute myocardial infarction; however, there are insufficient clinical trials related to this topic, and the available evidence is mainly from in vitro studies. We hope these preliminary reports will provide a better understanding of post-MI.PMID:39728467 | DOI:10.3390/metabo14120686

Metabolites. 2024 Dec 6;14(12):685. doi: 10.3390/metabo14120685.ABSTRACTBACKGROUND: Bloodstream infections (BSIs) pose a great challenge to treating patients, especially those with underlying diseases, such as immunodeficiency diseases. Early diagnosis helps to direct precise empirical antibiotic administration and proper clinical management. This study carried out a serum metabolomic analysis using blood specimens sampled from patients with a suspected infection whose routine culture results were later demonstrated to be positive.METHODS: A liquid chromatograph-mass spectrometry-based metabolomic analysis was carried out to profile the BSI serum samples. The serum metabolomics data could be used to successfully differentiate BSIs from non-BSIs.RESULTS: The major classes of the isolated pathogens (e.g., Gram-positive and Gram-negative bacteria) could be differentiated using our optimized statistical algorithms. In addition, by using different machine-learning algorithms, the isolated pathogens could also be classified at the species levels (e.g., Escherichia coli and Klebsiella pneumoniae) or according to their specific antibiotic-resistant phenotypes (e.g., extended-spectrum β-lactamase-producing and non-producing phenotypes) if needed.CONCLUSIONS: This study provides an early diagnosis method that could be an alternative to the traditional time-consuming culture process to identify BSIs. Moreover, this metabolomics strategy was less affected by several risk factors (e.g., antibiotics administration) that could produce false culture results.PMID:39728466 | DOI:10.3390/metabo14120685

Metabolites. 2024 Dec 5;14(12):682. doi: 10.3390/metabo14120682.ABSTRACTBACKGROUND: In recent years, titanium dioxide (TiO2) nanoparticles (NPs) have been widely used in various industries due to their favorable chemical properties, and their contamination of the environment has attracted much attention, especially to aquatic animals.METHODS: Therefore, we assessed the impact of TiO2 NPs (5 mg/L) on the marine bivalve, pearl oyster (Pinctada fucata martensii), especially gill metabolism. Pearl oysters were exposed to seawater containing 5 mg/L TiO2 NPs for 14 days, followed by 7 days of recovery in untreated seawater. Gill tissues and hepatopancreatic tissues were sampled on days 0, 14, and 21 of the experiment named C0, E14, and R7, respectively.RESULTS: Metabolomic analysis identified 102 significantly different metabolites (SDMs) on gills tissue in pearl oysters following exposure to TiO2 NPs (C0 vs. E14). Compared with group C0, group E14 had 76 SDMs (such as acetylcholine, itaconic acid, citric acid, and taurine) with higher concentrations and 26 (including L-arginine and isobutyryl-L-carnitine) with lower concentrations. KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis showed that these SDMs enriched 28 pathways, including glycine, serine, and threonine metabolism, neuroactive ligand-receptor interaction, and taurine and hypotaurine metabolism. In addition, 116 SDMs were identified in E14 and R7 pearl oysters. Compared with group E14, group R7 had 74 metabolites (such as acetylcholine, 6-phosphogluconic acid, isocitric acid, and itaconic acid) with higher concentrations and 42 (including uracil, glycerophosphocholine, N-Acetyl-D-glucosamine) with lower concentrations. The SDMs identified between E14 and R7 enriched 25 pathways, including the pentose phosphate pathway, glutathione metabolism, and citrate cycle (TCA cycle). In addition, analysis of the energy metabolism-associated enzymes revealed that exposure to TiO2 NPs reduced Ca2+/Mg2+-ATPase, Na+/K+-ATPase, and Total-ATPase activities.CONCLUSIONS: These findings suggested that TiO2 NPs may inhibit the energy metabolism function of gill and hepatopancreas of pearl oysters. Meanwhile, TiO2 NPs may affect the normal functioning of immune and osmoregulatory functions of pearl oysters gill and even may lead to oxidative stress and neurotoxicity. Therefore, this study may provide a reference for analyzing the bioadaptation of marine bivalves to TiO2 NPs and the potential negative effects of TiO2 NPs on bivalves.PMID:39728463 | DOI:10.3390/metabo14120682

Metabolites. 2024 Dec 4;14(12):681. doi: 10.3390/metabo14120681.ABSTRACTBACKGROUND AND AIM: The prevalence and adverse outcomes of metabolic dysfunction associated with steatotic liver disease (MAFLD) are increasing. The changes in the gut microbiota and metabolites associated with metabolic dysfunction-associated steatohepatitis (MASH) are regarded as an essential part of the progression of MAFLD. This study aimed to identify the gut microbiota and metabolites involved in the development of MAFLD in patients.METHOD: This study enrolled 90 patients (healthy controls, HC: n = 30; MASH: n = 30; MASH-related cirrhosis, MC: n = 30), and their fecal samples were collected for 16S rRNA sequencing and non-targeted LC-MS/MS metabolomics analysis. Data preprocessing and statistical analyses were performed using QIIME2 software, Pynast, QIIME2 package, Progenesis QI, and R program.RESULTS: The abundance of Prevotellaceae at the family level and Prevotella at the genus level was lower in the MASH and NC samples than in the HC samples. Both Prevotellaceae and Prevotella showed the strongest correlation with MASH progression via random forest analysis. Untargeted metabolomics was used to quantitatively screen for discrepant metabolites in the stool samples from the three groups. Linolenic acid (LA)-related metabolite levels were significantly lower in MASH and NC samples. Associations between Prevotella- or LA-related metabolites and liver function were discovered. A high abundance of Prevotella was associated with LA-related metabolites and MASH.CONCLUSION: This study identified that gut microbiota and metabolites are associated with MASH-related metabolic dysfunction. LA and Prevotella are depleted during MASH progression, and additional supplementation with Prevotella may be a potential strategy for the future treatment of MAFLD.PMID:39728462 | DOI:10.3390/metabo14120681

Metabolites. 2024 Dec 4;14(12):680. doi: 10.3390/metabo14120680.ABSTRACTBackground: General control nonderepressible 5 (Gcn5) is a lysine acetyltransferase (KAT) that is evolutionarily conserved across eukaryotes, with two homologs (Kat2a and Kat2b) identified in humans and one (Gcn5) in Drosophila. Gcn5 contains a P300/CBP-associated factor (PCAF) domain, a Gcn5-N-acetyltransferase (GNAT) domain, and a Bromodomain, allowing it to regulate gene expression through the acetylation of both histone and non-histone proteins. In Drosophila, Gcn5 is crucial for embryonic development, with maternal Gcn5 supporting early development. However, the functional mechanisms of Gcn5 after the depletion of maternal deposits remain unclear. Methods: Our study employed the Gal4/UAS-RNAi system to achieve whole-body or heart-specific Gcn5 knockdown in Drosophila and selected 96-hour-old surviving larvae for transcriptomic and metabolomic analyses. Results: Omics results revealed that Gcn5 knockdown significantly impacts various metabolic pathways, as well as lysosomes, non-homologous end-joining, Toll and Imd signaling pathways, and circadian rhythms, among others. Furthermore, defects in chitin synthesis may be associated with impaired pupation. Additionally, heart-specific Gcn5 knockdown affected cardiac physiology but appeared to have a potential protective effect against age-related cardiac decline. Conclusions: These findings deepen our understanding of Gcn5's roles in Drosophila development and provide valuable insights for developing Gcn5-targeted therapies, particularly considering its involvement in various human diseases.PMID:39728461 | DOI:10.3390/metabo14120680

Metabolites. 2024 Dec 3;14(12):677. doi: 10.3390/metabo14120677.ABSTRACTObjectives: This systematic review evaluates the effectiveness of fecal microbiota transplantation (FMT) in treating Clostridioides difficile infection (CDI) in mouse models using a metabolomics-based approach. Methods: A comprehensive search was conducted in three databases (PubMed, Scopus, Google Scholar) from 10 April 2024 to 17 June 2024. Out of the 460 research studies reviewed and subjected to exclusion criteria, only 5 studies met all the inclusion criteria and were analyzed. Results: These studies consistently showed that FMT effectively restored gut microbiota and altered metabolic profiles, particularly increasing short-chain fatty acids (SCFAs) and secondary bile acids, which inhibited C. difficile growth. FMT proved superior to antibiotic and probiotic treatments in re-establishing a healthy gut microbiome, as evidenced by significant changes in the amino acid and carbohydrate levels. Despite its promise, variability in the outcomes-due to factors such as immune status, treatment protocols, and donor microbiome differences-underscores the need for standardization. Rather than pursuing immediate standardization, the documentation of factors such as donor and recipient microbiome profiles, preparation methods, and administration details could help identify optimal configurations for specific contexts and patient needs. In all the studies, FMT was successful in restoring the metabolic profile in mice. Conclusions: These findings align with the clinical data from CDI patients, suggesting that FMT holds potential as a therapeutic strategy for gut health restoration and CDI management. Further studies could pave the way for adoption in clinical practice.PMID:39728458 | DOI:10.3390/metabo14120677

Metabolites. 2024 Dec 3;14(12):675. doi: 10.3390/metabo14120675.ABSTRACTBACKGROUND: Advancements in metabolomic technologies have revolutionized our understanding of feed efficiency (FE) in livestock, offering new pathways to enhance both profitability and sustainability in ruminant production.METHODS: This review offers a critical and systematic evaluation of the metabolomics methods used to measure and assess FE in ruminants. We conducted a comprehensive search of PubMed, Web of Science, and Scopus databases, covering publications from 1971 to 2023. This review synthesizes findings from 71 studies that applied metabolomic approaches to uncover the biological mechanisms driving interindividual variations in FE across cattle, sheep, goats, and buffaloes.RESULTS: Most studies focused on cattle and employed targeted metabolomics to identify key biomarkers, including amino acids, fatty acids, and other metabolites linked to critical pathways such as energy metabolism, nitrogen utilization, and muscle development. Despite promising insights, challenges remain, including small sample sizes, methodological inconsistencies, and a lack of validation studies, particularly for non-cattle species.CONCLUSIONS: By leveraging state-of-the-art metabolomic methods, this review highlights the potential of metabolomics to provide cost-effective, non-invasive molecular markers for FE evaluation, paving the way for more efficient and sustainable livestock management. Future research should prioritize larger, species-specific studies with standardized methods to validate identified biomarkers and enhance practical applications in livestock production systems.PMID:39728456 | DOI:10.3390/metabo14120675

Metabolites. 2024 Dec 2;14(12):671. doi: 10.3390/metabo14120671.ABSTRACTBackground: Electronic and electrical waste (e-waste) production has emerged to be of global environmental public health concern. E-waste workers, who are frequently exposed to hazardous chemicals through occupational activities, face considerable health risks. Methods: To investigate the metabolic and exposomic changes in these workers, we analyzed whole blood samples from 100 male e-waste workers and 49 controls from the GEOHealth II project (2017-2018 in Accra, Ghana) using LC-MS/MS. A specialized computational workflow was established for exposomics data analysis, incorporating two curated reference libraries for metabolome and exposome profiling. Two feature detection algorithms, asari and centWave, were applied. Results: In comparison to centWave, asari showed better sensitivity in detecting MS features, particularly at trace levels. Principal component analysis demonstrated distinct metabolic profiles between e-waste workers and controls, revealing significant disruptions in key metabolic pathways, including steroid hormone biosynthesis, drug metabolism, bile acid biosynthesis, vitamin metabolism, and prostaglandin biosynthesis. Correlation analyses linked metal exposures to alterations in hundreds to thousands of metabolic features. Functional enrichment analysis highlighted significant perturbations in pathways related to liver function, vitamin metabolism, linoleate metabolism, and dynorphin signaling, with the latter being observed for the first time in e-waste workers. Conclusions: This study provides new insights into the biological impact of prolonged metal exposure in e-waste workers.PMID:39728452 | DOI:10.3390/metabo14120671

Metabolites. 2024 Dec 2;14(12):670. doi: 10.3390/metabo14120670.ABSTRACTBackground: Diabetic encephalopathy (DE) is a neurological complication of diabetes marked by cognitive decline and complex metabolic disturbances. Salidroside (SAL), a natural compound with antioxidant and neuroprotective properties, has shown promise in alleviating diabetic complications. Exploring the spatial metabolic reprogramming in DE and elucidating SAL's metabolic effects are critical for deepening our understanding of its pathogenesis and developing effective therapeutic strategies. Methods: Air-flow-assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI) was employed to investigate spatial metabolic alterations in the brains of db/db mice, a spontaneous DE model. The mice were treated with SAL (30 and 150 mg/kg, orally) for 12 weeks. Differential metabolites were identified and characterized using high-resolution mass spectrometry and validated against public databases. Results: Our AFADESI-MSI analysis revealed significant changes in 26 metabolites in the brains of DE mice compared to the controls. These metabolic changes indicated disruptions in glucose, glutamate-glutamine, nucleotide, lipid, choline, aspartate, and L-carnitine metabolism. Notably, glucose 6-phosphate (G6P), glutamine, adenosine, L-carnitine, and choline exhibited similar trends in both db/db mice and STZ-induced rat models of DE, suggesting their potential as reliable biomarkers. Twelve weeks of SAL treatment demonstrated a positive regulatory effect on glucose metabolism, the glutamate-glutamine cycle, and lipid metabolism. Conclusions: This study identifies key metabolic alterations in DE and demonstrates the therapeutic potential of SAL in modulating these disturbances, offering valuable insights for targeted interventions in diabetic complications.PMID:39728451 | DOI:10.3390/metabo14120670

Metabolites. 2024 Dec 1;14(12):665. doi: 10.3390/metabo14120665.ABSTRACTBackground: The rapid development of refrigerated transportation technology for fresh vegetables has extended their shelf life. Some vegetables may appear undamaged on the surface, but their freshness may have decreased, often resulting in the phenomenon of passing off inferior vegetables as good. It is very important to establish a detection method for identifying and assessing the freshness of vegetables. Methods: Therefore, based on metabolomics methods, this study innovatively employed UHPLC-Q-Exactive Orbitrap MS and GC-MS techniques to investigate the metabolites in the refrigerated storage of four vegetables, namely chard (Beta vulgaris var. cicla L), lettuce (Lactuca sativa var. ramose Hort.), crown daisy (Glebionis coronaria (L.) Cass. ex Spach), and tomato (Solanum lycopersicum L.), exploring key biomarkers for assessing their freshness. UPLC-TQ MS was used for the quantitative analysis of key metabolites. Results: The results showed that arginine biosynthesis and the metabolism of alanine, aspartate, and glutamate are key pathways in vegetable metabolism. Four key metabolites were selected from chard, five from lettuce, three from crown daisy, and five from tomato. Conclusions: Comparing the content of substances such as alanine and arginine can help infer the freshness and nutritional value of the vegetables, providing important references for detecting spoilage, determining storage time, and improving transportation conditions. This research holds significant relevance for the vegetable transportation industry.PMID:39728447 | DOI:10.3390/metabo14120665

Metabolites. 2024 Dec 1;14(12):666. doi: 10.3390/metabo14120666.ABSTRACTBackground: The introduction of benchtop NMR instruments has made NMR spectroscopy a more accessible, affordable option for research and industry, but the lower spectral resolution and SNR of a signal acquired on low magnetic field spectrometers may complicate the quantitative analysis of spectra. Methods: In this work, we compare the performance of multiple neural network architectures in the task of converting simulated 100 MHz NMR spectra to 400 MHz with the goal of improving the quality of the low-field spectra for analyte quantification. Multi-layered perceptron networks are also used to directly quantify metabolites in simulated 100 and 400 MHz spectra for comparison. Results: The transformer network was the only architecture in this study capable of reliably converting the low-field NMR spectra to high-field spectra in mixtures of 21 and 87 metabolites. Multi-layered perceptron-based metabolite quantification was slightly more accurate when directly processing the low-field spectra compared to high-field converted spectra, which, at least for the current study, precludes the need for low-to-high-field spectral conversion; however, this comparison of low and high-field quantification necessitates further research, comparison, and experimental validation. Conclusions: The transformer method of NMR data processing was effective in converting low-field simulated spectra to high-field for metabolomic applications and could be further explored to automate processing in other areas of NMR spectroscopy.PMID:39728446 | DOI:10.3390/metabo14120666

Metabolites. 2024 Dec 1;14(12):664. doi: 10.3390/metabo14120664.ABSTRACTBackground/Objectives: Essential oils (EOs) have been exploited by humans for centuries, but many sources remain poorly investigated, mainly due to the low yields associated with conventional extraction. Recently, new techniques have been developed, like solvent-free microwave extraction (SFME), able to enhance efficiency and sustainability. The use of Papaver rhoeas L. in traditional medicine has led researchers to investigate non-volatile fractions, but there are little data available on EOs. Methods: In the present work, we prepared EOs from the petals and leaves of P. rhoeas by SFME. GC/MS analysis of EOs revealed the presence of 106 compounds belonging to 13 different classes. Isomers of the different alkenes were identified thanks to an alkylthiolation reaction. Results: The results highlighted a predominance of saturated and unsaturated hydrocarbons, alcohols, and esters that might suggest a specific relationship with pollinators. Each population has been compared using PCA, heatmap, and barplot tools, highlighting differences in terms of composition by both comparing leaves and flowers and hill and lowland samples. Furthermore, cantharidin, a metabolite usually produced by insects, was detected in the flowers, possible present for attractiveness purposes. Conclusions: These results could contribute to ensuring a better understanding of the pollination process and of the biological activities of EOs from P. rhoeas.PMID:39728445 | DOI:10.3390/metabo14120664

Metabolites. 2024 Dec 1;14(12):663. doi: 10.3390/metabo14120663.ABSTRACTBackground: Natto is a fermented product derived from soybeans through the action of Bacillus subtilis natto, possessing various pharmacological and health-promoting properties. However, due to the absence of large-scale and systematic investigations into its metabolite profile, the mechanisms governing the biological functions and flavor characteristics of natto remain incompletely elucidated. Methods: In this study, a comprehensive, widely targeted metabolome analysis was conducted using UHPLC-MS/MS to compare soybeans and natto. Results: A total of 569 metabolites were identified, of which 160 exhibited differential expression between natto and soybeans, including 28 amino acids and their derivatives, 19 flavonoids, 18 alkaloids, and 10 nucleotides and their derivatives. Pathway enrichment analysis further demonstrated significant differences in the metabolic pathways between natto and soybeans, with these 160 differentially expressed metabolites primarily distributed across 40 metabolic pathways. KEGG pathway enrichment analysis of natto metabolites revealed that the majority of these mapped to three key metabolic pathways. Variations in the content of flavonoids and alkaloids, as well as changes in amino acid and saccharide composition and abundance, were found to collectively contribute to the distinctive flavor and biological functionality of natto. Conclusions: This study lays the foundation for future efforts to enhance the quality of natto.PMID:39728444 | DOI:10.3390/metabo14120663

Metabolites. 2024 Nov 28;14(12):661. doi: 10.3390/metabo14120661.ABSTRACTBACKGROUND: Jujube is a homologous herb of medicine and food, and polyphenols are key in determining the functional effects of jujubes.METHODS: In this study, characteristic polyphenols in 15 varieties of Chinese jujubes were investigated based on untargeted metabolomics.RESULTS: The results showed that a total of 79 characteristic polyphenols were identified in the 15 varieties of Chinese jujube, and 55 characteristic polyphenols such as syringetin, spinosin and kaempferol were reported for the first time. Scopoletin (63.94% in LZYZ), pectolinarin (22.63% in HZ) and taxifolin (19.69% in HZ) contributed greatly and presented significant (p < 0.05) differences in the 15 varieties of Chinese jujubes. HZ was characterized by pectolinarin, erianin and wogonoside, while XSHZ, NYDZ and RQHZ, with similar polyphenol profiles, were characterized by (+)-catechin, combretastatin A4 and tectorigenin. JSBZ, HMDZ, TZ, JCJZ and HPZ had similar polyphenol profiles of galangin, isoferulic acid and hydroxysafflor yellow A.CONCLUSIONS: Metabolomics is critical in grasping the full polyphenol contents of jujubes, and the differences in the polyphenol profiles and characteristic individual polyphenols of the 15 varieties of Chinese jujubes were well analyzed by principal component analysis (PCA).PMID:39728442 | DOI:10.3390/metabo14120661

Metabolites. 2024 Nov 27;14(12):660. doi: 10.3390/metabo14120660.ABSTRACTBackground: Clinical findings have shown a negative correlation between the severity of depressive symptoms and serum uric acid levels in men, yet the role of metabolic regulation in the pathophysiology of depression remains largely unknown. Methods: In this study, we utilized an acute restraint-stress-induced male rat model of depression to investigate biochemical changes through NMR-based metabolomics combined with serum biochemical analysis. Additionally, we employed qPCR, immunoblotting, and enzyme activity assays to assess the expression and activity of xanthine oxidoreductase, the rate-limiting enzyme in uric acid production. Results: Our findings indicate the following: (1) restraint stress is a valid method for inducing a depressive phenotype in rats; (2) depressive rats exhibit decreased NAD(P) levels in the liver and increased nicotinamide N-oxide and nicotinate levels in urine, accompanied by decreased levels of uric acid, allantoin, and allantoic acid in serum or tissues; (3) xanthine dehydrogenase activity is diminished in depressive rats without corresponding changes in gene or protein expression. Conclusion: The increased urinary excretion of NAD(P) precursors results in reduced hepatic NAD(P) levels, thereby suppressing NAD-dependent xanthine dehydrogenase activity and diminishing the production of uric acid and its downstream metabolites (allantoin and allantoic acid).PMID:39728441 | DOI:10.3390/metabo14120660

Metabolites. 2024 Nov 25;14(12):658. doi: 10.3390/metabo14120658.ABSTRACTBackground: The rise of drug-resistant Leishmania strains presents a significant challenge in the treatment of Leishmaniasis, a neglected tropical disease. Extracellular vesicles (EVs) produced by these parasites have gained attention for their role in drug resistance and host-pathogen interactions. Methods: This study developed and applied a novel lipidomics workflow to explore the lipid profiles of EVs from three types of drug-resistant Leishmania infatum strains compared to a wild-type strain. EVs were isolated through ultracentrifugation, and their lipid content was extracted using a modified Matyash protocol. LC-MS analysis was performed, and data processing in MS-DIAL enabled lipid identification and quantification. Statistical analysis in MetaboAnalyst revealed strain-specific lipid alterations, highlighting potential links between lipid composition and drug resistance mechanisms. Results: Our results show distinct alterations in lipid composition associated with drug resistance. Specifically, drug-resistant strains exhibited reduced levels of phosphatidylcholine (PC) and phosphatidylglycerol (PG), particularly in the amphotericin B-resistant strain LiAmB1000.1. Sterol and glycerolipid species, including cholesteryl ester (CE) and triacylglycerol (TG) were also found to be diminished in LiAmB1000.1. These changes suggest significant lipid remodeling under drug pressure, potentially altering the biophysical properties of EV membranes and their capacity for molecule transfer. Furthermore, the lipidomic profiles of EVs from the other resistant strains, LiSb2000.1 and LiMF200.5, also displayed unique alterations, underscoring strain-specific adaptations to different drug resistance mechanisms. Conclusions: These significant alterations in lipid composition suggest potential lipid-based mechanisms underlying drug resistance in Leishmania, providing new avenues for therapeutic intervention.PMID:39728439 | DOI:10.3390/metabo14120658

Metabolites. 2024 Nov 25;14(12):656. doi: 10.3390/metabo14120656.ABSTRACTBackground/Objective: A dysregulated metabolism has been studied as a key aspect of the COVID-19 pathophysiology, but its longitudinal progression in severe cases remains unclear. In this study, we aimed to investigate metabolic dysregulation over time in patients with severe COVID-19 requiring mechanical ventilation (MV). Methods: In this single-center, prospective, observational study, we obtained 236 serum samples from 118 adult patients on MV in an ICU. The metabolite measurements were performed using capillary electrophoresis Fourier transform mass spectrometry, and we categorized the sampling time points into three time zones to align them with the disease progression: time zone 1 (T1) (the hyperacute phase, days 1-3 post-MV initiation), T2 (the acute phase, days 4-14), and T3 (the chronic phase, days 15-30). Using volcano plots and enrichment pathway analyses, we identified the differential metabolites (DMs) and enriched pathways (EPs) between the survivors and non-survivors for each time zone. The DMs and EPs were further grouped into early-stage, late-stage, and consistent groups based on the time zones in which they were detected. Results: With the 566 annotated metabolites, we identified 38 DMs and 17 EPs as the early-stage group, which indicated enhanced energy production in glucose, amino acid, and fatty acid metabolisms in non-survivors. As the late-stage group, 84 DMs and 10 EPs showed upregulated sphingolipid, taurine, and tryptophan-kynurenine metabolisms with downregulated steroid hormone synthesis in non-survivors. Three DMs and 23 EPs in the consistent group showed more pronounced dysregulation in the dopamine and arachidonic acid metabolisms across all three time zones in non-survivors. Conclusions: This study elucidated the temporal differences in metabolic dysregulation between survivors and non-survivors of severe COVID-19, offering insights into its longitudinal progression and disease mechanisms.PMID:39728437 | DOI:10.3390/metabo14120656

Metabolites. 2024 Nov 25;14(12):654. doi: 10.3390/metabo14120654.ABSTRACTBackground:Disanthus cercidifolius var. longipes is an ancient relic plant unique to China. However, the typical shade-loving plant is largely exposed to the sun, which poses a major challenge to its conservation. Methods: This study explored dynamic changes in primary and secondary metabolites in D. cercidifolius leaves at different stages of development, combining metabolomics and transcriptome analysis to discuss the differentially accumulated metabolites (DAMs) and differentially expressed genes (DEGs). Results: The DAMs and DEGs were enriched in pathways related to photosynthesis, carbon (C) metabolism, anthocyanin synthesis, plant hormone signal transduction, and flavonoid synthesis. At the initial stage of leaf development, many primary metabolites were synthesized in the leaves. Before leaf maturity, many primary metabolites were converted into secondary metabolites. Combined transcriptome and metabolome analysis showed that the metabolites and genes related to anthocyanin synthesis and flavonoid metabolism were upregulated. In contrast, the genes related to C metabolism and C fixation were downregulated. After leaf maturity, photosynthetic capacity increased, total flavonoid content peaked (implying the strongest photoprotection capacity), and the transformation of anthocyanins and flavonoids was weakened. Conclusions: Light intensity indirectly affects the accumulation of the primary and secondary metabolism of D. cercidifolius. With the enhancement of photoprotection, the photosynthetic energy capacity decreases. It is, therefore, inferable that D. cercidifolius has shading properties and achieves a stable nutrient supply during growth and development through these strategies. Thus, D. cercidifolius protection requires a shaded environment.PMID:39728434 | DOI:10.3390/metabo14120654

Metabolites. 2024 Nov 22;14(12):650. doi: 10.3390/metabo14120650.ABSTRACTBACKGROUND AND OBJECTIVES: Histomonas meleagridis, the causative agent of histomonosis (i.e., blackhead disease), threatens the poultry industry with serious economic losses due to its high mortality and morbidity in turkey and chicken flocks. In vitro studies are complicated by the inability to culture the parasite axenically. Histomonas meleagridis has been propagated in Dwyer's media, which contains a starch source and serum, for over 50 years. The presence of insoluble starch component in Dwyer's media represents an obstacle for the commercialization of such media, and the role of starch in media is poorly understood.METHODS: To investigate the intracellular metabolomic differences in H. meleagridis and undefined bacteria grown in Dwyer's media with rice starch (SD) and without rice starch (NR), we conducted a global metabolomics analysis using ultra-high-performance liquid chromatography-high-resolution mass spectrometry.RESULTS: SD significantly supported the growth of H. meleagridis compared to NR. There was no significant difference in bacterial growth between SD and NR media at various timepoints. From the intracellular metabolic analysis of samples collected from the SD and NR media, a total of 170 known metabolites were identified. H. meleagridis appears to be the major contributor to global metabolic differences.CONCLUSIONS: We found that riboflavin had the highest variable importance in the projection score, and metabolites involved in riboflavin biosynthesis significantly contributed to the differences between SD and NR in the media immediately after the inoculation of H. meleagridis and undefined bacteria, warranting further investigations into the role of riboflavin biosynthesis in H. meleagridis growth.PMID:39728431 | DOI:10.3390/metabo14120650

Metabolites. 2024 Nov 21;14(12):649. doi: 10.3390/metabo14120649.ABSTRACTBackground: Ammonia, a ubiquitous contaminant in aquatic ecosystems, poses multifaceted threats to fish species at elevated concentrations. Methods: In order to investigate the toxic effects of chronic ammonia stress on the liver of juvenile Micropterus salmoides, the present experiment was conducted to investigate the differences in changes in liver tissue structure, enzyme activities, and metabolomes after 28 days of ammonia exposure (0, 4, 8, and 16 mg/L). Results: The findings revealed that ammonia exposure induced significant oxidative stress in the liver, manifesting in decreased activities of antioxidant enzymes SOD and GSH-Px, elevated levels of GSH, GST, and MDA, and heightened activities of immune enzymes LZM, ALP, and ACP. An increase in ammonia concentration exacerbated liver tissue damage. Metabolome analysis further unveiled perturbations in liver metabolites of Micropterus salmoides exposed to ammonia, with Ala-His emerging as a potentially pivotal functional substance under chronic stress. Specifically, the 4 mg/L group responded to ammonia toxicity by augmenting GSH and L-Carnosine levels, the 8 mg/L group detoxified via upregulation of L-Glutamine, and the 16 mg/L group mitigated toxicity through the urea synthesis pathway. Conclusions: This research offers preliminary insights into the toxicological responses of Micropterus salmoides under chronic ammonia stress. It is suggested that the duration of ammonia concentration exceeding 4 mg/L in high-density aquaculture should not exceed 7 days.PMID:39728430 | DOI:10.3390/metabo14120649