Search Results (3,596)

Polystyrene nanoplastics (NPs) threaten agricultural ecosystems and the food chain; however, their hepatotoxicity in chickens, a key poultry species, remains unclear. This study investigated the effects of chronic NP exposure on hepatic metabolism to evaluate food safety risks in poultry products. Chickens were orally exposed to 100 nm polystyrene NPs via feed for 120 days. Histopathological evaluation, serum biochemical analysis revealed hepatotoxicity in NP-exposed poultry, characterized by histopathological liver injury, elevated lipid droplet accumulation, significantly increased alanine aminotransferase (ALT) activity, and elevated triglyceride (TG) levels (p < 0.05). Untargeted LC-MS/MS Metabolomics profiling identified 193 differentially abundant metabolites—predominantly organic acids and lipids—with L-leucine and NADH emerging as pivotal metabolic hubs. A KEGG pathway analysis demonstrated significant enrichment in purine metabolism and oxidative phosphorylation, while a gene set enrichment analysis (GSEA) confirmed the suppression of ABC transporters. Notably, the key biomarkers 9-cis-retinal and phenylalanyl phenylalanine were significantly altered, reflecting metabolic disturbances linked to NPs exposure. Overall, this study characterized exposure-associated metabolic signatures and established NP-induced hepatic injury phenotypes in poultry production systems. Full article

Epithelial–mesenchymal transition (EMT) is a key process in cancer progression and fibrogenesis. In this study, EMT was induced in Huh7 hepatocellular carcinoma cells via TGF-β1 treatment, and the resulting lipidomic and metabolomic alterations were characterized. Morphological changes and protein marker analyses confirmed the transition to a mesenchymal phenotype, with reduced E-cadherin and increased vimentin and N-cadherin expression. Lipidomic profiling revealed a dose-dependent reorganization of membrane lipids, with a pronounced increase in the levels of ceramides, cholesteryl esters, and lysophospholipids, consistent with alterations in membrane structure, potential cellular stress, and modulation of inflammatory pathways. Changes in the content of phospholipid classes, including phosphatidylethanolamines and phosphatidylserines, indicate possible variations in membrane dynamics and potentially point to modifications in mitochondrial function, cellular stress responses, and redox balance. Metabolomic analysis further indicates an alteration of choline and phosphatidylcholine metabolism, consistent with a shift from de novo membrane synthesis toward lipid turnover. Reduced glycolytic capacity and modified acylcarnitine levels indicated impaired metabolic flexibility and mitochondrial efficiency. The integration of phenotypic, lipidomic, and metabolomic data suggests that TGF-β1 induces EMT and drives a coordinated metabolic reprogramming. These findings highlight the involvement of lipid and energy metabolism in sustaining EMT and suggest that specific metabolic reprogramming events characterize the mesenchymal shift in hepatocellular carcinoma. By exploring this process in a tumor-specific context, we aim to deepen our understanding of EMT complexity and its implications for tumor progression and therapeutic vulnerability. Full article

Background/Objectives: The synergistic effects of epigallocatechin gallate (EGCG) and taurine in modulating lipid metabolism abnormalities in rats were investigated, and along with their potential mechanisms. Methods/Result: Compared to intervention with EGCG/taurine alone, EGCG combined with taurine (1:3) not only reduced triglyceride (TG) generation in HepG2 cells (46.2%, 75.2%, respectively), but also significantly decreased the total cholesterol (TC) (33.3%, 41.8%), low-density lipoprotein cholesterol (LDL-C) (32.3%, 29.2%) in rats, while the high-density lipoprotein cholesterol (HDL-C) increased by 12.7% and 33.5%. In addition, the combination of EGCG and taurine not only inhibited lipogenic enzyme activity, but also enhanced the levels of lipid catabolic enzymes and antioxidant enzymes, and alleviated hepatic injury. Furthermore, it significantly modulated gut microbiota composition by altering the abundances of Bacteroidetes, Firmicutes, and Proteobacteria, improving intestinal flora balance. Metabolomic profiling showed that reducing N-linoleoyl proline, cortisol, and 3-isocholanolic acid, and increasing phospholipid metabolites are the main ways methods for normalizing lipid metabolism in rats. The combination also elevated short-chain fatty acid (SCFA) synthesis, preserving intestinal barrier integrity; it also promoted lipid catabolism and energy expenditure via activating Peroxisome proliferator- activated receptor alpha (PPARα) and suppressing hepatic fatty acid synthase (FAS)- mediated lipogenesis. Conclusion: These findings indicated that EGCG and taurine can synergistically regulate lipid metabolism abnormalities, which may offer a strategy for regulating lipid metabolism anomalies. Full article

Somatic hybridization represents a powerful tool for generating novel chemotypes with enhanced biosynthetic capabilities. This study provides the first comprehensive phytochemical characterization of interspecific somatic hybrids between Gentiana cruciata L. and Gentiana tibetica King ex Hook.f., two medicinally important yet regionally rare gentians. A total of 107 compounds were detected using UHPLC-DAD-ESI-MS³, of which 31 were identified as metabolites across eight phytochemical classes. Comparative profiling revealed that all hybrids retained a conserved core of iridoids and secoiridoids while integrating lineage-specific compounds and producing hybrid-specific metabolites not detected in either parent. Despite inheriting plastids from G. tibetica, hierarchical clustering showed that the phytochemical profiles of hybrid lines were more similar to G. cruciata, the donor of the nuclear genome. Quantitative analysis of the major secoiridoids, such as gentiopicroside, swertiamarin, and sweroside, demonstrated that several hybrid lines, particularly F30A-5 and F30A-6, matched or surpassed the biosynthetic output of G. tibetica, the more productive parent. These lines also exhibited elevated antioxidant capacity, underscoring their phytochemical and functional potential. Altogether, our findings show that somatic hybridization not only preserves but may amplify the secondary metabolite capacity of the parental genotypes, offering a viable platform for sustainable in vitro production of pharmacologically relevant secoiridoids. Full article

Babesia divergens is a tick-borne apicomplexan parasite that causes human babesiosis, a malaria-like disease. B. divergens metabolism remains poorly characterized. Here, we employed a multiplatform mass spectrometry-based metabolomics approach (using CE-TOF/MS, GC-QTOF/MS, LC-QTOF/MS, and LC-QqQ/MS) to profile intra- and extracellular metabolic changes in B. divergens-infected and uninfected red blood cells (RBCs) and their supernatants. Our results indicate alterations in the metabolome caused by B. divergens infection and proliferation within RBCs. These findings are consistent with the major metabolic dependencies of B. divergens, including extracellular glucose, glutamine, and arginine, accompanied by the accumulation of glycolytic and TCA cycle intermediates. We identified altered nucleotide metabolism, pentose phosphate pathway activity, and redox imbalance. Depletion of lysoglycerophospholipids, glucose, arginine, and glutamine, and accumulation of free heme and sphingolipids suggested pathogenic effects. Growth experiments indicate that glucose and glutamine, but not hypoxanthine, are required for parasite growth. We additionally discovered a phosphorylated HEPES derivative (PEPES) produced upon B. divergens infection of RBCs in vitro. Collectively, these findings and their global interpretation provide insights into B. divergens metabolism and metabolic dependencies and host–parasite metabolic interactions and outline potential directions for future studies on human babesiosis diagnosis, prognosis assessment, and treatment. Full article

Fermentation plays a pivotal role in shaping the flavor and overall quality of Pu-erh tea, a microbially fermented dark tea. Here, we monitored physicochemical properties, chemical constituents, and microbial succession at 15 fermentation time points. Amplicon sequencing identified Staphylococcus, Bacillus, Kocuria, Aspergillus, Blastobotrys, Thermomyces, and Rasamsonia as dominant genera, with prokaryotic communities showing greater richness and diversity than eukaryotic ones. Beta diversity and clustering analyses revealed stable microbial structures during late fermentation stages. Non-targeted metabolomics detected 347 metabolites, including 56 significantly differential compounds enriched in caffeine metabolism and unsaturated fatty acid biosynthesis. Fermentation phases exhibited distinct metabolic patterns, with volatile aroma compounds (2-acetyl-1-pyrroline, 2,5-dimethylpyrazine) and health-beneficial fatty acids (linoleic acid, arachidonic acid) accumulating in later stages. OPLS-DA and KEGG PATHWAY analyses confirmed significant shifts in metabolite profiles relevant to flavor and biofunctionality. RDA revealed strong correlations between microbial taxa, environmental parameters, and representative metabolites. To functionally verify microbial contributions, 17 bacterial and 10 fungal strains were isolated. Six representative strains, mainly Bacillus and Aspergillus, exhibited high enzymatic activity on macromolecules, confirming their roles in polysaccharide and protein degradation. This integrative multi-omics investigation provides mechanistic insights into Pu-erh tea fermentation and offers a scientific basis for microbial community optimization in tea processing. Full article

Deoxynivalenol (DON) is a common mycotoxin that causes immunosuppression in pigs. Its effects on cellular metabolism remain unclear. In this study, we investigate DON-induced metabolic alterations in porcine alveolar macrophage cell line 3D4/21 using non-targeted metabolomics. MTT assays showed DON reduced cell viability in a concentration- and time-dependent manner. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) revealed distinct metabolic profiles between control and DON-treated groups. Metabolomic analysis identified 127 differential metabolites (VIP > 1, p < 0.05), primarily in purine metabolism, glutathione metabolism, and arginine–proline metabolism. Integration with transcriptomic data confirmed that these pathways play key roles in DON-induced immunotoxicity. Specifically, changes in purine metabolism suggested disrupted nucleotide synthesis and energy balance, while glutathione depletion indicated weakened antioxidant defense. These findings provided a systems biology perspective on DON’s metabolic reprogramming of immune cells and identified potential therapeutic targets to reduce mycotoxin-related immunosuppression in swine. Full article

In the coming decades, the agricultural system will predictably rely on organic material to produce crops and maintain food security. Currently, the use of inorganic fertilizers to grow crops and vegetables, such as Swiss chard, spinach, and lettuce, is on the rise and has been proven to be detrimental to the soil in the long run. Hence, there is a growing need to use organic waste material, such as spent coffee grounds (SCGs), to grow crops. Spent coffee grounds are made of depleted coffee beans that contain important soluble compounds. This study aimed to determine the influence of different levels (0.32 g, 0.63 g, 0.92 g, and 1.20 g) of spent coffee grounds on the metabolomic profile of Swiss chard. The 1H-nuclear magnetic resonance (NMR) results showed that Swiss chard grown with different levels of SCGs contains a total of 10 metabolites, which included growth-promoting metabolites (trehalose; betaine), defense mechanism metabolites (alanine; cartinine), energy-reserve metabolites (sucrose; 1,6 Anhydro-β-D-glucose), root metabolites (thymine), stress-related metabolites (2-deoxyadenosine), caffeine metabolites (1,3 Dimethylurate), and body-odor metabolites (trimethylamine). Interestingly, caprate, with the abovementioned metabolites, was detected in Swiss chard grown without the application of SCGs. The findings of the current study suggest that SCGs are an ideal organic material for growing Swiss chard for its healthy metabolites. Full article

Cardiovascular diseases (CVDs) are the leading global cause of death, with long-term hospitalization becoming increasingly frequent in advanced or chronic cases. In this context, the interplay between systemic factors such as lipid metabolism, circulating metabolites, gut microbiota, and oral health is gaining attention for its potential role in influencing inflammation, cardiometabolic risk, and long-term outcomes. Despite their apparent independence, these domains are increasingly recognized as interconnected and influential in cardiovascular pathophysiology. Methods: This narrative review was conducted by analyzing studies published between 2015 and 2024 from databases including PubMed, Scopus, and Web of Science. Keywords such as “lipid profile,” “metabolomics,” “gut microbiota,” “oral health,” and “cardiovascular disease” were used. Original research, meta-analyses, and reviews relevant to hospitalized cardiac patients were included. A critical integrative approach was applied to highlight cross-domain connections. Results and Discussion: Evidence reveals significant interrelations between altered lipid profiles, gut dysbiosis (including increased TMAO levels), metabolic imbalances, and oral inflammation. Each component contributes to a systemic pro-inflammatory state that worsens cardiovascular prognosis, particularly in long-term hospitalized patients. Despite isolated research in each domain, there is a paucity of studies integrating all four. The need for interdisciplinary diagnostic models and preventive strategies is emphasized, especially in populations with frailty or immobilization. Conclusions: Monitoring lipid metabolism, metabolomic shifts, gut microbial balance, and oral status should be considered part of comprehensive cardiovascular care. Gut microbiota exerts a dual role in cardiac health: when balanced, it supports anti-inflammatory and metabolic homeostasis; when dysbiotic, it contributes to systemic inflammation and worsened cardiac outcomes. Future research should aim to develop integrative screening tools and personalized interventions that address the multifactorial burden of disease. A systemic approach may improve both short- and long-term outcomes in this complex and vulnerable patient population. Full article

Tacrolimus (TAC)-induced chronic nephrotoxicity (TAC nephrotoxicity) remains a major contributor to late allograft dysfunction in kidney transplant recipients. Although detailed mechanisms remain incompletely understood, our previous metabolomic studies revealed disruptions in carnitine-related and redox pathways, suggesting impaired mitochondrial β-oxidation of fatty acids. To further characterize metabolic alterations associated with this condition, we conducted an untargeted lipidomic analysis of renal tissues using a murine model of TAC nephrotoxicity. TAC (1 mg/kg/day) or saline was subcutaneously administered to male ICR mice for 28 days, and kidney tissues were harvested for comprehensive lipidomic profiling. Lipidomic analysis was performed with liquid chromatography–tandem mass spectrometry (p < 0.05, n = 5/group). Triacylglycerols (TGs) were the predominant lipid class identified. TAC-treated mice exhibited reduced levels of unsaturated TG species with low carbon numbers, whereas TGs with higher carbon numbers and various degrees of unsaturation were increased. All detected TGs containing docosahexaenoic acid (DHA) showed an increasing trend in TAC-treated kidneys. Although accumulation of polyunsaturated TGs has been previously observed in chronic kidney disease, the preferential increase in DHA-containing TGs appears to be a unique feature of TAC-induced nephrotoxicity. These results suggest that DHA-enriched TGs may serve as a metabolic signature of TAC nephrotoxicity and offer new insights into its pathophysiology. Full article

Male infertility is a multifactorial condition often associated with disruptions in sperm metabolism and mitochondrial function, yet traditional semen analysis provides limited insight into these molecular mechanisms. Understanding sperm bioenergetics and metabolic dysfunctions is crucial for improving the diagnosis and treatment of conditions such as asthenozoospermia and azoospermia. This systematic review synthesizes recent literature, focusing on advanced tools and techniques—including omics technologies, advanced imaging, spectroscopy, and functional assays—that enable comprehensive molecular assessment of sperm metabolism and development. The reviewed studies highlight the effectiveness of metabolomics, proteomics, and transcriptomics in identifying metabolic biomarkers linked to male infertility. Non-invasive imaging modalities such as Raman and magnetic resonance spectroscopy offer real-time metabolic profiling, while the seminal microbiome is increasingly recognized for its role in modulating sperm metabolic health. Despite these advances, challenges remain in clinical validation and implementation of these techniques in routine infertility diagnostics. Integrating molecular metabolic assessments with conventional semen analysis promises enhanced diagnostic precision and personalized therapeutic approaches, ultimately improving reproductive outcomes. Continued research is needed to standardize biomarkers and validate clinical utility. Furthermore, these metabolic tools hold significant potential to elucidate the underlying causes of previously misunderstood and unexplained infertility cases, offering new avenues for diagnosis and treatment. Full article

Background/Objectives: COVID-19 is a systemic viral infection that may lead to serious complications including acute kidney injury that requires kidney replacement therapy. The primary aim of this study was to evaluate urinary SerpinA3 (uSerpinA3) excretion as a biomarker of kidney recovery at 90 days, and the mortality in patients with critical COVID-19 and AKI requiring kidney replacement therapy (KRT). Methods: The study included patients with critical COVID-19 on invasive mechanical ventilation (IMV) requiring KRT. Blood and urine samples were obtained when KRT was initiated (day zero), and thereafter on days 1, 3, 7, and 14 post-replacement. uSerpinA3, kidney injury molecule-1 (uKIM-1), and neutrophil gelatinase-associated lipocalin (uNGAL) were measured in urine, and interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor alpha (TNF-α) in peripheral blood. In addition, metabolomics in sample days zero and 3, and in the survivors on sample day 90 was performed by employing gas chromatography coupled with mass spectrometry. Results: A total of 60 patients were recruited, of whom 29 (48%) survived hospitalization and recovered kidney function by day 90. In the survivors, 79% presented complete recovery (CRR) and the remaining (21%) recovered partially (PRR). In terms of uSerpinA3, levels on days 7 and 14 predicted CRR, with AUC values of 0.68 (p = 0.041) and 0.71 (p = 0.030), respectively, as well as mortality, with AUC values of 0.75 (p = 0.007) and 0.76 (p = 0.015), respectively. Among the other biomarkers, the excretion of uKIM-1 on day zero of KRT had a superior performance as a CRR predictor [(AUC, 0.71 (p = 0.017)], and as a mortality predictor [AUC, 0.68 (p = 0.028)]. In the metabolomics analysis, we identified four distinct profiles; the metabolite that maintained statistical significance in predicting mortality was p-cresol glucuronide. Conclusions: This study strongly suggests that uSerpinA3 and uKIM-1 can predict CRR and mortality in patients with critical COVID-19 and AKI requiring KRT. Metabolic analysis appears promising for identifying affected pathways and their clinical impact in this population. Full article

High semen quality is vital for reproductive success in the swine industry; however, seasonal fluctuations often compromise this quality. The molecular mechanism underlying these seasonal effects on semen quality remains largely unclear. This study employed untargeted metabolomic profiling of boar seminal plasma (SP) to identify metabolites and metabolic pathways associated with semen quality during the summer and winter months. Semen samples were collected from mature Duroc boars at a commercial boar stud and classified as Passed or Failed based on motility and morphology. SP from five samples per group was analyzed using ultra-high-performance liquid chromatography–mass spectrometry (UHPLC-MS). In total, 373 metabolites were detected in positive ion mode and 478 in negative ion mode. Several differentially expressed metabolites (DEMs) were identified, including ergothioneine, indole-3-methyl acetate, and avocadyne in the summer, as well as LysoPC, dopamine, and betaine in the winter. These metabolites are associated with key sperm functions, including energy metabolism, antioxidant defense, and capacitation. KEGG pathway analysis indicated enrichment in starch and sucrose metabolism, pyrimidine metabolism, and amino acid metabolism across the seasons. Overall, the results reveal that SP metabolomic profiles vary with the season, thereby influencing semen quality. The identified metabolites may serve as potential biomarkers for assessing semen quality and enhancing reproductive efficiency in swine production. Full article

Cancer is a systemic disease rather than a localized pathology and is characterized by widespread effects, including whole-body exhaustion and chronic inflammation. A thorough understanding of cancer pathophysiology requires a systemic approach that accounts for the complex interactions between cancer cells and host tissues. To explore these dynamics, we employed a comprehensive metabolomic analysis of plasma samples from patients with either esophageal or head and neck squamous cell carcinoma (SCC). Plasma samples from 149 patients were metabolically profiled and correlated with clinical data. Among the metabolites identified, lysophosphatidylcholine (LPC) emerged as the sole biomarker strongly correlated with prognosis. A significant reduction in plasma LPC levels was linked to poorer overall survival. Plasma LPC levels demonstrated minimal correlation with patient-specific factors, such as tumor size and general condition, but showed significant association with the response to immune checkpoint inhibitor therapy. Proteomic and cytokine analyses revealed that low plasma LPC levels reflected systemic chronic inflammation, characterized by high levels of inflammatory proteins, the cytokines interleukin-6 and tumor necrosis factor-α, and coagulation-related proteins. These findings indicate that plasma LPC levels may be used as reliable biomarkers for predicting prognosis and evaluating the efficacy of immunotherapy in patients with SCC. Full article

Background/Objective: Pharmacological interventions often exert systemic effects beyond their primary targets, underscoring the need for a comprehensive evaluation of their metabolic impact. Etodolac is a nonsteroidal anti-inflammatory drug (NSAID) that alleviates pain, fever, and inflammation by inhibiting cyclooxygenase-2 (COX-2), thereby reducing prostaglandin synthesis. While its pharmacological effects are well known, the broader metabolic impact and potential mechanisms underlying improved clinical outcomes remain underexplored. Untargeted metabolomics, which profiles the metabolome without prior selection, is an emerging tool in clinical pharmacology for elucidating drug-induced metabolic changes. In this study, untargeted metabolomics was applied to investigate metabolic changes following a single oral dose of etodolac in healthy male volunteers. By analyzing serial blood samples over time, we identified endogenous metabolites whose concentrations were positively or inversely associated with the drug’s plasma levels. This approach provides a window into both therapeutic pathways and potential off-target effects, offering a promising strategy for early-stage drug evaluation and multi-target discovery using minimal human exposure. Methods: Thirty healthy participants received a 400 mg dose of Etodolac. Plasma samples were collected at five time points: pre-dose, before Cmax, at Cmax, after Cmax, and 36 h post-dose (n = 150). Samples underwent LC/MS-based untargeted metabolomics profiling and pharmacokinetic analysis. A total of 997 metabolites were significantly dysregulated between the pre-dose and Cmax time points, with 875 upregulated and 122 downregulated. Among these, 80 human endogenous metabolites were identified as being influenced by Etodolac. Results: A total of 17 metabolites exhibited time-dependent changes closely aligned with Etodolac’s pharmacokinetic profile, while 27 displayed inverse trends. Conclusions: Etodolac influences various metabolic pathways, including arachidonic acid metabolism, sphingolipid metabolism, and the biosynthesis of unsaturated fatty acids. These selective metabolic alterations complement its COX-2 inhibition and may contribute to its anti-inflammatory effects. This study provides new insights into Etodolac’s metabolic impact under healthy conditions and may inform future therapeutic strategies targeting inflammation. Full article