Search Results (3,744)

Cherry tomato is a notable dietary source of metabolites associated with antioxidant functions. However, how ripening reshapes primary, specialized, and volatile metabolites remains incompletely resolved. Green-ripe and red-ripe fruits were comparatively analyzed using targeted HPLC assays for quality indices and vitamins, UPLC–MS/MS for non-volatile metabolites, and HS-SPME–GC–MS for volatiles. Ripening was accompanied by a pronounced accumulation of lycopene and an increase in soluble solids, reflecting a shift of sugars toward glucose and fructose while sucrose remained low. Organic acids declined overall, with citric acid remaining predominant. The free-amino-acid pool expanded, with redistribution from GABA toward glutamate and aspartate. Vitamins exhibited stage-dependent patterns; antioxidant-related vitamins (A, E, and C) were higher at the red-ripe stage, indicating a compositional enhancement relevant to nutritional quality. Non-volatile metabolomics revealed 618 differentially accumulated metabolites, with phenolic acids, flavonoids, alkaloids, amino acids, and lipids as major classes. Phenolic acids and flavonols, dominated by hydroxycinnamoyl-quinic acids and quercetin/kaempferol glycosides, accumulated at the red-ripe stage, whereas steroidal glycoalkaloids decreased, suggesting conversion away from bitter or anti-nutritional constituents. GC–MS profiling identified 788 volatiles, with esters, terpenoids, and ketones contributing more than half of the volatilome. Ripening favored fruity–floral odorants such as β-ionone and (5Z)-octa-1,5-dien-3-one, while reducing green-leaf aldehydes. These stage-specific shifts in metabolite composition jointly define the sensory and nutritional maturation of cherry tomato. The identified metabolite markers provide a foundation for evaluating fruit maturity and guiding breeding toward improved quality attributes. Full article

Background/Objectives: Long-term hospitalization in cardiac patients is associated with significant metabolic and microbial alterations that may influence disease progression and prognosis. Although lipid imbalances, metabolomic shifts, and gut microbiome dysbiosis have each been linked individually to cardiovascular outcomes, their integrated evaluation in long-term-hospitalized patients remains underexplored. Methods: We conducted a retrospective observational study including 51 cardiac patients hospitalized for more than 25 days, compared with a control group of 41 patients hospitalized for short and intermediate durations (3–24 days). Clinical and demographic data were collected, alongside lipid profiling, metabolomic assessment through liquid chromatography–mass spectrometry (LC-MS), and gut microbiome analysis using GI360™ sequencing. Ethical approval was obtained, and all data were anonymized. Lipid-related findings are exploratory due to the small number of complete measurements. Results: Preliminary lipid trends were characterized by higher levels of LDL, triglycerides, and Lp(a), and lower HDL, in the long-term group. Metabolomic analyses revealed decreased energy-related metabolites (ATP, phosphocreatine ratio), altered amino acid patterns, and increased ketone utilization. Gut microbiome evaluation demonstrated a significant increase in dysbiosis index, with reduced diversity and dominance of potentially pathogenic taxa. These findings were correlated with clinical severity scores. Cross-domain relationships are exploratory and based on associative profiling rather than deep integrative modelling. Conclusions: Long-term hospitalization in cardiac patients is associated with distinct lipid, metabolomic, and gut microbiome profiles that may serve as predictive biomarkers of adverse outcomes. Future studies should validate these findings in larger cohorts and explore their integration into personalized management strategies. Full article

Background/Objectives: Pre-analytical variation is a major challenge in metabolomics, yet most stability studies have focused on healthy volunteers and have overlooked the impact of disease and medication. To address this gap, we conducted a pilot study in systemic lupus erythematosus (SLE) to assess serum metabolite stability under delayed centrifugation. Methods: Peripheral blood from 10 SLE patients and 5 healthy controls (HC) was stored at room temperature for 1–24 h before processing and analyzed by untargeted LC-MS-based metabolomics. This design enabled direct evaluation of the effect of pre-analytical delay within the context of clinical heterogeneity. Results: Principal component trajectories showed reproducible temporal shifts in HC but dispersed patterns in SLE, indicating disease- and treatment-related influences. Linear mixed-effects models identified metabolites with condition-specific kinetics, including glucose, choline, glycerophosphocholine, and pyroglutamic acid. Mycophenolate intake was further associated with distinct AMP dynamics. Conclusions: These findings demonstrate that both disease state and medication reshape apparent metabolite stability, highlighting the need for strictly controlled sample handling and well-characterized clinical cohorts in metabolomics studies. Full article

Background/Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental disorder typically characterized by impaired social communication. Previous reports have postulated gut microbiota to be an important non-genetic factor affecting ASD-like phenotypes in mice, as germ-free (GF) mice show impaired social communication. Results: In this study, we identified hippuric acid (HA) as a metabolite generated via a gut microbiome-dependent mechanism that plays a role in the acquisition of social behavior during mouse development. We discovered that oral or intraperitoneal HA administration to GF mice normalizes their social behavior. Furthermore, HA administration restored oxytocin expression in the hypothalamic paraventricular nucleus and secretin expression in the subfornical organ, suggesting that HA may activate the secretin–oxytocin system to influence the social behavior of mice. Conclusions: These findings indicate that HA may serve as an important gut microbiome-dependent mediator affecting the brain mechanisms involved in regulating social behavior. Full article

The rapidly advancing field of gut microbiota research has revealed its pivotal role in human health, with growing evidence implicating microbial dysbiosis in the development of metabolic diseases, particularly type 2 diabetes mellitus (T2DM). This narrative review synthesizes recent findings on the complex, bidirectional relationship between the gut microbiota–metabolic axis and T2DM, drawing upon data from human and experimental studies published in the past decade. Patients with T2DM consistently demonstrate marked gut dysbiosis, characterized by reduced microbial diversity and depletion of beneficial butyrate-producing taxa such as Faecalibacterium prausnitzii and Roseburia intestinalis. In contrast, increases in pro-inflammatory bacteria including Escherichia-Shigella and Lactobacillus are commonly observed. Such compositional changes are linked to metabolic dysfunction through altered microbial metabolites, including elevated trimethylamine N-oxide (TMAO), which has been associated with insulin resistance and increased diabetes risk. Moreover, gut microbiota imbalances correlate with systemic inflammation, as indicated by higher levels of cytokines such as IFN-γ and IL-6. These findings underscore the gut microbiota’s central role in energy metabolism and inflammation in T2DM. Understanding these mechanisms could inform novel therapeutic and preventive strategies—such as microbiota-targeted dietary, probiotic, or pharmacologic interventions—to improve metabolic outcomes and enhance clinical management of diabetes. Full article

Background: The entomopathogenic fungus Metarhizium brunneum (M. brunneum) is an effective biocontrol agent against various vector arthropods such as ticks, mosquitoes, and flies. However, its virulence mechanisms remain poorly understood, which hinders its broader application. This study aims to establish an integrative framework for prioritizing virulence-related pathways in M. brunneum to aid in the development of more effective biocontrol strategies. Methods: A multidimensional virulence pathway scoring framework was developed using publicly available protein annotation data of M. brunneum. This approach integrates protein pathway enrichment, Gene Ontology (GO) functional analysis, PHI-base virulence factor mapping, and literature-derived evidence. A total of 20 pathways were evaluated, and a scoring system was applied based on protein coverage, Gene Ontology Biological Process (GO-BP) support, PHI-base hits, and literature support. Results: Among the 20 pathways evaluated, five pathways, including MAPK signaling, apoptosis, endocytosis, carbon metabolism, and biosynthesis of secondary metabolites received the highest priority scores. These pathways were identified as key virulence-related candidates, supported by both functional annotation and existing biological evidence. Conclusions: The proposed framework provides a reliable and scalable strategy for prioritizing virulence pathways in entomopathogenic fungi. It offers a solid foundation for subsequent transcriptomic validation, target screening, and functional characterization. This framework can also be applied to other fungi, contributing to the development of optimized biocontrol formulations. Full article

Background/Objectives: Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by sustained inflammation, leading to diabetic kidney disease (DKD). This study investigated urinary tubular injury biomarkers and metabolomic profiles in relation to albuminuria and renal function across varying durations of T1D. Methods: A cross-sectional analysis was conducted in 247 youth-onset T1D patients categorized by disease duration: short ≤ 5 years (T1D-S, n = 62), medium 6–10 years (T1D-M, n = 67), and long > 10 years (T1D-L, n = 118). Urinary cytokines (MCP-1, KIM-1, NGAL) were measured by ELISA. Metabolomic profiling was performed using ¹H-NMR spectroscopy. Results: Urinary MCP-1/Cr, KIM-1/Cr, and NGAL/Cr levels were significantly elevated in T1D patients compared with non-diabetic controls, but did not correlate with disease duration. Metabolomic profiling identified distinct urinary signatures across T1D duration. Specifically, N-acetylcysteine (NAC) and N-delta-acetylornithine (NAO) increased progressively, while N-acetylaspartate (NAA) and pyruvic acid decreased with longer disease duration. These four metabolites remained statistically significant after both based on Mann–Whitney tests with false discovery rate (FDR) correction (q < 0.05) and application of a conservative alpha threshold (p < 0.01), suggesting potential disruptions in amino acid and carbohydrate metabolism. Conclusions: Urinary biomarkers (MCP-1/Cr, NGAL/Cr, and KIM-1/Cr) are sensitive indicators of subclinical kidney dysfunction in T1D patients, often preceding albuminuria. Alterations in amino acid-related metabolites (NAC, NAA, and NAO) and pyruvate highlight possible metabolic disturbances associated with T1D duration and oxidative stress. However, given the cross-sectional design, longitudinal studies are needed to confirm causality and clarify their predictive value in DKD progression. Full article

Growing market demand exists for strawberry, with nutrient-rich and health-promoting properties, beyond mere taste and flavor. Genetic biofortification is a powerful strategy to enhance nutrient metabolites in strawberry. Both GABA and organic acids contribute to human health by supporting nervous system relaxation and enhancing metabolic and digestive functions, respectively. However, the regulatory mechanisms underlying their accumulation remain poorly understood. In this study, we analyzed the accumulation patterns of GABA and organic acids across four fruit developmental stages in two representative cultivars, ‘Monterey’ and ‘Benihoppe’. Ripening ‘Benihoppe’ fruits accumulated higher levels of GABA and citric acid, whereas ‘Monterey’ fruits contained more malic acid. Integrated transcriptome analysis identified key structural genes and transcription factors (TFs) involved in GABA biosynthesis. Notably, functional characterization revealed that FaGAD4 significantly promotes GABA accumulation and simultaneously enhances the content of anthocyanin and ascorbic acid (AsA). Overall, this study provides novel insights into the regulatory mechanisms of GABA accumulation in strawberry fruit and identifies FaGAD4 and potential TFs as valuable genetic targets for molecular breeding. Full article

Background/Objectives: Coenzyme Q 10 is a lipid molecule that works as a mobile electron transporter in the mitochondrial respiratory chain and, in addition, plays the role of an antioxidant. Interestingly, CoQ10 synthesis in human cells derives from the mevalonate pathway, the same metabolic route that delivers endogenous cholesterol. Mutations leading to Familial Hypercholesterolemia (FH) alter the levels of CoQ10 production and remarkably, statin therapy associated muscular symptoms (SAMSs) might also be modulated by CoQ10 supplementation. CoQ10 is also provided by diet and only a few studies have calculated the dietary intake of this metabolite among populations. Methods: Here, we present our Spanish FH cohort (n = 261) and characterized relevant clinical, metabolic, and anthropometric parameters. Results: A cohort of 75.1% followed lipid-lowering treatment at inclusion, being the most prescribed drugs statin alone (32.7%) and statins combined with ezetimibe (56.6%). The average time on statin treatment was 3.7 years. Interestingly, 22% of cohort patients presented with SAMS. In addition, we performed an exhaustive literature review to define for the first time the CoQ10 content present in food typically found in Spain or other southern-European countries and classified them from very rich (over 50 mg/kg) to very poor (<1 mg/kg). With this information, we calculated the daily intake of CoQ10 from a small group (12) of selected FH patients using a validated food-frequency questionnaire (FFQ) and determined a daily intake 9.72 ± 2.64 mg/day, different to other described populations. Conclusions: we discussed the relevance of exogenous CoQ10 for FH development and potential SAMS. Interestingly, this information can be extrapolated to define the regular CoQ10 intake of the Spanish population, especially when following the MedDiet. Full article

Hepatocellular carcinoma (HCC), the most common primary liver malignancy, usually develops in patients with cirrhosis, yet the metabolic mechanisms that distinguish the two conditions remain poorly understood. This study aimed to explore metabolic dysregulations in HCC compared with cirrhosis and to identify potential biomarkers, especially lipids, with diagnostic and prognostic value. We prospectively studied 81 patients—41 with HCC and 40 with cirrhosis—using high-resolution UHPLC-QTOF-ESI⁺-MS to characterize their serum lipidome. Across both groups, 322 metabolites were identified, but their distribution was strikingly different. Patients with HCC showed higher levels of sphingolipids, glycerophospholipids, diglycerides, sterols, and certain fatty acids, reflecting tumor-related metabolic rewiring. In contrast, cirrhotic patients had increased D-glucose, 5-hydroxymethyluracil, lysophospholipids, acylcarnitines, and specific fatty acid derivatives. Several lipids, such as CerPE(d16:2/24:1(2OH)), SM(d18:0/14:0), PA(36:6), and GlcCer(d18:1/12:0), displayed excellent discriminative accuracy, highlighting their role as putative biomarkers. These findings underscore the importance of lipid metabolic reprogramming in HCC, characterized by membrane remodeling, energy adaptation, and oxidative stress resistance. Integrating lipidomic profiling into clinical practice could improve early detection and risk stratification in cirrhotic patients. Larger, multicenter studies are needed to validate these biomarkers and assess their therapeutic implications. Full article

Fatty acid desaturase 12 (FAD12) is a key enzyme in fatty acid biosynthesis, responsible for converting oleic acid to linoleic acid through desaturase activity. Euglena gracilis (Euglena) is an emerging platform for the industrial production of various metabolites, including lipids. However, a comprehensive understanding of Euglena’s fatty acid biosynthesis pathways remains incomplete, posing a significant barrier to the commercialization of Euglena bioproducts. To address this gap, we employed a bioinformatics approach to identify a Euglena gracilis FAD12 (Eg FAD12). We analyzed the evolutionary relationship of Eg FAD12 with its homologs from other organisms and revealed that the three canonical histidine box motifs are conserved among FAD12s. To characterize EgFAD12, we cloned it into the pEAQ-hyperstrans vector and overexpressed it in Nicotiana benthamiana to take advantage of its endogenous fatty acid pool, which could act as a substrate. The heterologous expression of FAD12 in N. benthamiana led to an increased linoleic acid content, demonstrating the suspected desaturase activity. To further confirm the function of Eg FAD12, we performed CRISPR-Cas9-mediated knockout of Eg FAD12 in Euglena, which resulted in a drastic reduction in linoleic acid (C18:2) without compromising biomass yield or lipid content. This work advances our understanding of fatty acid biosynthesis in Euglena and will aid in its adoption as a platform for producing customized lipids. Full article

Exercise performance is a critical trait for evaluating the economic and breeding value of working and athletic horses, with cardiac structure and function serving as essential physiological determinants of athletic capacity. This study aimed to investigate the multi-omics response mechanisms associated with varying degrees of cardiac remodeling under identical exercise intensity. Twenty 2-year-old Yili horses were selected and categorized based on echocardiographic parameters into a high cardiac remodeling group (BH; EDV > 500 mL, SV > 350 mL, EF > 66%) and a low cardiac remodeling group (BL; EDV < 450 mL, SV < 330 mL, EF < 64%). Blood samples were collected before and after the 1000 m constant-speed test (pre-test high cardiac remodeling group (BH, n = 10), post-test high cardiac remodeling group (AH, n = 10), pre-test low cardiac remodeling group (BL, n = 10), post-test low cardiac remodeling group (AL, n = 10)), and integrated metabolomic, transcriptomic, and miRNA profiling were conducted to systematically characterize molecular responses to exercise-induced stress. Metabolomic analysis identified a total of 1936 lipid metabolites, with the BH group exhibiting stronger post-exercise lipid mobilization and significant enrichment of sphingolipid signaling pathways. Transcriptomic and miRNA analyses further revealed that key miRNAs in the BH group, including miR-186, miR-23a/b, and the let-7 family, along with their target genes (e.g., GNB4, RGS5, ALAS2), were involved in fine regulation of cardiac electrophysiology, oxidative stress, and energy metabolism. Integrated analysis indicated that the AH vs. BH comparison uniquely enriched pathways related to glycine-serine-threonine metabolism and glycosylphosphatidylinositol (GPI)-anchor biosynthesis, whereas the AL vs. BL comparison showed unique enrichment of α-linolenic acid and arachidonic acid metabolism pathways. Ultimately, multi-omics integration identified that in the BH group, eca-let-7d, eca-let-7e, eca-miR-196b, eca-miR-2483, and eca-miR-98 regulate ALAS2 and, together with GCSH, influence the enrichment of lipids such as PS(17:0_16:1), PS(18:0_18:1), and PS(20:0_18:1). These lipids participate in glycine, serine, and threonine metabolism through complex pathways, collectively modulating energy supply, inflammatory responses, and muscle function during exercise. This study reveals the molecular mechanisms by which horses with high cardiac remodeling maintain energy homeostasis and myocardial protection during exercise. Full article

This study aimed to determine the antifungal activity of various compounds and develop a novel antifungal formulation against fungal pathogens, including Alternaria alternata, Botrytis cinerea, Penicillium expansum, and Rhizopus stolonifer. A total of 32 plant-derived secondary metabolites and three extracts (dichloromethane, ethyl acetate, and methanol) from Lawsonia inermis, Juglans regia, and Drosera intermedia were screened at a concentration of 250 ppm. The chemical composition of the D. intermedia ethyl acetate extract was characterized using chromatographic techniques. Subsequently, an emulsifiable concentrate formulation from this extract was prepared, and its efficacy was evaluated at concentrations ranging from 250 to 2000 ppm. The D. intermedia ethyl acetate extract was found to contain three flavonoids (1.4%) and three naphthoquinones (2.8%). The formulation exhibited optimal effect at 1000 ppm. Overall, the high efficacy of the formulation containing the dried D. intermedia extract (10:1, ethyl acetate) positions it as a promising and viable alternative to synthetic fungicides. Full article

Plant-derived extracellular vesicles (PDEVs) are nanoscale membrane vesicles released by edible plants that deliver proteins, lipids, nucleic acids, and small metabolites to recipient cells, thereby modulating inflammation, barrier function, metabolism, and intercellular signaling. In recent years, PDEV research has advanced from concept and in vitro observations to engineering-ready systems with validation in animal models, encompassing oral, transdermal, and intranasal delivery paradigms. Among edible plants, the apple has broad consumption and a favorable safety profile; however, studies on apple-derived extracellular vesicles (ADEVs) lag behind those on other plant EVs. Accordingly, this review systematically summarizes ADEV progress across extraction methods, characterization, molecular cargo, and roles in disease settings. We highlight evidence gaps in animal efficacy and translation, and propose priorities including process standardization, harmonized critical quality attributes, in vivo biodistribution, and long-term safety. Our aim is to provide a reference for ADEV research and to accelerate the development of safe, low-cost, scalable bionanocarriers for disease therapy. Full article

Background: Medicinal plants continue to offer a promising source of novel bioactive compounds for cancer therapy due to their affordability, biocompatibility, and low toxicity. Rhus punjabensis Stewart, an ethnomedicinal species from the family Anacardiaceae, has long been used in the traditional medicine of northern Pakistan to treat inflammatory, hepatic, and infectious diseases. However, its phytochemical composition and anticancer potential remain largely unexplored. Methods: This study employed a bioactivity-guided isolation strategy to identify and characterize anticancer constituents from R. punjabensis leaves. The plant material was sequentially fractionated using solvents of increasing polarity, followed by purification via column chromatography. Each fraction and purified compound was evaluated using antioxidant (DPPH, total antioxidant capacity, and total reducing power) and cytotoxic assays, including brine shrimp lethality, Sulfo-rhodamine B (SRB) against five human cancer cell lines, protein kinase inhibition, and NF-κB chemo-preventive assays. Results: Comparative analysis of spectral data (UV, 1D/2D NMR, and ESI-MS) led to the identification of three triterpenoid compounds—Lupeol, Cycloartenol, and β-sitosterol—reported for the first time from R. punjabensis. Among them, Lupeol displayed the most potent cytotoxicity against DU-145 prostate (IC₅₀ = 11.2 ± 1.2 μg/mL) and HL-60 leukemia (IC₅₀ = 15.2 ± 1.1 μg/mL) cell lines and showed significant NF-κB inhibitory activity (IC₅₀ = 19.4 ± 1.1 μg/mL), indicating its chemo-preventive potential. Cycloartenoland β-sitosterol exhibited moderate antioxidant and antimicrobial activities. Conclusion: The findings validate the ethnopharmacological use of R. punjabensis and confirm it as a new source of triterpenoids with notable anticancer activity. This study provides the first comprehensive account of its bioactive metabolites, reinforcing the significance of bioactivity-directed isolation as a powerful approach for discovering natural anticancer agents. Further in vivo and mechanistic evaluations are warranted to establish their therapeutic efficacy and safety profiles. Full article