Search Results (61)

Currently, the differences in the responses of the organic acid metabolism in rapeseed (Brassica napus L.) roots to saline and alkaline stresses are still unknown. To clarify the differences, different saline (100 (LS) and 200 (HS) mmol/L NaCl) and alkaline (20 (LA) and 40 (HA) mmol/L Na₂CO₃) treatments were applied to rapeseed. Then, targeted metabolomics was used to quantitatively analyze the changes in organic acid metabolism in the root system. The results showed that compared with the control group without stress (CK), 21, 18, 27, and 20 differentially accumulated organic acid metabolites were detected in the rapeseed roots under LS, HS, LA, and HA, respectively. In addition, 26, 6, 34, and 14 differentially accumulated organic acids were detected in the rapeseed root exudates under LS, HS, LA, and HA, respectively. Based on the activities of key enzymes related to the tricarboxylic acid cycle (TCA), antioxidant enzyme activities, organic acid metabolism, and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis in rapeseed roots, rapeseed mainly resisted saline and alkaline stresses by increasing organic acid synthesis and scavenging reactive oxygen species. Specifically, rapeseed resisted saline stress mainly by increasing the secretion of TCA cycle-related organic acids such as succinic acid, L-malic acid, fumaric acid, and cis-aconitic acid. In addition to secreting organic acids, rapeseed also resisted alkaline stress by increasing the secretion of phenolic acids such as 4-hydroxybenzoic acid, ferulic acid, and 4-coumaric acid. Notably, the number of secreted organic acid types and the increase in organic acid content under alkaline stress were higher than those under saline stress. The results of this study provide an important basis for the breeding of saline and alkaline stress-tolerant rapeseed varieties. Full article

The antimicrobial resistance crisis necessitates novel therapeutics. Selenium nanoparticles (SeNPs) offer promise, but their precise bactericidal mechanism remains poorly defined. This study aimed to define the antibacterial action of SeNPs synthesized via a green method with ascorbic acid and sodium citrate. The resulting SeNPs were monodisperse (17.8 ± 0.66 nm), crystalline, and highly stable (zeta potential: −69.9 ± 4.3 mV), exhibiting potent bactericidal activity against multidrug-resistant E. coli. To generate a mechanistic hypothesis, we integrated phenotypic analyses with a preliminary, single-replicate proteomic profiling. Recognizing this as an exploratory step, we focused our analysis on proteins with the most substantial changes. This revealed a coherent pattern of a targeted dual assault on core cellular processes. The data indicate that SeNPs simultaneously induce oxidative stress while severely depleting key components of the primary antioxidant glutathione system; key detoxification enzymes—glutathione S-transferase and glutaredoxin 2—were depleted 18- to 19-fold, while the stress protein HchA was reduced by over 63-fold. Concurrently, the patterns point toward a crippling of central energy metabolism; iron–sulfur enzymes in the TCA cycle, including aconitate hydratase (8.1-fold decrease) and succinate dehydrogenase (13.9-fold decrease), were severely suppressed, and oxidative phosphorylation was impaired (e.g., 4.7-fold decrease in NADH dehydrogenase subunit B). We propose that this coordinated disruption creates a lethal feedback loop leading to metabolic paralysis. Consequently, this work provides a detailed and testable mechanistic hypothesis for SeNPs action, positioning them as a candidate for a potent, multi-targeted antimicrobial strategy against drug-resistant pathogens. Full article

Itaconic acid (IA), one of the top twelve renewable platform chemicals, is a key precursor for polymer synthesis. Here, we engineered Myceliophthora thermophila for efficient consolidated biocatalytic IA production from lignocellulose by introducing the heterologous IA pathway (cis-aconitic acid decarboxylase (CAD), mitochondrial tricarboxylic transporter (MTT), major facilitator superfamily transporter (MFS) from Aspergillus terreus), and boosting CAD expression and precursor supply. A critical issue was temperature mismatch: optimal fungal growth vs. CAD activity. Transcriptomics analysis identified reduced expression of glycolytic rate-limiting enzymes (fructose-bisphosphate aldolase, FBA; phosphofructokinase, PFK) at 40 °C. Overexpressing these enzymes in strain IA32 generated strain IA41 (with 3.1-fold and 2.8-fold higher expression of pfk and fba, respectively), which accelerated glucose consumption by 53.2% and increased IA yield by 55.1% A two-stage temperature-shift strategy (45 °C for growth/saccharification, 40 °C for CAD activity) was developed. The engineered strain achieved 3.93 g/L IA in shake flasks and 10.51 g/L in corncob fed-batch fermentation—the highest reported titer for consolidated lignocellulose-to-IA processes. This establishes M. thermophila as a robust platform for cost-effective IA production from lignocellulose. Full article

Background: While the Mediterranean diet is well-established for its health benefits, the specific influence of organic versus conventional food sources within this pattern remains underexplored at the systemic metabolic level. Objective: This study investigated the metabolic effects of two matched Mediterranean diets, one based on organically produced foods (IMOD) and the other on conventionally produced equivalents (IMNOD), to assess the impact of food production methods on host metabolism and immune-inflammatory balance. Methods: Twelve healthy adults completed a crossover dietary intervention including IMOD and IMNOD phases. Urinary metabolite profiles were assessed via ¹H-NMR spectroscopy across 42 compounds. Multivariate and univariate analyses evaluated metabolic responses. Results: Both interventions normalized some out-of-range urinary metabolites. However, IMOD elicited broader and more significant changes, including increased levels of tricarboxylic acid (TCA) intermediates (e.g., isocitrate, trans-aconitate), plant-derived metabolites (e.g., trigonelline), and host–microbiota co-metabolites (e.g., N-phenylacetylglutamine, 1-methylnicotinamide). Simultaneously, fermentation-associated and xenobiotic-linked metabolites such as formate, acetate, and 2-furoylglycine decreased. These shifts collectively represent a beneficial modulation of the Microbiota–Immune–Inflammation Axis (MIIA effect). Conclusions: Organic food consumption within a Mediterranean framework promotes host–microbiota metabolic interplay and enhances immune-supportive biochemical pathways. The findings provide new mechanistic insight into how food production quality contributes to systemic metabolic health and support broader efforts to make organic foods more accessible. Full article

Background: Metabolomics is a powerful tool used for the evaluation of sugarcane components which are key factors influencing its response to biotic and abiotic stresses. However, little is known about the compositional variability and diversity of the sugarcane juice metabolome under practical field conditions in temperate climates. Methods: In this study, we characterized metabolomic differences and variability in sugarcane juice components during the maturation stage of nine cultivars grown in a temperate climate in Japan using a nuclear magnetic resonance-based metabolomics approach, aiming to provide insights into genotype-dependent adaptability to environmental and climate changes. Results: Principal component analysis revealed distinct metabolic profiles based on cultivar and maturation level. Notably, sucrose levels increased from September to December accompanied by decreased glucose and fructose levels across all cultivars. Early-maturing cultivars had high sucrose content even with shorter growing periods, suggesting particular advantages for sugar production in temperate climates. Additionally, 4-aminobutyric acid accumulated in all cultivars as maturation progressed. On the other hand, trans-aconitic acid, choline, and branched-chain amino acids showed cultivar-dependent trends. In one example, choline concentrations increased significantly in specific cultivars during maturation. Conclusions: These findings support a deeper understanding of metabolic adaptation and may aid in identifying cultivars better suited to environmental fluctuations. Full article

Organic acids, as natural metabolites, play crucial roles in human metabolism and health. Tumor Necrosis Factor (TNF), a pivotal mediator in immune regulation and inflammation, is a key therapeutic target. We evaluated ten organic acids as TNF modulators using in silico molecular docking, followed by detailed ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) profiling and molecular dynamics (MD) simulations for three lead candidates: gallic, aconitic, and crocetin acids. Their effects on TNF gene expression were then assessed in vivo using a mouse leukocyte model. The in silico results indicated that crocetin had the highest TNF binding affinity (−5.6 to −4.6 kcal/mol), while gallic acid formed the most stable protein-ligand complex during MD simulations, and aconitic acid established hydrogen bond interactions. ADMET analysis suggested potential pharmacokinetic limitations, including low permeability. Contrasting its high predicted binding affinity, in vivo gene expression analysis revealed that crocetin stimulated TNF synthesis, whereas gallic and aconitic acids acted as inhibitors. This research explores organic acids as potential TNF modulators, highlighting their complex interactions and providing a foundation for developing these compounds as anti-inflammatory agents targeting TNF-mediated diseases. Full article

Background: Walking ability is important for the quality of life of older adults. A self-reported walking ability index (WAI) covering the difficulty and ease of walking captures a broader spectrum of walking ability in healthy older persons. Methods: Using metabolomics in the Health, Aging and Body Composition study, we identified Year 2 metabolites cross-sectionally and longitudinally related to WAI (0–9, higher scores indicate better walking ability) using probabilistic index models and multinomial logistic models, respectively. Results: Among 2334 participants (mean age 74.6 years, 51% women, 37% Black), 27% scored 0–5, 36% scored 6–8, and 37% scored 9 at Year 2. Over 4 years, 52% maintained a stable WAI, 6% improved, while 42% declined (22% 1–2 points and 20% >2 points decline). We identified 81 metabolites significantly associated with both poorer concurrent WAI and faster decline, including higher acylcarnitine species, shorter-chain saturated diglycerides and triglycerides, and TCA cycle intermediates (cis-aconitic, fumaric, and malic acids), and lower phospholipids levels. Eighteen additional metabolites were only associated with faster WAI decline: higher short-chain saturated triglycerides and energy metabolism markers (ATP/ADP/AMP) and lower margaric acid and glycine levels. Notably, those with improved WAI, despite poorer baseline WAI and lifestyles, showed more favorable metabolic profiles than others. Conclusions: Metabolites linked to the TCA cycle and energy metabolism, as well as inflammation and protein catabolism, were related to mobility function. Some metabolites might be particularly important for the early detection of older adults at risk of mobility decline. Metabolic profiles may also help identify older individuals (i.e., with improving WAI) with greater metabolic resilience to lifestyle risk factors and health conditions. Full article

A divergent selection for resilience was carried out in rabbits over 12 generations. The selection criterion was increased (the HO line) and decreased litter size variability at birth (the HE line). The HO line (more resilient) shows higher litter size than the HE line (less resilient). The HO line sows higher litter size and embryo development than the HE line. The aim of this work is to investigate the plasma organic acid profile in both lines at mating and early gestation in order to analyze the effect of selection by resilience in the ovulation rate and early gestation. A total of 19 and 18 nonlactating multiparous females from the HE and HO lines were used. The ovulation rate, normal embryos, and percentage of compacted morulae at 72 h post-coitum (hpc) were studied, and blood samples were obtained at mating and 72 hpc. The organic profile was determined by HPLC. Bayesian methodology was used for statistical analysis. The HE line had 1.5% fewer normal embryos and 12.3% fewer compacted morulae than the HO line. The ovulation rate was similar in both lines. α-ketoglutaric acid and cis-aconitic acid were higher in the HE line than in the HO line. Citric acid, lactic acid, and pyruvic acid were higher at mating than at early gestation. In conclusion, the lower efficiency in the utilization of energy sources in the HE line could explain the reduced embryo production observed. The organic profile varies depending on the reproductive state in the female. Full article

Post-exertional malaise (PEM) is a defining condition of myalgic encephalomyelitis (ME/CFS). The concept requires that a provocation causes disabling limitation of cognitive and functional effort (“fatigue”) that does not respond to rest. Cerebrospinal fluid was examined as a proxy for brain metabolite and lipid flux and to provide objective evidence of pathophysiological dysfunction. Two cohorts of ME/CFS and sedentary control subjects had lumbar punctures at baseline (non-exercise) or after submaximal exercise (post-exercise). Cerebrospinal fluid metabolites and lipids were quantified by targeted Biocrates mass spectrometry methods. Significant differences between ME/CFS and control, non-exercise vs. post-exercise, and by gender were examined by multivariate general linear regression and Bayesian regression methods. Differences were found at baseline between ME/CFS and control groups indicating disease-related pathologies, and between non-exercise and post-exercise groups implicating PEM-related pathologies. A new, novel finding was elevated serine and its derivatives sarcosine and phospholipids with a decrease in 5-methyltetrahydrofolate (5MTHF), which suggests general dysfunction of folate and one-carbon metabolism in ME/CFS. Exercise led to consumption of lipids in ME/CFS and controls while metabolites were consumed in ME/CFS but generated in controls. In general, the frequentist and Bayesian analyses generated complementary but not identical sets of analytes that matched the metabolic modules and pathway analysis. Cerebrospinal fluid is unique because it samples the choroid plexus, brain interstitial fluid, and cells of the brain parenchyma. The quantitative outcomes were placed into the context of the cell danger response hypothesis to explain shifts in serine and phospholipid synthesis; folate and one-carbon metabolism that affect sarcosine, creatine, purines, and thymidylate; aromatic and anaplerotic amino acids; glucose, TCA cycle, trans-aconitate, and coenzyme A in energy metabolism; and vitamin activities that may be altered by exertion. The metabolic and phospholipid profiles suggest the additional hypothesis that white matter dysfunction may contribute to the cognitive dysfunction in ME/CFS. Full article

In this study, we first thoroughly assayed the response of the key enzymes of energy metabolism and the antioxidant system in Yarrowia lipolytica yeast at extreme pH. The activity of the tricarboxylic acid cycle enzymes, namely NAD-dependent isocitrate dehydrogenase, aconitate hydratase, NAD-dependent malate dehydrogenase, and fumarate hydratase, NADPH-producing enzymes of glucose-6-P dehydrogenase and NADP-dependent isocitrate dehydrogenase, and the enzymes of the glutathione system was assessed. All the enzymes that were tested showed a significant induction contrary to some decrease in the aconitate hydratase activity with acidic and alkaline stress. It is probable that a change in the enzyme activity in the mitochondria matrix is involved in the regulation of the cellular metabolism of Y. lipolytica, which allows the species to prosper at an extreme ambient pH. It distinguishes it from any other type of ascomycete. A close relationship between the induction of the Krebs cycle enzymes and the key enzymes of the glutathione system accompanied by an increased level of reduced glutathione was shown. The assumption that the increased activity of the Krebs cycle dehydrogenases and promotion of the pentose phosphate pathway at pH stress launches a set of events determining the adaptive response of Y. lipolytica yeast. Full article

The bioconversion of agricultural and industrial wastes is considered a green and sustainable alternative method for producing high-value biochemicals. As a major catalytic product of greenhouse gases and a by-product in the fermentation and lignocellulose processing industries, acetate is a promising bioconversion raw material. In this work, endogenous and heterologous enzymes were manipulated in Yarrowia lipolytica to achieve the conversion of acetate to high-value citric acid and itaconic acid, respectively. After the combinational expression of the key enzymes in the acetate metabolic pathway, the citric acid synthesis pathway, and the mitochondrial transport system, acetate could be efficiently converted to citric acid. Coupled with the down-regulation of fatty acid synthase expression in the competitive pathway, more acetyl-CoA flowed into the synthesis of citric acid, and the titer reached 15.11 g/L with a productivity of 0.51 g/g acetate by the engineered Y. lipolytica, which is comparable to the results using glucose as the substrate. On this basis, the heterologous cis-aconitate decarboxylase from Aspergillus terreus was introduced into the engineered Y. lipolytica to achieve the catalytic synthesis of itaconic acid from acetate. Combined with investigating the effects of multiple enzymes in the synthesis pathway, the titer of itaconic acid reached 1.87 g/L with a yield of 0.43 g/g DCW by the final engineered strain, which is the highest reported titer of itaconic acid derived from acetate by engineered microbes in shake flasks. It is demonstrated that acetate has the potential to replace traditional starch-based raw materials for the synthesis of high-value organic acids and our work lays a foundation for the rational utilization of industrial wastes and the catalytic products of greenhouse gases. Full article

Background/Objectives: The mechanisms of action of phosphine are diverse and include neurotoxicity, metabolic inhibition, and oxidative stress; however, its efficacy at low temperatures is unclear. Methods: Comparative metabolomics is suitable for investigating the response of the spotted-wing fly Drosophila suzukii to exposure toward a combination of cold stimuli and fumigant PH₃. Results: Under this combined exposure, 52 metabolites exhibiting significant differences in stress were identified and their physiological roles were analyzed in the Drosophila metabolic pathway. Most metabolites were involved in amino acids, TCA cycle, and nucleic acids. In addition, the alteration levels of cell membrane lipids, such as glycerophospholipids, sphingolipids, and glycerolipids, clearly showed changes in the combined treatment compared to PH₃ and low temperatures alone. Aconitic acid, a component of the TCA cycle, was completely inhibited by the combined treatment. Conclusions: These results suggest that treatment-specific indicators could be useful biomarkers to indicate the synergistic effects of PH₃ and low temperature on energy metabolism. Full article

(1) Background: Osteoarthritis (OA) is a heterogeneous disorder, and subgroup classification of OA remains elusive. The aim of our study was to identify endotypes of hip OA and investigate the altered pathways in the different endotypes. (2) Methods: Metabolomic profiling and genome-wide genotyping were performed on fasting blood. Transcriptomic profiling was performed on RNA extracted from cartilage samples. Machine learning methods were used to identify endotypes of hip OA. Pathway analysis was used to identify the altered pathways between hip endotypes and controls. GWAS was performed on each of the identified metabolites. Transcriptomic data was used to examine the expression levels of identified genes in cartilage. (3) Results: 180 hip OA patients and 120 OA-free controls were classified into three clusters based on metabolomic data. The combination of arginine, ornithine, and the average value of 7 lysophosphatidylcholines had an area under the curve (AUC) of 0.97 (95% CI: 0.96–0.99) to discriminate hip OA from controls, and the combination of γ-aminobutyric acid, spermine, aconitic acid, and succinic acid had an AUC of 0.96 (95% CI: 0.94–0.99) to distinguish two hip OA endotypes. GWAS identified 236 SNPs to be associated with identified metabolites at GWAS significance level. Pro-inflammatory cytokine levels were significantly different between two endotypes (all p < 0.05). (4) Conclusions: Hip OA could be classified into two distinct molecular endotypes. The primary differences between the two endotypes involve changes in pro-inflammatory factors and energy metabolism. Full article

To investigate the metabolomic mechanisms by which changes in cardiorespiratory fitness (CRF) levels affect metabolic syndrome (MetS) risk factors and to provide a theoretical basis for the improvement of body metabolism via CRF in people with MetS risk factors, a comparative blood metabolomics study of individuals with varying levels of CRF and varying degrees of risk factors for MetS was conducted. Methods: Ninety subjects between the ages of 40 and 45 were enrolled, and they were categorized into low-MetS (LM ≤ two items) and high MetS (HM > three items) groups, as well as low- and high-CRF (LC, HC) and LCLM, LCLM, LCHM, and HCHM groups. Plasma was taken from the early morning abdominal venous blood. LC-MS was conducted using untargeted metabolomics technology, and the data were statistically and graphically evaluated using SPSS26.0 and R language. Results: (1) There were eight common differential metabolites in the HC vs. LC group as follows: methionine (↓), γ-aminobutyric acid (↑), 2-oxoglutatic acid (↑), arginine (↑), serine (↑), cis-aconitic acid (↑), glutamine (↓), and valine (↓); the HM vs. LM group are contrast. (2) In the HCHM vs. LCLM group, trends were observed in 2-oxoglutatic acid (↑), arginine (↑), serine (↑), cis-aconitic acid (↑), glutamine (↓), and valine (↓). (3) CRF and MetS risk factors jointly affect biological metabolic pathways such as arginine biosynthesis, TCA cycle, cysteine and methionine metabolism, glycine, serine, and threonine metabolism, arginine and proline metabolism, and alanine, aspartate, and glutamate metabolism. Conclusion: The eight common differential metabolites can serve as potential biomarkers for distinguishing individuals with different CRF levels and varying degrees of MetS risk factors. Increasing CRF levels may potentially mitigate MetS risk factors, as higher CRF levels are associated with reduced MetS risk. Full article