Metabolomic analysis reveals key changes in amino acid metabolism in colorectal cancer patients

Amino Acids, Journal Year: 2025, Volume and Issue: 57(1)

Published: May 2, 2025

Language: Английский

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Exposure to Subclinical Doses of Fumonisins, Deoxynivalenol, and Zearalenone Affects Immune Response, Amino Acid Digestibility, and Intestinal Morphology in Broiler Chickens

Toxins, Journal Year: 2025, Volume and Issue: 17(1), P. 16 - 16

Published: Jan. 1, 2025

Fusarium mycotoxins often co-occur in broiler feed, and their presence negatively impacts health even at subclinical concentrations, so there is a need to identify the concentrations of these toxins that do not adversely affect chickens performance. The study was conducted evaluate least toxic effects combined fumonisins (FUM), deoxynivalenol (DON), zearalenone (ZEA) on production performance, immune response, intestinal morphology, nutrient digestibility chickens. A total 960 one-day-old broilers were distributed into eight dietary treatments: T1 (Control); T2: 33.0 FUM + 3.0 DON 0.8 ZEA; T3: 14.0 3.5 0.7 T4: 26.0 1.0 0.2 T5: 7.7 0.4 0.1 T6: 3.6 2.5 0.9 T7: 0.3 T8: 0.5 ZEA, all mg/kg diet. results showed exposure higher mycotoxin T2 T3, had significantly reduced body weight gain (BWG) by 17% d35 (p < 0.05). T2, T4 groups significant decrease villi length jejunum ileum 0.05) disruption tight junction proteins, occludin, claudin-4 Higher T6 reduction amino acids methionine 0.05), aspartate serine 0.05); CD4+, CD8+ T-cell populations an increase T regulatory cell percentages spleen splenic macrophage nitric oxide IgA upregulated cytochrome P450-1A1 1A4 gene expression Birds fed lower concentration groups, T7 T8, did have effect health, responses, suggesting pose negative These findings are essential for developing acceptable thresholds efficient feed management strategies improve

Language: Английский

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Bromine-Based Derivatization of Carboxyl-Containing Metabolites for Liquid Chromatography–Trapped Ion Mobility Spectrometry–Mass Spectrometry

Journal of the American Society for Mass Spectrometry, Journal Year: 2025, Volume and Issue: unknown

Published: March 7, 2025

The analysis of small carboxyl-containing metabolites (CCMs), such as tricarboxylic acid (TCA) cycle intermediates, provides highly useful information about the metabolic state cells. However, their detection using liquid chromatography–electrospray ionization–tandem mass spectrometry (LC-ESI-MS/MS) methods can face sensitivity and specificity challenges given low ionization efficiency presence isomers. Ion mobility (IMS), trapped ion (TIMS), additional specificity, but further signal loss occur during separation process. We, therefore, developed a solution to boost CCM chromatographic well leverage IMS. Inspired by carbodiimide-mediated coupling carboxylic acids with 4-bromo-N-methylbenzylamine (4-BNMA) for quantitative analysis, we newly report benefits this reagent TIMS-based measurement. We observed pronounced (orders magnitude) increase in enhanced isomer separations, particularly LC. found that utilization brominated reagent, 4-BNMA, offered unique untargeted Derivatized CCMs displayed shifted out metabolite lipid region TIMS-MS space characteristic isotope patterns, which were leveraged data mining Mass Spectrometry Query Language (MassQL) indication number carboxyl groups. utility our LC-ESI-TIMS-MS/MS method 4-BMA derivatization was demonstrated via characterization alterations expression bone marrow-derived macrophages upon activation lipopolysaccharide. While reprogramming activated has been characterized previously, especially respect TCA novel finding isomeric itaconic, mesaconic, citraconic after 24 h, indicating possible roles inflammatory response.

Language: Английский

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Gut microbiota metabolites impact immunologic responses to antiretroviral therapy in HIV-infected men who have sex with men

Infectious Diseases of Poverty, Journal Year: 2025, Volume and Issue: 14(1)

Published: March 18, 2025

Abstract Background The association between gut microbial metabolites and immunologic non-response among people living with HIV (PLHIV) receiving antiretroviral therapy (ART) has not been well established. We aimed to characterize HIV-infected men who have sex (MSM) different responses. Methods recruited MSM from Guangzhou Eighth People’s Hospital HIV-uninfected (healthy controls, HC) a local community-based organization in June October 2021. were grouped into good immunological responders (GIR) (CD4 + T cell count ≥ 350 cells/μl) poor (PIR) < after 24 months of ART treatment. Online questionnaires stool samples collected. Microbial obtained through ultra-performance liquid chromatography coupled tandem mass spectrometry (UPLC-MS/MS) system. Differential identified analyzed using the Kruskal–Wallis test, followed by pairwise comparisons Wilcoxon rank-sum test. least absolute selection shrinkage operator was used select potential biomarkers. Results A total 51 HC, 56 GIR, 42 PIR included. No statistically significant differences observed median time since diagnosis duration GIR PIR. Among 174 quantified metabolites, 81 significantly differed ( P 0.05). differential indole-3-propionic acid decreased HC (11.39 nmol/g) (8.16 (6.50 nmol/g). pathway analysis showed that tryptophan metabolism Four biomarkers (dimethylglycine, cinnamic acid, 3-hydroxyisovaleric propionic acid) distinguish identified, corresponding area under curve based on 0.773 (95% CI : 0.675–0.871). Conclusions This study These results indicate as novel disease progression markers therapeutic targets. Graphical

Language: Английский

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Asparagine transporter supports macrophage inflammation via histone phosphorylation

Science Advances, Journal Year: 2025, Volume and Issue: 11(15)

Published: April 9, 2025

Solute carrier (SLC) family is essential for immune responses; nevertheless, whether and how SLCs regulate macrophage inflammation remains unclear. Here, we demonstrate that K636 acetylation mediates high abundance of SLC6A14 in inflammatory macrophages. Notably, the pharmacological inhibition or genetic modulation reduces interleukin-1β (IL-1β) secretion dependently lower asparagine uptake subsequently enhanced nuclear LKB1. Mechanistically, LKB1 lessens MAPK pathway–mediated NLRP3 inflammasome activation by increased histone 3 S10/28 phosphorylation-dependent cyclin O transcription. Moreover, myeloid Slc6a14 deficiency alleviates pulmonary via suppressing responses. Overall, these results uncover a network which SLC6A14-mediated orchestrates through phosphorylation, providing crucial target diseases.

Language: Английский

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Integrated mass spectrometry imaging and metabolomics reveals sublethal effects of indoxacarb on the red fire ant Solenopsis invicta

Pest Management Science, Journal Year: 2023, Volume and Issue: 79(9), P. 3122 - 3132

Published: April 4, 2023

Abstract BACKGROUND Indoxacarb, representing an efficient insecticide, is normally made into a bait to spread the poison among red fire ants so that it can be widely applied in prevention and control of Solenopsis invicta . However, potential toxicity mechanism S. response indoxacarb remains explored. In this study, we integrated mass spectrometry imaging (MSI) untargeted metabolomics methods reveal disturbed metabolic expression levels spatial distribution within whole‐body tissue treated with indoxacarb. RESULTS Metabolomics results showed significantly altered level metabolites after treatment, such as carbohydrates, amino acids pyrimidine derivatives. Additionally, regulation several crucial resulting from pathway lipids visualized using label‐free MSI methods. Specifically, xylitol, aspartate, uracil were distributed throughout whole body , while sucrose‐6′‐phosphate glycerol mainly abdomen thymine was head chest Taken together, indicated closely associated disturbance key pathways, metabolism, aspartate pentose glucuronate interconversions, inhibited energy synthesis. CONCLUSION Collectively, these findings provide new perspective for understanding assessment between targeted organisms pesticides. © 2023 Society Chemical Industry.

Language: Английский

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Plasma metabolomics of schizophrenia with cognitive impairment: A pilot study

Frontiers in Psychiatry, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 28, 2022

Schizophrenia (SCZ) acts as a complex and burdensome disease, in which the functional outcome can be validly predicted by cognitive impairment, one of core features. However, there still lack considerable markers deficits SCZ. Based on metabolomics, it is expected to identify different metabolic characteristics SCZ with impairment. In present study, 17 patients impairment (CI), matched normal (CN), 20 healthy control subjects (HC) were recruited, whose plasma metabolites measured using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The result profiling indicated identification 46 differentially expressed between HC, CN, CI groups, 7 CN groups. Four differential (imidazolepropionic acid, Homoserine, Aspartic acid) repeatedly found both screenings, formed biomarker panel could discriminate from (AUC = 0.974) health 0.841), respectively. Several significant pathways highlighted pathway analysis, involving Alanine, aspartate glutamate metabolism, D-glutamine D-glutamate Citrate cycle (TCA cycle). this several identified providing novel insights into clinical treatment strategies.

Language: Английский

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Targeted metabolomics combined with network pharmacology to reveal the protective role of luteolin in pulmonary arterial hypertension

Food & Function, Journal Year: 2022, Volume and Issue: 13(20), P. 10695 - 10709

Published: Jan. 1, 2022

Pulmonary arterial hypertension (PAH) is a progressive disease that significantly endangers human health, where metabolism may drive pathogenesis: shift from mitochondrial oxidation to glycolysis occurs in diseased pulmonary vessels and the right ventricle. An increase vascular resistance patients with heart failure preserved ejection fraction portends poor prognosis. Luteolin exists numerous foods marketed as dietary supplement assisting many treatments. However, little known about protective effect of luteolin on disorders vessels. In this study, we found apparently reversed remodeling PAH rats by inhibiting abnormal proliferation artery smooth muscle cells (PASMCs). Moreover, network pharmacology metabolomics results revealed arachidonic acid pathway, amino pathway TCA cycle were dysregulated PAH. A total 14 differential metabolites changed during PAH, including DHA, PGE2, PGD2, LTB4, 12-HETE, 15-HETE, PGF2α, 8-iso-PGF2α L-asparagine, oxaloacetate, N-acetyl-L-ornithine, butane diacid, ornithine, glutamic pathways. treatment recovered PGF2α levels close normal. Meanwhile, showed also downregulated gene protein COX 1, 5-LOX, 12-LOX, 15-LOX pathway. Collectively, work highlighted metabolic mechanism luteolin-protected would hold great potential prevention.

Language: Английский

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Early Neuroprotective Effects of Bovine Lactoferrin Associated with Hypothermia after Neonatal Brain Hypoxia-Ischemia in Rats

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(21), P. 15583 - 15583

Published: Oct. 25, 2023

Neonatal hypoxic-ischemic (HI) encephalopathy (HIE) in term newborns is a leading cause of mortality and chronic disability. Hypothermia (HT) the only clinically available therapeutic intervention; however, its neuroprotective effects are limited. Lactoferrin (LF) major whey protein milk presenting iron-binding, anti-inflammatory anti-apoptotic properties has been shown to protect very immature brains against HI damage. We hypothesized that combining early oral administration LF with whole body hypothermia could enhance neuroprotection HIE rat model. Pregnant Wistar rats were fed an LF-supplemented diet (1 mg/kg) or control from (P6). At P7, male female pups had right common carotid artery occluded followed by hypoxia (8% O2 for 60') (HI). Immediately after hypoxia, (target temperature 32.5-33.5 °C) was performed (5 h duration) using Criticool®. The animals divided according diet, injury thermal condition. P8 (24 HI), brain neurochemical profile assessed magnetic resonance spectroscopy (1H-MRS) hyperintense T2W signal used measure lesions. mRNA levels genes related glutamatergic excitotoxicity, energy metabolism inflammation hippocampus. cell markers apoptosis expression immunofluorescence decreased metabolites increased lactate. neuronal-astrocytic coupling impairments observed groups reversed mainly HT. important effect on astrocyte function, decreasing excitotoxicity restoring metabolic support. When combined, HT presented synergistic prevented lactate accumulation, reduced damage, pointing out benefits these therapies. Overall, we showed through distinct mechanisms lactoferrin can induced following neonatal hypoxia-ischemia.

Language: Английский

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Glutamate oxaloacetate transaminase 1 is dispensable in macrophage differentiation and anti-pathogen response

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: July 5, 2024

Abstract Macrophages play a pivotal role in orchestrating the immune response against pathogens. While intricate interplay between macrophage activation and metabolism remains subject of intense investigation, glutamate oxaloacetate transaminase 1 ( Got1 ) this context has not been extensively assessed. Here, we investigate impact on polarization function, shedding light its reactive oxygen species (ROS) production, pathogen defense, paralysis. Using genetically modified mouse models, including both myeloid specific knockout overexpression, comprehensively demonstrate that depletion leads to reduced ROS production macrophages. Intriguingly, impairment generation does affect resistance KO mice pathogenic challenges. Furthermore, is dispensable for M2 differentiation influence onset LPS-induced Our findings underscore facets responses, suggesting discrete immunological processes.

Language: Английский

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