Integrating metabolomics and lipidomics revealed a decrease in plasma fatty acids but an increase in triglycerides in children with drug‐refractory epilepsy

Epilepsia Open, Год журнала: 2023, Номер 8(2), С. 466 - 478

Опубликована: Фев. 20, 2023

The drug-refractory epilepsy (DRE) in children is commonly observed but the underlying mechanisms remain elusive. We examined whether fatty acids (FAs) and lipids are potentially associated with pharmacoresistance to valproic acid (VPA) therapy.This single-center, retrospective cohort study was conducted using data from pediatric patients collected between May 2019 December at Children's Hospital of Nanjing Medical University. Ninety plasma samples 53 responders VPA monotherapy (RE group) 37 non-responders polytherapy (NR were collected. Non-targeted metabolomics lipidomics analysis for those performed compare potential differences small metabolites two groups. Plasma passing threshold variable importance projection value >1, fold change >1.2 or <0.8, p-value <0.05 regarded as statistically different substances.A total 204 433 comprising 16 lipid subclasses identified. well-established partial least squares-discriminant (PLS-DA) revealed a good separation RE NR group. FAs glycerophospholipids status significantly decreased group, their triglycerides (TG) levels increased. trend TG routine laboratory tests line analysis. Meanwhile, cases group characterized by level citric L-thyroxine, an increased glucose 2-oxoglutarate. top enriched metabolic pathways involved DRE condition biosynthesis unsaturated linoleic metabolism.The results this suggested association metabolism medically intractable epilepsy. Such novel findings might propose mechanism linked energy metabolism. Ketogenic supplementation therefore be high-priority strategies management.

Язык: Английский

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Mass Spectrometric Imaging of Anionic Phospholipids Desorbed from Human Hippocampal Sections: Discrimination between Temporal and Nontemporal Lobe Epilepsies

ACS Chemical Neuroscience, Год журнала: 2024, Номер 15(5), С. 983 - 993

Опубликована: Фев. 14, 2024

Temporal lobe epilepsy (TLE) is one of the most common neurological disorders, often accompanied by hippocampal sclerosis. The molecular processes underlying this epileptogenesis are poorly understood. To examine lipid profile, 39 fresh frozen sections human hippocampus obtained from surgery for TLE (n = 14) and non-TLE (control group; n 25) patients were subjected to desorption electrospray ionization mass spectrometry imaging in negative ion mode. In contrast our earlier report that showed striking downregulation positively charged phospholipids (e.g., phosphatidylcholine phosphatidylethanolamine, etc.) hippocampus, study finds complementary upregulation negatively phospholipids, notably, phosphatidylserine phosphatidylglycerol. This result may point an active metabolic pool produces these anionic at expense cationic phospholipids. shift could be due dysregulation Kennedy CDP-DG pathways responsible biosynthesizing lipids. Thus, further opens up opportunities investigate hallmarks potential therapeutic targets TLE.

Язык: Английский

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Role of inflammatory cytokine in mediating the effect of plasma lipidome on epilepsy: a mediation Mendelian randomization study

Frontiers in Neurology, Год журнала: 2024, Номер 15

Опубликована: Май 30, 2024

Background Epilepsy is one of the most prevalent serious brain disorders globally, impacting over 70 million individuals. Observational studies have increasingly recognized impact plasma lipidome on epilepsy. However, establishing a direct causal link between and epilepsy remains elusive due to inherent confounders complexities reverse causality. This study aims investigate relationship specific epilepsy, along with their intermediary mediators. Methods We conducted two-sample Mendelian randomization (MR) mediation MR analysis evaluate effects 179 lipidomes focus inflammatory cytokine as potential mediator based genome-wide association study. The primary methodological approach utilized inverse variance weighting, complemented by range other estimators. A set sensitivity analyses, including Cochran’s Q test, I 2 statistics, MR-Egger intercept MR-PRESSO global test leave-one-out analyses was performed assess robustness, heterogeneity horizontal pleiotropy results. Results Our findings revealed positive correlation Phosphatidylcholine (18:1_18:1) levels risk (OR = 1.105, 95% CI: 1.036–1.178, p 0.002). Notably, our results propose Tumor necrosis factor ligand superfamily member 12 (TNFSF12) (18,1_18:1) risk, explaining proportion 4.58% [mediation effect: ( b 0.00455, −0.00120-0.01030), Z 1.552]. Conclusion research confirms genetic emphasizing mediating role TNFSF12 provide valuable insights for future clinical investigations into

Язык: Английский

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Valproic Acid Treatment after Traumatic Brain Injury in Mice Alleviates Neuronal Death and Inflammation in Association with Increased Plasma Lysophosphatidylcholines

Cells, Год журнала: 2024, Номер 13(9), С. 734 - 734

Опубликована: Апрель 23, 2024

The histone deacetylase inhibitor (HDACi) valproic acid (VPA) has neuroprotective and anti-inflammatory effects in experimental traumatic brain injury (TBI), which have been partially attributed to the epigenetic disinhibition of transcription repressor RE1-Silencing Transcription Factor/Neuron-Restrictive Silencer Factor (REST/NRSF). Additionally, VPA changes post-traumatic (TBI) metabolism create a environment. To address interconnection neuroprotection, metabolism, inflammation REST/NRSF after TBI, we subjected C57BL/6N mice TBI intraperitoneal administration or vehicle solution at 15 min, 1, 2, 3 days post-injury (dpi). At 7 dpi, TBI-induced an up-regulation gene expression HDACi function on H3 acetylation were confirmed. Neurological deficits, lesion size, blood–brain barrier permeability, astrogliosis not affected, target genes only marginally influenced by VPA. However, attenuated structural damage hippocampus, microgliosis pro-inflammatory marker genes. Analyses plasma lipidomic polar metabolomic patterns revealed that treatment increased lysophosphatidylcholines (LPCs), inversely associated with interleukin 1 beta (Il1b) tumor necrosis factor (Tnf) brain. results show mild likely originating from favorable systemic metabolic resulting LPCs are known be actively taken up as carriers for polyunsaturated fatty acids.

Язык: Английский

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Untargeted metabolomics reveal the corrective effects of scorpion on epileptic mice

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 6, 2025

Scorpion is a commonly used drug in traditional Chinese medicine for treating epilepsy, although the exact mechanisms are not yet fully understood. This study aimed to compare treatment effects of water extract (SWE) and ethanol (SEE) on mice with pentetrazole-induced epilepsy investigate possible through metabolomics methods. A epileptic model was assess corrective SWE SEE. Untargeted metabolomics, utilizing UPLC-Q-TOF/MS, employed analyze metabolic profiles identify changes following scorpion treatment. The results revealed that only showed therapeutic mice. Metabolomics analysis demonstrated significant alterations signatures between groups. By orthogonal partial least squares discrimination analysis, 44 108 potential biomarkers mouse serum were identified positive negative ion modes, respectively. Differential metabolites related then pinpoint relevant pathways mice, such as linoleic acid metabolism, biosynthesis unsaturated fatty acids, glycerophospholipid ether lipid metabolism. In conclusion, this highlights provides insight into underlying involved its efficacy.

Язык: Английский

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Targeted lipidomics analysis of possible molecular mechanisms of lipid changes in temporal lobe epilepsy models

Frontiers in Pharmacology, Год журнала: 2025, Номер 15

Опубликована: Янв. 9, 2025

Lipids are vital biomolecules involved in the formation of various biofilms. Seizures can cause changes lipid metabolism brain. In-depth studies at multiple levels urgently needed to elucidate composition, distribution, and metabolic pathways brain after seizure. In this research, a cutting-edge targeted quantitative lipidomics study was conducted on hippocampal tissues six rats with temporal lobe epilepsy normal rats. Accurate quantification based linear equations calculated using an internal standard. The lipids were quantitatively qualitatively analyzed by ultra-high performance liquid chromatography (UPLC) mass spectrometry (MS). A total 21 classes identified. Among them, most abundant triacylglycerol (TG), phosphatidyl ethanolamine (PE-P), fatty acids (FA). Cholesteryl ester (ChE) exhibits considerable difference between epileptic samples. ChE found be significantly upregulated lipid, while FA observed downregulated lipid. Based absolute analysis rat specimens, contents change trends different observed. Upregulation dihydroceramide (DHCer) observed, distribution elucidated causes possible molecular mechanisms accumulation epilepsy. results methods described provide comprehensive new therapeutic target for treatment

Язык: Английский

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Integrated analysis of proteomics and metabolomics in infantile epileptic spasms syndrome

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Фев. 6, 2025

Infantile Epileptic Spasms Syndrome (IESS) is a severe developmental epileptic encephalopathy that manifests in infancy, significantly impacting the health and quality of life affected children. The treatment IESS poses significant challenge, primarily due to incomplete understanding its etiology pathogenesis. Objective: This study aims investigate pathogenic mechanisms IESS, utilizing metabolomics proteomics analyses uncover potential biomarkers for disease, thereby providing new insights diagnostic therapeutic strategies. Cerebrospinal fluid samples from 6 patients control subjects with benign intracranial hypertension were collected analyzed using techniques. Significant differential metabolites proteins identified correlated determine key associated specific metabolites. then expanded sample size 10 per group validated through ELISA analysis. A total 24 (12 upregulated 12 downregulated) 79 (18 61 identified. Metabolomic analysis suggests linoleic acid highly noteworthy metabolite cerebrospinal patients. protein HLA-A SEZ6L2 notably downregulated (p < 0.05). Linoleic metabolism-related could serve as into complex disease. Additionally, these findings also assist identifying targets developing more effective

Язык: Английский

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Metabolic aspects of epilepsy: prospects for metabolome research

Russian Journal of Child Neurology, Год журнала: 2025, Номер 20(1), С. 25 - 31

Опубликована: Апрель 18, 2025

Epilepsy is one of the most common neurological diseases. Despite availability modern antiepileptic drugs, up to 30 % patients fail achieve control over seizures and develop pharmacoresistancy, which leads decrease in quality life, social professional limitations as well their stigmatization society. closely connected with malfunction metabolically active systems our body – central nervous system can be cause this metabolic failure its consequence. Metabolomics a new, rapidly developing scientific area promising tool for postgenomic research by studying biological fluids. The study metabolome analysis combination low molecular weight substances (metabolites) an organism or sample, including various such aminoacids, organic acids, sugars, steroids, nucleotides lipids. This review summarizes results studies concerning role disorders epileptogenesis. publications devoted assessment profile epilepsy, features depending on phenotype disease, response therapy. Probably, further metabolism will allow us identify new biomarkers that used process diagnostic search, determining prognosis disease personification

Язык: Английский

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Phospholipidomics in Clinical Trials for Brain Disorders: Advancing our Understanding and Therapeutic Potentials

Molecular Neurobiology, Год журнала: 2023, Номер 61(6), С. 3272 - 3295

Опубликована: Ноя. 20, 2023

Abstract Phospholipidomics is a specialized branch of lipidomics that focuses on the characterization and quantification phospholipids. By using sensitive analytical techniques, phospholipidomics enables researchers to better understand metabolism activities phospholipids in brain disorders such as Alzheimer’s Parkinson’s diseases. In brain, identifying specific phospholipid biomarkers can offer valuable insights into underlying molecular features biochemistry these diseases through variety techniques. has emerged promising tool clinical studies, with immense potential advance our knowledge neurological enhance diagnosis treatment options for patients. present review paper, we discussed numerous applications tools particular focus field. exploring phospholipids’ functions research, provided could aid clinicians harnessing full prospective this innovative practice improve patient outcomes by providing more potent treatments Graphical

Язык: Английский

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Molecular Insights of Drug Resistance in Epilepsy: Multi-omics Unveil

Molecular Neurobiology, Год журнала: 2024, Номер unknown

Опубликована: Май 16, 2024

Язык: Английский

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