Kynurenine Pathway Metabolites as Potential Biomarkers in Chronic Pain

Auyeung, Andrew; Wang, Hank C; Aravagiri, Kannan; Knezevic, Nebojsa Nick

doi:10.3390/ph16050681

Cited by 5 publications

(2 citation statements)

References 72 publications

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“…The enrichment analysis aims to identify metabolic pathways that exhibit systemic disturbances. However, indicators of the metabolic pathway disruptions can comprise not only increased or decreased concentrations of the individual metabolites, but also the disturbances of coordination or correlation between the concentrations of metabolites implicated in the metabolic pathway 14 . Metabolites exhibiting disrupted correlations with other metabolites in the context of a pathological process may be termed as the secondary metabolomic markers 16 .…”

Section: Identification Of the Primary Metabolomic Markersmentioning

confidence: 99%

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AI-Assisted Identification of Primary and Secondary Metabolomic Markers for Post-Operative Delirium

Lomivorotov,

Ivanisenko,

Makarova

et al. 2024

Preprint

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Despite considerable investigative efforts, the molecular mechanisms of postoperative delirium (POD) remain unresolved. The present investigation employs innovative methodologies for identifying potential primary and secondary metabolic markers of POD by analyzing serum metabolomic profiles utilizing the genetic algorithm and artificial neural networks. The primary metabolomic markers constitute a combination of metabolites that optimally distinguish between POD and non-POD groups of patients. Our analysis revealed L-lactic acid, inositol, and methylcysteine as the most salient primary markers, upon which the prediction accuracy of POD manifestation achieved AUC = 99%. The secondary metabolomic markers represent metabolites that exhibit perturbed correlational patterns within the POD group. We identified 54 metabolites as the secondary markers of POD, incorporating neurotransmitters such as gamma-aminobutyric acid (GABA), serotonin. These findings imply a systemic disruption in metabolic processes in patients with POD. The deployment of gene network reconstruction techniques facilitated the postulation of hypotheses describing the role of established genomic POD markers in the molecular-genetic mechanisms of metabolic pathways dysregulation, involving the identified primary and secondary metabolomic markers. This study not only expands the understanding of POD pathogenesis but also introduces a novel technology for bioinformatic analysis of metabolomic data which could aid in uncovering potential primary and secondary markers in diverse research domains.

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Section: Identification Of the Primary Metabolomic Markersmentioning

confidence: 99%

“…Perturbations in the interplay among metabolites can offer insightful explanations of metabolic pathway dysfunction across an array of pathologies at a systemic level 14 . Metabolites that exhibit disrupted coordinated variability with their counterparts may be designated as secondary biomarkers 15,16 .…”

mentioning

confidence: 99%

AI-Assisted Identification of Primary and Secondary Metabolomic Markers for Post-Operative Delirium

Lomivorotov,

Ivanisenko,

Makarova

et al. 2024

Preprint

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Ketamine and Esketamine in Clinical Trials: FDA‐Approved and Emerging Indications, Trial Trends With Putative Mechanistic Explanations

Vekhova,

Namiot,

Jonsson

et al. 2024

Clin Pharma and Therapeutics

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Ketamine has a long and very eventful pharmacological history. Its enantiomer, esketamine ((S)‐ketamine), was approved by the US Food and Drug Administration (FDA) and EMA for patients with treatment‐resistant depression (TRD) in 2019. The number of approved indications for ketamine and esketamine continues to increase, as well as the number of clinical trials. This analysis provides a quantitative overview of the use of ketamine and its enantiomers in clinical trials during 2014–2024. A total of 363 trials were manually assessed from clinicaltrial.gov with the search term “Ketamine.” The highest number of trials were found for the FDA‐approved indications: anesthesia (~22%) and pain management (~28%) for ketamine and TRD for esketamine (~29%). Clinical trials on TRD for both ketamine and esketamine also comprised a large proportion of these trials, and interestingly, have reached phase III and phase IV status. Combinatorial treatment of psychiatric disorders and non‐psychiatric conditions with pharmacological and non‐pharmacological combinations (electroconvulsive therapy, psychotherapeutic techniques, virtual reality, and transcranial magnetic stimulation) is prevalent. Sub‐anesthetic doses of ketamine may represent novel therapeutic avenues in neuropsychiatric conditions, that is, major depression, schizophrenia, and bipolar disorder, where glutamate excitotoxicity and oxidative stress are likely to be involved. The study suggests that the number of ketamine studies will continue to grow and possible ketamine variants can be approved for treatment of additional indications.

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Altered kynurenine pathway metabolism and association with disease activity in patients with systemic lupus

Eryavuz Onmaz,

Tezcan,

Yilmaz

et al. 2023

Amino Acids

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Kynurenine Pathway Metabolites as Potential Biomarkers in Chronic Pain

Cited by 5 publications

References 72 publications

AI-Assisted Identification of Primary and Secondary Metabolomic Markers for Post-Operative Delirium

AI-Assisted Identification of Primary and Secondary Metabolomic Markers for Post-Operative Delirium

Ketamine and Esketamine in Clinical Trials: FDA‐Approved and Emerging Indications, Trial Trends With Putative Mechanistic Explanations

Altered kynurenine pathway metabolism and association with disease activity in patients with systemic lupus

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