APOE Polymorphism Is Associated with Changes in the Kynurenine Pathway DOI Open Access
Per G. Farup, Helge Rootwelt, Knut Hestad

et al.

Genes, Journal Year: 2023, Volume and Issue: 14(10), P. 1955 - 1955

Published: Oct. 18, 2023

Background: APOE polymorphism and the Kynurenine pathway (KP) are associated with many disorders, but little is known about associations between KP. This study explored KP in disorders changes Methods: Subjects morbid obesity before after bariatric surgery (numbers 139 95, respectively), depression (number 49), unspecified neurological symptoms 39) were included. The following grouping of genotypes was used: E2 = ɛ2ɛ2 + ɛ2ɛ3, E3 ɛ3ɛ3 ɛ2ɛ4, E4 ɛ3ɛ4 ɛ4ɛ4. metabolites Tryptophan, Kynurenine, Kynurenic acid, Quinolinic Xanthurenic acid quantified serum. Results: main findings a significant positive association (difference E2E4: 12.0 (3.5; 18.6) ng/mL); p 0.005), negative E2E3: −31.3 (−54.2; −3.2) ng/mL; 0.008). has been ascribed neurotoxic inflammatory effects, marker inflammation. Conclusions: indicate that might cause contribute to disease. Inflammation could be link

Language: Английский

Causal relationship between dementia and delirium: Insights from a bidirectional two-sample Mendelian randomization analysis DOI
Yongsong Cai, Jiachen Wang, Xinyi Wang

et al.

Journal of Affective Disorders, Journal Year: 2024, Volume and Issue: 349, P. 69 - 76

Published: Jan. 8, 2024

Language: Английский

Citations

4
Lipid Dysregulation and Delirium in Older Adults: A Review of the Current Evidence and Future Directions DOI Creative Commons

AnaLee Shaw,

Rujia Teng,

Toluwani Fasina

et al.

Brain Research Bulletin, Journal Year: 2025, Volume and Issue: 224, P. 111299 - 111299

Published: March 12, 2025

Delirium is a complex medical condition marked by acute episodes of cognitive dysfunction and behavioral disturbances, with multifaceted etiology challenging management across various clinical settings. Older adults, particularly in postoperative contexts, are at increased risk developing delirium. Despite extensive research, single underlying pathophysiological mechanism for delirium remains elusive. However, emerging evidence suggests correlation between lipid dysregulation development elderly patients, especially This connection has led to proposed treatments targeting dyslipidemia associated neuroinflammatory effects acute-phase review aims synthesize current literature on the relationship older highlighting need further research into specific neurolipidome constituents age-related profile changes, potentially uncovering novel therapeutic strategies

Language: Английский

Citations

0
AI-Assisted Identification of Primary and Secondary Metabolomic Markers for Postoperative Delirium DOI Open Access
В. А. Иванисенко, Artem D. Rogachev, A. A. Makarova

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(21), P. 11847 - 11847

Published: Nov. 4, 2024

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

Language: Английский

Citations

2
Lipopolysaccharide-Induced Delirium-like Behaviour in a Rat Model of Chronic Cerebral Hypoperfusion Is Associated with Increased Indoleamine 2,3-Dioxygenase Expression and Endotoxin Tolerance DOI Open Access
Hui Phing Ang, Suzana Makpol, Muhammad Luqman Nasaruddin

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(15), P. 12248 - 12248

Published: July 31, 2023

Indoleamine 2,3-dioxygenase (IDO) and the tryptophan–kynurenine pathway (TRP-KP) are upregulated in ageing could be implicated pathogenesis of delirium. This study evaluated role IDO/KP lipopolysaccharide (LPS)-induced delirium an animal model chronic cerebral hypoperfusion (CCH), a proposed for CCH was induced by permanent bilateral common carotid artery ligation (BCCAL) Sprague Dawley rats to trigger neuroinflammation-induced neurodegeneration. Eight weeks after BCCAL, were treated with single systemic LPS. The divided into three groups: (1) post-BCCAL intraperitoneal (i.p.) saline, (2) i.p. LPS 100 μg/kg, (3) sham-operated μg/kg. Each group consisted 10 male rats. To elucidate LPS-induced delirium-like behaviour, natural learned behaviour changes assessed buried food test (BFT), open field (OFT), Y-maze at 0, 24-, 48-, 72 h treatment. Serum collected each session behavioural assessment. euthanised last serum collection, hippocampi cortex collected. TRP-KP neuroactive metabolites measured both brain tissues using ELISA. Our data show that treatment associated acute, transient, fluctuated deficits consistent features These mild compared rats, which exhibited robust impairments. Additionally, heightened hippocampal IDO expression LPS-treated reduced KP activity together decrease quinolinic acid (QA) suggested presence endotoxin tolerance through immunomodulatory brain. provide new insight underlying mechanisms delirium, future studies should further explore modulation its therapeutic potential

Language: Английский

Citations

5
Mechanisms underlying delirium in patients with critical illness DOI Creative Commons
Yingying Fan,

Ruoyu Luo,

Meng-Tian Wang

et al.

Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 16

Published: Sept. 26, 2024

Delirium is an acute, global cognitive disorder syndrome, also known as acute brain characterized by disturbance of attention and awareness fluctuation symptoms. Its incidence high among critically ill patients. Once patients develop delirium, it increases the risk unplanned extubation, prolongs hospital stay, nosocomial infection, post-intensive care syndrome-cognitive impairment, even death. Therefore, great importance to understand how delirium occurs reduce in This paper reviews potential pathophysiological mechanisms patients, with aim better understanding its processes, guiding formulation effective prevention treatment strategies, providing a basis for clinical medication.

Language: Английский

Citations

1
The possible interaction between tryptophan and its metabolites with delirium in older patients with critical illnesses DOI Creative Commons
Korhan Kollu, Hüseyin Kurku, Ali Ünlü

et al.

European Geriatric Medicine, Journal Year: 2024, Volume and Issue: 15(6), P. 1937 - 1948

Published: Nov. 27, 2024

Abstract Aim The present study aimed to investigate the relationship between delirium and tryptophan its metabolites in critically ill older patients. Methods This prospective observational was conducted on patients who were > 60 years of age hospitalized for at least 24 h internal medicine ICU tertiary health care unit ( n = 120). All consecutively selected evaluated baseline follow-up period bedside by an intensive specialist. At end follow up, divided into two groups (with without delirium). Clinical properties (TRP) [kynurenine (KYN), kynurenic acid (KYNA), quinolinic (QA), 3-hydroxykynurenine (3-HK), 3-hydroxyanthranilic (3HAA)] compared groups. Results median 79.5 (62–95) 53.3% female. CCI score significantly higher among with than those P 0.001 0.031, respectively). level TRP (borderline) decreased 0.056). KYN/TRP QA/TRP ratios statistically < 0.016, best predictive values detecting calculated as ≤ 14,100 ng/mL (AUC: 0.601, 0.052), 1.12 ratio 0.704, 0.001), 0.75 0.627, 0.013). showed independent borderline significant association being multivariable regression analysis (Odds ratio: 2.007, 0.066). Conclusion demonstrated that obtained within first admission might have value determining high-risk delirium.

Language: Английский

Citations

1
AI-Assisted Identification of Primary and Secondary Metabolomic Markers for Post-Operative Delirium DOI Creative Commons
В. В. Ломиворотов, В. А. Иванисенко, A. A. Makarova

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: March 14, 2024

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

Language: Английский

Citations

0
Essential Oils and Their Eco-friendly Encapsulated Products for Mycotoxins Reduction: Current Situation and Future Prospects DOI
Marjan Mahboubifar, Rouhollah Karami‐Osboo, Amir Reza Jassbi

et al.

Food and Bioprocess Technology, Journal Year: 2024, Volume and Issue: unknown

Published: May 21, 2024

Language: Английский

Citations

0
APOE Polymorphism Is Associated with Changes in the Kynurenine Pathway DOI Open Access
Per G. Farup, Helge Rootwelt, Knut Hestad

et al.

Genes, Journal Year: 2023, Volume and Issue: 14(10), P. 1955 - 1955

Published: Oct. 18, 2023

Background: APOE polymorphism and the Kynurenine pathway (KP) are associated with many disorders, but little is known about associations between KP. This study explored KP in disorders changes Methods: Subjects morbid obesity before after bariatric surgery (numbers 139 95, respectively), depression (number 49), unspecified neurological symptoms 39) were included. The following grouping of genotypes was used: E2 = ɛ2ɛ2 + ɛ2ɛ3, E3 ɛ3ɛ3 ɛ2ɛ4, E4 ɛ3ɛ4 ɛ4ɛ4. metabolites Tryptophan, Kynurenine, Kynurenic acid, Quinolinic Xanthurenic acid quantified serum. Results: main findings a significant positive association (difference E2E4: 12.0 (3.5; 18.6) ng/mL); p 0.005), negative E2E3: −31.3 (−54.2; −3.2) ng/mL; 0.008). has been ascribed neurotoxic inflammatory effects, marker inflammation. Conclusions: indicate that might cause contribute to disease. Inflammation could be link

Language: Английский

Citations

0