Chemical Engineering Journal, Journal Year: 2025, Volume and Issue: unknown, P. 163217 - 163217
Published: May 1, 2025
Brain Behavior and Immunity, Journal Year: 2023, Volume and Issue: 114, P. 195 - 213
Published: Aug. 28, 2023
Language: Английский
Citations
26
Shock, Journal Year: 2023, Volume and Issue: 59(4), P. 583 - 590
Published: Feb. 23, 2023
Background: Sepsis-associated encephalopathy (SAE) is a dysfunction of the central nervous system experienced during sepsis with variable clinical and pathophysiologic features. We sought to identify distinct SAE phenotypes in relation outcomes. Methods: The Medical Information Mart for Intensive Care IV (MIMIC-IV) database eICU were used conduct retrospective cohort study. Adult patients included was defined as having Glasgow Coma Scale (GCS) score ˂15 or delirium. following our as: ischemic-hypoxic, metabolic, mixed (ischemic-hypoxic metabolic), unclassified. primary outcome in-hospital mortality. Results: study enrolled 4,120 patients, 2,239 from MIMIC-IV (including 1,489 SAE, 67%), 1,881 (1,291, 69%). For cohort, 2,780 total (median age, 67 years; interquartile range, 56-76.8; 1,589 (57%) male; median GCS 12 [8-14]; Sequential Organ Failure Assessment 6 [4-9]). phenotype distributions between cohorts follows (39% vs. 35% P = 0.043; 38% 40% 0.239; 15% mixed, 0.972; unclassified, 0.471). overall mortality unclassified 33.9% (95% confidence interval, 0.3-0.37), 28.4% (0.26-0.31), 41.5% (0.37-0.46), 14.2% (0.12-0.16), respectively. In multivariable logistic analysis, associated highest risk after adjusting sex, GCS, modified (adjusted odds ratio, 2.11; 95% 1.67-2.67; < 0.001). Conclusions: Four had different worst Further understanding these may improve trial design targeted management.
Language: Английский
Citations
22
International Immunopharmacology, Journal Year: 2023, Volume and Issue: 124, P. 110800 - 110800
Published: Aug. 22, 2023
Language: Английский
Citations
21
Journal of Neuroinflammation, Journal Year: 2023, Volume and Issue: 20(1)
Published: Nov. 30, 2023
Neuroinflammation mediated by microglial pyroptosis is an important pathogenic mechanism of septic encephalopathy (SAE). It has been reported that TRIM45 associated with tumours and inflammatory diseases. However, the role in SAE relationship between are unknown. In this study, we found played regulating molecular mechanism.SAE was induced intraperitoneal injection LPS WT AAV-shTRIM45 mice. BV2 cells were treated LPS/ATP vitro. Cognitive function assessed Morris water maze. Nissl staining used to evaluate histological structural lesions. ELISA dectect neuroinflammation. qPCR detect mRNA levels cytokines, NLRP3, autophagy genes. Western blotting immunofluorescence analysis analyse expression proteins. Changes reactive oxygen species (ROS) observed flow cytometry. mitochondrial membrane potential detected JC-1 staining. Peripheral blood mononuclear extracted from density gradient centrifugation then for qPCR, western detection. To further explore mechanism, overexpression plasmids Atg5 as well siRNA-TRIM45 siRNA-Atg5 downstream pathway NLRP3. The protein peripheral sepsis patients examined.Knocking down protected against neuronal damage cognitive impairment knockdown inhibited secretion cytokines vivo vitro, which NLRP3/Gsdmd-N activation. Overexpression could activate NLRP3 Further examination showed regulated activation altering autophagic flux. also affected changes ROS potential. Thus, knocking reduce pyroptosis, proinflammatory improve function. addition, level increased. There a positive linear correlation APACHE II score TRIM45, SOFA TRIM45. Compared group GCS > 9, increased ≤ 8.TRIM45 plays key neuroinflammation caused LPS, may involve TRIM45-mediated exacerbation via Atg5/NLRP3 axis.
Language: Английский
Citations
18
Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)
Published: Jan. 30, 2024
Abstract Background Sepsis-associated encephalopathy (SAE) is an acute cerebral dysfunction caused by sepsis. Neuroinflammation induced sepsis considered a potential mechanism of SAE; however, very little known about the role meningeal lymphatic system in SAE. Methods Sepsis was established male C57BL/6J mice intraperitoneal injection 5 mg/kg lipopolysaccharide, and function drainage assessed. Adeno-associated virus 1-vascular endothelial growth factor C (AAV1-VEGF-C) injected into cisterna magna to induce lymphangiogenesis. Ligation deep cervical lymph nodes (dCLNs) performed pre-existing dysfunction. Cognitive evaluated fear conditioning test, inflammatory factors were detected enzyme-linked immunosorbent assay. Results The aged with SAE showed significant decrease OVA-647 dCLNs coverage Lyve-1 lymphatic, indicating that impaired morphology. more vulnerable comparison young mice. also decreased protein levels caspase-3 PSD95, which accompanied reductions activity hippocampal neurons. Microglia significantly activated hippocampus mice, increase neuroinflammation, as indicated increases interleukin-1 beta, interleukin-6 Iba1 expression. However, AAV1-VEGF-C increased tracer dye uptake dCLNs, suggesting promotes lymphangiogenesis drainage. Furthermore, reduced microglial activation neuroinflammation improved cognitive Improvement lymphatics sepsis-induced expression disease-associated genes Pre-existing ligating bilateral aggravated impairment. Conclusion damaged sepsis, defects this exacerbate SAE-induced Promoting improves Manipulation could be new strategy for treatment
Language: Английский
Citations
7
Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)
Published: May 17, 2024
Sepsis-associated encephalopathy (SAE) causes acute and long-term cognitive deficits. However, information on the prevention treatment of dysfunction after sepsis is limited. The neuropeptide orexin-A (OXA) has been shown to play a protective role against neurological diseases by modulating inflammatory response through activation OXR1 OXR2 receptors. OXA in mediating neuroprotective effects SAE not yet reported.
Language: Английский
Citations
6
Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)
Published: May 11, 2024
Abstract MiRNAs in mesenchymal stem cells (MSCs)-derived exosome (MSCs-exo) play an important role the treatment of sepsis. We explored mechanism through which MSCs-exo influences cognitive impairment sepsis-associated encephalopathy (SAE). Here, we show that miR-140-3p targeted Hmgb1 . plus mimic (Exo) and antibiotic imipenem/cilastatin (ABX) improve survival, weight, cecal ligation puncture (CLP) mice. Exo ABX inhibit high mobility group box 1 (HMGB1), IBA-1, interleukin (IL)-1β, IL-6, iNOS, TNF-α, p65/p-p65, NLRP3, Caspase 1, GSDMD-N levels. In addition, upregulates S-lactoylglutathione levels hippocampus CLP Our data further demonstrates increase GSH LPS-induced HMC3 decrease LD GLO2 levels, inhibiting inflammatory responses pyroptosis. These findings suggest MSCs-exo-mediated delivery ameliorates mice with SAE by HMGB1 metabolism, providing potential therapeutic targets for clinical SAE.
Language: Английский
Citations
6
Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 177, P. 117092 - 117092
Published: July 7, 2024
Sepsis-associated encephalopathy (SAE) is a disease characterized by neuroinflammation and cognitive dysfunction caused systemic infection. Inflammation-induced microglial activation closely associated with in SAE. It widely understood that melatonin has strong anti-inflammatory immunomodulatory properties beneficial for sepsis-related brain damage. However, the mechanism of action SAE not been fully elucidated.
Language: Английский
Citations
6
ACS Nano, Journal Year: 2024, Volume and Issue: 18(41), P. 28228 - 28245
Published: Oct. 5, 2024
Sepsis-associated encephalopathy (SAE) is a devastating complication of sepsis, affecting approximately 70% patients with sepsis in intensive care units (ICU). Although the pathophysiological mechanisms remain elusive, typically accompanied by systemic inflammatory response syndrome (SIRS) and hyper-oxidative conditions. Here, we introduce biomimetic nanomodulator (mAOI NP) that specifically targets inflammation site simultaneously regulates oxidative stresses. mAOI NPs are constructed using metal-coordinated polyphenolic antioxidants (tannic acid) flavonoid quercetin, which then coated macrophage membrane to enhance pharmacokinetics enable SAE targeting. In cecal ligation puncture (CLP)-induced severe model, effectively mitigate stress purging reactive oxygen species, repairing mitochondrial damage activating Nrf2/HO-1 signaling pathway; while polarizing M1 macrophages or microglia toward anti-inflammatory M2 subtype. potently inhibit progress, prolong overall survival from 25 66% learning memory capabilities mice. Further proteomics analysis reveals modulate neurodevelopment processes related formation also exerting antioxidative effects on brain tissue responses associated pathology. This study offers significant potential for improving patient outcomes revolutionizing treatment landscape this sepsis.
Language: Английский
Citations
6
Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(36)
Published: Aug. 27, 2024
Sepsis-associated encephalopathy (SAE) is a critical neurological complication of sepsis and represents crucial factor contributing to high mortality adverse prognosis in septic patients. This study explored the contribution NAT10-mediated messenger RNA (mRNA) acetylation cognitive dysfunction associated with SAE, utilizing cecal ligation puncture (CLP)-induced SAE mouse model. Our findings demonstrate that CLP significantly upregulates NAT10 expression mRNA excitatory neurons hippocampal dentate gyrus (DG). Notably, neuronal-specific Nat10 knockdown improved function mice, highlighting its role SAE. Proteomic analysis, immunoprecipitation, real-time qPCR identified GABA B R1 as key downstream target NAT10. deletion reduced expression, subsequently weakened inhibitory postsynaptic currents DG neurons. Further analysis revealed microglia activation release inflammatory mediators lead increased Microglia depletion PLX3397 effectively neurons, ameliorated induced by In summary, our after CLP, promotes through acetylation, leading dysfunction.
Language: Английский
Citations
5