Neuropharmacology, Journal Year: 2024, Volume and Issue: unknown, P. 110285 - 110285
Published: Dec. 1, 2024
Language: Английский
Advanced Functional Materials, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 20, 2025
Abstract In the development of nasal‐to‐brain (N2B) drug delivery systems, key challenge lies in penetrating mucus, crossing nasal epithelial barrier, and achieving broad distribution within central nervous system (CNS) while ensuring biosafety. Non‐biomimetic systems raise concerns regarding metabolism, biomimetic though safer, still face premature release into tissues limited distribution. Moreover, N2B transport mechanisms most existing remain inadequately understood. This study proposed an efficient based on tetrahedral framework nucleic acids (tFNAs). These nanostructures, ≈10 nm size, possess densely negative‐charged surfaces that help evade protein capture facilitate rapid penetration mucus layer, travel along olfactory trigeminal nerve axons to achieve widespread CNS. The pathway is clearly elucidated. Additionally, tFNAs are used deliver peptide via intranasal administration treat sepsis‐associated encephalopathy (SAE). Results showed tFNA‐NAP can regulate microglial activity, reduce neuronal damage, improve behavioral outcomes. both short‐ long‐term safety experiments revealed no adverse effects. summary, tFNA‐based fills a gap this field, offering non‐invasive treatment approach for CNS diseases.
Language: Английский
Citations
2
Archives of Physiology and Biochemistry, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 11
Published: March 2, 2025
Objective: This study explores the mechanism of methyltransferase like 3 (METTL3) on sepsis-associated encephalopathy (SAE)-induced hippocampal neuronal injury.
Language: Английский
Citations
1
Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(10), P. 8123 - 8143
Published: March 12, 2024
Language: Английский
Citations
8
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
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
Journal of Affective Disorders, Journal Year: 2024, Volume and Issue: 362, P. 341 - 355
Published: May 29, 2024
Language: Английский
Citations
4
Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 178, P. 117279 - 117279
Published: Aug. 8, 2024
Sepsis-induced myocardial dysfunction (SIMD) is a severe complication in sepsis, manifested as systolic dysfunction, which associated with poor prognosis and higher mortality. Mitophagy, self-protective mechanism maintaining cellular homeostasis, plays an indispensable role cardioprotection. This study aimed to unveil the cardioprotective effects of Baricitinib on LPS-induced its effect mitophagy. Herein, we demonstrated that LPS induced initiated mitophagy septic mice hearts. Despite initiation mitophagy, significant number apoptotic cells damaged mitochondria persisted myocardium, energy metabolism remained impaired, indicating limited was insufficient mitigate damage. The JAK2-AKT-mTOR signaling pathway activated cardiomyocytes hearts mice. administration remarkably improved cardiac function, suppressed systemic inflammatory response, attenuated histopathological changes, inhibited cell apoptosis alleviated damage Furthermore, treatment significantly enhanced PINK1-Parkin-mediated increased autophagosomes, decreased impaired mitochondria, restored metabolism. Mechanically, myocardium p-ULK1 (Ser757), regulated by p-mTOR. reduced (Ser757) inhibiting pathway. Inhibition Mdivi-1 reversed protective anti-inflammatory These findings suggest attenuates SIMD enhancing via pathway, providing novel mechanistic therapeutic insight into SIMD.
Language: Английский
Citations
4
Theranostics, Journal Year: 2025, Volume and Issue: 15(8), P. 3257 - 3274
Published: Feb. 18, 2025
Rationale: The prelimbic cortex (PrL), enriched with oxytocin (OXT) receptors, plays a critical role in memory consolidation. However, the of OXT social consolidation within PrL microcircuit remains poorly understood. Methods: To examine signaling consolidation, we used biosensors and loss-of-function approaches, including tetanus toxin-mediated silencing neurons paraventricular nucleus (PVNOXT), optogenetic inhibition PVNOXT-PrL pathway during rapid-eye-movement (REM) sleep, local administration an receptor antagonist PrL. In vivo molecular for vasoactive intestinal peptide (VIP), somatostatin, presynaptic calcium imaging were employed to assess inhibitory microcircuit. Optogenetic activation intranasal evaluate resilience chronic sleep deprivation-induced deficits. Results: We identified that REM-sleep release via PVN supports deficiency reduces activity VIP parvalbumin (PV) neurons, thereby disrupting balance between somatic mediated by PV dendritic disinhibition microcircuits REM sleep. Chronic deprivation (SD) disrupts balance, leading pyramidal neuron hyperactivity impairments. Notably, REM-sleep-specific or restores rescues deficits SD mice. Conclusion: Our results reveal how modulates support suggesting potential therapeutic strategies treating sleep-related disorders.
Language: Английский
Citations
0
Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)
Published: Feb. 21, 2025
Sepsis-associated encephalopathy (SAE) is a severe neurological condition caused by sepsis, and presents with symptoms ranging from delirium coma to long-term cognitive dysfunction. SAE acknowledged as widespread brain impairment characterized the activation of microglia. However, specific pathological mechanisms that drive this are still not clearly understood. Growth differentiation factor 15 (GDF15) levels have been noted be considerably increased in patients where they linked disease severity can independently predict short- mortality risk. Serum GDF15 also negatively associated gray matter volume older individuals. impact on sepsis-induced memory impairments, well behind these effects, poorly To examine role SAE, sepsis model was created adult C57BL/6J mice using intraperitoneal administration lipopolysaccharide (LPS). plasma cerebrospinal fluid were measured ELISA. The anti-GDF15 monoclonal antibody ponsegromab injected intracerebroventricularly before modeling, functions septic assessed fear-conditioning novel object recognition tests. Microglial phagocytosis evaluated immunofluorescence Golgi staining. Additionally, an vitro investigation LPS-stimulated microglia conducted evaluate impacts inflammatory cytokine productions microglial phagocytic activity. Mechanisms explored RNA sequencing, qPCR, western blotting, flow cytometry, assays. In mice, notably elevated after injection LPS. Lateral ventricular alleviated both together hippocampus, thereby protecting against synaptic loss. brains mice. Targeting found improve reducing response phagocytosis. These results indicate could serve important therapeutic target for treating SAE.
Language: Английский
Citations
0
Journal of Mass Spectrometry and Advances in the Clinical Lab, Journal Year: 2025, Volume and Issue: 36, P. 19 - 28
Published: Feb. 22, 2025
Oxytocin is a 9-amino acid peptide that serves as neuromodulator in the human central nervous system. This implicated regulation of diverse behaviors and plays significant role positive social interaction. Currently, oxytocin levels are measured using immunoassays. However, these methods have several limitations can lead to false results erroneous interpretation. Given remarkably low endogenous level plasma (low ng/L levels), we developed rigorously validated novel highly sensitive LC-MS/MS method for quantification plasma. was initially extracted solid-phase extraction with an Oasis HLB 30 mg plate then subjected analysis. PBS-0.1 % BSA served surrogate matrix preparation validation samples calibration curve, ensuring no interference. The design followed Clinical Laboratory Standards Institute guidelines. Precision, accuracy, measurement uncertainty were determined single-nested analysis variance e.noval software. A lower limit 1 achieved. concentrations ranging from 75 ng/L, precision (coefficient variation) below 10 %, accuracy 94 108 15 %. In this work, Our methodology well-suited clinical applications.
Language: Английский
Citations
0