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Anti-glutamatergic agents may have neuroprotective effects against excitotoxicity that is known to be involved in the pathogenesis of Parkinson's disease (PD). One of these agents is kynurenic acid (KYNA), a tryptophan metabolite, which is an endogenous N-methyl-D-aspartic acid (NMDA) receptor antagonist. However, its pharmacological properties of poor water solubility and limited blood–brain barrier (BBB) permeability rules out its systemic administration in disorders affecting the central nervous system. Our aim in the present study was to investigate the neuroprotective effects of KYNA-loaded micelles (KYNA-MICs) against PD in vitro and in vivo. Lipid-based micelles (MICs) in conjunction with KYNA drug delivery have the potential to enhance the penetration of therapeutic drugs into a diseased brain without BBB obstacles. KYNA-MICs were characterized by particle size (105.8 ± 12.1 nm), loading efficiency (78.3 ± 4.23%), and in vitro drug release (approximately 30% at 24 h). The in vitro experiments showed that KYNA-MICs effectively reduced 2-fold protein aggregation. The in vivo studies revealed that KYNA was successfully delivered by 5-fold increase in neurotoxin-induced PD brains. The results showed significant enhancement of KYNA delivery into brain. We also found that the KYNA-MICs exhibited several therapeutic effects. The KYNA-MICs reduced protein aggregation of an in vitro PD model, ameliorated motor functions, and prevented loss of the striatal neurons in a PD animal model. The beneficial effects of KYNA-MICs are probably explained by the anti-excitotoxic activity of the treatment's complex. As the KYNA-MICs did not induce any appreciable side-effects at the protective dose applied to a chronic PD mouse model, our results demonstrate that KYNA provides neuroprotection and attenuates PD pathology. [ABSTRACT FROM AUTHOR]

Huntington's disease (HD) is associated with dysregulated choline metabolism, but the underlying mechanisms remain unclear. This study investigated the expression of key enzymes in this pathway in R6/2 HD mice and human HD postmortem brain tissues. We further explored the therapeutic potential of modulating choline metabolism for HD. Both R6/2 mice and HD patients exhibited reduced expression of glycerophosphocholine phosphodiesterase 1 (GPCPD1), a key enzyme in choline metabolism, in the striatum and cortex. The striatum of R6/2 mice also showed decreased choline and phosphorylcholine, and increased glycerophosphocholine, suggesting disruption in choline metabolism due to GPCPD1 deficiency. Treatment with citicoline significantly improved motor performance, upregulated anti‐apoptotic Bcl2 expression, and reduced oxidative stress marker malondialdehyde in both brain regions. Metabolomic analysis revealed partial restoration of disrupted metabolic patterns in the striatum and cortex following citicoline treatment. These findings strongly suggest the role of GPCPD1 deficiency in choline metabolism dysregulation in HD. The therapeutic potential of citicoline in R6/2 mice highlights the choline metabolic pathway as a promising target for future HD therapies. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions Implications for the Profession and/or Patient Care Impact Reporting Method This study aimed to investigate the factors influencing nurses' intentions to participate in advance care planning (ACP) by examining the mediating roles of attitude, subjective norm, and perceived behavioural control in the relationship between knowledge and intention, using an extended theory of planned behaviour and structural equation modelling.A descriptive cross‐sectional survey was conducted between January and April 2023, involving 515 registered nurses, selected through two‐stage sampling. Data were collected using a self‐administered online survey distributed via the internal communication system of hospital. Structural equation Modelling was employed to analyse the relationships among knowledge, attitude, subjective norm, perceived behavioural control and intention to participate in ACP.The results supported two hypotheses regarding the relationships between knowledge, attitude, subjective norm, perceived behavioural control, and intention (p < 0.05). While the direct effect of knowledge on intention was not significant (β = 0.087, p = 0.292), the total indirect effect through attitude, subjective norm and perceived behavioural control was significant (β = 0.449, p < 0.001), accounting for approximately 83.77% of the total effect on intention. This underscores the critical role of these mediators in influencing nurses' intention to participate in ACP.This study highlights the significant indirect influence of knowledge on nurses' intentions to participate in ACP through attitude, subjective norms and perceived behavioural control. These findings suggest that targeted educational is needed to enhance ACP participation among nurses.Understanding the role of attitude, subjective norm and perceived behavioural control can enhance nursing practice. Creating supportive environments and promoting interdisciplinary collaboration are crucial. Professional development through training, mentorship and role modelling can empower nurses in ACP. Comprehensive programs that increase knowledge and foster positive attitudes are essential for advancing ACP practice among nurses.Educational programs aimed at nurses should include components designed to strengthen knowledge and the identified mediators, equipping nurses with the necessary ACP skills. Organizational support through appropriate policy frameworks can facilitate these educational endeavours and ensure a sustainable impact on practice.The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for cross‐sectional studies. [ABSTRACT FROM AUTHOR]

Molecularly imprinted film was fabricated in the presence of a pentadecapeptide onto a quartz crystal microbalance (QCM) chip. This 15-met peptide has been known as the linear epitope of the dengue virus NS1 protein. Imprinting resulted in an increased polymer affinity toward the corresponding templates but also to the virus protein. Direct detection of the dengue virus protein was achieved quantitatively. The QCM chip response to the NS1 protein was obtained using epitope-mediated imprinting demonstrating a comparable frequency shift in chips immobilized with monoclonal antibodies. The binding effect was further enhanced and confirmed using a monoclonal antibody to form a sandwich with the MIP-NS1 protein complex on the chip. No pretreatment was required.

Alzheimer's disease (AD) is a progressive neurodegenerative disease with memory loss and cognitive decline. Neurofibrillary tangles (NFTs) formed by hyperphosphorylated Tau protein are one of the pathological hallmarks of several neurodegenerative diseases including AD. Heat shock protein family B (small) member 1 (HSPB1) is a molecular chaperone that promotes the correct folding of other proteins in response to environmental stress. Nuclear factor erythroid 2-like 2 (NRF2), a redox-regulated transcription factor, is the master regulator of the cellular response to excess reactive oxygen species. Tropomyosin-related kinase B (TRKB) is a membrane-bound receptor that, upon binding brain-derived neurotrophic factor (BDNF), phosphorylates itself to initiate downstream signaling for neuronal survival and axonal growth. In this study, four natural flavones such as 7,8-dihydroxyflavone (7,8-DHF), wogonin, quercetin, and apigenin were evaluated for Tau aggregation inhibitory activity and neuroprotection in SH-SY5Y neuroblastoma. Among the tested flavones, 7,8-DHF, quercetin, and apigenin reduced Tau aggregation, oxidative stress, and caspase-1 activity as well as improved neurite outgrowth in SH-SY5Y cells expressing ΔK280 TauRD-DsRed folding reporter. Treatments with 7,8-DHF, quercetin, and apigenin rescued the reduced HSPB1 and NRF2 and activated TRKB-mediated extracellular signal-regulated kinase (ERK) signaling to upregulate cAMP-response element binding protein (CREB) and its downstream antiapoptotic BCL2 apoptosis regulator (BCL2). Knockdown of TRKB attenuated the neuroprotective effects of these three flavones. Our results suggest 7,8-DHF, quercetin, and apigenin targeting HSPB1, NRF2, and TRKB to reduce Tau aggregation and protect cells against Tau neurotoxicity and may provide new treatment strategies for AD. [ABSTRACT FROM AUTHOR]

Convection-enhanced delivery (CED) is a promising technique for the delivery of drugs directly into the central nervous system (CNS) and, more specifically, the brain. CED can increase drug concentration within a brain tumour, thereby improving the therapeutic efficacy and limiting the systemic toxicity of tumoricidal agents. In this study, we evaluated a drug-liposome constructin vitroandin vivousing U87 tumour-bearing nude mice. Dipalmitoylphosphatidylcholine (DPPC)-based liposomes were designed to deliver a lipophilic temozolomide (TMZ) formulation (LipoTMZ). The LipoTMZ displayed good release of TMZin vitroover a suitable range of time and temperatures. Encapsulating the TMZ into liposomes enhanced its tumoricidal activity against U87MG human glioma cells. The LipoTMZ also displayed good release and distribution of TMZ when delivered intracerebrally to U87MG tumour-bearing mice by CED infusion. Histological examination revealed that CED did not damage normal brain tissue. Our data indicate that CED was an effective method to deliver LipoTMZ to U87MG tumour-bearing mice, significantly inhibiting tumour growth without evidence of systemic toxicity. [ABSTRACT FROM PUBLISHER]