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Nanoparticles modified with glucose analogs to enhance the permeability of the blood-brain barrier and their accumulation in the epileptic brain.
J Mater Chem B
January 2025
Department of Neurology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, P. R. China.
Drug delivery for epilepsy treatment faces enormous challenges, where the sole focus on enhancing the ability of drugs to penetrate the blood-brain barrier (BBB) through ligand modification is insufficient because of the absence of seizure-specific drug accumulation. In this study, an amphipathic drug carrier with a glucose transporter (GLUT)-targeting capability was synthesised by conjugating 2-deoxy-2-amino-D-glucose (2-DG) to the model carrier DSPE-PEG. A 2-DG-modified nano drug delivery system (NDDS) possessing robust stability and favourable biocompatibility was then fabricated using the nanoprecipitation method.
View Article and Find Full Text PDFElectrophysiological characterization of human KCNT1 channel modulators and the therapeutic potential of hydroquinine and tipepidine in KCNT1 mutation-associated epilepsy mouse model.
Acta Pharmacol Sin
January 2025
Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, 221004, China.
Patients suffering epilepsy caused by the gain-of-function mutants of the hKCNT1 potassium channels are drug refractory. In this study, we cloned a novel human KCNT1B channel isoform using the brain cDNA library and conducted patch-clamp and molecular docking analyses to characterize the pharmacological properties of the hKCNT1B channel using thirteen drugs. Among cinchona alkaloids, we found that hydroquinine exerted the strongest blocking effect on the hKCNT1B channel, especially the F313L mutant.
View Article and Find Full Text PDFFlunarizine as a Candidate for Drug Repurposing Against Human Pathogenic Mammarenaviruses.
Viruses
January 2025
Department of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA 92037, USA.
Lassa fever (LF), a viral hemorrhagic fever disease with a case fatality rate that can be over 20% among hospitalized LF patients, is endemic to many West African countries. Currently, no vaccines or therapies are specifically licensed to prevent or treat LF, hence the significance of developing therapeutics against the mammarenavirus Lassa virus (LASV), the causative agent of LF. We used in silico docking approaches to investigate the binding affinities of 2015 existing drugs to LASV proteins known to play critical roles in the formation and activity of the virus ribonucleoprotein complex (vRNP) responsible for directing replication and transcription of the viral genome.
View Article and Find Full Text PDFIntegrating 16S rRNA Gene Sequencing and Metabolomics Analysis to Reveal the Mechanism of L-Proline in Preventing Autism-like Behavior in Mice.
Nutrients
January 2025
Key Laboratory of Precision Nutrition and Food Quality, Key Laboratory of Functional Dairy, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.
Background/objectives: Autism spectrum disorder (ASD) is characterized by impaired social interaction and repetitive stereotyped behavior. Effective interventions for the core autistic symptoms are currently limited.
Methods: This study employed a valproic acid (VPA)-induced mouse model of ASD to assess the preventative effects of L-proline supplementation on ASD-like behaviors.
Anticonvulsant Effects of Synthetic -(3-Methoxybenzyl)oleamide and -(3-Methoxybenzyl)linoleamide Macamides: An In Silico and In Vivo Study.
Molecules
January 2025
Escuela Profesional de Farmacía y Bioquímica, Universidad Católica de Santa María, Urb. San José s/n, Umacollo, Arequipa 04000, Peru.
Epilepsy is a chronic neurological disorder that affects nearly 50 million people worldwide. Experimental evidence suggests that epileptic neurons are linked to the endocannabinoid system and that inhibition of the FAAH enzyme could have neuroprotective effects by increasing the levels of endogenous endocannabinoid anandamide. In this context, the use of macamides as therapeutic agents in neurological diseases has increased in recent years.
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