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Electrophysiological 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 PDFProtective Role of Oxycodone in Myocardial Oxidative Stress and Mitochondrial Dysfunction Induced by Ischemia-Reperfusion.
J Biochem Mol Toxicol
February 2025
Department of Cardiology, Affiliated Hospital of Hebei University, Baoding, China.
Ischemia-reperfusion (I/R) injury is a significant clinical problem impacting the heart and other organs, such as the kidneys and liver. This study explores the protective effects of oxycodone on myocardial I/R injury and its underlying mechanisms. Using a myocardial I/R model in Sprague-Dawley (SD) rats and an oxygen-glucose deprivation/reoxygenation (OGD/R) model in H9c2 cells, we administered oxycodone and inhibited AMP-activated protein kinase (AMPK) with Compound C (C.
View Article and Find Full Text PDFPre-injury narcotic drug use in isolated severe traumatic brain injury: effect on outcomes.
Eur J Trauma Emerg Surg
January 2025
Division of Acute Care Surgery, Department of Surgery, University of Southern California, 2051 Marengo Street, Los Angeles, CA, 90033, USA.
Purpose: The aim of this study was to explore the association between pre-injury narcotic drug use (opioids, methadone, and/or oxycodone) and outcomes in isolated severe traumatic brain injury (TBI) patients.
Methods: ACS TQIP study included adult trauma patients (≥ 16 years) with complete drug and alcohol screening. Isolated severe TBI was defined as head trauma with AIS 3-5 and without significant extracranial trauma.
Impact of β-casein variants on the formation of β-casomorphins in blue cheeses: Investigating key drivers through peptidomic analysis.
Food Res Int
February 2025
Department of Agriculture, University of Naples "Federico II", 80055 Portici, Italy.
β-Casomorphins (BCMs), food-associated peptides resulting from the proteolytic cleavage of β-casein (β-CN), have been widely investigated for their opioid-like activity. This research aimed to identify the presence of BCM7, BCM6, and BCM5 in different bovine milk-deriving blue cheese types and to describe the intricate mechanisms behind their formation, focusing on their origin from cheese with β-CN A1 and A2 variants. Using nanoLC-ESI-Q-Orbitrap-MS/MS and advanced computational tools, we explored the peptidomes of Bleu d'Auvergne, Gorgonzola, Stilton, and Bergader blue cheeses from milk containing both β-CN A1 and A2 variants.
View Article and Find Full Text PDFRescue-like behavior in a bystander mouse toward anesthetized conspecifics promotes arousal via a tongue-brain connection.
Sci Adv
January 2025
Department of Pain Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
Prosocial behaviors are advantageous to social species, but the neural mechanism(s) through which others receive benefit remain unknown. Here, we found that bystander mice display rescue-like behavior (tongue dragging) toward anesthetized cagemates and found that this tongue dragging promotes arousal from anesthesia through a direct tongue-brain circuit. We found that a direct circuit from the tongue → glutamatergic neurons in the mesencephalic trigeminal nucleus (MTN) → noradrenergic neurons in the locus coeruleus (LC) drives rapid arousal in the anesthetized mice that receive the rescue-like behavior from bystanders.
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