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VCP controls KCC2 degradation through FAF1 recruitment and accelerates emergence from anesthesia.
Proc Natl Acad Sci U S A
January 2025
Department of Medical Neuroscience, SUSTech Center for Pain Medicine, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, China.
Ubiquitin-proteasomal degradation of K/Cl cotransporter 2 (KCC2) in the ventral posteromedial nucleus (VPM) has been demonstrated to serve as a common mechanism by which the brain emerges from anesthesia and regains consciousness. Ubiquitin-proteasomal degradation of KCC2 during anesthesia is driven by E3 ligase Fbxl4. However, the mechanism by which ubiquitinated KCC2 is targeted to the proteasome has not been elucidated.
View Article and Find Full Text PDFMolecular basis for the stepwise and faithful maturation of the 20 proteasome.
Sci Adv
January 2025
Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
The proteasome degrades most superfluous and damaged proteins, and its decline is associated with many diseases. As the proteolytic unit, the 20 proteasome is assembled from 28 subunits assisted by chaperones PAC1/2/3/4 and POMP; then, it undergoes the maturation process, in which the proteolytic sites are activated and the assembly chaperones are cleared. However, mechanisms governing the maturation remain elusive.
View Article and Find Full Text PDFIn Vitro Induction of Hypertrophic Chondrocyte Differentiation of Naïve MSCs by Strain.
Cells
December 2024
AO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos, Switzerland.
In the context of bone fractures, the influence of the mechanical environment on the healing outcome is widely accepted, while its influence at the cellular level is still poorly understood. This study explores the influence of mechanical load on naïve mesenchymal stem cell (MSC) differentiation, focusing on hypertrophic chondrocyte differentiation. Unlike primary bone healing, which involves the direct differentiation of MSCs into bone-forming cells, endochondral ossification uses an intermediate cartilage template that remodels into bone.
View Article and Find Full Text PDFPyroptosis and sepsis-associated acute kidney injury.
Zhong Nan Da Xue Xue Bao Yi Xue Ban
August 2024
Department of Emergency, Xiangya Hospital, Central South University, Changsha 410008, China.
Pyroptosis is a form of programmed cell death triggered by inflammatory caspases, dependent on the gasdermin (GSDM) family proteins forming membrane pores in the plasma membrane, with GSDM proteins serving as the executors of pyroptosis. This process can activate a robust inflammatory response through a cascade effect. Sepsis-associated acute kidney injury (SA-AKI) is a classical inflammatory disease with no specific therapeutic drug available.
View Article and Find Full Text PDFEfficacy and safety of botulinum toxin injection in the management of chronic symptomatic anal fissure: a systematic review and meta-analysis of randomized controlled trials.
Tech Coloproctol
January 2025
Royal Glamorgan Hospital, Llantrisant, Wales, UK.
Background: Anal fissure is one of the most painful anal conditions. Various management options are available, including topical nitrites, calcium channel blockers, botulinum toxin injection, and lateral internal sphincterotomy. This study aimed to assess the efficacy and safety of botulinum toxin A (BT) injection for the management of symptomatic chronic anal fissures by conducting a systematic review of the literature and meta-analysis of published randomized controlled trials (RCTs).
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