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ERK-USP9X-coupled regulation of thymidine kinase 1 promotes both its enzyme activity-dependent and its enzyme activity-independent functions for tumor growth.
Nat Struct Mol Biol
January 2025
Zhejiang Provincial Key Laboratory of Pancreatic Disease, Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Thymidine kinase 1 (TK1), a crucial enzyme in DNA synthesis, is highly expressed in various cancers. However, the mechanisms underlying its elevated expression and the implications for tumor metabolism remain unclear. Here we demonstrate that activation of growth factor receptors enhances TK1 expression.
View Article and Find Full Text PDFBackground: Fibroblast growth factor 21 (FGF21) and Methyltransferase-like 14 (METTL14) have been identified to be involved in spinal cord injury (SCI). However, whether FGF21 functioned in SCI via METTL14-induced N6-methyladenosine (m6A) modification remains unclear.
Materials And Methods: PC12 cells were exposed to lipopolysaccharide (LPS) in vitro.
A physiologically-based quantitative systems pharmacology model for mechanistic understanding of the response to alogliptin and its application in patients with renal impairment.
J Pharmacokinet Pharmacodyn
January 2025
Department of Clinical Pharmacy and Pharmacy Administration, West China school of Pharmacy, Sichuan University, Chengdu, 610064, China.
Alogliptin is a highly selective inhibitor of dipeptidyl peptidase-4 and primarily excreted as unchanged drug in the urine, and differences in clinical outcomes in renal impairment patients increase the risk of serious adverse reactions. In this study, we developed a comprehensive physiologically-based quantitative systematic pharmacology model of the alogliptin-glucose control system to predict plasma exposure and use glucose as a clinical endpoint to prospectively understand its therapeutic outcomes with varying renal function. Our model incorporates a PBPK model for alogliptin, DPP-4 activity described by receptor occupancy theory, and the crosstalk and feedback loops for GLP-1-GIP-glucagon, insulin, and glucose.
View Article and Find Full Text PDFWhat a tangled web we weave: crosstalk between JAK-STAT and other signalling pathways during development in Drosophila.
FEBS J
January 2025
Department of Developmental Biology and Genetics, Indian Institute of Science (IISc), Bangalore, India.
The Janus kinase-signal transducer and activator of transcription (JAK-STAT) signalling pathway is a key player in animal development and physiology. Although it functions in a variety of processes, the net output of JAK-STAT signalling depends on its spatiotemporal activation, as well as extensive crosstalk with other signalling pathways. Drosophila, with its relatively simple signal transduction pathways and plethora of genetic analysis tools, is an ideal system for dissecting JAK-STAT signalling interactions.
View Article and Find Full Text PDFIntegrating network pharmacology with molecular docking and dynamics to uncover therapeutic targets and signaling mechanisms of vitamin D3 in Parkinson's disease.
Mol Divers
January 2025
School of Medicine, Zhejiang University, Hangzhou, 310000, Zhejiang, People's Republic of China.
Parkinson's disease (PD) is a chronic neurodegenerative disorder marked by dopaminergic neuron degeneration in the substantia nigra. Emerging evidence suggests vitamin D3 (VD) plays a therapeutic role in PD, but its precise molecular mechanisms remain unclear. This study employed network pharmacology and bioinformatics to identify VD's hub targets and related pathways.
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