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Discovery of Human PIM Kinase Inhibitors as a Class of Anthelmintic Drugs to Treat Intestinal Nematode Infections.
ACS Infect Dis
January 2025
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, Saint Louis, Missouri 63110, United States.
Soil-transmitted helminth (STH) infections affect one-fourth of the global population and pose a significant threat to human and animal health, with limited treatment options and emerging drug resistance. (whipworm) stands out as a neglected disease, necessitating new drugs to address this unmet medical need. We discovered that several different chemical series of related human Provirus Integration sites for Moloney murine leukemia virus (PIM) family kinase inhibitors possess potent anthelmintic activity by using whole-worm motility assays.
View Article and Find Full Text PDFConstitutive surface expression of the thromboxane A2 receptor is Pim kinase-dependent.
J Thromb Haemost
January 2025
Department of Life Sciences, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, United Kingdom; Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, United Kingdom. Electronic address:
Background: The thromboxane A2 receptor (TPαR) plays an important role in the amplification of platelet responses during thrombosis. Receptor activity is regulated by internalization and receptor desensitization. The mechanism by which constitutive surface expression of the TPαR is regulated is unknown.
View Article and Find Full Text PDFCXCR2 Activated JAK3/STAT3 Signaling Pathway Exacerbating Hepatotoxicity Associated with Tacrolimus.
Drug Des Devel Ther
January 2025
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy & School of Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People's Republic of China.
Purpose: Tacrolimus could induce hepatotoxicity during clinical use, and the mechanism was still unclear, which posed new challenge for the prevention and treatment of tacrolimus-induced hepatotoxicity. The aim of this study was to investigate the mechanism of tacrolimus-induced hepatotoxicity and provide reference for drug development target.
Methods: In this study, biochemical analysis, pathological staining, immunofluorescent staining, immunohistochemical staining, transcriptomic analysis, Western blotting was used to investigate the mechanism of tacrolimus-induced hepatotoxicity in gene knockout mice and Wistar rats.
PIM1 instigates endothelial-to-mesenchymal transition to aggravate atherosclerosis.
Theranostics
January 2025
Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Shandong, China.
Article Synopsis
- Endothelial-to-mesenchymal transition (EndMT) is a process where endothelial cells transform into a different cell type, contributing to the dysfunction that initiates atherosclerosis, but the exact triggers in atherosclerotic environments are not well understood.
- Research involving single-cell sequencing in mice on a high-fat diet showed that PIM1, a protein, is expressed in both endothelial cells and atherosclerotic lesions and plays a crucial role in the progression of atherosclerosis.
- Knockdown of PIM1 in endothelial cells reduced atherosclerosis and EndMT by affecting key proteins and pathways associated with cell transformation, suggesting that targeting this pathway could be a potential therapeutic approach.
RBM19 promotes the progression of prostate cancer under docetaxel treatment via SNHG21/PIM1 axis.
Cell Biol Toxicol
December 2024
Department of Urology, Jinjiang Municipal Hospital, Luoshan Section, No. 16 Jinguang Road, Luoshan Street, Jinjiang City, Quanzhou, Fujian, China.
RBM family proteins plays the critical role in the progression of numerous tumors. However, whether RBM family proteins involved in prostate cancer (PCa) progression is remain elucidated. In our study, an RNAi screen containing shRNA library targeting 54 members of the RBM family was applied to identify the critical RBM proteins involved in prostate cancer progression under docetaxel treatment, and RBM19 was selected.
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