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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 PDFInsights Into the Role of Bmi-1 Deregulation in Promoting Stemness and Therapy Resistance in Glioblastoma: A Narrative Review.
Cancer Med
January 2025
Faculty of Medical Sciences, Neuroscience Research Center, Lebanese University, Hadath, Lebanon.
Background: Glioblastoma (GBM) is the most common primary brain tumor in adults and has a median survival of less than 15 months. Advancements in the field of epigenetics have expanded our understanding of cancer biology and helped explain the molecular heterogeneity of these tumors. B-cell-specific Moloney murine leukemia virus insertion site-1 (Bmi-1) is a member of the highly conserved polycomb group (PcG) protein family that acts as a transcriptional repressor of multiple genes, including those that determine cell proliferation and differentiation.
View Article and Find Full Text PDFPrime editing enables precise genome modification of a hybrid.
aBIOTECH
December 2024
State Key Laboratory of Tree Genetics and Breeding, Key Laboratory of Tree Breeding of Zhejiang Province, Research Institute of Subtropical Forestry, Chinese Academy of Forestry, Hangzhou, 311400 China.
Unlabelled: CRISPR/Cas-based genome editing has been extensively employed in the breeding and genetic improvement of trees, yet precise editing remains challenging in these species. Prime editing (PE), a revolutionary technology for precise editing, allows for arbitrary base substitutions and the insertion/deletion of small fragments. In this study, we focused on the model tree poplar 84K ( × ).
View Article and Find Full Text PDFA multitask interpretable model with graph attention mechanism for activity prediction of low-data PIM inhibitors.
Mol Divers
November 2024
Department of Pharmacy, Honghui Hospital, Xi' an Jiaotong University, Xi' an, 710054, China.
The aberrant expression of proviral integration site for Moloney murine leukemia virus (PIM) kinases is closely related to various tumors and chemotherapy resistance, making them attractive targets for cancer therapy. However, due to the extremely high homology among the three PIM isoforms (PIM1, PIM2, PIM3) and the limited availability of existing bioactivity data, screening and designing selective PIM inhibitors remain a daunting challenge. To address this issue, this study constructed a multitask regression model that can simultaneously predict the half-maximal inhibitory concentration (IC values).
View Article and Find Full Text PDFLow miR-936-mediated upregulation of Pim-3 drives sorafenib resistance in liver cancer through ferroptosis inhibition by activating the ANKRD18A/Src/NRF2 pathway.
Front Oncol
October 2024
Department of Clinical Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
Article Synopsis
- Sorafenib, a common treatment for advanced liver cancer, faces limitations due to the development of drug resistance, which poses challenges in understanding and overcoming this resistance.
- The study involved observing liver cancer patients on sorafenib, creating resistant cell lines, and conducting various molecular assays to explore the mechanisms of resistance.
- Results revealed that high levels of Pim-3 predict poor outcomes for patients and are linked to resistance; this is influenced by reduced levels of microRNA-936, which normally suppresses Pim-3 expression and its associated pro-resistance pathways.
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