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Discovery of an Efficacious RET PROTAC Degrader with Enhanced Antiproliferative Activity against Resistant Cancer Cells Harboring RET Solvent-Front Mutations.
J Med Chem
December 2024
Department of Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Rearranged during transfection (RET) kinase is a validated therapeutic target for various cancers characterized by RET alterations. Although two selective RET inhibitors, selpercatinib and pralsetinib, have been approved by the FDA, acquired resistance through solvent-front mutations has been identified rapidly. Developing proteolysis targeting chimera (PROTAC) targeting RET mutations offers a promising strategy to combat drug resistance.
View Article and Find Full Text PDFCorrection to: Triamcinolone Acetonide Protects Against Light-Induced Retinal Degeneration by Activating Anti-Inflammatory STAT6/Arg1 Signaling in Microglia.
Inflammation
December 2024
Shenzhen Eye Hospital, Shenzhen Eye Institute, JinanUniversity, 18 Zetian Road, Shenzhen, 518040, Guangdong, China.
Microglia are highly specialized resident macrophages in the central nervous system that play a pivotal role in modulating neuroinflammation. Microglial plasticity is essential for their function, allowing them to polarize into proinflammatory M1-like or anti-inflammatory M2-like phenotypes. However, the mechanisms driving M1 and M2 microglial induction during retinal degeneration remain largely unexplored.
View Article and Find Full Text PDFA Prodrug Nanodevice Co-delivering Docetaxel and ROR1 siRNA for Enhanced Triple Negative Breast Cancer Therapy.
Acta Biomater
December 2024
Lingang Laboratory, Shanghai 200031, China. Electronic address:
Triple-negative breast cancer (TNBC) has been a clinical challenge due to its high recurrence and metastasis rates. Chemotherapy remains the primary treatment for TNBC after surgery ablation, but it lacks targeted specificity and causes side effects in normal tissues. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is significantly expressed in TNBC cells, and small interference RNA (siRNA) targeting ROR1 can effectively suppress ROR1 gene expression, thereby inhibiting proliferation and metastasis.
View Article and Find Full Text PDFOral colon-retentive inulin gels protect against radiation-induced hematopoietic and gastrointestinal injury by improving gut homeostasis.
Int J Biol Macromol
December 2024
Beijing Institute of Radiation Medicine, Beijing 100850, China. Electronic address:
Ionizing radiation-induced injury often occurs in nuclear accidents or large-dose radiotherapy, leading to acute radiation syndromes characterized by hematopoietic and gastrointestinal injuries even to death. However, current radioprotective drugs are only used in hospitals with unavoidable side effects. Here, we heated the aqueous solution of inulin, a polysaccharide dietary fiber, forming colon-retentive gel as a radiation protector in radiotherapy.
View Article and Find Full Text PDFEffects on Multimodal Connectivity Patterns in Female Schizophrenia During 8 Weeks of Antipsychotic Treatment.
Schizophr Bull
December 2024
Department of Psychiatry, Affiliated Brain Hospital of Nanjing Medical University, Nanjing, 210029, China.
Background And Hypothesis: Respective abnormal structural connectivity (SC) and functional connectivity (FC) have been reported in individuals with schizophrenia. However, transmodal associations between SC and FC following antipsychotic treatment, especially in female schizophrenia, remain unclear. We hypothesized that increased SC-FC coupling may be found in female schizophrenia, and could be normalized after antipsychotic treatment.
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