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Cullin-5 (Cul5) coordinates assembly of cullin-RING-E3 ubiquitin (Ub) ligase (CRL) complexes that include Suppressor of Cytokine Signaling (SOCS)-box-containing proteins. The SOCS-box proteins function to recruit specific substrates to the complex for ubiquitination and degradation. In hematopoiesis, SOCS-box proteins are best known for regulating the actions of cytokines that utilize the JAK-STAT signaling pathway.
View Article and Find Full Text PDFClozapine Induces Agranulocytosis via Inflammatory and Hematopoietic Cytokine Induction of the JAK-STAT Signaling Pathway: Evidence From Network Pharmacology and Molecular Docking.
CNS Neurosci Ther
January 2025
Computational Biology Center, Tianjin Anding Hospital, Nankai University Affiliated Tianjin Anding Hospital, Tianjin Mental Health Center of Tianjin Medical University, Tianjin, China.
Background: Clozapine exhibits significant therapeutic efficacy in schizophrenia, especially treatment-resistant schizophrenia. However, clozapine can cause agranulocytosis, a fatal adverse effect, and the aim of this study is to explore this mechanism based on network pharmacology and molecular docking.
Method: Six and two databases were used to identify targets associated with clozapine and agranulocytosis, respectively.
The β Common Cytokine Receptor Family Reveals New Functional Paradigms From Structural Complexities.
Immunol Rev
January 2025
Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, Australia.
Cytokines are small proteins that are critical for controlling the growth and activity of hematopoietic cells by binding to cell surface receptors and transmitting signals across membranes. The β common (βc) cytokine receptor family, consisting of the granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3, and IL-5 cytokine receptors, is an architype of the heterodimeric cytokine receptor systems. We now know that signaling by cytokine receptors is not always an "all or none" phenomenon.
View Article and Find Full Text PDFInterleukin-3 Modulates Macrophage Phagocytic Activity and Promotes Spinal Cord Injury Repair.
CNS Neurosci Ther
December 2024
Department of Orthopaedics, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.
Article Synopsis
- IL-3 plays a significant role in lipid debris clearance by macrophages, which is crucial for recovery after spinal cord injuries (SCI), with its expression peaking at 14 days post-injury.
- Neutralizing IL-3 results in increased lipid accumulation and decreased neuronal survival, leading to greater motor deficits, while augmenting IL-3 promotes neuron preservation and enhances axon regeneration.
- These findings suggest that targeting the IL-3/IL-3Rα pathway could be a promising therapeutic approach for improving recovery after SCI.
CD33-CD123 IF-THEN Gating Reduces Toxicity while Enhancing the Specificity and Memory Phenotype of AML-Targeting CAR-T Cells.
Blood Cancer Discov
January 2025
Division of Hematology and Oncology, Department of Pediatrics, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California.
Our study demonstrates the use of "IF-THEN" SynNotch-gated CAR-T cells targeting CD33 and CD123 in AML reduces off-tumor toxicity. This strategy enhances T-cell phenotype, improves expansion, preserves HSPCs, and mitigates cytokine release syndrome-addressing critical limitations of existing AML CAR-T therapies.
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