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Baicalein tethers CD274/PD-L1 for autophagic degradation to boost antitumor immunity.
Autophagy
December 2024
Institute of Energy Metabolism and Health, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Immune checkpoint inhibitors, especially those targeting CD274/PD-L1yield powerful clinical therapeutic efficacy. Thoughmuch progress has been made in the development of antibody-basedCD274 drugs, chemical compounds applied for CD274degradation remain largely unavailable. Herein,baicalein, a monomer of traditional Chinese medicine, isscreened and validated to target CD274 and induces itsmacroautophagic/autophagic degradation.
View Article and Find Full Text PDFFunctional assessment of the glycoproteins of a novel Hendra virus variant reveals contrasting fusogenic capacities of the receptor-binding and fusion glycoproteins.
mBio
December 2024
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Unlabelled: A novel Hendra virus (HeV) genotype (HeV genotype 2 [HeV-g2]) was recently isolated from a deceased horse, revealing high-sequence conservation and antigenic similarities with the prototypic strain, HeV-g1. As the receptor-binding (G) and fusion (F) glycoproteins of HeV are essential for mediating viral entry, functional characterization of emerging HeV genotypic variants is key to understanding viral entry mechanisms and broader virus-host co-evolution. We first confirmed that HeV-g2 and HeV-g1 glycoproteins share a close phylogenetic relationship, underscoring HeV-g2's relevance to global health.
View Article and Find Full Text PDFAdvances in the development of Wnt/β-catenin signaling inhibitors.
RSC Med Chem
December 2024
Division of Organic Chemistry, National Institute of Health Sciences 3-25-26, Tonomachi Kawasaki Kanagawa 210-9501 Japan
The Wnt/β-catenin signaling pathway plays a critical role in various biological processes, including cell proliferation, differentiation, and tissue homeostasis. Aberrant activation of this pathway is strongly associated with the development of various cancers, including colorectal, pancreatic, and gastric cancers, making it a promising therapeutic target. In recent years, inhibitors targeting different components of the Wnt/β-catenin pathway, including small molecules, peptides, and nucleic acid-based therapies, have been developed to suppress cancer cell growth.
View Article and Find Full Text PDFNanotechnology-Enabled Targeted Protein Degradation for Cancer Therapeutics.
Wiley Interdiscip Rev Nanomed Nanobiotechnol
December 2024
CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, National Center for Nanoscience and Technology, Beijing, China.
Targeted protein degradation (TPD) represents an innovative therapeutic strategy that has garnered considerable attention from both academic and industrial sectors due to its promising developmental prospects. Approximately 85% of human proteins are implicated in disease pathogenesis, and the FDA has approved around 400 drugs targeting these disease-related proteins, predominantly enzymes, transcription factors, and non-enzymatic proteins. However, existing therapeutic modalities fail to address certain "high-value" targets, such as c-Myc and Ras.
View Article and Find Full Text PDFDiscovery and engineering of the antibody response to a prominent skin commensal.
Nature
December 2024
Department of Bioengineering, Stanford University, Stanford, CA, USA.
The ubiquitous skin colonist Staphylococcus epidermidis elicits a CD8 T cell response pre-emptively, in the absence of an infection. However, the scope and purpose of this anti-commensal immune program are not well defined, limiting our ability to harness it therapeutically. Here, we show that this colonist also induces a potent, durable, and specific antibody response that is conserved in humans and non-human primates.
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