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A nanobody-enzyme fusion protein targeting PD-L1 and sialic acid exerts anti-tumor effects by C-type lectin pathway-mediated tumor associated macrophages repolarizing.
Int J Biol Macromol
January 2025
Department of Medical Microbiology, Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, School of Basic Medical Sciences, Fudan University, Shanghai, China; Translational Glycomics Research Center, Fudan Zhangjiang Institute, Shanghai, China. Electronic address:
Aberrant sialylated glycosylation in the tumor microenvironment is a novel immune suppression pathway, which has garnered significant attention as a targetable glycoimmune checkpoint for cancer immunotherapy to address the dilemma of existing therapies. However, rational drug design and in-depth mechanistic studies are urgently required for tumor sialic acid to become valuable glycoimmune targets. In this study, we explored the positive correlation of PD-L1 and sialyltransferase expression in clinical colorectal cancer tissues and identified their mutual regulation effects in macrophages.
View Article and Find Full Text PDFDecoding Extracellular Protein Glycosylation in Human Health and Disease.
Annu Rev Anal Chem (Palo Alto Calif)
January 2025
Department of Chemistry, Yale University, New Haven, Connecticut, USA;
Protein glycosylation, the covalent attachment of carbohydrate, or glycan, structures onto the protein backbone, is one of the most complex and heterogeneous post-translational modifications (PTMs). Extracellular protein glycosylation, in particular N- and mucin-type O-glycosylation, plays pivotal roles in a number of biophysical and biochemical processes, such as protein folding and stability, cell adhesion, signaling, and protection. As such, aberrant glycosylation is implicated in a variety of diseases, including cancer.
View Article and Find Full Text PDFMSAB limits osteoarthritis development and progression through inhibition of β-catenin-DDR2 signaling.
Bioact Mater
April 2025
Research Center for Computer-aided Drug Discovery, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
The aberrant activation of the canonical Wnt/β-catenin signaling has been identified as a significant contributor to the pathogenesis of osteoarthritis (OA), exacerbating OA symptoms and driving OA progression. Despite its potential as a therapeutic target, clinical translation is impeded by the lack of a targeting delivery system and effective drug candidate that can modulate steady-state protein levels of β-catenin at post-translational level. Our study addresses these challenges by offering a new approach for OA treatment.
View Article and Find Full Text PDFBreath biopsy is emerging as a rapid and non-invasive diagnostic tool that links exhaled chemical signatures with specific medical conditions. Despite its potential, clinical translation remains limited by the challenge of reliably detecting endogenous, disease-specific biomarkers in breath. Synthetic biomarkers represent an emerging paradigm for precision diagnostics such that they amplify activity-based biochemical signals associated with disease fingerprints.
View Article and Find Full Text PDFAssociation between stress-induced hyperglycemia ratio and sepsis risk in patients admitted to ICU.
Adv Clin Exp Med
January 2025
Department of Critical Care Medicine, the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, China.
Background: Sepsis is a life-threatening condition characterized by a dysregulated host immune response to infection. Currently, stress hyperglycemia is frequently associated with an unfavorable prognosis in cardiovascular and cerebrovascular disease. During sepsis, the progression of the immune response and inflammation often leads to aberrant metabolic indicators.
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