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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 PDFN-acetylneuraminic acid promotes ferroptosis of H9C2 cardiomyocytes with hypoxia/reoxygenation injury by inhibiting the Nrf2 axis.
Nan Fang Yi Ke Da Xue Xue Bao
January 2025
Department of Cardiovascular Diseases, First Affiliated Hospital of Bengbu Medical University, Bengbu 233000, China.
Objectives: To investigate the mechanism through which N-acetylneuraminic acid (Neu5Ac) exacerbates hypoxia/reoxygenation (H/R) injury in rat cardiomyocytes (H9C2 cells).
Methods: H9C2 cells were cultured in hypoxia and glucose deprivation for 8 h followed by reoxygenation for different durations to determine the optimal reoxygenation time. Under the optimal H/R protocol, the cells were treated with 0, 5, 10, 20, 30, 40, 50, and 60 mmol/L Neu5Ac during reoxygenation to explore the optimal drug concentration.
A Simple and Efficient Stereoselective Synthesis of a 2,3-Difluorosialic acid-based influenza virus neuraminidase inhibitor.
Chemistry
January 2025
Griffith University - Gold Coast Campus, Institute for Biomedicine and Glycomics, Parklands Drive, 4222, Southport, AUSTRALIA.
3-Fluoroneuraminosyl fluorides are invaluable probes for studying the catalytic mechanism of sialidases (neuraminidases), and as sialidase inhibitors. Significantly, when a C-3 equatorial fluorine is installed on a C-4 functionalised N-acylneuraminic acid (Neu)-based template, the compounds are potent and selective inhibitors of both influenza and parainfluenza sialidases, and of virus replication. Typically, the reported syntheses of 3-fluoroneuraminosyl fluorides involve either an enzymatic or a chemical synthesis that have uncontrolled stereoselectivity in the introduction of fluorine at C-3 of Neu and consequently yield a mixture of C-3 ax and C-3 eq fluoro derivatives.
View Article and Find Full Text PDFIsoleucine at position 137 of Hemagglutinin acts as a Mammalian adaptation marker of H9N2 Avian influenza virus.
Emerg Microbes Infect
January 2025
Key Laboratory of Livestock Infectious Diseases, Ministry of Education, Key Laboratory of Zoonosis, College of Animal Science and Veterinary Medicine, Liaoning Panjin Wetland Ecosystem National Observation and Research Station, Shenyang Agricultural University, Shenyang, People's Republic of China.
The H9N2 subtype of avian influenza virus (AIV) is widely distributed among poultry and wild birds and is also a threat to humans. During AIV active surveillance in Liaoning province from 2015 to 2016, we identified ten H9N2 strains exhibiting different lethality to chick embryos. Two representative strains, A/chicken/China/LN07/2016 (CKLN/07) and A/chicken/China/LN17/2016 (CKLN/17), with similar genomic background but different chick embryo lethality, were chosen to evaluate the molecular basis for this difference.
View Article and Find Full Text PDFTranscriptome analysis reveals molecular targets of erythrocyte invasion phenotype diversity in natural isolates from Cameroon.
Front Parasitol
May 2024
Disease Control and Elimination (DCE), Medical Research Council The Gambia Unit at the London School of Hygiene and Tropical Medicine (LSHTM), Fajara, Gambia.
Further understanding of the molecular mediators of alternative RBC invasion phenotypes in endemic malaria parasites will support malaria blood-stage vaccine or drug development. This study investigated the prevalence of sialic acid (SA)-dependent and SA-independent RBC invasion pathways in endemic parasites from Cameroon and compared the schizont stage transcriptomes in these two groups to uncover the wider repertoire of transcriptional variation associated with the use of alternative RBC invasion pathway phenotypes. A two-color flow cytometry-based invasion-inhibition assay against RBCs treated with neuraminidase, trypsin, and chymotrypsin and deep RNA sequencing of schizont stages harvested in the first replication cycle in culture were employed in this investigation.
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