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The Cryo-EM structure of human CD163 bound to haptoglobin-hemoglobin reveals molecular mechanisms of hemoglobin scavenging.
Nat Commun
December 2024
Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.
CD163, a macrophage-specific receptor, plays a critical role in scavenging hemoglobin released during hemolysis, protecting against oxidative effects of heme iron. In the bloodstream, hemoglobin is bound by haptoglobin, leading to its immediate endocytosis by CD163. While haptoglobin's structure and function are well understood, CD163's structure and its interaction with the haptoglobin-hemoglobin complex have remained elusive.
View Article and Find Full Text PDFTrivalent recombinant protein vaccine induces cross-neutralization against XBB lineage and JN.1 subvariants: preclinical and phase 1 clinical trials.
Nat Commun
December 2024
Laboratory of Aging Research and Cancer Drug Target, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
The immune escape capacities of XBB variants necessitate the authorization of vaccines with these antigens. In this study, we produce three recombinant trimeric proteins from the RBD sequences of Delta, BA.5, and XBB.
View Article and Find Full Text PDFNET formation-mediated in situ protein delivery to the inflamed central nervous system.
Nat Commun
December 2024
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
Delivering protein drugs to the central nervous system (CNS) is challenging due to the blood-brain and blood-spinal cord barrier. Here we show that neutrophils, which naturally migrate through these barriers to inflamed CNS sites and release neutrophil extracellular traps (NETs), can be leveraged for therapeutic delivery. Tannic acid nanoparticles tethered with anti-Ly6G antibody and interferon-β (aLy6G-IFNβ@TLP) are constructed for targeted neutrophil delivery.
View Article and Find Full Text PDFAntibodies to the RBD of SARS-CoV-2 spike mediate productive infection of primary human macrophages.
Nat Commun
December 2024
Department of Infectious Diseases, School of Immunology & Microbial Sciences, King's College London, London, SE1 9RT, UK.
The role of myeloid cells in the pathogenesis of SARS-CoV-2 is well established, in particular as drivers of cytokine production and systemic inflammation characteristic of severe COVID-19. However, the potential for myeloid cells to act as bona fide targets of productive SARS-CoV-2 infection, and the specifics of entry, remain unclear. Using a panel of anti-SARS-CoV-2 monoclonal antibodies (mAbs) we performed a detailed assessment of antibody-mediated infection of monocytes/macrophages.
View Article and Find Full Text PDFLow-Dose Emicizumab Versus Low-/Intermediate-Dose Factor VIII Secondary Prophylaxis for Noninhibitor Haemophilia A Patients With Severe Bleeding Phenotype.
Haemophilia
December 2024
Division of Pediatric Hematology and Oncology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
Background: Subcutaneous emicizumab, a factor VIII (FVIII)-mimicking bispecific monoclonal antibody, can effectively prevent bleeds in haemophilia A (HA) patients with/without inhibitors; however, its standard-dose regimens are financially burdensome. Low-dose emicizumab prophylaxis may alternatively be applied to noninhibitor HA patients in resource-limited settings.
Methods: During 2023, Thai patients with noninhibitor severe HA or moderate HA with severe bleeding phenotype (historical annualized bleeding rate [ABR] >5 bleeds/year before regular FVIII prophylaxis) who received low-/intermediate-dose FVIII secondary prophylaxis ≥8 months were enrolled.
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