Hookworms are intestinal parasitic nematodes that chronically infect ~500 million people, with reinfection common even after clearance by drugs. How infecting hookworms successfully overcome host protective mechanisms is unclear, but it may involve hookworm proteins that digest host tissues, or counteract the host's immune system, or both. To find such proteins in the zoonotic hookworm , we identified hookworm genes encoding excreted-secreted (ES) proteins, hookworm genes preferentially expressed in the hookworm intestine, and hookworm genes whose transcription is stimulated by the host immune system.
View Article and Find Full Text PDFFragment-based screening can catalyze drug discovery by identifying novel scaffolds, but this approach is limited by the small chemical libraries studied by biophysical experiments and the challenging optimization process. To expand the explored chemical space, we employ structure-based docking to evaluate orders-of-magnitude larger libraries than those used in traditional fragment screening. We computationally dock a set of 14 million fragments to 8-oxoguanine DNA glycosylase (OGG1), a difficult drug target involved in cancer and inflammation, and evaluate 29 highly ranked compounds experimentally.
View Article and Find Full Text PDFTogether with obesity and type 2 diabetes, metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global epidemic. Activation of the complement system and infiltration of macrophages has been linked to progression of metabolic liver disease. The role of complement receptors in macrophage activation and recruitment in MASLD remains poorly understood.
View Article and Find Full Text PDFPurpose: Limited data exists on the long-term course of fear of cancer recurrence (FCR) in head and neck cancer (HNC) patients. One in five patients was found to experience persistent high FCR in the first months after diagnosis. This study assessed the 3-year trajectories and associated factors of FCR in newly diagnosed HNC patients.
View Article and Find Full Text PDFThe immune system coordinates the response to cardiac injury and controls regenerative and fibrotic scar outcomes in the heart and subsequent chronic low-grade inflammation associated with heart failure. Adult mice and humans lack the ability to fully recover while adult zebrafish spontaneously regenerate after heart injury. Here we profile the inflammatory response to heart cryoinjury in zebrafish and coronary artery ligation in mouse using single cell transcriptomics.
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