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Lewy body diseases and the gut.
Mol Neurodegener
January 2025
Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815, USA.
Gastrointestinal (GI) involvement in Lewy body diseases (LBDs) has been observed since the initial descriptions of patients by James Parkinson. Recent experimental and human observational studies raise the possibility that pathogenic alpha-synuclein (⍺-syn) might develop in the GI tract and subsequently spread to susceptible brain regions. The cellular and mechanistic origins of ⍺-syn propagation in disease are under intense investigation.
View Article and Find Full Text PDFRhesus Cytomegalovirus-encoded Fcγ-binding glycoproteins facilitate viral evasion from IgG-mediated humoral immunity.
Nat Commun
January 2025
Institute of Virology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Human cytomegalovirus (HCMV) encodes four viral Fc-gamma receptors (vFcγRs) that counteract antibody-mediated activation in vitro, but their role in infection and pathogenesis is unknown. To examine their in vivo function in an animal model evolutionarily closely related to humans, we identified and characterized Rh05, Rh152/151 and Rh173 as the complete set of vFcγRs encoded by rhesus CMV (RhCMV). Each one of these proteins displays functional similarities to their prospective HCMV orthologs with respect to antagonizing host FcγR activation in vitro.
View Article and Find Full Text PDFStroma-derived Dickkopf-1 contributes to the suppression of NK cell cytotoxicity in breast cancer.
Nat Commun
January 2025
Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO, USA.
Mechanisms related to tumor evasion from NK cell-mediated immune surveillance remain enigmatic. Dickkopf-1 (DKK1) is a Wnt/β-catenin inhibitor, whose levels correlate with breast cancer progression. We find DKK1 to be expressed by tumor cells and cancer-associated fibroblasts (CAFs) in patient samples and orthotopic breast tumors, and in bone.
View Article and Find Full Text PDFSevere pulmonary arterial hypertension and cardiogenic shock in acute systemic lupus erythematosus.
BMJ Case Rep
January 2025
Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital, Melbourne, Victoria, Australia.
We describe a woman in her late 20s with newly diagnosed systemic lupus erythematosus (SLE), who presented with fulminant pulmonary arterial hypertension (PAH) requiring inotropic and extracorporeal support. She was established on triple pulmonary vasodilator therapy with concurrent aggressive immunosuppression; however, treatment was complicated by infection and diffuse alveolar haemorrhage, necessitating delays in immunosuppression and withdrawal of epoprostenol. Despite this, with ongoing suppression of her SLE, her pulmonary haemodynamics improved, with normal pressures on right heart catheterisation several months later allowing stepdown to sildenafil monotherapy.
View Article and Find Full Text PDFAgeing is a major risk factor for neurodegenerative diseases like Alzheimer's disease (AD). Microglia, as the principal innate immune cells within the brain, exert homeostatic and active immunological defense functions throughout human lifespan. The age-related dysfunction of microglia is currently recognized as a pivotal trigger for brain diseases associated with aging.
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