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Nat Commun
December 2024
Whitehead Institute for Biomedical Research, Cambridge, MA, 02142, USA.
Although respiratory symptoms are the most prevalent disease manifestation of infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), nearly 20% of hospitalized patients are at risk for thromboembolic events. This prothrombotic state is considered a key factor in the increased risk of stroke, which is observed clinically during both acute infection and long after symptoms clear. Here, we develop a model of SARS-CoV-2 infection using human-induced pluripotent stem cell-derived endothelial cells (ECs), pericytes (PCs), and smooth muscle cells (SMCs) to recapitulate the vascular pathology associated with SARS-CoV-2 exposure.
View Article and Find Full Text PDFAnn Clin Transl Neurol
December 2024
Transplant and Cell Therapy Program, Division of Hematology, Department of Medicine, The Ottawa Hospital, Ottawa, Ontario, Canada.
Objectives: Patients with refractory myasthenia gravis (MG) have few treatment options. Autologous hematopoietic stem cell transplantation (HSCT) has been used to treat immune diseases; however, its use in the treatment of MG is not broadly considered. Our objective is to report on the efficacy and safety of HSCT in refractory MG.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Biomedical Data Science Group, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg.
Introduction: Alzheimer's disease (AD) shows significant sex differences in prevalence and clinical manifestations, but the underlying molecular mechanisms remain unclear.
Methods: This study used a large-scale, single-cell transcriptomic atlas of the human prefrontal cortex to investigate sex-dependent molecular changes in AD. Our approach combined cell type-specific and sex-specific differential gene expression analysis, pathway enrichment, gene regulatory network construction, and cell-cell communication analysis to identify sex-dependent changes.
Elife
December 2024
Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, United States.
Background: Individuals with Down syndrome (DS), the genetic condition caused by trisomy 21 (T21), display clear signs of immune dysregulation, including high rates of autoimmunity and severe complications from infections. Although it is well established that T21 causes increased interferon responses and JAK/STAT signaling, elevated autoantibodies, global immune remodeling, and hypercytokinemia, the interplay between these processes, the clinical manifestations of DS, and potential therapeutic interventions remain ill defined.
Methods: We report a comprehensive analysis of immune dysregulation at the clinical, cellular, and molecular level in hundreds of individuals with DS, including autoantibody profiling, cytokine analysis, and deep immune mapping.
FEBS Open Bio
December 2024
Guangzhou National Laboratory, Guangzhou, China.
Mice are one of the most common biological models for laboratory use. However, wild-type mice are not susceptible to COVID-19 infection due to the low affinity of mouse ACE2, the entry protein for SARS-CoV-2. Although mice with human ACE2 (hACE2) driven by Ace2 promoter reflect its tissue specificity, these animals exhibit low ACE2 expression, potentially limiting their fidelity in mimicking COVID-19 manifestations and their utility in viral studies.
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