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Sickle cell disease (SCD) is the most common genetic disease in the world and a societal challenge. SCD is characterized by multi-organ injury related to intravascular hemolysis. To understand tissue-specific responses to intravascular hemolysis and exposure to heme, we present a transcriptomic atlas in the primary target organs of HbSS vs HbAA transgenic SCD mice.
View Article and Find Full Text PDFPerinatal dysfunction of innate immunity in cystic fibrosis.
Sci Transl Med
January 2025
First Department of Medicine, Cardiology, TUM University Hospital, Technical University of Munich, School of Medicine and Health, Munich 81675, Germany.
In patients with cystic fibrosis (CF), repeated cycles of infection and inflammation eventually lead to fatal lung damage. Although diminished mucus clearance can be restored by highly effective CFTR modulator therapy, inflammation and infection often persist. To elucidate the role of the innate immune system in CF etiology, we investigated a CF pig model and compared these results with those for preschool children with CF.
View Article and Find Full Text PDFVariants and vaccines impact nasal immunity over three waves of SARS-CoV-2.
Nat Immunol
January 2025
Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA, USA.
Viral variant and host vaccination status impact infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), yet how these factors shift cellular responses in the human nasal mucosa remains uncharacterized. We performed single-cell RNA sequencing (scRNA-seq) on nasopharyngeal swabs from vaccinated and unvaccinated adults with acute Delta and Omicron SARS-CoV-2 infections and integrated with data from acute infections with ancestral SARS-CoV-2. Patients with Delta and Omicron exhibited greater similarity in nasal cell composition driven by myeloid, T cell and SARS-CoV-2 cell subsets, which was distinct from that of ancestral cases.
View Article and Find Full Text PDFRSK1 is an exploitable dependency in myeloproliferative neoplasms and secondary acute myeloid leukemia.
Nat Commun
January 2025
Division of Hematology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Myeloid malignancies are heterogenous disorders characterized by distinct molecular drivers but share convergence of oncogenic signaling pathways and propagation by ripe pro-inflammatory niches. Here, we establish a comprehensive transcriptional atlas across the spectrum of myeloproliferative neoplasms (MPN) and secondary acute myeloid leukemia (sAML) through RNA-sequencing of 158 primary samples encompassing CD34+ hematopoietic stem/progenitor cells and CD14+ monocytes. Supported by mass cytometry (CyTOF) profiling, we reveal aberrant networks of PI3K/AKT/mTOR signalling and NFκB-mediated hyper-inflammation.
View Article and Find Full Text PDF[Molecular mechanism of Xinyang Tablets in improving myocardial fibrosis in uremic cardiomyopathy based on single-cell sequencing technology].
Zhongguo Zhong Yao Za Zhi
December 2024
State Key Laboratory of Traditional Chinese Medicine Syndrome, the First Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou 510407, China Geriatrics Department, the First Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou 510407, China Lingnan Medical Research Center, Guangzhou University of Chinese Medicine Guangzhou 510405, China Guangdong Clinical Research Institute of Chinese Medicine Guangzhou 510407, China.
This study aimed to investigate the ameliorative effect of Xinyang Tablets on myocardial fibrosis in uremic cardiomyopathy(UCM) using single-cell sequencing technology. UCM mouse models were established by 5/6 nephrectomy(NPM) and randomly divided into the model group, Xinyang Tablets group, and sham-operated(sham) group as the control. The Xinyang Tablets group received postoperative interventions of Xinyang Tablets(0.
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