A shared inflammatory signature across severe malaria syndromes manifested by transcriptomic, proteomic and metabolomic analyses.

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Tác giả: Drissa Coulibaly, Bryan E Cummings, Modibo Daou, Antoine Dara, Issa Diarra, Aichatou Diawara, Ogobara K Doumbo, David R Goodlett, Bouréima Guindo, Bourama Kane, Abdoulaye K Kone, Bourema Kouriba, Matthew B Laurens, Jonathan G Lawton, Kirsten E Lyke, Fayçal Maiga, James B Munro, Amadou Niangaly, Amed Ouattara, Christopher V Plowe, Savy Sebastian, Joana C Silva, Mody Sissoko, Rafal S Sobota, Emily M Stucke, Bourama M Tangara, Ali Thera, Mahamadou A Thera, Youssouf Tolo, Amidou Traore, Karim Traoré, Mark A Travassos, Noah T Ventimiglia

Ngôn ngữ: eng

Ký hiệu phân loại: 294.592 Sacred books and scriptures

Thông tin xuất bản: England : Nature communications , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 746754

Factors governing the clinical trajectory of Plasmodium falciparum infection remain an important area of investigation. Here we present transcriptomic, proteomic and metabolomic analyses comparing clinical subtypes of severe Plasmodium falciparum malaria to matched controls with uncomplicated disease in 79 children from Mali. MMP8, IL1R2, and ARG1 transcription is higher across cerebral malaria, severe malarial anemia, and concurrent cerebral malaria and severe malarial anemia, indicating a shared inflammatory signature. Tissue inhibitor of metalloproteinases 1 is the most upregulated protein in cerebral malaria, which along with elevated MMP8 and MMP9 transcription, underscores the importance of the metalloproteinase pathway in central nervous system pathophysiology. L-arginine metabolites are decreased in cerebral malaria, which coupled with increased ARG1 transcription suggests a putative mechanism impairing cerebral vasodilation. Using multi-omics approaches, we thus describe the inflammatory cascade in severe malaria syndromes, and identify potential therapeutic targets and biological markers.
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