Purpose: Emerging evidence suggest that infection-dependent hyperactivation of complement system (CS) may worsen COVID-19 outcome. We investigated the role of predicted high impact rare variants - referred as qualifying variants (QVs) - of CS genes in predisposing asymptomatic COVID-19 in elderly individuals, known to be more susceptible to severe disease.
Methods: Exploiting exome sequencing data and 56 CS genes, we performed a gene-based collapsing test between 164 asymptomatic subjects (aged ≥60 years) and 56,885 European individuals from the Genome Aggregation Database. We replicated this test comparing the same asymptomatic individuals with 147 hospitalized patients with COVID-19.
Results: We found an enrichment of QVs in 3 genes (MASP1, COLEC11, and COLEC10), which belong to the lectin pathway, in the asymptomatic cohort. Analyses of complement activity in serum showed decreased activity of lectin pathway in asymptomatic individuals with QVs. Finally, we found allelic variants associated with asymptomatic COVID-19 phenotype and with a decreased expression of MASP1, COLEC11, and COLEC10 in lung tissue.
Conclusion: This study suggests that genetic rare variants can protect from severe COVID-19 by mitigating the activity of lectin pathway and prothrombin. The genetic data obtained through ES of 786 asymptomatic and 147 hospitalized individuals are publicly available at http://espocovid.ceinge.unina.it/.
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http://dx.doi.org/10.1016/j.gim.2022.04.007 | DOI Listing |
Cell Commun Signal
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Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY, 13210, USA.
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January 2025
Department of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Peking University, No.38, Xueyuan Road, Haidian, Beijing, 100191, China. Electronic address:
Psoriasis is a chronic inflammatory skin disease with etiologies related to genetics, immunity, and the environment. It is characterized by excessive proliferation of keratinocytes and infiltration of inflammatory immune cells. Glycosylation is a post-translational modification of proteins that plays important roles in cell adhesion, signal transduction, and immune cell activation.
View Article and Find Full Text PDFZhongguo Zhong Yao Za Zhi
December 2024
School of Basic Medical Sciences, Guangzhou University of Chinese Medicine Guangzhou 511400, China.
The aim of this study was to investigate the underlying mechanism of chrysophanol(Chr) in reducing inflammation and foam cell formation induced by oxidized low-density lipoprotein(ox-LDL) and to investigate the targets and pathways related to effects of Chr on coronary atherosclerosis, providing a theoretical basis for the development of new clinical drugs. RAW264.7 macrophages were cultured in vitro, and after determining the appropriate concentrations of Chr and ox-LDL for treating RAW264.
View Article and Find Full Text PDFJ Ethnopharmacol
January 2025
Biochemistry Department, Center of Biosciences, Universidade Federal de Pernambuco, Recife, Brazil; Center for Therapeutic Innovation Suely Galdino (NUPIT-SG), Universidade Federal de Pernambuco, Recife, Brazil. Electronic address:
Ethnopharmacological Relevance: Anxiety and depression are leading causes of disability worldwide, often exacerbated by chronic stress. Schinus terebinthifolia Raddi. has been used in traditional medicine for several purposes.
View Article and Find Full Text PDFFree Radic Biol Med
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State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University. Electronic address:
Periodontitis is the sixth most common disease worldwide and is closely associated with various systemic diseases, impacting overall health. It is characterized by the over-differentiation and activity of osteoclasts, leading to increased bone resorption and subsequent bone loss. Current treatments for bone loss are not ideal, highlighting the need for new targeted therapeutic strategies.
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