The risk for severe illness from COVID-19 increases with age as older patients are at the highest risk. Although it is still unclear whether the virus is blood-transmitted, the viral RNA is detected in serum. Identifying how Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) interacts with specific blood components during aging is expected to guide proper therapies. Considering that all human coronavirus require host cellular molecules to promote infection, we investigated the aging whole blood transcriptome from the Genotype-Tissue Expression (GTEx) database to explore differentially expressed genes (DEGs) translated into proteins potentially interacting with viral proteins. From a total of 22 DEGs in aged blood, five genes (FASLG, CTSW, CTSE, VCAM1, and BAG3) changed expression during aging. These age-related genes are involved in immune response, inflammation, cell component and cell adhesion, and platelet activation/aggregation. Both males and females older than 50 overexpress FASLG compared with younger adults (20-30 years old), possibly inducing a hyper-inflammatory cascade that activates specific immune cells. Furthermore, the expression of cathepsins (CTSW and CTSE) and the anti-apoptotic co-chaperone molecule BAG3 was significantly increased throughout aging in both gender. By exploring publicly available Single-Cell RNA-Sequencing (scRNA-Seq) data on peripheral blood of SARS-CoV-2-infected patients, we found FASLG and CTSW expressed mainly in natural killer (NK) cells and CD8+ (cytotoxic) T lymphocytes whereas BAG3 was expressed in CD4+ T cells, naive T cells, and CD14+ monocytes. The increased expression of FASLG in blood during aging may explain why older patients are more prone to severe acute viral infection complications. These results indicate FASLG as a prognostic candidate and potential therapeutic target for more aggressive clinical manifestation of COVID-19.
The risk for severe COVID-19 increases with age as older patients are at the highest risk. Identifying how Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) interacts with blood components during aging is urgent. We investigated the aging whole blood transcriptome from the Genotype-Tissue Expression (GTEx) database to explore differentially expressed genes (DEGs) translated into proteins interacting with viral proteins. From 22 DEGs in aged blood, FASLG, CTSW, CTSE, VCAM1, and BAG3 changed their expression with involvement in immune response, inflammation, cell component and adhesion, and platelet activation/aggregation. Males and females older than 50 overexpress FASLG possibly inducing a hyper-inflammatory cascade. The expression of cathepsins (CTSW and CTSE) and the anti-apoptotic co-chaperone molecule BAG3 was increased throughout aging in both gender. By exploring publicly available Single-Cell RNA-Sequencing data on peripheral blood of SARS-CoV-2-infected patients, we found FASLG and CTSW expressed in natural killer cells and CD8 + T lymphocytes, whereas BAG3 was expressed in CD4 + T cells, naive T cells, and CD14 + monocytes. The expression of FASLG in aged blood may explain why older patients are more prone to viral infection complications. The results indicate FASLG as a prognostic candidate and potential therapeutic target for the more aggressive clinical manifestation of COVID-19. The reduction of FASLG could be helpul against disease progression.
Extracellular matrix (ECM) remodeling and inflammation have been reported in penile carcinomas (PeCa). However, the cell types and cellular crosstalk involved in PeCa are unexplored. We aimed to characterize the complexity of cells and pathways involved in the tumor microenvironment (TME) in PeCa and propose target molecules associated with the TME. We first investigated the prognostic impact of cell types with a secretory profile to identify drug targets that modulate TME-enriched cells. The secretome analysis using the PeCa transcriptome revealed the enrichment of inflammation and extracellular matrix pathways. Twenty-three secreted factors were upregulated, mainly collagens and matrix metalloproteinases (MMPs). The deregulation of collagens and MMPs was confirmed by Quantitative reverse transcription - polymerase chain reaction (RT-qPCR). Further, the deconvolution method (digital cytometry) of the bulk samples revealed a high proportion of macrophages and dendritic cells (DCs) and B cells. Increased DCs and B cells were associated with better survival. A high proportion of cancer-associated fibroblasts (CAFs) was observed in low-survival patients. Patients with increased CAFs had decreased immune cell proportions. The treatment with the MMP inhibitor GM6001 in CAF cells derived from PeCa resulted in altered cell viability. We reported a crosstalk between immune cells and CAFs, and the proportion of these cell populations was associated with prognosis. We demonstrate that a drug targeting MMPs modulates CAFs, expanding the therapeutic options of PeCa.
O objetivo da pesquisa foi analisar a fitossociologia e diversidade florística de um trecho de floresta ombrófila densa localizada na Amazônia Oriental. Com o método sistémico foram alocadas 5 parcelas de 1 ha, distanciadas em 0,5 km entre si, em um transecto de 5 km de comprimento por 0,3 km de largura. Parâmetros fitossociológicos foram utilizados para a estrutura horizontal e vertical. Inventariados 965 indivíduos, com DAP ≥ 20 cm, classificados em 35 famílias e 92 espécies arbóreas. A fórmula de Sturges Determinou 11 classes de DAP, formando um “J” investido. O índice de diversidade de Shannon foi de 2,39 nats ind-1 e o Índice de similaridade de Jaccard foi igual ou acima de 0,33. As famílias mais representativas na área de estudo foram a Fabaceae (232), Lecythidaceae (143), Sapotaceae (132), e as espécies com maiores valores na análise de valor de importância são Pouteria guianensis Aubl. (12,24 %), Licania paraensis (10,41 %) e Guatteria poeppigiana Mart. (10,10 %).
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