RESUMO
There is an urgent need to understand severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-host interactions involved in virus spread and pathogenesis, which might contribute to the identification of new therapeutic targets. In this study, we investigated the presence of SARS-CoV-2 in postmortem lung, kidney, and liver samples of patients who died with coronavirus disease (COVID-19) and its relationship with host factors involved in virus spread and pathogenesis, using microscopy-based methods. The cases analyzed showed advanced stages of diffuse acute alveolar damage and fibrosis. We identified the SARS-CoV-2 nucleocapsid (NC) in a variety of cells, colocalizing with mitochondrial proteins, lipid droplets (LDs), and key host proteins that have been implicated in inflammation, tissue repair, and the SARS-CoV-2 life cycle (vimentin, NLRP3, fibronectin, LC3B, DDX3X, and PPARγ), pointing to vimentin and LDs as platforms involved not only in the viral life cycle but also in inflammation and pathogenesis. SARS-CoV-2 isolated from a patient´s nasal swab was grown in cell culture and used to infect hamsters. Target cells identified in human tissue samples included lung epithelial and endothelial cells; lipogenic fibroblast-like cells (FLCs) showing features of lipofibroblasts such as activated PPARγ signaling and LDs; lung FLCs expressing fibronectin and vimentin and macrophages, both with evidence of NLRP3- and IL1ß-induced responses; regulatory cells expressing immune-checkpoint proteins involved in lung repair responses and contributing to inflammatory responses in the lung; CD34+ liver endothelial cells and hepatocytes expressing vimentin; renal interstitial cells; and the juxtaglomerular apparatus. This suggests that SARS-CoV-2 may directly interfere with critical lung, renal, and liver functions involved in COVID-19-pathogenesis.
Assuntos
COVID-19 , Humanos , COVID-19/patologia , Fibronectinas , Vimentina , SARS-CoV-2 , Células Endoteliais , Proteína 3 que Contém Domínio de Pirina da Família NLR , PPAR gama , Pulmão , Inflamação/patologia , Rim , FígadoRESUMO
BACKGROUND: Imaging the lower extremity reproducibly and accurately remains an elusive goal. This is particularly true in the high risk diabetic foot, where tissue loss, edema, and color changes are often concomitant. The purpose of this study was to evaluate the reproducibility of a novel and inexpensive stereotaxic frame in assessment of wound healing. METHODS: The main idea is to keep constant and reproducible the relative position of extremities related to the sensor used for the examination during a serial studies by stereotaxic digital photographic sequence. Ten healthy volunteers were evaluated at 10 different time moments to estimate the foot position variations in the stereotaxic frame. The evolution of 40 of DFU patients under treatment was evaluated before and during the epidemical grow factor intralesional treatment. RESULTS: The wound closing and granulation speeds, the relative contribution of the contraction and tissue restauration mechanism were evaluated by stereotaxic digital photography. CONCLUSIONS: The results of this study suggest that the stereotaxic frame is a robust platform for serial study of the evolution of wound healing which allow to obtain consistent information from a variety of visible and hyperspectral measurement technologies. New stereotaxic digital photography evidences related to the diabetic foot ulcer healing process under treatment has been presented.
Assuntos
Pé Diabético/diagnóstico por imagem , Diagnóstico por Imagem/métodos , Fotografação/métodos , Técnicas Estereotáxicas , Adulto , Diagnóstico por Imagem/instrumentação , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Masculino , Fotografação/instrumentação , Técnicas Estereotáxicas/instrumentaçãoRESUMO
The potentials of the magnetic resonance (MR) methods in the research of biomedical systems have been demonstrated during the 70 years of its existence. It is presented that the Cuban experience in quantitative magnetic resonance associated with molecular, preclinical and clinical studies of significant diseases and drugs development. MR "in vitro" and "in vivo" studies of sickle cell disease, the diabetic foot ulcer, the brain tumor response and the magnetic nano-particle pharmacokinetics, are presented as example. Furthermore, contributions and restrictions of magnetic resonance to diagnostic and optimization of therapeutic pathways are discussed in some concrete cases.