PI3K activation plays a central role in the development of pulmonary inflammation and tissue remodeling. PI3K inhibitors may thus offer an improved therapeutic opportunity to treat non-resolving lung inflammation but their action is limited by unwanted on-target systemic toxicity. Here we present CL27c, a prodrug pan-PI3K inhibitor designed for local therapy, and investigate whether inhaled CL27c is effective in asthma and pulmonary fibrosis. Mice inhaling CL27c show reduced insulin-evoked Akt phosphorylation in lungs, but no change in other tissues and no increase in blood glycaemia, in line with a local action. In murine models of acute or glucocorticoid-resistant neutrophilic asthma, inhaled CL27c reduces inflammation and improves lung function. Finally, inhaled CL27c administered in a therapeutic setting protects from bleomycin-induced lung fibrosis, ultimately leading to significantly improved survival. Therefore, local delivery of a pan-PI3K inhibitor prodrug reduces systemic on-target side effects but effectively treats asthma and irreversible pulmonary fibrosis.
The essential oils of the leaves of Eugenia brasiliensis, Eugenia beaurepaireana, and Eugenia umbelliflora were analyzed by GC-MS. The major compounds found in the oil of E. brasiliensis were spathulenol (12.6%) and tau-cadinol (8.7%), of E. beaurepaireana were beta-caryophyllene (8.0%) and bicyclogermacrene (7.2%), and of E. umbelliflora were viridiflorol (17.7%) and beta-pinene (13.2%). These oils were assayed to determine their antibacterial activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. All of the oils analyzed showed antibacterial activity, ranging from moderate to strong, which was most accentuated for the E. umbelliflora and E. brasiliensis oils, which strongly inhibited the growth of S. aureus giving values of MIC = 119.2 and 156.2 microg/mL, respectively.
A pandemia de coronavírus que atingiu o mundo no final de 2019 segue batendo recordes de novos casos e óbitos relacionados à doença. As orientações para o manejo clínico dos pacientes infectados e a prevenção de novos casos estão centradas nas medidas de controle dos sintomas, hábitos de higiene, isolamento social e diminuição da aglomeração de pessoas. Tal fato forçou uma mudança no modo como os serviços de saúde prestam cuidados, protagonizando a incorporação de novas tecnologias em saúde. Assim, este Ensaio objetiva compilar e analisar algumas experiências de uso das tecnologias digitais em saúde, para minimizar os impactos da COVID-19. Identificou-se o desenvolvimento de soluções tecnológicas de manejo clínico do paciente, diagnóstico por imagem, uso de inteligência artificial para análise de riscos, aplicativos de geolocalização, ferramentas para análise de dados e relatórios, autodiagnóstico e, inclusive, de orientação à tomada de decisão. A grande maioria das iniciativas listadas tem sido eficaz na minimização dos impactos da COVID-19 nos sistemas de saúde, de modo que visa à diminuição da aglomeração de pessoas e assim facilita o acesso aos serviços, bem como contribui para a incorporação de novas práticas e modos de cuidar, em saúde.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.