73 research outputs found
Inhalation of the prodrug PI3K inhibitor CL27c improves lung function in asthma and fibrosis
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
Efeito da idade sobre a fertilidade e perdas embrionĂĄrias de Ă©guas inseminadas com sĂȘmen asinino diluĂdo e resfriado a 5ÂșC por 12 horas de armazenamento
Diferenças em crescimento e produção de grãos entre quatro cultivares de milheto Pérola
Efeito dos nĂveis de concentrado sobre os componentes nĂŁo-carcaça de ovinos Morada Nova em confinamento
CaracterĂsticas morfomĂ©tricas e de carcaça de cabritos e cordeiros terminados em confinamento
CaracterĂsticas de carcaça e rendimento de buchada de caprinos alimentados com farelo grosso de trigo em substituição ao milho
Square-wave voltammetric determination of rutin in pharmaceutical formulations using a carbon composite electrode modified with copper (II) phosphate immobilized in polyester resin
Desempenho Produtivo de Novilhos Nelore, na Recria e na Engorda, Recebendo Dietas com Diferentes NĂveis de Concentrado e ProteĂna
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