RESUMO
In the present condition of COVID-19, the demand for antimicrobial products such as face masks and surgical gowns has increased. Because of this increasing demand, there is a need to conduct a study on the development of antimicrobial material. Therefore, this study was conducted on the development of Aloe Vera and Polyvinyl Alcohol (AV/PVA) electrospun nanofibers. Four different fibers were developed by varying the concentrations of Aloe vera (0.5%, 1.5%, 2.5%, and 3%) while maintaining the concentration of PVA constant. The developed samples were subjected to different characterization techniques such as SEM, FTIR, XRD, TGA, and ICP studies. After that, the antimicrobial activity of the developed Aloe Vera/PVA electrospun nanofibers was checked against Gram-positive (Staphylococcus aureus) bacteria and Gram-negative (Escherichia coli) bacteria. The developed nanofibers had high profile antibacterial activity against both bacteria, but showed excellent results against S. aureus bacteria as compared with E. coli. These nanofibers have potential applications in the development of surgical gowns, gloves, etc.
RESUMO
Dysregulation of the PI3K/mTOR pathway, either through amplifications, deletions, or as a direct result of mutations, has been closely linked to the development and progression of a wide range of cancers. Moreover, this pathway activation is a poor prognostic marker for many tumor types and confers resistance to various cancer therapies. Here, we describe VS-5584, a novel, low-molecular weight compound with equivalent potent activity against mTOR (IC(50) = 37 nmol/L) and all class I phosphoinositide 3-kinase (PI3K) isoforms IC(50): PI3Kα = 16 nmol/L; PI3Kß = 68 nmol/L; PI3Kγ = 25 nmol/L; PI3Kδ = 42 nmol/L, without relevant activity on 400 lipid and protein kinases. VS-5584 shows robust modulation of cellular PI3K/mTOR pathways, inhibiting phosphorylation of substrates downstream of PI3K and mTORC1/2. A large human cancer cell line panel screen (436 lines) revealed broad antiproliferative sensitivity and that cells harboring mutations in PI3KCA are generally more sensitive toward VS-5584 treatment. VS-5584 exhibits favorable pharmacokinetic properties after oral dosing in mice and is well tolerated. VS-5584 induces long-lasting and dose-dependent inhibition of PI3K/mTOR signaling in tumor tissue, leading to tumor growth inhibition in various rapalog-sensitive and -resistant human xenograft models. Furthermore, VS-5584 is synergistic with an EGF receptor inhibitor in a gastric tumor model. The unique selectivity profile and favorable pharmacologic and pharmaceutical properties of VS-5584 and its efficacy in a wide range of human tumor models supports further investigations of VS-5584 in clinical trials.
