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Biology subjects

Guimaraes, P. P. G.

Publications and source records attributed to Guimaraes, P. P. G..

2 recordsLinked to original sources

Improved antiproliferative activity of doxorubicin-loaded calcium phosphate nanoparticles against melanoma cells

The high incidence of melanoma has received significant attention. Despite advances in early detection and standard treatment options, new strategies that improve therapy with reduced side effects are highly desirable. Several studies have demonstrated the efficiency of doxorubicin (Dox) to treat melanoma, however, side effects limit its clinical use. Drug delivery systems, especially nanostructured ones, are a useful approach to enhance antitumor activity and reduce the toxicity of drugs. Here, we report the use of calcium phosphate nanoparticles functionalized with Dox and hyaluronic acid (N-Dox) to enhance Dox antiproliferative activity. The effects were accessed in A-375 melanoma cells, in which N-Dox significantly decreased IC50 over 48 hours (0.142 {+/-} 0.07) compared to the free drug (0.44 {+/-} 0.25). Treatment triggered DNA damage, increased nuclear area, and senescent phenotype. Furthermore, it did not form colonies after 14 days of incubation preceded by short exposure treatment. These preliminary results indicate that N-Dox hold promise for melanoma treatment, reducing the minimum effective dose and perhaps a reduction in the cost of treatment.

cancer biology↗

A suitable murine model for studying respiratory coronavirus infection and therapeutic countermeasures in BSL-2 laboratories

Several animal models are being used to explore important features of COVID-19, nevertheless none of them recapitulates all aspects of the disease in humans. The continuous refinement and development of other options of in vivo models are opportune, especially ones that are carried out at BSL-2 (Biosafety Level 2) laboratories. In this study, we investigated the suitability of the intranasal infection with the murine betacoronavirus MHV-3 to recapitulate multiple aspects of the pathogenesis of COVID-19 in C57BL/6J mice. We demonstrate that MHV-3 replicated in lungs 1 day after inoculation and triggered respiratory inflammation and dysfunction. This MHV-model of infection was further applied to highlight the critical role of TNF in cytokine-mediated coronavirus pathogenesis. Blocking TNF signaling by pharmacological and genetic strategies greatly increased the survival time and reduces lung injury of MHV-3-infected mice. In vitro studies showed that TNF blockage decreased SARS-CoV-2 replication in human epithelial lung cells and resulted in the lower release of IL-6 and IL-8 cytokines beyond TNF itself. Taken together, our results demonstrate that this model of MHV infection in mice is a useful BSL-2 screening platform for evaluating pathogenesis for human coronaviruses infections, such as COVID-19.

microbiology↗