Is THP-1 viability affected by the crystallinity of nanostructured carbonated hydroxyapatites?

In daily clinical practice, there is a notable variety of synthetic bone substitute, with various resorption rates, different chemical and structural characteristics that influence on bone regeneration and are not suitable for every clinical use. New biomaterials based on nanotechnology have been developed to be bioabsorbable as new bone is formed. This study intends to evaluate THP-1 cell viability when exposed to extracts of unsintered nanostructured carbonated hydroxyapatite (cHA) microspheres processed at 5 and 37°C compared to sintered hydroxyapatite processed at 90°C. cHA shows, in previous studies, biocompatibility, and better bioabsorption rates, consequently, improve the deposition of new bone and tissue repair. The results demonstrated that the tested biomaterials did not activate inflammatory role through THP-1 cells and did not affect activated macrophages independently of their crystallinities, suggesting their safety and biocompatibility. These results are of fundamental importance for the advancement of research on smart materials, especially in what controls the effect of nanostructured cHA microspheres in the biological environment, seems to be a promising biomaterial in clinical application on regenerative medicine.

Beyond Members of the Flaviviridae Family, Sofosbuvir Also Inhibits Chikungunya Virus Replication.

Chikungunya virus (CHIKV) causes a febrile disease associated with chronic arthralgia, which may progress to neurological impairment. Chikungunya fever (CF) is an ongoing public health problem in tropical and subtropical regions of the world, where control of the CHIKV vector, Aedes mosquitos, has failed. As there is no vaccine or specific treatment for CHIKV, patients receive only palliative care to alleviate pain and arthralgia. Thus, drug repurposing is necessary to identify antivirals against CHIKV. CHIKV RNA polymerase is similar to the orthologue enzyme of other positive-sense RNA viruses, such as members of the Flaviviridae family. Among the Flaviviridae, not only is hepatitis C virus RNA polymerase susceptible to sofosbuvir, a clinically approved nucleotide analogue, but so is dengue, Zika, and yellow fever virus replication. Here, we found that sofosbuvir was three times more selective in inhibiting CHIKV production in human hepatoma cells than ribavirin, a pan-antiviral drug. Although CHIKV replication in human induced pluripotent stem cell-derived astrocytes was less susceptible to sofosbuvir than were hepatoma cells, sofosbuvir nevertheless impaired virus production and cell death in a multiplicity of infection-dependent manner. Sofosbuvir also exhibited antiviral activity in vivo by preventing CHIKV-induced paw edema in adult mice at a dose of 20 mg/kg of body weight/day and prevented mortality in a neonate mouse model at 40- and 80-mg/kg/day doses. Our data demonstrate that a prototypic alphavirus, CHIKV, is also susceptible to sofosbuvir. As sofosbuvir is a clinically approved drug, our findings could pave the way to it becoming a therapeutic option against CF.