RESUMO
In the original publication [...].
RESUMO
Purpose: Hydroxyapatite-based nanoparticles have found diverse applications in drug delivery, gene carriers, diagnostics, bioimaging and tissue engineering, owing to their ability to easily enter the bloodstream and target specific sites. However, there is limited understanding of the potential adverse effects and molecular mechanisms of these nanoparticles with varying geometries upon their entry into the bloodstream. Here, we used two commercially available hydroxyapatite nanoparticles (HANPs) with different geometries (less than 100 nm in size each) to investigate this issue. Methods: First, the particle size, Zeta potential, and surface morphology of nano-hydroxyapatite were characterized. Subsequently, the effects of 2~2000 µM nano-hydroxyapatite on the proliferation, migration, cell cycle distribution, and apoptosis levels of umbilical vein endothelial cells were evaluated. Additionally, the impact of nanoparticles of various shapes on the differential expression of genes was investigated using transcriptome sequencing. Additionally, we investigated the in vivo biocompatibility of HANPs through gavage administration of nanohydroxyapatite in mice. Results: Our results demonstrate that while rod-shaped HANPs promote proliferation in Human Umbilical Vein Endothelial Cell (HUVEC) monolayers at 200 µM, sphere-shaped HANPs exhibit significant toxicity to these monolayers at the same concentration, inducing apoptosis/necrosis and S-phase cell cycle arrest through inflammation. Additionally, sphere-shaped HANPs enhance SULT1A3 levels relative to rod-shaped HANPs, facilitating chemical carcinogenesis-DNA adduct signaling pathways in HUVEC monolayers. In vivo experiments have shown that while HANPs can influence the number of blood cells and comprehensive metabolic indicators in blood, they do not exhibit significant toxicity. Conclusion: In conclusion, this study has demonstrated that the geometry and surface area of HANPs significantly affect VEC survival status and proliferation. These findings hold significant implications for the optimization of biomaterials in cell engineering applications.
Assuntos
Apoptose , Proliferação de Células , Durapatita , Células Endoteliais da Veia Umbilical Humana , Nanopartículas , Tamanho da Partícula , Durapatita/química , Durapatita/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Nanopartículas/química , Animais , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Camundongos , Movimento Celular/efeitos dos fármacosRESUMO
Adenovirus (HAdV) can cause severe respiratory infections in children and immunocompromised patients. There is a lack of specific therapeutic drugs for HAdV infection, and the study of anti-adenoviral drugs has far-reaching clinical implications. Elemental selenium can play a specific role as an antioxidant in the human immune cycle by non-specifically binding to the amino acid methionine in body proteins. Methods: The antiviral mechanism of selenomethionine was explored by measuring cell membrane status, intracellular DNA status, cytokine secretion, mitochondrial membrane potential, and ROS production. Conclusions: Selenomethionine improved the regulation of ROS-mediated apoptosis by modulating the expression of Jak1/2, STAT3, and BCL-XL, which led to the inhibition of apoptosis. It is anticipated that selenomethionine will offer a new anti-adenoviral therapeutic alternative.