RESUMO
Metal-organic frameworks (MOFs) are utilized as nanocarriers to enhance the efficiency of chemotherapy drugs, including cisplatin, which exhibit limitations such as side effects and resistance mechanisms. To evaluate the role of MOFs, we employed a molecular dynamics simulation, which, unlike other experiments, is cost-effective, less dangerous, and provides accurate results. Furthermore, we conducted molecular docking simulations to understand the interaction between cisplatin and MOF, as well as their internal interactions and how they bind to each other. Cisplatin and MOF molecules were parametrized using the Avogadro software and x2top command in GROMACS 5.1.2 and optimized by CP2K software; the Charmm-GUI site parametrized the cell cancer membrane. Three molecular dynamics simulations were conducted in four stages at various pHs, followed by simulated umbrella sampling. The simulations analyzed the pH responsiveness, total energy, Gibbs free energy, gyration radius, radial distribution function (RDF), solvent accessible surface area, and nanoparticles' toxicity. Results demonstrated that a neutral pH level (7.4) has greater adsorption and interaction compared to acidic pH values (6.4 and 5.4) because it displays the highest total energy (-17.1 kJ/mol), the highest RDF value (6.66), and the shortest distance (0.51 nm). Furthermore, the combination of cisplatin and MOFs displayed increased penetration compared to that of their individual forms. This study highlights the suitability of MOFs as nanocarriers and identifies the optimal pH values for desirable outcomes. Thus, it provides future studies with appropriate data to conduct their experiments in assessing MOFs.
RESUMO
Pathogen recognition receptors (PRRs), which play a crucial role in responding to pathogens, affect the function of mesenchymal stem cells (MSCs). One important group of PRRs is the toll-like receptors (TLRs). When PRRs are activated, they can alter the expression of specific surface markers, the ability of MSCs to differentiate, and the types of substances they secrete. These modifications in MSC function may have unexpected consequences for patients. In this study, we examined how Leishmania major (L. major) promastigotes affect the properties of MSCs. MSCs were isolated from adipose tissue and categorized into two groups: one group left untreated and the other group exposed to L. major. Giemsa staining was employed to accurately quantify the number of parasites that entered the cells. After 72 hours, real-time polymerase chain reaction was utilized to assess the expression of TLRs. Additionally, the flow cytometry technique was used to evaluate the expression of surface markers on the MSCs. Our results showed that MSCs can engulf parasites and increase the expression of TLR4 and TLR6. The pro-inflammatory cytokine increased, and the transforming growth factor-ß decreased significantly. The parasite exposure increased reactive oxygen species production. Additionally, the percentage of cluster differentiation (CD) 73 decreased, and the mean fluorescent index of CD29 and CD73 was down-regulated by L. major. Exposure to parasites diminishes the immunomodulatory capacity of MSCs. This discovery holds significance for the application of MSCs in addressing parasite infections and underscores the need for additional research to enhance their therapeutic effectiveness.