Search

Aim: This research assessed the mutagenicity and DNA damage of a novel type of nano-hydroxyapatite-silica glass ionomer cement (nano-HA-SiO2-GIC) and a conventional GIC (cGIC) using Ames and Comet assays. Methods: Cell viability was tested on human periodontal ligament fibroblasts (HPLFs) using 3.125 mg/ml, 6.25, 12.5, 25, 50, 100 and 200 mg/ml, on both types of GICs employing MTT assay. For the Comet assay, HPLFs were treated with IC50, IC25 and IC10 of test materials and the tail moments were measured. In the Ames test, four genotypic variants of strains of Salmonella typhimurium (TA100, TA98, TA1537 and TA1535) and a strain of Escherichia coli (WP2 uvrA) were employed. The material tested was extracted using sterile distilled water (0.2 g per ml) at 37 °C for 72 h. This was considered as 100 %, which was diluted to 50, 25, 12.5 and 6.25 % utilizing sterile distilled water. These five concentrations were incubated with the bacterial strains with and without metabolic activation (S9), along with appropriate positive controls. The number of revertant colonies was used to evaluate the outcome. Results: The highest cell viability (159.4 %) for nano-HA-SiO2-GIC was noticed at 3.125 mg/ml, while the lowest (24.26 %) was observed at 200 mg per ml. IC50, IC25 and IC10 values were 95.27, 51.4 and 20.1 mg/ml for cGIC, 106.9, 55.8 and 22.9 mg/ml for nano-HA-SiO2-GIC, respectively. The IC10 of both test materials showed no significant DNA damage compared to that of the negative control based on the Comet assay. The plate treated with nano-HA-SiO2-GIC showed less than double the average number of revertant colonies compared to that of negative control with regard to the Ames test. Conclusions: It can be concluded that nano-HA-SiO2-GIC is non-mutagenic based on the Ames test and did not cause DNA damage at the lowest concentration of IC10 based on the Comet assay.

A platform technology based on inorganic/organic nanoparticles for carrying drugs could be of enormous potential benefit in treating cancer. Surface modification of the nanoparticles with pH-responsive and biocompatible polymers can improve the selectivity and targeting toward the tumor cells. Polyethylene glycol (PEG) and its derivatives being present on the surface could enhance the ability to tailor nanomaterial hydrophilicity and to resist the adhesion of proteins and/or cells. Herein, we report a new nanoplatform based on mesoporous silica nanoparticles (MSNs) conjugated with poly(2-(diethylamino) ethyl methacrylate) (PDEAEMA) brushes as a candidate for stimuli-responsive intracellular drug delivery system. Alkyl bromide functional initiators (end-functionalized PDEAEMA brushes) were derivatized to amine, followed by the reaction with ethylene sulfide and poly(oligo(ethylene glycol) methyl ether acrylate (POEGMEA). Using X-ray photoelectron spectroscopy (XPS) to examine the attachment of POEGMEA, it was found that the POEGMEA molecules in the outer surface of PDEAEMA brushes have been successfully reacted with thiol groups, as indicated by the increase in the peak intensity of the C–O group at 286.5 eV. Brush-modified silica hybrids have an average diameter of ca. 250 nm, as estimated by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Rhodamine B dye was loaded into the brush-modified silica hybrids nanoparticles with loading capacity of ca. 74%. The accumulated dye released from brush-modified particles in acidic media was approximately 60%, whereas the dye amount release in basic media was less than 15% after 10 h exposure time. Alamar Blue assay was used to assess the cytotoxicity of MSNs–PDEAEMA, MSNs–PDEAEMA–SH, and MSNs–PDEAEMA–POEGMEA. The results show that all three nanosystems were non-toxic to hMSC with an increase in cell proliferation for MSNs–PDEAEMA–POEGMEA at 50 µg/mL after both 24 and 48 h of incubation.

Depression is a common psychiatric disorder that has been poorly understood. Consequently, current antidepressant agents have clinical limitations. Until today, most have exhibited the slow onset of therapeutic action and, more importantly, their effect on remission has been minimal. Thus, the need to find new forms of therapeutic intervention is urgent. The inflammation hypothesis of depression is widely acknowledged and is one that theories the relationship between the function of the immune system and its contribution to the neurobiology of depression. In this research, we utilized an environmental isolation (EI) approach as a valid animal model of depression, employing biochemical, molecular, and behavioral studies. The aim was to investigate the anti-inflammatory effect of etanercept, a tumor necrosis factor-α inhibitor on a toll-like receptor 7 (TLR 7) signaling pathway in a depressive rat model, and compare these actions to fluoxetine, a standard antidepressant agent. The behavioral analysis indicates that depression-related symptoms are reduced after acute administration of fluoxetine and, to a lesser extent, etanercept, and are prevented by enriched environment (EE) housing conditions. Experimental studies were conducted by evaluating immobility time in the force swim test and pleasant feeling in the sucrose preference test. The mRNA expression of the TLR 7 pathway in the hippocampus showed that TLR 7, MYD88, and TRAF6 were elevated in isolated rats compared to the standard group, and that acute treatment with an antidepressant and anti-inflammatory drugs reversed these effects. This research indicates that stressful events have an impact on behavioral well-being, TLR7 gene expression, and the TLR7 pathway. We also found that peripheral administration of etanercept reduces depressive-like behaviour in isolated rats: this could be due to the indirect modulation of the TLR7 pathway and other TLRs in the brain. Furthermore, fluoxetine treatment reversed depressive-like behaviour and molecularly modulated the expression of TLR7, suggesting that fluoxetine exerts antidepressant effects partially by modulating the TLR7 signaling pathway.