Graphical abstract

This study aims to investigate the Effects of Titanium dioxide nanoparticles (TiO 2 NPs) on the stereological parameters in the dentate gyrus and the morphology of granular hippocampal neurons in adult mice. Adult male mice (n=20, weight average: 45 g) were randomly divided into four groups including: group receiving saline (controls), low-dose (LD) 2.5 mg/kg TiO TiO 2 NPs, medium-dose (MD) 5 mg/kg TiO 2 NPs and high-dose (HD) 10 mg/kg TiO 2 NPs, daily using gavage for 35 days. To estimate the volume of the hippocampus, dentate gyrus, and sub-layers of dentate gyrus the Cavalieri principle was used. The physical dissector was used to determine the numerical density of dentate gyrus granular cells. For analyzing the morphology of dentate gyrus granular cells the qualitative Golgi staining was used. Our data showed that the total volume of the hippocampus, dentate gyrus and its sublayers including molecular, granular and polymorph in TiO 2 treated mice decreased significantly compared to the control group. Moreover, the total number and numerical density of dentate gyrus granular sub layer cells showed a significant reduction in all three experimental groups compared to the control group. The granular cells of the dentate gyrus had shorter dendritic length and decreased dendritic branches in the TiO 2-treated in comparison with the control mice. These data can justify the disorders related to memory, learning and hippocampus neurons damages due to using of TiO 2 NPs.

Doxorubicin is one of the most effective chemotherapeutic agents; however, it has various side effects, such as cardiotoxicity. Therefore, novel methods are needed to reduce its adverse effects. Quercetin is a natural flavonoid with many biological activities. Liposomes are lipid-based carriers widely used in medicine for drug delivery. In this study, liposomal doxorubicin with favorable characteristics was designed and synthesized by the thin-film method, and its physicochemical properties were investigated by different laboratory techniques. Then, the impact of the carrier, empty liposomes, free doxorubicin, liposomal doxorubicin, and quercetin were analyzed in animal models. To evaluate the interventions, measurements of cardiac enzymes, oxidative stress and antioxidant markers, and protein expression were performed, as well as histopathological studies. Additionally, cytotoxicity assay and cellular uptake were carried out on H9c2 cells. The mean size of the designed liposomes was 98.8 nm, and the encapsulation efficiency (EE%) was about 85%. The designed liposomes were anionic and pH-sensitive and had a controlled release pattern with excellent stability. Co-administration of liposomal doxorubicin with free quercetin to rats led to decreased weight loss, creatine kinase (CK-MB), lactate dehydrogenase (LDH), and malondialdehyde (MDA), while it increased the activity of glutathione peroxidase, catalase, and superoxide dismutase enzymes in their left ventricles. Additionally, it changed the expression of NOX1, Rac1, Rac1-GTP, SIRT3, and Bcl-2 proteins, and caused tissue injury and cell cytotoxicity. Our data showed that interventions can increase antioxidant capacity, reduce oxidative stress and apoptosis in heart tissue, and lead to fewer complications. Overall, the use of liposomal doxorubicin alone or the co-administration of free doxorubicin with free quercetin showed promising results.

Intermittent fasting diet (IF) as a restrictive regimen prevents neural degeneration and stimulates overexpression of various neurotropic factors in the hippocampus of animal models. This study evaluates the potential effect of the IF in the prevention of learning and memory dysfunction and improving the alterations in the number and volume of neurons in an ethidium bromide (EB) induced mouse model of demyelination.Mice were randomly assigned into N group (Normal Diet and normal saline injection), F group (IF and normal saline injection), EBN group (Normal Diet and EB injection), EBF group (IF and EB injection). The hidden platform test was carried out based on path length, escape latency and swim speeds of mice. Stereological studies were determined by the Cavalieri and the Optical Dissector technique. Maintenance of mice on the IF results in significantly decreased the body weight and biochemical parameters, increased total number of neurons and volume of the hippocampus, and improved learning and memory parameters of adult male mice. However, IF in EBF group did not show as excellently as F group. The EBF group displayed significantly spatial memory improvement than that in EBN group. There were no statistically significant differences between EBF and EBN groups in stereological and learning parameters, though the EBF group displayed faster escape latencies, and swam faster and shorter path lengths than the EBN group in these parameters. Therefore as a conclusion, The IF fairly improved some adverse effects of EB in experimental demyelination models.

Background: One of the most important factors in the fracture healing is the intracellular production of prostaglandins by osteoblast cells. Nonsteroidal anti-inflammatory drugs (NSAIDs) exert their effects through inhibition of prostaglandin synthesis. NSAIDs are widely used in orthopedic practices and their effect on bone healing is not fully understood yet. Objectives: The current study aimed at examining the effects of indomethacin and meloxicam on tibia fracture union in rats. Methods: The current study was conducted on 60 male rats. Mid-shaft tibia fracture was induced in rats using bone-breaker device. The animals were randomly divided into 3 groups; a control group that received distilled water and 2 other groups that received indomethacin and meloxicam respectively for 28 days. At the end of weeks 1, 2, 4, 8 and 12, four rats were randomly sacrificed from each group, and histological evaluation, measurement of the calcium, phosphorus, and alkaline phosphatase plasma levels, as well as radiographic examinations were performed on them. Results: After 4 weeks, a thin layer of woven bone was observed in the vast spaces of the bone marrow in the fracture area in the control group. In the meloxicam group in the week 4, the formation of immature blades of bone was observed, which were less organized and more irregular. In the indomethacin group in the week 4, new bone formation was less immature and more areas of cartilage were still observed. In the radiographic evaluations, delayed union in indomethacin and meloxicam groups was observed, which was more significant in the indomethacin group. Conclusions: Indomethacin and meloxicam had impact on the process of bone repair and delayed union in both groups of drugs. This delayed union was more significant in non-selective NSAIDs (COX-I and = II inhibitors) rather than selective NSAIDs (COX-II inhibitor).