Silica is among the most popular nanoparticles. Large-scale production and use have increased the risk of human exposure to silica nanoparticles (SiO2NPs). This study aimed to investigate the toxic effects on the kidney, liver and brain of the SiO2NPs. Twenty eight male Wistar albino rats were divided into four groups (n=7 rats) as control (1 mL/day physiological saline administration for 28 day), 6 nm SiO2NP (6 nm, 150 μg/mL/day for 28 day), 20 nm SiO2NP (20 nm, 150 μg/mL/day for 28 day) and 50 nm SiO2NP (50 nm, 150 μg/mL/day for 28 day) groups. After the last administration, rats were sacrificed and kidney, liver and brain samples were taken for biochemical and histological investigation. In all groups, malondialdehyde (MDA) levels, superoxide dismutase (SOD) and catalase (CAT) activities were measured using the spectrophotometric methods. Ultrastructural changes of tissues were evaluated using transmission electron microscopy. In the kidney tissue, the MDA level significantly increased in the 6 and 50 nm groups, while the similar increase was observed in the 6 nm group of the liver and 20 and 50 nm groups of the brain. SOD activity significantly increased in the 6, 20 and 50 nm groups in brain and kidney tissues, but no significant change was observed in the liver tissue groups. Catalase activity decreased in the kidneys at 6 and 50 nm groups and increased in the 20 and 50 nm groups in liver and brain tissues. Ultrastructurally, kidney and liver tissues had normal morphological features in all groups. Degenerative changes were observed in the nerve fibers and axoplasm of myelinated and unmyelinated nerve fibers in 6 nM, 20 nM and 50 nM SiO2NP groups in the brain. These findings showed that exposure to 6, 20 and 50 nm sizes SiO2 NPs may cause toxic effects in the liver, kidney and brain.

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Endometrial cancer is the most common cancer of the female reproductive system. Perifosine has shown anti-tumor activity in a variety of cancers by inhibition of AKT phosphorylation. The active metabolite of vitamin D (1,25(OH)2D3) has anti-proliferative and pro-apoptotic properties and is recognized as an agent with the great potential for cancer intervention. Combination treatment with specific agents has been widely used as targeted therapy for cancer. In this study, we aimed to investigate the anti-apoptotic effect of varying concentrations of perifosine and vitamin D on endometrial cancer cell line (HEC1A). The expression levels of P53, BCL2 and BAX were assessed in cultured HEC1A cells at 10 and 30 μM concentrations of perifosine, 50 and 200 nM of vitamin D and combination groups using qRT PCR. Apoptosis evaluation in HEC-1A cells was performed using flow cytometry after 48 and 72 h of treatment with perifosine, vitamin D and combinations of both. According to the obtained data, treatment with different doses of perifosine and vitamin D significantly induced apoptosis in a time and dose-dependent manner in HEC-1A cells. The mRNA expression levels of P53, BAX, BCL2 in HEC-1A cells were found to be significant in the experimental groups as compared with the control. Perifosine displayed substantial antitumor activity in HEC-1A. These effects were increased with vitamin D. Therefore, perifosine and vitamin D combinations should be further evaluated in clinical studies in endometrial cancer.

It has been clearly indicated that osteoarthritis (OA) is an inflammatory and degenerative disease that could be promoted by Rho-kinase (ROCK); however, little is known about the role of ROCK/inhibitor κB alpha (IκB-α)/nuclear factor-κB (NF-κB) p65 pathway activation in interleukin-1β (IL-1β) induced inflammatory response and oxidative stress in primary human chondrocytes. To test this hypothesis, we focused on determining ROCK-II, IκB-α, p-IκB-α, NF-κB p65, p-NF-κB p65, IL-6, tumor necrosis factor alpha (TNF-α), cyclooxygenase-2 (COX-2), p22phox, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subtype 4 (NOX4) protein expression, ROCK-II activity, NADPH oxidase levels, and total antioxidant capacity (TAC) in the presence and absence of ROCK-inhibitor fasudil. IL-1β (2 ng·mL–1, 24 h) increased the expression of ROCK-II, p-IκB-α, NF-κB p65, p-NF-κB p65, IL-6, TNF-α, COX-2, and p22phox proteins, and decreased the expression of IκB-α, and the NOX4 protein level did not alter. ROCK activity and NADPH oxidase levels were increased, whereas the TAC was decreased by IL-1β. Fasudil (10−5–10−7 M) reversed all these changes induced by IL-1β. These results demonstrate that ROCK/IκB-α/NF-κB p65 pathway activation contributes to the IL-1β-induced inflammatory response and oxidative stress, and thus, ROCK inhibition might be a beneficial treatment option for OA patients mainly based on its anti-inflammatory and antioxidant effects.

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