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Objective: Breast cancer is one of the most prevalent malignancies and leading causes of females’ mortality worldwide. Because of resistance to various treatment options, new treatments based on molecular targeting has introduced as noticeable strategies in cancer treatment. In this regard, heat shock protein 90 (Hsp90) inhibitors are proposed as effective anticancer drugs. The goal of the study was to utilize a combination of the doxorubicin (DOX) and NVP-AUY 922 on the MCF-7 breast cancer model to investigate the possible cytotoxic mechanisms. Methods: MCF-7 breast cancer cell line was prepared and treated with various concentrations of DOX and NVP-AUY922 in single-drug treatments. We investigated the growth-inhibitory pattern by MTT assay after continuous exposure to NVP-AUY922 and DOX in order to determine dose-response. Then the combinatorial effects were evaluated in concentrations of 0.5 × IC 50 , 0.2 × IC 50 , 1 × IC 50 and, 2 × IC 50 of each drugs. Based on MTT results of double combinations, low effective doses were selected for Real-time PCR [caspase3 and vascular endothelial growth factor (VEGF)] and caspase 3 enzyme activity. Results: A dose-dependent inhibitory effects were presented with increasing the doses of both drugs in single treatments. The upregulation of caspase 3 and downregulation of VEGF mRNA were observed in double combinations of NVP-AUY922 and DOX versus single treatments. Also, in these combinations in low doses of examined drugs (0.5 × IC 50 , 0.2 × IC 50 ), higher caspase 3 activity were presented in comparison to single treatments (p<0.05). Conclusions: Our findings indicate an effective action of NVP-AUY922 in combined with DOX in this cell line. These results can predict the treatment outcome in this model.

It seems that defects on micro-minerals levels have an etiologic role involved in type 1 diabetes mellitus pathogenicity. The aim of our study were to evaluate the serum levels of zinc and iron and investigate their possible relationship between these biochemical parameters with demographic conditions and glycemic control in patients with type 1 diabetes mellitus disorder. In this case-control based study , 68 female with type 1 diabetes mellitus with a mean age of 52.2 ± 2 as case group and 122 healthy women as a control group with a mean age of 49/4 ± 3/2 were investigated .for biochemical analysis ,10 mL fasting venous blood sample were obtained from each subjects. FBS (fasting blood glucose), fructosamine (glycemic control parameter) were determined (spectrophotometry method, (pars azmoon, Iran), nitroblue tetrazoline method respectively).serum zinc level with colorimetric method (Biorex-UK) and serum iron with photometric method (pars azmoon, Iran) were determined. Statistical analysis using SPSS software performed. Significant levels considered as P < 0.05. According to this study there is statistically significant difference between serum levels of iron and zinc in patients with type 1 diabetes compared to controls .indeed serum level of iron and zinc had lower level in patient group toward controls. In patients group, there are a positive correlation between age and decreased level of serum zinc (P < 0.05). Also there was a significant negative correlation between the glycemic control status and serum zinc. Other studied parameters concluded BMI (body mass index), Weight and height have not significant difference between groups. The decrease in serum iron and zinc level in women with type 1 diabetes may be related to low dietary intake or increased excretion of micro minerals or the presence of confounding factors that require more extensive intervention studies to confirm it.

Background: Drug delivery systems have been designed to achieve targeted delivery and control the release rate of the drugs. A serious challenge associated with drug delivery systems is the presence of the blood-brain barrier which limits drugs penetration. In the current study, the effects of cisplatin nanoparticles on A172 brain cancer cell line were investigated. Methods: Cisplatin nanoparticles were produced by miniemulsion polymerization technique and their properties were evaluated. Drug release assay was performed to characterize the nanoparticles' properties. Here, we examined the effects of cisplatin nanoparticles and free form of cisplatin on A172 cancer cell line. MTT assay was performed for different concentrations of the drug. To measure the apoptosis rate in A172 cell line in the presence of cisplatin nanoparticles or its free from, Annexin V staining method was used. Results: Our results indicated that loading type of cisplatin was physical loading and only 4.7% of cisplatin was released after 68 h. Furthermore, MTT assay showed that cisplatin nanoparticles in all concentrations had more cytotoxic effects on the cells comparing with the free form of cisplatin and control groups. We also showed that cisplatin nanoparticles could increase apoptosis in cancer cells more than the drug in the free form by using flow cytometry technique. Conclusion: Overall, these findings proved that cisplatin loaded on poly (Butylcyanoacrylate) nanoparticles, was more efficient than the free form of cisplatin in treating A172 cancer cell line.

Thyroid dysfunction is associated with elevated cardiovascular risk factors and atherosclerosis. It could be suggested that, hyperthyroidism is related to a higher prevalence of arterial abnormalities. Therefore, evaluating the endothelial dysfunction (ED) related biomarkers seem to be an important issue. It is not clear whether endothelial cells are biologically responsive to thyroid hormones (THs) or how THs induces the production of endothelial cells (EC)-derived proinflammatory mediators. Hence, in this study the effects of thyroxine (T 4 ) on ED and inflammatory related mediators were evaluated. Human umbilical vein endothelial cells was used as endothelial cell model which was treated with concentrations of 50, 100, 200 nmol/L of T 4 in various exposure times. In the following, gene and protein expression levels of EC-related markers including intercellular adhesion molecule-1 (ICAM-1), vascular endothelial growth factor (VEGF), and E-selectin were determined using real time polymerase chain reaction (RT-PCR) and western blotting methods. Also, interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) protein levels as proinflammatory cytokines were determined by enzyme linked immunosorbent assay (ELISA) method. Gene and protein expression analysis revealed that T 4 treatments up regulated the levels of VEGF, ICAM-1, and E-selectin as ED markers. In addition, T 4 -treated cells had higher significant levels of IL-6 and TNF-α versus untreated cells in different incubation times. This study proposed the atherosclerotic effects of thyroid hormone. Based on our findings, T4 had strong effects on the gene and protein expression levels of pro-inflammatory, angiogenesis, and ED major mediators associated with atherosclerosis development.