Silver nanoparticles (SNPs) have been widely used because of their antimicrobial activities in many cosmetics and other medical purposes. Nanoparticles could accumulated in the organs, and they may have toxic effect in persistence. Thus, the concerns have been raised on the potential risk of using AgNPs in medical applications. The nanosilver is more toxic than bulk silver. In this study we compared the nanotoxicties of two different concentrations of chitosan based hybrid silver nanoparticles with AgNO3 as a source of silver ions on albino rats. Seventy adult male albino rats with average body weight 200-250g were used in the investigation of this study. Rats were randomly divided into seven experimental groups; each contains 10 rats, the 1st and 2nd groups are kept as control The 3rd group orally administered (chitosan), The 4thand 5th groups administrated AgNO3 in 2 doses while the 6th and 7th groups administrated two different doses of chitosan based hybrid SNPs. We chosed the oral administration as it is the main route of exposure to SNPs from different products such as plastic food pins, toys, etc. The SNPs were administrated in doses of 50 and 100 mg\kg bw daily orally for 5 days. After 2 days from last administration, rats were sacrificed; blood and tissues samples were collected. The whole blood was used for hematological tests (erythrogram and leukogram). Liver enzymes (ALT, AST) and protein profile were tested in serum samples. Also, urea and creatinine were tested to evaluate kidney functions. While heart functions were tested from cTnI, CK-MB and LDH levels in serum samples. Histopathological examination of liver, kidney and heart were applied. Finally, tissue homogenates were tested for GSH and MDA levels to evaluate oxidative stress. The results of the study showed that the toxic effect and oxidative stress produced by SNPs were more than AgNO3 and occurred in a dose dependent manner.

Several subsets of regulatory CD4+ T cells (CD4+ Tregs) have been described in peripheral blood and tumor microenvironment and blood of breast cancer (BC) patients and may play a key role in the progression of BC. High-risk human papilloma virus (HPV) have a causal role in a significant proportion of cervical, and head, and neck tumors and may play an important role in evoking neoplasia in BC. In this study we assessed the prevalence of CD4+Tregs (CD4+CD25+ FOXP3+ cells) and CD3+ CD8+ T cells by flow cytometry in peripheral blood from a total of 55 Egyptian women, including 20 treatment-naïve BC, 15 with breast benign lesions (BBL) and 20 healthy volunteers (HV). High-risk HPV genotype type 16, 18, and 31 was investigated in breast tissue from all BC and BBL patients using Real-Time PCR. HPV was detected in 4 BC, but in none of BBL patients. The frequency of CD4+ Tregs was significantly higher in BC compared to BBL and HV, (p < 0.001). In addition, we observed a significantly higher frequency of CD3+ CD8+ T cells in peripheral blood of patients with late stage III compared to early stage I and II BC (p = 0.011). However, there was no significant association between the ratio of CD8+ T cell to CD4+ Tregs frequencies and the expression of Estrogen Receptor (ER), Progesterone Receptor (PR), and Human Epidermal Growth Factor Receptor 2 (HER2). In conclusion, CD4+ Tregs may contribute to 3 progression BC in Egyptian women with HPV infection. The potential role CD4+ Tregs as a prognostic or predictive parameter should be analyzed in a larger longitudinal study with sufficient follow-up time.

Background: Sulphonylureas are the oldest and commonly used to treat diabetic patients, but its efficacy declines by time. It was reported that quinazoline nucleus exhibits a potent hypoglycemic effect in diabetic animal models. Objective: The current study aimed to synthesize new quinazoline-sulfonylurea conjugates and evaluate their hypoglycemic effects in alloxan-induced diabetic rats. Method: The conjugates were synthesized by bioisosteric replacement of 5-chloro-2-methoxybenzamide moiety in glibenclamide or 1,3-dioxo-3,4-dihydroisoquinoline moiety in gliquidone with 6,7-dimethoxy-4-oxoquinazoline moiety (compounds 4a-4d, 9b-9c and 10b-10d). Diabetes was induced in rats by a single i.p. administration of alloxan, followed by treatment with the synthesized conjugates (5mg/kg Body weight). Results: All conjugates showed hypoglycemic effects with different efficacy indicated by the reduction in blood glucose and elevation of insulin levels. Moreover, these conjugates up-regulated the expression of pancreatic glucose transporter 2, muscle glucose transporter 4, and insulin receptor substrate-1 genes, compared to the diabetic group. A normal pancreatic tissue pattern was noticed in diabetic rats treated with compounds 9b, 9c, and 10c. Conclusion: Conjugation of sulfonylurea with quinazoline (especially 9b, 9c, 10c) possessed a significant hypoglycemic effect through improving blood insulin level and insulin action and consequently increased the glucose uptake by the skeletal muscles.