Nrf2 mutation at rs6721961 and its association with Nrf2 target genes in Breast Cancer Patients with No history of Chemotherapy

Objective: Owing to the putative role of Nrf2 in the activation of anti-oxidative genes, the present study aims at investigating the role of Nrf2 expression and its mutated form in breast cancer patients with no previous therapy. Patients and Methods: In the case-control study, breast cancer patients and controls from the Western Kurdish population of Iran were selected to evaluate the genotype of Nrf2 (rs6721961) by PCR- restriction fragment length polymorphism. In addition, the statistical association between Nrf2 (rs6721961) mutation and the expression of Nrf2, ER, PR, Her2, SOD, catalase, and other clinicopathological characteristics were analyzed. Results: The mean age of patients and controls were 43.55±1.89 and 46.44±2.16, respectively. In the control group, Nrf2 rs6721961 mutation deviated from Hardy-Weinberg Equation (HWE) with a p-value of 0.035 while in the patients’ group, SNP exact test for HWE showed a satisfied association with HWE (p=0.7). Besides, there was no significant relation between Nrf2 expression and catalase activity (p= 0.28) while SOD activity had a meaningful association with Nrf2 expression (p=0.02). There was no meaningful association of SNP with the expression levels of Her2 (p=0.30), ER (p=0.60) and PR (p=0.63). Besides, SNPSTAT showed that the expressions of Her2, ER and PR were in agreement with HWE. Conclusions: The results indicated that Nrf2 mutation is an imperative effector in the risk of breast cancer. Besides, the interplay of Nrf2 with other main biomarkers of oxidative stress seems to pave the way towards novel and convenient treatment options

In vitro and in vivo antidiabetic activity of Tamarix stricta Boiss.: Role of autophagy

Ethnopharmacological relevance: Type 2 diabetes mellitus (DM) is a complicated metabolic disorder with no definite treatment. Different species of the genus Tamarix (tamarisk) are used by local people to treat DM. Tamarix stricta Boiss. is an endemic species to Iran with several traditional therapeutic uses in Persian Medicine. This study aimed to assess the antidiabetic activity of T. stricta. Materials and methods: Hydroethanolic extract of the plant was prepared and analyzed by High-performance liquid chromatography (HPLC). The protective effect of the extract was evaluated in streptozotocin (STZ)-induced toxicity and markers of autophagy in pancreatic RIN-5F cells. The effect of intragastric 10 or 20 mg/kg of the extract was compared with negative control (water) or positive control (metformin) treatment during four weeks of administration in high-fat diet + STZ-induced DM in Balb/c mice. Results: Results showed the presence of 8.436 mg of gallic acid in each gram of the extract. A significant cytoprotective effect was observed by T. stricta in STZ-induced toxicity in RIN-5F cells, partially due to the modulation of autophagy. Also, animals treated with the extract showed a significant improvement in glycemic and lipid profiles, liver function, and histopathologic features of pancreas and liver compared with the negative control. Conclusion: T. stricta demonstrated beneficial effects in animal model of DM; though, further studies are recommended to confirm the clinical use of this plant in DM. © 2020 Elsevier B.V