Essential hypertension is a chronic medical condition affecting thousands of people worldwide. It is polygenic and multi-factorial disease resulting from the interaction between genetic and environmental factors. Essential hypertension is implicated in cerebrovascular, cardiovascular and renal diseases. MicroRNAs are considered endogenous, non-coding regulators of gene expression by targeting specific mRNAs for degradation and/ or translational repression. MicroRNAs participate in a variety of developmental processes as metabolism, cell proliferation, and apoptosis. Many studies have reported the possibility of using miRNAs as new biological markers for polygenic diseases as cancer, stem cell aging, coronary heart disease, and essential hypertension. The stability of these miRNAs as miRNA let-7e, miRNA 296-5p, miRNA 605, and miRNA 623 in biological fluids makes them amenable to detection and quantification. This review summarizes the mechanisms by which miRNAs can control normal cellular processes and gene expression and the association of some circulating miRNAs with the incidence of different diseases, particularly essential hypertension.

Background and Purpose: Metastasis in breast cancer is a leading cause of mortality among women in many countries. This study investigated the anti-cancer role of benzoimidazoquinazoline and benzimidazotriazin; two novel compounds that were designed, synthesized, structurally elucidated, and biologically evaluated as potent anti-angiogenic agents that act through inhibition of vascular endothelial growth factor receptor-2 (VEGFR2). A model of breast cancer was induced by inoculation of Ehrlich Ascites Carcinoma (EAC) cells. Experimental Approach: Seventy swiss albino mice were randomly divided into 7 groups, 10 animals each: (1) normal, (2) control EAC group, (3) cisplatin treated group, (4&5) benzoimidazoquinazoline treated (5mg/kg and 10mg/kg), (6&7) benzimidazotriazin treated (5mg/kg and 10 mg/kg). The expression of miRNA-122 was assessed in the tumor tissue by quantitative PCR, and the VEGF level was determined in serum by ELISA. VEGFR2 and cluster of differentiation (CD)34 were assessed by immunohistochemistry. Serum levels of ALT, AST, creatinine, and urea were measured. Key Results: Treatment with benzoimidazoquinazoline and benzimidazotriazin caused a decrease in tumor weight and a significant decrease in the serum levels of VEGF and the expression of VEGFR2 and CD34 in the tumor tissue.MiRNA-122 was significantly upregulated especially in the group treated by benzimidazotriazin (10mg/kg). Interestingly, the new compounds had less renal toxicity compared to cisplatin. Conclusion and Implication: The designed small molecules are promising anti-cancer candidates that act through inhibition of angiogenesis and can provide a new strategy for the advancement of chemotherapy through modulation of miRNA.

Despite the advanced treatment strategies, breast cancer remains the second cancer causing mortality across women worldwide. Notch signaling pathway has been found to be emerged in several cancers as well as in acquired and innate drug resistance. Therefore, understanding the role of Notch molecular mechanism could harbor beneficial impact to overcome chemoresistance and developing novel treatment strategies for cancer. Cisplatin (CIS) is an effective chemotherapeutic agent that is widely used against cancer but resistance is frequently occurs with limited therapeutic efficacy. One approach to overcome such unfavorable resistance is using complementary therapies with CIS. Thymoquinone (TQ) is a main compound in the essential oil of Nigella sativa. It has potent oncostatic activity by modulation of multiple regulatory pathways. Pentoxifylline (PTX) is a methylated xanthine derivative with remarkable anti-inflammatory and immunomodulatory actions. Combining TQ and PTX with CIS could be a promising strategy to suppress Notch signaling and overcome CIS resistance.