Punica granatum L. fruit aqueous extract suppresses reactive oxygen species-mediated p53/p65/miR-145 expressions followed by elevated levels of irs-1 in Alloxan-diabetic rats

Objective: reactive oxygen species [ROS] is an apoptosis inducer in pancreatic beta-cells that stimulates p53/p65 mediated microRNA [miR]-145 expression. Punica granatum L. [pomegranate] is an antioxidant fruit that attenuates ROS generation. This study examines the effects of pomegranate fruit aqueous extract [PGE] on the levels of ROS, p53, p65, miR-145, and its target insulin receptor substrate 1 [irs-1] mRNA in Alloxan-diabetic male Wistar rats

Materials and Methods: in this experimental study, diabetic rats received different doses of PGE. The effects of the PGE polyphenols were examined through a long-term PGE treatment period model, followed by an evaluation of the plasma and tissue contents of free fatty acids [FFAs], triglycerides [TG], and glycogen compared with diabetic controls [DC] and normal controls [NC]. We used real-time polymerase chain reaction [PCR] to investigate the modulation of p53, p65, miR-145, and irs-1 expression levels

Results: there was a noticeable reduction in fasting blood glucose [FBG] and ROS generation compared to DC. We observed marked decreases in p53, p65, miR-145 expression levels followed by an elevated level of irs-1, which contributed to improvement in insulin sensitivity

Conclusion: PGE administration downregulated miR-145 levels in Alloxan-diabetic Wistar rats by suppression of ROS-mediated p53 and p65 overexpression

Coexistence of KRAS and BRAF mutations in colorectal cancer: a case report supporting the concept of tumoral heterogeneity

The detection of KRAS and BRAF mutations is a crucial step for the correct therapeutic approach and predicting the epidermal growth factor receptor [EGFR]-targeted therapy resistance of colorectal carcinomas. The concomitant KRAS and BRAF mutations occur rarely in the colorectal cancers [CRCs] with the prevalence of less than 0.001% of the cases. In patients with KRAS-mutant tumors, BRAF mutations should not regularly be tested unless the patient is participating in a clinical trial enriching for the presence of KRAS or BRAF-mutated tumor. The current report demonstrates a case with advanced adenocarcinoma of the colon showing the coexistence of KRAS and BRAF mutations and may have profound clinical implications for disease progression and therapeutic responses