Hepatic stellate cells activation (HSCs) plays a crucial role in the pathogenesis of liver fibrosis. Specific microRNAs have been suggested to affect the activation of HSCs via various signalling pathways including TGF-β/smads and Wnt/β-catenin pathways. Dasatinib is a multitarget inhibitor of many tyrosine kinases has recently studied for its anti-fibrotic effects in a variety of fibrous diseases. This study investigated the role of modulation of miRNA-378 and miRNA-17 in the pathogenesis of liver fibrosis through altering Wnt/β-catenin and TGF-β/smads pathways and evaluated the beneficial effect of the tyrosine kinase inhibitor, dasatinib, in thioacetamide-induced liver fibrosis model in mice. Treatment with dasatinib down-regulated miRNA-17 expression, leading to the restoration of WiF-1 and smad-7 which cause the inhibition of both Wnt/β-catenin and TGF-β/smads signalling. In addition, it upregulated miRNA-378 leading to the decrease of Wnt-10 which contributes to the suppression of activated HSCs. Graphical Abstract

Early-stage detection of BC is a critical factor for effective treatment of the disease and can increase the survival rate of BC patients. Long non-coding RNAs can act as miRNA decoys by sequestering miRNAs, thus acting as competing endogenous RNAs and leading to re-expression of miRNA target genes. Maternally expressed 3 (MEG3) is LncRNA and it was reported to be tumor suppressor in breast cancer. The study aims to investigate the effect of MEG3 SNP (rs7158663 G/A) and its association with breast cancer risk in the Egyptian population. In addition, demonstrate the consequence of the MEG3 polymorphism on the expression levels of MEG3, miR-182, and miRNA-29. MEG3 rs7158663 G/A was genotyped and serum MEG3, miRNA-182, and miRNA-29 were measured in 180 breast cancer, 120 FA, and 150 controls by the qPCR. Frequencies of MEG3 rs7158663 GA/AA genotype and A allele were significantly higher in BC patients compared to the controls results showed that serum MEG3 levels were significantly lower, according to the presence of the A allele in different study groups while the expression of miR-182 and miRNA 29 were significantly elevated. MEG3, miR-182, and miRNA-29 are key genes involved in the development of BC, are considered as a novel potential non-invasive diagnostic biomarker for BC.

MicroRNAs (miRNAs) have critical roles in colorectal cancer (CRC) tumorigenesis and development. It has been reported that Eph receptor A7 (EphA7) was a potential target of miR-944 which is transcriptionally activated in cancer. The aim of this study was to explore the expression profile of miR-944 and its target gene EPHA7 in the serum of Egyptian CRC patients. 150 CRC patients, 50 adenomatous polyps (AP) patients, and 100 healthy controls were included. Serum miR-944 was downregulated (0.304 ± 0.0512) while serum EPHA7 was upregulated (3.163 ± 0.610) in CRC and AP patients versus controls and discriminated aganst these groups by Receiver operating characteristic curve (ROC) analysis. miR-944 presented the highest diagnostic accuracy for CRC patients from control (AUC = 0.90). Moreover obvious prognostic power in distinguishing AP from CRC (AUC = 0.87). In conclusion, miR-944 and EPHA7 are potential genetic markers of CRC predisposition and novel potential non-invasive diagnostic biomarkers for CRC.

Globally, myocardial infarction (MI) is one of the main causes of death. This study aims to investigate the role of miR-217 in the pathogenesis through targeting MAPK and PI3K/AKT signaling pathways in experimental model of myocardial infarction and studying the possible cardioprotective role of dihydromyricetin (DHM) through modulation of this pathway. Dihydromyricetin was injected (100 mg/kg; p.o.) in isoprenaline induced myocardial infarction rat model for 14 days. Rats were anaesthetized and blood samples were taken for serum separation, estimation of creatine kinase-MB (CK-MB), and troponin-I levels after 24 h had passed since the last isoprenaline injection. In addition, the hearts were also used for the other biochemical studies and the histological evaluation. DHM resulted in a significant suppression of the elevated levels miR-217 and MAPK compared to the MI control group and restored the normal level of serum CK-MB. Furthermore, DHM successfully restored the oxidative balance and halted the pro-inflammatory mediators in the cardiac tissue. Accordingly, our experiment emphasizes the anti-ischemic property that has been demonstrated through modulation of expression level of miR-217 and consequent deactivation of MAPK and PI3K/AKT signaling pathways, and this was assured by halting downstream pro-inflammatory markers.