Effect of dapagliflozin against NAFLD and dyslipidemia in type 2 diabetic albino rats: possible underlying mechanisms.

OBJECTIVE: The aim was to investigate the effect of dapagliflozin on non-alcoholic fatty liver disease and dyslipidemia in type 2 diabetic rats by studying the histopathological structure of the liver and detecting possible underlying mechanisms for this impact by evaluating the potential anti-inflammatory action of dapagliflozin. MATERIALS AND METHODS: 100 albino rats were used in this work and divided into five equal groups: group I (Control group), group II (Control diabetic group), group III (was administered dapagliflozin, 0.75 mg/kg, p.o.), group IV (was administered dapagliflozin, 1.5 mg/kg, p.o.), and group V (was administered dapagliflozin, 3 mg/kg, p.o.). RESULTS: In our study, the total body weight, liver weight, liver index, blood glucose level, insulin level, insulin resistance, total cholesterol, triglycerides, liver enzymes, IL-1 ß, and MDA were significantly higher in the control diabetic group than the normal group. The dapagliflozin reduced all the above variables significantly in a dose-dependent manner compared to the control diabetic group (p-value = 0.001 for all). CONCLUSIONS: Dapagliflozin may be a promising novel treatment strategy for treating T2DM-related non-alcoholic fatty liver disease (NAFLD), and dyslipidemia where it possesses anti-oxidative, anti-inflammatory and anti-dyslipidemic effects.

Identification of germline susceptibility loci in ETV6-RUNX1-rearranged childhood acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is a malignant disease of the white blood cells. The etiology of ALL is believed to be multifactorial and likely to involve an interplay of environmental and genetic variables. We performed a genome-wide association study of 355 750 single-nucleotide polymorphisms (SNPs) in 474 controls and 419 childhood ALL cases characterized by a t(12;21)(p13;q22) - the most common chromosomal translocation observed in childhood ALL - which leads to an ETV6-RUNX1 gene fusion. The eight most strongly associated SNPs were followed-up in 951 ETV6-RUNX1-positive cases and 3061 controls from Germany/Austria and Italy, respectively. We identified a novel, genome-wide significant risk locus at 3q28 (TP63, rs17505102, P(CMH)=8.94 × 10(-9), OR=0.65). The separate analysis of the combined German/Austrian sample only, revealed additional genome-wide significant associations at 11q11 (OR8U8, rs1945213, P=9.14 × 10(-11), OR=0.69) and 8p21.3 (near INTS10, rs920590, P=6.12 × 10(-9), OR=1.36). These associations and another association at 11p11.2 (PTPRJ, rs3942852, P=4.95 × 10(-7), OR=0.72) remained significant in the German/Austrian replication panel after correction for multiple testing. Our findings demonstrate that germline genetic variation can specifically contribute to the risk of ETV6-RUNX1-positive childhood ALL. The identification of TP63 and PTPRJ as susceptibility genes emphasize the role of the TP53 gene family and the importance of proteins regulating cellular processes in connection with tumorigenesis.