Micro ribonucleic acid-363 regulates the phosphatidylinositol 3-kinase/threonine protein kinase axis by targeting NOTCH1 and forkhead box C2, leading to hepatic glucose and lipids metabolism disorder in type 2 diabetes mellitus.

AIMS/INTRODUCTION: Glucose metabolic disorder is the main cause for type 2 diabetes progression. Exploring the molecular mechanisms of metabolic disorder are crucial for type 2 diabetes treatment. MATERIALS AND METHODS: Micro ribonucleic acid (miR)-363, NOTCH1 and forkhead box C2 (FOXC2) expressions in high glucose (HG)-treated HepG2 cells and the livers of type 2 diabetes mellitus rats were assessed using quantitative polymerase chain reaction. Protein levels of NOTCH1, FOXC2 and phosphatidylinositol 3-kinase (PI3K)/serine/threonine protein kinase (Akt)-related proteins were evaluated using western blot. Lipid accumulation was determined using Oil Red O staining. Then glucose consumption, blood glucose level and glycogen content were detected using kits. Finally, dual luciferase reporter assay was used to verify the binding relationship between miR-363 and NOTCH1, and the binding relationship between miR-363 and FOXC2. RESULTS: MiR-363 was significantly upregulated in the livers of diabetic rats and HG-induced HepG2 cells, whereas NOTCH1 and FOXC2 were downregulated. In HG-induced HepG2 cells, miR-363 inhibitor markedly increased glucose consumption and uptake, and reduced accumulation of lipid droplets. Then NOTCH1 and FOXC2 were identified as downstream targets of miR-363. NOTCH1 overexpression or FOXC2 overexpression could ameliorate glucose and lipids metabolism disorder in type 2 diabetes model cells. In addition, we found that FOXC2 inhibition abolished the effect of NOTCH1 overexpression on HG-induced HepG2 cells. Finally, we proved that the PI3K/Akt pathway was the downstream pathway of FOXC2. CONCLUSION: MiR-363 was considered as a key regulator of glucose and lipids metabolism in type 2 diabetes mellitus, which regulated PI3K/Akt axis by targeting NOTCH1 and FOXC2, thus leading to hepatic glucose and lipids metabolism disorder in type 2 diabetes.

Improvement of cardiac function by recombinant adenovirus Ad-hBNP in rats with chronic heart failure / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the therapeutic effect of hBNP on rats with chronic heart failure (CHF).</p><p><b>METHODS</b>Thirty CHF rats defined by echocardiography at 12 weeks post abdominal aortic constriction were randomly divided into Ad-hBNP group (2.5 × 10(10) VP/ml NS Ad-hBNP 1 ml/week × 4, n = 14), Ad-Track group (n = 8), placebo group (NS, n = 8), 10 sham-operated rats served as control group. After 4 weeks treatment, cardiac function was evaluated by echocardiography and hemodynamic measurements. Heart weight (HW) and HW/body weight (BW) ratio were determined.</p><p><b>RESULTS</b>IVS, LVPW, LVEDD and LVESD were significantly reduced in the Ad-hBNP group [(2.34 ± 0.29) mm, (2.28 ± 0.18) mm, (6.50 ± 0.42) mm, (3.54 ± 0.59) mm] than those in the Ad-Track group [(2.71 ± 0.35) mm, (3.02 ± 0.85) mm, (7.71 ± 0.83) mm, (4.72 ± 0.80) mm] and in the NS group [(2.78 ± 0.23) mm, (2.83 ± 0.53) mm, (7.34 ± 0.97) mm, (4.55 ± 0.77) mm, all P < 0.05]. The LVEF and LVFS of the Ad-hBNP group [(79.27 ± 7.01)%, (43.38 ± 6.73)%] were significantly higher than in the Ad-Track group [(70.85 ± 4.81)%, (35.72 ± 3.68)%] and in the NS group [(69.67 ± 6.90)%, (34.91 ± 5.10)%, all P < 0.01]. HR [(417.48 ± 32.57) beats/min, (446.85 ± 61.49) beats/min, P < 0.05; (440.83 ± 32.18) beats/min, P < 0.05], LVEDP [(-4.24 ± 4.00) mm Hg (1 mm Hg = 0.133 kPa); (21.99 ± 6.80) mm Hg, P < 0.01; (18.00 ± 12.25) mm Hg, P < 0.01] were significantly decreased and while LVSP [(131.79 ± 15.76) mm Hg; (112.99 ± 32.35) mm Hg, P < 0.05; (117.13 ± 15.26) mm Hg], +dP/dt(max) [(5037.20 ± 430.41) mm Hg/s; (4217.40 ± 1354.15) mm Hg/s, P < 0.05; (4310.50 ± 1293.97) mm Hg/s, P < 0.05] and -dP/dt(max) [(-4382.00 ± 1304.79) mm Hg/s; (-3725.00 ± 791.34) mm Hg/s, P < 0.05; (-3890.00 ± 1043.73) mm Hg/s, P < 0.05]were significantly increased in Ad-hBNP group than in Ad-Track group and NS group (all P < 0.05). HW and HW/BW were also decreased in Ad-hBNP group than in the Ad-Track group and the NS group.</p><p><b>CONCLUSION</b>Exogenous hBNP improved the cardiac function and attenuated remodeling in CHF rats.</p>