Publications (2)9.56 Total impact
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Article: Thymosin beta 4 ameliorates hyperglycemia and improves insulin resistance of KK Cg-Ay/J mouse.
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ABSTRACT: To evaluate the efficacy of thymosin beta 4 (Tβ(4)) on hyperglycemia and insulin sensitivity in a mouse model of type 2 diabetes mellitus (T2DM). KK mice were divided into the following groups: KK control group, with saline treatment; KK Tβ(4) group, with daily Tβ(4) 100ng/10g body weight intraperitoneal injection for 12 weeks. Non-diabetic C57BL mice were used as normal control. OGTT, plasma insulin, HbA1c, serum adiponectin, Tβ(4), cholesterol, and triglyceride were measured before and after Tβ(4) treatment. The phosphorylated AKT and total AKT protein levels of skeletal muscle from all groups were determined. After Tβ(4) treatment, repeat OGTT showed a significant decrease in glucose profiles in the KK Tβ(4) group compared with the KK control group. The KK-Tβ(4) group had reduced mean HbA1c and triglyceride levels, and increased adiponectin compared with KK control group. C57BL mice showed normal glucose homeostasis. The phosphorylated AKT levels of skeletal muscle were significantly increased in KK Tβ(4) group compared with KK control group after glucose stimulation. C57BL mice showed no changes in phosphorylated AKT levels after Tβ(4) treatment. Tβ(4) improved glucose intolerance and ameliorated insulin resistance in KK mouse. Tβ(4) may be a potential alternative insulin sensitizer for treatment of T2DM.Diabetes research and clinical practice 01/2012; 96(1):53-9. · 2.16 Impact Factor -
Article: Nanoparticle based delivery of hypoxia-regulated VEGF transgene system combined with myoblast engraftment for myocardial repair.
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ABSTRACT: A regulated promoter system to control gene expression is desirable for safe and efficacious over-expression of therapeutic transgene. Combined with skeletal myoblast (SkMs), we report the efficacy of hypoxia-regulated VEGF gene delivery for myocardial repair during acute myocardial infarction (AMI). A hypoxia-regulated VEGF plasmid (pHRE-VEGF) was developed. After optimization, ∼30% SkMs were transfected using polyethyleneimine (PEI) nanoparticles. The peak VEGF expression was higher in pHRE-VEGF transfected SkMs ((VEGF)SkMs) under hypoxia (151.34 ± 8.59 ng/ml) than that with normoxia (16.92 ± 2.74 ng/ml). The efficacy of hypoxia-regulated gene expression system was assessed in a rabbit model of AMI. The animals were grouped to receive basal M199 without cells (group-1) or containing non-transfected SkMs (group-2) or (VEGF)SkMs (group-3). In group-4, (VEGF)SkMs were injected into normal heart to serve as normoxia control. Improved SkM survival was observed in group-3 and -4 (p < 0.05 vs group-2) at day-3 and 7 after transplantation. Blood vessel density was 20.1 ± 1.3 in group-3 which was significantly higher than any other groups (p < 0.05) at 2 weeks after treatment. Improved blood flow (ml/min/g) in the left ventricle (LV) anterior wall was observed in group-3 (1.28 ± 0.09, p < 0.05) as compared with group-1 (0.76 ± 0.05) and group-2 (0.96 ± 0.06), and similar to group-4 (1.26 ± 0.05). LV ejection fraction was best preserved in group-3 (58.4 ± 1.75%) which was insignificantly different from group-4 (61.1 ± 1.8%), and group-2 (52.8 ± 1.4%), but significantly improved compared with group-1 (44.7 ± 2.2%, p < 0.05). The study demonstrates that nanoparticle based delivery of hypoxia-regulated VEGF transgene combined with SkMs during AMI effectively preserves LV regional blood flow and contractile function of the heart.Biomaterials 03/2011; 32(9):2424-31. · 7.40 Impact Factor
