Ectopic Overexpression of PPARγ2 in the Heart Determines Differences in Hypertrophic Cardiomyopathy After Treatment With Different Thiazolidinediones in a Mouse Model of Diabetes.

The clinical controversy of rosiglitazone as a hypoglycemic agent is potentially associated with heart failure, mainly due to its potent activation of peroxisome proliferator-activated receptor γ (PPARγ). PPARγ partial agonists showed superior pharmacological profiles to rosiglitazone. This study compared differences in cardiac morphology and function of the PPARγ partial agonist CMHX008 with rosiglitazone. High-fat diet (HFD) induced obese mice, ob/ob mice and cardiomyocytes overexpressing PPARγ2 were treated with CMHX008 or rosiglitazone. Heart function, myocardial morphology, and hypertrophy-related gene expression were examined. Clinical information from patients with type 2 diabetes mellitus (T2DM) who had taken rosiglitazone and undergone Doppler echocardiography was collected. HFD and ob/ob mice significantly developed cardiac contractile dysfunction, with upregulated PPARγ2 protein levels in heart tissues. Cardiomyocytes of HFD and ob/ob mice were disorderly arranged, the cell areas expanded, and collagen accumulated. In vitro cardiomyocytes overexpressing PPARγ2 displayed obvious structural abnormalities and high mRNA levels of ANP and BNP, critical cardiac hypertrophy-related genes. HFD-fed mice treated with rosiglitazone or CMHX008 had significantly improved cardiac function, but rosiglitazone induced higher expression of ANP and ßMHC and hypertrophic cardiomyopathy, while CMHX008 did not. Patients with T2DM taking rosiglitazone exhibited increased thickness of the posterior wall and the ventricular septum, suggesting cardiac hypertrophy. Our findings show that diabetic cardiomyopathy was associated with ectopic overexpression of PPARγ2. The full agonist rosiglitazone prevents cardiac dysfunction at the expense of compensatory hypertrophy, while the partial agonist CMHX008 shared a comparable protective effect without altering the structure of cardiomyocytes.

Neonatal overfeeding in mice aggravates the development of methionine and choline-deficient diet-induced steatohepatitis in adulthood.

Overfeeding in early life is associated with obesity and insulin resistance in adulthood. In the present study, a well-characterized mouse model was used to investigate whether neonatal overfeeding increases susceptibility to the development of non-alcoholic steatohepatitis (NASH) following feeding with a methionine and choline- deficient (MCD) diet. Neonatal overfeeding was induced by adjusting litters to 3 pups per dam (small litter size, SL) in contrast to 10 pups per dam as control (normal litter size, NL). At 11 weeks of age, mice were fed with standard (S) or a methionine and choline-deficient (MCD) diet for 4 weeks. Glucose tolerance tests, tissue staining with haematoxylin and eosin, oil-red O and immunohistochemistry for F4/80, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were performed. Compared with NL mice, SL mice exhibited higher body weight gain from 2 weeks of age throughout adulthood, and more profound glucose intolerance as adults. Sterol regulatory element-binding protein 1c and fatty acid synthase mRNA expression levels in liver were upregulated in SL mice at 3 weeks of age. MCD diet induced typical NASH, especially in SL-MCD mice, evidenced by marked fat accumulation, macrovescular steatosis, ballooned hepatocytes, inflammatory cells infiltration and tumour necrosis factor-α mRNA upregulation in the liver, as well as increased alanine aminotransferase and aspartate aminotransferase levels in the serum. There were no significant differences in liver fibrosis in all groups. Overfeeding during early life exhibited effect with administration of MCD diet in inducing adverse effects on the metabolic function and in promoting the progression of NASH in mice, possibly mediated through dysregulated lipid metabolism in hepatocytes and aggravated hepatic inflammation.

Fabrication of new chitosan-based composite sponge containing silver nanoparticles and its antibacterial properties for wound dressing.

The purpose of this research was to investigate chitosan-based composite sponge containing silver nanoparticles (Ag NPs) for wound dressing application. The composite sponge was prepared by a freeze-drying technique, and then immersed in AgNO3 solution with different concentration and autoclaved at 15 psi, 121 degrees C for 15 min for the formation of Ag NPs. The composite sponge containing Ag NPs was characterized by UV-vis spectra, XRD and SEM. The characteristic peaks of Ag in the UV-vis spectra and the XRD pattern revealed the formation of Ag-NPs. The SEM image showed that the silver particles homogeneously distributed on the surface of the composite sponge with an average particle diameter of about 60-80 nm. The contents of silver determined by ICP Single-channel scanning spectrometer were 0.032, 0.096 and 0.166 weight percentage, respectively, when the composite sponge was correspondingly treated with AgNO3 at concentrations of 0.1, 0.25 and 0.5 mM. The results of enzymic degradation in vitro indicated that the Ag-NPs could obviously promote the degradation of the composite sponge. The bacteriostatic and bactericidal properties of the new sponge were preliminarily studied in vitro by using S. aureus E. coli and P. aeruginosa as test microorganisms. The test results demonstrated that the new Ag NPs-loaded chitosan-based composite sponge possessed not only bacteriostatic, but also bactericidal activity against these test bacteria.