11β-HSD1 inhibition ameliorates diabetes-induced cardiomyocyte hypertrophy and cardiac fibrosis through modulation of EGFR activity

11β-HSD1 has been recognized as a potential therapeutic target for type 2 diabetes. Recent studies have shown that hyperglycemia leads to activation of 11β-HSD1, increasing the intracellular glucocorticoid levels. Excess glucocorticoids may lead to the clinical manifestations of cardiac injury. Therefore, the aim of this study is to investigate whether 11β-HSD1 activation contributes to the development of diabetic cardiomyopathy. To investigate the role of 11β-HSD1, we administered a selective 11β-HSD1 inhibitor in type 1 and type 2 murine models of diabetes and in cultured cardiomyocytes. Our results show that diabetes increases cortisone levels in heart tissues. 11β-HSD1 inhibitor decreased cortisone levels and ameliorated all structural and functional features of diabetic cardiomyopathy including fibrosis and hypertrophy. We also show that high levels of glucose caused cardiomyocyte hypertrophy and increased matrix protein deposition in culture. Importantly, inhibition of 11β-HSD1 attenuated these changes. Moreover, we show that 11β-HSD1 activation mediates these changes through modulating EGFR phosphorylation and activity. Our findings demonstrate that 11β-HSD1 contributes to the development of diabetic cardiomyopathy through activation of glucocorticoid and EGFR signaling pathway. These results suggest that inhibition of 11β-HSD1 might be a therapeutic strategy for diabetic cardiomyopathy, which is independent of its effects on glucose homeostasis

Formation of Ordered Coronene Clusters in Template Utilizing the Structural Transformation of Hexaphenylbenzene Derivative Networks on Graphite Surface

In the present work, we report the fabrication of regular coronene (COR) clusters on surfaces in ambient conditions in the two-dimensional network formed by hexaphenylbenzene derivatives (HPB) via structural transformation. HPB could form a stable snowflake network structure on the highly oriented pyrolytic graphite surface at the air–solid interface. When COR molecules were introduced into the system, the HPB snowflake network could transform to honeycomb structures, and the COR heptamers were subsequently aggregated and entrapped into the cavity. Scanning tunneling microscopic was employed to monitor the assembly behavior of both HPB and HPB/COR at a submolecule scale level, and density functional theory calculations were utilized to reveal that the structural transformation and the entrapment are the energetically favorable. The pores formed from HPB might also give a clue to immobilizing some functional molecule clusters, like COR, to fabricate their ordered monolayer in ambient conditions, so as to obtain complex supramolecular surface structures

Supramolecular Self-Assembly of Hexaphenylbenzene Derivatives with Different Symmetry and Number of Carboxylic Acid at Liquid/Solid Interfaces

Functional molecules, especially with carboxyl groups are crucial in building supramolecular structures. It is great important to study the effect of the symmetry, number of carboxyl groups on the self-assembly behavior of corresponding molecules. A series of hexaphenylbenzene (HPB) derivatives (<b>HPB-1,3,5-3A</b>, <b>HPB-1,2,4-3A</b>, and <b>HPB-1,4-2A</b>) substituted with different number of carboxyl groups at different position have been synthesized and their self-assembled structures were investigated at both 1-phenyloctane/HOPG and heptanoic acid/HOPG interfaces by using scanning tunneling microscopy (STM) technique. The self-assembled mechanisms of these HPB-based compounds were further studied with the help of density functional theory (DFT) calculations. The results indicate that symmetry and number of carboxyl groups as well as solvent play a significant role on the tuning self-assemble process resulting in various structures