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Probucol prevents atrial remodeling and suppresses AF development in alloxan-induced diabetic rabbits. Its inhibitory effects on oxidative stress, NF-κB, TGF-β, and TNF-α overexpression may contribute to its antiremodeling effects.

Objective: The purpose of this study was to investigate the effects of hyperglycemia on atrial interstitial fibrosis, ionic remodeling and vulnerability to atrial fibrillation (AF) in alloxan-induced diabetic rabbits. Methods: Sixty Japanese rabbits were randomly assigned to alloxan-induced diabetic group (n=30) and control group (n=30). Ten rabbits in each group were respectively used to electrophysiological and histological study, patch-clamp study and Western blotting analysis. Langendorff perfusion was used to record inter-atrial conduction time (IACT), atrial effective refractory period (AERP) and dispersion (AERPD) and vulnerability to AF. Histological study was measured by Sirius-red stain. Patch-clamp technique was used to measure action potential duration (APD) and atrial ionic currents (INa and ICaL). Western blotting was applied to assess atrial protein expression of transforming growth factor beta 1 (TGFβ1). Results: Compared with control group, electrophysiological studies showed IACT was prolonged (37.91±6.81 vs. 27.43±1.63ms, p<0.01), AERPD was increased (30.37±8.33 vs. 14.70±5.16ms, p<0.01) in diabetic group. Inducibility of AF in diabetic group was significantly higher than in controls (8/10 vs. 1/10 of animals, p<0.01). Collagen volume fraction was increased (6.20±0.64% vs. 2.15±0.21%, p<0.01) in diabetic group. Patch-clamp studies demonstrated APD90 and APD50 were prolonged in diabetic rabbits (p<0.05 vs. control). The densities of INa were reduced and the densities of ICaL were increased (p<0.01 vs. control). Protein expression of TGFβ1 was increased in diabetic group (p<0.001 vs. control). Conclusion: Our study suggests that hyperglycemia contributes to atrial interstitial fibrosis, ionic remodeling and vulnerability to AF in diabetic rabbits, resulting in atrial structural remodeling and electrical remodeling for the development and perpetuation of AF. (Anadolu Kardiyol Derg 2012; 12: 543-50)

Graphene consists of two-dimensional sp2-bonded carbon sheets, a single or a few layers thick, which has attracted considerable interest in recent years due to its good conductivity and biocompatibility. Three-dimensional graphene foam (3DG) has been demonstrated to be a robust scaffold for culturing neural stem cells (NSCs) in vitro that not only supports NSCs growth, but also maintains cells in a more active proliferative state than 2D graphene films and ordinary glass. In addition, 3DG can enhance NSCs differentiation into astrocytes and especially neurons. However, the underlying mechanisms behind 3DG's effects are still poorly understood. Metabolism is the fundamental characteristic of life and provides substances for building and powering the cell. Metabolic activity is tightly tied with the proliferation, differentiation, and self-renewal of stem cells. This study focused on the metabolic reconfiguration of stem cells induced by culturing on 3DG. This study established the correlation between metabolic reconfiguration metabolomics with NSCs cell proliferation rate on different scaffold. Several metabolic processes have been uncovered in association with the proliferation change of NSCs. Especially, culturing on 3DG triggered pathways that increased amino acid incorporation and enhanced glucose metabolism. These data suggested a potential association between graphene and pathways involved in Parkinson's disease. Our work provides a very useful starting point for further studies of NSC fate determination on 3DG.

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The effect of mesenchymal stem cell (MSCs)-based therapy on treating acute myocardial infarction (MI) is limited due to poor engraftment and limited regenerative potential. Here we engineered MSCs with integrin-linked kinase (ILK), a pleiotropic protein critically regulating cell survival, proliferation, differentiation, and angiogenesis. We firstly combined ferumoxytol with poly-L-lysine (PLL), and found this combination promisingly enabled MRI visualization of MSCs in vitro and in vivo with good safety. We provided visually direct evidence that intracoronary ILK-MSCs had substantially enhanced homing capacity to infarct myocardium in porcine following cardiac catheterization induced MI. Intracoronary transplantation of allogeneic ILK-MSCs, but not vector-MSCs, significantly enhanced global left ventricular ejection fraction (LVEF) by 7.8% compared with baseline, by 10.3% compared with vehicles, and inhibited myocardial remodeling compared with vehicles at 15-day follow-up. Compared with vector-MSCs, ILK-MSCs significantly improved regional LV contractile function, reduced scar size, fibrosis, cell apoptosis, and increased regional myocardial perfusion and cell proliferation. This preclinical study indicates that ILK-engineered MSCs might promote the clinical translation of MSC-based therapy in post-MI patients, and provides evidence that ferumoxytol labeling of cells combined with PLL is feasible in in vivo cell tracking.

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