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Phosphodiesterase (PDE) 3B, a major isoform of PDE in adipocytes, mediates the antilipolytic action of insulin. PDE3B gene expression is generally reduced in adipocytes of either monogenic or polygenic rodent models of obese, insulin-resistance. An increased fat cell size, a common feature of obesity, could account for this reduction. Insulin receptor substrate-1 (IRS-1) (−/−) mice are lean with a reduced fat cell size and have insulin resistance due to a primary defect of insulin signaling. To determine whether the regulation of PDE3B gene expression is correlated with fat cell size, we examined this gene expression in adipose tissues of IRS-1 (−/−) mice. In IRS-1 (−/−) mice, PDE3B mRNA and protein levels were increased 1.24- and 1.35-fold those in C57BL/6J control mice, respectively. Independently, the fold induction of PDE activity by insulin (insulin-induced/basal) was 1.7-fold in control mice, but was reduced to 1.35-fold in IRS-1 (−/−) mice. Thus, PDE3B gene expression may be inversely correlated with a fat cell size, whereas insulin-induced PDE3B activation is mediated through IRS-1. [Copyright &y& Elsevier]

Ghrelin is a novel growth hormone-releasing peptide, which has been shown to exert beneficial effects on cardiac function and ventricular remodeling. The present study aimed to investigate the expression of ghrelin and the growth hormone (GH) secretagogue receptor 1a (GHSR-1a), and the association with cardiac remodeling in rats with myocardial infarction (MI). Twenty-four hours after ligation of the anterior descending artery (LAD), adult male Sprague–Dawley rats were randomized to 3 d, 7 d and 28 d group. Sham animals underwent thoracotomy and pericardiotomy, but not LAD ligation. Expression of both ghrelin and GHSR-1a was assessed by means of immunohistochemistry and real-time PCR. Plasma ghrelin levels were measured by ELISA kit. In addition, cardiac remodeling was assessed by echocardiographic and hemodynamic measurements. Plasma and cardiac expression of ghrelin decreased on days 3, 7 and 28 compared with the sham group (P < 0.05). In contrast the GHSR-1a mRNA levels increased during the same days (P < 0.05). Decreased positive immunoreaction for ghrelin and increased positive GHSR-1a were also observed in the infarcted heart. Interestingly, plasma ghrelin correlated negatively with left ventricular end-diastolic pressure (r = − 0.59, P = 0.002) and left ventricular end-diastolic dimension (r = − 0.73, P < 0.01). The ghrelin system may play an important role regulating cardiac remodeling after MI and present as a potential significant target for pharmacological modulation and treating cardiac remodeling. [ABSTRACT FROM AUTHOR]

Abstract: Kindlin-2, as a focal adhesion protein, has been found to regulate tumor progression. However, the mechanism underlying Kindlin-2 regulation of tumor progression is largely unknown. Here, we report that Kindlin-2 regulates breast cancer cell proliferation, apoptosis and chromosomal abnormalities in both gain and loss of function assays. Functionally, overexpression of Kindlin-2 promotes tumor formation in implanted xenograft while knockdown of Kindlin-2 inhibits tumor growth in mice. Mechanistically, an array-based comparative genomic hybridization and karyotype analyses indicate that ectopic expression of Kindlin-2 leads to genome instability in breast cancer cells. Our data suggest a novel mechanism that Kindlin-2 regulates breast cancer progression by inducing genome instability. [Copyright &y& Elsevier]

Abstract: Previous studies have shown that sinomenine possesses potent immunoregulatory properties. However, little is known about its exact mechanisms of action. Increasing recognition of the importance of renal tubular epithelial cells (TECs) in renal diseases raises the question whether sinomenine can regulate TEC activity. In this study, cultured human TECs were exposed to proinflammatory factors interferon-γ (IFN-γ) and tumor necrotic factor-α (TNF-α) in presence or absence of sinomenine for 72 h, followed by analysis of surface expression of costimulatory molecules. Flow cytometric analysis revealed that various costimulatory molecules were expressed on TECs and that they were significantly up-regulated by the simulation of IFN-γ and TNF-α. However, sinomenine especially down-regulated B7-H1 and B7-DC expression on TECs at both mRNA and protein levels. Moreover, the significant damping effect of sinomenine on B7-H1 and B7-DC signals could promote IL-2 and IFN-γ production by co-cultured CD4+ T cell. Our results indicated that sinomenine could regulate TECs activity via B7-H1 and B7-DC, in addition to previously reported its effects on some pro-inflammatory factors production by macrophages and peripheral blood mononuclear cells. [Copyright &y& Elsevier]