The brain starts to eat itself after chronic sleep deprivation

Sleep loss in mice sends the brain’s immune cells into overdrive. This might be helpful in the short term, but could increase the risk of dementia in the long run

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β-Cyclodextrin induces the differentiation of resident cardiac stem cells to cardiomyocytes through autophagy

Publication date: August 2017
Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1864, Issue 8
Author(s): Xingxing Shi, Wenjing Li, Honghong Liu, Deling Yin, Jing Zhao
Cardiac stem cells (CSCs) have emerged as promising cell candidates to regenerate damaged hearts, because of the potential in differentiating to cardiomyocytes. However, the differentiation is difficult to trigger without inducers. Here we reported that β-cyclodextrin (β-CD) increased the expression of cardiac transcription factors (Nkx2.5 and GATA4), structural proteins (cardiac Troponin T, cTnt), transcriptional enhancer (Mef2c) and induced GATA4 nucleus translocation in adult resident CSCs, thus β-CD could be used to enhance myogenic transition. As the differentiation process was accompanied by autophagy, we constructed the Atg5 knockdown cell line by using the Atg5 siRNA lentivirus, and the myogenic conversion was blocked in Atg5 knockdown cells, which suggested that β-CD induces the cardiomyocytes transition of resident CSCs through autophagy. Furthermore, we found that JNK/STAT3 and GSK3β/β-catenin was the downstream pathways of β-CD-induced autophagy and differentiation using the inhibitors. Moreover, β-CD performed its functions through improving intracellular cholesterol levels and affecting cholesterol efflux. Collectively, our results reveal that β-CD as a novel tool to induce myogenic transition of CSCs, which could mobilize the resident CSCs or used together with CSCs to enhance the therapy effects of CSCs on damaged hearts. In addition, the clarified molecular mechanisms supported the new targets for inducing cardiomyocyte differentiation.

Graphical abstract

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Comparison of early outcomes of surgical ablation procedures for atrial fibrillation concomitant to non-mitral cardiac surgery: a Japan Adult Cardiovascular Surgery Database study

Abstract

Objective

Although the benefit of surgical ablation for atrial fibrillation (AF) performed concomitant to mitral valve surgery is established, whether that performed concomitant to non-mitral cardiac surgery is beneficial remains unclear. In non-mitral, non-left-atriotomy cardiac surgery, the optimal surgical approach for AF remains to be established. Therefore, using the Japan Adult Cardiovascular Surgery Database (JACVSD), we compared 2 surgical ablation procedures [the maze procedure and pulmonary vein isolation (PVI)] performed concomitant to non-mitral cardiac surgery.

Methods

Of 3402 JACVSD patients who had undergone elective non-mitral cardiac surgery by 2012, 1797 (53%) had undergone concomitant PVI, and 1339 (39%) had undergone the maze procedure. To compensate for patient heterogeneity, we conducted a propensity score-matched analysis of 1952 patients who had undergone PVI or the maze procedure (976 patients each).

Results

Operative procedures took significantly longer in the Maze Group. Although postoperative AF occurred in 34.3% of the PVI Group patients and in 31.9% of the Maze Group patients (p = 0.371), the incidence of first-time pacemaker implantation was significantly lower in the PVI Group (1.9 vs. 4.1%, respectively; p = 0.005). There was no significant difference in other morbidities or in operative mortality. Postoperative hospital and ICU stays tended to be longer in the Maze Group.

Conclusions

Our data indicate that surgical ablation of AF concomitant to non-mitral cardiac surgery is beneficial. Furthermore, PVI and the maze procedure appear to be of equal benefit in this context, except that the maze procedure may more frequently result in the need for pacemaker implantation.

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MEK Inhibitors in the Treatment of Metastatic Melanoma and Solid Tumors

Abstract

The mitogen-activated protein kinase (MAPK) cascade is an intracellular signaling pathway involved in the regulation of cellular proliferation and the survival of tumor cells. Several different mutations, involving BRAF or NRAS, exert an oncogenic effect by activating the MAPK pathway, resulting in an increase in cellular proliferation. These mutations have become targets for new therapeutic strategies in melanoma and other cancers. Selective MEK inhibitors have the ability to inhibit growth and induce cell death in BRAF- and NRAS-mutant melanoma cell lines. MEK inhibitor therapy in combination with a BRAF inhibitor is more effective and less toxic than treatment with a BRAF inhibitor alone, and has become the standard of care for patients with BRAF-mutated melanoma. Trametinib was the first MEK inhibitor approved for the treatment of BRAF-mutated metastatic melanoma not previously treated with BRAF inhibitors, and is also approved in combination with the BRAF inhibitor dabrafenib. Furthermore, cobimetinib is another MEK inhibitor approved for the treatment of BRAF-mutated metastatic melanoma in combination with a BRAF inhibitor, vemurafenib. The MEK inhibitor binimetinib in combination with the BRAF inhibitor encorafenib is in clinical development. The addition of an anti-PD-1/PD-L1 agent, such as pembrolizumab, durvalumab or atezolizumab, to combined BRAF and MEK inhibition has shown considerable promise, with several trials ongoing in metastatic melanoma. Binimetinib has also shown efficacy in NRAS-mutated melanoma patients. Future possibilities for MEK inhibitors in advanced melanoma, as well as other solid tumors, include their use in combination with other targeted therapies (e.g. anti-CDK4/6 inhibitors) and/or various immune-modulating antibodies.

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Microbicidal activity of N-chlorotaurine in combination with hydrogen peroxide

N-chlorotaurine (NCT) and hydrogen peroxide are powerful endogenous antiseptics. In vivo, the reaction between hydrogen peroxide and metal ions leads to the formation of free hydroxyl rad...

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Thermostabilization of the uronate dehydrogenase from Agrobacterium tumefaciens by semi-rational design

Aldaric acids represent biobased ‘top value-added chemicals’ that have the potential to substitute petroleum-derived chemicals. Until today they are mostly produced from corresponding aldoses using strong chem...

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Identification of diacetonamine from soybean curd residue as a sporulation-inducing factor toward Bacillus spp.

Under bioassay-guided investigation, a sporulation-inducing factor (SIF) toward Bacillus spp. was searched for in methanol (MeOH) extracts of soybean curd residues, and diacetonamine (1) was identified as the act...

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