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Work 1-3 of 3

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Article

Ischaemic conditioning and targeting reperfusion injury: a 30 year voyage of discovery

by Derek J. Hausenloy; Jose A. Barrabes; Hans Erik Botker; Sean M. Davidson; Fabio Di Lisa; James Downey; Thomas Engstrom; Péter Ferdinandy; Hector A. Carbrera-Fuentes; Gerd Heusch; Borja Ibanez; Efstathios K. Iliodromitis; Javier Inserte; Robert Jennings; Neena Kalia; Rajesh Kharbanda; Sandrine Lecour; Michael Marber; Tetsuji Miura; Michel Ovize; Miguel A. Perez-Pinzon; Hans Michael Piper; Karin Przyklenk; Michael Rahbek Schmidt; Andrew Redington; Marisol Ruiz-Meana; Gemma Vilahur; Jakob Vinten-Johansen; Derek M. Yellon; David Garcia-Dorado

2016

Subjects
  • Health Sciences, Medicine and Surgery
  • Health Sciences, General
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Abstract:Close

To commemorate the auspicious occasion of the 30th anniversary of IPC, leading pioneers in the field of cardioprotection gathered in Barcelona in May 2016 to review and discuss the history of IPC, its evolution to IPost and RIC, myocardial reperfusion injury as a therapeutic target, and future targets and strategies for cardioprotection. This article provides an overview of the major topics discussed at this special meeting and underscores the huge importance and impact, the discovery of IPC has made in the field of cardiovascular research.

Article

Flow-Dependent Epigenetic DNA Methylation in Endothelial Gene Expression and Atherosclerosis

by Jessilyn Dunn; Salim Thabet; Hanjoong Jo

2015

Subjects
  • Biology, Genetics
  • Engineering, Biomedical
  • Health Sciences, General
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Abstract:Close

Epigenetic mechanisms that regulate endothelial cell gene expression are now emerging. DNA methylation is the most stable epigenetic mark that confers persisting changes in gene expression. Not only is DNA methylation important in rendering cell identity by regulating cell type-specific gene expression throughout differentiation, but it is becoming clear that DNA methylation also plays a key role in maintaining endothelial cell homeostasis and in vascular disease development. Disturbed blood flow causes atherosclerosis, whereas stable flow protects against it by differentially regulating gene expression in endothelial cells. Recently, we and others have shown that flow-dependent gene expression and atherosclerosis development are regulated by mechanisms dependent on DNA methyltransferases (1 and 3A). Disturbed blood flow upregulates DNA methyltransferase expression both in vitro and in vivo, which leads to genome-wide DNA methylation alterations and global gene expression changes in a DNA methyltransferase-dependent manner. These studies revealed several mechanosensitive genes, such as HoxA5, Klf3, and Klf4, whose promoters were hypermethylated by disturbed blood flow, but rescued by DNA methyltransferases inhibitors such as 5Aza-2-deoxycytidine. These findings provide new insight into the mechanism by which flow controls epigenomic DNA methylation patterns, which in turn alters endothelial gene expression, regulates vascular biology, and modulates atherosclerosis development.

Article

Edible ginger-derived nanoparticles: A novel therapeutic approach for the prevention and treatment of inflammatory bowel disease and colitis-associated cancer

by Mingzhan Zhang; Emilie Viennois; Meena Prasad; Yunchen Zhang; Lixin Wang; Zhan Zhang; Moon Kwon Han; Bo Xiao; Changlong Xu; Shanthi Srinivasan; Didier Merlin

2016

Subjects
  • Health Sciences, General
  • File Download
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Abstract:Close

There is a clinical need for new, more effective treatments for chronic and debilitating inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. In this study, we characterized a specific population of nanoparticles derived from edible ginger (GDNPs 2) and demonstrated their efficient colon targeting following oral administration. GDNPs 2 had an average size of ~230 nm and exhibited a negative zeta potential. These nanoparticles contained high levels of lipids, a few proteins, ~125 microRNAs (miRNAs), and large amounts of ginger bioactive constituents (6-gingerol and 6-shogaol). We also demonstrated that GDNPs 2 were mainly taken up by intestinal epithelial cells (IECs) and macrophages, and were nontoxic. Using different mouse colitis models, we showed that GDNPs 2 reduced acute colitis, enhanced intestinal repair, and prevented chronic colitis and colitis-associated cancer (CAC). 2D-DIGE/MS analyses further identified molecular target candidates of GDNPs 2 involved in these mouse models. Oral administration of GDNPs 2 increased the survival and proliferation of IECs and reduced the pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β), and increased the anti-inflammatory cytokines (IL-10 and IL-22) in colitis models, suggesting that GDNPs 2 has the potential to attenuate damaging factors while promoting the healing effect. In conclusion, GDNPs 2, nanoparticles derived from edible ginger, represent a novel, natural delivery mechanism for improving IBD prevention and treatment with an added benefit of overcoming limitations such as potential toxicity and limited production scale that are common with synthetic nanoparticles.
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