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Poliseno L.,CNR Institute of Clinical Physiology | Poliseno L.,CNR Institute of Neuroscience | Pandolfi P.P.,Beth Israel Deaconess Medical Center
Methods | Year: 2015

In multiple human cancer types, a close link exists between the expression levels of Phosphatase and Tensin Homolog deleted on chromosome 10 (PTEN) and its oncosuppressive activities. Therefore, an in depth understanding of the molecular mechanisms by which PTEN expression is modulated is crucial in order to achieve a comprehensive knowledge of its biological roles. In recent years, the competition between PTEN mRNA and other RNAs for shared microRNA molecules has emerged as one such mechanism and has brought into focus the coding-independent activities of PTEN and other mRNAs. In this review article, we examine the competing endogenous RNA (ceRNA) partners of PTEN that have been identified so far. We also discuss how PTEN-centered ceRNA networks can contribute to a deeper understanding of PTEN function and tumorigenesis. © 2015. Source

Del Ry S.,CNR Institute of Clinical Physiology
Peptides | Year: 2013

Natriuretic peptides are endogenous hormones released by the heart in response to myocardial stretch and overload. While atrial and brain natriuretic peptides (ANP, BNP) were immediately considered cardiac hormones and their role was well-characterized and defined in predicting risk in cardiovascular disease, evidence indicating the role of C-type natriuretic peptide (CNP) in cardiovascular regulation was slow to emerge until about 8 years ago. Since then, considerable literature on CNP and the cardiovascular system has been published; the aim of this review is to examine current literature relating to CNP and cardiovascular disease, in particular its role in heart failure (HF) and myocardial infarction (MI). This review retraces the fundamental steps in research that led understanding the role of CNP in HF and MI; from increased CNP mRNA expression and plasmatic concentrations in humans and in animal models, to detection of CNP expression in cardiomyocytes, to its evaluation in human leukocytes. The traditional view of CNP as an endothelial peptide has been surpassed by the results of many studies published in recent years, and while its physiological role is still under investigation, information is now available regarding its contribution to cardiovascular function. Taken together, these observations suggest that CNP and its specific receptor, NPR-B, can play a very important role in regulating cardiac hypertrophy and remodeling, indicating NPR-B as a new potential drug target for the treatment of cardiovascular disease. © 2013 Elsevier Inc. All rights reserved. Source

Iozzo P.,CNR Institute of Clinical Physiology
Nutrition, Metabolism and Cardiovascular Diseases | Year: 2010

There is convincing evidence that alterations in myocardial substrate use play an important role in the normal and diseased heart. In this review, insights gained by using quantitative molecular imaging by positron emission tomography and magnetic resonance spectroscopy in the study of human myocardial metabolism will be discussed, and attention will be paid to the effects of nutrition, gender, aging, obesity, diabetes, cardiac hypertrophy, ischemia, and heart failure. The heart is an omnivore organ, relying on metabolic flexibility, which is compromised by the occurrence of defects in coronary flow reserve, insulin-mediated glucose disposal, and metabolic-mechanical coupling. Obesity, diabetes, and ischemic cardiomyopathy appear as states of high uptake and oxidation of fatty acids, that compromise the ability to utilize glucose under stimulated conditions, and lead to misuse of energy and oxygen, disturbing mechanical efficiency. Idiopathic heart failure is a complex disease frequently coexisting with diabetes, insulin resistance and hypertension, in which the end stage of metabolic toxicity manifests as severe mitochondrial disturbance, inability to utilize fatty acids, and ATP depletion. The current literature provides evidence that the primary events in the metabolic cascade outlined may originate in extra-cardiac organs, since fatty acid, glucose levels, and insulin action are mostly controlled by adipose tissue, skeletal muscle and liver, and that a broader vision of organ cross-talk may further our understanding of the primary and the adaptive events involved in metabolic heart toxicity. © 2009 Elsevier B.V. All rights reserved. Source

Capobianco E.,University of Miami | Capobianco E.,CNR Institute of Clinical Physiology | Lio' P.,University of Cambridge
Trends in Molecular Medicine | Year: 2013

Comorbidity represents an extremely complex domain of research. An individual entity, the patient, is the center of gravity of a system characterized by multiple, complex, and interrelated conditions, disorders, or diseases. Such complexity is influenced by uncertainty that is difficult to decipher and is proportional to the number of associated morbidities. Computational scientists usually provide meta-analysis studies aimed at integrating various types of evidence, but in our opinion they may help reformulate comorbidity by emphasizing, in particular, two aspects: (i) a systems approach, which allows for an ensemble view of comorbidity, and offers a model representation generalizable to multimorbidity; and (ii) a dynamic network inference approach, which is indicated for the analysis of links among morbidities and evaluation of risk. Notably, the main question remains whether such instruments suggest a shift of paradigm providing prospective impact on medical practice. We have identified in the simultaneous consideration of multiple dimensions linked to comorbidity complexity the rationale for such translation. © 2013 Elsevier Ltd. Source

Ferrannini E.,CNR Institute of Clinical Physiology | DeFronzo R.A.,University of Texas Health Science Center at San Antonio
European Heart Journal | Year: 2015

Type 2 diabetes mellitus (T2DM) is characterized by multiple pathophysiologic abnormalities. With time, multiple glucose-lowering medications are commonly required to reduce and maintain plasma glucose concentrations within the normal range. Type 2 diabetes mellitus individuals also are at a very high risk for microvascular complications and the incidence of heart attack and stroke is increased two-to three-fold compared with non-diabetic individuals. Therefore, when selecting medications to normalize glucose levels in T2DM patients, it is important that the agent not aggravate, and ideally even improve, cardiovascular risk factors (CVRFs) and reduce cardiovascular morbidity and mortality. In this review, we examine the effect of oral (metformin, sulfonylureas, meglitinides, thiazolidinediones, DPP4 inhibitors, SGLT2 inhibitors, and α-glucosidase inhibitors) and injectable (glucagon-like peptide-1 receptor agonists and insulin) glucose-lowering drugs on established CVRFs and long-term studies of cardiovascular outcomes. Firm evidence that in T2DM cardiovascular disease can be reversed or prevented by improving glycaemic control is still incomplete and must await large, long-term clinical trials in patients at low risk using modern treatment strategies, i.e. drug combinations designed to maximize HbA1c reduction while minimizing hypoglycaemia and excessive weight gain. © 2015 The Author 2015. Source

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