Loss of miR‐101 expression promotes Wnt/β‐catenin signalling pathway activation and malignancy in colon cancer cells

Colorectal cancer (CRC) is the second leading cause of cancer‐related mortality in Western countries. Although the aberrant expression of several microRNAs (oncomiRs) is associated with CRC progression, the molecular mechanisms of this phenomenon are still under investigation. Here we show that miR‐101 expression is differentially impaired in CRC specimens, depending on tumour grade. miR‐101 re‐expression suppresses cell growth in 3D, hypoxic survival and invasive potential in CRC cells showing low levels of miR‐101. Additionally, we provide molecular evidence of a bidirectional regulatory mechanism between miR‐101 expression and important CRC pro‐malignant features, such as inflammation, activation of the Wnt/β‐catenin signalling pathway and epithelial–mesenchymal transition (EMT). We then propose that up‐regulated miR‐101 may function as a tumour suppressor in CRC and that its pharmacological restoration might hamper the aggressive behaviour of CRC in vivo. MiR‐101 expression may also represent a cancer biomarker for CRC diagnosis and prognosis. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Excessive daytime sleepiness and fatigue in neurological disorders

Sleep and Breathing - Excessive daytime sleepiness (EDS) and fatigue are some of the most frequent symptoms in neurological diseases and could impact on quality of life by increasing the risk of...     

Prediction of incident type 2 diabetes mellitus based on a twenty-year follow-up of the Ventimiglia heart study

A novel algorithm to predict incident type 2 diabetes mellitus (iT2DM) is presented considering data from a 20-year prospective study in a Southern Italy population. Eight hundred and fifty-eight out of 1,351 subjects (24?C85?years range of age) were selected. Incident type 2 diabetes was diagnosed in 103 patients in a 20-year follow-up. The Finnish Diabetes Risk Score (FINDRISC) and the Framingham Offspring Study simple clinical model (FOS) have been used as reference algorithms. Two custom algorithms have been created using Cox parametric hazard models followed by PROBIT analyses: the first one (VHSRISK) includes all the study subjects and the second one (VHS95RISK) evaluates separately subjects with baseline fasting blood glucose (FBG) above/below 5.2?mmol/L (95?mg/dL). The 44 iT2DM cases below 5.2?mmol/L of baseline FBG were predicted by high LDL cholesterol, metabolic syndrome (ATPIII criteria), BMI?>?30?kg/m², and high factor VII activity. The 59 cases above the FBG threshold were predicted by FBG classes, hypertension, and age. ROC areas for iT2DM prediction were: FINDRISC?=?0.759, FOS?=?0.762, VHSRISK?=?0.789, and VHS95RISK?=?0.803. In a Mediterranean population, the use of a custom generated algorithm evaluating separately low/high FBG subjects improves the prediction of iT2DM in subjects classified at lower risk by common estimation algorithms.     

Adult-onset mitochondrial movement disorders: a national picture from the Italian Network

Journal of Neurology - Both prevalence and clinical features of the various movement disorders in adults with primary mitochondrial diseases are unknown. Based on the database of the...     

Myoclonus in mitochondrial disorders

Myoclonus is a possible manifestation of mitochondrial disorders, and its presence is considered, in association with epilepsy and the ragged red fibers, pivotal for the syndromic diagnosis of MERRF (myoclonic epilepsy with ragged red fibers). However, its prevalence in mitochondrial diseases is not known. The aims of this study are the evaluation of the prevalence of myoclonus in a big cohort of mitochondrial patients and the clinical characterization of these subjects. Based on the database of the “Nation‐wide Italian Collaborative Network of Mitochondrial Diseases,” we reviewed the clinical and molecular data of mitochondrial patients with myoclonus among their clinical features. Myoclonus is a rather uncommon clinical feature of mitochondrial diseases (3.6% of 1,086 patients registered in our database). It is not strictly linked to a specific genotype or phenotype, and only 1 of 3 patients with MERRF harbors the 8344A>G mutation (frequently labeled as “the MERRF mutation”). Finally, myoclonus is not inextricably linked to epilepsy in MERRF patients, but more to cerebellar ataxia. In a myoclonic patient, evidences of mitochondrial dysfunction must be investigated, even though myoclonus is not a common sign of mitochondriopathy. Clinical, histological, and biochemical data may predict the finding of a mitochondrial or nuclear DNA mutation. Finally, this study reinforces the notion that myoclonus is not inextricably linked to epilepsy in MERRF patients, and therefore the term “myoclonic epilepsy” seems inadequate and potentially misleading. © 2014 International Parkinson and Movement Disorder Society