Circulating miRNA as fine regulators of the physiological responses to physical activity: Pre-analytical warnings for a novel class of biomarkers.

MicroRNAs are endogenous non-coding RNAs that post-transcriptionally regulate gene expression by specifically binding the target mRNA and by consequently inducing its degradation. miRNAs can be released into the circulation where they remain stable and they can be measured. Their changes reflect individual biologic adaptation to exposures to specific environmental conditions. As such, measurement of circulating microRNAs represents an opportunity to evaluate biologic changes associated with interventions such as exercise and diet. Physical activity is, indeed, a very important modifying factor for circulating miRNAs. Toward their use in clinical settings several issues should be still solved. Their clinical application is hindered by the high heterogeneity of the analytical procedures used for their measurements. Furthermore, several pre-analytical concerns equally reduce the clinical applicability of miRNA. Pre-analytical phase in sports medicine is an important issue both because, often the conditions in which sampling are performed are peculiar (and not always canonical) and because some of the tested parameters, in the case of professional athletes, enters in routine anti-doping testing and, as such, they should be treated according to precise rules in order to avoid any false positive results. Aim of this review is to give an overview of the main available knowledges about the pre-analytical management of the sample for circulating miRNA evaluation along with the importance of miRNA as regulators of the response to physical activity and their possible future use in anti-doping settings.

Functional characterization of a CRH missense mutation identified in an ADNFLE family.

Nocturnal frontal lobe epilepsy has been historically considered a channelopathy caused by mutations in subunits of the neuronal nicotinic acetylcholine receptor or in a recently reported potassium channel. However, these mutations account for only a minority of patients, and the existence of at least a new locus for the disease has been demonstrated. In 2005, we detected two nucleotide variations in the promoter of the CRH gene coding for the corticotropin releasing hormone in 7 patients. These variations cosegregated with the disease and were demonstrated to alter the cellular levels of this hormone. Here, we report the identification in an Italian affected family of a novel missense mutation (hpreproCRH p.Pro30Arg) located in the region of the CRH coding for the protein pro-sequence. The mutation was detected in heterozygosity in the two affected individuals. In vitro assays demonstrated that this mutation results in reduced levels of protein secretion in the short time thus suggesting that mutated people could present an altered capability to respond immediately to stress agents.