MicroRNAs (miRNAs) are highly conserved ∼22‐mer RNA molecules, encoded by plants and animals that regulate the expression of genes binding to the 3^′‐UTR of specific target mRNAs. The amount of miRNAs in a total RNA sample depends on the recovery efficiency that may be significantly affected by the different purification methods employed. Traditional approaches may be inefficient at recovering small RNAs, and common spectrophotometric determination is not adequate to quantify selectively these low molecular weight (LMW) species from total RNA samples. Here, we describe the use of qualitative and quantitative lab-on-a-chip tools for the analysis of these LMW RNA species. Our data emphasize the close correlation of LMW RNAs with the expression levels of some miRNAs. We therefore applied our result to the comparison of some miRNA expression profiles in different tissues. Finally, the methods we used in this paper allowed us to analyze the efficiency of extraction protocols, to study the small (but significant) differences among various preparations and to allow a proper comparison of some miRNA expression profiles in various tissues.

Breast milk exerts pivotal regulatory functions early in development whereby it contributes to the maturation of brain and associated cognitive functions. However, the specific components of maternal milk mediating this process have remained elusive. Sialylated human milk oligosaccharides (HMOs) represent likely candidates since they constitute the principal neonatal dietary source of sialic acid, which is crucial for brain development and neuronal patterning. We hypothesize that the selective neonatal lactational deprivation of a specific sialylated HMOs, sialyl(alpha2,3)lactose (3′SL), may impair cognitive capabilities (attention, cognitive flexibility, and memory) in adulthood in a preclinical model. To operationalize this hypothesis, we cross-fostered wild-type (WT) mouse pups to B6.129-St3gal4^tm1.1Jxm/J dams, knock-out (KO) for the gene synthesizing 3′SL, thereby providing milk with approximately 80% 3′SL content reduction. We thus exposed lactating WT pups to a selective reduction of 3′SL and investigated multiple cognitive domains (including memory and attention) in adulthood. Furthermore, to account for the underlying electrophysiological correlates, we investigated hippocampal long-term potentiation (LTP). Neonatal access to 3′SL-poor milk resulted in decreased attention, spatial and working memory, and altered LTP compared to the control group. These results support the hypothesis that early-life dietary sialylated HMOs exert a long-lasting role in the development of cognitive functions.

MicroRNAs (miRNAs) are ~22 nucleotide non-coding RNAs that control gene expression post-transcriptionally by base pairing to mRNAs. MiRNAs are predicted to target ~50% of all protein-coding genes and functional studies indicate that they participate in the regulation of almost every cellular process. They also play a key role in pathogenetic mechanisms underlying several diseases, e.g. cancer, cardiovascular diseases, autoimmune diseases, and neurodegenerative diseases. Several miRNAs are expressed in the human brain where they contribute to equilibrium between maintenance and differentiation of neural stem cells. MiRNAs specific mechanisms of action and their roles in brain development and synaptic plasticity resulted in a great interest in the analysis of their potential role in the pathogenesis and pathophysiology of neuropsychiatric disorders. Currently, schizophrenia is one of the fields in psychiatry where miRNAs have been most widely investigated. The understanding of miRNAs role in schizophrenia has been achieved through association, functional and expression profiling studies on post mortem brain and peripheral tissues. Several studies identified association between neuropsychiatric disorders and variants in miRNAs including variations in miRNA/primary-/precursor-miRNAs sequences, in miRNAs biogenesis machinery genes, in the 3’UTR of target genes and in miRNAs expression. In summary, there is growing evidence that miRNAs exert a crucial role in gene expression regulation in the central nervous system and are altered in the development, presentation and response to treatment of psychiatric disorders. In this review we summarize the most significant results of experimental studies aimed at highlighting the involvement of human miRNAs in schizophrenia.

Background: IHD is determined by an inadequate coronary blood supply to the myocardium, and endothelial dysfunction may represent one of the main pathophysiological mechanisms involved. Genetic predisposition to endothelial dysfunction has been associated with IHD and its clinical manifestation. However, studies are often confounding and inconclusive for several reasons, such as interethnic differences. Validation of results in larger cohorts and new populations is needed. The aim of this study is to evaluate the associations between the allelic variants of the eNOS rs1799983 single-nucleotide polymorphism, IHD susceptibility and its clinical presentation. Methods: A total of 362 consecutive patients with suspected myocardial ischemia were enrolled. Patients were divided into three groups: G1, coronary artery disease (CAD); G2, coronary microvascular dysfunction (CMD); and G3, a control group with anatomically and functionally normal coronary arteries. Analysis of three allelic variants, GT, GG and TT, of rs1799983 for the NOS3 gene, encoding for eNOS, was performed. Results: rs1799983_GT was significantly more expressed by the ischemic groups (G1 and G2) compared to G3. The TT variant was significantly more expressed by the G1 group, compared to the G2 group. Among ischemic patients, GT was significantly more expressed in patients with acute coronary syndrome (ACS) presentation, compared to other clinical presentations. In the multivariate analysis, the allelic variant GT was found to potentially represent an independent predictor of IHD and ACS presentation. Conclusion: The presence of the SNP rs1799983_GT, encoding for eNOS, is an independent risk factor for IHD and, remarkably, for ACS presentation, independently of cardiovascular risk factors. These results may be useful for the prediction of IHD development, particularly with an acute clinical manifestation. They may allow the early identification of patients at high risk of developing IHD with an ACS, promoting a genetic-based prevention strategy against IHD.