35 research outputs found

    Establishment and characterization of induced pluripotent stem cell (iPSCs) line UNIBSi014-A from a healthy female donor.

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    Abstract Peripheral blood mononuclear cells (PBMCs) derived from a healthy 40-year-old female were successfully transformed into induced pluripotent stem cells (iPSCs) by using the integration-free CytoTune-iPS Sendai Reprogramming method. The resulting iPSCs line exhibits a normal karyotype, expresses stemness markers and displays the differentiation capacity into the three germ layers. This human iPSCs line can be used as healthy control in disease modelling studies

    Transcriptional Profiling of Rat Prefrontal Cortex after Acute Inescapable Footshock Stress

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    Stress is a primary risk factor for psychiatric disorders such as Major Depressive Disorder (MDD) and Post Traumatic Stress Disorder (PTSD). The response to stress involves the regulation of transcriptional programs, which is supposed to play a role in coping with stress. To evaluate transcriptional processes implemented after exposure to unavoidable traumatic stress, we applied microarray expression analysis to the PFC of rats exposed to acute footshock (FS) stress that were sacrificed immediately after the 40 min session or 2 h or 24 h after. While no substantial changes were observed at the single gene level immediately after the stress session, gene set enrichment analysis showed alterations in neuronal pathways associated with glia development, glia-neuron networking, and synaptic function. Furthermore, we found alterations in the expression of gene sets regulated by specific transcription factors that could represent master regulators of the acute stress response. Of note, these pathways and transcriptional programs are activated during the early stress response (immediately after FS) and are already turned off after 2 h-while at 24 h, the transcriptional profile is largely unaffected. Overall, our analysis provided a transcriptional landscape of the early changes triggered by acute unavoidable FS stress in the PFC of rats, suggesting that the transcriptional wave is fast and mild, but probably enough to activate a cellular response to acute stress

    miR-9-5p IN NEURONAL DENDRITIC REMODELING: THE ROLE OF STRESS

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    miR-9-5p IN NEURONAL DENDRITIC REMODELING: THE ROLE OF STRESSmiR-9-5p IN NEURONAL DENDRITIC REMODELING: THE ROLE OF STRES

    Genome-wide analysis of consistently RNA edited sites in human blood reveals interactions with mRNA processing genes and suggests correlations with cell types and biological variables

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    A-to-I RNA editing is a co-/post-transcriptional modification catalyzed by ADAR enzymes, that deaminates Adenosines (A) into Inosines (I). Most of known editing events are located within inverted ALU repeats, but they also occur in coding sequences and may alter the function of encoded proteins. RNA editing contributes to generate transcriptomic diversity and it is found altered in cancer, autoimmune and neurological disorders. Emerging evidences indicate that editing process could be influenced by genetic variations, biological and environmental variables

    miRNA Editing: New Insights into the Fast Control of Gene Expression in Health and Disease

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    Post-transcriptional modifications are essential mechanisms for mRNA biogenesis and function in eukaryotic cells. Beyond well-characterized events such as splicing, capping, and polyadenylation, there are several others, as RNA editing mechanisms and regulation of transcription mediated by miRNAs that are taking increasing attention in the last years. RNA editing through A-to-I deamination increases transcriptomic complexity, generating different proteins with amino acid substitution from the same transcript. On the other hand, miRNAs can regulate gene expression modulating target mRNA decay and translation. Interestingly, recent studies highlight the possibility that miRNAs might undergo editing themselves. This mainly translates in the degradation or uncorrected maturation of miRNAs but also in the recognition of different targets. The presence of edited and unedited forms of the same miRNA may have important biological implications in both health and disease. Here we review ongoing investigations on miRNA RNA editing with the aim to shed light on the growing importance of this mechanism in adding complexity to post-transcriptional regulation of gene expression

    Stress, microRNAs, and stress-related psychiatric disorders: an overview

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    : Stress is a major risk factor for psychiatric disorders. During and after exposure to stressors, the stress response may have pro- or maladaptive consequences, depending on several factors related to the individual response and nature of the stressor. However, the mechanisms mediating the long-term effects of exposure to stress, which may ultimately lead to the development of stress-related disorders, are still largely unknown. Epigenetic mechanisms have been shown to mediate the effects of the environment on brain gene expression and behavior. MicroRNAs, small non-coding RNAs estimated to control the expression of about 60% of all genes by post-transcriptional regulation, are a fundamental epigenetic mechanism. Many microRNAs are expressed in the brain, where they work as fine-tuners of gene expression, with a key role in the regulation of homeostatic balance, and a likely influence on pro- or maladaptive brain changes. Here we have selected a number of microRNAs, which have been strongly implicated as mediators of the effects of stress in the brain and in the development of stress-related psychiatric disorders. For all of them recent evidence is reported, obtained from rodent stress models, manipulation of microRNAs levels with related behavioral changes, and clinical studies of stress-related psychiatric disorders. Moreover, we have performed a bioinformatic analysis of the predicted brain-expressed target genes of the microRNAs discussed, and found a central role for mechanisms involved in the regulation of synaptic function. The complex regulatory role of microRNAs has suggested their use as biomarkers for diagnosis and treatment response, as well as possible therapeutic drugs. While, microRNA-based diagnostics have registered advancements, particularly in oncology and other fields, and many biotech companies have launched miRNA therapeutics in their development pipeline, the development of microRNA-based tests and drugs for brain disorders is comparatively slower
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