1,869 research outputs found
Studio dell'espressione di microRNA, geni target e pathways indotti da NGF in cellule epiteliali di cornea: confronto tra differenti bioformulazioni.
No full textNerve Growth Factor (NGF) is a member of the neurotrophins family that plays a key role in the maintenance and functions of both the central and peripheral nervous systems, as well as in non-neuronal cells. It exerts its action through two classes of transmembrane receptors, one high affinity, TrkA, and one low affinity, p75NTR, regulating different and important biological functions. Besides several neuropathies, some studies showed that NGF revealed translational clinical application for ulcers of the eye’s anterior segment, and a NGF bioformulation has been EMA and FDA approved as first-in-class treatment for neurotrophic keratitis (NK), a rare degenerative corneal disease due to corneal trigeminal innervation defects causing spontaneous injuries and wounds. However, NGF-induced biomolecular mechanisms in corneal cells are still unknown.
MicroRNAs (or miRNAs) are a novel class of endogenous, small non-coding RNAs (~22 nucleotides), able to regulate target genes, at the post-transcriptional level, in plants and animals. MiRNAs are involved in maintaining cell homeostasis and tuning fundamental biological processes, such as growth, proliferation, apoptosis, cell metabolism; dysregulated expression of miRNAs’ is observed and strictly linked to relevant human diseases (e.g. viral, immune, neurodegenerative and cardiovascular diseases, cancer).
In this study we evaluated miRNAs’ expression modulation in corneal cells after treatment with different NGF bioformulations, by focusing the analysis on target genes and pathways as well.
Tens of miRNAs were significantly dysregulated, mainly hypo-expressed, after treatment. Among those, 3 were shared by all the bioformulations, 37 by 2 of them, whereas 12, 16 and 20 were correlated to each single bioformulation. A total number of 91 unique pathways were identified by DIANA experimentally-supported Tarbase analysis: 46, including the neurotrophin signalling pathway, were shared by all three bioformulations, 28 by 2 of them, whereas 9, 2 and 6 were related to each single bioformulation. More than 2.000 experimentally supported target genes were identified. After focusing the analysis on the neurotrophin signalling pathway, no relevant differences were globally detected among the NGF bioformulations, all appearing to drive through proliferative and survival signals. However, one of the three bioformulations here used appeared to be more specific than the remaining two, as, when proportionally compared to them, it involved less significant miRNAs which, however, can target higher numbers of genes involved in this pathway. The same result was achieved when analysis was restricted to miRNAs’ sub-groups specifically related to each single bioformulation. Genemania gene and functional enrichment analysis further confirmed data. Futhermore, the gene list can be in depth analysed in order to identify targets suitable for further molecular analyses and validations, especially for each single bioformulation, with the aim to possibly identify target genes and functions specifically related to them. For this reason, more experiments by immunoblotting to evaluate expression levels of interesting target genes are ongoing.
We examined the effects induced by different NGF bioformulations on epithelial corneal cells, by focusing the attention on miRNAs expression levels, and in silico target genes and pathways analysis. Although further functional studies to validate results are needed, original and novel insights about genes and epigenetics mechanisms induced by NGFs were provided. Our data may leave to hypothesize that NGF1 might be more specific and effective in inducing neurotrophin signalling pathway compared with NGF2 and NGF3. Importantly, given the putative role of miRNAs as biomarkers or therapeutic targets, this study makes available data potentially exploitable in clinical practice
Investigational neuroprotective compounds in clinical trials for retinal disease
No full textIntroduction: Retinal neurodegeneration causes irreversible vision loss, impairing quality of life. By targeting neurotoxic conditions, such as oxidative stress and ischemia, neuroprotectants can slow or stop sight loss resulting from eye disease. Despite limimted clinical use of neuroprotectants, there are several promising compounds in early clinical trials (pre-phase III) which may fulfil new therapeutic roles. Search terms relating to neuroprotection and eye disease were used on ClinicalTrials.gov to identify neuroprotective candidates. Areas covered: Research supporting neuroprotection in eye diseases is focused on, ranging from preclinical to phase II, according to the ClinicalTrials.gov database. The compounds discussed are explored in terms of future clinical applications. Expert opinion: The major challenge in neuroprotection research is translation from basic research to the clinic. A number of potential neuroprotectants have progressed to ophthalmology clinical trials in recent years, with defined mechanisms of action–saffron and CoQ10–targeting mitochondria, and both CNTF and NGF showing anti-apoptotic effects. Enhancements in trial design and patient cohorts in proof-of-concept trials with enriched patient populations and surrogate endpoints should accelerate drug development. A further important consideration is optimising drug delivery to improve individualised management and patient compliance. Progress in these areas means that neuroprotective strategies have a much improved chance of translational success
Chiara Lubich, Meditazioni: letteratura come relazione
No full textChiara Lubich (1920–2008), although the author of 32 books published in 26 countries (178 editions, 3.2 million copies), is better known for her social engagement, as reflected in numerous awards. She began to be regarded as a literary author only in the early 2000s, and primarily from a linguistic rather than literary perspective. This article focuses on her book Meditazioni (Meditations), reconstructs its genesis by tracing the writing process from the late 1950s to her death and the 2021 critical edition, and offers a literary analysis. This reveals Lubich as a forerunner of a new conception of literature: literature as relationship – not only between author and reader, but also among subject, inspiration, and the editorial process
Mitotic phosphorylation of Tau/MAPT modulates cell cycle progression in prostate cancer cells
No full textPurposeTau/MAPT (microtubule associated protein tau) protein is actively studied for the pathologic consequences of its aberrant proteostasis in central nervous system leading to neurodegenerative diseases. Besides its ability to generate insoluble toxic oligomers, Tau homeostasis has attracted attention for its involvement in the formation of the mitotic spindle. This evidence, in association with the description of Tau expression in extra-neuronal tissues, and mainly in cancer tissues, constitutes the rationale for a more in-depth investigation of Tau role also in neoplastic diseases.MethodsIn our study, we investigated the expression of phosphorylated Tau in prostate cancer cell lines with particular focus on the residue Thr231 present in microtubule binding domain.ResultsThe analysis of prostate cancer cells synchronized with nocodazole demonstrated that the expression of Tau protein phosphorylated at residue Thr231 is restricted to G2/M cell cycle phase. The phosphorylated form was unable to bind tubulin and it does not localize on mitotic spindle. As demonstrated by the use of specific inhibitors, the phosphorylation status of Tau is under the direct control of cdk5 and PP2A, while cdk1 activation was able to exert an indirect control. These mechanisms were also active in cells treated with docetaxel, where counteracting the expression of the dephosphorylated form, by kinase inhibition or protein silencing, determined resistance to drug toxicity.ConclusionsWe hypothesize that phosphorylation status of Tau is a key marker for G2/M phase in prostate cancer cells and that the forced modulation of Tau phosphorylation can interfere with the capacity of cell to efficiently progress through G2/M phase
Chiara Lubich: A Saint for a New Global Unity
No full textIn this article the author offers an introduction to the life, thought, and impact of Chiara Lubich. He begins with a brief biographical overview and draws attention to some important features of her spiritual teaching: Jesus in the midst, Jesus Forsaken, Mary Desolate, the four nights. He draws attention to the Economy of Communion and as an expression of this spirituality in the world of business and economics, and to the figure of Chiara Luce Badano, a young adherent to the Spirituality of Unity who has been recognized as an example of how this spirituality can lead to holiness of life. The author’s judgment is that Chiara Lubich is “a saint of dialogue.
Manifesto per il museo post-etnografico
No full textThe author signes a poetic manifesto for the future of ethnographic museums, beyond colonial representational stereotypes and methodologies
Il museo come metodo. E tu, che cosa vedi?
No full textThe chapter reflects upon the current achievements, at international scale, in reference to the education of the adolescents in the museum context. Drawing upon the experience of the "Che cosa vedi?" project, developed by the author herself at the Museo del Novecento, Milan, the chapter explores the scientific horizons, the best practices and the educational methodologies more suit for working with teenagers, such as peer education and debating. "Che cosa vedi?" was focused of the work of 4 prominent Italian artists of the XX century (Lucio Fontana, Toti Scialoja, Luciano Fabro and Mario Merz)
Innovative unattended SEM-EDS analysis for asbestos fiber quantification
No full textScanning electron microscopy with energy dispersive spectrometry (SEM-EDS) is the only affordable analytical
technique that can discriminate both morphology and elemental composition of inorganic fibers. SEM-EDS is
indeed required to quantify asbestos in confounding natural matrixes (e.g. ophiolites), but is also time-consuming,
operator dependent, and strongly relies on the stochastic distribution of the fibers on the filter surface.
The balance between analytical time/cost and the method sensibility allows only about 0.5% of the filter to be
analyzed, strongly affecting the statistical significance of results. To improve sensitivity and precision and enhance
productivity, an unattended quantitative measurement of the asbestos fibers by SEM-EDS is proposed. The
method identifies the particle shape first and determines their chemical composition later, saving EDS analytical
time. Our approach was tested on four asbestos standards and the relative error on replicated measurements
was< 10%. The proposed unattended method quantifies asbestos in natural confounding matrix, also with a
very low asbestos content
From Canvas to Music: Mathematics as a Tool for the Composition of Jackson Time
No full textThe creation of ``Jackson time'' is a project which involves a composer, Davide Amodio, and
a mathematician, Chiara de Fabritiis.
Our common aim was to to ``translate'' a painting by Jackson Pollock, Summertime n. 9,
into a piece of music, making use of different mathematical tools to detect the quantities needed for the
composition. We were inspired by the idea that the painting itself contained some kind of inner--music,
due to the fact that Pollock's moves during the dripping on the canvas had a sort of rhythm, indeed they were often
described by witnesses as a dance.
This paper describes the mathematical background, in particular it illustrates both the analysis
of the painting which was carried out by the two of us and the choice of the mathematical techniques applied to
compute the parameters needed for the composition, which is due to the author. The reader will find a more detailed
report on the composition itself in Davide Amodio's contribution
L'edilizia popolare e ordinaria in Francia: un patrimonio da valorizzare. Il Progetto AMuLoP
No full textThe author describes the practices, methodologies and outcomes of a museum project located in the Northern area of Paris and aimed at representing the life of the working class in the aftermath of the Second World War up to the present, with a focus on immigration
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