29 research outputs found
Molecular mechanisms governing microRNA-125a expression in human hepatocellular carcinoma cells
No full textMicroRNA-125a-5p (miR-125a) is a vertebrate homolog of lin-4, the first discovered microRNA, and plays a fundamental role in embryo development by downregulating Lin-28 protein. MiR-125a is also expressed in differentiated cells where it generally acts as an antiproliferative factor by targeting membrane receptors or intracellular transductors of mitogenic signals. MiR-125a expression is downregulated in several tumors, including hepatocellular carcinoma (HCC) where it targets sirtuin-7, matrix metalloproteinase-11, VEGF-A, Zbtb7a, and c-Raf. In this study, we have isolated the transcription promoter of human miR-125a and characterized its activity in HCC cells. It is a TATA-less Pol II promoter provided with an initiator element and a downstream promoter element, located 3939 bp upstream the genomic sequence of the miRNA. The activity of the promoter is increased by the transcription factor NF-kB, a master regulator of inflammatory response, and miR-125a itself was found to strengthen this activation through inhibition of TNFAIP3, a negative regulator of NF-kB. This finding contributes to explain the increased levels of miR-125a observed in the liver of patients with chronic hepatitis B.MicroRNA-125a-5p (miR-125a) is a vertebrate homolog of lin-4, the first discovered microRNA, and plays a fundamental role in embryo development by downregulating Lin-28 protein. MiR-125a is also expressed in differentiated cells where it generally acts as an antiproliferative factor by targeting membrane receptors or intracellular transductors of mitogenic signals. MiR-125a expression is downregulated in several tumors, including hepatocellular carcinoma (HCC) where it targets sirtuin-7, matrix metalloproteinase-11, VEGF-A, Zbtb7a, and c-Raf. In this study, we have isolated the transcription promoter of human miR-125a and characterized its activity in HCC cells. It is a TATA-less Pol II promoter provided with an initiator element and a downstream promoter element, located 3939 bp upstream the genomic sequence of the miRNA. The activity of the promoter is increased by the transcription factor NF-kB, a master regulator of inflammatory response, and miR-125a itself was found to strengthen this activation through inhibition of TNFAIP3, a negative regulator of NF-kB. This finding contributes to explain the increased levels of miR-125a observed in the liver of patients with chronic hepatitis B
Human MiR-544a Modulates SELK Expression in Hepatocarcinoma Cell Lines.
No full textHepatocellular carcinoma (HCC) is a multi-factorial cancer with a very poor prognosis; therefore, there are several investigations aimed at the comprehension of the molecular mechanisms leading to development and progression of HCC and at the definition of new therapeutic strategies. We have recently evaluated the expression of selenoproteins in HCC cell lines in comparison with normal hepatocytes. Recent results have shown that some of them are down- and others up-regulated, including the selenoprotein K (SELK), whose expression was also induced by sodium selenite treatment on cells. However, so far very few studies have been dedicated to a possible effect of microRNAs on the expression of selenoproteins and their implication in HCC. In this study, the analysis of SELK 3'UTR by bioinformatics tools led to the identification of eight sites potentially targeted by human microRNAs. They were then subjected to a validation test based on luciferase reporter constructs transfected in HCC cell lines. In this functional screening, miR-544a was able to interact with SELK 3'UTR suppressing the reporter activity. Transfection of a miR-544a mimic or inhibitor was then shown to decrease or increase, respectively, the translation of the endogenous SELK mRNA. Intriguingly, miR-544a expression was found to be modulated by selenium treatment, suggesting a possible role in SELK induction by selenium
Un riparo per l’antico. Progetto di una copertura archeologica a Piazza Bellini Napoli, 2023
No full textLa città è fatta di strata spesso invisibili e poco intellegibili, soprattutto quando non vi è un’architettura chiamata a renderli manifesti. È il caso delle mura greche del V-IV secolo a.C. di Piazza Bellini a Napoli che – rinvenute per caso nel 1954 e lasciate scoperte e inaccessibili, sottoposte e recintate – non riescono a stabilire alcun chiaro rapporto con la città “di sopra” che, a sua volta, si organizza secondo un ordine completamente differente.
Il progetto, esito di un workshop-tirocinio con giovani studentesse, si pone l’obiettivo di risistemare l’intera piazza Bellini, posta sul limite del centro greco-romano della città, a partire dalla necessità di proteggere, ma anche e forse soprattutto di ‘rivelare’, le mura della cui presenza si rischia di non accorgersi neppure per l’assenza di un disegno sintetico che vede oggi lo spazio sgombrato rappresentato nel Settecento da Antonio Joli inutilmente affollato di alberature, monumenti – innanzitutto quello al musicista catanese Vincenzo Bellini formatosi a Napoli nel Collegio di Musica di San Sebastiano, oggi Conservatorio di San Pietro a Majella, adiacente la piazza – dehors e arredo urbano.
Razionalizzato lo scavo, un alto riparo dorato rende manifesta la giacitura ruotata delle mura, nella foratura e nel disegno della pavimentazione, e trova il suo contrappunto in un portico che ordina gli spazi all’aperto di bar, caffe letterari e ristoranti che “abitano” la piazza, reimmettendo in tal modo le rovine nella dinamica urbana e costruendo un doppio registro seguendo il quale la città rende manifesta e non finge o dissimula le radici millenarie dalle quali proviene. La copertura in acciaio dipinto di giallo oro – di “giallo Napoli” – vuole essere un riparo per l’antico che, nel riprendere allineamenti, altezze e scansioni dei fronti degli edifici esistenti, introduce una nuova singolarità urbana, chiamata a caratterizzare lo spazio pubblico, e, nell’affondare nelle profondità ctonie tufacee, al tempo stesso, si libera come una grande pergola a segnalare le antiche vestigia che ombreggia e protegge. Un abri souverain, come nella nota definizione di Auguste Perret, che nella esattezza delle proporzioni – un quadrato in pianta, due quadrati in alzato – e nella essenzialità logica della costruzione tettonica – quattro coppie di piedritti a sorreggere due travi mediane a sezione variabile che a loro volta sorreggono una graticcio pergolato – ha il compito di mettere in opera e in scæna la grandezza dell’antico senza mimetismi ma neppure irrisioni perché, seguendo il noto aforisma di Karl Kraus, Ursprung ist das Ziel
Description of a low‐cost picture archiving and communication system based on network‐attached storage
No full textHigh costs for installing, maintaining, and updating a standard picture archiving and communication system (PACS) can be prohibitive for small/medium‐sized veterinary facilities. The aims of this prospective, exploratory study were to describe the design, implementation, and author experiences for 1 year's use of a low‐cost PACS based on network‐attached storage. The system described here was easily installed and resiliently stored redundant copies of data. It excellently balanced data recovery, system speed, security, and available memory for storage. A virtual private network also allowed off‐site data review. This system can also be used for future off‐site backup of data in the cloud
Liver microRNA hsa-miR-125a-5p may exert an oncosuppressor effect on hepatocellular carcinoma (HCC).
No full textIl bilancio integrato : il caso Autogrill
No full textLAUREA MAGISTRALEA valle della recente crisi finanziaria l’importanza di un’informazione trasparente ha assunto un peso maggiore: gli stakeholder richiedono conoscenza in merito ai rischi e alle opportunità cui l’organizzazione è soggetta. I documenti di contabilità economica e sociale non rispondono più a tali aspettative, perciò è necessaria una nuova forma di reportistica che integri tutte le leve strategiche e che indirizzi l’operato aziendale verso un business sempre più sostenibile.
Oggi esistono documenti che rispecchiano le caratteristiche citate, i Bilanci Integrati, ma la diffusione è ancora limitata: solo il 3% delle prime 250 aziende per capitalizzazione di mercato ne produce uno simile.
Dato il carattere in evoluzione dell’argomento e del dibattito internazionale, il presente lavoro di Tesi si propone di fornire maggior chiarezza in merito al contesto attuale e su quello in divenire. Inoltre, lo studio di una realtà aziendale, che sta intraprendendo la strada verso la rendicontazione integrata, ha permesso di entrare direttamente nel vivo della problematica. Quindi, da un lato lo studio di documenti provenienti da associazioni internazionali e nazionali attive nel dibattito sulla rendicontazione integrata, l’analisi di alcuni fra i Bilanci Integrati ad oggi pubblicati e una collezione di interviste ad esperti riguardo al tema in questione, ha permesso di delineare diversi aspetti dello stato dell’arte della nuova forma di rendicontazione. Dall’altro lato, per lo studio del caso reale, si è seguito un approccio di case study, che consente di analizzare un fenomeno contemporaneo all’interno di un contesto reale, e una strategia di action research, per la sua natura di indagine in cui i partecipanti e i ricercatori co – generano conoscenza attraverso la reciproca collaborazione.
In conclusione, lo studio ha permesso sia di delineare un quadro riassuntivo delle variabili di contesto in cui si inseriscono le organizzazioni che producono un Bilancio integrato ed alcune peculiarità proprie di tali documenti, sia proposte abilitanti al proseguimento del percorso verso la rendicontazione integrata per l’azienda oggetto di studio.Following the recent financial crisis, the importance of financial trasperancy has become even more important: the stakeholders ask for more information riguarding risks and opportunities, to which the company may be exposed.
Existing social and economic accounting documentation, do not deliver this. Therefore, a new form of integrated reporting is necessary. One that shows all strategics options which drive the company towards a more sustainable form of business.
Today this type of document does exist, but only three per cent of top two hundred and fifty companies (in FORTUNE 2000 ranking) adopt a similar report.
Given the everchanging topic and International debate reguarding this report, the following thesis proposes detailed information and analysis in order to throw some light on the issue.
Accountability has proven a key factor, allowing us to get to the core of the question.
On one hand, we find a series of documents from National and International sources and a series of interviews and debite on integrated accounting accountability, which allowed us to underline the state of art in new accounting accountability.
On the other hand case study was carried out giving us the opportunity of analyzing a real contemporary fenomena in a even more real context, an action research, an investigation in which the partecipant and the resourchers generate knowledge throw reciprical collaboration.
To wind up, our studies have produced a summary of the variables with which companies working with an integrated balance live their daily lives.
Taking a close look at these documents and some similarities, we have underlined some proposals in order to go in the direction of integrated reporting
MicroRNA-125a-5p Is a Downstream Effector of Sorafenib in Its Antiproliferative Activity Toward Human Hepatocellular Carcinoma Cells
No full textSorafenib is an antitumor drug for treatment of advanced hepatocellular carcinoma (HCC). It acts as a multikinase inhibitor suppressing cell proliferation and angiogenesis. Human microRNA-125a-5p (miR-125a) is endowed with similar activities and is frequently downregulated in HCC. Looking for a potential microRNA-based mechanism of action of the drug, we found that sorafenib increases cellular expression of miR-125a in cultured HuH-7 and HepG2 HCC cells. Upregulation of the microRNA inhibited cell proliferation by suppression of sirtuin-7, a NAD(+)-dependent deacetylase, and p21/p27-dependent cell cycle arrest in G1. Later, recruitment of miR-125a in the antiproliferative activity of sorafenib was inquired by modulating its expression in combination with the drug treatment. This analysis showed that intracellular delivery of miR-125a had no additive effect on the antiproliferative activity of sorafenib, whereas a miR-125a inhibitor could counteract it. Finally, evaluation of other oncogenic targets of miR-125a revealed its ability to interfere with the expression of matrix metalloproteinase-11, Zbtb7a proto-oncogene, and c-Raf, possibly contributing to the antiproliferative activity of the drug. J. Cell. Physiol. 232: 1907–1913, 2017. © 2016 Wiley Periodicals, Inc
The Use of Partial Least Squares–Path Modelling to Understand the Impact of Ambivalent Sexism on Violence-Justification among Adolescents
No full textGender violence is generally conceived as a phenomenon concerning only adults.
Nonetheless, it is also perpetrated within teenagers’ relationships, as many empirical studies have
shown. We therefore have focused our attention on a non-probabilistic sample consisting of 400
adolescents living in Naples (Italy), to study the association between sexism and the justification of
violent attitudes. Generally, sexism is recognised as a discriminatory attitude towards people, based
on their biological sex. However, it is conventional to talk about sexism as a prejudice against
women. The Ambivalent Sexism Inventory (ASI) for adolescents was used to evaluate the two
dimensions of ambivalent sexism, i.e., hostile sexism (HS) and benevolent sexism (BS). Moreover,
the questionnaire regarding attitudes towards diversity and violence (CADV) was administered to
assess participants’ attitudes towards violence. A Partial Least Square–Second Order Path Model
reveals that girls’ ambivalent sexism is affected more by benevolent sexism than hostile sexism. On
the contrary, among boys, hostile sexism has a higher impact. Finally, benevolent sexist girls justify
domestic violence more than boys do
MicroRNA-423-5p promotes autophagy in cancer cells and is increased in serum from hepatocarcinoma patients treated with sorafenib
No full textHepatocellular carcinoma (HCC) is the third cause of cancer-related deaths worldwide. Sorafenib is the only approved drug for patients with advanced HCC but has shown limited activity. microRNAs (miRs) have been involved in several neoplasms including HCC suggesting their use or targeting as good tools for HCC treatment. The purpose of this study was to identify novel approaches to sensitize HCC cells to sorafenib through miRs. miR-423-5p was validated as positive regulator of autophagy in HCC cell lines by transient transfection of miR and anti-miR molecules. miR-423-5p expression level was evaluated by real-time polymerase chain reaction (PCR) in sera collected from 39 HCC patients before and after treatment with sorafenib. HCC cells were cotreated with sorafenib and miR-423-5p and the effects on cell cycle, apoptosis, and autophagy were evaluated. Secretory miR-423-5p was upregulated both in vitro and in vivo by sorafenib treatment and its increase was correlated with response to therapy since 75% of patients in which an increase of secretory miR423-5p was found were in partial remission or stable disease after 6 moths from the beginning of therapy. HCC cells transfected with miR-423-5p showed an increase of cell percentage in S-phase of cell cycle paralleled by a similar increase of autophagic cells evaluated at both fluorescence activated cell sorter (FACS) and transmission electron microscopy. Our results suggest the miR423-5p can be used as a useful tool to predict response to sorafenib in HCC patients and is involved in autophagy regulation in HCC cells
