Graphene oxide nanoribbons induce autophagic vacuoles in neuroblastoma cell lines

Since graphene nanoparticles are attracting increasing interest in relation to medical applications, it is important to understand their potential effects on humans. In the present study, we prepared graphene oxide (GO) nanoribbons by oxidative unzipping of single-wall carbon nanotubes (SWCNTs) and analyzed their toxicity in two human neuroblastoma cell lines. Neuroblastoma is the most common solid neoplasia in children. The hallmark of these tumors is the high number of different clinical variables, ranging from highly metastatic, rapid progression and resistance to therapy to spontaneous regression or change into benign ganglioneuromas. Patients with neuroblastoma are grouped into different risk groups that are characterized by different prognosis and different clinical behavior. Relapse and mortality in high risk patients is very high in spite of new advances in chemotherapy. Cell lines, obtained from neuroblastomas have different genotypic and phenotypic features. The cell lines SK-N-BE(2) and SH-SY5Y have different genetic mutations and tumorigenicity. Cells were exposed to low doses of GO for different times in order to investigate whether GO was a good vehicle for biological molecules delivering individualized therapy. Cytotoxicity in both cell lines was studied by measuring cellular oxidative stress (ROS), mitochondria membrane potential, expression of lysosomial proteins and cell growth. GO uptake and cytoplasmic distribution of particles were studied by Transmission Electron Microscopy (TEM) for up to 72 h. The results show that GO at low concentrations increased ROS production and induced autophagy in both neuroblastoma cell lines within a few hours of exposure, events that, however, are not followed by growth arrest or death. For this reason, we suggest that the GO nanoparticle can be used for therapeutic delivery to the brain tissue with minimal effects on healthy cells

Action of HMGB1 on miR221/222 cluster in neuroblastoma cell lines

microRNA (miR/miRNA) are small non-coding RNAs that control gene expression at the post-transcriptional level by targeting mRNAs. Aberrant expression of miRNAs is often observed in different types of cancer. Specific miRNAs function as tumor suppressors or oncogenes and interfere with various aspects of carcinogenesis, including differentiation, proliferation and invasion. Upregulation of miRNAs 221 and 222 has been shown to induce a malignant phenotype in numerous human cancers via inhibition of phosphatase and tensin homolog (PTEN) expression. Neuroblastoma is the most common extracranial solid malignancy in children, which is characterized by cellular heterogeneity that corresponds to different clinical outcomes. The different cellular phenotypes are associated with different gene mutations and miRs that control genetic and epigenetic factors. For this reason miRs are considered a potential therapeutic target in neuroblastoma. The aim of the present study was to investigate the mechanisms by which extracellular high mobility group box 1 (HMGB1) promotes cell growth in neuroblastoma. SK-N-BE(2) and SH-SY5Y neuroblastoma derived cell lines were transfected with the antisense oligonucleotides, anti-miR-221 and -222, followed by treatment with HMGB1 to investigate the expression of the oncosuppressor PTEN. In this study, it was demonstrated that HMGB1, which is released by damaged cells and tumor cells, upregulates miR-221/222 oncogenic clusters in the two human neuroblastoma derived cell lines. The results revealed that the oncogenic cluster miRs 221/222 were more highly expressed by the most undifferentiated cell line [SK-N-BE(2)] compared with the the less tumorigenic cell line (SH-SY5Y) and that exogenous HMGB1 increases this expression. In addition, HMGB1 modulates PTEN expression via miR-221/222, as demonstrated by transiently blocking miR-221/222 with anti-sense oligonucleotides. These results may lead to the development of novel therapeutic strategies for neuroblastoma

Il disturbo da gioco d’azzardo: un confronto tra giocatori «puri» e con dipendenza da sostanze

Gli aspetti distintivi del gioco d’azzardo costituiscono il fulcro di un ampio corpus di studio all’interno della letteratura sulle dipendenze. Questa parte da un forte accordo nel ritenere i vari livelli di gioco come punti di un continuum, da livelli non patologici alla manifestazione di una vera e propria dipendenza, piuttosto che come categorie indipendenti tra di loro. Nonostante le diverse classificazioni proposte dagli studi compiuti in materia, è importante sottolineare l’enorme variabilità interindividuale presente tra i giocatori, che influisce, ovviamente, tanto nella prognosi quanto nel trattamento; infatti, è fondamentale tener conto degli aspetti legati all’eziologia, alle caratteristiche di personalità, psicopatologiche e cognitive, nonché ai fattori motivazionali dei giocatori, che sembrerebbero essere alla base dello sviluppo e del mantenimento della dipendenza. Cercando di colmare un gap di letteratura, si propone questo studio, il cui intento è quello di estendere la ricerca empirica, ponendo attenzione sulle differenze che vi sono tra i giocatori “puri” (assenza di altre dipendenze) e giocatori con dipendenza da sostanze, per favorire la comprensione delle caratteristiche personologiche e psicopatologiche dei giocatori d’azzardo, nelle sue peculiarità. Data l’elevata comorbidità del disturbo da gioco d’azzardo patologico con il disturbo da uso di sostanze, indagare il primo, concentrandosi principalmente sui giocatori d’azzardo puri, potrebbe fornire una migliore comprensione dei fattori sottostanti coinvolti nello sviluppo e nel mantenimento del comportamento patologico. Inoltre, risulta importante per fornire indicazioni utili per la prevenzione del disturbo, oltre che per fornire interventi clinici efficaci su misura per le caratteristiche individuali, compatibilmente con la specificità della dipendenza. Nell’elaborato, a seguito di un inquadramento nosografico del gioco d’azzardo, a partire dalla sua nascita fino alla categorizzazione all’interno dei manuali diagnostici psichiatrici, è stato dedicato uno spazio anche agli aspetti normativi nazionali e internazionali che regolano il gioco d’azzardo, oltre ad un focus sulle motivazioni che sottendono la condotta di gioco. Successivamente ci si focalizza sul tema del gioco d’azzardo patologico e le similarità e le differenze con il disturbo da uso di sostanze, passando per i costrutti che integrano variabili di tipo clinico per arrivare ad aspetti più prettamente cognitivi. Questa panoramica teorica pone le basi per lo studio empirico, condotto al fine di indagare se vi siano elementi comuni o di distinzione tra i cosiddetti giocatori d’azzardo “puri”, giocatori in comorbidità con altre dipendenze e un gruppo di controllo. La ricerca proposta è stata condotta all’interno di due comunità residenziali di recupero. Tutti i partecipanti sono stati valutati tramite misure self-report e task comportamentali. In particolare, nell’ambito di questo studio è stato costruito un task ad hoc (Gambling Affective Task) con il fine di indagare come uno specifico mood, indotto dagli stimoli presentati, possa influire sulle scelte di gioco. Lo studio, integrando aspetti clinici e cognitivi, ha permesso di rilevare peculiarità dei giocatori d’azzardo che, se ulteriormente approfondite, potrebbero rappresentare fattori su cui porre primariamente attenzione tanto nella prevenzione quanto nella riabilitazione dei giocatori

Could gestational diabetes mellitus be managed through dietary bioactive compounds? Current knowledge and future perspectives

Gestational diabetes mellitus (GDM) is a serious problem growing worldwide that needs to be addressed with urgency in consideration of the resulting severe complications for both mother and fetus. Growing evidence indicates that a healthy diet rich in fruit, vegetables, nuts, extra-virgin olive oil and fish has beneficial effects in both the prevention and management of several human diseases and metabolic disorders. In this review, we discuss the latest data concerning the effects of dietary bioactive compounds such as polyphenols and PUFA on the molecular mechanisms regulating glucose homoeostasis. Several studies, mostly based on in vitro and animal models, indicate that dietary polyphenols, mainly flavonoids, positively modulate the insulin signalling pathway by attenuating hyperglycaemia and insulin resistance, reducing inflammatory adipokines, and modifying microRNA (miRNA) profiles. Very few data about the influence of dietary exposure on GDM outcomes are available, although this approach deserves careful consideration. Further investigation, which includes exploring the 'omics' world, is needed to better understand the complex interaction between dietary compounds and GDM

HMGB1-Induced Cross Talk between PTEN and miRs 221/222 in Thyroid Cancer

High mobility group box 1 (HMGB1) is an ubiquitous protein that plays different roles in the nucleus, cytoplasm and extra-cellular space. It is an important DAMP molecule that allows communication between damaged or tumor cells and the immune system. Tumor cells exploit HMGB1’s ability to activate intracellular pathways that lead to cell growth and migration. Papillary thyroid cancer is a well differentiated tumor and is often used to study relationships between cells and the inflammatory microenvironment as the latter is characterized by high levels of inflammatory cells and cytokines. Anaplastic thyroid cancer is one of the most lethal human cancers in which many microRNAs and tumor suppressor genes are de-regulated. Up-regulation of microRNAs 221 and 222 has been shown to induce the malignant phenotype in many human cancers via inhibition of PTEN expression. In this study we suggest that extracellular HMGB1 interaction with RAGE enhances expression of oncogenic cluster miR221/222 that in turn inhibits tumor suppressor gene PTEN in two cell lines derived from human thyroid anaplastic and papillary cancers. The newly identified pathway HMGB1/RAGE/miR 221/222 may represent an effective way of tumor escape from immune surveillance that could be used to develop new therapeutic strategies against anaplastic tumors

Metal free graphene oxide (GO) nanosheets and pristine-single wall carbon nanotubes (p-SWCNTs) biocompatibility investigation: a comparative study in different human cell lines

The in vitro biocompatibility of Graphene Oxide (GO) nanosheets, which were obtained by the electrochemical exfoliation of graphite electrodes in an electrolytic bath containing salts, was compared with the pristine Single Wall Carbon Nanotubes (p-SWCNTs) under the same experimental conditions in different human cell lines. The cells were treated with different concentrations of GO and SWCNTs for up to 48 h. GO did not induce any significant morphological or functional modifications (demonstrating a high biocompatibility), while SWNCTs were toxic at any concentration used after a few hours of treatment. The cell viability or cytotoxicity were detected by the trypan blue assay and the lactate dehydrogenase LDH quantitative enzymatic test. The Confocal Laser Scanning Microscopy (CLSM) and transmission electron microscopy (TEM) analysis demonstrated the uptake and internalization of GO sheets into cells, which was localized mainly in the cytoplasm. Different results were observed in the same cell lines treated with p-SWCNTs. TEM and CLSM (Confocal Laser Scanning Microscopy) showed that the p-SWCNTs induced vacuolization in the cytoplasm, disruption of cellular architecture and damage to the nuclei. The most important result of this study is our finding of a higher GO biocompatibility compared to the p-SWCNTs in the same cell lines. This means that GO nanosheets, which are obtained by the electrochemical exfoliation of a graphite-based electrode (carried out in saline solutions or other physiological working media) could represent an eligible nanocarrier for drug delivery, gene transfection and molecular cell imaging tests

Dependência de Redes Sociais, Fear of Missing Out (FoMO) e Vulnerabilidade Online em estudantes universitários

Despite the growing research on social networks sites (SNS), the associations between the abuse of these platforms, the phenomenon of Fear of Missing Out (FOMO) and Online Vulnerability has been understudied. The aim of this research was to provide a framework of attitudes and behaviors related to the use of the social network in young university students. In this study, the sample was composed to 306 Italian university students aged 18 to 30 (152 women; mean of age = 21.8; standard deviation = 3.19) who responded to an online survey regarding their SNS behaviors, Fear of Missing Out (FOMO), Basic Psychological Needs, Self-Esteem and Online Vulnerability. Correlations analysis showed a positive relationship between FOMO, Online Vulnerability, and Social Media Addiction. The results showed that women have a higher level of Social Media Addiction and the Need for Relatedness. The regression analysis showed that FOMO is the best predictor of Social Media Addiction. Implications of the findings in the educational field are discussed.Si bien existe un crecimiento en investigación sobre las redes sociales, es necesario señalar que las asociaciones entre el abuso de estas plataformas, el fenómeno del Fear of Missing Out (FOMO) o Miedo a perderse experiencias y de la Vulnerabilidad en línea han sido poco estudiadas. En ese sentido, esta investigación tiene como objetivo proporcionar un marco de las actitudes y comportamientos relacionados con el uso de las redes sociales en jóvenes universitarios. Para ello, se realizó una muestra que contó con la participación de 306 estudiantes universitarios de 18 a 30 años (152 mujeres y 154 hombres; edad promedio = 21.8; desviación estándar = 3.19) y respondió a un cuestionario en línea, respecto al uso de las redes ociales, Fear of Missing Out (FOMO), Necesidades psicológicas básicas, Auto-estima y Vulnerabilidad en línea. El análisis de correlaciones mostró una relación positiva entre el FOMO, la Vulnerabilidad en línea y la Adicción a redes sociales. Los resultados evidenciaron que las mujeres tienen mayores niveles de adicción a redes sociales y de necesidad de apoyo. El análisis de regresión mostró que el FOMO es el mejor predictor de la Adicción a redes sociales. Finalmente, se discuten las repercusiones en el ámbito educativo de los resultados.Apesar da crescente pesquisa sobre as redes sociais, as associações entre o abuso destas plataformas, o fenômeno do Fear of Missing Out (FOMO) e da Vulnerabilidade Online foram pouco estudadas. Esta investigação destina-se a proporcionar um quadro de atitudes e comportamentos relacionados com a utilização das redes sociais em jovens universitários. Neste estudo, a amostra foi composta por 306 universitários de 18 a 30 anos (152 mulheres; idade média = 21,8; desvio padrão = 3.19) e respondeu a um questionário on-line sobre o uso das redes sociais, Fear of Missing Out (FOMO), Necessidades psicológicas básicas, Auto-estima e Vulnerabilidade online. A análise de correlação mostrou uma relação positiva entre o FOMO, a Vulnerabilidade online e a dependencia de redes sociais. Os resultados mostraram que as mulheres têm um nível mais alto de dependência de redes sociais e de necessidade de apoio. A análise de regressão mostrou que o FOMO é o melhor preditor da Dependencia de redes sociais. Finalmente, discutem-se as implicações em âmbito educativo dos resultados

From human Megakaryocytes to platelets: Effects of aspirin on high-mobility group Box 1/receptor for advanced glycation end products axis

Platelets (PLTs) are the major source of high-mobility group box 1 (HMGB1), a protein that is involved in sterile inflammation of blood vessels and thrombosis. Megakaryocytes (MKs) synthesize HMGB1 and transfer both protein and mRNA into PLTs and PLT-derived microvesicles (MV). Free HMGB1 found in supernatants of in vitro differentiated MKs and in a megakaryoblastic cell line (DAMI cells). Aspirin “in vivo” and “in vitro” not only reduces HMGB1 and receptor for advanced glycation end products expression on MKs and PLTs but also drives the movement of HMGB1 from MKs into PLTs and PLT-derived MV. These findings suggest that consumption of low doses of aspirin reduces the risk of atherosclerosis complications as well as reducing PLT aggregation by the inhibition of COX-1

Novel 1,3-thiazolidin-4-one derivatives as promising anti-Candida agents endowed with anti-oxidant and chelating properties

Pursuing our recent outcomes regarding the antifungal activity of N-substituted 1,3-thiazolidin-4-ones, we synthesized thirty-six new derivatives introducing aliphatic, cycloaliphatic and heteroaromatic moieties at N1-hydrazine connected with C2 position of the thiazolidinone nucleus and functionalizing the lactam nitrogen with differently substituted (NO2, NH2, Cl and F) benzyl groups. These compounds were tested to evaluate their minimum inhibitory concentration (MIC) against several clinical Candida spp. with respect to topical and systemic reference drugs (clotrimazole, fluconazole, ketoconazole, mi- conazole, tioconazole, amphotericin B). Moreover, anti-oxidant properties were also evaluated by using different protocols including free radical scavenging (DPPH and ABTS), reducing power (CUPRAC and FRAP), metal chelating and phosphomolybdenum assays. Moreover, for the most active derivatives we assessed the toxicity (CC50) against Hep2 human cells in order to characterize them as multi-target agents for fungal infections

O ensino de língua portuguesa e os universais musicais: uma amostragem de prática interpretativa

Esse trabalho é parte de um projeto de pesquisa desenvolvido em doutoramento em Língua Portuguesa eLínguística do Programa de Pós-graduação em Letras da PUC Minas, que visa compreender e discutir a utilização dos universais musicais – ritmo e melodia – como ferramentas no ato interpretativo de um texto, potencializando a compreensão do mesmo. A interpretação textual é uma prática de linguagem. O trabalho de compreender um texto ultrapassa o domínio do sujeito comunicante e do sujeito interpretante. Patrick Chauredau (2008) afirma que a encenação discursiva é condição primordial para comunicação. Segundo Chauredeau (2008) o ato de linguagem é composto de vários sujeitos – Euc - EUe/ Tui -TUd – e que comunicar é proceder a uma encenação. Para este trabalho pretende-se limitar a pesquisa a dois desses sujeitos comunicantes, respectivamente: TUi-TUd, encenados pelo sujeito interpretante no ato comunicativo. Pretende-se apresentar uma parte dessa pesquisa que tem por eixo as abordagens experencialista e corporificada, afirmando que a construção de sentido depende da interação de trêsdimensões: cérebro, corpo em ação e interação organismo-ambiente. Tem-se a hipótese de que ao utilizar dos universais musicais no ato da interpretação TUi-TUd constroem-se esquemas imagéticos, por meio dos quais TUi-TUd experencia o mundo. Para tanto, baseia-se na Teoria da Integração Experencial (AUCHLIN, 2003) em que se integram dois espaços de entrada: o experencial sensório-motor e a elaboração linguística e o Modelo Semiótico de Brandt (2005), em que o espaço-base é discursivo, pois é construído a partir do “ato de dizer e aquilo que é dito”. Tentar-se-á integrar ambos os modelos para apresentar um modelo próprio de análise e confirmar a hipótese que rege  esse trabalho