Poly(ADP-ribosyl)ation is involved in the epigenetic control of TET1 gene transcription

TET enzymes are the epigenetic factors involved in the formation of the Sixth DNA base 5-hydroxymethylcytosine, whose deregulation has been associated with tumorigenesis. In particular, TET1 acts as tumor suppressor preventing cell proliferation and tumor metastasis and it has frequently been found down-regulated in cancer. Thus, considering the importance of a tight control of TET1 expression, the epigenetic mechanisms involved in the transcriptional regulation of TET1 gene are here investigated. The involvement of poly(ADP-ribosyl)ation in the control of DNA and histone methylation on TET1 gene was examined. PARP activity is able to positively regulate TET1 expression maintaining a permissive chromatin state characterized by DNA hypomethylation of TET1 CpG island as well as high levels of H3K4 trimethylation. These epigenetic modifications were affected by PAR depletion causing TET1 downregulation and in turn reduced recruitment of TET1 protein on HOXA9 target gene. In conclusion, this work shows that PARP activity is a transcriptional regulator of TET1 gene through the control of epigenetic events and it suggests that deregulation of these mechanisms could account for TET1 repression in cancer

Morphological and Biochemical Profiles of the Gonadal Cycle in the Sea Urchin Paracentrotus lividus: Wild Type vs. Bred

Paracentrotus lividus gonads represent a valued gourmet delicacy, particularly appreciated in Europe and in Japan. Their commercial value is generally associated to their size, freshness, colour and texture. Diet, gametogenesis and environmental conditions have a marked influence, promoting the indispensable mechanisms of synthesis, selective storage and mobilization of the bioactive compounds, as lipids, proteins and carbohydrates of gonads in order to obtain nutrients. The objective of this work is to compare the morphological and biochemical profiles of reproductive life cycle of the gonads of adult P. lividus in its marine natural environment and adult captured sea urchins breeding into a fish aquaculture system. The reproductive cycle of male and female wild and breeding P. lividus was characterized during 1 year by analysing variations of the gonadal content of lipids, proteins and carbohydrates of animals captured at four different locations of the south-western coast of Salento, Italy, with the animals grown in a fish farm and fed with four different types of diet. The gonadal and repletion indexes were determined before the specimen dissection for evaluation of sex, development stages and physiological aspects. Gonads were processed for histological and biochemical analysis. The gonadal content of lipids, proteins and carbohydrates was performed by the gas chromatography-mass spectrometry (GC-MS) and by spectrometry, respectively

The formulation of the N-Acetylglucosamine as nanoparticles increases its anti-inflammatory activities: an in vitro study

Nanomedicine can represent a new strategy to treat several types of diseases such as those with inflammatory aetiology. Through this strategy, it is possible to obtain nanoparticles with controlled shape, size, and eventually surface charge. Moreover, the use of molecules in nanoform may allow more effective delivery into the diseased cells and tissues, reducing toxicity and side effects of the used compounds. The aim of the present manuscript was the evaluation of the effects of N-acetylglucosamine in nanoform (GlcNAc NP) in an in vitro model of osteoarthritis (OA). Human primary chondrocytes were treated with Tumor Necrosis Factor (TNF)-α to simulate a low-grade inflammation and then treated with both GlcNAc and GlcNAc NP, in order to find the lowest concentrations able to counteract the inflammatory state of the cells and ensure a chondroprotective action. The findings showed that GlcNAc NP was able to decrease the pro-inflammatory mediators, IL-6 and IL-8, which are among the main effectors of inflammation; moreover, the nanoparticles downregulated the production of metalloprotease enzymes. GlcNAc NP was effective at a very low concentration compared to GlcNAc in its native form. Furthermore, GlcNAc NP stimulated an increase in collagen type II synthesis. In conclusion, the GlcNAc in nanoform showed better performance than GlcNAc, at concentrations lower than those reached in the joints after oral administration to patients of 1.5 g/die of glucosamine

Core-shell nano-architectures: the incorporation mechanism of hydrophobic nanoparticles into the aqueous core of a microemulsion

This work presents an in-depth investigation of the molecular interactions in the incorporation mechanism of colloidal hydrophobic-capped nanoparticles into the hydrophilic core of reverse microemulsions. 1H Nuclear Magnetic Resonance (NMR) was employed to obtain molecular level details of the interaction between the nanoparticles capping amphiphiles and the microemulsion surfactants. The model system of choice involved oleic acid (OAC) and oleylamine (OAM) as capping molecules, while igepal-CO520 was the surfactant. The former were studied both in their ‘‘free’’ state and ‘‘ligated’’ one, i.e., bound to nanoparticles. The latter was investigated either in cyclohexane (micellar solution) or in water/cyclohexane microemulsions. The approach was extremely useful to gain a deeper understanding of the equilibria involved in this complex system (oleic acid capped-Bi2S3 in igepal/water/cyclohexane microemulsions). In difference to previously proposed mechanisms, the experimental data showed that the high affinity of the capping ligands for the reverse micelle interior was the driving force for the incorporation of the nanoparticles. A simple ligand-exchange mechanism could be ruled out. The collected information about the nanoparticle incorporation mechanism is extremely useful to develop new synthetic routes with an improved/tuned coating efficiency, in order to tailor the core–shell structure preparation

Machine Learning-based Query Augmentation for SPARQL Endpoints

Linked Data repositories have become a popular source of publicly-available data. Users accessing this data through SPARQL endpoints usually launch several restrictive yet similar consecutive queries, either to find the information they need through trial-and-error or to query related resources. However, instead of executing each individual query separately, query augmentation aims at modifying the incoming queries to retrieve more data that is potentially relevant to subsequent requests. In this paper, we propose a novel approach to query augmentation for SPARQL endpoints based on machine learning. Our approach separates the structure of the query from its contents and measures two types of similarity, which are then used to predict the structure and contents of the augmented query. We test the approach on the real-world query logs of the Spanish and English DBpedia and show that our approach yields high-accuracy prediction. We also show that, by caching the results of the predicted (More)This work has been supported by the European Union's Horizon 2020 research and innovation program (grant H2020-MSCA-ITN-2014-642963), the Spanish Ministry of Science and Innovation (contract TIN2015-65316, project RTC-2016-4952-7 and contract TIN2016-78011-C4-4-R), the Spanish Ministry of Education, Culture and Sports (contract CAS18/00333) and the Generalitat de Catalunya (contract 2014-SGR-1051). The authors would also like to thank Toni Cortes for his feedback.Peer ReviewedPostprint (author's final draft

Vitiligo: A new side effect of everolimus therapy for metastatic renal cell carcinoma

Patients with metastatic renal cell carcinoma (mRCC) have always had a poor prognosis. Recently new targeted drugs were developed. A 73-year-old female patient affected from mRCC was assessed at our Department. She underwent before a multitargeted tyrosine kinase inhibitor (TKI) therapy, but she developed progressive liver metastases so she was treated after with everolimus, an allosteric inhibitor of the mammalian target of rapamycin (mTOR), but started developing depigmented lesions over the neck. Vitiligo is a common cutaneous disorder and drug-induced vitiligo is reported. Our case can suggest a new type of drug-induced vitiligo, caused by a melanocyte-specific mechanism of toxicity

Alternativas para el contenido de un curso en linea de precálculo

El presente artículo muestra algunos desarrollos iniciales del Massive Open Online Course (MOOC) que apoya al curso tradicional de precálculo. Los aspectos teórico metodológicos que se tomaron en cuenta para su elección descansan en los entorpecimientos y las confusiones que los profesores actores del proyecto han detectado en sus propios estudiantes. Un grupo multidisciplinario de académicos, han plasmado a través del MOOC una alternativa de ayuda para los alumnos, donde se plantean, reflexionan y resuelven problemas o ejercicios, los cuales se clasificaron en: introductorios, representativos, difíciles o confusos. Cuando se tenga un resultado parcial, se efectuará una experimentación con alguno de los temas, contrastando su eficacia con respecto a estudiantes que lo emplean y los que no lo usan. El producto final se comparará con grupos de dos instituciones educativas de Nivel Superior

Repositioned natural compounds and nanoformulations: a promising combination to counteract cell damage and inflammation in respiratory viral infections

Respiratory viral diseases are among the most important causes of disability, morbidity, and death worldwide. Due to the limited efficacy or side effects of many current therapies and the increase in antiviral-resistant viral strains, the need to find new compounds to counteract these infections is growing. Since the development of new drugs is a time-consuming and expensive process, numerous studies have focused on the reuse of commercially available compounds, such as natural molecules with therapeutic properties. This phenomenon is generally called drug repurposing or repositioning and represents a valid emerging strategy in the drug discovery field. Unfortunately, the use of natural compounds in therapy has some limitations, due to their poor kinetic performance and consequently reduced therapeutic effect. The advent of nanotechnology in biomedicine has allowed this limitation to be overcome, showing that natural compounds in nanoform may represent a promising strategy against respiratory viral infections. In this narrative review, the beneficial effects of some promising natural molecules, curcumin, resveratrol, quercetin, and vitamin C, which have been already studied both in native form and in nanoform, against respiratory viral infections are presented and discussed. The review focuses on the ability of these natural compounds, analyzed in in vitro and in vivo studies, to counteract inflammation and cellular damage induced by viral infection and provide scientific evidence of the benefits of nanoformulations in increasing the therapeutic potential of these molecules

PARP inhibitor ABT-888 affects response of MDA-MB-231 cells to doxorubicin treatment, targeting Snail expression

To overcome cancer cells resistance to pharmacological therapy, the development of new therapeutic approaches becomes urgent. For this purpose, the use of poly(ADP-ribose) polymerase (PARP) inhibitors in combination with other cytotoxic agents could represent an efficacious strategy. Poly(ADP-ribosyl)ation (PARylation) is a post-translational modification that plays a well characterized role in the cellular decisions of life and death. Recent findings indicate that PARP-1 may control the expression of Snail, the master gene of epithelial-mesenchymal transition (EMT). Snail is highly represented in different resistant tumors, functioning as a factor regulating anti-apoptotic programmes. MDA-MB-231 is a Snail-expressing metastatic breast cancer cell line, which exhibits chemoresistance properties when treated with damaging agents. In this study, we show that the PARP inhibitor ABT-888 was capable to modulate the MDA-MB-231 cell response to doxorubicin, leading to an increase in the rate of apoptosis. Our further results indicate that PARP-1 controlled Snail expression at transcriptional level in cells exposed to doxorubicin. Given the increasing interest in the employment of PARP inhibitors as chemotherapeutic adjuvants, our in vitro results suggest that one of the mechanisms through which PARP inhibition can chemosensitize cancer cells in vivo, is targeting Snail expression thus promoting apoptosi