Evaluation of two different Cannabis sativa extracts as antioxidant and neuroprotective agents

Cannabis sativa L. is a plant that contains numerous chemically active compounds including cannabinoids such as trans-Δ-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), and flavone derivatives, such as luteolin-7-O-glucuronide and apigenin glucuronide. In particular, the polar fraction of hemp including many phenolic compounds has been overlooked when compared with the more lipophilic fraction containing cannabinoids. Therefore, the aim of this study was to assess two extracts of industrial hemp (C. sativa) of different polarity (aqueous and hexane) by evaluating their antioxidant profile and their neuroprotective potential on pharmacological targets in the central nervous system (CNS). Several assays on in vitro antioxidant capacity (DPPH, superoxide radical, FRAP, ORAC), as well as inhibition of physiological enzymes such as acetylcholinesterase (AChE) and monoaminooxidase A (MAO-A) were carried out in order to find out how these extracts may be helpful to prevent neurodegenerative disorders. Neuro-2a cell line was selected to test the cytotoxic and neuroprotective potential of these extracts. Both extracts showed striking antioxidant capacity in the FRAP and ORAC assays, particularly the hexane extract, and interesting results for the DPPH and superoxide radical uptake assays, with the aqueous extract standing out especially in the latter. In enzyme inhibition assays, the aqueous extract showed AChE and MAO-A inhibitory activity, while the hexane extract only reached IC50 value for AChE inhibitory bioassay. Neuro-2a assays demonstrated that polyphenolic extract was not cytotoxic and exhibited cytoprotective properties against hydrogen peroxide and antioxidant response decreasing reactive oxygen species (ROS) production. These extracts could be a source of compounds with potential benefit on human health, especially related to neurodegenerative disorders

Management of pandemic influenza A (H1N1) 2009 in the major University Hospital of Sicily

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Predictive and Prognostic Molecular Factors in Diffuse Large B-Cell Lymphomas

Diffuse large B-cell lymphoma (DLBCL) is the commonest form of lymphoid malignancy, with a prevalence of about 40% worldwide. Its classification encompasses a common form, also termed as "not otherwise specified" (NOS), and a series of variants, which are rare and at least in part related to viral agents. Over the last two decades, DLBCL-NOS, which accounts for more than 80% of the neoplasms included in the DLBCL chapter, has been the object of an increasing number of molecular studies which have led to the identification of prognostic/predictive factors that are increasingly entering daily practice. In this review, the main achievements obtained by gene expression profiling (with respect to both neoplastic cells and the microenvironment) and next-generation sequencing will be discussed and compared. Only the amalgamation of molecular attributes will lead to the achievement of the long-term goal of using tailored therapies and possibly chemotherapy-free protocols capable of curing most (if not all) patients with minimal or no toxic effects

Jolie community on the rise

© 2016 IEEE.Jolie is a programming language that follows the microservices paradigm. As an open source project, it has built a community of developers worldwide - both in the industry as well as in academia - taken care of the development, continuously improved its usability, and therefore broadened the adoption. In this paper, we present some of the most recent results and work in progress that has been made within our research team

Materials with Colossal Dielectric Constant: Do They Exist?

Experimental evidence is provided that colossal dielectric constants, epsilon >= 1000, sometimes reported to exist in a broad temperature range, can often be explained by Maxwell-Wagner type contributions of depletion layers at the interface between sample and contacts, or at grain boundaries. We demonstrate this on a variety of different materials. We speculate that the largest intrinsic dielectric constant observed so far in non-ferroelectric materials is of order 100.Comment: 3 figure

Scn1a gene reactivation after symptom onset rescues pathological phenotypes in a mouse model of Dravet syndrome

Dravet syndrome is a severe epileptic encephalopathy caused primarily by haploinsufficiency of the SCN1A gene. Repetitive seizures can lead to endurable and untreatable neurological deficits. Whether this severe pathology is reversible after symptom onset remains unknown. To address this question, we generated a Scn1a conditional knock-in mouse model (Scn1a Stop/+) in which Scn1a expression can be re-activated on-demand during the mouse lifetime. Scn1a gene disruption leads to the development of seizures, often associated with sudden unexpected death in epilepsy (SUDEP) and behavioral alterations including hyperactivity, social interaction deficits and cognitive impairment starting from the second/third week of age. However, we showed that Scn1a gene re-activation when symptoms were already manifested (P30) led to a complete rescue of both spontaneous and thermic inducible seizures, marked amelioration of behavioral abnormalities and normalization of hippocampal fast-spiking interneuron firing. We also identified dramatic gene expression alterations, including those associated with astrogliosis in Dravet syndrome mice, that, accordingly, were rescued by Scn1a gene expression normalization at P30. Interestingly, regaining of Nav1.1 physiological level rescued seizures also in adult Dravet syndrome mice (P90) after months of repetitive attacks. Overall, these findings represent a solid proof-of-concept highlighting that disease phenotype reversibility can be achieved when Scn1a gene activity is efficiently reconstituted in brain cells

Dual targeting of the DNA damage response pathway and BCL-2 in diffuse large B-cell lymphoma

Standard chemotherapies for diffuse large B-cell lymphoma (DLBCL), based on the induction of exogenous DNA damage and oxidative stress, are often less effective in the presence of increased MYC and BCL-2 levels, especially in the case of double hit (DH) lymphomas harboring rearrangements of the MYC and BCL-2 oncogenes, which enrich for a patient’s population characterized by refractoriness to anthracycline-based chemotherapy. Here we hypothesized that adaptive mechanisms to MYC-induced replicative and oxidative stress, consisting in DNA damage response (DDR) activation and BCL-2 overexpression, could represent the biologic basis of the poor prognosis and chemoresistance observed in MYC/BCL-2-positive lymphoma. We first integrated targeted gene expression profiling (T-GEP), fluorescence in situ hybridization (FISH) analysis, and characterization of replicative and oxidative stress biomarkers in two independent DLBCL cohorts. The presence of oxidative DNA damage biomarkers identified a poor prognosis double expresser (DE)-DLBCL subset, characterized by relatively higher BCL-2 gene expression levels and enrichment for DH lymphomas. Based on these findings, we tested therapeutic strategies based on combined DDR and BCL-2 inhibition, confirming efficacy and synergistic interactions in in vitro and in vivo DH-DLBCL models. These data provide the rationale for precision-therapy strategies based on combined DDR and BCL-2 inhibition in DH or DE-DLBCL

Colossal dielectric constants in transition-metal oxides

Many transition-metal oxides show very large ("colossal") magnitudes of the dielectric constant and thus have immense potential for applications in modern microelectronics and for the development of new capacitance-based energy-storage devices. In the present work, we thoroughly discuss the mechanisms that can lead to colossal values of the dielectric constant, especially emphasising effects generated by external and internal interfaces, including electronic phase separation. In addition, we provide a detailed overview and discussion of the dielectric properties of CaCu3Ti4O12 and related systems, which is today's most investigated material with colossal dielectric constant. Also a variety of further transition-metal oxides with large dielectric constants are treated in detail, among them the system La2-xSrxNiO4 where electronic phase separation may play a role in the generation of a colossal dielectric constant.Comment: 31 pages, 18 figures, submitted to Eur. Phys. J. for publication in the Special Topics volume "Cooperative Phenomena in Solids: Metal-Insulator Transitions and Ordering of Microscopic Degrees of Freedom

Minor Keywords of Political Theory: Migration as a Critical Standpoint. A collaborative project of collective writing

Coordinated and Edited by: N De Genova, M Tazzioli Co-Authored by: Claudia Aradau, Brenna Bhandar, Manuela Bojadzijev, Josue David Cisneros, N De Genova, Julia Eckert, Elena Fontanari, Tanya Golash-Boza, Jef Huysmans, Shahram Khosravi, Clara Lecadet, Patrisia Macías-Rojas, Federica Mazzara, Anne McNevin, Peter Nyers, Stephan Scheel, Nandita Sharma, Maurice Stierl, Vicki Squire, M Tazzioli, Huub van Baar and William Walter

NR1H3 (LXRα) is associated with pro-inflammatory macrophages, predicts survival and suggests potential therapeutic rationales in diffuse large b-cell lymphoma

The role of macrophages (Mo) and their prognostic impact in diffuse large B-cell lymphomas (DLBCL) remain controversial. By regulating the lipid metabolism, Liver-X-Receptors (LXRs) control Mo polarization/inflammatory response, and their pharmacological modulation is under clinical investigation to treat human cancers, including lymphomas. Herein, we surveyed the role of LXRs in DLBCL for prognostic purposes. Comparing bulk tumors with purified malignant and normal B-cells, we found an intriguing association of NR1H3, encoding for the LXR-α isoform, with the tumor microenvironment (TME). CIBERSORTx-based purification on large DLBCL datasets revealed a high expression of the receptor transcript in M1-like pro-inflammatory Mo. By determining an expression cut-off of NR1H3, we used digital measurement to validate its prognostic capacity on two large independent on-trial and real-world cohorts. Independently of classical prognosticators, NR1H3high patients displayed longer survival compared with NR1H3low cases and a high-resolution Mo GEP dissection suggested a remarkable transcriptional divergence between subgroups. Overall, our findings indicate NR1H3 as a Mo-related biomarker identifying patients at higher risk and prompt future preclinical studies investigating its mouldability for therapeutic purposes