Zika Virus: A New Therapeutic Candidate for Glioblastoma Treatment

Glioblastoma (GBM) is the most aggressive among the neurological tumors. At present, no chemotherapy or radiotherapy regimen is associated with a positive long-term outcome. In the majority of cases, the tumor recurs within 32–36 weeks of initial treatment. The recent discovery that Zika virus (ZIKV) has an oncolytic action against GBM has brought hope for the development of new therapeutic approaches. ZIKV is an arbovirus of the Flaviviridae family, and its infection during development has been associated with central nervous system (CNS) malformations, including microcephaly, through the targeting of neural stem/progenitor cells (NSCs/NPCs). This finding has led various groups to evaluate ZIKV’s effects against glioblastoma stem cells (GSCs), supposedly responsible for GBM onset, progression, and therapy resistance. While preliminary data support ZIKV tropism toward GSCs, a more accurate study of ZIKV mechanisms of action is fundamental in order to launch ZIKV-based clinical trials for GBM patients.     

A Comparative Analysis of Global and Local Processing of Hierarchical Visual Stimuli in Young Children (Homo sapiens) and Monkeys (Cebus apella).

Results obtained with preschool children (Homo sapiens) were compared with results previously obtained from capuchin monkeys (Cebus apella) in matching-to-sample tasks featuring hierarchical visual stimuli. In Experiment 1, monkeys, in contrast with children, showed an advantage in matching the stimuli on the basis of their local features. These results were replicated in a 2nd experiment in which control trials enabled the authors to rule out that children used spurious cues to solve the matching task. In a 3rd experiment featuring conditions in which the density of the stimuli was manipulated, monkeys' accuracy in the processing of the global shape of the stimuli was negatively affected by the separation of the local elements, whereas children's performance was robust across testing conditions. Children's response latencies revealed a global precedence in the 2nd and 3rd experiments. These results show differences in the processing of hierarchical stimuli by humans and monkeys that emerge early during childhood. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Protective Role of Prolyl Oligopeptidase (POP) Inhibition in Kidney Injury Induced by Renal Ischemia–Reperfusion

Ischemia/reperfusion injury (IRI) is a complex pathophysiological process characterized by blood circulation disorder caused by various factors, such as traumatic shock, surgery, organ transplantation, and thrombus. Severe metabolic dysregulation and tissue structure destruction are observed upon restoration of blood flow to the ischemic tissue. The kidney is a highly perfused organ, sensitive to ischemia and reperfusion injury, and the incidence of renal IRI has high morbidity and mortality. Several studies showed that infiltration of inflammatory cells, apoptosis, and angiogenesis are important mechanisms involved in renal IRI. Despite advances in research, effective therapies for renal IRI are lacking. Recently it has been demonstrated the role of KYP2047, a selective inhibitor of prolyl oligopeptidase (POP), in the regulation of inflammation, apoptosis, and angiogenesis. Thus, this research focused on the role of POP in kidney ischemia/reperfusion (KI/R). An in vivo model of KI/R was performed and mice were subjected to KYP2047 treatment (intraperitoneal, 0.5, 1 and 5 mg/kg). Histological analysis, Masson’s trichrome and periodic acid shift (PAS) staining, immunohistochemical and Western blots analysis, real-time PCR (RT-PCR) and ELISA were performed on kidney samples. Moreover, serum creatinine and blood urea nitrogen (BUN) were quantified. POP-inhibition by KYP2047 treatment, only at the doses of 1 and 5 mg/kg, significantly reduced renal injury and collagen amount, regulated inflammation through canonical and non-canonical NF-κB pathway, and restored renal function. Moreover, KYP2047 modulated angiogenesis markers, such as TGF-β and VEGF, also slowing down apoptosis. Interestingly, treatment with KYP2047 modulated PP2A activity. Thus, these findings clarified the role of POP inhibition in AKI, also offering novel therapeutic target for renal injury after KI/R.     

CD44, γ-H2AX,and p-ATM Expressions in Short-Term Ex Vivo Culture of Tumour Slices Predict the Treatment Response in Patients with Oral Squamous Cell Carcinoma

Squamous cell carcinoma is the most common type of head and neck cancer (HNSCC) with a disease-free survival at 3 years that does not exceed 30%. Biomarkers able to predict clinical outcomes are clearly needed. The purpose of this study was to investigate whether a short-term culture of tumour fragments irradiated ex vivo could anticipate patient responses to chemo- and/or radiotherapies. Biopsies were collected prior to treatment from a cohort of 28 patients with non-operable tumours of the oral cavity or oropharynx, and then cultured ex vivo. Short-term biopsy slice culture is a robust method that keeps cells viable for 7 days. Different biomarkers involved in the stemness status (CD44) or the DNA damage response (pATM and γ-H2AX) were investigated for their potential to predict the treatment response. A higher expression of all these markers was predictive of a poor response to treatment. This allowed the stratification of responder or non-responder patients to treatment. Moreover, the ratio for the expression of the three markers 24 h after 4 Gy irradiation versus 0 Gy was higher in responder than in non-responder patients. Finally, combining these biomarkers greatly improved their predictive potential, especially when the γ-H2AX ratio was associated with the CD44 ratio or the pATM ratio. These results encourage further evaluation of these biomarkers in a larger cohort of patients.     

Cavitation-driven Deformable Microchambers Inspired by Fast Microscale Movements of Ferns

Annulus cells of fern sporangia spontaneously deform driven by water transpiration and cavitation, resulting in the peculiar macroscale catapult-like movement of the sporangium. Annulus cells' behavior, if artificially replicated, can inspire a novel class of fast actuators composed of annulus-mimicking units. However, the transpiration and cavitation-driven dynamics observed in annulus cells is never reproduced. Here, prismatic microcavities are assembled with a polydimethylsiloxane (PDMS) microfilm to realize artificial microchambers that mimic the annulus cells, replicating for the first time their evaporation-driven collapse and their fast return triggered by the nucleation of bubbles. The microchambers, in turn, can be fabricated in adjacency, resulting in bending arrays driven by transpiration. Working with an artificial system allows this study to investigate the fluidic phenomena arising from the interplay of a soft, semi-permeable membrane with a micro-confined liquid bounded by rigid walls. First, the microchambers aspect ratio influences the membrane dynamics and the bubble shape (either spherical or non-spherical). Second, the growth rate of the bubble interplay with the membrane in the expansion dynamics. This study's results demonstrate the artificial replication of annulus cells' behavior, offering a plant-like solution to realize fast, microscale movements, and a novel tool to investigate complex fluidic mechanisms involving micro-confined cavitation.     

Microbial inactivation by high pressure homogenization: Effect of the disruption valve geometry

Microbial inactivation by high pressure homogenization (HPH) was studied in two very different disruption chambers, one based on a piston micrometric valve and the other on an orifice valve, in order to relate the geometrical and fluid dynamics aspects with the rate of death of Escherichia coli, Lactobacillus delbrueckii and Saccharomyces cerevisiae.     

Improving In Vitro Detection of Sensitization to Lipid Transfer Proteins: A New Molecular Multiplex IgE Assay

Scope

LTP-syndrome is characterized by sensitization (IgE) to multiple non-specific lipid transfer proteins (nsLTPs) with a variable clinical outcome. The treatment is primarily based on offending food avoidance. However, the determination of Pru p 3-specific IgE is currently the main diagnostic tool to assess sensitization to nsLTPs. Herein, the study evaluates improvement of LTP-syndrome diagnosis and clinical management using a new IgE multiplex-immunoblot assay with a high diversity of food nsLTPs.

Methods and results

An EUROLINE-LTP strip with 28 recombinant nsLTPs from 18 allergenic sources is designed. In total the study investigates 38 patients with LTP-syndrome and compares results from the nsLTPs (LTP-strip) with the respective food extracts of Prick-by-prick (PbP) testing. The agreement exceeds 70% for most nsLTPs, e.g., Pru p 3 (100%), Mal d 3 (97%), Pru av 3 (89%), Pha v 3 isoforms (87%/84%), Ara h 9 (82%), Cor a 8 (82%), and Jug r 3 (82%). The functionality and allergenic relevance of nine recombinant nsLTPs are proven by Basophil activation testing (BAT).

Conclusions

The new IgE multiplex-immunoblot nsLTP assay shows a good diagnostic performance allowing culprit food assessment. Negative results from LTP-strip may indicate potentially tolerable foods, improving diet intervention and patients’ quality of life.     

Nanoencapsulation systems to improve solubility and antioxidant efficiency of a grape marc extract into hazelnut paste

Encapsulation of a phenolic grape marc extract to enhance its lipid solubility and antioxidant efficiency for application as a natural preserving agent of hazelnut paste was investigated. Three nanoemulsion based encapsulation systems were tested: an oil/water nanoemulsion; a powder obtained by maltodextrin-assisted spray-drying of the previous and an ethanol/solid–lipid nanoemulsion (the third also applied to resveratrol for comparison). All the samples were mixed with hazelnut paste at different phenolic concentrations (from 1200 to less than 10 ppm of gallic acid equivalents for the original and encapsulated extracts, respectively). An accelerated shelf-life test at 60 °C was carried out until 59 and 98 days (for the original and encapsulated extracts, respectively) with peroxides value monitoring. Paste oxidation followed a first-order kinetics model and was significantly inhibited by extract addition. Encapsulation improved phenolic efficiency against lipid oxidation, by increasing extract dispersability in the paste and preserving the antioxidant activity, with the oil/water nanoemulsion resulting as the best system.     

Criteria and methodologies for determining the causes of swelling of canned tomatoes in tinplate containers

This review provides the current laboratory criteria for the detection and evaluation of the possible causes of alteration of non-concentrated industrial derivatives of tomatoes (peeled tomatoes, pulps, purees, sauces, and fillets), packaged in coated or uncoated tinplate cans. We discuss how the product alterations are typically the consequence of technological errors either in the can production, or in the storage process, or in the product sterilization. The described procedures include the quantitative determination of the distribution of gases (H₂, CO₂, N₂, and O₂) present in the headspace of the container. The gas composition and ratios can be used as markers to allow easy diagnosis of the causes of microbiologic and/or physical–chemical alterations of the tomatoes, which are usually made evident by swelling of the containers. These tests should be integrated by microbiological analyses aimed at a restricted group of microorganisms, with the chemical analysis of the container and the chemical analysis of the altered product. By way of example, we report the assessment of the causes of alteration in four different case-studies.     

A set‐oriented method definition language for object databases and its semantics

In this paper we propose a set‐oriented rule‐based method definition language for object‐oriented databases. Most existing object‐oriented database systems exploit a general‐purpose imperative object‐oriented programming language as the method definition language. Because methods are written in a general‐purpose imperative language, it is difficult to analyze their properties and to optimize them. Optimization is important when dealing with a large amount of objects as in databases. We therefore believe that the use of an ad hoc, set‐oriented language can offer some advantages, at least at the specification level. In particular, such a language can offer an appropriate framework to reason about method properties. In this paper, besides defining a set‐oriented rule‐based language for method definition, we formally define its semantics, addressing the problems of inconsistency and non‐determinism in set‐oriented updates. Moreover, we characterize some relevant properties of methods, such as conflicts among method specifications in sibling classes and behavioral refinement in subclasses. Copyright © 2003 John Wiley & Sons, Ltd.