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

Nitric oxide alleviates cadmium- but not arsenic-induced damages in rice roots

Nitric oxide (NO) has signalling roles in plant stress responses. Cadmium (Cd) and arsenic (As) soil pollutants alter plant development, mainly the root-system, by increasing NO-content, triggering reactive oxygen species (ROS), and forming peroxynitrite by NO-reaction with the superoxide anion. Interactions of NO with ROS and peroxynitrite seem important for plant tolerance to heavy metal(oid)s, but the mechanisms underlying this process remain unclear. Our goal was to investigate NO-involvement in rice (Oryza sativa L.) root-system after exposure to Cd or As, to highlight possible differences in NO-behaviour between the two pollutants. To the aim, morpho-histological, chemical and epifluorescence analyses were carried out on roots of different origin in the root-system, under exposure to Cd or As, combined or not with sodium nitroprusside (SNP), a NO-donor compound. Results show that increased intracellular NO levels alleviate the root-system alterations induced by Cd, i.e., inhibition of adventitious root elongation and lateral root formation, increment in lignin deposition in the sclerenchyma/endodermis cell-walls, but, even if reducing As-induced endodermis lignification, do not recover the majority of the As-damages, i.e., enhancement of AR-elongation, reduction of LR-formation, anomalous tissue-proliferation. However, NO decreases both Cd and As uptake, without affecting the pollutants translocation-capability from roots to shoots. Moreover, NO reduces the Cd-induced, but not the As-induced, ROS levels by triggering peroxynitrite production. Altogether, results highlight a different behaviour of NO in modulating rice root-system response to the toxicity of the heavy metal Cd and the metalloid As, which depends by the NO-interaction with the specific pollutant

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

Measles among healthcare workers in Italy. Is it time to act?

Vaccination of healthcare workers (HCWs) against measles is strongly recommended in Europe. In this study, we examined the impact of measles on Italian HCWs by systematically and quantitatively analyzing measles cases involving HCWs over time and by identifying the epidemiological characteristics of the respective measles outbreaks. We retrieved data on measles cases from the Italian national integrated measles and rubella surveillance system from January 2013 to May 2019. Additionally, we performed a systematic review of the literature and an analysis of the measles and rubella aggregate outbreaks reporting forms from 2014 to 2018. Our review suggests that preventing measles infection among HCWs in disease outbreaks may be crucial for the elimination of measles in Italy. National policies aiming to increase HCW immunization rates are fundamental to the protection of HCWs and patients, will limit the economic impact of outbreaks on the institutions affected and will help achieve the elimination goal

Status and perspectives of the neutron time-of-flight facility n_TOF at CERN

The neutron time-of-flight facility of CERN, called n TOF, started its operation in 2001, and since then it plays a major role in the field of neutron cross-section measurements. The two beam-lines available provide an excellent combination of good energy resolution and high instantaneous neutron flux, combining the time-of-flight method with a powerful neutron spallation source. So far, a large number of experiments has been performed on a variety of isotopes of interest for nuclear astrophysics, advanced nuclear technologies, nuclear medicine, and for basic nuclear physics. After the CERN long shutdown, a new phase of data taking is planned to start in 2021. The R&D of a new spallation target is ongoing and its upgrade will bring important improvements in both beam lines, allowing the n TOF Collaboration to perform new, challenging measurements

How to improve the distribution maps of habitat types at national scale

Annex I habitat types are a key factor for biodiversity conservation in Europe and distribution maps are essential for assessing their conservation status. We aim to increase the responsiveness to habitat knowledge needs and to propose the use of data collected at local scale for assessing a key indicator such as the Area of Occupancy (AOO) of habitats. In this paper, starting from the 4th Report of Habitats Directive data, we present a multi-source approach that allows national habitat distribution maps to be refined and their AOO estimated, by combining certified available information on habitat maps and vegetation databases. For the first time a comprehensive up-to-date knowledge on habitat distribution at national scale is now available; our approach will be an essential tool for the implementation of the Habitats Directive and to achieve the goals of EU biodiversity strategy in Italy

FIB/SEM and SEM/EDS microstructural analysis of metal-ceramic and zirconia-ceramic interfaces

Recently introduced FIB/SEM analysis in microscopy seems to provide a high-resolution characterization of the samples by 3D (FIB) cross-sectioning and (SEM) high resolution imaging. The aim of this study was to apply the FIB/SEM and SEM/EDS analysis to the interfaces of a metal-ceramic vs. two zirconiaceramic systems. Plate samples of three different prosthetic systems were prepared in the dental lab following the manufacturers’ instructions, where metal-ceramic was the result of a ceramic veneering (porcelain-fused-tometal) and the two zirconia- ceramic systems were produced by the dedicated CAD-CAM procedures of the zirconia cores (both with final sintering) and then veneered by layered or heat pressed ceramics. In a FIB/SEM equipment (also called DualBeam), a thin layer of platinum (1μm) was deposited on samples surface crossing the interfaces, in order to protect them during milling. Then, increasingly deeper trenches were milled by a focused ion beam, first using a relatively higher and later using a lower ion current (from 9 nA to 0.28 nA, 30KV). Finally, FEG-SEM (5KV) micrographs (1000–50,000X) were acquired. In a SEM the analysis of the morphology and internal microstructure was performed by 13KV secondary and backscattered electrons signals (in all the samples). The compositional maps were then performed by EDS probe only in the metal-ceramic system (20kV). Despite the presence of many voids in all the ceramic layers, it was possible to identify: (1) the grain structures of the metallic and zirconia substrates, (2) the thin oxide layer at the metalceramic interface and its interactions with the first ceramic layer (wash technique), (3) the roughness of the two different zirconia cores and their interactions with the ceramic interface, where the presence of zirconia grains in the ceramic layer was reported in two system possibly due to sandblasting before ceramic firing

Phosphodiesterase inhibitors: Could they be beneficial for the treatment of COVID-19?

In March 2020, the World Health Organization declared the severe acute respiratory syndrome corona virus 2 (SARS-CoV2) infection to be a pandemic disease. SARS-CoV2 was first identified in China and, despite the restrictive measures adopted, the epidemic has spread globally, becoming a pandemic in a very short time. Though there is growing knowledge of the SARS-CoV2 infection and its clinical manifestations, an effective cure to limit its acute symptoms and its severe complications has not yet been found. Given the worldwide health and economic emergency issues accompanying this pandemic, there is an absolute urgency to identify effective treatments and reduce the post infection outcomes. In this context, phosphodiesterases (PDEs), evolutionarily conserved cyclic nucleotide (cAMP/cGMP) hydrolyzing enzymes, could emerge as new potential targets. Given their extended distribution and modulating role in nearly all organs and cellular environments, a large number of drugs (PDE inhibitors) have been developed to control the specific functions of each PDE family. These PDE inhibitors have already been used in the treatment of pathologies that show clinical signs and symptoms completely or partially overlapping with post-COVID-19 conditions (e.g., thrombosis, inflammation, fibrosis), while new PDE-selective or pan-selective inhibitors are currently under study. This review discusses the state of the art of the different pathologies currently treated with phosphodiesterase inhibitors, highlighting the numerous similarities with the disorders linked to SARS-CoV2 infection, to support the hypothesis that PDE inhibitors, alone or in combination with other drugs, could be beneficial for the treatment of COVID-19

Enhanced composite plate impact damage detection and characterisation using X-Ray refraction and scattering contrast combined with ultrasonic imaging

Ultrasonic imaging and radiography are widely used in the aerospace industry for non-destructive evaluation of damage in fibre-reinforced composites. Novel phase-based X-ray imaging methods use phase effects occurring in inhomogeneous specimens to extract additional information and achieve improved contrast. Edge Illumination employs a coded aperture system to extract refraction and scattering driven signals in addition to conventional absorption. Comparison with ultrasonic immersion C-scan imaging and with a commercial X-ray CT system for impact damage analysis in a small cross-ply carbon fibre-reinforced plate sample was performed to evaluate the potential of this new technique. The retrieved refraction and scattering signals provide complementary information, revealing previously unavailable insight on the damage extent and scale, not observed in the conventional X-ray absorption and ultrasonic imaging, allowing improved damage characterisation

From Data to Phenomena: A Kantian Stance

This paper investigates some metaphysical and epistemological assumptions behind Bogen and Woodward's data-to-phenomena inferences. I raise a series of points and suggest an alternative possible Kantian stance about data-to-phenomena inferences. I clarify the nature of the suggested Kantian stance by contrasting it with McAllister's view about phenomena as patterns in data sets