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

Building Process Management In Green Public Procurements

Today more than ever, the world of Public Procurement is regulated by a large and diverse body of law, constantly updated and enriched. The environmental issue is one of the subjects that is gaining more and more on the international level and so the new regulations of Procurement must consider it in its articles. The process, therefore, must meet the requirements of convenience, considering both time and costs, but also the quality of supply, which will be evaluated both on the basis of the design proposals (traditional requirements) and on the convenience of its life cycle (current requirements, LCC and LCA). The forecast period of each tender will be no more evaluated from the moment ("now"-the day of submission of the tender) but to the future ("then"-the ordinary value of the subject of the contract). The present study aims to determine the state of the art of the existing regulations and the current procedures for the award of public supply, to highlight what are the (new) criteria and the critical issues that follow their implementation; the goal is to determine whether the management of procurement actions, as we face today, is appropriate or not to the "green" needs and, if not, what new ways may configure

The effectiveness of an Intelligent System For Real-time Hygrothermal Management In Low Energy Buildings

This paper proposes an intelligent model for realtime control of the hygrothermal behaviour in low energy buildings. Through the management of information related to internal and external conditions combined with the design and context data, the built network lead to assess the correct strategy for an adequate hygrothermal behaviour (choosing between active and passive systems for control of indoor air-quality). The expected benefits are a healthy environment, the stable performances of materials, the containment of maintenance costs, the reduction of the use of passive systems in order to cut CO2 emissions

Eco-friendly physical activation methods for suzuki-miyaura reactions

Eco-compatible activation methods in Suzuki–Miyaura cross-coupling reactions offer challenging opportunities for the design of clean and efficient synthetic processes. The main enabling technologies described in the literature are microwaves, ultrasound, grinding (mechanochemistry) and light. These methods can be performed in water or other green solvents with phase-transfer catalysis or even in solventless conditions. In this review, the authors will summarize the progress in this field mainly from 2010 up to the present day

Hyperphosphatasia with mental retardation syndrome 3: Cerebrospinal fluid abnormalities and correction with pyridoxine and Folinic acid

Glycosylphosphatidylinositol anchored proteins (GPI-APs) represent a class of molecules attached to the external leaflet of the plasma membrane by the GPI anchor where they play important roles in numerous cellular processes including neurogenesis, cell adhesion, immune response and signalling. Within the group of GPI anchor defects, six present with the clinical phenotype of Hyperphosphatasia with Mental Retardation Syndrome (HPMRS, Mabry Syndrome) characterized by moderate to severe intellectual disability, dysmorphic features, hypotonia, seizures and persistent hyperphosphatasia. We report the case of a 5-year-old female with global developmental delay associated with precocious puberty and persistently raised plasma alkaline phosphatase. Targeted next generation sequencing analysis of the HPMRS genes identified novel compound heterozygous variants in the PGAP2 gene (c.103del p.(Leu35Serfs*90)and c.134A > Gp.(His45Arg)) consistent with the diagnosis of HPMRS type 3. Cerebrospinal fluid (CSF) neurotransmitter analysis showed low levels of pyridoxal phosphate and 5-methyltetrahydrofolate and raised homovanillic acid. Supplementation with pyridoxine and folinic acid led to normalization of biochemical abnormalities. The patient continues to make developmental progress with significant improvement in speech and fine motor skills. Our reported case expands the clinical spectrum of HPMRS3 in which multisystem involvement is being increasingly recognized. Furthermore, it shows that miss-targeting GPI-APs and the effect on normal cellular function could provide a physiopathologic explanation for the CSF biochemical abnormalities with management implications for a group of disorders that currently has no treatment that can lead possibly to improved clinical outcomes