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

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

Prevalence and risk factors for atopic disease in a population of preschool children in Rome: Challenges to early intervention

Background: Allergic diseases are complex identities determined by an interplay of genetic and environmental factors, resulting in the clinical manifestation of the disease. So far in Italy, updated data about the prevalence and risk factors of respiratory and allergic diseases in preschool children are not available. Methods: Children aged 3-5 years, attending four different nursery schools in an urban district of the city of Rome. A standardized questionnaire developed under the SIDRIA-2 protocol was administered to the parents of the children for the assessment of the potential risk factors and the outcomes. Results: A total of 494 children were enrolled in the study; 289 of them (60.3%) performed a skin prick test (SPT). In the 12 months preceding the interviews, 15% of children experienced at least one episode of wheezing, 5.5% of allergic rhinitis, 11% of children had a doctor diagnosis of asthma, 12% of children who underwent the SPT were positive to at least one of the tested allergens, being diagnosed as atopic. The univariate analysis for the health outcomes of the study shows that asthma was positively associated with daycare attendance, mother's history of atopy, siblings' history of atopy, recurrent siblings' bronchitis, and dermatitis. Atopy was positively associated with mother's history of atopy and dermatitis, whereas there is a borderline protective association with recurrent siblings' bronchitis. Conclusions: This study represents a first comprehensive epidemiological evaluation of prevalence of respiratory and allergic diseases in children aged 3-5 years in the city of Rome and an updating of the evolution of allergic diseases

CONGENITAL DIAPHRAGMATIC HERNIA AND ESOPHAGEAL ATRESIA: THE IMPORTANCE OF RESPIRATORY FOLLOW-UP IN CONGENITAL THORACIC MALFORMATION

Esophageal atresia, congenital diaphragmatic hernia, pulmonary function test, respiratory morbidity, Long-term follow-u

Cardiorespiratory fitness and sports activities in children and adolescents with solitary functioning kidney

Background: An increasing number of children with chronic disease require a complete medical examination to be able to practice physical activity. Particularly children with solitary functioning kidney (SFK) need an accurate functional evaluation to perform sports activities safely. The aim of our study was to evaluate the influence of regular physical activity on the cardiorespiratory function of children with solitary functioning kidney. Method: Twenty-nine patients with congenital SFK, mean age 13.9 ± 5.0 years, and 36 controls (C), mean age 13.8 ± 3.7 years, underwent a cardiorespiratory assessment with spirometry and maximal cardiopulmonary exercise testing. All subjects were divided in two groups: sedentary (S) and trained (T) patients, by means of a standardized questionnaire about their weekly physical activity. Results: We found that mean values of maximal oxygen consumption (VO2max) and exercise time (ET) were higher in T subjects than in S subjects. Particularly SFK-T presented mean values of VO2max similar to C-T and significantly higher than C-S (SFK-T: 44.7 ± 6.3 vs C-S: 37.8 ± 3.7 ml/min/kg; p < 0.0008). We also found significantly higher mean values of ET (minutes) in minutes in SFK-T than C-S subjects (SFK-T: 12.9 ± 1.6 vs C-S: 10.8 ± 2.5 min; p <0.02). Conclusion: Our study showed that regular moderate/high level of physical activity improve aerobic capacity (VO2max) and exercise tolerance in congenital SFK patients without increasing the risks for cardiovascular accidents and accordingly sports activities should be strongly encouraged in SFK patients to maximize health benefit

Hydrolyzed rice formula. an appropriate choice for the treatment of cow’s milk allergy

Cow’s milk allergy (CMA) is a common condition in the pediatric population. CMA can induce a diverse range of symptoms of variable intensity. It occurs mainly in the first year of life, and if the child is not breastfed, hypoallergenic formula is the dietary treatment. Extensively hydrolyzed cow’s milk formulas (eHF) with documented hypo-allergenicity can be recommended as the first choice, while amino acid-based formulas (AAF) are recommended for patients with more severe symptoms. Hydrolyzed rice-based formulas (HRFs) are a suitable alternative for infants with CMA that cannot tolerate or do not like eHF and in infants with severe forms of CMA. In the present paper, we reviewed the nutritional composition of HRFs as well as studies regarding their efficacy and tolerance in children, and we provided an updated overview of the recent evidence on the use of HRFs in CMA. The available studies provide evidence that HRFs exhibit excellent efficacy and tolerance and seem to be adequate in providing normal growth in healthy children as well as in children with CMA

An overview on the primary factors that contribute to non-allergic asthma in children

The prevalence of non-allergic asthma in childhood is low, peaking in late adulthood. It is triggered by factors other than allergens, like cold and dry air, respiratory infections, hormonal changes, smoke and air pollution. In the literature, there are few studies that describe non-allergic asthma in pediatric age. Even though it is a less common disorder in kids, it is crucial to identify the causes in order to keep asthma under control, particularly in patients not responding to conventional treatments. In this review, we discuss non-IgE-mediated forms of asthma, collecting the latest research on etiopathogenesis and treatment

The GOODSTEP project: General Object-Oriented Database for Software Engineering Processes

The goal of the GOODSTEP project is to enhance and improve the functionality of a fully object-oriented database management system to yield a platform suited for applications such as software development environments (SDEs). The baseline of the project is the O2 database management system (DBMS). The O2 DBMS already includes many of the features regulated by SDEs. The project has identified enhancements to O2 in order to make it a real software engineering DBMS. These enhancements are essentially upgrades of the existing O2 functionality, and hence require relatively easy extensions to the O2 system. They have been developed in the early stages of the project and are now exploited and validated by a number of software engineering tools built on top of the enhanced O2 DBMS. To ease tool construction, the GOODSTEP platform encompasses tool generation capabilities which allow for generation of integrated graphical and textual tools from high-level specifications. In addition, the GOODSTEP platform provides a software process toolset which enables modeling, analysis and enaction of software processes and is also built on top of the extended O2 database. The GOODSTEP platform is to be validated using two CASE studies carried out to develop an airline application and a business application

Vernal Keratoconjunctivitis: an update focused on clinical grading system

Vernal keratoconjunctivitis (VKC) is a severe disease with a prevalence of &lt; 1 case out of 10,000 in Europe, which occurs mainly in pediatric age and is characterized by a severe and often bilateral chronic inflammation of the ocular surface. The diagnosis is generally confirmed by the finding at the ocular examination of conjunctival hyperemia, papillary hypertrophy in the tarsal conjunctiva, giant papillae, papillae in the limbus region