miR-210: More than a silent player in hypoxi

Multiple studies have consistently established that miR (microRNA)-210 induction is a feature of the hypoxic response in both normal and transformed cells. Here, we discuss the emerging biochemical functions of this miRNA and anticipate potential clinical applications. miR-210 is a robust target of hypoxia-inducible factor, and its overexpression has been detected in a variety of cardiovascular diseases and solid tumors. High levels of miR-210 have been linked to an in vivo hypoxic signature and associated with adverse prognosis in cancer patients. A wide spectrum of miR-210 targets have been identified, with roles in mitochondrial metabolism, angiogenesis, DNA repair, and cell survival. Such targets may broadly affect the evolution of tumors and other pathological settings, such as ischemic disorders. Harnessing the knowledge of miR-210's actions may lead to novel diagnostic and therapeutic approaches

Tadalafil improves lean mass and endothelial function in nonobese men with mild ED/LUTS: in vivo and in vitro characterization

PURPOSE: Phosphodiesterase type-5 inhibitor administration in diabetic men with erectile dysfunction (ED) is associated with reduced waist circumference. We evaluated potential effects of daily tadalafil administration on body composition and investigated its possible mechanism(s) of action in C2C12 skeletal muscle cells in vitro. METHODS: Forty-three men on stable caloric intake (mean age 48.5 ± 7; BMI 25.5 ± 0.9 kg/m2) complaining mild ED and/or low urinary tract symptoms (LUTS) were randomly assigned to receive tadalafil (TAD) 5 mg/daily (once-a-day=OAD-TAD; n = 23) or 20 mg on-demand (on-demand=OD-TAD; n = 20) for 2 months. Primary outcomes were variations of body composition measured by Dual-energy X-ray absorptiometry; secondary outcomes were ED/LUTS questionnaire scores along with hormone (testosterone, estradiol, insulin) and endothelial function (Endopat2000) variations. RESULTS: OAD-TAD increased abdominal lean mass (p < 0.01) that returned to baseline after 2 months withdrawal. LUTS scores improved (p<0.01) in OD-TAD while ED scores improved (p < 0.01) in both groups. We found significant improvements in endothelial function (p < 0.05) that directly correlated with serum insulin (p < 0.01; r = 0.3641) and inversely correlated with estradiol levels (p < 0.01; r = 0.3655) even when corrected for potential confounders. Exposure of C2C12 cells upon increasing tadalafil concentrations (10-7 to 10-6 M) increased total androgen receptor mRNA and protein expression as well as myogenin protein expression after 24 and 72 h (2.8 ± 0.4-fold and 1.4 ± 0.02-fold vs. control, respectively, p < 0.05). CONCLUSIONS: Daily tadalafil improved lean mass content in non-obese men probably via enhanced insulin secretion, estradiol reduction, and improvement of endothelial function in vivo. The in vitro increased myogenin and androgen receptor protein expression in skeletal muscle cells suggests a translational action of phosphodiesterase type-5 on this receptor

Tadalafil modulates aromatase activity and androgen receptor expression in a human osteoblastic cell in vitro model

Purpose Phosphodiesterase type-5 inhibitor (PDE5i) tadalafil administration in men with erectile dysfunction is associated with increased testosterone/estradiol ratio, leading to hypothesize a potential increased effect of androgen action on target tissues. We aimed to characterize, in a cellular model system in vitro, the potential modulation of aromatase and sex steroid hormone receptors upon exposure to tadalafil (TAD). Methods Human osteoblast-like cells SAOS-2 were chosen as an in vitro model system since osteoblasts are target of steroid hormones. Cells were tested for viability upon TAD exposure, which increased cell proliferation. Then, cells were treated with/without TAD for several times to evaluate potential modulation in PDE5, aromatase (ARO), androgen (AR) and estrogen (ER) receptor expression. Results Osteoblasts express significant levels of both PDE5 mRNA and protein. Exposure of cells to increasing concentrations of TAD (10−8–10−7 M) decreased PDE5 mRNA and protein expression. Also, TAD inhibited ARO mRNA and protein expression leading to an increase in testosterone levels in the supernatants. Interestingly, TAD increased total AR mRNA and protein expression and decreased ERα, with an increased ratio of AR/ER, suggesting preferential androgenic vs estrogenic pathway activation. Conclusions Our results demonstrate for the first time that TAD decreases ARO expression and increases AR protein expression in human SAOS-2, strongly suggesting a new control of steroid hormones pathway by PDE5i. These findings might represent the first evidence of translational actions of PDE5i on AR, which leads to hypothesize a growing relevance of this molecule in men with prostate cancer long-term treated with TAD for sexual rehabilitation. Keywords Tadalafil · Osteoblasts · Aromatase · Androgen receptor · Estrogen recepto

Physical activity and hypocaloric diet recovers osteoblasts homeostasis in women affected by abdominal obesity.

Obesity is a multifactorial disease linked to metabolic chronic disorders such as diabetes, and hypertension. Also, it has recently been associated with skeletal alterations and low bone mineral density. We previously demonstrated that exposure of osteoblasts to sera of sedentary subjects affected by obesity alters cell homeostasis in vitro, leading to disruption of intracellular differentiation pathways and cellular activity. Thus, the purpose of the present study has been to evaluate whether sera of sedentary obese women, subjected to physical activity and hypocaloric diet, could recover osteoblast homeostasis in vitro as compared to the sera of same patients before intervention protocol. To this aim, obese women were evaluated at time 0 and after 4, 6, and 12 months of individualized prescribed physical activity and hypocaloric diet. Dual-energy-X-ray absorptiometry measurements were performed at each time point, as well as blood was collected at the same points. Cells were incubated with sera of subjects before and after physical activity as described: obese at baseline and after for 4, 6, and 12 months of physical activity and nutritional protocol intervention. Osteoblasts exposed to sera of patients, who displayed increased lean and decreased fat mass (from 55.5 ± 6.5 to 57.1 ± 5.6% p ≤ 0.05; from 44.5 ± 1.1 to 40.9 ± 2.6% p ≤ 0.01 respectively), showed a time-dependent increase of Wnt/β-catenin signaling, versus cells exposed to sera of obese patients before intervention protocol, suggesting recovery of osteoblast homeostasis upon improvement of body composition. An increase in β-catenin nuclear accumulation and nuclear translocation was also observed, accompanied by an increase in Adiponectin receptor 1 protein expression, suggesting positive effect on cell differentiation program. Furthermore, a decrease in sclerostin amount and an increase of type 1 procollagen amino-terminal-propeptide were depicted as compared to baseline, proportionally to the time of physical activity, suggesting a recovery of bone remodeling modulation and an increase of osteoblast activity induced by improvement of body composition. In conclusion, our results show for the first time that sera of obese sedentary women who increased lean mass and decreased fat mass, by physical activity and hypocaloric diet, rescue osteoblasts differentiation and activity likely due to a reactivation of Wnt/β-catenin-pathway, suggesting that a correct life style can improve skeletal metabolic alteration induced by obesity

A multiple criteria methodology for prioritizing and selecting portfolios of urban projects

This paper presents an integrated methodology supporting decisions in urban planning. In particular, it deals with the prioritization and the selection of a portfolio of projects related to buildings of some values for the cultural heritage in cities. More precisely, our methodology has been validated to the historical center of Naples, Italy. Each project is assessed on the basis of a set of both quantitative and qualitative criteria with the purpose to determine their level of priority for further selection. This step was performed through the application of the Electre Tri-nC method which is a multiple criteria outranking based method for ordinal classification (or sorting) problems and allows to assign a priority level to each project as an analytical "recommendation" tool. To identify the efficient portfolios and to support the selection of the most adequate set of projects to activate, a set of resources (namely budgetary constraints) as well as some logical constraints related to urban policy requirements have to be taken into consideration together with the priority of projects in a portfolio analysis model. The process has been conducted by means of the interaction between analysts, municipality representative and experts. The proposed methodology is generic enough to be applied to other territorial or urban planning problems. We strongly believe that, given the increasing interest of historical cities to restore their cultural heritage, the integrated multiple criteria decision aiding analytical tool proposed in this paper has significant potential to be used in the future

Elevations of inflammatory markers PTX3 and sST2 after resuscitation from cardiac arrest are associated with multiple organ dysfunction syndrome and early death

BACKGROUND: A systemic inflammatory response is observed after cardiopulmonary resuscitation. We investigated two novel inflammatory markers, pentraxin 3 (PTX3) and soluble suppression of tumorigenicity 2 (sST2), in comparison with the classic high-sensitivity C-reactive protein (hsCRP), for prediction of early multiple organ dysfunction syndrome (MODS), early death, and long-term outcome after out-of-hospital cardiac arrest. METHODS: PTX3, sST2, and hsCRP were assayed at ICU admission and 48 h later in 278 patients. MODS was defined as the 24 h non-neurological Sequential Organ Failure Assessment (SOFA) score 6512. Intensive care unit (ICU) death and 12-month Cerebral Performance Category (CPC) were evaluated. RESULTS: In total, 82% of patients survived to ICU discharge and 48% had favorable neurological outcome at 1 year (CPC 1 or 2). At ICU admission, median plasma levels of hsCRP (2.8 mg/L) were normal, while levels of PTX3 (19.1 ng/mL) and sST2 (117 ng/mL) were markedly elevated. PTX3 and sST2 were higher in patients who developed MODS (p<0.0001). Admission levels of PTX3 and sST2 were also higher in patients who died in ICU and in those with an unfavorable 12-month neurological outcome (p<0.01). Admission levels of PTX3 and sST2 were independently associated with subsequent MODS [OR: 1.717 (1.221-2.414) and 1.340, (1.001-1.792), respectively] and with ICU death [OR: 1.536 (1.078-2.187) and 1.452 (1.064-1.981), respectively]. At 48 h, only sST2 and hsCRP were independently associated with ICU death. CONCLUSIONS: Higher plasma levels of PTX3 and sST2, but not of hsCRP, at ICU admission were associated with higher risk of MODS and early death

Visibilité des publications des géographes de ULiège dans les bases de données bibliographiques commerciales et Google Scholar

Cet article s’intéresse à la visibilité de la littérature scientifique produite par les géographes de l’Université de Liège, à travers des bases de données bibliographiques traditionnelles et du moteur de recherche Google Scholar (GS). La contribution du répertoire institutionnel ORBi pour la meilleure visibilité des références est évalué également. Une analyse du référencement d’un échantillon de publications par les bases de données commerciales multidisciplinaires, Scopus et WoS, et spécialisée GeoRef, ainsi que par le moteur de recherche GS est effectuée. D’autres facteurs tels que la langue de publication, la distribution entre les domaines des sciences et techniques (ST) et des sciences humaines et sociales (SHS) ont été pris en compte. Les résultats montrent que la distribution des publications des membres du Département de Géographie entre les types de documents est différente en fonction de l’orientation du sujet vers les ST ou les SHS, même si les articles de périodiques constituent le principal type de publications, quelle que soit la sous-discipline. En SHS, les chapitres et parties de livres ainsi que les articles et communications sont majoritairement en français. Les performances de GS sont supérieures à celles des BD pour notre échantillon de publications des géographes de l'ULiège. En conclusion, le répertoire institutionnel ORBi contribue incontestablement à améliorer les performances de GS quant au recouvrement de notre échantillon de publications et à donner une meilleure visibilité de la littérature francophone en Géographie.This article firstly examines the visibility of a sample of scientific literature produced by ULiège geographers in the commercial bibliographic databases and the Google Scholar search engine. The role of our institutional repository, ORBi, in the better visibility of references is also assessed. In our study we analysed the referencing of a sample of publications by the multidisciplinary commercial databases, Scopus and WoS, the specialized GeoRef, and the search engine GS. Factors such as the language of publication, the distribution between S&T and SS&H were also considered in the study. The results show that the distribution of the publications of the members of the Geography Department between the types of documents is different according to the orientation of the subject towards SS&H or S&T, even if the journal articles constitute the main type of publications, whatever the sub-discipline. In SS&H, the chapters, the parts of books, as well as the articles and communications are mainly in French. Compared to commercial DBs the performances of GS are superior for our sample of publications. These findings support the contribution of the ORBi institutional repository to improving GS’s 'performance with regard to the indexing of geographers' publications and to giving better visibility of French-speaking geographic literature

Integrare l’Educazione Fisica nel curriculum della scuola primaria. Un approccio collaborativo per l’insegnamento interdisciplinare

Interdisciplinary teaching connects two or more disciplines within content, activity, or experiencebased teaching proposals. Interdisciplinary teaching models allow to combine different areas of knowledge and, at the same time, to maintain the integrity of each discipline curriculum. In an interdisciplinaryprogram that includes the goals of physical education, movement is not simply considered as a tool for the realization of activities of other school subjects, but it allows the integration of the meanings of a knowledge sphere that pervades and enhances the embodied dimension of the human nature within a learning experience. The main purpose of the research was to analyze the resultsof a collaborative model application in planning teaching units that better the integration of physical education into primary school curricula. Focus groups and workshops on interdisciplinary planning were carried out with a group of 32 teachers and 1 school sports tutor in a primary school.Results showed that the choice of an interdisciplinary approach and integration of the physical education in the curriculum involve both technical aspect of planning and carrying out lessons – such as a deeper reflection on the objectives of each subject – and the personal vision of teaching practice, knowledge, and the meaning of school.L’insegnamento interdisciplinare connette due o più discipline scolastiche all’interno di proposte didattiche basate su contenuti, attività o esperienze. I modelli di insegnamento interdisciplinare consentono di unire diverse aree della conoscenza e di mantenere, al tempo stesso, l’integrità di ciascun curricolo disciplinare. In un programma interdisciplinare che comprende gli obiettivi dell’educazione fisica, il movimento non viene considerato semplicemente come strumento per la realizzazione di attività di altre discipline scolastiche, ma vengono integrati i significati di un ambito della conoscenza che riguarda e valorizza la dimensione incorporata della natura umana all’interno diun’esperienza.La finalità principale della ricerca è stata quella di analizzare i risultati dell’applicazione di un modello collaborativo nella programmazione di unità didattiche che integrano l’educazione fisica nel curriculum della scuola primaria.Sono stati realizzati focus group e laboratori per la progettazione interdisciplinare con un gruppo di 32 insegnanti e 1 tutor sportivo scolastico di una scuola primaria.I risultati hanno mostrato che la scelta di un approccio interdisciplinare e l’integrazione dell’educazione fisica nel curriculum coinvolgono sia aspetti tecnici della progettazione e della realizzazione della didattica, tra cui una riflessione più profonda sugli obiettivi disciplinari, sia il modo stesso in cui i docenti interpretano la professione, la conoscenza e il significato stesso di scuola