• Publicationsclose
• Research dataclose
• Other research productsclose
• Article close
• EU close
• IRIS - Università degli Studi di Verona close

Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout. © 2013 Nature America, Inc. All rights reserved.

Neutrophils are the first line of defense in the innate immune system, helping to maintain tissue homeostasis as well as eliminating pathogens and self-components. The traditional view of neutrophils as simple phagocytes has been revised over the last decade as new research reveals their unappreciated complexity. Neutrophils are phenotypically and functionally heterogeneous, allowing them to act as modulators of both inflammation and immune responses. During acute inflammation, neutrophils perform a variety of beneficial effector functions, but when inflammation is induced by injury (sterile inflammation) the benefits of neutrophils in tissue repair are more controversial. In several pathological conditions, including cancer and autoimmune diseases, neutrophils can trigger harmful tissue damage. Interestingly, neutrophils are also key players in neuroinflammatory disorders, during which they transmigrate in the central nervous system, acquire a toxic phenotype, home in on neurons, and release harmful molecules that compromise neuronal functions. In this review, we discuss recent data that redefine the cell biology and phenotype of neutrophils, focusing on the role of these cells in multiple sclerosis and Alzheimer's disease, both of which feature strong neuroinflammatory components.

In vivo estimates of tibiotalar and the subtalar joint kinematics can unveil unique information about gait biomechanics, especially in the presence of musculoskeletal disorders affecting the foot and ankle complex. Previous literature investigated the ankle kinematics on ex vivo data sets, but little has been reported for natural walking, and even less for pathological and juvenile populations. This paper proposes an MRI-based morphological fitting methodology for the personalised definition of the tibiotalar and the subtalar joint axes during gait, and investigated its application to characterise the ankle kinematics in twenty patients affected by Juvenile Idiopathic Arthritis (JIA). The estimated joint axes were in line with in vivo and ex vivo literature data and joint kinematics variation subsequent to inter-operator variability was in the order of 1°. The model allowed to investigate, for the first time in patients with JIA, the functional response to joint impairment. The joint kinematics highlighted changes over time that were consistent with changes in the patient's clinical pattern and notably varied from patient to patient. The heterogeneous and patient-specific nature of the effects of JIA was confirmed by the absence of a correlation between a semi-quantitative MRI-based impairment score and a variety of investigated joint kinematics indexes. In conclusion, this study showed the feasibility of using MRI and morphological fitting to identify the tibiotalar and subtalar joint axes in a non-invasive patient-specific manner. The proposed methodology represents an innovative and reliable approach to the analysis of the ankle joint kinematics in pathological juvenile populations.

Pancreatic cancer remains a formidable challenge for oncologists and patients alike. Despite intensive efforts, attempts at improving survival in the past 15 years, particularly in advanced disease, have failed. This is true even with the introduction of molecularly targeted agents, chosen on the basis of their action on pathways that were supposedly important in pancreatic cancer development and progression: indeed, with the notable exception of the epidermal growth factor receptor (EGFR) inhibitor erlotinib, that has provided a minimal survival improvement when added to gemcitabine, other agents targeting EGFR, matrix metallo-proteases, farnesyl transferase, or vascular endothelial growth factor have not succeeded in improving outcomes over standard gemcitabine monotherapy for a variety of different reasons. However, recent developments in the molecular epidemiology of pancreatic cancer and an ever evolving understanding of the molecular mechanisms underlying pancreatic cancer initiation and progression raise renewed hope to find novel, relevant therapeutic targets that could be pursued in the clinical setting. In this review we focus on molecular epidemiology of pancreatic cancer, epithelial-to-mesenchymal transition and its influence on sensitivity to EGFR-targeted approaches, apoptotic pathways, hypoxia-related pathways, developmental pathways (such as the hedgehog and Notch pathways), and proteomic analysis as keys to a better understanding of pancreatic cancer biology and, most importantly, as a source of novel molecular targets to be exploited therapeutically.

This study aims at clarifying the prognostic role of high-grade tumor budding (TB) in pancreatic ductal adenocarcinoma (PDAC) with the first systematic review and meta-analysis on this topic. Furthermore, we analyzed with a systematic review the relationship between TB and a recently suggested TB-associated mechanism: the epithelial to mesenchymal transition (EMT). Analyzing a total of 613 patients, 251 of them (40.9%) with high grade-TB, we found an increased risk of all-cause mortality (RR, 1.46; 95% CI, 1.13-1.88, p = 0.004; HR, 2.65; 95% CI, 1.79-3.91; p < 0.0001) and of recurrence (RR, 1.61; 95% CI, 1.05-2.47, p = 0.03) for PDAC patients with high-grade TB. Moreover, we found that EMT is a central process in determining the presence of TB in PDAC. Thanks to this meta-analysis, we demonstrate the potential clinical significance of high-grade TB for prognostic stratification of PDAC. TB also shows a clear association with the process of EMT. Based on the results of the present study, TB should be conveyed in pathology reports and taken into account by future oncologic staging systems. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

Burkholderia fungorum DBT1 is a bacterial strain isolated from an oil refinery discharge and capable of transforming dibenzothiophene, phenanthrene, naphthalene, and fluorene. In order to evaluate the influence of a policyclic aromatic hydrocarbon (PAH)-transforming bacterial strain on the phytoremediation of organic contaminants, B. fungorum DBT1 was inoculated into hybrid poplar (Populus deltoides×Populus nigra). The poplar plants were grown for 18-wk with or without naphthalene, phenanthrene, fluorene and dibenzothiophene (488mgkg(-1) soil each) in non-sterile sand-peat substrate. Evidences were gained that B. fungorum DBT1 was present in high concentration in poplar root tissues (2.9-9.5×10(3)CFUg(-1)), while the strain was not detected in stem, leaves and rhizosphere. When poplar was planted in uncontaminated substrate, the infection caused negative effects on biomass index, leaves and stem dry weight, without showing however any disease symptoms. On the other hand, plants inoculated with the strain DBT1 resulted in better tolerance against the toxic effects of PAHs, in terms of root dry weight. Although the presence of plants acted as the main effective treatment for PAH dissipation (82-87%), the inoculum with DBT1 strain lead to the highest PAH abatement (up to 99%). In the present study, an environmental isolate with proper metabolic features was demonstrated to be possibly suitable as a poplar endophyte for improving microbe-assisted phytoremediation in PAH contaminated matrices.