158 research outputs found

    Upon oxidative stress, the antiapoptotic Hsp60/procaspase-3 complex persists in mucoepidermoid carcinoma cells.

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    Hsp60, a mitochondrial chaperonin highly conserved during evolution, has been found elevated in the cytosol of cancer cells, both in vivo and in vitro, but its role in determining apoptosis during oxidative stress (OS) has not yet been fully elucidated. The aim of the present work was to study the effects of OS on Hsp60 levels and its interactions with procaspase- 3 (p-C3) and p53 in tumor cells. NCI-H292 (mucoepidermoid carcinoma) cells were exposed to various concentrations of hydrogen peroxide (H2O2) for 24 hours. Cell viability was determined by Trypan blue and MTT assays. DNA damage was assessed by the Comet assay, and apoptosis was measured by the AnnexinV cytofluorimetric test. Exposure to increasing concentrations of H2O2 resulted in a reduction of cell viability, DNA damage, and early apoptotic phenomena. Hsp60, p-C3, p53, and p21 were assessed by Western blotting and immunocytochemistry before and after OS. Hsp60 and p-C3 were present before and after OS induction. Immunoprecipitation experiments showed an Hsp60/p-C3 complex before OS that persisted after it, while an Hsp60/p53 complex was not detected in either condition. The presence of wild type (wt) p53 was confirmed by RT-PCR, and p21 detection suggested p53 activation after OS. We postulate that, although OS may induce early apoptosis in NCI-H292 cells, Hsp60 exerts an anti-apoptotic effect in these cells and, by extension, it may do so in other cancer cell

    Ultrasonographic Evaluation of Intestinal Fibrosis and Inflammation in Crohn's Disease. The State of the Art

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    The evaluation of the degree of inflammation and fibrosis, intrinsic elements in intestinal wall damage of Crohn's disease, is essential to individuate the extent of the lesions and the presence of strictures. This information will contribute to the choice of the appropriate therapeutic approach, the prediction of the response to therapy and the course of the disease. The accurate evaluation of the extent and severity of inflammation and/or fibrosis in Crohn's disease currently requires histopathological analysis of the intestinal wall. However, in clinical practice and research, transmural assessment of the intestinal wall with cross sectional imaging is increasingly used for this purpose. The B-mode ultrasonograhic characteristics of the intestinal wall, the assessment of its vascularization by color Doppler and I.V. contrast agents, and the evaluation of the mechanical and elastic properties by sonoelastography, may provide useful and accurate information on the severity and extent of inflammation and intestinal fibrosis in Crohn's disease. The purpose of this review is to provide an update on current sonographic methods to discriminate inflammation and fibrosis in Crohn's disease

    Circulating fibroblast activation protein as potential biomarker in patients with inflammatory bowel disease

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    A major concern in the management of Inflammatory Bowel Disease (IBD) is the absence of accurate and specific biomarkers to drive diagnosis and monitor disease status timely and non-invasively. Fibroblast activation protein (FAP) represents a hallmark of IBD bowel strictures, being overexpressed in stenotic intestinal myofibroblasts. The present study aimed at evaluating the potential of circulating FAP (cFAP) as an accessible blood biomarker of IBD. Quantitative determination of cFAP was performed by enzyme-linked immunosorbent assay on plasma samples prospectively collected from patients with IBD and control subjects. A discrimination model was established on a training set of 50% patients and validated on independent samples. Results showed that cFAP concentration was reduced in patients with IBD when compared to controls (p < 0.0001). Age, sex, smoking, disease location and behavior, disease duration and therapy were not associated with cFAP. The sensitivity and specificity of cFAP in discriminating IBD from controls were 70 and 84%, respectively, based on the optimal cutoff (57.6 ng mL(-1), AUC = 0.78). Predictions on the test set had 57% sensitivity, 65% specificity, and 61% accuracy. There was no strong correlation between cFAP and routine inflammatory markers in the patients' population. A subgroup analysis was performed on patients with Crohn's disease undergoing surgery and revealed that cFAP correlates with endoscopic mucosal healing. In conclusion, cFAP deserves attention as a promising blood biomarker to triage patients with suspected IBD. Moreover, it might function as a biomarker of post-operative remission in patients with Crohn's disease

    Space-Time Landslide Predictive Modelling

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    Landslides are nearly ubiquitous phenomena and pose severe threats to people, properties, and the environment. Investigators have for long attempted to estimate landslide hazard to determine where, when, and how destructive landslides are expected to be in an area. This information is useful to design landslide mitigation strategies, and to reduce landslide risk and societal and economic losses. In the geomorphology literature, most attempts at predicting the occurrence of populations of landslides rely on the observation that landslides are the result of multiple interacting, conditioning and triggering factors. Here, we propose a novel Bayesian modelling framework for the prediction of space-time landslide occurrences of the slide type caused by weather triggers. We consider log-Gaussian cox processes, assuming that individual landslides stem from a point process described by an unknown intensity function. We tested our prediction framework in the Collazzone area, Umbria, Central Italy, for which a detailed multi-temporal landslide inventory spanning 1941-2014 is available together with lithological and bedding data. We tested five models of increasing complexity. Our most complex model includes fixed effects and latent spatio-temporal effects, thus largely fulfilling the common definition of landslide hazard in the literature. We quantified the spatio-temporal predictive skill of our model and found that it performed better than simpler alternatives. We then developed a novel classification strategy and prepared an intensity-susceptibility landslide map, providing more information than traditional susceptibility zonations for land planning and management. We expect our novel approach to lead to better projections of future landslides, and to improve our collective understanding of the evolution of landscapes dominated by mass-wasting processes under geophysical and weather triggers

    Use of Kluyveromyces marxianus to Increase Free Monoterpenes and Aliphatic Esters in White Wines

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    An increasing interest in novel wine productions is focused on non-Saccharomyces yeasts due to their potential in improving sensory profiles. Although Kluyveromyces marxianus has been originally isolated from grapes and its enzymatic activities are used in oenology, rarely it has been used as co-starter. The K. marxianus Km L2009 strain has been characterized here and selected as a co-starter both at laboratory- and winery-scale fermentation. The Km L2009 strain showed growth of up to 40 (mg/L) of sulfites and 6% (v/v) of ethanol. Gas chromatographic analysis demonstrates that wines produced by mixed fermentation contain remarkably higher quantities of free monoterpenes and aliphatic esters than wines produced only by commercial strains of Saccharomyces cerevisiae. Differences in the volatile organic compound composition produced sensorially distinct wines. In light of these results, it is possible to state that even within the K. marxianus species it is possible to select strains capable of improving the aromatic quality of wines

    Immune-Mediated Inflammatory Diseases and Cancer - a dangerous liaison

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    Patients with Immune-Mediated Inflammatory Diseases (IMIDs) are known to have an elevated risk of developing cancer, but the exact causative factors remain subject to ongoing debate. This narrative review aims to present the available evidence concerning the intricate relationship between these two conditions. Environmental influences and genetic predisposition lead to a dysregulated immune response resulting in chronic inflammation, which is crucial in the pathogenesis of IMIDs and oncogenic processes. Mechanisms such as the inflammatory microenvironment, aberrant intercellular communication due to abnormal cytokine levels, excessive reparative responses, and pathological angiogenesis are involved. The chronic immunosuppression resulting from IMIDs treatments further adds to the complexity of the pathogenic scenario. In conclusion, this review highlights critical gaps in the current literature, suggesting potential avenues for future research. The intricate interplay between IMIDs and cancer necessitates more investigation to deepen our understanding and improve patient management

    Exploitation of large archives of ERS and ENVISAT C-band SAR data to characterize ground deformations

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    In the last few years, several advances have been made in the use of radar images to detect, map and monitor ground deformations. DInSAR (Differential Synthetic Aperture Radar Interferometry) and A-DInSAR/PSI (Advanced DInSAR/Persistent Scatterers Interferometry) technologies have been successfully applied in the study of deformation phenomena induced by, for example, active tectonics, volcanic activity, ground water exploitation, mining, and landslides, both at local and regional scales. In this paper, the existing European Space Agency (ESA) archives (acquired as part of the FP7-DORIS project), which were collected by the ERS-1/2 and ENVISAT satellites operating in the microwave C-band, were analyzed and exploited to understand the dynamics of landslide and subsidence phenomena. In particular, this paper presents the results obtained as part of the FP7-DORIS project to demonstrate that the full exploitation of very long deformation time series (more than 15 years) can play a key role in understanding the dynamics of natural and human-induced hazards. © 2013 by the authors
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