Clinical significance of epithelial-to-mesenchymal transition in laryngeal carcinoma: Its role in the different subsites

Background: During epithelial-to-mesenchymal transition, cancer cells lose adhesion capacity gaining migratory properties. The role of the process on prognosis has been evaluated in 50 cases of laryngeal carcinoma. Methods: E-cadherin, N-cadherin, β-catenin, α-catenin, γ-catenin, caveolin-1, and vimentin immunohistochemical expression were evaluated using a double score based on staining intensity and cellular localization. Results: Cytoplasmic E-cadherin and α/γ catenin staining were associated with a decrease in survival, cytoplasmic β-catenin was associated with advanced stage, and N-cadherin and vimentin expression were associated with poor differentiation and tumor relapse. On the basis of cancer cells, epithelial or mesenchymal morphological and immunophenotypic similarity we identified 4 main subgroups correlated with a transition to a more undifferentiated phenotype, which have a different pattern of relapse and survival. Conclusion: The negative prognostic role of epithelial-to-mesenchymal transition has been confirmed and a predictive role in glottic tumors has been suggested, leading us to propose epithelial-to-mesenchymal transition as an additional adverse feature in laryngeal carcinoma

Involvement of pro-inflammatory cytokines and growth factors in the pathogenesis of Dupuytren's contracture: a novel target for a possible future therapeutic strategy?

Dupuytren's contracture (DC) is a benign fibro-proliferative disease of the hand causing fibrotic nodules and fascial cords which determine debilitating contracture and deformities of fingers and hands. The present study was designed to characterize pro-inflammatory cytokines and growth factors involved in the pathogenesis, progression and recurrence of this disease, in order to find novel targets for alternative therapies and strategies in controlling DC. The expression of pro-inflammatory cytokines and of growth factors was detected by immunohistochemistry in fibrotic nodules and normal palmar fascia resected respectively from patients affected by DC and carpal tunnel syndrome (CTS; as negative controls). Reverse transcription (RT)-PCR analysis and immunofluorescence were performed to quantify the expression of transforming growth factor (TGF)-β1, interleukin (IL)-1β and vascular endothelial growth factor (VEGF) by primary cultures of myofibroblasts and fibroblasts isolated from Dupuytren's nodules. Histological analysis showed high cellularity and high proliferation rate in Dupuytren's tissue, together with the presence of myofibroblastic isotypes; immunohistochemical staining for macrophages was completely negative. In addition, a strong expression of TGF-β1, IL-1β and VEGF was evident in the extracellular matrix and in the cytoplasm of fibroblasts and myofibroblasts in Dupuytren's nodular tissues, as compared with control tissues. These results were confirmed by RT-PCR and by immunofluorescence in pathological and normal primary cell cultures. These preliminary observations suggest that TGF-β1, IL-1β and VEGF may be considered potential therapeutic targets in the treatment of Dupuytren's disease (DD)

Mass accretion rates of clusters of galaxies: CIRS and HeCS

We use a new spherical accretion recipe tested on N-body simulations to measure the observed mass accretion rate (MAR) of 129 clusters in the Cluster Infall Regions in the Sloan Digital Sky Survey (CIRS) and in the Hectospec Cluster Survey (HeCS). The observed clusters cover the redshift range of $0.01<z<0.30$ and the mass range of $\sim 10^{14}-10^{15} {h^{-1}~\rm{M_\odot}}$. Based on three-dimensional mass profiles of simulated clusters reaching beyond the virial radius, our recipe returns MARs that agree with MARs based on merger trees. We adopt this recipe to estimate the MAR of real clusters based on measurements of the mass profile out to $\sim 3R_{200}$. We use the caustic method to measure the mass profiles to these large radii. We demonstrate the validity of our estimates by applying the same approach to a set of mock redshift surveys of a sample of 2000 simulated clusters with a median mass of $M_{200}= 10^{14} {h^{-1}~\rm{M_{\odot}}}$ as well as a sample of 50 simulated clusters with a median mass of $M_{200}= 10^{15} {h^{-1}~\rm{M_{\odot}}}$: the median MARs based on the caustic mass profiles of the simulated clusters are unbiased and agree within $19\%$ with the median MARs based on the real mass profile of the clusters. The MAR of the CIRS and HeCS clusters increases with the mass and the redshift of the accreting cluster, which is in excellent agreement with the growth of clusters in the $\Lambda$CDM model.Comment: 25 pages, 19 figures, 7 table

Influence of pasture feeding on milk and meat products in terms of human health and product quality

Cows are fed either indoors on a diet of mixed ration or in areas with temperate climates, such as Ireland and New Zealand, the feeding regime of dairy and beef herds is almost entirely pasture-based. Animal feeding regimes and herd management practices are linked to differences in organoleptic and nutritional quality attributes of milk, dairy and meat/beef products, with pasture-based feeding systems being associated with superior quality produce. Consumers generally perceive that milk and meat products produced from outdoor grazing pastures are “healthier” than produce derived from indoor feeding systems, based on animals fed typical indoor rations and concentrates. However, while research has demonstrated differences in milk and meat quality, especially in terms of fatty acids, based on different feeding systems, data are limited on the impact of dairy and meat products produced from different feeding systems on human health

Effects of a natural extract from Mangifera indica L, and its active compound, mangiferin, on energy state and lipid peroxidation of red blood cells

Following oxidative stress, modifications of several biologically important macromolecules have been demonstrated. In this study we investigated the effect of a natural extract from Mangifera indica L (Vimang), its main ingredient mangiferin and epigallocatechin gallate (EGCG) on energy metabolism, energy state and malondialdehyde (MDA) production in a red blood cell system. Analysis of NIDA, high energy phosphates and ascorbate was carried out by high performance liquid chromatography (HPLC). Under the experimental conditions, concentrations of NIDA and ATP catabolites were affected in a dose-dependent way by H2O2. Incubation with Vimang (0.1, 1, 10, 50 and 100 mu g/mL), mangiferin (1, 10, 100 mu g/mL) and EGCG (0.01, 0.1, 1, 10 mu M) significantly enhances erythrocyte resistance to H2O2-induced reactive oxygen species production. In particular, we demonstrate the protective activity of these compounds on ATP, GTP and total nucleotides (NT) depletion after H2O2-induced damage and a reduction of NAD and ADP, which both increase because of the energy consumption following H2O2 addition. Energy charge potential, decreased in H2O2-treated erythrocytes, was also restored in a dose-dependent way by these substances. Their protective effects might be related to the strong free radical scavenging ability described for polyphenols. (c) 2006 Elsevier B.V All rights reserved

Efficacy and safety of flash glucose monitoring in patients with type 1 and type 2 diabetes: a systematic review and meta-analysis

INTRODUCTION: Flash glucose monitoring (FGM) is a factory-calibrated sensor-based technology for the measurement of interstitial glucose. We performed a systematic review and meta-analysis to assess its efficacy and safety in patients with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: PubMed, CENTRAL, Scopus and Web of Science were searched in July 2019. Twelve studies with a follow-up longer than 8 weeks, evaluating 2173 patients on prandial insulin, multiple daily insulin injections or continuous subcutaneous insulin infusion were included. The following data were extracted: HbA1c, time in range, time above 180 mg/dL, time below 70 mg/dL, frequency of hypoglycemic events, number of self-monitoring of blood glucose (SMBG) measurements, total daily insulin dose, patient-reported outcomes, adverse events, and discontinuation rate. A comparison with SMBG was conducted. RESULTS: FGM use was associated with a reduction in HbA1c (-0.26% (-3 mmol/mol); p=0.002) from baseline to the last available follow-up, which correlated with HbA1c levels at baseline (-0.4% (-4 mmol/mol) for each 1.0% (11 mmol/mol) of HbA1c above 7.2% (55 mmol/mol)). Also, a decrease in time below 70 mg/dL was found (-0.60 hours/day; p=0.04). Favorable findings in patient-reported outcomes and no device-related serious adverse events were reported. When compared with SMBG, FGM was characterized by no statistically different change in HbA1c (p=0.09), with lower number of SMBG measurements per day (-3.76 n/day; p&lt;0.001) and risk of discontinuation (relative risk=0.42; p=0.001). A limited number of studies, with a heterogeneous design and usually with a short-term follow-up and without specific training, were found. CONCLUSIONS: The present review provides evidence for the use of FGM as an effective strategy for the management of diabetes

Modulation of the proteolytic activity of matrix metalloproteinase-2 (gelatinase A) on fibrinogen

The proteolytic processing of bovine fibrinogen by MMP-2 (gelatinase A), which brings about the formation of a product unable to form fibrin clots, has been studied at 37 degrees C. Catalytic parameters, although showing a somewhat lower catalytic efficiency with respect to thrombin and plasmin, indeed display values indicating a pathophysiological significance of this process. A parallel molecular modelling study predicts preferential binding of MMP-2 to the beta-chain of fibrinogen through its haemopexin-like domain, which has been directly demonstrated by the inhibitory effect in the presence of the exogenous haemopexin-like domain. However, the removal of this domain does not impair the interaction between MMP-2 and fibrinogen, but it dramatically alters the proteolytic mechanism, producing different fragmentation inter-mediates. The investigation at various pH values between 6.0 and 9.3 indicates a proton-linked behaviour, which is relevant for interpreting the influence on the process by environmental conditions occurring at the site of an injury. Furthermore, the action of MMP-2 on peroxynitrite-treated fibrinogen has been investigated, a situation possibly occurring under oxidative stress. The chemical alteration of fibrinogen, which has been shown to abolish its clotting activity, brings about only limited modifications of the catalytic parameters without altering the main enzymatic mechanism

Simple system using natural mineral water for high-throughput phenotyping of Arabidopsis thaliana seedlings in liquid culture

Background: Phenotyping for plant stress tolerance is an essential component of many research projects. Because screening of high numbers of plants and multiple conditions remains technically challenging and costly, there is a need for simple methods to carry out large-scale phenotyping in the laboratory.Methods: We developed a method for phenotyping the germination and seedling growth of Arabidopsis (Arabidopsis thaliana) Col-0 in liquid culture. Culture was performed under rotary shaking in multiwell plates, using Evian natural mineral water as a medium. Nondestructive and accurate quantification of green pixels by digital image analysis allowed monitoring of growth. Results: The composition of the water prevented excessive root elongation growth that would otherwise lead to clumping of seedlings observed when classic nutrient-rich medium or deionized water is used. There was no need to maintain the cultures under aseptic conditions, and seedlings, which are photosynthetic, remained healthy for several weeks. Several proof-of-concept experiments demonstrated the usefulness of the approach for environmental stress phenotyping. Conclusion: The system described here is easy to set up, cost-effective, and enables a single researcher to screen large numbers of lines under various conditions. The simplicity of the method clearly makes it amenable to high-throughput phenotyping using robotics

Bifidobacteria Strain Typing by Fourier Transform Infrared Spectroscopy

Fourier transform infrared (FTIR) spectroscopy, a technology traditionally used in chemistry to determine the molecular composition of a wide range of sample types, has gained growing interest in microbial typing. It is based on the different vibrational modes of the covalent bonds between atoms of a given sample, as bacterial cells, induced by the absorption of infrared radiation. This technique has been largely used for the study of pathogenic species, especially in the clinical field, and has been proposed also for the typing at different subspecies levels. The high throughput, speed, low cost, and simplicity make FTIR spectroscopy an attractive technique also for industrial applications, in particular, for probiotics. The aim of this study was to compare FTIR spectroscopy with established genotyping methods, pulsed-field gel electrophoresis (PFGE), whole-genome sequencing (WGS), and multilocus sequence typing (MLST), in order to highlight the FTIR spectroscopy potential discriminatory power at strain level. Our study focused on bifidobacteria, an important group of intestinal commensals generally recognized as probiotics. For their properties in promoting and maintaining health, bifidobacteria are largely marketed by the pharmaceutical, food, and dairy industries. Strains belonging to Bifidobacterium longum subsp. longum and Bifidobacterium animalis subsp. lactis were taken into consideration together with some additional type strains. For B. longum subsp. longum, it was possible to discriminate the strains with all the methods used. Although two isolates were shown to be strictly phylogenetically related, constituting a unique cluster, based on PFGE, WGS, and MLST, no clustering was observed with FTIR. For B. animalis subsp. lactis group, PFGE, WGS, and MLST were non-discriminatory, and only one strain was easily distinguished. On the other hand, FTIR discriminated all the isolates one by one, and no clustering was observed. According to these results, FTIR analysis is not only equivalent to PFGE, WGS, and MLST, but also for some strains, in particular, for B. animalis subsp. lactis group, more informative, being able to differentiate strains not discernible with the other two methods based on phenotypic variations likely deriving from certain genetic changes. Fourier transform infrared spectroscopy has highlighted the possibility of using the cell surface as a kind of barcode making tracing strains possible, representing an important aspect in probiotic applications. Furthermore, this work constitutes the first investigation on bifidobacterial strain typing using FTIR spectroscopy

Protective cultures against foodborne pathogens in a nitrite reduced fermented meat product

In the present work, a combined hurdle approach for fermented meat preservation was investigated. Challenge tests were performed in Chorizo sausage model using the maximum allowed NaNO2 amount (150 mg/kg), a reduced amount (75 mg/kg) and no nitrite, with and without protective cultures inoculation. Cocktail strains of L. monocytogenes and Salmonella spp. were used as indicator strains. In a nitrite reduced sausage model, L. monocytogenes growing trend did not significantly change (p &gt; 0.05) when compared with that containing higher nitrite concentration (150 mg/kg NaNO2). The addition of L. plantarum PSC20 significantly lowered L. monocytogenes growth when compared with control batches without PCS20 (p &lt; 0.05), obtaining 3.84 log cfu/g and 2.62 log cfu/g lower counts in the batches with 150 mg/kg NaNO2 and 75 mg/kg NaNO2 respectively. None of the protective cultures demonstrated in situ antagonistic activity against Salmonella spp. This work pointed out that the reduction of nitrites with the combined use of a protective culture could be a feasible approach to control L. monocytogenes growth in fermented meat foods