Angiotensin type-2 (AT-2)-receptor activation reduces renal fibrosis in cyclosporine nephropathy: evidence for blood-pressure independent effect

Compound 21 (C21), selective agonist of AT2 receptors, shows antinflammatory effects in hypertension and nephroprotection in diabetes. The aim of this study was to evaluate the effects of C21 in cyclosporine nephropathy, which is characterized mainly by tubulo-interstitial fibrosis. Ten days before and during the experimental periods, low-salt diet was administered to Sprague Dawley rats. Cyclosporine-A (15mg/kg/day, i.p.) and cyclosporine-A plus C21 (0.3 mg/kg /day, i.p) were administered for 1 and 4 weeks. Control groups was left without any treatment. Blood pressure (plethysmographic method) and 24 hour albuminuria were measured once a week. At the end of the experiments, the kidneys were excised for histomorphometric analysis of renal fibrosis and for immunohistochemical evaluation of inflammatory infiltrates and type I and IV collagen expression.After 1 and 4 weeks, the rats treated with cyclosporine showed a significant increase (p <0.01) in blood pressure, no significant changes in albuminuria, a significant increase (p <0.01) in glomerular and tubulo-interstitial fibrosis and inflammatory infiltrates as compared to the control rats. Treatment with C21 did not modify the cyclosporine dependent increase of blood pressure, which was higher than in control rats, but after 4 weeks of treatment significantly reduced (p <0.01) glomerular and tubulo-interstitial fibrosis, type 1 collagen expression and macrophage infiltration, as compared to rats treated with cyclosporine.The administration of C21 showed a protective effect on cyclosporine nephropathy, decreasing renal fibrosis and macrophage infiltration. These data suggest that C21 may counteract tubulo-interstitial fibrosis, the most potent predictor of the progression of renal diseases

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

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

The Oxidative Cleavage of 9,10-Dihydroxystearic Triglyceride with Oxygen and Cu Oxide-based Heterogeneous Catalysts

This paper deals with a new heterogeneous catalyst for the second step in the two-step oxidative cleavage of unsaturated fatty acids triglycerides derived from vegetable oil, a reaction aimed at the synthesis of azelaic and pelargonic acids. The former compound is a bio-monomer for the synthesis of polyesters; the latter, after esterification, is used in cosmetics and agrochemicals. The reaction studied offers an alternative to the currently used ozonization process, which has severe drawbacks in terms of safety and energy consumption. The cleavage was carried out with oxygen, starting from the glycol (dihydroxystearic acid triglyceride), the latter obtained by the dihydroxylation of oleic acid triglyceride. The catalysts used were based on Cu2+, in the form of either an alumina-supported oxide or a mixed, spinel-type oxide. The CuO/Al2O3 catalyst could be recovered, regenerated, and recycled, yielding promising results for further industrial exploitation

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)

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

The fate of bacteria in urban wastewater-irrigated peach tree: a seasonal evaluation from soil to canopy

Irrigation with wastewater can be a solution to preserve and mitigate freshwater demand, in particular during drought periods. Unfortunately, wastewater, although being treated at different levels, could be a carrier of human pathogens (e.g., E. coli) and potentially contaminate crops for human consumptions.This study investigated the seasonal microbiological concentrations, on soil, shoot and fruit tissues of potted peach trees, following two irrigation treatments: freshwater (FW) and secondary urban wastewater without the final disinfection treatment (SW). E. coli was only detected in SW irrigated soil, whereas total coliforms (TC) and total bacteria counts (TBC) were similar in both treatments throughout the season. EndophyticE. coli, Salmonella spp. and TC were not detected in shoot and fruit, but a higher presence of total bacteria (TBC) was observed in SW-irrigated tree compared to FWirrigated tree. In particular, SW shoots had a higher load compared to fruits, thus showing a potential effect of leaf transpiration, that promoted the transfer of water-borne bacteria from soil to the epigeal part (shoot). The adoption of low-quality SW (even above the microbiological limits of the European Regulation 2020/741 for wastewater re-use in agriculture), when a drip irrigation method is applied, could be a valid alternative to save fresh water without compromising fruit safety

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