Double-Stranded RNA Attenuates the Barrier Function of Human Pulmonary Artery Endothelial Cells

Circulating RNA may result from excessive cell damage or acute viral infection and can interact with vascular endothelial cells. Despite the obvious clinical implications associated with the presence of circulating RNA, its pathological effects on endothelial cells and the governing molecular mechanisms are still not fully elucidated. We analyzed the effects of double stranded RNA on primary human pulmonary artery endothelial cells (hPAECs). The effect of natural and synthetic double-stranded RNA (dsRNA) on hPAECs was investigated using trans-endothelial electric resistance, molecule trafficking, calcium (Ca2+) homeostasis, gene expression and proliferation studies. Furthermore, the morphology and mechanical changes of the cells caused by synthetic dsRNA was followed by in-situ atomic force microscopy, by vascular-endothelial cadherin and F-actin staining. Our results indicated that exposure of hPAECs to synthetic dsRNA led to functional deficits. This was reflected by morphological and mechanical changes and an increase in the permeability of the endothelial monolayer. hPAECs treated with synthetic dsRNA accumulated in the G1 phase of the cell cycle. Additionally, the proliferation rate of the cells in the presence of synthetic dsRNA was significantly decreased. Furthermore, we found that natural and synthetic dsRNA modulated Ca2+ signaling in hPAECs by inhibiting the sarco-endoplasmic Ca2+-ATPase (SERCA) which is involved in the regulation of the intracellular Ca2+ homeostasis and thus cell growth. Even upon synthetic dsRNA stimulation silencing of SERCA3 preserved the endothelial monolayer integrity. Our data identify novel mechanisms by which dsRNA can disrupt endothelial barrier function and these may be relevant in inflammatory processes

Flavonoids in Lemon and Grapefruit IntegroPectin**

Following the analysis of terpenes present in new lemon and grapefruit “IntegroPectin” pectins obtained via the hydrodynamic cavitation of industrial lemon and grapefruit processing waste, the HPLC-MS analysis of flavonoid and other phenolic compounds reveals the presence of eriocitrin, naringin, hesperidin and kaempferol typical of the respective citrus fruits. The pectic fibers rich in rhamnogalacturonan-I regions act as chemical sponges adsorbing and concentrating at their outer surface highly bioactive citrus flavonoids and terpenes. These findings, together with the unique molecular structure of these new whole citrus pectins, provide preliminary insight into the broad-scope biological activity of these new biomaterials. Numerous new biomedical applications are anticipated, including likely use in the prevention and treatment of microbial infections and neurodegenerative disease

Exceptional Antioxidant, Non-Cytotoxic Activity of Integral Lemon Pectin from Hydrodynamic Cavitation

Lemon pectin extracted along with water-soluble flavonoids and other phytochemicals from citrus industry's waste lemon peel via hydrodynamic cavitation in water, directly at pre-industrial scale and further isolated via freeze drying, shows exceptionally high antioxidant and non-cytotoxic activity. Preliminary investigation indicates also significant antimicrobial activity. These findings open the route to the development of new nutraceutical and healthcare applications of a versatile biopolymer endowed with new functionality, rapidly and conveniently obtained from an abundant by-product of the agri-food industry

Volatile Compounds of Lemon and Grapefruit IntegroPectin

An HS-SPME GC-MS analysis of the volatile compounds adsorbed at the outer surface of lemon and grapefruit pectins obtained via the hydrodynamic cavitation of industrial waste streams of lemon and grapefruit peels in water suggests important new findings en route to understanding the powerful and broad biological activity of these new pectic materials. In agreement with the ultralow degree of esterification of these pectins, the high amount of highly bioactive α-terpineol and terpinen-4-ol points to limonene (and linalool) decomposition catalyzed by residual citric acid in the citrus waste peel residue of the juice industrial production

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Increased S100A4 expression in the vasculature of human COPD lungs and murine model of smoke-induced emphysema

BACKGROUND: Chronic obstructive lung disease (COPD) is a common cause of death in industrialized countries often induced by exposure to tobacco smoke. A substantial number of patients with COPD also suffer from pulmonary hypertension that may be caused by hypoxia or other hypoxia-independent stimuli - inducing pulmonary vascular remodeling. The Ca(2+) binding protein, S100A4 is known to play a role in non-COPD-driven vascular remodeling of intrapulmonary arteries. Therefore, we have investigated the potential involvement of S100A4 in COPD induced vascular remodeling. METHODS: Lung tissue was obtained from explanted lungs of five COPD patients and five non-transplanted donor lungs. Additionally, mice lungs of a tobacco-smoke-induced lung emphysema model (exposure for 3 and 8 month) and controls were investigated. Real-time RT-PCR analysis of S100A4 and RAGE mRNA was performed from laser-microdissected intrapulmonary arteries. S100A4 immunohistochemistry was semi-quantitatively evaluated. Mobility shift assay and siRNA knock-down were used to prove hypoxia responsive elements (HRE) and HIF binding within the S100A4 promoter. RESULTS: Laser-microdissection in combination with real-time PCR analysis revealed higher expression of S100A4 mRNA in intrapulmonary arteries of COPD patients compared to donors. These findings were mirrored by semi-quantitative analysis of S100A4 immunostaining. Analogous to human lungs, in mice with tobacco-smoke-induced emphysema an up-regulation of S100A4 mRNA and protein was observed in intrapulmonary arteries. Putative HREs could be identified in the promoter region of the human S100A4 gene and their functionality was confirmed by mobility shift assay. Knock-down of HIF1/2 by siRNA attenuated hypoxia-dependent increase in S100A4 mRNA levels in human primary pulmonary artery smooth muscle cells. Interestingly, RAGE mRNA expression was enhanced in pulmonary arteries of tobacco-smoke exposed mice but not in pulmonary arteries of COPD patients. CONCLUSIONS: As enhanced S100A4 expression was observed in remodeled intrapulmonary arteries of COPD patients, targeting S100A4 could serve as potential therapeutic option for prevention of vascular remodeling in COPD patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12931-015-0284-5) contains supplementary material, which is available to authorized users

Early Devonian (Late Emsian) shark fin remains (Chondrichthyes) from the Paraná Basin, southern Brazil

This is an open-access article distributed under the terms of the Creative Commons Attribution License [Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)]. The attached file is the published version of the article

Performance of an echo canceller based on pseudo-noise training sequences

Different design issues and performance aspects of a lowcomplexity echo canceller for digital On-Channel Repeaters (OCRs) are described in this paper. Locally generated lowpower PN sequences are injected in the repeated signal to facilitate the estimation process of the coupling channel between the transmitting and the receiving antennas. In particular, we analyse a low-complexity channel estimation technique based on the autocorrelation properties of the training sequence. An expression for the cancelling performance is found analytically, in terms of Mean Rejection Ratio (MRR), and the impact of the filtering stages within the repeater is also addressed