TLR4 Up-regulation and Reduced Foxp3 Expression in Mechanically Ventilated Smokers with Obstructive Chronic Bronchitis

Background: Chronic bronchitis (CB) is a risk factor in chronic obstructive pulmonary disease (COPD) for accelerated lung function decline and increased mortality. The lung and systemic inflammatory and immunological profile of COPD patients with CB which acutely experience respiratory failure upon a disease exacerbation is unknown. Methods: In this study, we explored the expression of Foxp3 by western blot analysis, TLR4 by immunocytochemistry and the concentrations of IP-10 and IL-8 by ELISA in the mini-bronchoalveolar lavages (mini-BAL) and in the peripheral blood of patients with respiratory failure requiring intubation and mechanical ventilation. The recruited subjects were separated into three different groups: smokers with CB and COPD (COPD, n = 18), smokers with CB but without COPD (S, n = 8) and patients without CB and without COPD (C, n = 10). Results: In mini-BAL of COPD group, Foxp3 and IP-10 were significantly reduced while TLR4 was significantly increased in comparison to C. TLR4 was also increased in mini-BAL of S. In COPD peripheral blood, Foxp3 was reduced in comparison to C but no significant differences were observed for TLR4 and for IP-10. No significant differences were observed for IL-8 concentrations in the mini-BAL and in the blood of the recruited patients. The mini-BAL TLR4 expression correlated with the Clinical Infective Pulmonary Score. Conclusions: In exacerbated COPD patients with respiratory failure, lung and systemic reduced immune regulatory events (low Foxp3 expression) and lung increased innate immunity responses (high TLR4 expression) occur. These events may contribute to the increased inflammatory events leading to respiratory failure

Nuclear Cusps and Cores in Early-type Galaxies As Relics of Binary Black Hole Mergers

We present an analysis of the central cusp slopes and core parameters of early-type galaxies using a large database of surface brightness profiles obtained from Hubble Space Telescope observations. We examine the relation between the central cusp slopes, core parameters, and black hole masses in early-type galaxies, in light of two models that attempt to explain the formation of cores and density cusps via the dynamical influence of black holes. Contrary to the expectations from adiabatic-growth models, we find that the cusp slopes do not steepen with increasing black hole mass fraction. Moreover, a comparison of kinematic black hole mass measurements with the masses predicted by the adiabatic models shows that they overpredict the masses by a factor of approximately 3. Simulations involving binary black hole mergers predict that both the size of the core and the central mass deficit correlate with the final black hole mass. These relations are qualitatively supported by the present data.Comment: To appear in ApJ. 8 page

Cellular models and assays to study NLRP3 inflammasome biology

The NLRP3 inflammasome is a multi-protein complex that initiates innate immunity responses when exposed to a wide range of stimuli, including pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs). Inflammasome activation leads to the release of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 and to pyroptotic cell death. Over-activation of NLRP3 inflammasome has been associated with several chronic inflammatory diseases. A deep knowledge of NLRP3 inflammasome biology is required to better exploit its potential as therapeutic target and for the development of new selective drugs. To this purpose, in the past few years, several tools have been developed for the biological characterization of the multimeric inflammasome complex, the identification of the upstream signaling cascade leading to inflammasome activation, and the downstream effects triggered by NLRP3 activation. In this review, we will report cellular models and cellular, biochemical, and biophysical assays that are currently available for studying inflammasome biology. A special focus will be on those models/assays that have been used to identify NLRP3 inhibitors and their mechanism of action

Influence of bicarbonate/carbonate removal on magnesium hydroxide slurry: A pilot study

Nowadays, the continuous increase in raw materials demand is leading research to seek alternative and unconventional sources, such as waste industrial brine or seawater. Indeed, seawater and seawater brines (e.g. produced by seawater reverse osmosis (RO) desalination plant) can be exploited in order to recover fresh water but also to produce many other valuable minerals such as magnesium. The importance of the magnesium recovery stands for its high risk of supply and significant economic importance for key sectors in the European economy. Thus, magnesium has been defined as one of thirty-four Critical Raw Materials (CRMs) by the European Commission. In the framework of the Horizion 2020 European Project Water Mining, a novel and unconventional selective reactive crystallizer designed by ResourSEAs was tested for the recovery of magnesium in form of hydroxide by means of direct mixing with an alkaline solution (i.e. sodium hydroxide solution). This crystallizer is called Multiple Feed Plug Flow Reactor (MF-PFR). The MF-PFR was installed within an integrated demonstration plant aiming at the production of magnesium hydroxide, chemicals (such as sodium hydroxide and hydrochloric acid), fresh water, sodium sulfate, and sodium chloride, combining together (i) nanofiltration, (ii) MF-PFR, (iii) Eutetic Freez Crystallizer (EFC), (iv) Electro-dialysis with bipolar membrane, and (v) Multiple Effect Distillation (MED). A wide experimental campaign has been carried out aiming at investigating how the settling rate and purity are influenced by operative conditions, such brine feed or recycle flow-rates, and by the nature of the feed brine itself (i.e. NF retentate or RO retentate). The results obtained show that decreasing feed brine flow-rate is consistent with an increase in the settling rate, while conversely decreasing recycle flow rate leads to a clear decrease. This behavior was observed for both feed brine solutions. Moreover, also the influence of the presence of carbonate and bicarbonates in the feed stream on product settling rate and purity was investigated by applying an acidification pretreatment step. After this step, a purity increase from 94% up to 98/99% along with an increase in sedimentation rate (up to two times) was obtained. These outcomes were observed for both feed brine solutions

Performance of the first reverse electrodialysis pilot plant for power production from saline waters and concentrated brines

This work reports experimental data collected for the first time on a full-scale RED pilot plant operated with natural streams in a real environment. The plant - located in the South of Italy - represents the final accomplishment of the REAPower project (www.reapower.eu). A RED unit equipped with almost 50m2 of IEMs (125 cell pairs, 44x44cm2) was tested, using both artificial and natural feed solutions, these latter corresponding to brackish water (≈0.03M NaClequivalent) and saturated brine (4-5M NaClequivalent). A power output up to around 40W (i.e. 1.6W/m2 of cell pair) was reached using natural solutions, while an increase of 60% was observed when testing the system with artificial NaCl solutions, reaching up to ≈65W (2.7W/m2 of cell pair). The unit performance was monitored over a period of five months under, and no significant performance losses were observed due to scaling, fouling or ageing phenomena. Such results are of paramount importance to assess the potential of the technology, towards the successful development on the industrial scale. A scale-up of the pilot plant is planned through the installation of two additional RED modules, with an expected power output in the order of 1 kW

MED parallel system powered by concentrating solar power (CSP): model and case study: Trapani, Sicily

This work presents an overlook on a new model that simulates the physical operation in steady state of a multi-effect distillation (MED) plant with parallel-feed (P) configuration. This model includes the consumption of steam with steam ejectors, and its validation was done using data from a real MED industrial plant using a thermal vapor compressor (TVC) operating in Italy, in the Sicilian city of Trapani. Results show that the MED model returns accurate predictions of the plant behavior, very useful for a first analysis on such type of investments. This MED model was also integrated into the system advisor model developed by the US National Renewable Energy Laboratory. Simulations with this new tool were run using the location of Trapani as case study for a concentrating solar power (CSP) plant working in cogeneration with a low-temperature MED-P plant vs. other cooling options available for CSP plants (wet cooling, dry cooling, and a once through seawater cooling circuit). These results were compared with the existing TVC-MED plant, and indicate that CSP+MED has the potential to be economically attractive

Multi-scale modelling of an electrodialysis with bipolar membranes pilot plant and economic evaluation of its potential

Sodium hydroxide and hydrochloric acid are widely used chemicals in different industrial sectors. To minimize costs and risks associated with transportation, handling and storage, these hazardous chemicals can be produced in situ employing electrodialysis with bipolar membranes (EDBM). This work presents a multi-scale model capable of simulating large scale EDBM units with complex stack configuration (i.e., internal staging) that can be used to design and optimize the process. The model was validated in two different process configurations using experimental results obtained from an EDBM pilot plant. Discrepancies between model and experimental results in the range of 2–11 % were obtained. The validated model was used to conduct a techno-economic evaluation adopting the feed and bleed configuration. Results show that current efficiency increases as the current density rises. At 600 A m−2, values of current efficiency between 72 % and 96 % were found for sodium hydroxide concentration in the range of 0.5–1 mol L−1. The levelized cost of sodium hydroxide (LCoNaOH) was evaluated, in the same range of concentrations, demonstrating that values between 280 and 370 € ton−1 can be obtained, fixing the electricity prince (0.1 kWh kg−1) and the triplet specific cost (600 US$m−2). Moreover, assuming a reduced cost of electricity and triplet to 0.05 kWh kg−1 and 300 US$ m−2, respectively, an absolute minimum of 140 € ton−1 was found for the target 0.5 mol L−1. A double stage EDBM configuration was simulated to show the scale-up potentials of the multi-scale model. A reduction in the LcoNaOH of 10 % was obtained for a target concentration of 1 mol L−1. These results prove the attractiveness of the EDBM technology for producing in situ chemicals

Electrochemical Synthesis of Zinc Oxide Nanostructures on Flexible Substrate and Application as an Electrochemical Immunoglobulin-G Immunosensor

Immunoglobulin G (IgG), a type of antibody, represents approximately 75% of serum antibodies in humans, and is the most common type of antibody found in blood circulation. Consequently, the development of simple, fast and reliable systems for IgG detection, which can be achieved using electrochemical sandwich-type immunosensors, is of considerable interest. In this study we have developed an immunosensor for human (H)-IgG using an inexpensive and very simple fabrication method based on ZnO nanorods (NRs) obtained through the electrodeposition of ZnO. The ZnO NRs were treated by electrodepositing a layer of reduced graphene oxide (rGO) to ensure an easy immobilization of the antibodies. On Indium Tin Oxide supported on Polyethylene Terephthalate/ZnO NRs/rGO substrate, the sandwich configuration of the immunosensor was built through different incubation steps, which were all optimized. The immunosensor is electrochemically active thanks to the presence of gold nanoparticles tagging the secondary antibody. The immunosensor was used to measure the current density of the hydrogen development reaction which is indirectly linked to the concentration of H-IgG. In this way the calibration curve was constructed obtaining a logarithmic linear range of 10–1000 ng/mL with a detection limit of few ng/mL and good sensitivity

Cellular and Molecular Signatures of Oxidative Stress in Bronchial Epithelial Cell Models Injured by Cigarette Smoke Extract

Exposure of the airways epithelium to environmental insults, including cigarette smoke, results in increased oxidative stress due to unbalance between oxidants and antioxidants in favor of oxidants. Oxidative stress is a feature of inflammation and promotes the progression of chronic lung diseases, including Chronic Obstructive Pulmonary Disease (COPD). Increased oxidative stress leads to exhaustion of antioxidant defenses, alterations in autophagy/mitophagy and cell survival regulatory mechanisms, thus promoting cell senescence. All these events are amplified by the increase of inflammation driven by oxidative stress. Several models of bronchial epithelial cells are used to study the molecular mechanisms and the cellular functions altered by cigarette smoke extract (CSE) exposure, and to test the efficacy of molecules with antioxidant properties. This review offers a comprehensive synthesis of human in-vitro and ex-vivo studies published from 2011 to 2021 describing the molecular and cellular mechanisms evoked by CSE exposure in bronchial epithelial cells, the most used experimental models and the mechanisms of action of cellular antioxidants systems as well as natural and synthetic antioxidant compounds

Anti-Apoptotic and Anti-Inflammatory Properties of Grapefruit IntegroPectin on Human Microglial HMC3 Cell Line

In this study, we investigated the beneficial effects of grapefruit IntegroPectin, derived from industrial waste grapefruit peels via hydrodynamic cavitation, on microglia cells exposed to oxidative stress conditions. Grapefruit IntegroPectin fully counteracted cell death and the apoptotic process induced by cell exposure to tert-butyl hydroperoxide (TBH), a powerful hydroperoxide. The protective effects of the grapefruit IntegroPectin were accompanied with a decrease in the amount of ROS, and were strictly dependent on the activation of the phosphoinositide 3-kinase (PI3K)/Akt cascade. Finally, IntegroPectin treatment inhibited the neuroinflammatory response and the basal microglia activation by down-regulating the PI3K- nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB)- inducible nitric oxide synthase (iNOS) cascade. These data strongly support further investigations aimed at exploring IntegroPectin's therapeutic role in in vivo models of neurodegenerative disorders, characterized by a combination of chronic neurodegeneration, oxidative stress and neuroinflammation