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.     

A simple model for deep dynamic stall conditions

The present study is focused on modeling of dynamic stall behavior of a pitching airfoil. The deep stall regime is in particular considered. A model is proposed, which has a low implementation and computational complexity but yet is able to deal with different types of dynamic stall conditions, including those characterized by multiple vortex shedding at the airfoil leading edge. The proposed model is appraised against an extensive data set of experimental (α,C_L) curves for NACA0012. The results of an existing widely used model, having comparable complexity, are also shown for comparison. The proposed model is able to well reproduce not only the classic curves of deep dynamic stall but also the curves characterized by lift oscillations at high angles of attack due to the shedding of multiple vortices. Furthermore, the model appears to be robust to variations of its parameters from the optimal values and of the airfoil geometry. Finally, the model is successfully implemented in a commercial CFD software and applied to the simulation of a vertical axis wind turbine within the actuator cylinder approach. The accuracy of the prediction of the turbine power coefficient in the whole rotation cycle is very good for the optimal working condition of the turbine, for which the model parameters were calibrated. Fairly good accuracy is also obtained in significantly different working conditions without any further calibration.     

Biotransformation of Waste Bile Acids: A New Possible Sustainable Approach to Anti-Fungal Molecules for Crop Plant Bioprotection?

Phytopathogenic fungi are among the main causes of productivity losses in agriculture. To date, synthetic chemical pesticides, such as hydroxyanilides, anilinopyrimidines and azole derivatives, represent the main treatment tools for crop plant defence. However, the large and uncontrolled use of these substances has evidenced several side effects, namely the resistance to treatments, environmental damage and human health risks. The general trend is to replace chemicals with natural molecules in order to reduce these side effects. Moreover, the valorisation of agri-food industry by-products through biotransformation processes represents a sustainable alternative to chemical synthesis in several sectors. This research is aimed at comparing the anti-phytopathogenic activity of waste bovine and porcine bile with secosteroids obtained by biotransformation of bile acids with Rhodococcus strains. The ultimate goal is to apply these natural products on food crops affected by phytopathogenic fungi.     

Electroporation-Induced Cell Modifications Detected with THz Time-Domain Spectroscopy

Electroporation (electropermeabilization) increases the electrical conductivity of biological cell membranes and lowers transport barriers for normally impermeant materials. Molecular simulations suggest that electroporation begins with the reorganization of water and lipid head group dipoles in the phospholipid bilayer interface, driven by an externally applied electric field, and the evolution of the resulting defects into water-filled, lipid pores. The interior of the electroporated membrane thus contains water, which should provide a signature for detection of the electropermeabilized state. In this feasibility study, we use THz time-domain spectroscopy, a powerful tool for investigating biomolecular systems and their interactions with water, to detect electroporation in human cells subjected to permeabilizing pulsed electric fields (PEFs). The time-domain response of electroporated human monocytes was acquired with a commercial THz, time-domain spectrometer. For each sample, frequency spectra were calculated, and the absorption coefficient and refractive index were extracted in the frequency range between 0.2 and 1.5 THz. This analysis reveals a higher absorption of THz radiation by PEF-exposed cells, with respect to sham-exposed ones, consistent with the intrusion of water into the cell through the permeabilized membrane that is presumed to be associated with electroporation.     

Nonalcoholic Fatty Liver: A Possible New Target for Type 2 Diabetes Prevention and Treatment

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder worldwide. Several lines of evidence have indicated a pathogenic role of insulin resistance, and a strong association with type 2 diabetes (T2MD) and metabolic syndrome. Importantly, NAFLD appears to enhance the risk for T2MD, as well as worsen glycemic control and cardiovascular disease in diabetic patients. In turn, T2MD may promote NAFLD progression. The opportunity to take into account NAFLD in T2MD prevention and care has stimulated several clinical studies in which antidiabetic drugs, such as metformin, thiazolidinediones, GLP-1 analogues and DPP-4 inhibitors have been evaluated in NAFLD patients. In this review, we provide an overview of preclinical and clinical evidences on the possible efficacy of antidiabetic drugs in NAFLD treatment. Overall, available data suggest that metformin has beneficial effects on body weight reduction and metabolic parameters, with uncertain effects on liver histology, while pioglitazone may improve liver histology. Few data, mostly preclinical, are available on DPP4 inhibitors and GLP-1 analogues. The heterogeneity of these studies and the small number of patients do not allow for firm conclusions about treatment guidelines, and further randomized, controlled studies are needed.     

A 3D moisture-stress FEM analysis for time dependent problems in timber structures

This paper presents a 3D moisture-stress numerical analysis for timber structures under variable humidity and load conditions. An orthotropic viscoelastic-mechanosorptive material model is specialized on the basis of previous models. Both the constitutive model and the equations needed to describe the moisture flow across the structure are implemented into user subroutines of the Abaqus finite element code and a coupled moisture-stress analysis is performed for several types of mechanical loads and moisture changes. The presented computational approach is validated by analyzing some wood tests described in the literature and comparing the computational results with the reported experimental data.     

Design and analysis of an integrated antiresonant reflecting optical waveguide refractive-index sensor

An integrated optical waveguide refractometer, believed to be novel, is presented. The sensor is based on an antiresonant reflecting optical waveguide and uses the strong attenuation dependence on the refractive index of antiresonant cladding layers as the sensing principle. The theory and the operation of the sensor are discussed in terms of one- and two-dimensional geometry. The theoretical predictions and numerical analysis show that a versatile sensor can be realized. The design trade-offs are discussed, and the sensitivity and measurement range are presented.     

Hourly indoor radon measurements in a research house

This paper reports and discusses the behaviour of radon concentration with time in an uninhabited dwelling. The relationship between variations in radon concentrations and indoor-outdoor temperatures and wind intensity has also been discussed. Radon concentration was measured hourly in a house located at a height of 800 m in the Lombard Prealps, at the top of the Valassina valley. The wind velocity and indoor-outdoor temperatures were measured by means of a meteorological station located on the terrace of the house. The data were analysed using the LBL model for indoor-outdoor air exchange and the models for the indoor accumulation of radon due to exhalation from building materials and pressure-driven infiltrations located underground. The role of wind and indoor-outdoor temperatures were analysed. The agreement of measurements with modelling clearly demonstrates the importance of the different sources of indoor radon. As the investigation was conducted in an uninhabited house, the measurements were not affected by the behaviour of people, e.g. opening and closing of windows. Measurements of the outdoor atmospheric concentrations of (222)Rn provide an index of the atmospheric stability, the formation of thermal inversions and convective turbulence.     

A cyclic CCK8 analogue selective for the cholecystokinin type A receptor: design, synthesis, NMR structure and binding measurements

A cyclic CCK8 analogue, cyclo(29,34)[Dpr(29),Lys(34)]-CCK8 (Dpr=L-2,3-diaminopropionic acid), has been designed on the basis of the NMR structure of the bimolecular complex between the N-terminal fragment of the CCK(A) receptor and its natural ligand CCK8. The conformational features of cyclo(29,34)[Dpr(29),Lys(34)]-CCK8 have been determined by NMR spectroscopy in aqueous solution and in water containing DPC-d(38) micelles (DPC=dodecylphosphocholine). The structure of the cyclic peptide in aqueous solution is found to be in a relaxed conformation, with the backbone and Dpr29 side chain atoms making a planar ring and the N-terminal tripeptide extending approximately along the plane of this ring. In DPC/water, the cyclic peptide adopts a "boat-shaped" conformation, which is more compact than that found in aqueous solution. The cyclic constraint between the Dpr29 side chain and the CCK8 carboxyl terminus (Lys34) introduces a restriction in the backbone conformational freedom. However, the interaction of cyclo(29,34)[Dpr(29),Lys(34)]-CCK8 with the micelles still plays an important role in the stabilisation of the bioactive conformation. A careful comparison of the NMR structure of the cyclic peptide in a DPC micelle aqueous solution with the structure of the rationally designed model underlines that the turn-like conformation in the Trp30-Met31 region is preserved, such that the Trp30 and Met31 side chains can adopt the proper spatial orientation to interact with the CCK(A) receptor. The binding properties of cyclo(29,34)[Dpr(29),Lys(34)]-CCK8 to the N-terminal receptor fragment have been investigated by fluorescence spectroscopy in a micellar environment. Estimates of the apparent dissociation constant, K(d), were in the range of 70-150 nM, with a mean value of 120+/-27 nM. Preliminary nuclear medicine studies on cell lines transfected with the CCK(A) receptor indicate that the sulfated-Tyr derivative of cyclo(29,34)[Dpr(29),Lys(34)]-CCK8 displaces the natural ligand with an IC(50) value of 15 microM.