Treatment of Chronic Kidney Disease with Extracellular Vesicles from Mesenchymal Stem Cells and CD133+ Expanded Cells: A Comparative Preclinical Analysis

Chronic kidney disease (CKD) is characterized by structural abnormalities and the progressive loss of kidney function. Extracellular vesicles (EVs) from human umbilical cord tissue (hUCT)-derived mesenchymal stem cells (MSCs) and expanded human umbilical cord blood (hUCB)-derived CD133⁺ cells (eCD133⁺) maintain the characteristics of the parent cells, providing a new form of cell-free treatment. We evaluated the effects of EVs from hUCT-derived MSCs and hUCB-derived CD133⁺ cells on rats with CDK induced by an adenine-enriched diet. EVs were isolated by ultracentrifugation and characterized by nanoparticle tracking analysis (NTA) and electron microscopy. The animals were randomized and divided into the MSC-EV group, eEPC-EV group and control group. Infusions occurred on the seventh and 14th days after CKD induction. Evaluations of kidney function were carried out by biochemical and histological analyses. Intense labeling of the α-SMA protein was observed when comparing the control with MSC-EVs. In both groups treated with EVs, a significant increase in serum albumin was observed, and the increase in cystatin C was inhibited. The results indicated improvements in renal function in CKD, demonstrating the therapeutic potential of EVs derived from MSCs and eCD133⁺ cells and suggesting the possibility that in the future, more than one type of EV will be used concurrently.     

The BDNF/TrkB Neurotrophin System in the Sensory Organs of Zebrafish

The brain-derived neurotrophic factor (BDNF) was discovered in the last century, and identified as a member of the neurotrophin family. BDNF shares approximately 50% of its amino acid with other neurotrophins such as NGF, NT-3 and NT-4/5, and its linear amino acid sequences in zebrafish (Danio rerio) and human are 91% identical. BDNF functions can be mediated by two categories of receptors: p75NTR and Trk. Intriguingly, BDNF receptors were highly conserved in the process of evolution, as were the other NTs’ receptors. In this review, we update current knowledge about the distribution and functions of the BDNF-TrkB system in the sensory organs of zebrafish. In fish, particularly in zebrafish, the distribution and functions of BDNF and TrkB in the brain have been widely studied. Both components of the system, associated or segregated, are also present outside the central nervous system, especially in sensory organs including the inner ear, lateral line system, retina, taste buds and olfactory epithelium.     

The L467F-F508del Complex Allele Hampers Pharmacological Rescue of Mutant CFTR by Elexacaftor/Tezacaftor/Ivacaftor in Cystic Fibrosis Patients: The Value of the Ex Vivo Nasal Epithelial Model to Address Non-Responders to CFTR-Modulating Drugs

Loss-of-function mutations of the CFTR gene cause cystic fibrosis (CF) through a variety of molecular mechanisms involving altered expression, trafficking, and/or activity of the CFTR chloride channel. The most frequent mutation among CF patients, F508del, causes multiple defects that can be, however, overcome by a combination of three pharmacological agents that improve CFTR channel trafficking and gating, namely, elexacaftor, tezacaftor, and ivacaftor. This study was prompted by the evidence of two CF patients, compound heterozygous for F508del and a minimal function variant, who failed to obtain any beneficial effects following treatment with the triple drug combination. Functional studies on nasal epithelia generated in vitro from these patients confirmed the lack of response to pharmacological treatment. Molecular characterization highlighted the presence of an additional amino acid substitution, L467F, in cis with the F508del variant, demonstrating that both patients were carriers of a complex allele. Functional and biochemical assays in heterologous expression systems demonstrated that the double mutant L467F-F508del has a severely reduced activity, with negligible rescue by CFTR modulators. While further studies are needed to investigate the actual prevalence of the L467F-F508del allele, our results suggest that this complex allele should be taken into consideration as plausible cause in CF patients not responding to CFTR modulators.     

Evaluation of layout and atmospheric stability effects in wind farms using large‐eddy simulation

Large‐eddy simulation (LES) has been used previously to study the effect of either configuration or atmospheric stability on the power generated by large wind farms. This is the first study to consider both stability and wind farm configuration simultaneously and methodically with LES. Two prevailing wind directions, two layouts (turbines aligned versus staggered with respect to the wind) and three stabilities (neutral and moderately unstable and stable) were evaluated. Compared with neutral conditions, unstable conditions led to reduced wake losses in one configuration, to enhanced wake losses in two and to unchanged wake losses in one configuration. Conversely, stable conditions led to increased wake losses in one, decreased wake losses in two and unchanged wake losses in one configuration. Three competing effects, namely, rates of wake recovery due to vertical mixing, horizontal spread of wakes and localized regions of acceleration caused by multiple upstream wakes, were identified as being responsible for the observed trends in wake losses. The detailed flow features responsible for these non‐linear interactions could only be resolved by the LES. Existing analytical models ignore stability and non‐linear configuration effects, which therefore need to be incorporated. Copyright © 2017 John Wiley & Sons, Ltd.     

CFD model performance benchmark of fast filling simulations of hydrogen tanks with pre-cooling

High gas temperatures can be reached inside a hydrogen tank during the filling process because of the large pressure increase (up to 70–80 MPa) and because of the short time (∼3 min) of the process. High temperatures can potentially jeopardize the structural integrity of the storage system and one of the strategies to reduce the temperature increase is to pre-cool the hydrogen before injecting it into the tank. Computational Fluid Dynamics (CFD) tools have the capabilities of capturing the flow field and the temperature rise in the tank. The results of CFD simulations of fast filling with pre-cooling are shown and compared with experimental data to assess the accuracy of the CFD model.     

CFD analysis of fast filling scenarios for 70 MPa hydrogen type IV tanks

High injection pressure is combined with high refueling rate for vehicles storing pressurized gaseous hydrogen onboard. As a drawback, high temperatures are developed inside the tank, which can jeopardize the structural integrity of the storage system. Computational Fluid Dynamics (CFD) codes already proved to be a valuable tool for predicting the temperature distribution within the tank during fast refueling. Results of hydrogen fast filling CFD simulations for a type IV tank, filled to 70 MPa at different working conditions are presented as follow up of the CFD model validation performed against experimental data. Alternative rates of pressure rise, adiabatic and cold filling are investigated to evaluate the effect on maximum hydrogen temperatures inside the tank. Results confirmed that the developed CFD model could be a suitable tool for investigating fast filling scenarios when experimental data are not yet available or of difficult realization.     

Quality and safety of maize (Zea mays L.) from Rondônia state storage units,Northern Brazil

The quality and safety of maize (Zea mays L.) from different grain storage units (GSUs), located in the main producing region of Rondônia State, Northern Brazil, were evaluated. Maize grains (n = 76) stored in four GSUs were collected from July to November 2014 and evaluated for grain damages, humidity, fungi and fumonisins (FBs) content. The climate conditions data were also obtained from plant growing to storage periods. Regarding the moisture content and water activity (a_w), these varied from 10.0% to 16.1% and 0.5 to 0.8, respectively. As expected, fungi spores were present in 94.8% of the samples, prevailing Fusarium genera, with a fungi colony maximum of 2.2 × 10⁴ CFU g^?1. Regarding FBs, 60.5% of the samples were contaminated, below Brazilian and United States maximum limits, but 9.2% had levels higher than the European legislation.     

Microencapsulation of Propolis in Protein Matrix Using Spray Drying for Application in Food Systems

Propolis presents several health benefits due to the presence of bioactive compounds, mainly phenolic compounds; however, its application in food is limited due to undesirable odor and low water solubility. The bioactive compounds are usually susceptible to degradation by exposure to light, heat, or oxygen or by interaction with other compounds, which may limit its biological activity. The study aimed the propolis extract microencapsulation using rice, pea, soybean, and ovoalbumin proteins as wall material by spray drying and to analyze their in vitro digestion. The propolis extract presented a high concentration of apigenin. Encapsulation efficiency was greater than 70%, and it was maintained the antioxidant activity of propolis (88% inhibition of DPPH for propolis extract and >?73% for the microparticles). The DSC, ATR-FTIR, and X-ray diffraction techniques confirmed the encapsulation. The microparticles showed different shapes, sizes, and physical characteristics. The microparticles encapsulated with pea protein could be used in formulations of Minas Frescal cheese due to the controlled released, whereas the other microparticles could be used in pudding formulations.