Mast Cell Chymase and Kidney Disease

A sizable part (~2%) of the human genome encodes for proteases. They are involved in many physiological processes, such as development, reproduction and inflammation, but also play a role in pathology. Mast cells (MC) contain a variety of MC specific proteases, the expression of which may differ between various MC subtypes. Amongst these proteases, chymase represents up to 25% of the total proteins in the MC and is released from cytoplasmic granules upon activation. Once secreted, it cleaves the targets in the local tissue environment, but may also act in lymph nodes infiltrated by MC, or systemically, when reaching the circulation during an inflammatory response. MC have been recognized as important components in the development of kidney disease. Based on this observation, MC chymase has gained interest following the discovery that it contributes to the angiotensin-converting enzyme’s independent generation of angiotensin II, an important inflammatory mediator in the development of kidney disease. Hence, progress regarding its role has been made based on studies using inhibitors but also on mice deficient in MC protease 4 (mMCP-4), the functional murine counterpart of human chymase. In this review, we discuss the role and actions of chymase in kidney disease. While initially believed to contribute to pathogenesis, the accumulated data favor a more subtle view, indicating that chymase may also have beneficial actions.     

Biodegradability Study of the Biosurfactant Contained in a Crude Extract from Corn Steep Water

Over the last few years, the global biosurfactant market has raised due to the increasing awareness among consumers, for the use of biological or bio-based products. Because of their composition, it can be speculated that these are more biocompatible and more biodegradable than their chemical homologous. However, at the moment, no studies exist in the literature about the biodegradability of biosurfactants. In this work, a biosurfactant contained in a crude extract, obtained from a corn wet-milling industry stream that ferments spontaneously in the presence of lactic acid bacteria, was subjected to a biodegradation study, without addition of external microbial biomass, under different conditions of temperature (5–45 °C), biodegradation time (15–55 days), and pH (5–7). For that, a Box–Behnken factorial design was applied, which allowed to predict the percentage of biodegradation for the biosurfactant contained in the crude extract, between the range of the independent variables selected in the study, obtaining biodegradation values between 3 and 80%. The percentage of biodegradation for the biosurfactant was calculated based on the increase in the surface tension of samples of the crude extract. Furthermore, it was also possible to predict the variation in t_1/2 for the biosurfactant (time to achieve the 50% of biodegradation) under different conditions.     

Ga-doped IZO films obtained by magnetron sputtering as transparent conductors for visible and solar applications

C-axis textured thin films of gallium-doped indium zinc oxide (GIZO) with a 2% ratio of Ga/Zn, were obtained via RF-magnetron sputtering with high transparency and electrical conductivity. A Box-Behnken response surface design was used to evaluate the effects of the deposition parameters (In₂O₃ target power, deposition time, and substrate temperature) on the chemical composition, optical, electrical, and structural properties of the GIZO films. The optical constants and the electrical properties were obtained using optical models. The GIZO stoichiometry, and therefore the In/Zn atomic ratio, affected the crystallinity, crystalline parameters, band gap, and charge carrier mobility of the GIZO films. The charge carrier density was related to the change in the crystalline parameters of the hexagonal structure and the In/Zn atomic ratio. The best electrical conductivity values (1.75?×?10³ Ω^?1 cm^?1) were obtained for GIZO films with In/Zn ratio ≥?1. Several figures of merit (FOM) defined for the visible and solar regions were comparatively used to select the optimal In/Zn atomic ratio that provided the best balance between the conductivity and the transparency. The optimal In/Zn ratio was in a range of 0.85–0.90 for the GIZO films.     

Supramolecular Assembly of Aminoethylene‐Lipopeptide PMO Conjugates into RNA Splice‐Switching Nanomicelles

Phosphorodiamidate morpholino oligomers (PMOs) are oligonucleotide analogs that can be used for therapeutic modulation of pre‐mRNA splicing. Similar to other classes of nucleic acid‐based therapeutics, PMOs require delivery systems for efficient transport to the intracellular target sites. Here, artificial peptides based on the oligo(ethylenamino) acid succinyl‐tetraethylenpentamine (Stp), hydrophobic modifications, and an azide group are presented, which are used for strain‐promoted azide‐alkyne cycloaddition conjugation with splice‐switching PMOs. By systematically varying the lead structure and formulation, it is determined that the type of contained fatty acid and supramolecular assembly have a critical impact on the delivery efficacy. A compound containing linolenic acid with three cis double bonds exhibits the highest splice‐switching activity and significantly increases functional protein expression in pLuc/705 reporter cells in vitro and after local administration in vivo. Structural and mechanistic studies reveal that the lipopeptide PMO conjugates form nanoparticles, which accelerate cellular uptake and that the content of unsaturated fatty acids enhances endosomal escape. In an in vitro Duchenne muscular dystrophy exon skipping model using H2K‐mdx52 dystrophic skeletal myotubes, the highly potent PMO conjugates mediate significant splice‐switching at very low nanomolar concentrations. The presented aminoethylene‐lipopeptides are thus a promising platform for the generation of PMO‐therapeutics with a favorable activity/toxicity profile.     

Synergistic antimicrobial effect of lactocin AL705 and nisin combined with organic acid salts against Listeria innocua 7 in broth and a hard cheese

The effectiveness of antimicrobial mixtures against Listeria innocua 7, used as a L. monocytogenes surrogate, was investigated in broth and a food system. Synergistic effects were found for nisin (Nis), potassium sorbate (PS), calcium propionate (CP) and sodium lactate (SL), Nis + PS being the most effective binary mixture that exhibited listericidal activity in broth. To assess the effect of adding lactocin AL705 (AL705) to Nis + organic acid salt combinations, tridimensional isobolograms were generated. Sub-MIC combinations of the antimicrobials exerted bactericidal activity against L. innocua 7 after AL705 addition to the binary mixtures. However, when applied on Sardo cheese contaminated with L. innocua 7 (initial inoculum 4.45 ± 0.06 CFU g⁻¹), only Nis + PS + AL705 produced count reductions respect to the control, reaching 3.04 ± 0.35 CFU g⁻¹ counts after 15 days at 15 °C. Ternary combinations containing AL705 showed potential to reduce antimicrobial usages for L. innocua 7 inhibition.     

Hierarchical micro-nanostructured albite-based glass-ceramic for high dielectric strength insulators

A novel glass-ceramic material based on albite type Na-rich feldspar has been synthesized by conventional ceramic process. High crystallinity, >94%?Vol.% is obtained by fast sintering which allows energy saving processing. Albite is the main crystalline phase and tetragonal SiO₂ is a secondary phase. Electrical properties were examined by complex impedance, DC measurements, and dielectric breakdown test. Dielectric characterization shows a non-Debye type dielectric behavior with low dielectric constant, 4.6 at 1?MHz, low dielectric losses, (～10^?3 at 1?MHz, and a large dielectric strength, ～60?kV/mm), that it is the largest value reported in ceramic insulators. Those dielectric properties are attained by the low glassy phase content in the samples and their unique micro-nanostructure. All these properties make this novel material a very promising candidate in the market of ceramic electrical insulator, highlighting for high-voltage applications.