Prospects of the use of beta-carotene enriched food products in the prevention and therapy of radiation injuries]

Radio-protective effectiveness of short-term (19 and 4 h before, 4 and 24 h after irradiation), long-term (3 times/week during 30 days after irradiation) and delayed (1 or 2 days after irradiation) enrichment with crystallized beta-carotene, in single doses of 0.1, 1.0 or 5.0 mg was evaluated in experimental acute external gamma-irradiation (0.029 Gy/sec) within the range of absorbed doses 9--6 Gy. The results obtained have permitted the authors to recommend the ration enriched with carotinoid for prevention and therapy of acute radiation injuries.     

Near-infrared spectroscopy to assist authentication and labeling of Asiago d’allevo cheese

This study investigated the possibility of using near-infrared spectroscopy (NIRS) for the authentication of Asiago d’allevo, a protected designation of origin cheese from northern Italy. Latent variable models applied on spectral data were developed and used to estimate several chemical properties and to classify the available dataset according to the location and management of the cheesemaking factory (lowland and alpine), the ripening age (6, 12, 18 and 36 months), the altitude of milk production (low, medium, medium–high and high), and the period of the year of the cheese production (May, July and September). The variable importance in projection index was used to identify the most informative spectral regions for discrimination. Results showed that NIR spectra can be used both to accurately estimate several chemical properties and to classify the samples according to the different experimental conditions under investigation with the same discrimination capacity provided by traditional chemical analysis.     

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.     

Microbial communities and malt quality of durum wheat used in brewing

Durum wheat (Triticum durum Desf.) has potential as an adjunct in brewing given its agronomic, chemical and technological properties. The aim of this work were to identify the cultivable microflora and evaluate the technological quality of the durum wheat variety ‘Senatore Cappelli’ grown and used by a craft brewery in Sardinia, Italy. The isolated bacterial strains were mainly rhizospheric (Kocuria rizophila, Microbacterium aerolatum and Bacillus pumilus) and associated with the microbiota of wheat (Staphylococcus spp.). None have been reported previously as spoilage species in brewing. The dominant yeast genera were Cryptococcus spp. and Rhodotorula spp., followed by Saccharomyces cerevisiae. The dominant filamentous fungus genera were Alternaria and Rhizopus. Low levels of mycotoxigenic Fusarium spp., Aspergillus spp. and Penicillium spp. were isolated. However, the levels of deoxynivalenol, T2‐HT2, fumonisin, aflatoxin and ochratoxin detected in the malt and grain were below the thresholds defined by European law. Malt obtained from raw grain showed interesting technological properties, but required specific malting parameters different from those of common wheat and barley. These data suggest that the use of locally grown durum wheat in brewing can increase sustainability and reduce costs, while reinforcing the link with the terroir and promoting reduced mycotoxin levels. © 2019 The Institute of Brewing & Distilling     

Use of pulsed Doppler tissue imaging to assess regional left ventricular diastolic dysfunction in hypertrophic cardiomyopathy

In this study, regional diastolic patterns and their relations with transmitral Doppler inflow were investigated in hypertrophic cardiomyopathy (HC) by pulsed Doppler tissue imaging (DTI). Doppler echocardiography and DTI of basal septum and lateral wall (apical 4-chamber view) were performed in 20 patients (15 men and 5 women) with HC and in 10 healthy subjects (7 men and 3 women). Diabetes, hypertension, coronary artery and valvular disease, mitral regurgitation, New York Heart Association functional classes III to IV, sinus tachycardia, atrial fibrillation, and inadequate echocardiograms were exclusion criteria. Peak velocity and time-velocity integral of early and late waves and their ratios, and deceleration and isovolumic relaxation times were determined by standard Doppler and by DTI at the septal and lateral wall levels. The 2 groups were comparable for age, heart rate, blood pressure, and ejection fraction. Transmitral peak velocity and time-velocity integral E/A ratios were reduced (both p <0.05) and deceleration and isovolumic relaxation times prolonged (both p <0.00001) in HC. Septal DTI showed lower peak velocity and time-velocity integral e/a ratios (p <0.00001 and p <0.001, respectively) and lengthened regional deceleration (p <0.01) and isovolumic (p <0.001) relaxation times. DTI of the lateral wall showed a prolongation of deceleration and isovolumic relaxation times (both p <0.01). By dividing HC according to transmitral E/A, 8 patients with E/A <1 had lower DTI septal e/a ratio (p <0.01) and prolonged septal deceleration and isovolumic relaxation times (both p <0.01) but no changes in DTI pattern of lateral wall than 12 patients with E/A > 1. In conclusion, DTI is useful and complementary to standard Doppler imaging to characterize diastolic properties in HC, reflecting a typical pattern of intramyocardial impaired relaxation at the level of hypertrophied septum and also providing information about the degree of this regional impairment. The lateral wall presents minor changes in diastolic times, which indicate how diastolic asynchrony is not confined to the hypertrophied segment in HC.     

Genomic Analysis Made It Possible to Identify Gene-Driver Alterations Covering the Time Window between Diagnosis of Neuroblastoma 4S and the Progression to Stage 4

Neuroblastoma (NB) is a tumor of the developing sympathetic nervous system. Despite recent advances in understanding the complexity of NB, the mechanisms that determine its regression or progression are still largely unknown. Stage 4S NB is characterized by a favorable course of disease and often by spontaneous regression, while progression to true stage 4 is a very rare event. Here, we focused on genomic analysis of an NB case that progressed from stage 4S to stage 4 with a very poor outcome. Array-comparative genomic hybridization (a-CGH) on tumor-tissue DNA, and whole-exome sequencing (WES) on exosomes DNA derived from plasma collected at the onset and at the tumor progression, pointed out relevant genetic changes that can explain this clinical worsening. The combination of a-CGH and WES data allowed for the identification iof somatic copy number aberrations and single-nucleotide variants in genes known to be responsible for aggressive NB. KLRB1, MAPK3 and FANCA genes, which were lost at the time of progression, were studied for their possible role in this event by analyzing in silico the impact of their expression on the outcome of 786 NB patients.     

The Inhibition of the Inducible Nitric Oxide Synthase Enhances the DPSC Mineralization under LPS-Induced Inflammation

Nitric oxide (NO) is a key messenger in physiological and pathological processes in mammals. An excessive NO production is associated with pathological conditions underlying the inflammation response as a trigger. Among others, dental pulp inflammation results from the invasion of dentin by pathogenic bacteria. Vital functions of pulp mesenchymal stem cells (DPSCs, dental pulp stem cells), such as mineralization, might be affected by the inducible NOS (iNOS) upregulation. In this context, the iNOS selective inhibition can be considered an innovative therapeutic strategy to counteract inflammation and to promote the regeneration of the dentin-pulp complex. The present work aims at evaluating two acetamidines structurally related to the selective iNOS inhibitor 1400W, namely CM544 and FAB1020, in a model of LPS-stimulated primary DPSCs. Our data reveal that CM544 and even more FAB1020 are promising anti-inflammatory compounds, decreasing IL-6 secretion by enhancing CD73 expression-levels, a protein involved in innate immunity processes and thus confirming an immunomodulatory role of DPSCs. In parallel, cell mineralization potential is retained in the presence of compounds as well as VEGF secretion, and thus their angiogenetic potential. Data presented lay the ground for further investigation on the anti-inflammatory potential of acetamidines selectively targeting iNOS in a clinical context.     

Binding Mode and Structure–Activity Relationships around Direct Inhibitors of the Nrf2–Keap1 Complex

An X‐ray crystal structure of Kelch‐like ECH‐associated protein (Keap1) co‐crystallised with (1S,2R)‐2‐[(1S)‐1‐[(1,3‐dioxo‐2,3‐dihydro‐1H‐isoindol‐2‐yl)methyl]‐1,2,3,4‐tetrahydroisoquinolin‐2‐carbonyl]cyclohexane‐1‐carboxylic acid (compound (S,R,S)‐ 1 a ) was obtained. This X‐ray crystal structure provides breakthrough experimental evidence for the true binding mode of the hit compound (S,R,S)‐ 1 a , as the ligand orientation was found to differ from that of the initial docking model, which was available at the start of the project. Crystallographic elucidation of this binding mode helped to focus and drive the drug design process more effectively and efficiently.     

Structural defects in (100) 3C-SiC heteroepitaxy: Influence of the buffer layer morphology on generation and propagation of stacking faults and microtwins

Growth of 3C-SiC on (100) Si has been performed via chemical vapor deposition under two pressure regimes (low and atmospheric pressure) in the early stage of growth. Atomic force microscopy (AFM) and transmission electron microscopy (TEM) have been conducted to study the initial stage of growth while X-ray diffractometry (XRD) and TEM have been used to analyze thicker films and to detect and quantify defects, resulting in a comprehensive and detailed investigation of 3C-SiC structural defects. We have found out that the secondary nucleation of 3C-SiC island growth leads to a higher defect generation rate and, at the same time, to a more effective defect elimination rate. Hillocks found on the surface of thin samples grown under reduced pressure conditions are more pronounced as they seem to be a consequence of twins created in the early stage of growth. Finally, a different initial nucleation density (in the two pressure regimes considered) does not strongly influence stacking fault and microtwin density when growth of thick 3C-SiC films is performed. A very strong influence is indeed observed when 3C-SiC thickness is limited to hundreds of nanometers.     

Influence of synthesis conditions on carbonate entrapment in perovskite SrSnO3

Strontium stannate (SrSnO₃), a perovskite material, was synthesized by the polymeric precursor method, with different routes to eliminate organic matter. The utilization of pure oxygen for the elimination of organic matter changed the Raman spectra, especially in the low frequency region. Some peaks, which were previously assigned to the perovskite phase, were not noticed when the carbonate amount was lower. On the other hand, the profile of the IR spectra and XRD patterns did not change. These results suggest that carbonate may be present inside the perovskite lattice.