Systematic Review: Drug Repositioning for Congenital Disorders of Glycosylation (CDG)

Advances in research have boosted therapy development for congenital disorders of glycosylation (CDG), a group of rare genetic disorders affecting protein and lipid glycosylation and glycosylphosphatidylinositol anchor biosynthesis. The (re)use of known drugs for novel medical purposes, known as drug repositioning, is growing for both common and rare disorders. The latest innovation concerns the rational search for repositioned molecules which also benefits from artificial intelligence (AI). Compared to traditional methods, drug repositioning accelerates the overall drug discovery process while saving costs. This is particularly valuable for rare diseases. AI tools have proven their worth in diagnosis, in disease classification and characterization, and ultimately in therapy discovery in rare diseases. The availability of biomarkers and reliable disease models is critical for research and development of new drugs, especially for rare and heterogeneous diseases such as CDG. This work reviews the literature related to repositioned drugs for CDG, discovered by serendipity or through a systemic approach. Recent advances in biomarkers and disease models are also outlined as well as stakeholders’ views on AI for therapy discovery in CDG.     

Characterization of charge trapping in SiO2/Al2O3 dielectric stacks by pulsed C–V technique

In this work, charge trapping in SiO₂/Al₂O₃ dielectric stacks is characterized by means of pulsed capacitance–voltage measurements. The proposed technique strongly reduces the measurement time and, as a consequence, the impact of charge trapping on the measurement results. Flat band voltage shift and fast current transient during short stress pulses are systematically monitored and the centroid and the amount of the trapped charge are extracted using a first-order model.     

Astringency sub-qualities of red wines and the influence of wine–saliva aggregates

Astringency is a sensory attribute, related to the quality and mouthfeel of red wines. However, the origin of astringency sub-qualities, such as the typical drying astringency found in immature grapes, is still unknown. Astringency of red wines with similar tannin content but different astringency sub-qualities, from different harvest dates, is studied. Astringency was characterised in terms of friction coefficient, polyphenol content, sensory analysis and tannin/salivary–proteins aggregates characterisation. A different evolution during ripening was found for both Cabernet Sauvignon and Carménère, and tannin–protein aggregates showed differences in size, shape and surface. The velvety sub-quality appears to be related to aggregates with low precipitation, and with specific surface characteristics as roundness and Feret diameter. Results from this work propose an effect of aggregates on sensory perception and opens the possibility to explore their effect on oral lubrication.     

Enhancing the sweetening power of lactose by enzymatic modification in the reformulation of dairy products

Lactose solutions of up to 50% (w/v) were incubated with lactases and glucose isomerases for subsequent implementation in dairy product samples to enhance sweetness. A degree of hydrolysis of >90% and of isomerisation of 50% were attainable. The sensory sweetening power of lactose in solutions of up to 50% (w/v) can be enhanced 2–3 times. Based on sensory experiments, application of this bi‐enzymatic system in yoghurt and pudding samples allowed for a 10–20% (w/w) reduction in the total sugar content, whilst retaining equal sweetness. The growth of yoghurt starter cultures was not affected, yet furosine formation more than doubled in high heated, enzyme‐modified milk.     

Relationship Between Chemical Markers and Sensory Score of Traditional Balsamic Vinegars Using a Screening Approach Combined with Rapid Assessment Methods

In this study, 200 samples of traditional balsamic vinegar (TBV) of Reggio-Emilia, a typical Italian “aged dressing” with Protected Denomination of Origin, were analyzed to model the relationship between sensory scores with some pre-selected compounds/parameters, such as Brix value, water activity (a _w), titratable acidity, color, polymeric compounds, and electronic nose signal. Statistical techniques, such as nonlinear regression and Principal Component Analysis (PCA) were used to model the relationship among vinegars composition. The sensory score of panelists was mainly correlated with Brix (r?=?0.85) followed by brown color at 445 nm (r?=?0.74) and water activity (a _w) (r?=??0.79), whereas the polymeric compounds content showed a negative correlation with water activity (r?=?–0.73). In particular, the water activity of TBVs at different Brix values followed a nonlinear trend with good fitting (r?=?0.857) with K?=?3.10 that was consistent with the value reported in the literature for fructose and glucose. Electronic nose (enose) data from TBVs and six marker compounds (acetic acid, butyric acid, vanillin, ethyl-phenylacetate, phenylethyl alcohol, and furfural) combined with PCA revealed a pattern related to the ageing of TBVs.     

Soft-Seeded Pomegranate (<Emphasis Type="Italic">Punica granatum</Emphasis> L.) Varieties: Preliminary Characterization and Quality Changes of Minimally Processed Arils During Storage

A preliminary characterization of two new soft-seeded pomegranate varieties (MR-100® and KINGDOM®) based on their main physico-chemical and nutritional parameters was reported. The two varieties showed significant differences (p ≤ 0.05) in polyphenols, anthocyanins and antioxidant activity. Kingdom pomegranate had higher polyphenols (2524.73 mg GAE/L), anthocyanins (752.49 mg C₃gE/L) and antioxidant activity (EC₅₀ 13.58 μL/mL) than MR-100 (1792.74 mg GAE/L, 141.29 mg C₃gE/L and EC₅₀ 47.53 μL/mL, respectively). Moreover, minimally processed arils of the two varieties were packaged in semipermeable and micro-perforated film at 5 °C, and the quality changes that occurred during storage condition (15 days) were investigated. During storage, Kingdom arils exhibited a better performance in terms of antioxidant activity, polyphenols and anthocyanin content with respect to MR-100. Furthermore, the packaging systems did not affect the estimated quality parameters for both varieties. Based on the sensory evaluation and microbial counts, both aril varieties reached, at 15-day storage, suitable values for commercial purpose.     

Brazilian red propolis: unreported substances, antioxidant and antimicrobial activities

BACKGROUND: Chloroform, ethyl acetate and methanol extracts of a sample of red propolis from the state of Alagoas (northeast Brazil) were analyzed by gas chromatography–mass spectrometry and high‐performance liquid chromatography–diode array detection–electrospray ionization‐mass spectrometry. Antimicrobial and antioxidant activities were also obtained. RESULTS: The propolis sample contained low content of narigenin‐8‐C‐hexoside, this being the first report of a C‐glycoside in propolis. The main constituent found was characterized as 3,4,2′,3′‐tetrahydroxychalcone. Other important constituents were the chalcone isoliquiritigenin, the isoflavans (3S)‐vestitol, (3S)‐7‐O‐methylvestitol, the pterocarpan medicarpin, the phenylpropenes trans‐anethol, methyl eugenol, elimicin, methoxyeugenol and cis‐asarone, and the triterpenic alcohols lupeol and α‐ and β‐ amyrins. The methanol extract exhibited high antioxidant activities by 2,2‐diphenyl‐1‐picrylhydrazyl and β‐carotene/linoleic acid assay methods, and antimicrobial activity toward Gram‐positive and Gram‐negative bacteria. CONCLUSION: Structures are suggested for new substances never before seen in any kind of propolis. This is the first report of 3,4,2′,3′‐tetrahydroxychalcone and a flavone C‐glycoside in a propolis sample. Copyright © 2011 Society of Chemical Industry     

Survival of Lactobacillus rhamnosus strains in the upper gastrointestinal tract

In the present study six probiotic Lactobacillus rhamnosus strains were investigated for their ability to survive in the human upper gastrointestinal tract through a dynamic gastric model of digestion. MRS broth was used as delivery vehicle and survival was investigated during in vitro gastric and gastric plus duodenal digestion. Results highlighted that all tested strains showed good survival rate during both gastric and duodenal digestion. In particular, three strains exhibited a great survival showing a recovery percentage in the range between 117 and 276%. In agreement with survival data, high lactic acid production was detected for all strains, confirming their metabolic activity during digestion.