Bioaccessibility and antioxidant activity of phenolic compounds in cooked pulses

The aim of this study was to evaluate the bioaccessibility of polyphenols and antioxidant activity in cooked pulses and to study the effect of cooking on their total phenolic content (TPC) and antioxidant capacity. Cooked faba beans showed the highest TPC, followed by soybeans and lentils or peas. TPC ranged from 10.4 ± 0.2 to 52.9 ± 0.3 mg/100 g and was positively correlated with antioxidant activity. Cooking resulted in increased TPC and antioxidant activity of the methanolic extracts, caused by cell disruption and improved extraction of polyphenols. Although polyphenols were lost in the cooking water, boiled legumes had more polyphenols than those resulting cooking broths. In vitro gastrointestinal digestion resulted in increased TPC and antioxidant capacity of the extracts. Soybeans showed the highest amount of bioaccessible polyphenols. The release of phenolics from cooked legumes was mainly achieved during the intestinal phase. Literature data may underestimate the TPC and antioxidant capacity of pulses.     

A Review of Guidance Approaches in Visual Data Analysis: A Multifocal Perspective

Visual data analysis can be envisioned as a collaboration of the user and the computational system with the aim of completing a given task. Pursuing an effective system‐user integration, in which the system actively helps the user to reach his/her analysis goal has been focus of visualization research for quite some time. However, this problem is still largely unsolved. As a result, users might be overwhelmed by powerful but complex visual analysis systems which also limits their ability to produce insightful results. In this context, guidance is a promising step towards enabling an effective mixed‐initiative collaboration to promote the visual analysis. However, the way how guidance should be put into practice is still to be unravelled. Thus, we conducted a comprehensive literature research and provide an overview of how guidance is tackled by different approaches in visual analysis systems. We distinguish between guidance that is provided by the system to support the user, and guidance that is provided by the user to support the system. By identifying open problems, we highlight promising research directions and point to missing factors that are needed to enable the envisioned human‐computer collaboration, and thus, promote a more effective visual data analysis.     

Effects of Spray‐Drying Parameters on In Vitro Functional Properties of Camu‐Camu (Myrciaria dubia Mc. Vaugh): A Typical Amazonian Fruit

Camu‐camu (Myrciaria dubia) fruit is a rich source of bioactive compounds but its shelf life is rather short. Therefore, this study was aimed to evaluate the effect of inlet air temperature (T) and concentration (C) of maltodextrin and arabic gum on the spray‐drying process of commercial camu‐camu pulps (São Paulo and Manaus). Moisture, solubility, total phenolics (TP), ascorbic acid (AA), and proanthocyanidins (PAC) contents, and in vitro antioxidant capacity of the powders (FRAP, DPPH, Folin–Ciocalteu's reducing capacity were measured). Arabic gum resulted in better yields (22% to 30%), powder solubility (84% to 90%), and lower losses of analyzed compounds than the powders manufactured with maltodextrin. Overall, inlet air temperature had a lower impact on the responses studied than the concentration of carrier agents. Polynomial equations were generated for AA (R² = 0.993), TP (R² = 0.735), PAC (R² = 0.946), and for the antioxidant capacity assays (0.867 ≤ R² ≤ 0.963). In addition, principal component analysis showed that the lowest concentration of carrier agents (6%) in spray drying resulted in the lowest losses of bioactive compounds and, consequently, the highest antioxidant capacity.     

Functional Properties of Lactic Acid Bacteria Isolated from Romanian Fermented Vegetables

A total of 139 lactic acid bacterium (LAB) strains isolated from Romanian traditionally fermented vegetables were screened for the ability to produce exopolysaccharides and for their antagonistic activity against a set of nine LAB strains, three Bacillus strains, and four Gram-negative bacteria. Eighty-five of the tested strains showed a variable antimicrobial activity against Listeria monocytogenes ATCC 1911, 35 of the strains showed a limited inhibition zone against Escherichia coli ATCC25922, and 26 strains against Salmonella enterica ATCC 14024, while 19 strains showed inhibition against one or all three Bacillus strains used as indicators. None of the tested strains showed an antimicrobial activity against Staphylococcus aureus ATCC 25923. Several strains showed antibacterial activity against more than one indicator strain. For instance, Lactobacillus plantarum 307, Lactobacillus brevis 308, and Lactobacillus plantarum/pentosus 358 were active against five of the indicator strains used, while other 23 LAB were active against three indicator strains. In the case of two strains, namely Leuconostoc citreum 344 and Lactobacillus brevis 183, the activity was maintained after neutralizing the pH of the cell-free supernatant likely due to the production of bacteriocins. The gel permeation chromatography-based screening revealed seven EPS-producing LAB strains. Two of the positive strains, namely Leuconostoc citreum 177 and Leuconostoc citreum 52, have been shown to produce large amounts of EPS, of about 20 g/L. All isolated EPS have a high molecular mass, of above 1400 KDa, and a monomer composition dominated by the presence of glucose.     

Metabolic Syndrome and Male Fertility: Beyond Heart Consequences of a Complex Cardiometabolic Endocrinopathy

Metabolic syndrome (MetS) is a highly prevalent condition among adult males, affecting up to 41% of men in Europe. It is characterized by the association of obesity, hypertension, and atherogenic dyslipidemia, which lead to premature morbidity and mortality due to cardiovascular disease (CVD). Male infertility is another common condition which accounts for about 50% of cases of couple infertility worldwide. Interestingly, male infertility and MetS shares several risk factors (e.g., smoking, ageing, physical inactivity, and excessive alcohol consumption), leading to reactive oxygen species (ROS) production and increased oxidative stress (OS), and resulting in endothelial dysfunction and altered semen quality. Thus, the present narrative review aims to discuss the pathophysiological mechanisms which link male infertility and MetS and to investigate the latest available evidence on the reproductive consequences of MetS.     

Variants of HCMV UL18 Sequenced Directly from Clinical Specimens Associate with Antibody and T-Cell Responses to HCMV

Around 80% of adults worldwide carry human cytomegaloviris (HCMV). The HCMV gene UL18 is a homolog of HLA class I genes and encodes a protein with high affinity for the NK and T-cell cytotoxicity inhibitor LIR-1. UL18 was deep sequenced from blood, saliva or urine from Indonesian people with HIV (PWH) (n = 28), Australian renal transplant recipients (RTR) (n = 21), healthy adults (n = 7) and neonates (n = 4). 95% of samples contained more than one variant of HCMV UL18, as defined by carriage of nonsynonymous variations. When aligned with immunological markers of the host’s burden of HCMV, the S318N variation associated with high levels of antibody reactive with HCMV lysate in PWH over 12 months on antiretroviral therapy. The A107T variation associated with HCMV antibody levels and inflammatory biomarkers in PWH at early timepoints. Variants D32G, D248N, V250A and E252D aligned with elevated HCMV antibody levels in RTR, while M191K, E196Q and F165L were associated with HCMV-reactive T-cells and proportions of Vδ2⁻ γδ T-cells—populations linked with high burdens of HCMV. We conclude that UL18 is a highly variable gene, where variation may alter the persistent burden of HCMV and/or the host response to that burden.     

Ficolin-2 Plasma Level Assesses Liver Fibrosis in Non-Alcoholic Fatty Liver Disease

Fibrosis is the strongest predictor for disease-specific mortality in non-alcoholic fatty liver diseases (NAFLD), but the need for liver biopsy limits its diagnosis. We assessed the performance of plasma ficolin-2 (FCN-2) as a biomarker of fibrosis identified by an in silico discovery strategy. Two hundred and thirty-five morbidly obese (MO) subjects with biopsy-proven NAFLD stratified by fibrosis stage (F0, n = 44; F1, n = 134; F2, n = 46; F3/F4, n = 11) and 40 cirrhotic patients were enrolled. The cohort was subdivided into discovery (n = 76) and validation groups (n = 159). The plasma level of FCN-2 and other candidate markers was determined. FCN-2 was inversely correlated with the stage of liver fibrosis (ρ = −0.49, p < 0.001) independently of steatosis (p = 0.90), inflammation (p = 0.57), and ballooning (p = 0.59). In the global cohort, FCN-2 level decreased significantly in a stepwise fashion from F0/F1 (median 4753 ng/mL) to F2–F3–F4 (2760 ng/mL) and in cirrhotic subjects (1418 ng/mL). The diagnostic performance of FCN-2 in detecting F ≥ 2 was higher than other indexes (APRI, FIB-4) (AUROC 0.82, 0.68, and 0.6, respectively). The accuracy improved when combined with APRI score and HDL values (FCNscore, AUROC 0.85). Overall, the FCN-2 plasma level can accurately discriminate liver fibrosis status (minimal vs. moderate/advanced) significantly improving the fibrosis diagnostic algorithms.     

Overcoming Multidrug Resistance (MDR): Design,Biological Evaluation and Molecular Modelling Studies of 2,4-Substituted Quinazoline Derivatives

Some 2,4-disubstituted quinazolines were synthesized and studied as multidrug resistance (MDR) reversers. The new derivatives carried the quinazoline-4-amine scaffold found in modulators of the ABC transporters involved in MDR, as the TKIs gefitinib and erlotinib. Their behaviour on the three ABC transporters, P-gp, MRP1 and BCRP, was investigated. Almost all compounds inhibited the P-gp activity in MDCK-MDR1 cells overexpressing P-gp, showing EC₅₀ values in the nanomolar range ( 1 d , 1 e , 2 a , 2 c , 2 e ). Some compounds were active also towards MRP1 and/or BCRP. Docking results obtained by in silico studies on the P-gp crystal structure highlighted common features for the most potent compounds. The P-gp selective compound 1 e was able to increase the doxorubicin uptake in HT29/DX cells and to restore its antineoplastic activity in resistant cancer cells in the same extent of sensitive cells. Compound 2 a displayed a dual inhibitory effect showing good activities towards both P-gp and BCRP.     

Synthesis, biological activity, and ADME properties of novel S-DABOs/N-DABOs as HIV reverse transcriptase inhibitors

Previous studies aimed at exploring the SAR of C2-functionalized S-DABOs demonstrated that the substituent at this position plays a key role in the inhibition of both wild-type RT and drug-resistant enzymes, particularly the K103N mutant form. The introduction of a cyclopropyl group led us to the discovery of a potent inhibitor with picomolar activity against wild-type RT and nanomolar activity against many key mutant forms such as K103N. Despite its excellent antiviral profile, this compound suffers from a suboptimal ADME profile typical of many S-DABO analogues, but it could, however, represent a promising candidate as an anti-HIV microbicide. In the present work, a new series of S-DABO/N-DABO derivatives were synthesized to obtain additional SAR information on the C2-position and in particular to improve ADME properties while maintaining a good activity profile against HIV-1 RT. In vitro ADME properties (PAMPA permeation, water solubility, and metabolic stability) were also experimentally evaluated for the most interesting compounds to obtain a reliable indication of their plasma levels after oral administration.