Probiotic fermented milk with high content of polyphenols: Study of viability and bioaccessibility after simulated digestion

This research evaluated the functional potential of a fermented milk made with Streptococcus thermophilus, a probiotic (Bifidobacterium animalis subsp. lactis) and pomegranate juice. Ferric‐reducing antioxidant potential, Trolox equivalent antioxidant capacity, scavenging effect on 1,1‐diphenyl‐2‐picrylhydrazyl free radical, oxygen radical absorbance capacity and Folin–Ciocalteu assays were used to estimate antioxidant activity and phenolic content. Probiotic survival, release and absorption of polyphenols were evaluated using in vitro gastrointestinal digestion. The concentration of polyphenols increased during digestion from 608 mg to 1417  gallic acid equivalents (GAE) /L. About 14% of polyphenols were found on the dialysate portion. The beverage presented high viability of probiotics with high survival rate after digestion (above 7 log cfu/mL).     

Application of kernel principal component analysis for single-lead-ECG-derived respiration

Recent studies show that principal component analysis (PCA) of heartbeats is a well-performing method to derive a respiratory signal from ECGs. In this study, an improved ECG-derived respiration (EDR) algorithm based on kernel PCA (kPCA) is presented. KPCA can be seen as a generalization of PCA where nonlinearities in the data are taken into account by nonlinear mapping of the data, using a kernel function, into a higher dimensional space in which PCA is carried out. The comparison of several kernels suggests that a radial basis function (RBF) kernel performs the best when deriving EDR signals. Further improvement is carried out by tuning the parameter σ(2) that represents the variance of the RBF kernel. The performance of kPCA is assessed by comparing the EDR signals to a reference respiratory signal, using the correlation and the magnitude squared coherence coefficients. When comparing the coefficients of the tuned EDR signals using kPCA to EDR signals obtained using PCA and the algorithm based on the R peak amplitude, statistically significant differences are found in the correlation and coherence coefficients (both p<0.0001), showing that kPCA outperforms PCA and R peak amplitude in the extraction of a respiratory signal from single-lead ECGs.     

Low Sulfur Amino Acid,High Polyunsaturated Fatty Acid Diet Inhibits Breast Cancer Growth

Cancer cells may acquire resistance to stress signals and reprogram metabolism to meet the energetic demands to support their high proliferation rate and avoid death. Hence, targeting nutrient dependencies of cancer cells has been suggested as a promising anti-cancer strategy. We explored the possibility of killing breast cancer (BC) cells by modifying nutrient availability. We used in vitro models of BC (MCF7 and MDA-MB-231) that were maintained with a low amount of sulfur amino acids (SAAs) and a high amount of oxidizable polyunsatured fatty acids (PUFAs). Treatment with anti-apoptotic, anti-ferroptotic and antioxidant drugs were used to determine the modality of cell death. We reproduced these conditions in vivo by feeding BC-bearing mice with a diet poor in proteins and SAAs and rich in PUFAs (LSAA/HPUFA). Western blot analysis, qPCR and histological analyses were used to assess the anti-cancer effects and the molecular pathways involved. We found that BC cells underwent oxidative damage to DNA and proteins and both apoptosis and ferroptosis were induced. Along with caspases-mediated PARP1 cleavage, we found a lowering of the GSH-GPX4 system and an increase of lipid peroxides. A LSAA/HPUFA diet reduced tumor mass and its vascularization and immune cell infiltration, and induced apoptosis and ferroptotic hallmarks. Furthermore, mitochondrial mass was found to be increased, and the buffering of mitochondrial reactive oxygen species limited GPX4 reduction and DNA damage. Our results suggest that administration of custom diets, targeting the dependency of cancer cells on certain nutrients, can represent a promising complementary option for anti-cancer therapy.     

Staphylococcus aureus Exfoliative Toxin E,Oligomeric State and Flip of P186: Implications for Its Action Mechanism

Staphylococcal exfoliative toxins (ETs) are glutamyl endopeptidases that specifically cleave the Glu381-Gly382 bond in the ectodomains of desmoglein 1 (Dsg1) via complex action mechanisms. To date, four ETs have been identified in different Staphylococcus aureus strains and ETE is the most recently characterized. The unusual properties of ETs have been attributed to a unique structural feature, i.e., the 180° flip of the carbonyl oxygen (O) of the nonconserved residue 192/186 (ETA/ETE numbering), not conducive to the oxyanion hole formation. We report the crystal structure of ETE determined at 1.61 Å resolution, in which P186(O) adopts two conformations displaying a 180° rotation. This finding, together with free energy calculations, supports the existence of a dynamic transition between the conformations under the tested conditions. Moreover, enzymatic assays showed no significant differences in the esterolytic efficiency of ETE and ETE/P186G, a mutant predicted to possess a functional oxyanion hole, thus downplaying the influence of the flip on the activity. Finally, we observed the formation of ETE homodimers in solution and the predicted homodimeric structure revealed the participation of a characteristic nonconserved loop in the interface and the partial occlusion of the protein active site, suggesting that monomerization is required for enzymatic activity.     

The Generation of Nitric Oxide from Aldehyde Dehydrogenase-2: The Role of Dietary Nitrates and Their Implication in Cardiovascular Disease Management

Reduced bioavailability of the nitric oxide (NO) signaling molecule has been associated with the onset of cardiovascular disease. One of the better-known and effective therapies for cardiovascular disorders is the use of organic nitrates, such as glyceryl trinitrate (GTN), which increases the concentration of NO. Unfortunately, chronic use of this therapy can induce a phenomenon known as “nitrate tolerance”, which is defined as the loss of hemodynamic effects and a reduction in therapeutic effects. As such, a higher dosage of GTN is required in order to achieve the same vasodilatory and antiplatelet effects. Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is a cardioprotective enzyme that catalyzes the bio-activation of GTN to NO. Nitrate tolerance is accompanied by an increase in oxidative stress, endothelial dysfunction, and sympathetic activation, as well as a loss of the catalytic activity of ALDH2 itself. On the basis of current knowledge, nitrate intake in the diet would guarantee a concentration of NO such as to avoid (or at least reduce) treatment with GTN and the consequent onset of nitrate tolerance in the course of cardiovascular diseases, so as not to make necessary the increase in GTN concentrations and the possible inhibition/alteration of ALDH2, which aggravates the problem of a positive feedback mechanism. Therefore, the purpose of this review is to summarize data relating to the introduction into the diet of some natural products that could assist pharmacological therapy in order to provide the NO necessary to reduce the intake of GTN and the phenomenon of nitrate tolerance and to ensure the correct catalytic activity of ALDH2.