Review of the role of fluid dairy in delivery of polyphenolic compounds in the diet: chocolate milk, coffee beverages, matcha green tea, and beyond

Dairy-based functional beverages have been a growing segment as consumer demands for health foods have shifted focus from simply enhancing lifespan to protecting health. Green tea is often limited in use because of poor bioavailability and disagreeable taste. However, milk is considered an ideal platform for the delivery of active polyphenolic compounds in green tea. Furthermore, the antioxidant enzymatic activity and antioxidant index of polyphenols in green tea have been known to be protected through interaction with dairy proteins inside the unstable intestinal environment. In addition, consumption of green tea infused with milk has been found to have a significant impact on reducing skin wrinkles and roughness in elderly subjects, through a decrease in lipid peroxidation and a concomitant reduction in oxidative stress. A similar affinity has been observed between antioxidants in coffee and milk proteins. Dark chocolate has been known to contain significant phenolic content and antioxidant activity. The activation of protein complex NF-kappa B, which is responsible for cell survival, was found to be significantly reduced upon consumption of cocoa with water, whereas consuming cocoa with milk had no effect on the bioavailability of the phenolic compounds in cocoa. The popularity of dairy as the source for polyphenol fortified beverages in the diet will be dictated by optimization of the technology for maximizing the bioavailability of the antioxidants.info:eu-repo/semantics/publishedVersio

Biochemical and Electrophysiological Modification of Amyloid Transthyretin on Cardiomyocytes

Transthyretin (TTR) amyloidoses are familial or sporadic degenerative conditions that often feature heavy cardiac involvement. Presently, no effective pharmacological therapy for TTR amyloidoses is available, mostly due to a substantial lack of knowledge about both the molecular mechanisms of TTR aggregation in tissue and the ensuing functional and viability modifications that occur in aggregate-exposed cells. TTR amyloidoses are of particular interest regarding the relation between functional and viability impairment in aggregate-exposed excitable cells such as peripheral neurons and cardiomyocytes. In particular, the latter cells provide an opportunity to investigate in parallel the electrophysiological and biochemical modifications that take place when the cells are exposed for various lengths of time to variously aggregated wild-type TTR, a condition that characterizes senile systemic amyloidosis. In this study, we investigated biochemical and electrophysiological modifications in cardiomyocytes exposed to amyloid oligomers or fibrils of wild-type TTR or to its T4-stabilized form, which resists tetramer disassembly, misfolding, and aggregation. Amyloid TTR cytotoxicity results in mitochondrial potential modification, oxidative stress, deregulation of cytoplasmic Ca(2+) levels, and Ca(2+) cycling. The altered intracellular Ca(2+) cycling causes a prolongation of the action potential, as determined by whole-cell recordings of action potentials on isolated mouse ventricular myocytes, which may contribute to the development of cellular arrhythmias and conduction alterations often seen in patients with TTR amyloidosis. Our data add information about the biochemical, functional, and viability alterations that occur in cardiomyocytes exposed to aggregated TTR, and provide clues as to the molecular and physiological basis of heart dysfunction in sporadic senile systemic amyloidosis and familial amyloid cardiomyopathy forms of TTR amyloidoses

S-Homocysteinylation effects on transthyretin: Worsening of cardiomyopathy onset

Background: L-Homocysteine (Hcy) is a non-proteinogenic α-amino acid synthesized from dietary methionine. In healthy humans, high Hcy levels are a risk factor for cardiovascular diseases, stroke and type 2 diabetes. A recent study reports that Hcy reacts with Cys10 of transthyretin (TTR), generating a stable covalent adduct. However, to date the effect of S-homocysteinylation on TTR conformational stability remains unknown. Methods: The effect of Hcy on the conformational properties of wt- and L55P-TTR were analysed using a set of biophysical techniques. The cytotoxicity of S-homocysteinylated L55P-TTR was also evaluated in the HL-1 cardiomyocyte cell line, while the effects of the assemblies on kinematic and dynamics properties of cardiac muscle cells were analysed in cardiomyocyte syncytia. Results: We found that Hcy stabilizes tetrameric wt-TTR, while it destabilizes the tetrameric structure of the L55P mutant, promoting the accumulation of self-assembly-prone monomeric species. Conclusions: Our study demonstrated that S-homocysteinylation of the L55P-TTR mutant impairs protein stability, favouring the appearance of toxic monomers. Interestingly, S-homocysteinylation affected only mutant, not wt-TTR. Moreover, we also show that assemblies of S-homocysteinylated L55P-TTR impair cardiomyocytes functional parameters. General significance: Our study offers new insights on the negative impact of S-homocysteinylation on L55P-TTR stability, whose aggregation is considered the causative agent of a form of early-onset familial amyloid polyneuropathy and cardiomyopathy. Our results suggest that high homocysteine levels are a further risk factor for TTR cardiomyopathy in patients harbouring the L55P-TTR mutation.Cardiomiopathy Amyloid disease FAP FAC L55P-TTR Homocystein

Co-fibrillogenesis of Wild-type and D76N β2-Microglobulin: THE CRUCIAL ROLE OF FIBRILLAR SEEDS

The amyloidogenic variant of β2-microglobulin, D76N, can readily convert into genuine fibrils under physiological conditions and primes in vitro the fibrillogenesis of the wild-type β2-microglobulin. By Fourier transformed infrared spectroscopy, we have demonstrated that the amyloid transformation of wild-type β2-microglobulin can be induced by the variant only after its complete fibrillar conversion. Our current findings are consistent with preliminary data in which we have shown a seeding effect of fibrils formed from D76N or the natural truncated form of β2-microglobulin lacking the first six N-terminal residues. Interestingly, the hybrid wild-type/variant fibrillar material acquired a thermodynamic stability similar to that of homogenous D76N β2-microglobulin fibrils and significantly higher than the wild-type homogeneous fibrils prepared at neutral pH in the presence of 20% trifluoroethanol. These results suggest that the surface of D76N β2-microglobulin fibrils can favor the transition of the wild-type protein into an amyloid conformation leading to a rapid integration into fibrils. The chaperone crystallin, which is a mild modulator of the lag phase of the variant fibrillogenesis, potently inhibits fibril elongation of the wild-type even once it is absorbed on D76N β2-microglobulin fibrils

Disclosing the Nutritional Quality Diversity of Portuguese Common Beans—The Missing Link for Their Effective Use in Protein Quality Breeding Programs

© 2021 by the authors.The common bean (Phaseolus vulgaris L.) represents a sustainable and affordable source of protein, namely, to populations with vegetarian dietary habits. Despite the national germplasm genetic diversity, little is known about the Portuguese accessions’ nutritional and protein quality, leading to their underuse in breeding programs. To fill this gap, a representative collection (106 accessions) was cropped under two contrasting environments (traditional versus heat stress) and evaluated in terms of nutritional quality by near-infrared spectroscopy. Protein quality was assessed, under the stressful environment, considering the individual amino acid contents and the activity of trypsin inhibitors through mass spectrometry (LC-MS/MS) and spectrophotometry, respectively. On top of strong genotypic control, the nutritional composition (protein, fat, fiber, moisture and ash) was also highly influenced by the environment and by genotype × environment interaction, with a clear nutritional quality ranking change for the accessions in heat stress conditions. Classified into three clusters, the accessions from the cluster with the highest individual amino acid and protein contents also showed higher trypsin inhibitor activity (TIA). Since different levels of TIA had no translation into contrasting protein digestibility, breeders focusing on common beans’ protein quality improvement, especially under challenging warming climate conditions, may take advantage of this group of accessions.This research was funded by FCT, Portugal, through BEGEQA project (PTDC/AGRTEC/3555/2012), E.M. PhD fellowship (SFRH/BD/89287/2012 and R&D unit, UIDB/04551/2020 (GREEN-IT–Bioresources for sustainability), PORTUGAL 2020, grant number LISBOA-01-0145- FEDER-402-022125 and PDR2020 Operação 7.8.4, Recursos genéticos (PDR2020-784-042734).Peer reviewe