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Simple Summary: We have previously identified deflamin, an oligomeric protein isolated from the white lupine seeds (Lupinus albus) with anti-MMPs and anti-inflammatory properties. Given the involvement of MMPs and inflammation in the carcinogenesis process, we aimed to assess deflamin's role in cancer development and progression. Using colorectal cancer cell lines and zebrafish xenotransplant models, we found that deflamin exhibits anti-MMP-2 and anti-MMP-9 activity, being able to reduce tumor size and metastasis formation in vivo. Deflamin was shown to impair cancer cell migration and invasion, as well as collagen remodeling and angiogenesis in the tumor microenvironment, highly impacting cancer behavior. Overall, our results unravel the nutraceutical potential of deflamin in colorectal cancer treatment. Matrix metalloproteinases (MMPs) are proteolytic enzymes that play a crucial role in tumor microenvironment remodeling, contributing to inflammatory and angiogenic processes, and ultimately promoting tumor maintenance and progression. Several studies on bioactive polypeptides isolated from legumes have shown anti-migratory, anti-MMPs, and anti-tumor effects, potentially constituting novel strategies for both the prevention and progression of cancer. In this work, we investigated the anti-tumor role of deflamin, a protein oligomer isolated from white lupine seeds (Lupinus albus) reported to inhibit MMP-9 and cell migration in colorectal cancer (CRC) cell lines. We found that deflamin exerts an inhibitory effect on tumor growth and metastasis formation, contributing to increased tumor apoptosis in the xenotransplanted zebrafish larvae model. Furthermore, deflamin resulted not only in a significant reduction in MMP-2 and MMP-9 activity but also in impaired cancer cell migration and invasion in vitro. Using the xenograft zebrafish model, we observed that deflamin inhibits collagen degradation and angiogenesis in the tumor microenvironment in vivo. Overall, our work reveals the potential of deflamin as an agent against CRC development and progression. [ABSTRACT FROM AUTHOR]

Cell-penetrating peptides (CPP) have been shown to be efficient in the transport of cargoes into the cells, namely siRNA and DNA, proteins and peptides, and in some cases, small therapeutics. These peptides have emerged as a solution to increase drug concentrations in different tissues and various cell types, therefore having a relevant therapeutic relevance which led to clinical trials. One of them, MAP, is a model amphipathic peptide with an α-helical conformation and both hydrophilic and hydrophobic residues in opposite sides of the helix. It is composed of a mixture of alanines, leucines, and lysines (KLALKLALKALKAALKLA). The CPP MAP has the ability to translocate oligonucleotides, peptides and small proteins. However, taking advantage of its unique properties, in recent years innovative concepts were developed, such as in silico studies of modelling with receptors, coupling and repurposing drugs in the central nervous system and oncology, or involving the construction of dual-drug delivery systems using nanoparticles. In addition to designs of MAP-linked vehicles and strategies to achieve highly effective yet less toxic chemotherapy, this review will be focused on unique molecular structure and how it determines its cellular activity, and also intends to address the most recent and frankly motivating issues for the future. [ABSTRACT FROM AUTHOR]

Nanoparticulate systems have been widely investigated as delivery vectors for efficient drug delivery in different diseases. Nanostructured lipid carriers (NLC) are composed of both solid and liquid lipids (glyceryl dibehenate and diethylene glycol monoethyl ether) and have demonstrated enhanced biological compatibility and increased drug loading capability. Furthermore, the use of peptides, in particular cell-penetrating peptides, to functionalize nanoparticles and enhance cell membrane permeation was explored in this paper. In this paper, we described the synthesis of a new conjugated of tranylcypromine with MAP. In addition, taking into consideration our previous results, this study developed different NLCs loaded with three central nervous system (CNS) drugs (tacrine (TAC), rasagiline (RAS), and tranylcypromine (TCP)) functionalized with model amphipathic peptide (MAP) and evaluated their activity against cancer cells. Particle size analysis demonstrated NLC presented less than 200 nm and a polydispersity index less than 0.3. Moreover, in vitro results showed that conjugation of MAP with drugs led to a higher decrease in cell viability of a neuroblastoma cell line and Caco-2 cell line, more than MAP alone. Furthermore, NLC encapsulation contributed to higher cellular delivery and enhanced toxic activity at lower concentrations when compared with free or co-administration drug-MAP conjugate. [ABSTRACT FROM AUTHOR]

Functionalization of nanoparticles surfaces have been widely used to improve diagnostic and therapeutic biological outcome. Several methods can be applied to modify nanoparticle surface; however, in this article we focus toward a simple and less time-consuming method. We applied an adsorption method on already formulated nanostructured lipid carriers (NLC) to functionalize these nanoparticles with three distinct peptides sequences. We selected a cell-penetrating peptide (CPP), a lysine modified model amphipathic peptide (Lys(N3)-MAP), CPP/drug complex, and the neuropeptide Y. The aim of this work is to evaluate the effect of several parameters such as peptide concentration, different types of NLC, different types of peptides, and incubation medium on the physicochemical proprieties of NLC and determine if adsorption occurs. The preliminary results from zeta potential analysis indicate some evidence that this method was successful in adsorbing three types of peptides onto NLC. Several non-covalent interactions appear to be involved in peptide adsorption with the possibility of three adsorption peptide hypothesis that may occur with NLC in solution. Moreover, and for the first time, in silico docking analysis demonstrated strong interaction between CPP MAP and NPY Y1 receptor with high score values when compared to standard antagonist and NPY. [ABSTRACT FROM AUTHOR]

Spent yeast waste streams are a byproduct obtained from fermentation process and have been shown to be a rich secondary source of bioactive compounds such as phenolic compounds and peptides. The latter are of particular interest for skin care and cosmetics as they have been shown to be safe and hypoallergenic while simultaneously being able to exert various effects upon the epidermis modulating immune response and targeting skin metabolites, such as collagen production. As the potential of spent yeast's peptides has been mainly explored for food-related applications, this work sought to understand if peptide fractions previously extracted from fermentation engineered spent yeast (Saccharomyces cerevisiae) waste streams possess biological potential for skin-related applications. To that end, cytotoxic effects on HaCat and HDFa cells and whether they were capable of exerting a positive effect upon the production of skin metabolites relevant for skin health, such as collagen, hyaluronic acid, fibronectin and elastin, were evaluated. The results showed that the peptide fractions assayed were not cytotoxic up to the highest concentration tested (500 µg/mL) for both cell lines tested. Furthermore, all peptide fractions showed a capacity to modulate the various target metabolites production with an overall positive effect being observed for the four fractions over the six selected targets (pro-collagen IαI, hyaluronic acid, fibronectin, cytokeratin-14, elastin, and aquaporin-9). Concerning the evaluated fractions, the overall best performance (Gpep > 1 kDa) was of an average promotion of 41.25% over the six metabolites and two cell lines assessed at a concentration of 100 µg/mL. These results showed that the peptide fractions assayed in this work have potential for future applications in skin-related products at relatively low concentrations, thus providing an alternative solution for one of the fermentation industry's waste streams and creating a novel and highly valuable bioactive ingredient with encompassing activity to be applied in future skin care formulations. [ABSTRACT FROM AUTHOR]

Codfish blood and sardine cooking wastewaters were processed using membrane ultrafiltration that allowed for the preparation of bioactive peptides enriched fractions. The raw materials and corresponding permeates were characterized chemically and in terms of biological properties. The fractionation process was evaluated by analyzing the selective permeation of small peptides (<1 kDa) from larger compounds when using membranes with different molecular weight cut-offs (MWCOs) combined with different materials (MW, PW, and UP010 for codfish blood) and when operated at different transmembrane pressures (with GH for sardine cooking wastewaters). A rejection of the protein/peptides >10 kDa was achieved for both raw materials with the studied membranes. Also, low values of rejection of peptides <1 kDa were accomplished, namely 2% with UP010 from codfish blood and 23% when operated at minimum pressure (1.0 bar) with GH from sardine wastewaters. The peptide fractions from codfish blood with MW and UP010 exhibited the highest ABTS+ and ORAC values. Peptide fractions from sardine wastewaters with GH demonstrated no improvement in antioxidant activity compared to sardine wastewaters. The antimicrobial results showed that the peptide fractions from codfish blood with UP010 and from sardine with GH at 1.0 bar were capable of inhibiting Escherichia coli growth. [ABSTRACT FROM AUTHOR]

Sardine cooking effluents contain a high level of organic matter, such as proteins and lipids, which allows them to be forward into a chain exploiting high added-value compounds attained from these effluents, increasing their economic value while reducing their environmental effect. Thus, the purpose of this work was to develop an innovative pilot-scale integrated membrane process, with or without enzymatic hydrolysis, to obtain fractions with high protein/peptide and low NaCl contents, as well as optimized bioactive properties. The research strategy followed involved the use of ultrafiltration (UF) and nanofiltration (NF) technologies of the pretreated sardine cooking effluent followed by reverse osmosis (RO) at a pilot scale levels. Moreover, it allowed for the attainment of fractions rich in protein/peptides that might be used in the food, pharmaceutical, or cosmetic industries, particularly after RO, as they present a lower NaCl content. The RO retentate (hydrolyzed sample) coupled with UF and NF resulted in the fractions with the best bioactive properties (higher antioxidant capacity and antimicrobial activity) of all the analyzed samples. Overall, the current work demonstrated the feasibility of exploiting liquid by-products as a source of functional components as well as reinforcing this strategy's potential relevance in future effective management strategies for this type of effluents. [Display omitted] • Protein/peptide recovery from fish effluents using membrane technology. • Bioactive properties of proteins/peptides recovered from fishery effluents. • Efficiently valorizing fishery effluents. • Removing the mono-valent salts from sardine cooking effluents by NF membrane. [ABSTRACT FROM AUTHOR]

Recent metagenomic studies have demonstrated that the overall functional potential of the intestinal microbiome is rather conserved between healthy individuals. Here we assessed the biological processes undertaken in-vivo by microbes and the host in the intestinal tract by conducting a metaproteome analysis from a total of 48 faecal samples of 16 healthy adults participating in a placebo-controlled probiotic intervention trial. Half of the subjects received placebo and the other half consumed Lactobacillus rhamnosus GG for three weeks (1010 cfu per day). Faecal samples were collected just before and at the end of the consumption phase as well as after a three-week follow-up period, and were processed for microbial composition and metaproteome analysis. A common core of shared microbial protein functions could be identified in all subjects. Furthermore, we observed marked differences in expressed proteins between subjects that resulted in the definition of a stable and personalized microbiome both at the mass-spectrometry-based proteome level and the functional level based on the KEGG pathway analysis. No significant changes in the metaproteome were attributable to the probiotic intervention. A detailed taxonomic assignment of peptides and comparison to phylogenetic microarray data made it possible to evaluate the activity of the main phyla as well as key species, including Faecalibacterium prausnitzii. Several correlations were identified between human and bacterial proteins. Proteins of the human host accounted for approximately 14% of the identified metaproteome and displayed variations both between and within individuals. The individually different human intestinal proteomes point to personalized host-microbiota interactions. Our findings indicate that analysis of the intestinal metaproteome can complement gene-based analysis and contributes to a thorough understanding of the activities of the microbiome and the relevant pathways in health and disease. [ABSTRACT FROM AUTHOR]