By-Products Valorization: Peptide Fractions from Milk Permeate Exert Antioxidant Activity in Cellular and In Vivo Models.

The discarding of agri-food by-products is a stringent problem due to their high environmental impact. Recovery strategies can lead to a reduction of waste and result in new applications. Agri-food waste represents a source of bioactive molecules, which could promote health benefits.

Bioactive peptides from food waste: New innovative bio-nanocomplexes to enhance cellular uptake and biological effects.

Mastitis is the most important bovine disease, causing dramatic economic losses to the dairy industry, worldwide. This study explores the valorization of whey from cows affected by mastitis, through a novel separation approach. Surface Active Maghemite Nanoparticles (SAMNs) were used as magnetic baits to selectively bind bioactive peptides with potential health benefits.

Thiamine disulfide derivatives in thiol redox regulation: Role of thioredoxin and glutathione systems.

Thiamine (vitamin B1), under the proper conditions, is able to reversibly open the thiazole ring, forming a thiol-bearing molecule that can be further oxidized to the corresponding disulfide. To improve the bioavailability of the vitamin, several derivatives of thiamine in the thioester or disulfide form were developed and extensively studied over time, as apparent from the literature. We have examined three thiamine-derived disulfides: thiamine disulfide, sulbutiamine, and fursultiamine with reference to their intervention in modulating the thiol redox state.

The Role of Antioxidant Foods and Nutraceuticals in Ageing.

The free radical theory of aging proposed by Denham Harman in the 1950s identified the accumulation of oxidative damage over time as a cause of aging [...

Sunflower seed-derived bioactive peptides show antioxidant and anti-inflammatory activity: From in silico simulation to the animal model.

The evolving field of food technology is increasingly dedicated to developing functional foods. This study explored bioactive peptides from sunflower protein isolate (SPI), obtained from defatted flour, a by-product of the oil processing industry. SPI underwent simulated gastrointestinal digestion and the obtained peptide-enriched fraction (PEF) showed antioxidant properties in vivo, in zebrafish.

Exploring the Anticancer Activity of Tamoxifen-Based Metal Complexes Targeting Mitochondria.

Two new 'hybrid' metallodrugs of Au(III) (AuTAML) and Cu(II) (CuTAML) were designed featuring a tamoxifen-derived pharmacophore to ideally synergize the anticancer activity of both the metal center and the organic ligand. The compounds have antiproliferative effects against human MCF-7 and MDA-MB 231 breast cancer cells. Molecular dynamics studies suggest that the compounds retain the binding activity to estrogen receptor (ERα) and studies showed that the Au(III) derivative is an inhibitor of the seleno-enzyme thioredoxin reductase, while the Cu(II) complex may act as an oxidant of different intracellular thiols.

From In Silico to a Cellular Model: Molecular Docking Approach to Evaluate Antioxidant Bioactive Peptides.

The increasing need to counteract the redox imbalance in chronic diseases leads to focusing research on compounds with antioxidant activity. Among natural molecules with health-promoting effects on many body functions, bioactive peptides are gaining interest. They are protein fragments of 2-20 amino acids that can be released by various mechanisms, such as gastrointestinal digestion, food processing and microbial fermentation.

Nrf2-Activating Bioactive Peptides Exert Anti-Inflammatory Activity through Inhibition of the NF-κB Pathway.

Redox status and inflammation are related to the pathogenesis of the majority of diseases. Therefore, understanding the role of specific food-derived molecules in the regulation of their specific pathways is a relevant issue. Our previous studies indicated that and , milk and soy-derived bioactive peptides, respectively, exert antioxidant effects through activation of the Keap1/Nrf2 pathway.

SOD1 in ALS: Taking Stock in Pathogenic Mechanisms and the Role of Glial and Muscle Cells.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the loss of motor neurons in the brain and spinal cord. While the exact causes of ALS are still unclear, the discovery that familial cases of ALS are related to mutations in the Cu/Zn superoxide dismutase (SOD1), a key antioxidant enzyme protecting cells from the deleterious effects of superoxide radicals, suggested that alterations in SOD1 functionality and/or aberrant SOD1 aggregation strongly contribute to ALS pathogenesis. A new scenario was opened in which, thanks to the generation of SOD1 related models, different mechanisms crucial for ALS progression were identified.

Mitochondrial depletion of glutaredoxin 2 induces metabolic dysfunction-associated fatty liver disease in mice.

Glutaredoxin 2 (Grx2) is a glutathione-dependent oxidoreductase that facilitates glutathionylation/de-glutathionylation of target proteins. The main variants of Grx2 are the mitochondrial Grx2a and the cytosolic Grx2c. The aim of this study was to investigate the specific role of mitochondrial Grx2 in vivo using a mitochondrial Grx2 depleted (mGD) mouse model.

New Platinum(II) Complexes Affecting Different Biomolecular Targets in Resistant Ovarian Carcinoma Cells.

Resistance to platinum-based anticancer drugs represents an important limit for their clinical effectiveness and one of the most important field of investigation in the context of platinum compounds. From our previous studies, Pt complexes containing the triphenylphosphino moiety have been emerging as promising agents, showing significant cytotoxicity to resistant ovarian carcinoma cells. Two brominated triphenylphosphino trans-platinum derivatives were prepared and evaluated on human tumor cell lines, sensitive and resistant to cisplatin.

Fermented Soy-Derived Bioactive Peptides Selected by a Molecular Docking Approach Show Antioxidant Properties Involving the Keap1/Nrf2 Pathway.

Bioactive peptides are a group of molecules with health beneficial properties, deriving from food matrices. They are protein fragments consisting of 2-20 amino acids that can be released by microbial fermentation, food processing and gastrointestinal digestion. Once hydrolyzed from their native proteins, they can have different functions including antioxidant activity, which is important for cell protection by oxidant agents.

The Determining Role of Mitochondrial Reactive Oxygen Species Generation and Monoamine Oxidase Activity in Doxorubicin-Induced Cardiotoxicity.

Doxorubicin cardiomyopathy is a lethal pathology characterized by oxidative stress, mitochondrial dysfunction, and contractile impairment, leading to cell death. Although extensive research has been done to understand the pathophysiology of doxorubicin cardiomyopathy, no effective treatments are available. We investigated whether monoamine oxidases (MAOs) could be involved in doxorubicin-derived oxidative stress, and in the consequent mitochondrial, cardiomyocyte, and cardiac dysfunction.

Platinum(II) Complexes Bearing Triphenylphosphine and Chelating Oximes: Antiproliferative Effect and Biological Profile in Resistant Cells.

Platinum(II) complexes of the type [Pt(Cl)(PPh ){(κ -N,O)-(1{C(R)=N(OH)-2(O)C H })}] with R=Me, H, (1 and 2) were synthesized and characterized. Single-crystal X-ray diffraction confirmed the proposed (SP4-3) configuration for 1. Study of the antiproliferative activity, performed on a panel of human tumor cell lines and on mesothelial cells, highlighted complex 2 as the more effective.

Identification of New Peptides from Fermented Milk Showing Antioxidant Properties: Mechanism of Action.

Due to their beneficial properties, fermented foods are considered important constituents of the human diet. They also contain bioactive peptides, health-promoting compounds studied for a wide range of effects. In this work, several antioxidant peptides extracted from fermented milk proteins were investigated.

Small Structural Differences between Two Ferrocenyl Diphenols Determine Large Discrepancies of Reactivity and Biological Effects.

The ferrocenyl diphenol complexes 1,1-bis(4'-hydroxyphenyl)-2-ferrocenyl-but-1-ene (1) and 1,2-bis(4'-hydroxyphenyl)-1-ferrocenyl-but-1-ene [(Z)-2], which differ by the relative position of the two phenolic substituents, display dramatically different antiproliferative activities on cancer cells (1 is far more cytotoxic than 2). In this study, our goal was to discover the origin of this difference by comparing their reactivity and biological behaviour. In terms of common behaviour, we found that 1 and 2 are both efficient inhibitors of thioredoxin reductase (TrxR) in vitro after oxidation by a horseradish peroxidase/H O system.

Dimers of glutaredoxin 2 as mitochondrial redox sensors in selenite-induced oxidative stress.

Glutaredoxin 2 (Grx2) has been previously shown to link thioredoxin and glutathione systems receiving reducing equivalents by both thioredoxin reductase and glutathione. Grx2 catalyzes protein glutathionylation/de-glutathionylation and can coordinate an iron-sulfur cluster, forming inactive dimers stabilized by two molecules of glutathione. This protein is mainly located in the mitochondrial matrix, though other isoforms have been found in the cytosolic and nuclear cell compartments.

Antioxidant Properties of Fermented Soy during Shelf Life.

Glycine max (soybean) is a fundamental food in human nutrition, largely utilized by the consumers, and in particular, fermented soy is mainly used. However, health benefits of the products can change during the shelf life as oxidation processes occur determining alterations of protein and lipid constituents leading to a decrease of nutritional quality. Therefore, the oxidative stability of the fermented soy during the shelf life was studied.

Insight into antioxidant properties of milk-derived bioactive peptides in vitro and in a cellular model.

Milk is a nutritionally important source of bioactive peptides with anti-inflammatory, immunomodulatory, anticancer, and antioxidant properties. These compounds can be useful as ingredients of functional food. For this reason, in the last decades, bioactive peptides attracted the interest of researchers and food companies.

Significance of the mitochondrial thioredoxin reductase in cancer cells: An update on role, targets and inhibitors.

Thioredoxin reductase 2 (TrxR2) is a key component of the mitochondrial thioredoxin system able to transfer electrons to peroxiredoxin 3 (Prx3) in a reaction mediated by thioredoxin 2 (Trx2). In this way, both the level of hydrogen peroxide and thiol redox state are modulated. TrxR2 is often overexpressed in cancer cells conferring apoptosis resistance.

Oxidative changes in lipids, proteins, and antioxidants in yogurt during the shelf life.

Oxidation processes in milk and yogurt during the shelf life can result in an alteration of protein and lipid constituents. Therefore, the antioxidant properties of yogurt in standard conditions of preservation were evaluated. Total phenols, free radical scavenger activity, degree of lipid peroxidation, and protein oxidation were determined in plain and skim yogurts with or without fruit puree.

Characterization of Hydrophilic Gold(I) N-Heterocyclic Carbene (NHC) Complexes as Potent TrxR Inhibitors Using Biochemical and Mass Spectrometric Approaches.

We report here on the synthesis of a series of mono- and dinuclear gold(I) complexes exhibiting sulfonated bis(NHC) ligands and novel hydroxylated mono(NHC) Au(I) compounds, which were also examined for their biological activities. Initial cell viability assays show strong antiproliferative activities of the hydroxylated mono(NHC) gold compounds (8 > 9 > 10) against 2008 human ovarian cancer cells even after 1 h incubation. In order to gain insight into the mechanism of biological action of the gold compounds, their effect on the pivotal cellular target seleno-enzyme thioredoxin reductase (TrxR), involved in the maintenance of intracellular redox balance, was investigated in depth.

Exploring the C^N^C theme: Synthesis and biological properties of tridentate cyclometalated gold(III) complexes.

A family of cyclometalated Au(III) complexes featuring a tridentate C^N^C scaffold has been synthesized and characterized. Microwave assisted synthesis of the ligands has also been exploited and optimized. The biological properties of the thus formed compounds have been studied in cancer cells and demonstrate generally moderate antiproliferative effects.

Tamoxifen-like metallocifens target the thioredoxin system determining mitochondrial impairment leading to apoptosis in Jurkat cells.

Tamoxifen-like metallocifens (TLMs) of the group-8 metals (Fe, Ru, and Os) show strong anti-proliferative activity on cancer cell lines resistant to apoptosis, owing to their unique redox properties. In contrast, the thioredoxin system, which is involved in cellular redox balance, is often overexpressed in cancer cells, especially in tumour types resistant to standard chemotherapies. Therefore, we investigated the effect of these three TLMs on the thioredoxin system and evaluated the input of the metallocene unit in comparison with structurally related organic tamoxifens.