This study established the appropriate amounts of a functional Saskatoon berry fruit powder in fortified rye bread acceptable to consumers and determined the potential relative bioaccesibility of bioactive compounds exhibiting antioxidant activity, and enzymatic in vitro inhibitory activity against lipoxygenase, cyclooxigenase-1, cyclooxigenase-2, acetylcholinesterase, pancreatic lipase α-glucosidase, and α-amylase, as well as the relative digestibility of nutrients. The content of polyphenolic compounds and antioxidant capability were strongly, positively correlated with the content of the functional additive. The highest phenolics content and antioxidant activity were determined in the products enriched with the powders microencapsulated with maltodextrin (an increase by 91% and 53%, respectively, compared with the control). The highest overall acceptability was shown for the products with 3% addition of the functional additive, regardless of its type. The simulated in vitro digestion released phenols (with the highest bioaccessibility shown for anthocyanins) and enhanced the antioxidant activity of rye bread. In turn, the microencapsulation contributed to the improvement in the relative bioaccesibility of antioxidant compounds. Bread fortification led to an increased inhibitory activity against α-amylase, α-glucosidase, and lipoxygenase. Furthermore, the additive microencapsulated with maltodextrin and inulin improved the capacity to inhibit the activities of pancreatic lipase and cyclooxigenase-2. The results presented allowed concluding that the powders from Saskatoon berry fruits, especially microencapsulated ones, may be a promising functional additive dedicated for the enrichment of rye bread. Full article

Infertility is an important health problem that affects up to 16% of couples worldwide. Male infertility is responsible for 50% of the cases. Currently, a physical examination, hormone profiling and the evaluation of two consecutive semen samples (to determine the sperm concentration, motility, morphology and, in very few cases, sperm DNA integrity) are the sole tools that physicians have to evaluate infertility in men. Antioxidant therapy is often used to improve sperm quality and function in infertile men. However, there are controversial results regarding the efficacy of these treatments. Prdx6^−/− male mice are subfertile, displaying significant oxidative damage in the lipids, proteins and DNA of their spermatozoa. Here, we used Prdx6^−/− male mice to test whether a novel combination of tocopherols that contained 60% γ-tocopherol and ascorbic acid could restore their fertility. These mice were fed with the supplemented (Vit. Mix) or control diets. To assess sperm quality, we determined the motility, levels of lipid peroxidation, DNA oxidation and tyrosine nitration in the spermatozoa. The number of pups sired by the Prdx6^−/− mice fed with the Vit. Mix diet was higher than that sired by the males fed with the control diet, and the pups’ mortality was lower. The sperm quality was improved in the males fed with the supplemented diet. We concluded that treatment with a supplement composed of tocopherols and rich in γ-tocopherol and ascorbic acid is effective in restoring fertility in cases where oxidative stress and high levels of tyrosine nitration are associated with male infertility. Full article

For most infertile couples, in vitro fertilization (IVF) represents the only chance to conceive. Given the limited success of IVF procedures, novel approaches are continuously tested with the aim of improving IVF outcomes. Growing attention is devoted today to the potential benefit of natural antioxidants in the optimization of infertility treatments. This review summarizes current data in this context, focusing on both experimental studies on oocytes/embryos and clinical trials on antioxidants supplementation. Based on information gained from experimental studies, antioxidant supplementation may have beneficial effects on IVF outcomes in terms of quality and cryotolerance of in vitro produced embryos, together with positive effects on in vitro maturation oocytes and on early embryonic development. Unfortunately, from the clinical side, there is a paucity of evidence favoring the protective qualities of antioxidants. Among the antioxidants considered, coenzyme Q10 may be regarded as one of the most promising for its positive role in rescuing the oxidative stress-induced damages, but further data are needed. It is concluded that further trials are necessary to characterize the potential clinical value of antioxidants in IVF treatments. Full article

Skin aging is a biological process influenced by intrinsic and extrinsic factors. The last ones, mainly exposure to UV radiation, increases reactive oxygen species (ROS) production leading to a loss of extracellular matrix, also enhanced by enzymatic degradation of matrix supporting molecules. Thus, and with the growing demand for eco-friendly skin products, natural compounds extracted from brown seaweeds revealed to be good candidates due to their broad range of bioactivities, especially as antioxidants. The aim of this study was to assess the dermo-cosmetic potential of different fractions obtained from the brown seaweed Fucus spiralis. For this purpose, in vitro antioxidant (Total Phenolic Content (TPC), 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, Ferric Reducing Antioxidant Power (FRAP), Oxygen Radical Absorbance Capacity (ORAC)), anti-enzymatic (collagenase, elastase and hyaluronidase), antimicrobial, anti-inflammatory (NO production) and photoprotective (ROS production) capacities were evaluated. Although nearly all fractions evidenced antioxidant effects, fraction F10 demonstrated the highest antioxidant ability (EC₅₀ of 38.5 µg/mL, DPPH assay), and exhibited a strong effect as an inhibitor of collagenase (0.037 µg/mL) and elastase (3.0 µg/mL). Moreover, this fraction was also the most potent on reducing ROS production promoted by H₂O₂ (IC₅₀ of 41.3 µg/mL) and by UVB (IC₅₀ of 31.3 µg/mL). These bioactivities can be attributed to its high content of phlorotannins, as evaluated by LC-MS analysis, reinforcing the potential of F. spiralis for further dermatological applications. Full article

The gastrointestinal (GI) tract is crucial for food digestion and nutrient absorption in humans. However, the GI tract is usually challenged with oxidative stress that can be induced by various factors, such as exogenous pathogenic microorganisms and dietary alterations. As a part of gut microbiota, Lactobacillus spp. play an important role in modulating oxidative stress in cells and tissues, especially in the GI tract. Oxidative stress is linked with excessive reactive oxygen species (ROS) that can be formed by a few enzymes, such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs). The redox mechanisms of Lactobacillus spp. may contribute to the downregulation of these ROS-forming enzymes. In addition, nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf-2) and nuclear factor kappa B (NF-κB) are two common transcription factors, through which Lactobacillus spp. modulate oxidative stress as well. As oxidative stress is closely associated with inflammation and certain diseases, Lactobacillus spp. could potentially be applied for early treatment and amelioration of these diseases, either individually or together with prebiotics. However, further research is required for revealing their mechanisms of action as well as their extensive application in the future. Full article

Neurodegenerative disorders have emerged as a serious health issue in the current era. The most common neurodegenerative disorders are Alzheimer’s disease (AD), Parkinson’s disease, multiple sclerosis, and amyotrophic lateral sclerosis (ALS). These diseases involve progressive impairment of neurodegeneration and memory impairment. A wide range of compounds have been identified as potential neuroprotective agents against different models of neurodegeneration both in vivo and in vitro. Hesperetin, a flavanone class of citrus flavonoid, is a derivative of hesperidin found in citrus fruits such as oranges, grapes, and lemons. It has been extensively reported that hesperetin exerts neuroprotective effects in experimental models of neurodegenerative diseases. In this systematic review, we have compiled all the studies conducted on hesperetin in both in vivo and in vitro models of neurodegeneration. Here, we have used an approach to lessen the bias in each study, providing a least biased, broad understanding of findings and impartial conclusions of the strength of evidence and the reliability of findings. In this review, we collected different papers from a wide range of journals describing the beneficial effects of hesperetin on animal models of neurodegeneration. Our results demonstrated consistent neuroprotective effects of hesperetin against different models of neurodegeneration. In addition, we have summarized its underlying mechanisms. This study provides the foundations for future studies and recommendations of further mechanistic approaches to conduct preclinical studies on hesperetin in different models. Full article

The aim of this study was to examine the in vitro effects of the slow-releasing H₂S donor GYY4137 on the immune cells involved in the pathogenesis of the central nervous system (CNS) autoimmune disease, multiple sclerosis (MS). GYY4137 specifically potentiated TGF-β expression and production in dendritic cells and significantly reduced IFN-γ and IL-17 production in the lymph node and spinal cord T cells obtained from mice immunized with CNS antigens. Both the proportion of FoxP3+ regulatory CD4+ T cells in the lymph node cells, and the percentage of IL-17⁺ CD4+ T cells in the spinal cord cells were reduced upon culturing with GYY4137. Interestingly, the peripheral blood mononuclear cells obtained from the MS patients had a lower expression of the H₂S-producing enzyme, 3-mercaptopyruvate-sulfurtransferase (MPST), in comparison to those obtained from healthy donors. A significant inverse correlation between the expression of MPST and several pro-inflammatory factors was also observed. Further studies on the relevance of the observed results for the pathogenesis and therapy of MS are warranted. Full article

Nowadays, the obesity pandemic is one of the most relevant health issues worldwide. This condition is tightly related to comorbidities such as non-alcoholic fatty liver disease (NAFLD) and cardiovascular diseases (CVDs), namely atherosclerosis. Dysregulated lipid metabolism and inflammation link these three diseases, leading to a subsequent increase of oxidative stress (OS) causing severe cellular damage. On the other hand, microRNAs (miRNAs) are short, single-stranded, non-coding RNAs that act as post-transcriptional negative regulators of gene expression, thus being involved in the molecular mechanisms that promote the development of many pathologies including obesity and its comorbidities. The involvement of miRNAs in promoting or opposing OS in disease progression is becoming more evident. Some miRNAs, such as miR-200a and miR.421, seem to play important roles in OS control in NAFLD. On the other hand, miR-92a and miR-133, among others, are important in the development of atherosclerosis. Moreover, since both diseases are linked to obesity, they share common altered miRNAs, being miR-34a and miR-21 related to OS. This review summarizes the latest advances in the knowledge about the mechanisms of oxidative stress (OS) generation in obesity-associated NAFLD and atherosclerosis, as well as the role played by miRNAs in the regulation of such mechanisms. Full article

The expression of pluripotency factors is a key regulator of tumor differentiation status and cancer stem cells. The purpose of this study was to examine the expression of pluripotency factors and differentiation status of human mesothelioma and the role of mitochondria in their regulation. We tested the expression of OCT4/POU5F1, NANOG, SOX2, PI3K-AKT pathway and BCL2 genes and proteins in 65 samples of human mesothelioma and 19 samples of normal mesothelium. Mitochondrial membrane potential, reactive oxygen species (ROS) generation and expression of pluripotency factors were also tested in human mesothelioma cell line. Human mesothelium and mesothelioma expressed SOX2, NANOG, PI3K and AKT genes and proteins and POU5F1 gene, whereby NANOG, SOX2 and phosphorylated (activated) AKT were upregulated in mesothelioma. NANOG protein expression was elevated in less differentiated samples of human mesothelioma. The expression of genes of PI3K-AKT pathway correlated with pluripotency factor genes. Mesothelioma cells had functional, but depolarized mitochondria with large capacity to generate ROS. Mitochondrial ROS upregulated NANOG and mitoTEMPO abrogated it. In conclusion, human mesothelioma displays enhanced expression of NANOG, SOX2 and phosphorylated AKT proteins, while elevated NANOG expression correlates with poor differentiation of human mesothelioma. Mitochondria of mesothelioma cells have a large capacity to form ROS and thereby upregulate NANOG, leading to dedifferentiation of mesothelioma. Full article

One interesting aspect of antioxidant organic molecules is their use as probes for the detection and quantitation of biologically relevant reactive oxidant species (ROS). In this context, a small library of dihydroterphenyl derivatives has been synthesised and studied as fluorescent chemodosimeters for detecting reactive oxygen species and hypochlorite. The fluorescence quantum yields of these molecules are negligible, while the corresponding aromatized compounds formed upon oxidation show moderate to high native fluorescence, depending on their structures. The fluorescence signal is quickly developed in the presence of trace amounts of the probe and the analytes in acetonitrile media at room temperature, with good analytical figures. ROS detection in aqueous media required incubation at 37 °C in the presence of horseradish peroxidase, and was applied to glucose quantitation by coupling glucose oxidation by O₂ to fluorescence detection of H₂O₂. The mild reaction conditions and sensitive fluorescent response lead us to propose dihydroterphenyls with an embedded anthranilate moiety as chemosensors/chemodosimeters for ROS detection. Full article

The apoplast comprises the intercellular space, the cell walls, and the xylem. Important functions for the plant, such as nutrient and water transport, cellulose synthesis, and the synthesis of molecules involved in plant defense against both biotic and abiotic stresses, take place in it. The most important molecules are ROS, antioxidants, proteins, and hormones. Even though only a small quantity of ROS is localized within the apoplast, apoplastic ROS have an important role in plant development and plant responses to various stress conditions. In the apoplast, like in the intracellular cell compartments, a specific set of antioxidants can be found that can detoxify the different types of ROS produced in it. These scavenging ROS components confer stress tolerance and avoid cellular damage. Moreover, the production and accumulation of proteins and peptides in the apoplast take place in response to various stresses. Hormones are also present in the apoplast where they perform important functions. In addition, the apoplast is also the space where microbe-associated molecular Patterns (MAMPs) are secreted by pathogens. In summary, the diversity of molecules found in the apoplast highlights its importance in the survival of plant cells. Full article

The aim of this study is to assess the role of l-cysteine desulfhydrase (l-DES) and endogenous hydrogen sulfide (H₂S) in glutathione (GSH)-induced tolerance to salinity stress (SS) in sweet pepper (Capsicum annuum L.). Two weeks after germination, before initiating SS, half of the pepper seedlings were retained for 12 h in a liquid solution containing H₂S scavenger, hypotaurine (HT), or the l-DES inhibitor dl-propargylglycine (PAG). The seedlings were then exposed for three weeks to control or SS (100 mmol L⁻¹ NaCl) and supplemented with or without GSH or GSH+NaHS (sodium hydrosulfide, H₂S donor). Salinity suppressed dry biomass, leaf water potential, chlorophyll contents, maximum quantum efficiency, ascorbate, and the activities of dehydroascorbate reductase, monodehydroascorbate reductase, and glyoxalase II in plants. Contrarily, it enhanced the accumulation of hydrogen peroxide, malondialdehyde, methylglyoxal, electrolyte leakage, proline, GSH, the activities of glutathione reductase, peroxidase, catalase, superoxide dismutase, ascorbate peroxidase, glyoxalase I, and l-DES, as well as endogenous H₂S content. Salinity enhanced leaf Na⁺ but reduced K⁺; however, the reverse was true with GSH application. Overall, the treatments, GSH and GSH+NaHS, effectively reversed the oxidative stress and upregulated salt tolerance in pepper plants by controlling the activities of the AsA-GSH and glyoxalase-system-related enzymes as well as the levels of osmolytes. Full article

The valorisation of food wastes is a challenging opportunity for the green, sustainable, and competitive development of industry. The recovery of phenols contributes to the sustainability of olive waste sector, reducing its environmental impact and promoting the development of innovative formulations of interest for pharmaceutical, nutraceutical, and cosmeceutical applications. In this work, olive mill wastewater was treated through a combination of microfiltration (MF), nanofiltration (NF), and reverse osmosis (RO) in a sequential design to produce polyphenol-enriched fractions that have been investigated for their chemical profile using ultra-high-performance liquid chromatography (UHPLC), and their potential antioxidant, hypolipidemic, and hypoglycaemic activities. RO retentate exhibited the highest content of hydroxytyrosol, tyrosol, oleuropein, verbascoside, vanillic acid, and luteolin. In particular, a content of hydroxytyrosol of 1522.2 mg/L, about five times higher than the MF feed, was found. RO retentate was the most active extract in all in vitro tests. Interestingly, this fraction showed a 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic) acid (ABTS) radicals scavenging activity with an IC₅₀ value of 6.9 μg/mL and a potential inhibition of lipid peroxidation evaluated by the β-carotene bleaching test with IC₅₀ values of 25.1 μg/mL after 30 min of incubation. Moreover, RO retentate inhibited α-amylase and α-glucosidase with IC₅₀ values of 65.3 and 66.2 μg/mL, respectively. Full article

Background: Chronic pulmonary diseases are characterized by airway remodeling due to complex multicellular responses and the production of free oxygen radicals. They lead to a progressive decline of pulmonary functions. Adelmidrol is an analogue of palmitoylethanolamide (PEA), which is a well-known anti-inflammatory and anti-oxidant compound. In this study, we investigated the efficacy of adelmidrol (10 mg/Kg) for bleomycin-induced pulmonary fibrosis in mice. Methods: Bleomycin intratracheal administration was performed on the first day and for the following twenty-one days, mice were treated with adelmidrol (10 mg/Kg). Results: The survival rate and body weight gain were recorded daily. At the end of the experiment, adelmidrol-administered animals showed reduced airway infiltration by inflammatory cells, Myeloperoxidase (MPO) activity, and pro-inflammatory cytokine overexpression (IL,6 IL-1β, TNF-α, and TGF-1β). Moreover, adelmidrol treatment was able to manage the significant incapacity of antioxidants and elevation of the oxidant burden, as shown by the MDA, SOD, and GSH levels and decreased nitric oxide production. It was also able to significantly modulate the JAK2/STAT3 and IκBα/NF-kB pathway. Histologic examination of the lung tissues showed reduced sample injury, mast cell degranulation, chymase activity, and collagen deposition. Conclusions: In sum, our results propose adelmidrol as a therapeutic approach in the treatment of pulmonary fibrosis. Full article

Oxidative stress is a key mediator in the development and progression of Parkinson’s disease (PD). The antioxidant N-acetylcysteine (NAC) has generated interest as a disease-modifying therapy for PD but is limited due to poor bioavailability, a short half-life, and limited access to the brain. The aim of this study was to formulate and utilise mitochondria-targeted nanocarriers for delivery of NAC alone and in combination with the iron chelator deferoxamine (DFO), and assess their ability to protect against oxidative stress in a cellular rotenone PD model. Pluronic F68 (P68) and dequalinium (DQA) nanocarriers were prepared by a modified thin-film hydration method. An MTT assay assessed cell viability and iron status was measured using a ferrozine assay and ferritin immunoassay. For oxidative stress, a modified cellular antioxidant activity assay and the thiobarbituric acid-reactive substances assay and mitochondrial hydroxyl assay were utilised. Overall, this study demonstrates, for the first time, successful formulation of NAC and NAC + DFO into P68 + DQA nanocarriers for neuronal delivery. The results indicate that NAC and NAC + DFO nanocarriers have the potential characteristics to access the brain and that 1000 μM P68 + DQA NAC exhibited the strongest ability to protect against reduced cell viability (p = 0.0001), increased iron (p = 0.0033) and oxidative stress (p ≤ 0.0003). These NAC nanocarriers therefore demonstrate significant potential to be transitioned for further preclinical testing for PD. Full article