A 12.4 kDa laminarin (LM) composed of β(1→3)-glucan with β(1→6)-branches was extracted from brown seaweed Lobophora variegata and modified via carboxylation using dielectric barrier discharge (LMC), conjugation with gallic acid (LMG), and sulfation (LMS). Analyses of the chemical composition of LMC, LMG, and LMS yielded 11.7% carboxyl groups, 1.5% gallic acid, and 1.4% sulfate content, respectively. Antioxidant activities of native and modified laminarins were assessed using six different in vitro methods. Sulfation stopped the antioxidant activities of LM. On the other hand, carboxylation improved cooper chelation (1.2 times). LMG was found to be a more efficient antioxidant agent than LM in terms of copper chelation (1.3 times), reducing power (1.3 times), and total antioxidant capacity (80 times). Gallic acid conjugation was further confirmed using Fourier transform infrared spectroscopy (FT-IR) and one- and two-dimensional NMR spectroscopy analyses. LMG also did not induce cell death or affect the cell cycle of Madin–Darby canine kidney (MDCK) cells. On the contrary, LMG protected MDCK cells from H₂O₂-induced oxidative damage. Taken together, these results show that LMG has the potent antioxidant capacity, and, therefore, potential applications in pharmacological and functional food products. Full article

Heme oxygenase-1 (HO-1) is an inducible antioxidant enzyme that catalyzes heme group degradation. Decreased level of HO-1 is correlated with disease progression, and HO-1 induction suppresses development of metabolic and neurological disorders. Natural compounds with antioxidant activities have emerged as a rich source of HO-1 inducers with marginal toxicity. Here we discuss the therapeutic role of HO-1 in obesity, hypertension, atherosclerosis, Parkinson’s disease and hepatic fibrosis, and present important signaling pathway components that lead to HO-1 expression. We provide an updated, comprehensive list of natural HO-1 inducers in foodstuff and medicinal herbs categorized by their chemical structures. Based on the continued research in HO-1 signaling pathways and rapid development of their natural inducers, HO-1 may serve as a preventive and therapeutic target for metabolic and neurological disorders. Full article

Background: Human SP-A1 and SP-A2, encoded by SFTPA1 and SFTPA2, and their genetic variants differentially impact alveolar macrophage (AM) functions and regulation, including the miRNome. We investigated whether miRNome differences previously observed between AM from SP-A2 and SP-A1/SP-A2 mice are due to continued qualitative differences or a delayed response of mice carrying a single gene. Methods: Human transgenic (hTG) mice, carrying SP-A2 or both SP-A genes, and SP-A-KO mice were exposed to filtered air (FA) or ozone (O₃)_. AM miRNA levels, target gene expression, and pathways determined 18 h after O₃ exposure. RESULTS: We found (a) differences in miRNome due to sex, SP-A genotype, and exposure; (b) miRNome of both sexes was largely downregulated by O₃, and co-ex had fewer changed (≥2-fold) miRNAs than either group; (c) the number and direction of the expression of genes with significant changes in males and females in co-ex are almost the opposite of those in SP-A2; (d) the same pathways were found in the studied groups; and (e) O₃ exposure attenuated sex differences with a higher number of genotype-dependent and genotype-independent miRNAs common in both sexes after O₃ exposure. Conclusion: Qualitative differences between SP-A2 and co-ex persist 18 h post-O₃, and O₃ attenuates sex differences. Full article

This study evaluated the effects of 2 weeks of betaine supplementation on apoptosis, oxidative stress, and aerobic capacity after exhaustive endurance exercise (EEE). A double-blind, crossover, and counterbalanced design was adopted, with 10 healthy male participants asked to consume betaine (1.25 g of betaine mixed with 300 mL of sports beverage, twice per day for 2 weeks) or placebo (300 mL of sports beverage). All participants performed a graded exercise test on a treadmill to determine the maximal oxygen consumption (VO_2max) before supplementation and then performed the EEE test at an intensity of 80% VO_2max after 2 weeks of supplementation. The time to exhaustion, peak oxygen consumption, maximal heart rate, and average heart rate were recorded during the EEE test. Venous blood samples were drawn before, immediately after, and 3 h after the EEE test to assess apoptosis and the mitochondrial transmembrane potential (MTP) decline of lymphocytes as well as the concentrations of thiobarbituric acid reactive substance and protein carbonyl. The results indicated that lymphocyte apoptosis was significantly higher immediately after and 3 h after EEE than before exercise in participants in the placebo trial. However, lymphocyte apoptosis exhibited no significant differences among the three time points in participants in the betaine trial. Moreover, apoptosis in the betaine trial was significantly lower immediately after and 3 h after exercise compared with the placebo trial. No differences were noted for other variables. Thus, 2 weeks of betaine supplementation can effectively attenuate lymphocyte apoptosis, which is elevated by EEE. However, betaine supplementation exhibited no effects on MTP decline, oxidative stress, or aerobic capacity. Full article

Cancer cells are characterized by higher levels of reactive oxygen species (ROS) compared to normal cells as a result of an imbalance between oxidants and antioxidants. However, cancer cells maintain their redox balance due to their high antioxidant capacity. Recently, a high level of oxidative stress is considered a novel target for anticancer therapy. This can be induced by increasing exogenous ROS and/or inhibiting the endogenous protective antioxidant system. Additionally, the immune system has been shown to be a significant ally in the fight against cancer. Since ROS levels are important to modulate the antitumor immune response, it is essential to consider the effects of oxidative stress-inducing treatments on this response. In this review, we provide an overview of the mechanistic cellular responses of cancer cells towards exogenous and endogenous ROS-inducing treatments, as well as the indirect and direct antitumoral immune effects, which can be both immunostimulatory and/or immunosuppressive. For future perspectives, there is a clear need for comprehensive investigations of different oxidative stress-inducing treatment strategies and their specific immunomodulating effects, since the effects cannot be generalized over different treatment modalities. It is essential to elucidate all these underlying immune effects to make oxidative stress-inducing treatments effective anticancer therapy. Full article

Aging is a major risk for cardiovascular diseases (CVD). Age-related disorders include oxidative stress, mitochondria dysfunction, and exacerbation of the NF-κB/NLRP3 innate immune response pathways. Some of the molecular mechanisms underlying these processes, however, remain unclear. This study tested the hypothesis that NLRP3 inflammasome plays a role in cardiac aging and melatonin is able to counteract its effects. With the aim of investigating the impact of NLRP3 inflammasome and the actions and target of melatonin in aged myocardium, we analyzed the expression of proteins implied in mitochondria dynamics, autophagy, apoptosis, Nrf2-dependent antioxidant response and mitochondria ultrastructure in heart of wild-type and NLRP3-knockout mice of 3, 12, and 24 months-old, with and without melatonin treatment. Our results showed that the absence of NLRP3 prevented age-related mitochondrial dynamic alterations in cardiac muscle with minimal effects in cardiac autophagy during aging. The deficiency of the inflammasome affected Bax/Bcl2 ratio, but not p53 or caspase 9. The Nrf2-antioxidant pathway was also unaffected by the absence of NLRP3. Furthermore, NLRP3-deficiency prevented the drop in autophagy and mice showed less mitochondrial damage than wild-type animals. Interestingly, melatonin treatment recovered mitochondrial dynamics altered by aging and had few effects on cardiac autophagy. Melatonin supplementation also had an anti-apoptotic action in addition to restoring Nrf2-antioxidant capacity and improving mitochondria ultrastructure altered by aging. Full article

Autism spectrum disorders (ASD) are a group of neurodevelopmental syndromes with both genetic and environmental origins. Several recent studies have shown that inflammation and oxidative stress may play a key role in supporting the pathogenesis and the severity of ASD. Thus, the administration of anti-inflammatory and antioxidant molecules may represent a promising strategy to counteract pathological behaviors in ASD patients. In the current review, results from recent literature showing how natural antioxidants may be beneficial in the context of ASD will be discussed. Interestingly, many antioxidant molecules available in nature show anti-inflammatory activity. Thus, after introducing ASD and the role of the vitamin E/vitamin C/glutathione network in scavenging intracellular reactive oxygen species (ROS) and the impairments observed with ASD, we discuss the concept of functional food and nutraceutical compounds. Furthermore, the effects of well-known nutraceutical compounds on ASD individuals and animal models of ASD are summarized. Finally, the importance of nutraceutical compounds as support therapy useful in reducing the symptoms in autistic people is discussed. Full article

Mycosporines and mycosporine-like amino acids have been described as natural sunscreens and antioxidant compounds presenting a great potential for health and cosmetic applications. Herein, an untargeted screening approach for mycosporines and mycosporine-like amino acids (MAAs) was developed by the coupling of zwitterionic hydrophilic interaction liquid chromatography (HILIC) with multistage electrospray mass spectrometry MS²/MS³ using an Orbitrap analyzer and fragment ion search (FISh). This method was applied to study the mycosporine and MAA contents of five algae extracted using a 50% methanol solution and sonication. Candidate-MAAs were detected by mining eight characteristic fragment ions in their HILIC data-dependent MS² mass spectrum. Their exact masses were measured with 3 ppm mass accuracy and their structures were elucidated on the basis of the MS³/MS⁴ mass spectra. The method developed was validated with a targeted analysis using an extract of Gymnogongrus devoniensis which confirmed the detection of 14 MAAs reported in the literature. In addition, 23 previously unreported MAAs were detected and the structures could be assigned for seven of them. The developed method was applied to the analysis of four algae: Gelidium sesquipedale, Halopithys incurva, Porphyra rosengurtii and Cystoseira tamariscifolia allowing the detection of MAAs, including some reported here for the first time. Full article

In this study, we examined the effect of six months of positive airway pressure (PAP) therapy on Obstructive Sleep Apnea (OSA) red blood cell (RBC) proteome by two dimensional difference gel electrophoresis (2D-DIGE) - based proteomics followed by Western blotting (WB) validation. The discovered dysregulated proteins/proteoforms are associated with cell death, H₂O₂ catabolic/metabolic process, stress response, and protein oligomerization. Validation by nonreducing WB was performed for peroxiredoxin-2 (PRDX2) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by using antibodies against the sulfinylated/sulfonylated cysteine of these proteins to better evaluate their redox–oligomeric states under OSA and/or in response to PAP therapy. The results indicated that the redox–oligomeric state of GAPDH and PRDX2 involving overoxidation by sulfinic/sulfonic acids were differentially modulated in OSA RBC, which might be compromising RBC homeostasis. PAP therapy by restoring this modulation induced a higher oligomerization of overoxidized GAPDH and PRDX2 in some patients that could be associated with eryptosis and the chaperone “gain” of function, respectively. This varied response following PAP may result from the complex interplay between OSA and OSA metabolic comorbidity. Hence, information on the redox status of PRDX2 and GAPDH in RBC will help to better recognize OSA subtypes and predict the therapeutic response in these patients. GAPDH monomer combined with body mass index (BMI) and PRDX2 S-S dimer combined with homeostatic model assessment for insulin resistance (HOMA-IR) showed to be very promising biomarkers to predict OSA and OSA severity, respectively. Full article

The marine environment represents a prosperous existing resource for bioprospecting, covering 70% of the planet earth, and hosting a huge biodiversity. Advances in the research are progressively uncovering the presence of unknown microorganisms, which have evolved unique metabolic and genetic pathways for the production of uncommon secondary metabolites. Fungi have a leading role in marine bioprospecting since they represent a prolific source of structurally diverse bioactive metabolites. Several bioactive compounds from marine fungi have already been characterized including antibiotics, anticancer, antioxidants and antivirals. Nowadays, the search for natural antioxidant molecules capable of replacing those synthetic currently used, is an aspect that is receiving significant attention. Antioxidants can inactivate reactive oxygen and nitrogen species, preventing the insurgence of several degenerative diseases including cancer, autoimmune disorders, cardiovascular and neurodegenerative diseases. Moreover, they also find applications in different fields, including food preservation, healthcare and cosmetics. This review focuses on the production of antioxidants from marine fungi. We begin by proposing a survey of the available tools suitable for the evaluation of antioxidants, followed by the description of various classes of marine fungi antioxidants together with their extraction strategies. In addition, a view of the future perspectives and trends of these natural products within the “blue economy” is also presented. Full article

Severe disease commonly manifests as a systemic inflammatory process. Inflammation is associated withthe enhanced production of reactive oxygen and nitrogen species and with a marked reduction in the plasma concentrations of protective antioxidant molecules. This imbalance gives rise to oxidative stress, which is greater in patients with more severe conditions such as sepsis, cancer, cardiovascular disease, acute respiratory distress syndrome, and burns. In these patients, oxidative stress can trigger cell, tissue, and organ damage, thus increasing morbidity and mortality. Ascorbic acid (ASC) is a key nutrient thatserves as an antioxidant and a cofactor for numerous enzymatic reactions. However, humans, unlike most mammals, are unable to synthesize it. Consequently, ASC must be obtained through dietary sources, especially fresh fruit and vegetables. The value of administering exogenous micronutrients, to reestablish antioxidant concentrations in patients with severe disease, has been recognized for decades. Despite the suggestion that ASC supplementation may reduce oxidative stress and prevent several chronic conditions, few large, randomized clinical trials have tested it in patients with severe illness. This article reviews the recent literature on the pharmacological profile of ASC and the role of its supplementation in critically ill patients. Full article

Phaseolus vulgaris L. (common bean) is a leguminous species that is an important dietary component due to its high content of proteins, unsaturated fatty acids, minerals, dietary fibers and vitamins. Due to the high content of polyphenols, several biological activities have been described for bean extracts, making it possible to include P. vulgaris among food with beneficial effects for human health. Moreover, more than 40,000 varieties of beans have been recognised with different nutraceutical properties, pointing out the importance of food biodiversity. In this work, we describe for the first time the chemical composition and biological activity of a newly recognized Italian variety of P. vulgaris grown in a restricted area of the Tuscany region and named “Fagiola di Venanzio”. Fagiola di Venanzio water extract is rich in proteins, sugars and polyphenols and displays antioxidant, anti-inflammatory and antiproliferative activities in in vitro assays on colon cancer cellular models. Our data indicate that this variety of P. vulgaris appears to be a promising source of bioactive compounds and encourage more in-depth studies to better elucidate the implications of its consumption for public health. Full article

Epidemiological studies and clinical investigations proposed that catechins extracts alone may not provide a sufficient level of bioactivities and promising therapeutic effects to achieve health benefits due to a number of constraints related to poor oral absorption, limited bioavailability, sensitivity to oxidation, etc. Modern scientific studies have reported numerous techniques for the design of micro- and nano-bio-delivery systems as novel and promising strategies to overcome these obstacles and to enhance catechins’ therapeutic activity. The objective assessment of their benefits, however, requires a critical comparative estimation of the advantages and disadvantages of the designed catechins-biocarrier systems, their biological activities and safety administration aspects. In this respect, the present review objectively outlines, compares and assesses the recent advances related to newly developed design concepts of catechins’ encapsulation into various biopolymer carriers and their release behaviour, with a special emphasis on the specific physiological biofunctionalities of the innovative bioflavonoid/biopolymer delivery systems. Full article

Methylglyoxal (MG), a potent precursor of advanced glycation end-products (AGE), is increased in metabolic disorders such as diabetes and obesity. MG and other dicarbonyl metabolites are detoxified by the glyoxalase system in which glyoxalase 1, coded by the Glo1 gene, serves as the rate-limiting enzyme. In this study, we analyzed the effects of Glo1 downregulation on glucose and lipid metabolism parameters in spontaneously hypertensive rats (SHR) by targeting the Glo1 gene (SHR-Glo1^+/− heterozygotes). Compared to SHR wild-type animals, SHR-Glo1^+/− rats showed significantly reduced Glo1 expression and lower GLO1 activity in tissues associated with increased MG levels. In contrast to SHR controls, SHR-Glo1^+/− rats exhibited lower relative weight of epididymal fat, reduced ectopic fat accumulation in the liver and heart, and decreased serum triglycerides. In addition, compared to controls, SHR-Glo1^+/− rats showed reduced serum insulin and increased basal and insulin stimulated incorporation of glucose into white adipose tissue lipids (lipogenesis). Reduced ectopic fat accumulation in the heart was associated with significantly increased pAMPK/AMPK ratio and GLUT4 activity. These results provide evidence that Glo1 downregulation in SHR is associated with reduced adiposity and ectopic fat accumulation, most likely mediated by AMPK activation in the heart. Full article

UV radiation is a well-established environmental risk factor known to cause oxidative stress and disrupt the metabolism of keratinocyte phospholipids. Cannabidiol (CBD) is a phytocannabinoid with anti-inflammatory and antioxidant effects. In this study, we examined changes in the keratinocyte phospholipid profile from nude rat skin exposed to UVA and UVB radiation that was also treated topically with CBD. UVA and UVB radiation promoted up-regulation of phosphatidylcholines (PC), lysophosphatidylcholines (LPC), phosphatidylethanolamines (PE) and down-regulation of sphingomyelin (SM) levels and enhanced the activity of phospholipase A2 (PLA2) and sphingomyelinase (SMase). Application of CBD to the skin of control rats led to down-regulation of SM and up-regulation of SMase activity. After CBD treatment of rats irradiated with UVA or UVB, SM was up-regulated and down-regulated, respectively, while ceramide (CER) levels and SMase activity were down-regulated and up-regulated, respectively. CBD applied to the skin of UV-irradiated rats down-regulated LPC, up-regulated PE and phosphatidylserines (PS) and reduced PLA2 activity. In conclusion, up-regulation of PS may suggest that CBD inhibits their oxidative modification, while changes in the content of PE and SM may indicate a role of CBD in promoting autophagy and improving the status of the transepidermal barrier. Full article