Catalase-associated immune responses in plant-microbe interactions: A review.

Catalase, an enzyme central to maintaining redox balance and combating oxidative stress in plants, has emerged as a key player in plant defense mechanisms and interactions with microbes. This review article provides a comprehensive analysis of catalase-associated immune responses in plant-microbe interactions. It underscores the importance of catalase in plant defense mechanisms, highlights its influence on plant susceptibility to pathogens, and discusses its implications for understanding plant immunity and host-microbe dynamics. This review contributes to the growing body of knowledge on catalase-mediated immune responses and offers insights that can aid in the development of strategies for improved plant health and disease resistance.

Construction of a redox-coupled pathway co-metabolizing glucose and acetate for high-yield production of butyl butyrate in Escherichia coli.

The carbon and energy efficiency of a biomanufacturing process is of crucial importance in determining its economic viability. Formate dehydrogenase has been demonstrated to be beneficial in regenerating NADH from formate produced during sugar metabolism, thereby creating energy-efficient systems. Nevertheless, introducing enzyme(s) for butyryl butyrate (BB) biosynthesis based on this system, only 1.64 g/L BB with 14.3 % carbon yield was obtained due to an imbalance in NADH-NAD+ turnover. To address the issue of NADH accumulation, a joint redox-balanced pathway for BB biosynthesis was developed in this study by coupling acetate and glucose metabolism. Following overexpression of acetyl-CoA synthetase in the BB-producing strain, acetate and glucose were co-utilized stoichiometrically and intracellular redox homeostasis was achieved. The engineered strain produced 29.02 g/L BB with carbon yield of 43.3 %, representing the highest yield ever reported for fermentative production of BB. It indicated the potential for developing a carbon- and energy-effective route for biomanufacturing.

Acute and prolonged effects of Bacillus amyloliquefaciens GF424-derived SOD on antioxidant defense in healthy individuals challenged with intense aerobic exercise.

Reactive oxygen species (ROS) play a vital role in cellular functions but can lead to oxidative stress and contribute to degenerative diseases when produced in excess. Maintaining redox balance is essential and can be achieved through innate defense mechanisms or external antioxidants. Superoxide dismutase (SOD) is a key enzyme that mitigates intracellular oxidative stress by converting harmful free radicals into hydrogen peroxide, which is subsequently neutralized by catalase and glutathione peroxidase. Previous studies have demonstrated the antioxidant capabilities of SOD derived from Bacillus amyloquefaciens GF424 (BA-SOD) in murine models exposed to either irradiation or SOD1 gene deletion. In this study, a randomized clinical trial was conducted to evaluate the antioxidative benefits of BA-SOD in healthy individuals undergoing acute aerobic exercise (AAE). Eighty participants were randomly assigned to receive either BA-SOD or a placebo for 8 weeks. Antioxidant enzyme activities and glutathione levels were measured before, immediately after, and 30 min post-exercise. A single dose of BA-SOD significantly reduced ROS levels induced by AAE, primarily by enhancing SOD activity in erythrocytes and activating glutathione peroxidase. Continuous BA-SOD administration was associated with a sustained increase in catalase activity and elevated levels of reduced glutathione (GSH). Transcriptomic and metabolomic analyses revealed that a single BA-SOD dose facilitated GSH oxidation, as evidenced by decreased levels of serine, glutamine, and glycine, and increased pyroglutamate levels. Additionally, repeated dosing led to increased expression of genes encoding isocitrate dehydrogenase and malic enzyme, which are involved in NADPH synthesis, as well as nicotinamide phosphoribosyl transferase and NAD kinase, which are essential for NADP availability-critical for converting oxidized glutathione (GSSG) back to GSH. These molecular insights align with clinical observations, suggesting that both acute and long-term BA-SOD supplementation may effectively enhance antioxidant defenses and maintain redox balance under oxidative stress conditions.

Unraveling the Peroxidase Activity in Peroxiredoxins: A Comprehensive Review of Mechanisms, Functions, and Biological Significance.

Peroxiredoxins (Prxs) are members of the antioxidant enzymes necessary for every living object in the three domains of life and play critical roles in controlling peroxide levels in cells. This comprehensive literature review aims to elucidate the peroxidase activity of Prxs, examining their roles and significance for organisms across various taxa. Ironically, the primary role of the Prxs is the peroxidase activity, which comprises the reduction of hydrogen peroxide and other organic hydroperoxides and decreases the risk of oxidative damage in the cells. The above enzymatic activity occurs through the reversible oxidation-reduction catalyzed by cysteine residues in the active site by forming sulfenic acid and reduction by intracellular reductants. Structurally and functionally, Prxs function as dimers or decamers and show different catalytic patterns according to their subfamilies or cellular compartments. Compared to the mechanisms of the other two subgroups of Prxs, including 2-Cys Prxs and atypical Prxs, the 1-Cys Prxs have monomer-dimer switch folding coupled with catalytic activity. In addition to their peroxidase activity, which is widely known, Prxs are becoming acknowledged to be involved in other signaling processes, including redox signaling and apoptosis. This aversion to oxidative stress and regulation by the cellular redox state places them at the heart of adaptive cellular responses to changes in the environment or manifestations of diseases. In conclusion, based on the data obtained and on furthering the knowledge of Prxs' structure and function, these enzymes may be classified as a diverse yet essential family of proteins that can effectively protect cells from the adverse effects of oxidative stress due to peroxidase activity. This indicates secondary interactions, summarized as peroxide detoxification or regulatory signaling, and identifies their applicability in multiple biological pathways. Such knowledge is valuable for enhancing the general comprehension of essential cellular functions and disclosing further therapeutic approaches to the diseases caused by the increased production of reactive oxygen species.

Oxidative stress and food as medicine.

There has been a sea of change in our understanding of the contribution of food to both our well-being and disease states. When one addresses "food as medicine," the concept of oxidative stress needs to be included. This review interconnects the basic science findings of oxidative stress and redox balance with the medicinal use of food, emphasizing optimization of the redox balance. To better illustrate the impacts of oxidative stress, the concept of the "triple oxidant sink" is introduced as a theoretical gauge of redox balance. Utilizing the concept, the true importance of dietary and lifestyle factors can be emphasized, including the limitations of supplements or a handful of "superfoods," if the remainder of the factors are pro-oxidant. The effects of a whole plant food diet compared with those of dietary supplements, processed foods, animal based nutrients, or additional lifestyle factors can be visually demonstrated with this concept. This paper provides an overview of the process, acknowledging that food is not the only mechanism for balancing the redox status, but one that can be strategically used to dramatically improve the oxidative state, and thus should be used as medicine.

Increased oxidative stress biomarkers in central serous chorioretinopathy.

Current data suggest that oxidative stress may play an important role in the occurrence of acute central serous chorioretinopathy (CSC), as chorioretinal integrity may be affected by disruption of the patient's metabolic redox balance, indicating the need for biomarkers. In addition to oxidative stress, high-density lipoprotein (HDL) dysfunction due to dyslipidemia can also lead to many types of physical discomfort. However, little is known about the pathophysiology of the disease resulting from oxidative stress and HDL dysfunction in CSC. The aim of this study was to investigate whether serum oxidative stress and HDL functionality markers have an impact on CSC disease. The case series of this study included 33 consecutive patients with treatment-naïve acute CSC. Thirty-five healthy volunteers of similar age were included in this study as non-CSC controls. Serum samples of the participants were taken and routine lipid values, serum Total Antioxidant Status (TAS), Total Oxidant Status (TOS), Oxidized Low Density Lipoprotein (ox-LDL), and Paraoxonase (PON1) levels were measured quantitatively. Serum oxidative stress index (OSI) was then calculated. Serum Ox-LDL, TOS and OSI levels in the acute CSC group, consisting of patients who had never been treated before and had no other disease, were statistically significantly higher than the control group. Conversely, serum PON1 and TAS levels were lower in CSC than in the control group. The relationship between CSC and deterioration in serum redox balance and decrease in PON1 activity, an important marker of HDL functionality, was demonstrated for the first time through this study. According to the literature, serum levels of these biomarkers, which identify acute/chronic inflammation and oxidative stress, have not been measured before in CSC disease. Finally, it is conceivable that redox balance and HDL functionality may be important in the diagnosis and treatment of the acute phase of CSC.

Tributyltin-induced visceral adiposity is associated with impaired redox balance in white adipose tissue of male rats.

Tributyltin (TBT) is an organotin compound that has several adverse health effects, including the development of obesity. Although obesity is strongly associated with adipose redox imbalance, there is a lack of information on whether TBT promotes a pro-oxidative environment in WAT. Thus, adult male Wistar rats were randomly exposed to either vehicle (ethanol 0.4%) or TBT (1000 ng/kg) for 30 days. Body and fat pad masses, visceral fat morphology, lipid peroxidation, protein carbonylation, redox status markers, and catalase activity were evaluated. TBT promoted increased adiposity and visceral fat, with hypertrophic adipocytes, but did not alter body mass and subcutaneous fat. ROS production and lipid peroxidation were elevated in TBT group, as well as catalase protein expression and activity, although protein oxidation and glutathione peroxidase protein expression remained unchanged. In conclusion, this is the first study to demonstrate that subacute TBT administration leads to visceral adipose redox imbalance, with increased oxidative stress. This enlights the understanding of the metabolic toxic outcomes of continuous exposure to TBT in mammals.

Dynamic and Static Regulation of Nicotinamide Adenine Dinucleotide Phosphate: Strategies, Challenges, and Future Directions in Metabolic Engineering.

Reduced nicotinamide adenine dinucleotide phosphate (NADPH) is a crucial cofactor in metabolic networks. The efficient regeneration of NADPH is one of the limiting factors for productivity in biotransformation processes. To date, many metabolic engineering tools and static regulation strategies have been developed to regulate NADPH regeneration. However, traditional static regulation methods often lead to the NADPH/NADP+ imbalance, causing disruptions in cell growth and production. These methods also fail to provide real-time monitoring of intracellular NADP(H) or NADPH/NADP+ levels. In recent years, various biosensors have been developed for the detection, monitoring, and dynamic regulate of the intracellular NADP(H) levels or the NADPH/NADP+ balance. These NADPH-related biosensors are mainly used in the cofactor engineering of bacteria, yeast, and mammalian cells. This review analyzes and summarizes the NADPH metabolic regulation strategies from both static and dynamic perspectives, highlighting current challenges and potential solutions, and discusses future directions for the advanced regulation of the NADPH/NADP+ balance.

Asthma exacerbations and airway redox imbalance under type 2 inflammatory conditions.

Asthma is a chronic inflammatory airway disease characterized by bronchial hyperresponsiveness and reversibility. Despite considerable advances in asthma treatment based on our understanding of its pathophysiology, asthma exacerbations remain challenging. To reduce asthma exacerbations, it is essential to identify triggers, patients' risk factors, and underlying mechanisms. While exposure to viruses and environmental stimuli are known common triggers for asthma exacerbations, the key factors involved in asthma exacerbations have been identified as type 2 inflammation. Type 2 inflammatory biomarkers have been demonstrated to be useful in predicting individuals at risk of exacerbations. Furthermore, recent clinical trials of targeted biological therapy, which blocks the type 2 pathway, have supported the critical role of type 2 inflammation in asthma exacerbations. Although the specific mechanisms linking type 2 inflammation to asthma exacerbations have not yet been fully elucidated, increasing evidence shows that reduction/oxidation (redox) imbalance likely plays an important role in this association. Under type 2 inflammatory conditions, human airway epithelial cells activate 15-lipoxygenase-1 in complex with phosphatidylethanolamine binding protein-1, leading to the generation of electrophilic hydroperoxyl-phospholipids. When the accumulation of reactive lipid peroxidation surpasses a specific glutathione-dependent activity, these electrophilic compounds are not neutralized, leading to programmed cell death, ferroptosis. Reduced glutathione levels, caused by type 2 inflammation, may impair its ability to neutralize reactive lipid peroxidation. The accumulation of lipid peroxidation with intracellular redox imbalance may contribute to asthma exacerbations in individuals with type 2 inflammation. Inhibiting the ferroptotic pathway holds promise as a therapeutic strategy to alleviate asthma exacerbations.

Effects of inclusion of the blend of essential oils, organic acids, curcumin, tannins, vitamin E, and zinc in the maternal diet, and of incubation temperature on early and late development of quail.

The maternal diet and egg incubation temperature are some of the factors that can influence the embryonic development and performance of the newly chicks at 15 d of age. This study evaluated the effects of adding a blend of organic acids, essential oils, curcumin, tannins, vitamin E, and zinc microencapsulated in to the diet of female quails (Coturnix coturnix japonica) on their productive, reproductive performance and redox parameters of their eggs and the interaction of maternal diet × incubation temperature on embryo (E16 and E18) and chicks development. At 98 d of age, 64 female quails with a mean body weight of 150 g ± 0.5 were distributed into two treatments: a Basal diet or a diet supplemented with blend (Sannimix). The eggs from each female were incubated at 37.5°C (Control) and 38.5°C (High Temperature) throughout the incubation period. After hatching, chicks were distributed in a 2 (maternal diet) × 2 (incubation temperature) factorial design. Female quails supplemented with Sannimix showed better productive and reproductive performance and produced higher-quality embryos. Their offspring had greater weight at hatch and at 15 d of age. The eggs and offspring of supplemented with Sannimix female quails showed better oxidative stability. At E16 and E18, High Temperature increased yolk sac utilization and gene expression of the growth hormone receptor (GHR). At E16, embryos from supplemented with Sannimix female quail had higher expression of insulin-like growth factor type I (IGFI) and heat shock protein 70 kDa genes. At 15 d of age, highest expression of the GHR and IGFI genes was observed in chicks from female quails fed the Sannimix diet, regardless of incubation temperature. Regarding the maternal diet × incubation temperature an improved result was observed for chicks from female quails fed with Sannimix even when eggs are exposed to High Temperature during the incubation. The supplementation of quail diets with blend Sannimix improves productive and reproductive performance, egg quality and their embryos, as well as their offspring quality.

Traffic-related ultrafine particles impair mitochondrial functions in human olfactory mucosa cells - Implications for Alzheimer's disease.

Constituents of air pollution, the ultrafine particles (UFP) with a diameter of ≤0.1 µm, are considerably related to traffic emissions. Several studies link air pollution to Alzheimer's disease (AD), yet the exact relationship between the two remains poorly understood. Mitochondria are known targets of environmental toxicants, and their dysfunction is associated with neurodegenerative diseases. The olfactory mucosa (OM), located at the rooftop of the nasal cavity, is directly exposed to the environment and in contact with the brain. Mounting evidence suggests that the UFPs can impact the brain directly through the olfactory tract. By using primary human OM cultures established from nasal biopsies of cognitively healthy controls and individuals diagnosed with AD, we aimed to decipher the effects of traffic-related UFPs on mitochondria. The UFP samples were collected from the exhausts of a modern heavy-duty diesel engine (HDE) without aftertreatment systems, run with renewable diesel (A0) and petroleum diesel (A20), and from an engine of a 2019 model diesel passenger car (DI-E6d) equipped with state-of-the-art aftertreatment devices and run with renewable diesel (Euro6). OM cells were exposed to three different UFPs for 24-h and 72-h, after which cellular processes were assessed on the functional and transcriptomic levels. Our results show that UFPs impair mitochondrial functions in primary human OM cells by hampering oxidative phosphorylation (OXPHOS) and redox balance, and the responses of AD cells differ from cognitively healthy controls. RNA-Seq and IPA® revealed inhibition of OXPHOS and mitochondrial dysfunction in response to UFPs A0 and A20. Functional validation confirmed that A0 and A20 impair cellular respiration, decrease ATP levels, and disturb redox balance by altering NAD and glutathione metabolism, leading to increased ROS and oxidative stress. RNA-Seq and functional assessment revealed the presence of AD-related alterations in human OM cells and that different fuels and engine technologies elicit differential effects.

Impact of Intermittent Fasting and Dietary Restriction on Redox State, Energetic Metabolism, and Liver Injury in Common Bile Duct Ligation Model.

The aim of this work was to test whether we can treat cholestasis with dietary approaches applied after the onset of the disease. The effects of intermittent fasting and dietary restriction on liver damage caused by common bile duct ligation (BDL) in rats were studied, with particular attention paid to changes in the activity of enzymes of energy metabolism and antioxidant protection. Morphological changes in liver tissue and serum markers of liver damage were assessed in rats with BDL kept for one month on ad libitum diet, intermittent fasting, or 35% dietary restriction. We studied parameters of glucose metabolism (activity of glycolysis and gluconeogenesis enzymes), TCA cycle, and indicators of oxidative stress and redox status of the liver tissue. Dietary restriction resulted in an increase in gluconeogenesis activity, antioxidant capacity, and autophagy activation. When implemented after BDL, none of the dietary restriction protocols reduced the level of oxidative stress, detrimental morphological and biochemical alterations, or the fibrosis progression. Thus, under severe damage and oxidative stress developing in cholestasis, dietary restrictions are not hepatoprotective and can only be used in a pre-treatment mode.

Metformin attenuates high-carbohydrate diet-induced redox imbalance, inflammation, and mitochondrial dysfunction in Megalobrama amblycephala.

This study aimed to investigate the effects of dietary metformin supplementation on the redox balance, inflammation, mitochondrial biogenesis, and function in blunt snout bream fed a high-carbohydrate (HC) diet. Fish (45.12 ± 0.36 g) were randomly offered four diets, including a control diet (33% carbohydrate), an HC diet (45% carbohydrate), and the HC diet supplemented with 0.06% (HCM1) and 0.12% (HCM2) metformin respectively for 12 weeks. Compared with the control, feeding the HC diet significantly increased the hepatosomatic index (HSI), the mesenteric fat index, liver and muscle glycogen contents, liver and adipose tissue lipid contents, plasma glucose and glycation end products (AGES) levels and aspartate transaminase activity, plasma and liver malondialdehyde (MDA) contents, hepatic adenosine triphosphate (ATP) and adenosine monophosphate (AMP) contents, mitochondrial cytochrome c content, mitochondrial complex IV activity and ATP 6 transcription, but decreased plasma catalase (CAT) activity, muscle superoxide dismutase (SOD) activity, hepatic antioxidant enzymes activities, and the transcriptions of transforming growth factor ß (tgfß) and interleukin 10 (il10). Compared with the HC group, metformin treatment (especially the HCM2 group) significantly elevated tissue glycogen contents, muscle SOD activity, plasma and liver antioxidant enzymes activities, the transcriptions of tgfß and il10, the sodium/potassium ATPase activity, the contents of mitochondrial protein and AMP, the level of p-AMP activated protein kinase (AMPK), and the p-AMPK/t-AMPK ratio, but lowered the HSI, tissue lipid contents, plasma levels of glucose, AGES and glycated serum protein, plasma, and liver MDA contents, the transcriptions of il1ß, NADH dehydrogenase subunit 1 and ATP 6, the contents of ATP and cytochrome c, the ATP/AMP ratio, and the activities of complexes I and IV. In conclusion, metformin could attenuate the HC diet-induced redox imbalance, inflammation, and mitochondrial dysfunction in blunt snout bream.

Antibiotic-driven dysbiosis in early life disrupts indole-3-propionic acid production and exacerbates allergic airway inflammation in adulthood.

Antibiotic use in early life disrupts microbial colonization and increases the risk of developing allergies and asthma. We report that mice given antibiotics in early life (EL-Abx), but not in adulthood, were more susceptible to house dust mite (HDM)-induced allergic airway inflammation. This susceptibility was maintained even after normalization of the gut microbiome. EL-Abx decreased systemic levels of indole-3-propionic acid (IPA), which induced long-term changes to cellular stress, metabolism, and mitochondrial respiration in the lung epithelium. IPA reduced mitochondrial respiration and superoxide production and altered chemokine and cytokine production. Consequently, early-life IPA supplementation protected EL-Abx mice against exacerbated HDM-induced allergic airway inflammation in adulthood. These results reveal a mechanism through which EL-Abx can predispose the lung to allergic airway inflammation and highlight a possible preventative approach to mitigate the detrimental consequences of EL-Abx.

Two faces of one coin: Beneficial and deleterious effects of reactive oxygen species during short-term acclimation to hypo-osmotic stress in a decapod crab.

Exposure to environmental changes often results in the production of reactive oxygen species (ROS), which, if uncontrolled, leads to loss of cellular homeostasis and oxidative distress. However, at physiological levels these same ROS are known to be key players in cellular signaling and the regulation of key biological activities (oxidative eustress). While ROS are known to mediate salinity tolerance in plants, little is known for the animal kingdom. In this study, we use the Mediterranean crab Carcinus aestuarii, highly tolerant to salinity changes in its environment, as a model to test the healthy or pathological role of ROS due to exposure to diluted seawater (dSW). Crabs were injected either with an antioxidant [N-acetylcysteine (NAC), 150 mg·kg-1] or phosphate buffered saline (PBS). One hour after the first injection, animals were either maintained in seawater (SW) or transferred to dSW and injections were carried out at 12-h intervals. After ≈48 h of salinity change, all animals were sacrificed and gills dissected for analysis. NAC injections successfully inhibited ROS formation occurring due to dSW transfer. However, this induced 55% crab mortality, as well as an inhibition of the enhanced catalase defenses and mitochondrial biogenesis that occur with decreased salinity. Crab osmoregulatory capacity under dSW condition was not affected by NAC, although it induced in anterior (non-osmoregulatory) gills a 146-fold increase in Na+/K+/2Cl- expression levels, reaching values typically observed in osmoregulatory tissues. We discuss how ROS influences the physiology of anterior and posterior gills, which have two different physiological functions and strategies during hyper-osmoregulation in dSW.

Multi-omics revealed anti-fatigue property of polyphenol from areca nut.

BACKGROUND: Areca nut polyphenols (AP) that extracted from areca nut, have been demonstrated for their potential of anti-fatigue effects. However, the underlying mechanisms for the anti-fatigue properties of AP has not been fully elucidated to date. Previous studies have predominantly concentrated on single aspects, such as antioxidation and anti-inflammation, yet have lacked comprehensive multi-dimensional analyses. PURPOSE: To explore the underlying mechanism of AP in exerting anti-fatigue effects. METHODS: In this study, we developed a chronic sleep deprivation-induced fatigue model and used physiological, hematological, and biochemical indicators to evaluate the anti- fatigue efficacy of AP. Additionally, a multi-omics approach was employed to reveal the anti-fatigue mechanisms of AP from the perspective of microbiome, metabolome, and proteome. RESULTS: The detection of physiology, hematology and biochemistry index indicated that AP markedly alleviate mice fatigue state induced by sleep deprivation. The 16S rRNA sequencing showed the AP promoted the abundance of probiotics (Odoribacter, Dubosiella, Marvinbryantia, and Eubacterium) and suppressed harmful bacteria (Ruminococcus). On the other hand, AP was found to regulate the expression of colonic proteins, such as increases of adenosine triphosphate (ATP) synthesis and mitochondrial function related proteins, including ATP5A1, ATP5O, ATP5L, ATP5H, NDUFA, NDUFB, NDUFS, and NDUFV. Serum metabolomic analysis revealed AP upregulated the levels of anti-fatigue amino acids, such as taurine, leucine, arginine, glutamine, lysine, and l-proline. Hepatic proteins express levels, especially tricarboxylic acid (TCA) cycle (CS, SDHB, MDH2, and DLST) and redox-related proteins (SOD1, SOD2, GPX4, and PRDX3), were significantly recovered by AP administration. Spearman correlation analysis uncovered the strong correlation between microbiome, metabolome and proteome, suggesting the anti-fatigue effects of AP is attribute to the energy homeostasis and redox balance through gut-liver axis. CONCLUSION: AP increased colonic ATP production and improve mitochondrial function by regulating gut microbiota, and further upregulated anti-fatigue amino acid levels in the blood. Based on the gut-liver axis, AP upregulated the hepatic tricarboxylic acid cycle and oxidoreductase-related protein expression, regulating energy homeostasis and redox balance, and ultimately exerting anti-fatigue effects. This study provides insights into the anti-fatigue mechanisms of AP, highlighting its potential as a therapeutic agent.

Regulatory mechanisms of amino acids in ferroptosis.

Ferroptosis, an iron-dependent non-apoptotic regulated cell death process, is associated with the pathogenesis of various diseases. Amino acids, which are indispensable substrates of vital activities, significantly regulate ferroptosis. Amino acid metabolism is involved in maintaining iron and lipid homeostasis and redox balance. The regulatory effects of amino acids on ferroptosis are complex. An amino acid may exert contrasting effects on ferroptosis depending on the context. This review systematically and comprehensively summarized the distinct roles of amino acids in regulating ferroptosis and highlighted the emerging opportunities to develop clinical therapeutic strategies targeting amino acid-mediated ferroptosis.

Hydrogen-Rich Alkaline Water Supplementation Restores a Healthy State and Redox Balance in H2O2-Treated Mice.

Water is a major requirement for our bodies, and alkaline water has induced an antioxidant response in a model of natural aging. A series of recent reports have shown that aging is related to reduced water intake. Hydrogen-rich water has been suggested to exert a general antioxidant effect in relation to both improving lifestyle and preventing a series of diseases. Here, we wanted to investigate the effect of the daily intake of hydrogen-rich alkaline water (HAW) in counteracting the redox imbalance induced in a model of H2O2-treated mice. Mice were treated with H2O2 for two weeks and either left untreated or supplied with HAW. The results show that HAW induced a reduction in the ROS plasmatic levels that was consistent with the increase in the circulating glutathione. At the same time, the reduction in plasmatic 8-hydroxy-2'-deoxyguanosine was associated with reduced DNA damage in the whole body. Further analysis of the spleen and bone marrow cells showed a reduced ROS content consistent with a significantly reduced mitochondrial membrane potential and superoxide accumulation and an increase in spontaneous proliferation. This study provides evidence for a clear preventive and curative effect of HAW in a condition of systemic toxic condition and redox imbalance.

Modulation of Redox and Inflammatory Signaling in Human Skin Cells Using Phytocannabinoids Applied after UVA Irradiation: In Vitro Studies.

UVA exposure disturbs the metabolism of skin cells, often inducing oxidative stress and inflammation. Therefore, there is a need for bioactive compounds that limit such consequences without causing undesirable side effects. The aim of this study was to analyse in vitro the effects of the phytocannabinoids cannabigerol (CBG) and cannabidiol (CBD), which differ in terms of biological effects. Furthermore, the combined use of both compounds (CBG+CBD) has been analysed in order to increase their effectiveness in human skin fibroblasts and keratinocytes protection against UVA-induced alternation. The results obtained indicate that the effects of CBG and CBD on the redox balance might indeed be enhanced when both phytocannabinoids are applied concurrently. Those effects include a reduction in NOX activity, ROS levels, and a modification of thioredoxin-dependent antioxidant systems. The reduction in the UVA-induced lipid peroxidation and protein modification has been confirmed through lower levels of 4-HNE-protein adducts and protein carbonyl groups as well as through the recovery of collagen expression. Modification of antioxidant signalling (Nrf2/HO-1) through the administration of CBG+CBD has been proven to be associated with reduced proinflammatory signalling (NFκB/TNFα). Differential metabolic responses of keratinocytes and fibroblasts to the effects of the UVA and phytocannabinoids have indicated possible beneficial protective and regenerative effects of the phytocannabinoids, suggesting their possible application for the purpose of limiting the harmful impact of the UVA on skin cells.

Malate dehydrogenase (MDH) in cancer: a promiscuous enzyme, a redox regulator, and a metabolic co-conspirator.

Malate dehydrogenase (MDH) is an essential enzyme in the tricarboxylic acid cycle that functions in cellular respiration and redox homeostasis. Recent studies indicate that MDH facilitates metabolic plasticity in tumor cells, catalyzing the formation of an oncometabolite, contributing to altered epigenetics, and maintaining redox capacity to support the rewired energy metabolism and biosynthesis that enables cancer progression. This minireview summarizes current findings on the unique supporting roles played by MDH in human cancers and provides an update on targeting MDH in cancer chemotherapy.