Cereal crops, such as oats and barley, possess a number of valuable properties that meet the requirements for functional diet components. This review summarized the available information about bioactive compounds of oat and barley grain. The results of studying the structure and physicochemical properties of the cell wall polysaccharides of barley and oat are presented. The main components of the flavonoids formation pathway are shown and data, concerning anthocyanins biosynthesis in various barley tissues, are discussed. Moreover, we analyzed the available information about structural and regulatory genes of anthocyanin biosynthesis in Hordeum vulgare L. genome, including β-glucan biosynthesis genes in Avena sativa L species. However, there is not enough knowledge about genes responsible for biosynthesis of β-glucans and corresponding enzymes and plant polyphenols. The review also covers contemporary studies about collections of oat and barley genetic resources held by VIR. This review intended to provide information on the processes of biosynthesis of biologically active compounds in cereals that will promote further researches devoted to transcription factors controlling expression of structural genes and their role in other physiological processes in higher plants. Found achievements will allow breeders to create new highly productive varieties with the desirable properties.

Oxidative stress initiates and facilitates the disruption of the structural integrity of hepatic mitochondria, which leads to steatosis, steatohepatitis, fibrosis, and cirrhosis. It is now evident that mitochondrial dysfunction could be responsible for alcoholic liver disease (ALD). The challenge in treating ALD has been the limited availability of hepatoprotective agents and the lack of highly efficient delivery systems. Recent studies have shown that mitochondria-targeted therapies could address mitochondrial dysfunction (MD), which may greatly improve hepatoprotection and ALD treatment. This mini-review discusses the potential role of mitochondria-targeted antioxidants (MTAs) in the maintenance of hepatocellular integrity. This report also considers the mechanism of liver injury induced by alcohol and the progression of ALD from a mitochondrial oxidative damage perspective as well as the possible mechanistic actions of hepatoprotective antioxidants. Preliminary studies suggest the prospect of MTAs as anti-ALD and hepatoprotective agents.

Growing evidence from neurodegenerative disease research supports an early pathogenic role for mitochondrial dysfunction in affected neurons that precedes morphological and functional deficits. Resulting oxidative stress and respiratory malfunction contribute to neuronal toxicity and may enhance the vulnerability of neurons to continued assault by aggregation-prone proteins. Consequently, targeting mitochondria with antioxidant therapy may be a non-invasive, inexpensive, and viable means of strengthening neuronal health and slowing disease progression, thereby extending quality of life. We review the pre-clinical and clinical findings available to date of the natural bioactive phenol resveratrol and two synthetic mitochondrial-targeted antioxidants MitoQ and SkQ.

Elevated salinity is one of the major environmental limitation factors of plant growth and development and salinity stress compromises the production and survival of plantation and urban forests and agricultural crops in the arid, semi-arid, and intertidal zones. Ulmus pumila, a salt- indigenous tree species in Asia and is widely deployed in salt-affected areas in China, and U.pumila is promising for multi-varietal forestry in plantation and urban forests. The comprehensive mechanism of the intraspecific salt tolerance is still not clear yet. Here, we investigated the physiological responses of the salinity stress based on the antioxidant enzyme activities, osmotic adjustments, and gas exchange among salt-tolerant U. pumila genotypes for 100 days under five different NaCl levels (0%, 0.3%, 0.5%, 0.7%, and 0.9% w/v) with natural surroundings and rain shade at age-2. Salt stress decreased height (HR), ground diameter (DR), and dry weight (biomass) were significantly different among genotypes. HR and performance indices were positively correlated with photosynthesis rate (Pn), apparent mesophyll conductance (AMC), and chlorophyll (CHLL) with (r= 0.7 - 0.8 ***), but were negatively related to the free proline, sugar, and protein accumulation (r=-0.5 ~ -0.7***). We found that high accumulation of sugars and more activities of SOD enzyme in leaf tissue contribute to the osmotic adjustment and ROS scavenging system under salinity treatment; the sugar content and SOD activity play key roles in U. pumila’s tolerance to salt stress, and are promising indicators for U. pumila species ex vitro selections. The ex vitro selection results align with the previous in vitro studies [37] and is promising for the MVF development.

A prominent feature of stress-tolerant microalgae is their versatile metabolism allowing then to synthesize a broad spectrum of molecules with beneficial effects on many aspects of human body functioning. This is in line with the current understanding that many stress-induced deleterious processes in the human body and in photosynthetic cell are mediated by the same mechanisms such as free-radical attacks and lipid peroxidation. These related risks are kept at bay by optical screening of harmful UV, enzymatic ROS elimination systems, and potent low-molecular antioxidants. Microalgae synthesize a broad spectrum of compounds exerting antioxidant and/or UV-absorbing properties. In microalgae, they increase stress-resilience of these organisms. In human body, they exhibit photoprotective, antiaging, and sunscreen activities. Therefore, these algal metabolites were recognized as promising ingredients for innovative cosmetics and cosmeceutical formulations. Ever increasing effort is being invested into the search for new natural biologically active substances from microalgae. This trend is also fueled by the growing demand for natural raw materials for food, pharmaceuticals and cosmetology associated with the global transition to a "greener" lifestyle. Here, we review the currently accumulated knowledge about the main groups of cosmeceutical compounds from microalgae.

Sickle cell disease (SCD) is the most common hereditary disorder of hemoglobin (Hb) that affects approximately a millions people worldwide. It is characterized by a single nucleotide substitution on the β-globin gene, leading to the production of abnormal sickle hemoglobin with multi-system consequences. Mutated Hb leads to profound changes in: i) red blood cell metabolism and physiology; ii) endothelial signaling; and iii) immune response. Oxidative stress is an important hallmark of SCD. It plays a key role in the pathophysiology of hemolysis, vessel occlusion and the following organ damage in sickle cell patients. For this reason, reactive oxidizing species and the (end)-products of their oxidative reactions have been proposed as markers of both tissue pro-oxidant status and disease severity. Although more studies are needed to clarify their role, antioxidant agents have been shown to be effective in reducing pathological consequences of the disease by preventing oxidative damage in SCD, i.e. by decreasing the oxidant formation or repairing the induced damage. An improved understanding of oxidative stress will lead to targeted antioxidant therapies that should prevent or delay the development of organ complications in this patient population.

Recently, a breakdown of paracellular and vascular pathways and activated neuroimmune and oxidative pathways were established in (deficit) schizophrenia. The aim of the current study was to delineate a) the differences in these pathways between stable phase, first (FES) and multiple (MES) episode schizophrenia, and b) the pathways that determine the behavioral-cognitive-physical-psychosocial (BCPS)-worsening in FES/MES. This study included 21 FES and 58 FES patients and 40 healthy controls and measured indicants of serum IgA to C1q, and leaky gut, immune activation, and oxidative stress toxicity (OSTOX) biomarkers. We constructed a BCPS-worsening index by extracting a latent vector from symptomatic, neurocognitive, and quality of life data. FES patients showed significantly higher IgA to C1q, cadherin, catenin, plasmalemma vesicle-associated protein, and IgA/IgM to Gram-negative bacteria than FES patients and controls. In FES patients, the BCPS-worsening score was predicted (48.7%) by IgA to Klebsiella pneumoniae and lowered paraoxonase 1 activity. In MES patients, the BCPS-worsening score was explained (42.7%) by increased tumor necrosis factor-α, OSTOX, and number of episodes. In schizophrenia, 34.0% of the variance in the BCPS-worsening score was explained by IgA to K. pneumoniae, OSTOX, and number of episodes. Increased IgA to K. pneumoniae was the single best predictor of residual psychotic symptoms in FES and MES. This study delineated different mechanistic processes in FES, including breakdown of adherens junctions, bacterial translocation, and C1q circulating immune complexes; and FES, including immune and oxidative stress neurotoxic pathways. FES and MES comprise different staging subtypes, i.e., FES and MES with and without worsening.

Recently we showed that schizophrenia and, especially, deficit schizophrenia is accompanied by neurocognitive impairments as measured with different cognitive batteries. The aim of this study was to examine whether a single trait underpins aberrations in 9 key Cambridge Neuropsychological Test Automated Battery (CANTAB) probes, verbal fluency (VFT), world list memory (WLM), true recall, and the Mini Mental State Examination (MMSE). We recruited 80 patients with schizophrenia and 40 healthy controls. All patients were assessed using CANTAB tests, namely paired-association learning (PAL), rapid visual information (RVP), spatial working memory (SWM), one touch stocking (OTS), intra/extradimensional set shifting (IED), and emotional recognition test (ERT). We found that a single latent trait, which is essentially unidimensional, underlies the CANTAB tests, VFT, WLM, True Recall and MMSE. The latent trait shows excellent psychometric properties and fits a reflective model and, therefore, reflects a generalized cognitive decline (GCoDe), which is the cause of aberrations in semantic and episodic memory, recall, executive functions, strategy use, rule acquisition, visual sustained attention, attention set-shifting and emotional recognition. 40.5% of the variance in GCode was explained by CCL11, IgA to tryptophan catabolites, and increased oxidative toxicity. GCoDe explains 44.8% of the variance in a single latent trait extracted from psychosis, hostility, excitation, mannerism, negative symptoms, formal thought disorders, and psychomotor retardation and 40.9% in quality of life scores. GCoDe is significantly greater in deficit than in nondeficit schizophrenia. In conclusion, GCoDe mediates the effects of neuro-immune and neuro-oxidative toxicity on the phenome of (deficit) schizophrenia.

Riboflavin transporter deficiency (RTD) is a childhood-onset neurodegenerative disorder characterized by sensorineural deafness and motor neuron degeneration. Since riboflavin plays key functions in biological oxidation-reduction reactions, energy metabolism pathways involving flavoproteins are affected in RTD. We recently generated iPSC lines from affected individuals as an in vitro model of the disease and documented mitochondrial impairment in these cells dramatically impacting cell redox status. In the present work, we extend our study to motor neurons (MNs), i.e., the cell type mostly affected in patients with RTD. Altered intracellular distribution of mitochondria was detected by confocal microscopic analysis, following immunofluorescence for superoxide dismutase 2 (SOD2), as a dual mitochondrial and antioxidant marker, and βIII Tubulin, as neuronal marker. We demonstrate significantly lower SOD2 levels in RTD MNs, as compared to their healthy counterparts. Mitochondrial ultrastructural abnormalities were also assessed by Focused Ion Beam/Scanning Electron Microscopy. Moreover, we investigated the effects of combination treatment using riboflavin and N-acetylcysteine, which is a widely employed antioxidant. Overall, our findings further support the potential of patient specific RTD models, and provide evidence of mitochondrial alterations in RTD-related iPSC-derived MNs, emphasizing oxidative stress involvement in this rare disease. We also provide new clues for possible therapeutic strategies, aimed at correcting mitochondrial defects, based on the use of antioxidants.

The interaction of ultraviolet radiation with biological matter results in direct damage such as pyrimidine dimers in DNA. It also results in indirect damage provoked by the production of Reactive Oxygen Species (ROS) catalyzed by photo-sensitizers. Photosensitizers can be endogenous (e.g. Tryptophan) or exogenous (e.g. TiO2 and other photo-stable UVA sunscreens). Direct damage triggers an inflammatory response and the oxidative and proteolytic bursts that characterize its onset. The inflammatory reaction multiplies the effects of one single photon. Indirect damage, such as the peroxidative cascade in membrane lipids, can extend to thousands of molecular modifications per absorbed photon. Sunscreens should therefore be formulated in the presence of appropriate anti-oxidants. Superoxide and Singlet Oxygen are the main ROS that need to be tackled: this review describes some of the molecular, biochemical, cellular and clinical consequences of exposure to UV radiation as well as some results associated with scavengers and quenchers of Superoxide and Singlet Oxygen, as well as with inhibitors of singlet Oxygen production.

Psychiatry remains in a permanent state of crisis, which fragmented psychiatry from the field of medicine. The crisis in psychiatry is evidenced by the many different competing approaches to psychiatric illness including psychodynamic, biological, molecular, pan-omics, precision, cognitive and phenomenological psychiatry, folk psychology, mind-brain dualism, descriptive psychopathology, and postpsychiatry. The current “gold standard” DSM/ICD taxonomies of mood disorders and schizophrenia are unreliable and preclude to employ a deductive reasoning approach. Therefore, it is not surprising that mood disorders and schizophrenia research was unable to revise the conventional classifications and did not provide more adequate therapeutic approaches. The aim of this paper is to explain the new nomothetic network psychiatry (NNP) approach, which uses machine learning methods to build data-driven causal models of mental illness by ensembling risk-resilience, adverse outcome pathways (AOP), cognitome, brainome, symptomatome, and phenomenome latent scores in a causal model. The latter may be trained, tested and validated with Partial Least Squares (PLS) analysis. This approach not only allows to compute pathway-phenotypes or biosignatures, but also to construct reliable and replicable nomothetic networks, which are, therefore, generalizable as disease models. After integrating the validated feature vectors into a well-fitting nomothetic network, clustering analysis may be applied on the latent variable scores of the R/R, AOP, cognitome, brainome, and phenome latent vectors. This pattern recognition method may expose new (transdiagnostic) classes of patients which if cross-validated in independent samples may constitute new (transdiagnostic) nosological categories.

We compare the effect on amyloid fibril formation by two homologous proteins from the family of cystatins, human stefin B (stB) and cystatin C (cysC) in presence of 3 polyphenols: curcumin, resveratrol and quercetin and 2 non-phenolic anti-oxidants: vitamin C (VitC) and N-acetyl cystein (NAC). Some of the experimental data have already been presented, here we compare, further discuss and highlight the results. The amyloid fibril formation was followed by ThT fluorescence and transmission electron microscopy. Inhibitory effects on amyloid fibrillation reaction depended on anti-oxidant class and concentration. The fact that different effect of polyphenols was observed with the two cystatins; Cur acted inhibitory on stB but not on cysC fibril formation, could be explained if the 3 polyphenols would not bind to the same binding site in the fibrils core. Other differences are pointed out and discussed. Synergistic effects of VitC and chosen polyphenols on amyloid fibrilllation of human stB have been explored and are reported here for the first time.

The main focus of this work is to extend the knowledge about the complexity of issues of oxidative stress. Natural compounds play a serious role in multiple aspects of both human, leading to clear health-promoting effects. This work is focused on the potential application cosmetic formulations containing including but not limited to of clove water and isolated clove oils on their aid in the control of the diseases. The aim of our work was to prepare to evaluate cosmetic formulations containing clove oil, eugenol or new eugenol ester derivative (eugenyl dichloroacetate - EDChA) but also cosmetic formulations containing the aqueous phase obtained after separation of essential oil following the clove buds steam distillation. To evaluate the antioxidants transdermal delivery system, in vitro permeation experiments in a Franz diffusion cell were performed using pig skin. The antioxidative capacity of the cosmetic formulations obtained was determined by the DPPH free radical reduction method. In the next stage, the antioxidant activity (DPPH, ABTS, and Folin–Ciocalteu methods) of the fluid that penetrated through pig skin and of the fluid obtained after skin extraction, were also evaluated. For comparison, studies of cosmetic formulation containing alone dichloroacetic acid (DChAA) were as well carried out. The obtained cosmetic formulations were characterized by of antioxidant activity estimated after 24 hours of conducting the experiment, which indicates long-term protection against reactive oxygen species (ROS) in the deeper layers of the skin. The results of this work contribute to the development of cosmetic formulations with antioxidant potential, emphasizing that the water phases are waste from the process of cloves steam distillation and are not used to prepare cosmetic formulations. The use of waste water from the clove buds steam distillation process is environmentally friendly and not allows us to waste, containing however valuable biologically active compounds (furfural, methyl salicylate, 4-allilofenol, eugenol, α- and β-caryophyllene, eugenyl acetate, β-caryophyllene oxide). Together, these results suggest that cosmetic formulations may be potential drug candidates for chemopreventive, antineoplastic and antimutagenic therapy.

Thai basil is a renowned medicinal plant and a rich source of bioactive antioxidant compounds having several health benefits, with actions to prevent of cancer, diabetes and cardiovascular disease. Plant cell and tissue culture technologies can be routinely established as an important, sustainable and low-cost biomass source for the production of high-value phytochemicals. The current study aimed at developing an effective protocol for the production of Thai basil leaf derived callus cultures with sustainable and high production of biomass and antioxidants as an alternative of leaves production. MS basal medium with various concentrations of plant growth regulators (PGRs) compatible with nutraceutical applications (i.e., gibberellic acid (GA3) and 6-benzylaminopurine (BAP) either alone or in combination with naphthalene acetic acid (NAA)) were evaluated. Among all tested PGRs, the combination BAP:NAA (5 mg/L:1 mg/L) yield maximum biomass accumulation (fresh weight (FW): 190 g/L and dry weight (DW): 13.05 g/L) as well as enhanced phenolic (346.08 mg/L) production. HPLC quantification analysis indicated high productions of chicoric acid (35.77 mg/g DW) and rosmarinic acid (7.35 mg/g DW) under optimized callus culture conditions. Antioxidant potential was assessed using both in vitro cell free and in vivo cellular antioxidant assays. Maximum in vitro antioxidant activity DPPH (93.2 % of radical scavenging activity) and ABTS (1322 µM Trolox equivalent antioxidant capacity) was also observed for the extracts from callus cultures grown on optimal conditions. In vivo cellular antioxidant activity assay confirmed the effective protection against oxidative stress of the corresponding extract by the maximum inhibition of ROS and RNS production. Compared to commercial leaves, callus extracts showed higher production of chicoric acid and rosmarinic acid associated with higher antioxidant capacity. In addition, this biological system also has a large capacity for continuous biomass production, thus demonstrating its high potential for possible nutraceutical applications.

Background. There is strong comorbidity between atherosclerosis (ATS) and depression which is attributed to increased atherogenicity, insulin resistance (IR), and immune and oxidative stress.Aim of the study. To examine the role of the above pathways and mu opioid receptor (MOR), β-endorphin, zinc, copper, vitamin D3, calcium, and magnesium in depression due to ATS / unstable angina (UA).Methods. Biomarkers were assayed in 58 controls and 120 ATS patients divided into those with moderate and severe depression according to the Beck Depression Inventory (BDI)-II score > 19 and > 29, respectively. Results. Neural network and logistic regression models showed that severe depression due to ATS/UA was best predicted by IL-6, UA, MOR, zinc, β-endorphin, calcium and magnesium and that moderate depression was associated with IL-6, zinc, MOR, β-endorphin, UA, atherogenicity, IR, and calcium. These neural networks yielded a significant discrimination of severe and moderate depression with an area under the ROC curve of 0.831 and 0.931, respectively. Using Partial Least Squares analysis, 66.2% of the variance in a latent vector extracted from the ATS/UA clinical features, BDI-II scores, atherogenicity, and IR could be explained by the regression on IL-6, IL-10, zinc, copper, calcium, MOR, and age. The BDI-II scores increased from controls to ATS to UA class III to UA class IV.Conclusions. Depression due to ATS/UA is a reflective manifestation of increased atherogenicity and IR, which are modulated by immune activation, aberrations in the endogenous opioid system, antioxidants, trace elements, and macrominerals.

Water stress (drought and waterlogging) is drastic abiotic stress to plant growth and development. Melatonin, bioactive plant hormone, has been widely tested in drought situations in diverse plant species, while a few studies on the role of melatonin in waterlogging stress conditions have been published. In the current review, we analyze the bio-stimulatory functions of melatonin on plants under both drought and waterlogging stress. Melatonin controls the levels of reactive oxygen and nitrogen species and positively changes the molecular defense to improve plant tolerance against drought and waterlogging stress. Moreover, the crosstalk of melatonin and other phytohormones is a key element on plant survival under drought stress, while this relationship needs further investigation under waterlogging stress. In this review, we draw the complete story of water stress on both sides: drought and waterlogging through discussing the previous critical studies under both conditions. Moreover, we suggest several research directions, especially for waterlogging, which remains a big vague piece of melatonin and water stress puzzle.

Patients with transfusion-dependent thalassemia (TDT) show disorders in calcium metabolism. The α-klotho protein is predominantly expressed in tissues that are involved in calcium homeostasis, and lowered levels are associated with bone disease. Aim of the study. To study the associations between low α-klotho status and calcium metabolism in relation to iron status in children with TDT. Methods. α-klotho, calcium, parathyroid hormone (PTH), calcyphosin, vitamin D3, phosphorous, fibroblast growth factor receptor 2 (FGFR2), as well as iron and erythron biomarkers were measured in 60 children with TDT and 30 healthy control children. Results. A meaningful part of TDT patients showed lowered α-klotho levels, and those children also showed low serum total and ionized calcium concentrations. TDT patients showed increased PTH, FGFR2, and calcyphosin and lowered vitamin D3 as compared with healthy children. The α-klotho levels were significantly correlated with total and ionized calcium (positively) and with iron overload biomarkers and the number of blood transfusions (inversely). Partial Least Squares path analysis showed that 40.1% of the variance in serum total calcium could be explained by the regression on α-klotho, vitamin D3 (both positively), and calcyphosin (inversely) and that the effects of the latter are mediated by iron overload and the number of blood transfusions. Conclusion. In TDT, iron overload and its consequences may induce lowered levels of α-klotho which in turn may lead to lower calcium thereby explaining at least in part the effects of TDT on bone metabolism including spontaneous pathological fractures, osteoporosis, osteopenia, and skeletal deformities.

Background: Aberrations in endothelial cells, immune and oxidative pathways are associated with atherosclerosis (ATS) and unstable angina (UA). The role of trace elements, minerals, and the endogenous opioid system (EOS) in UA are less well established. Methods: We measured lipid, insulin resistance (IR), and immune, trace element (copper and zinc), mineral (magnesium, calcium), EOS (β-endorphin and mu-opioid receptor (MOR)) and antioxidant (vitamin D3) biomarkers in patients with ATS (n=60) and UA (n=60) and healthy controls (n=58). Results: ATS patients showed increased atherogenic and IR indices, IL-6, IL-10, β-endorphin, copper and magnesium, and lower zinc than healthy controls. Logistic regression showed that UA was significantly discriminated from ATS without UA with an accuracy of 85.5% using calcium, IL-10, β-endorphin, MOR, triglycerides, IR (all positively), and copper and vitamin D3 (inversely). Neural networks showed that UA was discriminated from ATS without UA with an area under the ROC curve of 0.942 using MOR, β-endorphin, calcium, insulin resistance, vitamin D3 and copper as input variables. We found that 50.0% of the variance in IR was explained by the regression on copper, IL-10, IL-6 (all positively), and zinc (inversely), while 32.9% of the variance in the atherogenic index of plasma was explained by copper, IL-10 (both positively), and magnesium (inversely). Conclusion: UA is not only mediated by insulin resistance, atherogenicity, and immune disorders, but also by aberrations in the endogenous opioid system and trace elements as well as lowered antioxidant levels. Copper appears to play a key role in IR and atherogenicity.

Manganosalen complexes are coordination compounds that possess a chelating salen-type ligand, a class of bis-Schiff bases obtained by condensation of salicylaldehyde and a diamine. They may act as catalytic antioxidants mimicking both the structure and the reactivity of the native antioxidant enzymes active site. Thus, manganosalen complexes have shown to exhibit superoxide dismutase, catalase, and glutathione peroxidase activities, and they could potentially facilitate the scavenging of excess ROS, thereby restoring the redox balance in the damaged cells and organs. Initial catalytic studies compared the potency of these compounds as antioxidants in terms of rate constants of the chemical reactivity against ROS, giving catalytic values approaching and even exceeding that of the native antioxidative enzymes. Although most of these catalytic studies lack of biological relevance, subsequent in vitro studies have confirmed the efficiency of many manganosalen complexes in oxidative stress models. These synthetic catalytic scavengers, cheaper than natural antioxidants, have accordingly attracted intensive attention for the therapy of ROS-mediated injuries. The aim of this review is to focus on in vivo studies performed on manganosalen complexes and their activity on the treatment of several pathological disorders associated with oxidative damage. This disorders, ranging from the prevention of fetal malformations to the extension of lifespan, include neurodegenerative, inflammatory and cardiovascular diseases, tissue injury, and other damages related to liver, kidney or lungs.

Fenugreek seeds are widely used in Asia and other places of the world for their nutritive and medicinal properties. In Asia, Fenugreek seeds are also widely recommended for the geriatric populations. Here, we evaluated for the first time the effect of fenugreek seed feed supplementation on the liver antioxidant defense systems in aging mice. The study was conducted on 12 months aged mice which were given fenugreek seed dietary supplement. We have evaluated the activities of various antioxidant defense enzymes like superoxide dismutase (SOD), glutathione reductase (GR), and glutathione peroxidase (GPx), and estimated the phenolics and free radical scavenging properties in mice liver upon fenugreek supplementation. The estimation of SOD, GPx and GR activities in aged mice liver revealed a significant (P<0.01) difference among all the liver enzymes. Overall, this study reveals that fenugreek seed dietary supplementation has a positive effect in on the activities of the hepatic antioxidant defense enzymes in the aged mice.

Introduction: Lowered thiol or sulfhydryl (-SH) groups and glutathione (GSH) metabolism may be associated with prostate cancer (PCa) and benign prostatic hyperplasia (BPH). The main objectives of this study were to systematically review and meta-analyze the evidence on the associations among -SH groups, GSH, GSH peroxidase (GPx), GSH reductase (GR) and GSH transferase (GST) and PCa/BPH. Methods: Four electronic databases were searched for studies that reported -SH and GSH variables in PCa/BPH and healthy controls (HC) and the data were meta-analyzed by calculating Hedges’s g with 95% confidence intervals. Results: Twenty studies were included in this meta-analysis including 800 PCa and 791 BPH patients and 592 HC. Total -SH (g=-1.750, -2.341/-1.159), GPx (g=-0.789, -1.234/-0.344), GSH (g=-2.219, -4.132/-0.305), and the combination of -SH, GPx, and GSH (g=-1.271, -1.271/-0.800) were significantly lower in PCa patients than in HC. -SH (g=-1.752, -3.123/-0.381) and the combination of -SH, GPx, and GSH (g=-0.813, -1.298/-0.327) were significantly lower in BPH patients than in HC. GPx was significantly lower in PCa than in BPH patients (g=-0.455, -0.896/-0.014). Heterogeneity levels were very high, but Egger’s test showed that none of the biomarkers showed significant publication bias. Conclusion: Thiol/GPx antioxidant defenses are significantly attenuated in patients with PCa while patients with BPH occupy an intermediate risk group position between PCa patients and HC. Those results suggest that reduced thiol-related antioxidant mechanisms play a crucial role in prostatic disorders, especially in PCa. Future research should examine whether thiols/GPx antioxidants are associated with the onset of PCa/BHP.

Measurements of copper and zinc in transfusion-dependent thalassemia (TDT) show contradictory results.Aim of the study: To examine serum levels of these minerals in TDT in relation to iron overload indices and erythron variables. Methods: This study recruited 60 children with TDT and 30 healthy children aged 3-12 years old.Results: Zinc was significantly higher in TDT children than in control children, whilst copper and the copper to zinc ratio were significantly lowered in TDT. Serum zinc was significantly associated with the number of blood transfusions and iron overload variables (including serum iron and TS%) and negatively with erythron variables (including hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin). Serum copper was significantly and negatively associated with the same iron overload and erythron variables. The copper to zinc ratio was significantly correlated with iron, TS%, ferritin, hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin. Albumin levels were significantly higher in TDT children than in control children. Conclusion: Our results suggest that the increase in zinc in children with TDT may be explained by iron loading anemia and hemolysis and the consequent shedding of high amounts of intracellular zinc into the plasma. Increased albumin levels and treatment with Desferral may further contribute towards higher zinc levels in TDT. We suggest that the elevations in zinc in TDT are a compensatory mechanism protecting against infection, inflammation, and oxidative stress. Previous proposals for prophylactic use of zinc supplements in TDT may not be warranted.

Background: Hypertension, atherogenicity and insulin resistance are major risk factors of cardiovascular disorder (CVD), which shows a strong comorbidity with major depression (MDD) and bipolar disorder (BD). Activated oxidative and nitrosative stress (O&NS), inflammatory pathways, and increased atherogenicity are shared pathways underpinning CVD and mood disorders. Methods: The current study examined the effects of lipid hydroperoxides (LOOH), superoxide dismutase (SOD), nitric oxide metabolites (NOx), advanced oxidation protein products (AOPP), and malondialdehyde (MDA) on systolic (SBP) and diastolic (DBP) blood pressure in 96 mood disordered patients and 60 healthy controls. Results: A large part of the variance in SBP (31.6%) was explained by the regression on a z unit-weighted composite score (based on LOOH, AOPP, SOD, NOx) reflecting nitro-oxidative stress toxicity (NOSTOX), coupled with highly sensitive C-reactive protein, body weight and use of antihypertensives. Increased DBP was best predicted (23.8%) by body mass index and NOSTOX. The most important O&NS biomarkers predicting an increased SBP were in descending order of significance: LOOH, AOPP and SOD. Higher levels of the atherogenic index of plasma, HOMA2 insulin resistance index and basal thyroid-stimulating hormone also contributed to increased SBP independently from NOSTOX. Although there were no significant changes in SBP/DBP in mood disorders, the associations between NOSTOX and blood pressure were significant in patients with mood disorders but not in healthy controls. Conclusions: Activated O&NS pathways including increased lipid peroxidation and protein oxidation, which indicates hypochlorous stress, are the most important predictors of an increased BP, especially in patients with mood disorders.

Background: There is now evidence that schizophrenia and deficit schizophrenia are neuro-immune conditions and that oxidative stress toxicity (OSTOX) may play a pathophysiological role. Aims of the study: To compare OSTOX biomarkers and antioxidant (ANTIOX) defenses in deficit versus non-deficit schizophrenia. Methods: We examined lipid hydroperoxides (LOOH), malondialdehyde (MDA), advanced oxidation protein products (AOPP), sulfhydryl (-SH) groups, paraoxonase 1 (PON1) activity and PON1 Q192R genotypes, total radical-trapping antioxidant parameter (TRAP) as well as immune biomarkers in patients with deficit (n=40) and non-deficit (n=40) schizophrenia and healthy controls (n=40). Results: Deficit schizophrenia is characterized by significantly increased levels of AOPP and lowered -SH, and PON1 activity, while no changes in the OSTOX/ANTIOX biomarkers were found in non-deficit schizophrenia. An increased OSTOX/ANTIOX ratio was significantly associated with deficit versus non-deficit schizophrenia (Odds ratio=3.15, p<0.001). Partial least squares analysis showed that 47.6% of the variance in a latent vector extracted from psychosis, excitation, hostility, mannerism, negative symptoms, psychomotor retardation, formal thought disorders, and neurocognitive test scores was explained by LOOH+AOPP, PON1 genotype + activity, CCL11, tumor necrosis factor (TNF)-α, IgA responses to neurotoxic tryptophan catabolites (TRYCATs), whereas -SH groups and IgM responses to MDA showed indirect effects mediated by OSTOX and neuro-immune biomarkers. Discussion: Our findings indicate that with increasing overall severity of schizophrenia, neuro-immune and neuro-oxidative (especially protein oxidation indicating chlorinative stress) toxicities become more prominent and together with lowered antioxidant defenses and impairments in innate immunity-associated resilience against neurotoxic processes shape a distinct nosological entity, namely deficit schizophrenia.

Introduction: Increased oxidative stress, including elevated homocysteine (Hcy) plasma levels, and lowered levels of antioxidants participate in the pathophysiology and progression of chronic kidney disease (CKD). Paraoxonase (PON)1 activity and folic acid are antioxidants which play a role in Hcy metabolism. However, there are no data whether, in CKD, treatment with folic acid improves glomerular filtration rate (GFR) through effects on PON1 activity and Hcy concentrations. Methods: In the current study, we determined PON1 genotypes and activity, Hcy and estimated GFR (eGFR) both before and after treatment with folic acid (5 mg/d) versus no treatment during three consecutive months in 113 outpatients with CKD classified into stages 4, 3b and 3a. Results: PON1 CMPAase and AREase activities were significantly lower in patients allocated to CKD stage 4 as compared with stages 3b and 3a. Treatment with folic acid significantly improved eGFR and increased levels of CMPAase and AREase in patients allocated to classes 4 and 3b, but not 3a. The improvement of eGFR was associated with increased CMPAase and AREase activities, while the latter were associated with increased levels of folic acid. Treatment with folic acid significantly reduced plasma Hcy levels and the Hcy/PON1 activity ratio. The effects of folic acid increasing PON1 activities were not mediated by changes in Hcy. Discussion: Treatment of CKD patients in early/intermediate stages of CKD patients improves oxidative stress by rebalancing the prooxidant (Hcy) / antioxidant (PON1 activities) ratio. Treatment with folic acid significantly improves eGFR and these effects are mediated via increased PON1 activities. Treatment with folic acid in phase G3b and G4 may reduce renal disease progression by enhancing antioxidant defenses.

Objective: To examine the associations between menstruation features and symptoms and hormone-immune-metabolic biomarkers. Methods: Forty-one women completed questionnaires assessing characteristic menstruation symptoms, duration of menstrual cycle and number of pads used/day and completed the Daily Record of Severity of Problems (DRSP) during the consecutive days of their menstrual cycle. Menses-related symptoms (MsRS) were computed from the sum of 10 pre- and post-menses symptoms and the menstruation blood and duration index (MBDI) was computed based on the daily number of pads and duration of menses. We assayed serum levels of various biomarkers at days 7, 14, 21, and 28 of the subjects’ menstrual cycle. Results: MBDI was significantly associated with a) MsRS including low abdominal cramps, and gastro-intestinal (GI) and pain symptoms (positively); b) plasma levels of haptoglobin (Hp), CCL5, insulin growth factor (IGF)-1, and plasminogen activator inhibitor (PAI)1 (all positively); and c) estradiol and paraoxonase (PON)1 arylesterase activity (both inversely). MsRS were significantly predicted by CCL5 and IGF-1 (both positively) and progesterone (inversely). Low-abdominal cramps, and gastro-intestinal and pain symptoms were associated with lower progesterone levels. The MBDI+MsRS score was significantly predicted by the cumulative effects of (in descending order of importance): Hp, IGF-1, PON1 arylesterase, estradiol and PAI. Conclusion: Menstruation-related features including estimated blood loss, duration of menses, cramps, pain and GI symptoms are associated with hormone-immune-metabolic biomarkers, which mechanistically may explain those features. Women with an increased MBDI+MsRS index ≥ 0.666 percentile may be considered to have menstruation-related distress, including dysmenorrhea symptoms.

Background: Temporal lobe epilepsy (TLE) is the most common focal epilepsy subtype in adults and is frequently accompanied by depression, anxiety and psychosis. Aberrations in total paraoxonase (PON)1 status may occur in TLE and those psychiatric conditions. Methods: We examined paraoxonase (PON)1 status, namely Q192R PON1 genotypes and PON1 enzymatic activities, in 40 normal controls and 104 TLE patients, 27 without comorbidities, and 77 with comorbidities including mood disorders (n=25), anxiety disorders (n=27) and psychosis (n=25). Outcomes: CMPAase and arylesterase activities were significantly lower in TLE and mesial temporal sclerosis (MTS) with and without psychiatric comorbidities than in normal controls. The areas under the ROC curve of CMPAase were 0.893 (0.037) for TLE and 0.895 (±0.037) for MTS. Partial Least Squares (PLS) path analysis showed that there were specific indirect effects of PON1 genotype on TLE severity (p<0.0001) and psychopathology (p<0.0001), which were both mediated by lowered CMPAase activity, while arylesterase activity was not significant. The severity of TLE was significantly associated with psychopathology scores. Furthermore, PON1 CMPAase activity was inversely associated with Mini Mental State Examination scores. Interpretation: The severity of TLE and comorbidities are to a large extent explained by lowered PON1 enzyme activities and by effects of the Q192R genotype which are mediated by lowered CMPAase activity. Total PON1 status plays a key role in the pathophysiology of TLE, MTS and psychiatric comorbidities by increasing the risk of oxidative toxicity. PON1 enzyme activities are new drug targets in TLE to treat seizure frequency and psychiatric comorbidities.

Present-day lifestyle associated with high calorie-fat intake and accumulation, as well as energy imbalance, has led to the development of obesity and its comorbidities, which have emerged as some of the major health issues globally. To combat the disease, many studies have reported the anti-obesity effects of natural compounds in foods, with some advantages over chemical treatments. Carotenoids, particularly xanthophyll derived from seaweeds, have attracted the attention of researchers due to their notable biological activities, which are associated mainly with their antioxidant properties. Their involvement in oxidative stress modulation, regulation of major transcription factors and enzymes as well as their antagonistic effects on various obesity parameters have been examined in both in-vitro and in-vivo studies. The present review is a collation of published research over the last decade on the anti-oxidant properties of seaweed xanthophyll carotenoids, with a focus on fucoxanthin and astaxanthin and their mechanisms of action in obesity prevention and treatment.

Objective: To examine whether 1) immune and nitro-oxidative stress (IO&NS) biomarkers are associated with premenstrual syndrome (PMS); and 2) changes in IO&NS biomarkers during the menstrual cycle (MC) are associated with PMS symptoms and plasma estradiol and progesterone. Methods: Forty-one women completed the Daily Record of Severity of Problems (DRSP) rating scale during 28 consecutive days and MC Associated Syndrome (MCAS) was diagnosed when the summed DRSP score during the MC is > 0.666 percentile. We assayed plasma levels of complement C3 and C4, highly sensitive C-reactive protein (hsCRP), haptoglobin (Hp), advanced oxidation protein products (AOPP), lipid hydroperoxides (LOOH), nitric oxide metabolites (NOx), total radical-trapping antioxidant parameter (TRAP), sulfhydryl (-SH) groups and the activity of paraoxonase (PON)1 at days 7 (D7), 14 (D14), 21 (D21) and 28 (D28) of the MC. Results: All biomarkers, except hsCRP, showed significant alterations during the MC. Arylesterase (AREase) was lowered at D28, while LOOH increased at D14 and C4 at D21 in women with MCAS. The total DRSP score was predicted by the combined effects of C4 (positively) and AREase and malondialdehyde (MDA) (both inversely associated). Progesterone lowered levels of LOOH, AOPP and C3 and estradiol lowered levels of Hp while both sex hormones increased 4-(chloromethyl)phenyl acetate (CMPA)ase and AREase activities and levels of -SH groups. Conclusion: PMS/MCAS is not accompanied by a peripheral inflammatory response. Lowered MDA and antioxidant defenses and increased C4 may play a role in MC-associated symptoms while sex hormones may have a protective effect against oxidative stress toxicity.

Premenstrual syndrome (PMS) frequently occurs in women of childbearing age. There are different case definitions of PMS, one proposed by the American College of Obstetricians and Gynecologists (ACOG) and another based on the Daily Record of Severity of Problems (DRSP) scores. Here we review our recent papers indicating that the discovery of biomarkers of menstrual cycle-related symptoms is strongly dependent on the case definitions used and that the gold standard methods used to asses PMS, including the ACOG case definition, induce a high degree of false-negative findings. We propose a new case definition of the menstrual cycle-associated syndrome (MCAS), which is characterized by increased DRSP scores during the menstrual cycle and additionally by an exaggerated increase in symptoms the week prior to the menses. This case definition performed well and was externally validated by diverse biomarkers including plasma levels of progesterone and estradiol, chemokines (e.g. CCL2, CCL5 and CCL11), epidermal growth factor, hydroperoxides, paraoxonase 1 activity and complement C4. In conclusion, when evaluating menstrual cycle-related symptoms and their associations with biomarkers, we propose to assess daily measurements of the DRSP and based on those scores to a) use the diagnosis of MCAS as an indicant of menstrual cycle-related symptoms; and b) examine the associations of the time series in the DRSP and its subdomains (e.g. depression, physio-somatic, anxiety) and those in biomarkers including distributed lag models.

Accumulating evidence suggests that TNF-α-mediated immune-neurotoxicity contributes to cognitive impairments and the overall severity of schizophrenia (OSOS). There are no data whether peripheral IL-6 and IL-4 may affect the phenome of schizophrenia above and beyond the effects of TNF-α and whether those cytokines are regulated by lowered natural IgM to malondialdehyde (MDA) and paraoxonase 1 enzyme activity. We assessed the aforementioned biomarkers in schizophrenia patients with (n=40) and without (n=40) deficit schizophrenia and 40 healthy controls. Deficit schizophrenia was best predicted by a combination of increased IL-6 and PON1 status (QQ genotype and lowered CMPAase activity) and lowered IgM to MDA. Partial Least Squares bootstrapping shows that 41.0% of the variance in negative symptoms, psychosis, hostility, excitation, mannerism, psychomotor retardation, and formal thought disorders was explained by increased TNF-α and PON1 status (QQ genotype and lowered CMPAase activity), lowered IL-4 and IgM to MDA as well as male sex and lowered education. We found that 47.9% of the variance in verbal fluency, word list memory, true recall, Mini-Mental State Examination, and executive functions was predicted by increased TNF-α and lowered IL-4, IgM to MDA and education. In addition, both TNF-α and IL-4 levels were significantly associated with lowered IgM to MDA, while TNF-α was correlated with PON1 status. These data provide evidence that the symptomatic (both the deficit subtype and OSOS) and cognitive impairments in schizophrenia are to a large extent mediated by the effects of immune-mediated neurotoxicity as well as lowered regulation by the innate immune system.

The rates of production of secondary metabolites obtained by employing conventional plant breeding may be low for practical purposes. Thus, innovative approaches for increasing their rates of production are being developed. Here, we propose the use of elicited suspension plant cultured cells (PSCC) with cyclodextrins (CDs) as an alternative method for the production of bioactive compounds from Bryophyllum species. For the purpose, we analyzed the effects of methyl--cyclodextrin and 2-hydroxypropyl--cyclodextrin on cell culture growth and on the intra- and extracellular production of phenols and flavonoids. Results clearly show that CDs enhance the biosynthesis of polyphenols by PSCC favoring their accumulation outside the cells. CDs shift the homeostatic equilibrium by complexing extracellular phenolics, causing stress in cells that respond by increasing the production of intracellular phenolics. We also analyzed the radical scavenging activity of the culture medium extracts against DPPH• radical, which increased with respect to the control samples (no added CDs). Our results suggest that both the increase in the production of polyphenols and their radical scavenging activity are a consequence of their inclusion in the CD cavities. Overall, based on our findings, CDs can be employed as hosts for increasing the production of polyphenols from Bryophyllum species.

The current study aims to study the optimal fermentation conditions for producing microbial bioactive compounds. The microwave parameters consist on 2450 MHz, and 500-watt for 20, 30, and 40 seconds. The solubility of solvents was tested for the extraction of antioxidant compounds from fermented rice (Koji) by A. flavus, Ethyl acetate was the best solvent used for extraction purposes. Antioxidant properties were differentiated by blocking the oxidation of the linoleic acid with an inhibition rate of 73.13% at a concentration of 200 mg/mL, in addition to increasing its effectiveness for free radical extraction and reduction strength by increasing concentrations gradually. The bond ability to irons was lower compared to the EDTA-2Na, in addition to the obtained total content corresponding to phenolic compounds in the ethyl acetate extract of fermented rice (Koji) by A. flavus was 232.11 mg, on the basis of galic acid/mg. The stability of the antioxidant compounds of the ethyl acetate extract of fermented rice (Koji) by A. flavus was also studied; showing stability under neutral conditions, as well as at high temperatures (185 °C during two hours). However, no stability was obtained under acidic and alkaline conditions.

Background: Primary deficit schizophrenia (DS) is characterized by enduring negative symptoms and represents a qualitatively different disease entity with respect to non-deficit schizophrenia (NDS). No studies investigated the association between the enzyme paraoxonase 1 (PON1) and DS and its phenomenology. Methods: In this case-control study, Thai women and men, aged 18-65 years, were divided in DS (n=40) and NDS (n=40) and were compared to controls (n=40). PON1 activities against 4-(chloromethyl)phenyl acetate (CMPA) and phenylacetate were determined. Moreover, subjects were genotyped for their PON1 Q192R polymorphism and IgA levels responses directed to Gram-negative bacteria were measured. Results: DS is significantly associated with the QQ genotype and the Q allele as compared with NDS and controls. PON1 activities are significantly and inversely associated with negative symptoms, formal thought disorders, psychomotor retardation, excitation and DS. The presence of the Q allele is associated with increased IgA responses to Pseudomonas aeruginosa, Morganella morganii, and Pseudomonas putida as compared with RR carriers. Conclusions: The PON1 Q allele and lower PON1 activities especially against CMPA are associated with DS, indicating lowered quorum quenching abilities as well as lowered defenses against lipoperoxidation and immune activation. It is suggested that lowered PON1 activity in DS constitutes an impairment in the innate immune system which together with lowered natural IgM may cause lower immune regulation thereby predisposing towards greater neurotoxic effects of immune-inflammatory, oxidative and nitrosative pathways and Gram-negative microbiota.

Beta-thalassemia major (β-TM) patients are treated with repeated blood transfusions, which may cause iron overload (IO), which in turn may induce immune aberrations. Patients with β-TM have an increased risk of major depressive disorder (MDD). The aims of the present study are to examine whether repeated blood transfusions, IO and immune-inflammatory responses are associated with MDD in children (6-12 years) with β-TM. The Children’s Depression Inventory (CDI), iron status (serum iron, ferritin, transferrin, TS%) and serum levels of CCL11, IL-1β, IL-10, and TNF-α were measured in β-TM with (n=54) and without (n=57) MDD and in healthy children (n=55). The results show that MDD in β-TM is associated with a greater number of blood transfusions, increased IO and IL-1β levels. Partial Least Squares path analysis shows that 68.8% of the variance in the CDI score is explained by the number of blood transfusions, IO, and increased levels of IL-1β and TNF-α. The latter two cytokines partly mediate the effects of IO on the CDI score, while the effects of blood transfusions on the CDI score are partly mediated by IO and the path from IO to immune activation. IO is also associated with increased IL-10 and lower CCL11 levels but these alterations are not significantly associated with MDD. In conclusion, blood transfusions may be causally related to MDD in β-TM children and their effects are in part mediated by increased IO and the consequent immune-inflammatory response. The results suggest that not only IO and its consequences including inflammation and ferroptosis, but also other factors related to the number of transfusions may cause MDD including psychosocial stressors. Current treatment modalities with folic acid and vitamin C are insufficient to attenuate IO and immune-inflammatory responses and to prevent MDD is children with β-TM undergoing blood transfusions.

In schizophrenia, a single latent trait underlies psychosis, hostility, excitation, mannerism, negative (PHEMN) symptoms, formal thought disorders (FTD) and psychomotor retardation (PMR). Schizophrenia is accompanied by a breakdown of gut and blood-brain-barrier (BBB) pathways, increased tryptophan catabolite (TRYCAT) levels, bacterial translocation, and lowered natural IgM and paraoxonase (PON)1 activity. The aim of this study was to examine the factor structure of schizophrenia symptom domains and the biomarker correlates of these factors. We recruited 80 patients with schizophrenia and 40 healthy subjects and assessed the IgA/IgM responses to paracellular/transcellular (PARA/TRANS) ratios, IgA responses to TRYCATs, natural IgM to malondialdehyde and Gram-negative bacteria, and PON1 enzymatic activity.Direct Hierarchical Exploratory Factor Analysis showed a bifactorial oblique model with a) a general factor which loaded highly on all symptom domains, named overall severity of schizophrenia (“OSOS”); and b) a single-group factor (SGF) loading on negative symptoms and PMR. We found that 40% of the variance in the OSOS score was explained by IgA/IgM to PARA/TRANS ratio, male sex and education while 36.9% of the variance in SGF score was explained by IgA to PARA/TRANS, IgM to Gram-negative bacteria, female sex (positively associated) and IgM to MDA, and PON1 activity (negatively associated). Schizophrenia phenomenology comprises two biologically-validated dimensions, namely a general OSOS dimension and a single-group negative symptom dimension, which are associated with a breakdown of gut/BBB barriers, increased bacterial translocation and lowered protection against oxidation, inflammation and bacterial infections through lowered PON1 and natural IgM.

Cistus incanus L. (CI) has been proposed as an innovative functional supplement of food products, and hence the present study aimed to evaluate the effect of the addition of dried CI on the properties of bread. Bread was prepared from white wheat flour supplemented with the addition of 1%, 2%, 3%, 4%, and 5% of ground CI. After the completion of baking process, various characteristics of the obtained bread product, such as yield, volume, porosity, acidity, color, and texture, were evaluated. In addition, total phenolic content (TPC), ABTS radical scavenging activity, CHEL chelating power, and ability to quench OH∙ radicals were measured. The results showed that the addition of CI to bread caused a reduction in the volume of bread, but texture of the crumbs was acceptable. Acidity and moisture content of bread were found to be increased following CI enrichment. Significant changes in the ash content and the color of bread crumbs were also observed. Bread incorporated with CI was characterized by significantly higher TPC and much higher antioxidant activity, as measured by ABTS, CHEL, and OH∙ radicals, compared to control bread. Supplementation of bread with 3% CI produced a product with desirable characteristics which was also favored by consumers.

Plants and its corresponding botanical preparations have been used for centuries due to their remarkable potentialities in both treatment and prevention of numerous affections. Hundreds of biologically active constituents are present in each whole plant matrice, working in synergism and conferring both its own protection against invaders and even providing promissory bioactive effects for human beings. The worldwide population has devoted increasing attention and preference by medicinal plants use for health promotion and disease prevention, and more recently for oxidative-stress related disorders protection. Indeed, oxidative stress-related disorders, like cardiovascular and (neuro) degenerative disorders, and even cancer have raised exponentially. Although oxidative stress is in itself intrinsic to our own metabolism, allarming sources of free radicals are daily affecting us. In fact, plant-derived bioactives present a broad spectrum of biological effects, and its antioxidant, anti-inflammatory and more recently anti-aging effects have been considered a hot topic among the medical and scientific community. Nonetheless, and although its numerous biological effects, it should not also be forgotten that some bioactive molecules are prone to oxidation and can even exert pro-oxidant effects. In this sense, the objective of the present review is to provide a detailed overview on plant-derived bioactives in oxidative stress-related disorders. Specifically, the role of phytochemicals as antioxidants and pro-oxidant agents is carefully addressed, as is its therapeutic relevance in disease prevention. Finally, an eye-opening look in overall evidence in humans is also ensured.

Scarcity of water is one of the most serious concerns in plant biology with diverse implications at all the levels of molecular, biochemical, and physiological phenomena of plant growth, development, and consequently the productivity. Most of the strategies to induce or enhance drought tolerance in plants are unreasonably expensive and/or time-consuming. Some studies conducted in the recent past have shown that plant growth regulators (PGRs) may induce/improve physiological tolerance in plants to cope with adverse environmental conditions including drought. The present study was aimed at investigating the effects of foliar spray of GABA (0, 1, 2, and 4 mM) applied 20 days following the germination of seeds, on vegetative growth, morphological characteristics, integrity of cell-membrane, and the levels of photosynthetic pigments and enzymatic antioxidants in carrot cvs. Supertaj and Bharat, grown under 100% and 50% field capacity of soil moisture. The treated and untreated (control) carrot plants were harvested and analyzed 2 weeks following the GABA application. The results revealed that foliar application of GABA improved the vegetative growth and significantly increased the levels of free amino acids, plastid pigments, enzymatic antioxidants, and the relative water content in the root crop grown under 50% field capacity of soil moisture, compared to control. Additionally, the GABA application decreased the electrolyte leakage of ions and melondialdehyde (MDA) content in carrot leaves. The carrots harvested from GABA-treated or untreated (control) plants were not significantly different for their protein contents. In conclusion, the incorporation of GABA in the production management of carrots may help plants to mitigate the adverse effects of water deficit stress.

Chaenomeles plants are adapted to diverse ecological zones particularly the temperate areas of Korea, Japan and China. In China, Chaenomeles speciosa mainly planted in Chongqing, Anhui and Hubei provinces. Most of the studies till date have been focused on the anti-inflammatory activities of C. speciosa fractions. The present study aimed to review the maximum literature reported for the presence of various phytochemicals in C. speciosa. In addition, the pharmacological properties of these chemical compounds of this plant shall also be discussed. The extracts of the various parts of the plant are rich in diversity of antioxidants, organic acids, phenolics, terpenoides and many different phytochemicals that bear strong anticancer, antioxidant, anti-viral, antibacterial properties, anti-inflammation, anti-hyperlipidemic, anti-hyperglycemic and anti-parkinson properties. C. speciosa fruits have broad scope in industry as well as in medicines. Not only the leaves and fruits of C. speciosa plant, but various other parts including roots, seeds, bark twigs, and flowers all have long history of clinical trials in curing many human ailments. However, the maximum accessible data concerning the chemical composition and their broad pharmacological properties of C. speciosa plant parts is pretty restricted that make it more appealing for indepth investigations.

Selenium (Se) is an essential element of the human diet. Therefore, it is necessary to implement Se in agricultural fertilization, although it is not considered as an essential element for plants, Se provides benefits at the level of redox metabolism, increasing the resistance of plants to various stress factors. The increase of the availability of selenium with the use of biopolymer complexes was sought in Great Lakes lettuce grown in substrate pots treated with SeO₂ (5 mg L Se), Cs-PAA + Se (5 mg L Se), and Cs-PAA. The redox metabolism was modified by increasing the enzymatic activity of glutathione peroxidase. The use of Cs-PAA + Se biopolymer complexes increase selenium up to 24 mg/Kg dry weight (DW) in plant tissues.

Variations in liver metabolism as a result of hepatitis C virus have been established by numerous clinical trials. The use of antioxidants supplements has been reported to minimize the implication of this disease. In this regard, we examined the suitability of Solanum fruit juice, a natural source of vitamin C and citrus flavoniod as a precursor for the treatment of patients with chronic hepatitis C. Forty adult patients who were diagnosed with chronic hepatitis C and were under antiviral therapy were divided into two equal groups. Group 1 patients received their antiviral therapy with normal food and water and served as the control group while patients in group 2 were supplemented with Solanum fruit juice for eight consecutive weeks. Measurements for Anthropometric data, C reactive protein (CRP), atherogenic indices, biochemical parameters and activities of liver marker enzymes were recorded before and after eight weeks. No alterations were found in waist circumference, body mass and body fat following regular use of Solanum fruit juice. The serum levels of oxidative stress markers, LDL-cholesterol, total cholesterol, CRP and atherogenic indices decreased in the Solanum fruit juice group when compared to the control group. Moreover, the activities of the liver marker enzyme AST decreased in those who had high levels before the intervention. These results underscore the benefits of Solanum fruit juice in the diet of patients with HCV as a result of decreased cholesterol in blood serum, decreased inflammation, and increase in antioxidant capacity as well as maintaining body mass index. This clinical trial is registered at Pan African Clinical Trial Registry (www.pactr.org) with unique identification number PACTR201802003092138.

Non-Alcoholic Fatty Liver Disease (NAFLD) is a term that covers a range of hepatic disorders involving fat deposits in the liver. NAFLD begins with simple steatosis and progresses into non-alcoholic steatohepatitis (NASH) characterised by inflammation, fibrosis, apoptosis, oxidative stress, lipid peroxidation, mitochondrial dysfunction and release of adipokines and pro-inflammatory cytokines. Oxidative stress and antioxidants are known to play a vital role in the pathogenesis and severity of NAFLD/NASH. A number of oxidative stress and antioxidant markers are employed in the assessment of the pathological state and progression of the disease. In this article, we review several biomarkers of oxidative stress and antioxidants that have been measured at clinical and experimental levels. The levels/ activity in various models reviewed are also included. Also included is a comprehensive description of oxidative stress, sources and contribution to the pathogenesis of NAFLD/NASH

Chronic unpredictable environmental stress (CUES) may induce predisposition to diabetes mellitus. This study investigates the role of CUES on impaired homeostasis. Stressed group mice (n = 20) were exposed to CUES for 16 weeks. Weekly body weight, feed consumption, feed efficiency ratio, fasting blood glucose were monitored. Plasma HbA1c, plasma cortisol, plasma epinephrine and plasma insulin, serum lipids, antioxidants and carbohydrate metabolizing enzymes activity were assessed along with DNA damage and histopathological examination of liver, kidney, pancreas, spleen and skeletal muscles. Fasting blood glucose levels & HbA1c in the stressed were significantly higher compared to control (p < 0.001). Serum lipids were found insignificantly higher in stressed mice compared to control. Body weights of the stressed mice and feed efficiency ratio were found significant (p < 0.001). Plasma corticosterone, plasma epinephrine, HOMA-IR was found to be significantly higher in the stressed group (p < 0.001). Plasma insulin level was found to be significantly lower in the stressed group (p < 0.001). Significant changes were observed in antioxidants level, carbohydrate metabolizing enzymes activity, peripheral tissues and DNA integrity. CUES initiates pathogenesis of diabetes.

Two biotinylated derivatives of the main hop chalcone xanthohumol (1) were prepared by a one-step synthesis via esterification using biotin and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC HCl) and 4-dimethylaminopyridine (DMAP) as coupling reagents. The products were characterized spectroscopically and their antiproliferative activity toward MCF-7, MCF-10A, HepG2, MDA-MB-231, 4T1 and Balb/3T3 cell lines was investigated using the SRB assay. For all three tested compounds the best activity was noted in the case of human (MCF-7) and mice (4T1) breast cancer cell lines (IC₅₀ values < 9 μM). Both biotinylated derivatives showed higher anticancer activity than xanthohumol (1) towards all types of tested breast cancer cells. Double biotinylated xanthohumol (3) proved to be the most active in inhibiting cell growth, with IC₅₀ values equal to 5.35 ± 1.5 μM for 4T1 and 8.03 ± 0.53 µM for MCF-7 cell lines. Compound 3 was also more active than 1 and 2 against liver cancer cells HepG2 (IC₅₀ = 17.37 ± 5.1 μM), while the IC₅₀ values for 1 and 2 were equal to 21.5 ± 2.7 and 22.1 ± 3.9 µM, respectively. 4‑O‑biotinylxanthohumol (2) was the second most active growth inhibitor, particularly with respect to MCF-7 (IC₅₀ = 6.19 ± 1.7 μM) and 4T1 (IC₅₀ = 6.64 ± 0.4 μM) cell lines. The antioxidant activity was evaluated using the 1.1-diphenyl-2-picrylhydrazyl radical (DPPH) method. All tested compounds (1-3) have antioxidant activity between 2.73 and 3.38 mM. It was reported for the first time that new prenylated chalcones containing the biotin moiety effectively inhibited proliferation of cancer cells in vitro.

The purpose of the present study is survey of extraction conditions and exploring antioxidant potential of the non-traditional for the Bulgarian ethno-medicine wild herb Cistus incanus widespread in Strandja Mountain. The influence of the extraction time (0–500 min) and solvent composition (0–50% ethanol in water) on the polyphenols, flavonoids yields and on antioxidant capacity of the extracts of leaves, stalks (wood parts) and buds mixture were studied. The antioxidant capacity (AOC) was evaluated by use of scavenging assays of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals. Total polyphenol and flavonoid contents were quantified using UV–vis spectrometry. Optimal yield of desired components has been obtained with 30% ethanol in water solvent at 390^th min extraction time. In addition, the influence of the seasonality (winter and summer Cistus incanus), and of the different areal parts - hard-coated seeds; buds, and mixture of leaves and stalks of the wild plant on the presence of polyphenols, flavonoids and AOC were investigated. Present work revealed the high values of the polyphenols, flavonoids, the high AOC not only in the summer leaves, but also found in the winter leaves, hard-coated seeds, buds and stalks. Based on the obtained results the Cistus incanus from Strandja mountain could be a new excellent source of natural antioxidants in food and pharmaceutical industries.

Oxidative and nitrosative stress are a common problem when manipulating gametes in vitro. In vitro development in mammalian embryos is highly affected by culture conditions, especially by reactive oxygen species (ROS) and reactive nitrogen species (RNS), because its absence or over production causes embryo arrest and changes in gene expression. Melatonin in gamete co-incubation during IVF has deleterious or positive effects depending on the concentration used in culture medium, demonstrating the delicate balance that must exist between antioxidant and pro-oxidant activity. Further research is needed to better understand the possible impact of melatonin on the different IVP steps in domestic animals, especially in seasonal breeds where this neuro-hormone system highly regulates its reproduction physiology.

Environmental contamination has exposed humans to various metal agents, including mercury. It has been determined that mercury is not only harmful to the health of vulnerable populations such as pregnant women and children, but is also toxic to ordinary adults in various ways. For many years, mercury was used in a wide variety of human activities. Nowadays, the exposure to this metal from both natural and artificial sources is significantly increasing. Recent studies suggest that chronic exposure, even to low concentration levels of mercury, can cause cardiovascular, reproductive and developmental toxicity, neurotoxicity, nephrotoxicity, immunotoxicity, and carcinogenicity. Possible biological effects of mercury, including the relationship between mercury toxicity and diseases of the cardiovascular system, such as hypertension, coronary heart disease and myocardial infarction, are being studied. As heart rhythm and function are under autonomic nervous system control, it has been hypothesized that the neurotoxic effects of mercury might also impact cardiac autonomic function. Mercury exposure could have a long-lasting effect on cardiac parasympathetic activity and some evidence show that mercury exposure might affect heart rate variability, particularly early exposures in children. The mechanism by which mercury produces toxic effects on the cardiovascular system is not fully elucidated, but this mechanism is believed to involve an increase in oxidative stress. The exposure to mercury increases the production of free radicals, potentially because of the role of mercury in the Fenton reaction and a reduction in the activity of antioxidant enzymes, such as glutathione peroxidase. In this review we report an overview on the toxicity of mercury and focus our attention on the toxic effects on the cardiovascular system.