Inside the genome: understanding genetic influences on oxidative stress.

Genetics is a key factor that governs the susceptibility to oxidative stress. In the body, oxidative burden is regulated by the balance between the prooxidant genes that orchestrate processes that produce oxidant species, while the antioxidant genes aid those involved in scavenging these species. Together, the two components aid in maintaining the oxidative balance in the body. Genetic variations can influence the expression and activity of the encoded proteins which can then affect their efficiency in regulating redox processes, thereby increasing the risk of oxidative stress. This review studies single nucleotide polymorphisms (SNPs) that bear relevance to oxidative stress by exploring the variations in the prooxidant genes, such as XDH, CYBA, CYP1A1, PTGS2, NOS, and MAO and antioxidant genes including SOD, CAT, GPX, GSS, GLUL, GSR, GSTM1, GSTM5, GSTP1, TXN and HMOX1. Early identification of individuals at the increased risk of oxidative stress is possible from the assessment of sequence of these genes. Integrating genetic insights into oxidative stress management measures can pave the way for personalized medicine that tailors' healthcare approaches to individual genetic profiles. Effective genetic assessment along with routine quantification of biological markers can improve and monitor treatment strategies, enhancing mitigation approaches that maintain cellular health and promote longevity.

Effects of dietary supplementation of cobiotic based on Agave fructans on growth performance, blood parameters, oxidative damage and immune status of broiler.

This study evaluated the effect of cobiotic (CO) composed of organic fructans powder of Agave tequilana and turmeric powder of Curcuma longa L. as an alternative of antibiotic growth promoters (AGPs) on growth performance, blood parameters, intestinal pH, oxidative stress, and cytokines serum levels of broiler chickens. A total of 135 one-day-old Ross 308 broilers distributed to five experimental groups, which included starter or finisher standard diets without AGPs (CON), CON + 0.25 COLI-ZIN g/kg feed (AGP), CON + 0.1 g Agave fructans/kg feed (AF), CON + 0.5 g turmeric powder/kg feed (TP) and CON + 0.1 g AF + 0.5 g TP /kg feed (CO), for 49 days. AF followed by TP, decreased feed intake, obtaining the best FCR. AGP increased the heterophil-lymphocyte ratio compared to other groups. CO significantly decreased the pH of the cecal content. AF increased IL-10 levels, while TP decreased it. AF decreased the IL-1ß levels. The present study showed that including a cobiotic based on AF and TP or components separately in a broilers diet improved growth performance, modified intestinal and cecum pH, and stimulated the immune system, which suggests CO as a safe alternative to AGP.

Resveratrol ameliorates mitochondrial biogenesis and reproductive outcomes in women with polycystic ovary syndrome undergoing assisted reproduction: a randomized, triple-blind, placebo-controlled clinical trial.

BACKGROUND: This study was designed to examine the effect of resveratrol on mitochondrial biogenesis, oxidative stress (OS), and assisted reproductive technology (ART) outcomes in individuals with polycystic ovary syndrome (PCOS). METHODS: Fifty-six patients with PCOS were randomly assigned to receive 800 mg/day of resveratrol or placebo for 60 days. The primary outcome was OS in follicular fluid (FF). The secondary outcome involved assessing gene and protein expression related to mitochondrial biogenesis, mitochondrial DNA (mtDNA) copy number, and adenosine triphosphate (ATP) content in granulosa cells (GCs). ART outcomes were evaluated at the end of the trial. RESULTS: Resveratrol significantly reduced the total oxidant status (TOS) and oxidative stress index (OSI) in FF (P = 0.0142 and P = 0.0039, respectively) while increasing the total antioxidant capacity (TAC) (P < 0.0009). Resveratrol consumption also led to significant increases in the expression of critical genes involved in mitochondrial biogenesis, including peroxisome proliferator-activated receptor gamma coactivator (PGC-1α) and mitochondrial transcription factor A (TFAM) (P = 0.0032 and P = 0.0003, respectively). However, the effect on nuclear respiratory factor 1 (Nrf-1) expression was not statistically significant (P = 0.0611). Resveratrol significantly affected sirtuin1 (SIRT1) and PGC-1α protein levels (P < 0.0001 and P = 0.0036, respectively). Resveratrol treatment improved the mtDNA copy number (P < 0.0001) and ATP content in GCs (P = 0.0014). Clinically, the resveratrol group exhibited higher rates of oocyte maturity (P = 0.0012) and high-quality embryos (P = 0.0013) than did the placebo group. There were no significant differences between the groups in terms of chemical or clinical pregnancy rates (P > 0.05). CONCLUSIONS: These findings indicate that resveratrol may be a promising therapeutic agent for patients with PCOS undergoing assisted reproduction. TRIAL REGISTRATION NUMBER: http://www.irct.ir ; IRCT20221106056417N1; 2023 February 09.

Effectiveness of edaravone in preventing contrast-induced nephropathy in high-risk patients undergoing coronary angiography: A randomized, double-blind trial.

Contrast-induced nephropathy (CIN) is a serious complication that occurs subsequent to the administration of contrast media for therapeutic angiographic interventions. As of present, no effective therapy exists to prevent its occurrence. This single-center double-blind randomized controlled trial aimed to evaluate the effect of edaravone, an antioxidant, in a group of high-risk patients undergoing coronary angiography. Ninety eligible patients with chronic kidney disease Stages 3-4 were randomly assigned to either the control group (n = 45) or the intervention group (n = 45). In the intervention group, one dosage of edaravone (60 mg) in 1 L of normal saline was infused via a peripheral vein 1 h prior to femoral artery-directed coronary angiography. Patients in the control group received an equal amount of infusion in their last hour before angiography. Both groups received intravenous hydration with 0.9% sodium 1 mL/kg/h starting 12 h before and continuing for 24 h after angiography. The primary outcome measure was the onset of CIN, defined as a 25% increase in serum creatinine levels 120 h after administration of contrast media. The occurrence of CIN was observed in 5.5% (n = 5) of the studied population: 2.2% of patients in the intervention group (n = 1) and 8.9% of controls (n = 4). However, this difference was not statistically significant. Administration of a single dosage of edaravone 1 h prior to infusion of contrast media led to a reduction in the incidence of CIN. Further investigations, employing larger sample sizes, are warranted to gain a comprehensive understanding of its efficacy.

Interpreting the role of antioxidants in vivo: A cautionary tale.

Bacteria have a remarkable ability to sense environmental stresses and to respond to these stressors by adapting their metabolism and physiology. In recent publications, investigators have suggested that multiple stresses that cause cell death share the mechanistic feature of stimulating the formation of reactive oxygen species (ROS). A central piece of evidence cited in these claims is the ability of exogenous antioxidant compounds to mitigate stress-related cell death. The validity of attributing a positive effect of exogenous antioxidants to ROS-mediated stress is challenged by an important study by Korshunov and Imlay in this issue of Molecular Microbiology. This study reports biochemical data that convincingly show that some commonly used antioxidants quench oxidants orders of magnitude too slowly to have a significant effect on the concentration of ROS in the cell. Under conditions where antioxidants minimize cell death, they also slow growth. Significantly, slowing cell growth by other means has the same restorative effect as adding an antioxidant. Based on the solid biochemical and genetic data, Korshunov and Imlay make the case for discarding the use of antioxidants to diagnose conditions that generate increased internal ROS production.

Comprehensive elucidation of the differential physiological kale response to cytokinins under in vitro conditions.

BACKGROUND: Kale, a versatile cruciferous crop, valued for its pro-health benefits, stress resistance, and potential applications in forage and cosmetics, holds promise for further enhancement of its bioactive compounds through in vitro cultivation methods. Micropropagation techniques use cytokinins (CKs) which are characterized by various proliferative efficiency. Despite the extensive knowledge regarding CKs, there remains a gap in understanding their role in the physiological mechanisms. That is why, here we investigated the effects of three CKs - kinetin (Kin), 6-benzylaminopurine (BAP), and 2-isopentenyladenine (2iP) - on kale physiology, antioxidant status, steroidal metabolism, and membrane integrity under in vitro cultivation. RESULTS: Our study revealed that while BAP and 2iP stimulated shoot proliferation, they concurrently diminished pigment levels and photosynthetic efficiency. Heightened metabolic activity in response to all CKs was reflected by increased respiratory rate. Despite the differential burst of ROS, the antioxidant properties of kale were associated with the upregulation of guaiacol peroxidase and the scavenging properties of ascorbate rather than glutathione. Notably, CKs fostered the synthesis of sterols, particularly sitosterol, pivotal for cell proliferation and structure of membranes which are strongly disrupted under the action of BAP and 2iP possibly via pathway related to phospholipase D and lipoxygenase which were upregulated. Intriguingly, both CKs treatment spurred the accumulation of sitostenone, known for its ROS scavenging and therapeutic potential. The differential effects of CKs on brassicasterol levels and brassinosteroid (BRs) receptor suggest potential interactions between CKs and BRs. CONCLUSION: Based on the presented results we conclude that the effect evoked by BAP and 2iP in vitro can improve the industrial significance of kale because this treatment makes possible to control proliferation and/or biosynthesis routes of valuable beneficial compounds. Our work offers significant insights into the nuanced effects of CKs on kale physiology and metabolism, illuminating potential avenues for their application in plant biotechnology and medicinal research.

Oxidative stress and acute pancreatitis (Review).

Acute pancreatitis (AP) is a common inflammatory disorder of the exocrine pancreas that causes severe morbidity and mortality. Although the pathophysiology of AP is poorly understood, a substantial body of evidence suggests some critical events for this disease, such as dysregulation of digestive enzyme production, cytoplasmic vacuolization, acinar cell death, edema formation, and inflammatory cell infiltration into the pancreas. Oxidative stress plays a role in the acute inflammatory response. The present review clarified the role of oxidative stress in the occurrence and development of AP by introducing oxidative stress to disrupt cellular Ca2+ balance and stimulating transcription factor activation and excessive release of inflammatory mediators for the application of antioxidant adjuvant therapy in the treatment of AP.

Melatonin differentially refines the metabolome to improve seed formation during grain developmental stages and enhances yield in two contrasting rice cultivars, grown in arsenic-contaminated soil.

The manuscript revealed the ameliorative effects of exogenous melatonin in two distinct reproductive stages, i.e., developing grains (20 days after pollination) and matured grains (40 days after pollination) in two contrasting indica rice genotypes, viz., Khitish (arsenic-susceptible) and Muktashri (arsenic-tolerant), irrigated with arsenic-contaminated water throughout their life-cycle. Melatonin administration improved yield-related parameters like rachis length, primary and secondary branch length, number of grains per panicle, number of filled and empty grains per panicle, grain length and breadth and 1000-grain per weight. Expression of GW2, which negatively regulates grain development, was suppressed, along with concomitant induction of positive regulators like GIF1, DEP1 and SPL14 in both Khitish and Muktashri. Melatonin lowered arsenic bioaccumulation in grains and tissue biomass, more effectively in Khitish. Unregulated production of reactive oxygen species, leading to cellular necrosis caused by arsenic, was reversed in presence of melatonin. Endogenous melatonin level was stimulated due to up-regulation of the key biosynthetic genes, SNAT and ASMT. Melatonin enhanced the production of diverse antioxidants like anthocyanins, flavonoids, total phenolics and ascorbic acid and also heightened the production of thiol-metabolites (cysteine, reduced glutathione, non-protein thiols and phytochelatin), ensuring effective chelation and arsenic detoxification. Altogether, our observation, supported by principal component analysis, proved that melatonin re-programs the antioxidative metabolome to enhance plant resilience against arsenic stress to mitigate oxidative damages and reduce arsenic translocation from the soil to tissue biomass and edible grains.

One stone two birds: Endophytes alleviating trace elements accumulation and suppressing soilborne pathogen by stimulating plant growth, photosynthetic potential and defense related gene expression.

In the present investigation, we utilized zinc nanoparticles (Zn-NPs) and bacterial endophytes to address the dual challenge of heavy metal (HM) toxicity in soil and Rhizoctonia solani causing root rot disease of tomato. The biocontrol potential of Bacillus subtilis and Bacillus amyloliquefaciens was harnessed, resulting in profound inhibition of R. solani mycelial growth and efficient detoxification of HM through strong production of various hydrolytic enzymes and metabolites. Surprisingly, Zn-NPs exhibited notable efficacy in suppressing mycelial growth and enhancing the seed germination (%) while Gas chromatography-mass spectrometry (GC-MS) analysis unveiled key volatile compounds (VOCs) crucial for the inhibition of pathogen. Greenhouse trials underscored significant reduction in the disease severity (%) and augmented biomass in biocontrol-mediated plants by improving photosynthesis-related attributes. Interestingly, Zn-NPs and biocontrol treatments enhanced the antioxidant enzymes and mitigate oxidative stress indicator by increasing H2O2 concentration. Field experiments corroborated these findings, with biocontrol-treated plants, particularly those receiving consortia-mediated treatments, displayed significant reduction in disease severity (%) and enhanced the fruit yield under field conditions. Root analysis confirmed the effective detoxification of HM, highlighting the eco-friendly potential of these endophytes and Zn-NPs as fungicide alternative for sustainable production that foster soil structure, biodiversity and promote plant health.

Crosstalk between gut-brain axis: unveiling the mysteries of gut ROS in progression of Parkinson's disease.

"Path to a good mood lies through the gut." This statement seems to imply that it has long been believed that the gut is connected with the brain. Research has shown that eating food activates the reward system and releases dopamine (DA), establishing a link between the peripheral and central nervous system. At the same time, researchers also trust that the gut is involved in the onset of many diseases, including Parkinson's disease (PD), in which gastrointestinal dysfunction is considered a prevalent symptom. Reports suggest that PD starts from the gut and reaches the brain via the vagus nerve. Recent studies have revealed an intriguing interaction between the gut and brain, which links gut dysbiosis to the etiology of PD. This review aims to explore the mechanistic pathway how reactive oxygen species (ROS) generation in the gut affects the makeup and operation of the dopamine circuitry in the brain. Our primary concern is ROS generation in the gut, which disrupts the gut microbiome (GM), causing α-synuclein accumulation and inflammation. This trio contributes to the loss of DA neurons in the brain, resulting in PD development. This review also compiles pre-clinical and clinical studies on antioxidants, demonstrating that antioxidants reduce ROS and increase DA levels. Collectively, the study highlights the necessity of comprehending the gut-brain axis for unraveling the riddles of PD pathogenesis and considering new therapeutic approaches.

Enhancing water stress tolerance of bread wheat during seed germination and seedling emergence: caffeine-induced modulation of antioxidative defense mechanisms.

Better crop stand establishment, a function of rapid and uniform seedling emergence, depends on the activities of germination-related enzymes, which is problematic when there is insufficient soil moisture. Different ways are in practice for counteracting this problem, including seed priming with different chemicals, which are considered helpful in obtaining better crop stand establishment to some extent through improved seed germination and seedling emergence. In this growth room experiment, caffeine was used as a seed priming agent to improve germination under moisture scarcity. Polyethylene glycol-8000 (18%) was added to Hoagland's nutrient solution to create drought stress (-0.65 MPa). The experiment was arranged in a completely randomized design (CRD), having four replications of each treatment. A newly developed wheat genotype SB-1 was used for the experimentation. Different doses of caffeine, i.e., 4 ppm, 8 ppm, 12 ppm, and 16 ppm, including no soaking and water soaking, were used as seed priming treatments. Water deficit caused oxidative stress and adversely affected the seed germination, seedling vigor, activities of germination enzymes, photosynthetic pigments, and antioxidative defense mechanism in roots and shoots of seedlings. Caffeine seed priming ameliorated the negative effects of water deficit on seed germination and seedling vigor, which was attributed to the reduction in lipid peroxidation and improvement in the activities of germination-related enzymes like glucosidase, amylase, and protease. Conclusively, seed priming with 12 ppm caffeine outperformed the other treatments and hence is recommended for better crop stand establishment under conditions of soil moisture deficit.

Antimicrobial Potential of Pomegranate and Lemon Extracts Alone or in Combination with Antibiotics against Pathogens.

Amidst the growing concern of antimicrobial resistance as a significant health challenge, research has emerged, focusing on elucidating the antimicrobial potential of polyphenol-rich extracts to reduce reliance on antibiotics. Previous studies explored the antifungal effects of extracts as potential alternatives to conventional therapeutic strategies. We aimed to assess the antibacterial and antifungal effects of standardised pomegranate extract (PE) and lemon extract (LE) using a range of Gram-negative and Gram-positive bacteria and two yeast species. Additionally, we assessed the antimicrobial activities of common antibiotics (Ciprofloxacin, Imipenem, Gentamicin, and Ceftazidime), either alone or in combination with extracts, against Staphylococcus aureus and Escherichia coli. PE displayed substantial antibacterial (primarily bactericidal) and antifungal effects against most pathogens, while LE exhibited antibacterial (mostly bacteriostatic) and antifungal properties to a lesser extent. When compared with antibiotics, PE showed a greater zone of inhibition (ZOI) than Ciprofloxacin and Ceftazidime (p < 0.01) and comparable ZOI to Gentamicin (p = 0.4) against Staphylococcus aureus. However, combinations of either PE or LE with antibiotics exhibited either neutral or antagonistic effects on antibiotic activity against Staphylococcus aureus and Escherichia coli. These findings contribute to the existing evidence regarding the antimicrobial effects of PE and LE. They add to the body of research suggesting that polyphenols exert both antagonistic and synergistic effects in antimicrobial activity. This highlights the importance of identifying optimal polyphenol concentrations that can enhance antibiotic activity and reduce antibiotic resistance. Further in vivo studies, starting with animal trials and progressing to human trials, may potentially lead to recommendation of these extracts for therapeutic use.

Evaluation of the role of some non-enzymatic antioxidants among Iraqi patients with non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD), characterized by hepatic fat accumulation in individuals consuming little or no alcohol, has become highly prevalent globally. Oxidative stress plays a central role in instigating inflammation and cell death pathways driving NAFLD progression. This case-control study aimed to elucidate the association between circulating levels of the pivotal non-enzymatic antioxidants - coenzyme Q10 and vitamins E and C - and liver injury parameters among 60 Iraqi NAFLD patients versus 30 healthy controls. NAFLD diagnosis entailed over 5% hepatic steatosis on ultrasound excluding other etiologies. Patients spanned three age groups: 20-29, 30-39, and 40-49. Substantially diminished antioxidant levels concurrent with elevated alkaline phosphatase enzyme were unveiled in NAFLD patients relative to controls (all p < 0.001). Age-based analysis reinforced widespread antioxidant depletion and liver enzyme augmentation across NAFLD patients. Significant correlations also emerged between antioxidants and liver parameters. Our novel observations confirm an antioxidant inadequacy likely perpetuating pathogenic oxidative reactions in NAFLD. Restoring such deficits through lifestyle or therapeutic interventions may confer preventative and disease-modifying value.

Effects of Thymbra spicata extract and Thymol on morphine withdrawal syndrome in mice (insights to the liver function, antioxidant, and behavioral responses).

Safe chemicals for drug withdrawal can be extracted from natural sources. This study investigates the effects of clonidine and Thymbra spicata extract (TSE) on mice suffering from morphine withdrawal syndrome. Thymol, which is the active constituent in TSE, was also tested. A total of 90 mice were divided into nine groups. Group 1 was the control group, while Group 2 was given only morphine, and Group 3 received morphine and 0.2 mg/kg of clonidine. Groups 4-6 were given morphine along with 100, 200, and 300 mg/kg of TSE, respectively. Groups 7-9 received morphine plus 30, 60, and 90 mg/kg of Thymol, respectively, for 7 days. An oral naloxone challenge of 3 mg/kg was used to induce withdrawal syndrome in all groups. Improvement of liver enzyme levels (aspartate aminotransferase, alkaline phosphatase, and alanine transaminase) (p < .01) and behavioral responses (frequencies of jumping, frequencies of two-legged standing, Straub tail reaction) (p < .01) were significantly observed in the groups receiving TSE and Thymol (Groups 4-9) compared to Group 2. Additionally, antioxidant activity in these groups was improved compared to Group 2. Nitric oxide significantly decreased in Groups 4 and 6 compared to Groups 2 and 3 (p < .01). Superoxide dismutase increased dramatically in Groups 5, 8, and 9 compared to Groups 2 and 3 (p < .01). Groups 5-9 were significantly different from Group 2 in terms of malondialdehyde levels (p < .01). Certain doses of TSE and Thymol were found to alleviate the narcotics withdrawal symptoms. This similar effect to clonidine can pave the way for their administration in humans.

A new active packaging system based on chickpea-based edible coatings added with microcapsules of Cosmos sulphureus Cav. flower extract.

BACKGROUND: The Cosmos sulphureus Cav. plant is studied for its high polyphenolic content with antioxidant properties. Its flowers, rich in phenolic acids, flavonoids, and tannins, hold promise as antioxidants in food preservation. The inclusion of these compounds in chickpea-based coatings with a previously studied preservative effect would be an excellent option as a food preservation method and microencapsulation addresses challenges like dispersion and degradation of polyphenols in the coating. The objective of this research was to evaluate the in vitro antioxidant activity of Cosmos sulphureus leaves, seed, and flower extracts and explore the protective effects of chickpea-based coatings containing microcapsules of flower polyphenolic extract on the chemical quality of stored roasted sunflower seeds during storage. RESULTS: The ethanolic leaf extract exhibited the highest antiradical activity, followed by the aqueous flower extract. After a storage period of 15 days, at 40 °C, the chickpea-based coatings effectively delayed lipid oxidation in the roasted sunflowers seeds, and the inclusion of polyphenolic microcapsules with 0.01% extract (SMC 0.01%) in the coating significantly improved the protective effect. By day 15 of storage, SMC 0.01% showed comparable peroxide value, conjugated dienes, and linoleic acid content to samples containing the synthetic antioxidant BHT (butylated hydroxytoluene). Samples that only contained chickpea-based coating and coating with polyphenolic microcapsules with 0.005% extract exhibited significantly greater reduction in fatty acid content compared to the 0.01% SMC treatment. CONCLUSION: The chickpea-based coating with polyphenolic microcapsules demonstrated antioxidant activity akin to synthetic BHT, offering a promising biopackaging solution for lipid-rich foods like roasted sunflower seeds. © 2024 Society of Chemical Industry.

Computational studies on a selection of phosphite esters as antioxidants for polymeric materials.

CONTEXT: Phosphite esters, a class of organo-phosphorus compounds, are widely used as non-discolouring antioxidants in many polymeric products. Apart from normal radical scavenging, they prevent the splitting of hydroperoxides (ROOH), one of the initial products of autoxidation, from forming extremely reactive free radicals such as alkoxy (RO.) and hydroxy (.OH) radicals. The inherent molecular properties of antioxidants and the chemistry of their action are essential for researchers working in this field of science. Four organo-phosphorous compounds well-known for their antioxidant activity are selected here for theoretical analysis: Tri(m-methylphenyl) phosphite (m-TMPP), Tri(4-methyl-2,6-di-tert-butylphenyl) phosphite (TMdtBPP), Tri(allylphenyl) phosphite (TAPP) and Tri(mercaptobenzothiazoyl) thiophosphate (TMBTTP). The antioxidant activity exhibited by these compounds is theoretically verified, and the results are consistent with the available experimental data. Such theoretical predictions offer advantages in scientific research, particularly when researchers need to select certain molecules as antioxidants for experiments from a pool of molecular systems. METHODS: The chemical computations presented in this report are done in Gaussian 16 program package. The procedure of density functional theory (DFT) with the model chemistry B3LYP/6-31G(d,p) is used to generate computational data. Global reactivity indices, thermochemical data, Fukui functions, molecular electrostatic potential and NMR spectra are computed for the chosen molecular systems from their optimized geometries.

The General Neurocognitive Decline in Patients with Methamphetamine Use and Transient Methamphetamine-induced Psychosis Primarily Determined by Oxidative and AGE-RAGE Stress.

BACKGROUND: Chronic Methamphetamine (MA) usage is linked to oxidative and AGE (advanced glycation end products) - RAGE (receptors for AGEs) stress, changes in magnesium, calcium, and copper, increased psychotic symptoms, and neurocognitive deficits. Nevertheless, it is still unclear whether these biological pathways mediate the latter impairments. OBJECTIVE: This study aimed to investigate the relationships between neurocognition, the aforementioned biomarkers, and psychotic symptoms. METHODS: We recruited 67 participants, namely 40 patients diagnosed with MA-substance use and 27 healthy controls, and assessed the Brief Assessment of Cognition in Schizophrenia (BACS), symptoms of psychosis, excitation, and formal thought disorders, oxidative toxicity (computed as the sum of myeloperoxidase (MPO), oxidized high-density lipoprotein (HDL), oxidized low-DL (malondialdehyde), antioxidant defenses (catalase, glutathione peroxidase, total antioxidant capacity, zinc, and HDL), and increased AGEs and RAGEs. RESULTS: We were able to extract one validated latent vector from the Mini-Mental State Examination score and the BACS test results (including executive functions, verbal fluency, and attention), labeled general cognitive decline (G-CoDe). We found that 76.1% of the variance in the G-CoDe was explained by increased oxidative toxicity, lowered antioxidant defenses, number of psychotic episodes, and MA dose. In patients with MA use, MPO was significantly associated with the GCoDe. CONCLUSION: The use of MA induced mild cognitive impairments through MA-induced activation of detrimental outcome pathways, including oxidative and AGE-RAGE stress, and suppression of protective antioxidant pathways. Increased MPO, oxidative, and AGE-RAGE stress are new drug targets to prevent neurocognitive deficits and psychosis due to MA use.

Overexpression of Genes to Enhance Abiotic Stress Tolerance in Arabidopsis.

Abiotic environmental stressors cause various types of damage to plants and cause significant loss in yield. Abiotic stress tolerance in plants refers to the ability to withstand environmental factors and maintain growth, development, and production. Since this tolerance is controlled by a gene or a set of genes, transgenic activating of these genes in plants often enhances tolerance under abiotic stress. Therefore, this methodology chapter describes a strategy and the corresponding protocols needed to induce a gene by an abiotic stressor, clone the corresponding cDNA into plasmids and Agrobacterium cells, and genetic transformation to the Arabidopsis plants using the floral dip method. The chapter also describes standard assays to evaluate the transgene's effect on the plant's tolerance. Finally, the techniques outlined in this chapter for cloning and generating transgenic plants tolerant to abiotic stress are a versatile approach that can be implemented across various plant species and genes.

The importance of paraoxonase 1 activity in chronic kidney disease.

Paraoxonase 1 (PON1) is one of the most significant antioxidative enzymes associated with high-density lipoprotein (HDL). It has been proved that is involved in the pathogenesis of many diseases including chronic kidney disease (CKD). The association between PON1 and CKD seems to be mutual, such that the disease produces a significant decrease in PON1 activity levels, while the genetics of PON1 may affect the risk of susceptibility to CKD. Recent studies reveal that the decrease in serum PON1 activity observed in non-dialyzed and dialyzed CKD patients as well as in renal transplant (RT) patients is linked to an increased vulnerability to atherosclerosis. We intend to summarize current literature concerning PON1 activity in CKD, highlighting on the main determinants of PON1 activity, its association with oxidative stress, the impact of its genetic polymorphism on the disease development, the effect of drugs and nutritional state. Furthermore, evidence supporting the implication of reduced PON1 activity in the incident of cardiovascular disease in CKD patients, is also examined. It appears that despite the lack of standardization of PON1 activity measurement, PON1 remains a valuable biomarker for the researchers through the last decades, which contributes to the assessment of the antioxidant status having prognostic benefit on adverse clinical outcomes at various stages and etiologies of kidney disease.

Cannabidiol effectively prevents oxidative stress and stabilizes hypoxia-inducible factor-1 alpha (HIF-1α) in an animal model of global hypoxia.

Cannabidiol (CBD) is a non-psychotomimetic phytocannabinoid derived from Cannabis sativa. It has therapeutic effects in different paradigms of brain injury, acting as a neuroprotectant. As oxidative stress is a primary risk factor for brain damage after neonatal hypoxia, we tested the effect of CBD on oxidative status and non-protein-bound iron accumulation in the immature brain after hypoxia. Moreover, we tested whether cannabidiol affects the accumulation of hypoxia-inducible factor-1 alpha (HIF-1α) which plays a key role in the regulation of cellular adaptation to hypoxia and oxidative stress. We used 7-day-old mice randomly assigned to hypoxic or control groups. Immediately after hypoxia or control exposure, pups were randomly assigned to a vehicle or CBD treatment. 24 h later, they were decapitated and the brains were immediately removed and stored for further biochemical analyses. We found that CBD reduced lipid peroxidation and prevented antioxidant depletion. For the first time, we also demonstrated that CBD upregulated HIF-1α protein level. This study indicates that CBD may effective agent in attenuating the detrimental consequences of perinatal asphyxia.