Glutathione-Dependent Mechanisms of Antioxidant Defense in Men with Pathozoospermia after COVID-19 Infection

The article presents results of studying the influence of COVID-19 infections on glutathione metabolism in men with pathozoospermia and COVID-19. In erythrocyte cytolysate, we determined concentration of reduced (GSH) and oxidized (GSSG) glutathione and the GSH/GSSG ratio as the main indication of cell redox-status and an important factor in cell redox-dependent signaling control along with the effect GSH-dependent enzymes. Results of our study allowed us to determine the peculiarity of the influence of COVID-19 infection on thee glutathione metabolic pathway. The understanding of the influence mechanisms of SARS-CoV-2 on metabolic processes in the body of men with pathozoospermia has been expanded. The data obtained give grounds and opportunities for a more reasonable approach to the organization of preventive, curative, and rehabilitative measures for COVID-19 infection.

Integration of MsrB1 and MsrB2 in the Redox Network during the Development of Orthodox and Recalcitrant Acer Seeds

Two related tree species, Norway maple (Acer platanoides L.) and sycamore (Acer pseudoplatanus L.), produce desiccation-tolerant (orthodox) and desiccation-sensitive (recalcitrant) seeds, respectively. We compared the seeds of these two species to characterize the developmentally driven changes in the levels of peptide-bound methionine sulfoxide (MetO) and the abundance of methionine sulfoxide reductases (Msrs) B1 and B2, with respect to the cellular redox environment. Protein oxidation at the Met level was dynamic only in Norway maple seeds, and the reduced MsrB2 form was detected only in this species. Cell redox status, characterized by the levels of reduced and oxidized ascorbate, glutathione, and nicotinamide adenine dinucleotide (NAD)/phosphate (NADP), was clearly more reduced in the Norway maple seeds than in the sycamore seeds. Clear correlations between MetO levels, changes in water content and redox status were reported in orthodox Acer seeds. The abundance of Msrs was correlated in both species with redox determinants, mainly ascorbate and glutathione. Our data suggest that MsrB2 is associated with the acquisition of desiccation tolerance and that ascorbate might be involved in the redox pathway enabling the regeneration of Msr via intermediates that are not known yet.

Role of Melatonin in Plant Tolerance to Soil Stressors: Salinity, pH and Heavy Metals

Melatonin (MT) is a pleiotropic molecule with diverse and numerous actions both in plants and animals. In plants, MT acts as an excellent promotor of tolerance against abiotic stress situations such as drought, cold, heat, salinity, and chemical pollutants. In all these situations, MT has a stimulating effect on plants, fomenting many changes in biochemical processes and stress-related gene expression. Melatonin plays vital roles as an antioxidant and can work as a free radical scavenger to protect plants from oxidative stress by stabilization cell redox status; however, MT can alleviate the toxic oxygen and nitrogen species. Beyond this, MT stimulates the antioxidant enzymes and augments antioxidants, as well as activates the ascorbate–glutathione (AsA–GSH) cycle to scavenge excess reactive oxygen species (ROS). In this review, we examine the recent data on the capacity of MT to alleviate the effects of common abiotic soil stressors, such as salinity, alkalinity, acidity, and the presence of heavy metals, reinforcing the general metabolism of plants and counteracting harmful agents. An exhaustive analysis of the latest advances in this regard is presented, and possible future applications of MT are discussed.

Salicylic Acid Binding Proteins (SABPs): The Hidden Forefront of Salicylic Acid Signalling

Salicylic acid (SA) is a phytohormone that plays important roles in many aspects of plant life, notably in plant defenses against pathogens. Key mechanisms of SA signal transduction pathways have now been uncovered. Even though details are still missing, we understand how SA production is regulated and which molecular machinery is implicated in the control of downstream transcriptional responses. The NPR1 pathway has been described to play the main role in SA transduction. However, the mode of SA perception is unclear. NPR1 protein has been shown to bind SA. Nevertheless, NPR1 action requires upstream regulatory events (such as a change in cell redox status). Besides, a number of SA-induced responses are independent from NPR1. This shows that there is more than one way for plants to perceive SA. Indeed, multiple SA-binding proteins of contrasting structures and functions have now been identified. Yet, all of these proteins can be considered as candidate SA receptors and might have a role in multinodal (decentralized) SA input. This phenomenon is unprecedented for other plant hormones and is a point of discussion of this review.

Assaying Chlamydia pneumoniae persistence in monocyte-derived macrophages identifies schisandrin lignans as phenotypic switchers

Antibiotic-tolerant persister bacteria involve frequent treatment failures, relapsing infections and the need for extended antibiotic treatment. Taking persisters into account in susceptibility assays is thus an essential success factor in antibacterial drug discovery. The virulence of the obligate intracellular bacterium Chlamydia pneumoniae is tightly linked to its propensity for persistence, but current susceptibility screening on this gram-negative respiratory pathogen relies on permissive epithelial cells. To establish an improved antichlamydial susceptibility assay allowing the analysis of both actively growing and persister bacteria, we studied C. pneumoniae clinical isolate CV-6 infection kinetics in THP-1 macrophages by qPCR and quantitative culture. Indicated by the steady increase of chlamydial genome copy numbers and infectious progeny as well as the failure of azithromycin to eradicate the intracellular forms of the bacterium, the macrophages were found to harbor a subpopulation of persister C. pneumoniae cells. The potential of the assay for the discovery of anti-persister molecules against intracellular bacteria was demonstrated by the identification of the differential effects of two dibenzocyclooctadiene lignans on C. pneumoniae infection. While schisandrin reverted C. pneumoniae persistence and promoted productive infection, schisandrin C was superior to azithromycin in eradicating the C. pneumoniae infection. The phenotypic switch was associated with the suppression of cellular glutathione pools, implying that targeting glutathione homeostasis may provide a novel means for intracellular bacteria resuscitation. In conclusion, these data highlight the value of macrophages over permissive cell lines in anti-persister agent discovery on intracellular bacteria and targeting host cell redox status to fight persistent infections.

One-Carbon Metabolism: Biological Players in Epithelial Ovarian Cancer

Metabolism is deeply involved in cell behavior and homeostasis maintenance, with metabolites acting as molecular intermediates to modulate cellular functions. In particular, one-carbon metabolism is a key biochemical pathway necessary to provide carbon units required for critical processes, including nucleotide biosynthesis, epigenetic methylation, and cell redox-status regulation. It is, therefore, not surprising that alterations in this pathway may acquire fundamental importance in cancer onset and progression. Two of the major actors in one-carbon metabolism, folate and choline, play a key role in the pathobiology of epithelial ovarian cancer (EOC), the deadliest gynecological malignancy. EOC is characterized by a cholinic phenotype sustained via increased activity of choline kinase alpha, and via membrane overexpression of the alpha isoform of the folate receptor (FRα), both of which are known to contribute to generating regulatory signals that support EOC cell aggressiveness and proliferation. Here, we describe in detail the main biological processes associated with one-carbon metabolism, and the current knowledge about its role in EOC. Moreover, since the cholinic phenotype and FRα overexpression are unique properties of tumor cells, but not of normal cells, they can be considered attractive targets for the development of therapeutic approaches.

Effects of exogenous vitamins A, C, and E and NADH supplementation on proliferation, cytokines release, and cell redox status of lymphocytes from healthy aged subjects

Aging is an inevitable biological event that is associated with immune alterations. These alterations are related to increased cellular oxidative stress and micronutrient deficiency. Antioxidant supplementation could improve these age-related abnormalities. The aim of this study was to determine in vitro effects of vitamin A, vitamin C, vitamin E, and nicotinamide adenine dinucleotide (NADH) on T cell proliferation, cytokine release, and cell redox status in the elderly compared with young adults. Peripheral blood lymphocytes were isolated using a density gradient of Histopaque. They were cultured in vitro and stimulated with concanavalin A in the presence or absence of vitamins. Cell proliferation was determined by conducting MTT assays, and based on interleukin-2 and interleukin-4 secretions. Cell oxidant/antioxidant balance was assessed by assaying reduced glutathione (GSH), malondialdehyde, carbonyl protein levels, and catalase activity. The present study demonstrated that T-lymphocyte proliferation was decreased with aging and was associated with cytokine secretion alterations, GSH depletion, and intracellular oxidative stress. In the elderly, vitamin C, vitamin E, and NADH significantly improved lymphocyte proliferation and mitigated cellular oxidative stress, whereas vitamin A did not affect cell proliferation or cell redox status. In conclusion, vitamin C, vitamin E, and NADH supplementation improved T-lymphocytes response in the elderly, and could contribute to the prevention of age-related immune alterations. Consumption of food items containing these vitamins is recommended, and further investigation is necessary to evaluate the effect of vitamin supplementation in vivo.

Involvement of the modulation of cancer cell redox status in the anti-tumoral effect of phenolic compounds

The association between the anti-tumoral properties of phenolics, the generation of ROS in culture medium and modulation of redox homeostasis was analyzed. In AGS cells, the anti-proliferative effect of quercetin was not reverted by catalase or SOD.