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1.
Use of Thiols in the Treatment of COVID-19: Current Evidence.
Cazzola, M, Rogliani, P, Salvi, SS, Ora, J, Matera, MG
Lung. 2021;(4):335-343
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Abstract
There is a possible role for oxidative stress, a state characterized by an altered balance between the production of free radicals or reactive oxygen species (ROS) and antioxidant defences, in coronavirus disease 2019 (COVID-19), the genesis of which is quite complex. Excessive oxidative stress could be responsible for the alveolar damage, thrombosis, and red blood cell dysregulation observed in COVID-19. Apparently, deficiency of glutathione (GSH), a low-molecular-weight thiol that is the most important non-enzymatic antioxidant molecule and has the potential to keep the cytokine storm in check, is a plausible explanation for the severe manifestations and death in COVID-19 patients. Thiol drugs, which are considered mucolytic, also possess potent antioxidant and anti-inflammatory properties. They exhibit antibacterial activity against a variety of medically important bacteria and may be an effective strategy against influenza virus infection. The importance of oxidative stress during COVID-19 and the various pharmacological characteristics of thiol-based drugs suggest a possible role of thiols in the treatment of COVID-19. Oral and intravenous GSH, as well as GSH precursors such as N-acetylcysteine (NAC), or drugs containing the thiol moiety (erdosteine) may represent a novel therapeutic approach to block NF-kB and address the cytokine storm syndrome and respiratory distress observed in COVID-19 pneumonia patients.
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2.
Oxygen and reactive oxygen species-dependent regulation of plant growth and development.
Considine, MJ, Foyer, CH
Plant physiology. 2021;(1):79-92
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Abstract
Oxygen and reactive oxygen species (ROS) have been co-opted during evolution into the regulation of plant growth, development, and differentiation. ROS and oxidative signals arising from metabolism or phytohormone-mediated processes control almost every aspect of plant development from seed and bud dormancy, liberation of meristematic cells from the quiescent state, root and shoot growth, and architecture, to flowering and seed production. Moreover, the phytochrome and phytohormone-dependent transmissions of ROS waves are central to the systemic whole plant signaling pathways that integrate root and shoot growth. The sensing of oxygen availability through the PROTEOLYSIS 6 (PRT6) N-degron pathway functions alongside ROS production and signaling but how these pathways interact in developing organs remains poorly understood. Considerable progress has been made in our understanding of the nature of hydrogen peroxide sensors and the role of thiol-dependent signaling networks in the transmission of ROS signals. Reduction/oxidation (redox) changes in the glutathione (GSH) pool, glutaredoxins (GRXs), and thioredoxins (TRXs) are important in the control of growth mediated by phytohormone pathways. Although, it is clear that the redox states of proteins involved in plant growth and development are controlled by the NAD(P)H thioredoxin reductase (NTR)/TRX and reduced GSH/GRX systems of the cytosol, chloroplasts, mitochondria, and nucleus, we have only scratched the surface of this multilayered control and how redox-regulated processes interact with other cell signaling systems.
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3.
Deterioration of orthodox seeds during ageing: Influencing factors, physiological alterations and the role of reactive oxygen species.
Zhang, K, Zhang, Y, Sun, J, Meng, J, Tao, J
Plant physiology and biochemistry : PPB. 2021;:475-485
Abstract
Seed viability is an important trait in agriculture which directly influences seedling emergence and crop yield. However, even when stored under optimal conditions, all seeds will eventually lose their viability. Our primary aims were to describe factors influencing seed deterioration, determine the morphological, physiological, and biochemical changes that occur during the process of seed ageing, and explore the mechanisms involved in seed deterioration. High relative humidity and high temperature are two factors that accelerate seed deterioration. As seeds age, frequently observed changes include membrane damage and the destruction of organelle structure, an increase in the loss of seed leachate, decreases of respiratory rates and ATP production, and a loss of enzymatic activity. These phenomena could be inter-related and reflect the general breakdown in cellular organization. Many processes can result in seed ageing; it is likely that oxidative damage caused by free radicals and reactive oxygen species (ROS) is primarily responsible. ROS can have vital interactions with any macromolecule of biological interest that result in damage to various cellular components caused by protein damage, lipid peroxidation, chromosomal abnormalities, and DNA lesions. Further, ROS may also cause programmed cell death by inducing the opening of mitochondrial permeability transition pores and the release of cytochrome C. Some repairs can occur in the early stages of imbibition, but repair processes fail if sufficient damage has been caused to critical functional components. As a result, a given seed will lose its viability and eventually fail to germinate in a relatively short time period.
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4.
Atorvastatin and pravastatin stimulate nitric oxide and reactive oxygen species generation, affect mitochondrial network architecture and elevate nicotinamide N-methyltransferase level in endothelial cells.
Dymkowska, D, Wrzosek, A, Zabłocki, K
Journal of applied toxicology : JAT. 2021;(7):1076-1088
Abstract
Statins belong to the most often prescribed medications, which efficiently normalise hyperlipidaemia and prevent cardiovascular complications in obese and diabetic patients. However, beside expected therapeutic results based on the inhibition of 3-hydroxyl-3-methylglutaryl-CoA reductase, these drugs exert multiple side effects of poorly understood characteristic. In this study, side effects of pravastatin and atorvastatin on EA.hy926 endothelial cell line were investigated. It was found that both statins activate proinflammatory response, elevate nitric oxide and reactive oxygen species (ROS) generation and stimulate antioxidative response in these cells. Moreover, only slight stimulation of the mitochondrial biogenesis and significant changes in the mitochondrial network organisation have been noted. Although biochemical bases behind these effects are not clear, they may partially be explained as an elevation of AMP-activated protein kinase (AMPK) activity and an increased activating phosphorylation of sirtuin 1 (Sirt1), which were observed in statins-treated cells. In addition, both statins increased nicotinamide N-methyltransferase (NNMT) protein level that may explain a reduced fraction of methylated histone H3. Interestingly, a substantial reduction of the total level of histone H3 in cells treated with pravastatin but not atorvastatin was also observed. These results indicate a potential additional biochemical target for statins related to reduced histone H3 methylation due to increased NNMT protein level. Thus, NNMT may directly modify gene activity.
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5.
Oxidative damage and antioxidants in cervical cancer.
Preci, DP, Almeida, A, Weiler, AL, Mukai Franciosi, ML, Cardoso, AM
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society. 2021;(2):265-271
Abstract
The pathogenesis of cervical cancer is related to oxidative damage caused by persistent infection by one of the oncogenic types of human papillomavirus (HPV). This damage comes from oxidative stress, which is the imbalance caused by the increase in reactive oxygen and nitrogen species and impaired antioxidant mechanisms, promoting tumor progression through metabolic processes. The incorporation of HPV into the cellular genome leads to the expression of oncoproteins, which are associated with chronic inflammation and increased production of reactive oxygen species, oxidizing proteins, lipids and DNA. The increase in these parameters is related, in general, to the reduction of circulating levels of enzymatic antioxidants-superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase; and non-enzymatic antioxidants-reduced glutathione, coenzyme Q10 and vitamins A, C and E, according to tumor staging. In contrast, some enzymatic antioxidants suffer upregulation in the tumor tissue as a way of adapting to the oxidative environment generated by themselves, such as glutathione-S-transferase, reduced glutathione, glutathione peroxidase, superoxide dismutase 2, induced nitric oxide synthase, peroxiredoxins 1, 3 and 6, and thioredoxin reductase 2. The decrease in the expression and activity of certain circulatory antioxidants and increasing the redox status of the tumor cells are thus key to cervical carcinoma prognosis. In addition, vitamin deficit is considered a possible modifiable risk factor by supplementation, since the cellular functions can have a protective effect on the development of cervical cancer. In this review, we will discuss the impact of oxidative damage on cervical cancer progression, as well as the main oxidative markers and therapeutic potentialities of antioxidants.
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Regulation of Reactive Oxygen Species and Antioxidant Defense in Plants under Salinity.
Hasanuzzaman, M, Raihan, MRH, Masud, AAC, Rahman, K, Nowroz, F, Rahman, M, Nahar, K, Fujita, M
International journal of molecular sciences. 2021;(17)
Abstract
The generation of oxygen radicals and their derivatives, known as reactive oxygen species, (ROS) is a part of the signaling process in higher plants at lower concentrations, but at higher concentrations, those ROS cause oxidative stress. Salinity-induced osmotic stress and ionic stress trigger the overproduction of ROS and, ultimately, result in oxidative damage to cell organelles and membrane components, and at severe levels, they cause cell and plant death. The antioxidant defense system protects the plant from salt-induced oxidative damage by detoxifying the ROS and also by maintaining the balance of ROS generation under salt stress. Different plant hormones and genes are also associated with the signaling and antioxidant defense system to protect plants when they are exposed to salt stress. Salt-induced ROS overgeneration is one of the major reasons for hampering the morpho-physiological and biochemical activities of plants which can be largely restored through enhancing the antioxidant defense system that detoxifies ROS. In this review, we discuss the salt-induced generation of ROS, oxidative stress and antioxidant defense of plants under salinity.
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7.
Micronutrient fertilization enhances ROS scavenging system for alleviation of abiotic stresses in plants.
Tavanti, TR, Melo, AAR, Moreira, LDK, Sanchez, DEJ, Silva, RDS, Silva, RMD, Reis, ARD
Plant physiology and biochemistry : PPB. 2021;:386-396
Abstract
Reactive oxygen species (ROS) such as hydrogen peroxide at low concentrations act as signaling of several abiotic stresses. Overproduction of hydrogen peroxide causes the oxidation of plant cell lipid phosphate layer promoting senescence and cell death. To mitigate the effect of ROS, plants develop antioxidant defense mechanisms (superoxide dismutase, catalase, guaiacol peroxidase), ascorbate-glutathione cycle enzymes (ASA-GSH) (ascorbate peroxidase, monodehydroascorbate reductase, dehydroascorbate reductase and glutathione reductase), which have the function of removing and transforming ROS into non-toxic substances to maintain cellular homeostasis. Foliar or soil application of fertilizers containing B, Cu, Fe, Mn, Mo, Ni, Se and Zn at low concentrations has the ability to elicit and activate antioxidative enzymes, non-oxidizing metabolism, as well as sugar metabolism to mitigate damage by oxidative stress. Plants treated with micronutrients show higher tolerance to abiotic stress and better nutritional status. In this review, we summarized results indicating micronutrient actions in order to reduce ROS resulting the increase of photosynthetic capacity of plants for greater crop yield. This meta-analysis provides information on the mechanism of action of micronutrients in combating ROS, which can make plants more tolerant to several types of abiotic stress such as extreme temperatures, salinity, heavy metals and excess light.
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8.
Fucoidan induces ROS-dependent epigenetic modulation in cervical cancer HeLa cell.
Mustafa, S, Pawar, JS, Ghosh, I
International journal of biological macromolecules. 2021;:180-192
Abstract
Fucoidan is a sulfated polysaccharide obtained from marine algae and known for various pharmacological activities. In this study, we investigated the effect of Fucoidan on cell viability, redox balance, cytoskeletal component F-actin, HDAC inhibition, autophagy, and senescence phenomenon in human cervical cancer HeLa cell line in comparison to positive control suberoylanilide hydroxamic acid by flow cytometry, fluorescence microscopy, and western blotting. Our observations revealed that Fucoidan exposure induces cytotoxicity in HeLa cells via ROS and mitochondrial superoxide generation and loss of ATP. Colorimetrical studies suggested that Fucoidan impairs the function of HDAC expression. Fucoidan treatment also contributes to the change in the granularity of cells, senescence-associated heterochromatin foci formation that leads to senescence in HeLa cells. Moreover, we visualize that Fucoidan exhibits autophagosomes formation with monodansylcadaverine, and flow cytometry analysis by acridine orange further substantiates that Fucoidan triggers autophagy in HeLa cells. Additionally, the changes in the expression of proteins p21, p16, BECN1, and HDAC1 were seen as markers of senescence, autophagy, and HDAC inhibition by FACS and immunoblotting. Molecular docking study validates Fucoidan-HDAC1 association in corroboration with the experimental data. Collectively, these mechanistic studies demonstrated that Fucoidan could be a therapeutic molecule for targeting HDACs in cervical cancer.
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9.
Melatonin interferes with COVID-19 at several distinct ROS-related steps.
Camp, OG, Bai, D, Gonullu, DC, Nayak, N, Abu-Soud, HM
Journal of inorganic biochemistry. 2021;:111546
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Abstract
Recent studies have shown a correlation between COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and the distinct, exaggerated immune response titled "cytokine storm". This immune response leads to excessive production and accumulation of reactive oxygen species (ROS) that cause clinical signs characteristic of COVID-19 such as decreased oxygen saturation, alteration of hemoglobin properties, decreased nitric oxide (NO) bioavailability, vasoconstriction, elevated cytokines, cardiac and/or renal injury, enhanced D-dimer, leukocytosis, and an increased neutrophil to lymphocyte ratio. Particularly, neutrophil myeloperoxidase (MPO) is thought to be especially abundant and, as a result, contributes substantially to oxidative stress and the pathophysiology of COVID-19. Conversely, melatonin, a potent MPO inhibitor, has been noted for its anti-inflammatory, anti-oxidative, anti-apoptotic, and neuroprotective actions. Melatonin has been proposed as a safe therapeutic agent for COVID-19 recently, having been given with a US Food and Drug Administration emergency authorized cocktail, REGEN-COV2, for management of COVID-19 progression. This review distinctly highlights both how the destructive interactions of HOCl with tetrapyrrole rings may contribute to oxygen deficiency and hypoxia, vitamin B12 deficiency, NO deficiency, increased oxidative stress, and sleep disturbance, as well as how melatonin acts to prevent these events, thereby improving COVID-19 prognosis.
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10.
Shifting paradigms and novel players in Cys-based redox regulation and ROS signaling in plants - and where to go next.
Meyer, AJ, Dreyer, A, Ugalde, JM, Feitosa-Araujo, E, Dietz, KJ, Schwarzländer, M
Biological chemistry. 2021;(3):399-423
Abstract
Cys-based redox regulation was long regarded a major adjustment mechanism of photosynthesis and metabolism in plants, but in the recent years, its scope has broadened to most fundamental processes of plant life. Drivers of the recent surge in new insights into plant redox regulation have been the availability of the genome-scale information combined with technological advances such as quantitative redox proteomics and in vivo biosensing. Several unexpected findings have started to shift paradigms of redox regulation. Here, we elaborate on a selection of recent advancements, and pinpoint emerging areas and questions of redox biology in plants. We highlight the significance of (1) proactive H2O2 generation, (2) the chloroplast as a unique redox site, (3) specificity in thioredoxin complexity, (4) how to oxidize redox switches, (5) governance principles of the redox network, (6) glutathione peroxidase-like proteins, (7) ferroptosis, (8) oxidative protein folding in the ER for phytohormonal regulation, (9) the apoplast as an unchartered redox frontier, (10) redox regulation of respiration, (11) redox transitions in seed germination and (12) the mitochondria as potential new players in reductive stress safeguarding. Our emerging understanding in plants may serve as a blueprint to scrutinize principles of reactive oxygen and Cys-based redox regulation across organisms.