The Role of Reactive Species on Innate Immunity

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ROS generation is important for effective antimicrobial defense, which can prevent inflammation and excessive tissue injury.

“Therefore, ROS generation is important for effective antimicrobial defense, which can prevent inflammation and excessive tissue injury.”

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•O2− and hydrogen peroxide H2O2 are the two primary products of electron transport chain leakage.

“•O2− and hydrogen peroxide H2O2 are the two primary products of this leakage.”

• cites [8] Guo, 2013, Oxidative stress, mitochondrial damage and neurodegenerative diseases, Neural Regenerat. Res.Not checked yet

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Physiological levels of reactive species (ROS and RNS) are important in cellular signaling, but higher concentrations and prolonged exposure can fight infections by damaging important microbial biomolecules.

“Physiological levels of reactive species (ROS and RNS) are important in cellular signaling, but higher concentrations and prolonged exposure can fight infections by damaging important microbial biomolecules [6].”

• cites [6] Zucca, 2020, Lifestyle, oxidative stress, and antioxidants: Back and forth in the pathophysiology of chronic diseases, Front. Physiol. sourceNot checked yet

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OSCN− is harmless to cells in the human body but is cytotoxic to bacteria.

“OSCN− is harmless to cells in the human body but is cytotoxic to bacteria, so it has been widely investigated for its capabilities as an alternative antibiotic agent.”

Probably not a substantial claim: may not pass S3 (load-bearing).

In the recognition and response process of phagocytosis, reactive oxygen species ROS and reactive nitrogen species RNS are produced.

“In the recognition and response process of phagocytosis, reactive oxygen species ROS and reactive nitrogen species RNS are produced [5].”

• cites [5] Li, 2021, Reactive oxygen species in pathogen clearance: The killing mechanisms, the adaption response, and the side effects, Front. Microbiol. sourceNot checked yet

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The chemical changes mediated by reactive species RS are detrimental to cell function because they cause oxidation and nitration, altering the structures of cellular proteins, DNA, and lipids, and impairing their normal function.

“The chemical changes mediated by reactive species RS are detrimental to cell function because they cause oxidation and nitration, altering the structures of cellular proteins, DNA, and lipids, and impairing their normal function.”

• cites [7] Juan, 2022, The Nitration of Proteins, Lipids and DNA by Peroxynitrite Derivatives-Chemistry Involved and Biological Relevance, Stresses sourceNot checked yet

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In the event of bacterial and fungal infection, rapid generation of ROS is essential for host defense.

“In the event of bacterial and fungal infection, rapid generation of ROS is essential for host defense.”

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OSCN− is formed by peroxidase enzyme catalysis of hydrogen peroxide and thiocyanate.

“OSCN− is formed by peroxidase enzyme catalysis of hydrogen peroxide and thiocyanate: H2O2 + SCN− → OSCN− + H2O.”

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HOCl is a very reactive and oxidizing agent, can act as a chlorinating agent, and is the main strong oxidant generated by neutrophils in appreciable quantities.

“The reaction catalyzed by MPO is the oxidation of the Cl− anion by H2O2 to give hypochlorous acid HOCl, a very reactive and oxidizing agent, which can also act as a chlorinating agent and is the main strong oxidant generated by neutrophils in appreciable quantities [30].”

• cites [30] Davies, 2010, Myeloperoxidase-derived oxidation: Mechanisms of biological damage and its prevention, J. Clin. Biochem. Nutr. sourceNot checked yet

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Reactive species have a dual role: at physiological levels they are cellular signalers, and when there is an imbalance between their production and the antioxidant system they are involved in harmful biological processes such as protein denaturation and lipid peroxidation.

“These radical species have a dual role, at the physiological level they are cellular signalers, and when there is an imbalance between their production and the antioxidant system they are involved in several harmful biological processes, such as protein denaturation and lipid peroxidation.”

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•NO2 and •OH can modify proteins by reacting with tyrosine, tryptophan, cysteine, and methionine residues, promoting hydroxylation and nitration in peptides and proteins, impairing their normal function.

“•NO2 and •OH can modify proteins by reacting with tyrosine, tryptophan, cysteine, and methionine residues, promoting hydroxylation and nitration in peptides and proteins, impairing their normal function [7].”

• cites [7] Juan, 2022, The Nitration of Proteins, Lipids and DNA by Peroxynitrite Derivatives-Chemistry Involved and Biological Relevance, Stresses sourceNot checked yet

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The human body generates approximately 5 g ROS/day mainly from the leakage of the electron transport chain during oxidative phosphorylation, in the inner membrane of the mitochondrial matrix.

“The human body generates approximately 5 g ROS/day mainly from the leakage of the electron transport chain during oxidative phosphorylation, in the inner membrane of the mitochondrial matrix [8].”

• cites [8] Guo, 2013, Oxidative stress, mitochondrial damage and neurodegenerative diseases, Neural Regenerat. Res.Not checked yet

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H2O2 induces activation of nuclear factor NF-κβ, including tyrosine phosphorylation of IkB and activation of IKK.

“H2O2 induces activation of factor nuclear NF-κβ (the factor that controls DNA transcription), including tyrosine phosphorylation of IkB and activation of IKK [77].”

• cites [77] Schoonbroodt, 2000, Crucial role of the amino-terminal tyrosine residue 42 and the carboxyl-terminal PEST domain of IκBα in NF-κB activation by an oxidative stress, J. Immunol. sourceNot checked yet

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H2O2, in biochemical reactions, produces the hydroxyl radical •OH + −OH, highly reactive in the mitochondrial matrix.

“H2O2, in biochemical reactions, produces the hydroxyl radical •OH + −OH, highly reactive in the mitochondrial matrix [13].”

• cites [13] Juan, C.A., Pérez de la Lastra, J.M., Plou, F.J., and Pérez-Lebeña, E. (2021). The chemistry of reactive oxygen species (ROS) revisited: Outlining their role in biological macromolecules (DNA, lipids and proteins) and induced pathologies. Int. J. Mol. Sci., 22. sourceNot checked yet

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NOx is involved in pathogen clearance and the regulation of associated inflammation and plays an important role in physiological and pathological conditions, such as acute lung injury and bacterial or fungal infections.

“NOx is involved in pathogen clearance and the regulation of associated inflammation plays an important role in physiological and pathological conditions, such as acute lung injury and bacterial or fungal infections.”

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In addition to mitochondria, ROS are produced by a variety of enzymes such as NOx, xanthine oxidase, nitric oxide synthase NOS, and in other cell organelles such as the endoplasmic reticulum, peroxisomes, and cytosol.

“In addition to mitochondria, ROS are produced by a variety of enzymes such as NOx, xanthine oxidase, nitric oxide synthase NOS, and in other cell organelles such as the endoplasmic reticulum, peroxisomes, and cytosol [11].”

• cites [11] Snezhkina, A.V., Kudryavtseva, A.V., Kardymon, O.L., Savvateeva, M.V., Melnikova, N.V., Krasnov, G.S., and Dmitriev, A.A. (2019). ROS generation and antioxidant defense systems in normal and malignant cells. Oxidative Med. Cell. Longev., 2019. sourceNot checked yet

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H2O2 can modulate gene expression by epigenetic modification and activate transcription factors such as AP-1, NRF2, CREB, HSF1, HIF-1, TP53, NF-κβ, NOTCH, SP1, SCREB-1 and FOXO family.

“For example, H2O2 can also modulate genes expression by epigenetic modification and activate transcription factors such as AP-1, NRF2, CREB, HSF1, HIF-1, TP53, NF-κβ, NOTCH, SP1, SCREB-1 and FOXO family [14,15,16,17,18,19,20,21,22].”

• cites [14] Kunkel, 1986, Cloning the gene for an inherited human disorder—chronic granulomatous disease—On the basis of its chromosomal location, Nature sourceNot checked yet

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• cites [15] Dinauer, 1987, The glycoprotein encoded by the X-linked chronic granulomatous disease locus is a component of the neutrophil cytochrome b complex, Nature sourceNot checked yet

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• cites [16] Parkos, 1987, Purified cytochrome b from human granulocyte plasma membrane is comprised of two polypeptides with relative molecular weights of 91,000 and 22,000, J. Clin. Investig. sourceNot checked yet

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• cites [17] Segal, 1987, Absence of both cytochrome b−245 subunits from neutrophils in X-linked chronic granulomatous disease, Nature sourceNot checked yet

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• cites [18] Segal, 1985, Stimulated neutrophils from patients with autosomal recessive chronic granulomatous disease fail to phosphorylate a Mr-44,000 protein, Nature sourceNot checked yet

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• cites [19] Volpp, 1988, Two cytosolic neutrophil oxidase components absent in autosomal chronic granulomatous disease, Science sourceNot checked yet

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• cites [20] Wientjes, 1993, p40phox, a third cytosolic component of the activation complex of the NADPH oxidase to contain src homology 3 domains, Biochem J. sourceNot checked yet

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• cites [21] Abo, 1991, Purification and characterization of a third cytosolic component of the superoxide-generating NADPH oxidase of macrophages, J. Biol. Chem. sourceNot checked yet

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• cites [22] Roberts, 1999, Deficiency of the Hematopoietic Cell-Specific Rho Family GTPase Rac2 Is Characterized by Abnormalities in Neutrophil Function and Host Defense, Immunity sourceNot checked yet

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The most common sources of MPO are neutrophils, where the enzyme is located at the lysosomal level.

“The most common sources are neutrophils, where the enzyme is located at the lysosomal level [29].”

• cites [29] Hurst, 2012, What really happens in the neutrophil phagosome?, Free Radic. Biol. Med. sourceNot checked yet

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Superoxide anion •O2− is a by-product of mitochondrial respiration and a crucial element of the innate immune defense system.

“O2− anion is a by-product of mitochondrial respiration and a crucial element of the innate immune defense system.”

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SYK tyrosine kinase is also involved in innate immunity and non-immune functions.

“However, recent studies indicate that it is also involved in innate immunity and non-immune functions.”

• cites [96] Ruland, 2010, The SYK tyrosine kinase: A crucial player in diverse biological functions, Nat. Rev. Immunol. sourceNot checked yet

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NOx activation depends on increased Ca2+ concentration in the cytoplasm and, in some cases, on the generation of mitochondrial ROS.

“NOx activation depends on increased Ca2+ concentration in the cytoplasm and, in some cases, on the generation of mitochondrial ROS.”

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Neutrophil priming is the ability to increase superoxide anion and also improves adhesion, phagocytosis, cytokine secretion, leukotriene synthesis, degranulation, and bactericidal activity.

“Neutrophil “priming” is the ability to increase superoxide anion. In fact, this capacity is not limited to •O2− production, but also to improved adhesion, phagocytosis, cytokine secretion, leukotriene synthesis, degranulation, and, ultimately, bactericidal activity.”

• cites [83] Kobayashi, 2009, Role of neutrophils in innate immunity: A systems biology-level approach, Wiley Interdiscp. Rev. Syst. Biol. Med. sourceNot checked yet

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Neutrophils are particularly effective at killing invading bacteria by engulfing them, activating the respiratory burst, and generating lethal oxidative molecules such as hydrogen peroxide and hypochlorite ions, which kill most invading bacteria.

“neutrophils, which are particularly effective at killing invading bacteria by engulfing them, activating the respiratory burst, and generating lethal oxidative molecules such as hydrogen peroxide and hypochlorite ions, which kill most invading bacteria”

• cites [49] Slauch, 2011, How does the oxidative burst of macrophages kill bacteria? Still an open question, Mol. Microbiol. sourceNot checked yet

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Peroxynitrite ONOO- is a potent oxidizing and nitrating agent, with a short half-life of about 10−2 s.

“Peroxynitrite ONOO— is a potent oxidizing and nitrating agent, with a short half-life of about 10−2 s [26].”

• cites [26] Radi, 2001, Unraveling peroxynitrite formation in biological systems, Free Radic. Biol. Med. sourceNot checked yet

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•O2− is unstable and cannot pass through membranes but is rapidly converted to hydrogen peroxide H2O2, a membrane-permeable species.

“•O2− is unstable and cannot pass through membranes but is rapidly converted to hydrogen peroxide H2O2, a membrane-permeable specie [12].”

• cites [12] Juan, 2022, Chemistry of Hydrogen Peroxide Formation and Elimination in Mammalian Cells, and Its Role in Various Pathologies, Stresses sourceNot checked yet

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NOx catalyzes the reduction reaction of O2 to •O2− and/or H2O2 using NADPH as an electron donor and is located extracellularly.

“NOx catalyzes the reduction reaction of O2 to •O2− and/or H2O2 using NADPH as an electron donor and it is located extracellularly [88].”

• cites [88] Vermot, A., Petit-Härtlein, I., Smith, S.M., and Fieschi, F. (2021). NADPH oxidases (NOX): An overview from discovery, molecular mechanisms to physiology and pathology. Antioxidants, 10. sourceNot checked yet

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M1-like macrophages contain the lethal antimicrobial •NO and can kill neutrophil-resistant organisms.

“They contain the lethal antimicrobial •NO and can kill neutrophil-resistant organisms.”

• cites [49] Slauch, 2011, How does the oxidative burst of macrophages kill bacteria? Still an open question, Mol. Microbiol. sourceNot checked yet

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When neutrophils arrive at the site of invasion, they bind to invading bacteria and ingest them by phagocytosis, a process mediated by a metabolic pathway called a respiratory burst, which generates oxidative species such as H2O2 and hypochlorous acid HOCl.

“When neutrophils arrive at the site of invasion, they bind to invading bacteria and ingest them by phagocytosis, a process mediated by a metabolic pathway called a respiratory burst, which generates oxidative species such as H2O2 and hypochlorous acid HOCl [58].”

• cites [58] Ulfig, 2021, The effects of neutrophil-generated hypochlorous acid and other hypohalous acids on host and pathogens, Cell. Mol. Life Sci. sourceNot checked yet

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In the cytosolic SOD-Cu/Zn, SOD transforms •O2− to O2 reducing Cu(II) to Cu(I); another •O2− molecule causes the oxidation of Cu(I) to Cu(II), producing an H2O2 molecule.

“In the cytosolic SOD-Cu/Zn (it contains Cu and Zn in the catalytic site), SOD transforms the •O2− to O2 reducing Cu(II) to Cu(I). Another •O2− molecule causes the oxidation of Cu(I) to Cu(II), producing an H2O2 molecule.”

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Peptidoglycan recognition protein (PGRP) plays a role in the neutrophil killing of Gram-positive bacteria, inhibiting their growth.

“Peptidoglycan recognition protein (PGRP) plays a role in the neutrophil killing of Gram-positive bacteria [38], inhibiting their growth.”

• cites [38] DeLeo, 2009, Host defense and pathogenesis in Staphylococcus aureus infections, Infect. Dis. Clin. N. Am. sourceNot checked yet

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NETosis induction depends on ROS, the main source being NOx.

“Its induction depends on ROS, the main source being NOx [61].”

• cites [61] Azzouz, 2021, ROS induces NETosis by oxidizing DNA and initiating DNA repair, Cell Death Discov. sourceNot checked yet

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Following NOx activation, there is a rapid expenditure of O2 in neutrophils, and this mechanism is called the respiratory burst.

“Following NOx activation, there is a rapid expenditure of O2 in neutrophils, and this mechanism is called the “respiratory burst”.”

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H2O2 can trigger the release of high mobility group 1 protein from macrophages, with a follow-on increase of proinflammatory stimuli.

“H2O2 can trigger the release of high mobility group 1 protein from macrophages, follow-on increase of proinflammatory stimuli [78].”

• cites [78] Tang, 2007, Hydrogen peroxide stimulates macrophages and monocytes to actively release HMGB1, J. Leukoc. Biol. sourceNot checked yet

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Two forms of NETosis have been described: classical or suicidal NETosis, leading to cell death, and vital NETosis, where the cell retains its viability and many effector functions.

“Two forms of NETosis have now been described: classical or suicidal NETosis (leading to cell death), and vital NETosis, where the cell retains its viability and many of its effector functions [62].”

• cites [62] Huang, S.U.-S., and O’Sullivan, K.M. (2022). The expanding role of extracellular traps in inflammation and autoimmunity: The new players in casting dark webs. Int. J. Mol. Sci., 23. sourceNot checked yet

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Nitric oxide •NO is a ubiquitous cellular signaling molecule, found in a variety of cell types, including vascular endothelium, platelets, macrophages, and neuronal cells.

“Nitric oxide •NO is a ubiquitous cellular signaling molecule, found in a variety of cell types, including vascular endothelium, platelets, macrophages, and neuronal cells [23].”

• cites [23] Pacher, 2007, Nitric oxide and peroxynitrite in health and disease, Physiol. Rev. sourceNot checked yet

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The oxidation of the terminal guanidino-nitrogen atoms of L-arginine produces •NO.

“The oxidation of the terminal guanidino-nitrogen atoms of L-arginine produces •NO [25].”

• cites [25] Babu, 1999, l-arginine binding to nitric-oxide synthase: The role of H-bonds to the nonreactive guanidinium nitrogens, J. Biol. Chem. sourceNot checked yet

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Mitochondrial ROS are involved in NOx activation and in the induction of classical NETosis by various stimuli.

“Mitochondrial ROS are involved in NOx activation and in the induction of classical NETosis by various stimuli [63,64].”

• cites [63] Vorobjeva, 2017, Mitochondrial reactive oxygen species are involved in chemoattractant-induced oxidative burst and degranulation of human neutrophils in vitro, Eur. J. Cell Biol. sourceNot checked yet

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• cites [64] Vorobjeva, 2020, Mitochondrial permeability transition pore is involved in oxidative burst and NETosis of human neutrophils, Biochim. Biophys. Acta Mol. Basis Dis. sourceNot checked yet

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Tissues contain a variety of antimicrobial peptides, including defensins or cathelicidins, enzymes such as lysozyme that kill many Gram-positive bacteria, and iron-binding proteins such as hepcidin or haptoglobin that prevent bacterial growth by depriving bacteria of vital iron.

“These include antimicrobial peptides, such as defensins or cathelicidins, enzymes such as lysozyme that kill many Gram-positive bacteria, and iron-binding proteins such as hepcidin or haptoglobin that prevent the growth of bacteria by depriving them of vital iron [70].”

• cites [70] Shooshtarizadeh, 2010, Antimicrobial peptides present in mammalian skin and gut are multifunctional defence molecules, Curr. Pharm. Design sourceNot checked yet

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Superoxide anion •O2− is also produced in the mitochondrial matrix at complexes I to IV during the mitochondrial respiration process.

“Superoxide anion •O2− is also produced in the mitochondrial matrix at complexes I to IV during the mitochondrial respiration process [10].”

• cites [10] Turrens, 2003, Mitochondrial formation of reactive oxygen species, J. Physiol. sourceNot checked yet

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Myeloperoxidase MPO is a hydrogen peroxide oxidoreductase present in macrophages, in different biological fluids, and in different tissues.

“The enzyme myeloperoxidase MPO is a hydrogen peroxide oxidoreductase, present in macrophages, in different biological fluids (saliva, synovial fluid, and semen, among others), and in different tissues (heart, kidney, skin, liver, and placenta) [28].”

• cites [28] Tobler, A., and Koeffler, H.P. (1991). Blood Cell Biochemistry Volume 3, Springer.Not checked yet

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When macrophages encounter foreign molecules, they are activated by up-regulation of NF-kβ, which, together with JAK-STAT-induced inflammatory cytokines, increases iNOS expression and •NO production.

“When macrophages encounter foreign molecules, they are activated by up-regulation of NF-kβ, which, together with JAK-STAT-induced inflammatory cytokines, increases iNOS expression and •NO production [118].”

• cites [118] Yan, 2018, Role of the JAK/STAT signaling pathway in regulation of innate immunity in neuroinflammatory diseases, Clin. Immunol. sourceNot checked yet

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Reactive species RS are the heart of the innate immune system, and they are necessary for microbial lysis in infections that can affect mammals throughout their lives.

“In summary, reactive species RS are the heart of the innate immune system, and they are necessary for microbial lysis in infections that can affect mammals throughout their lives.”

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iNOS produces large amounts of •NO as a defense mechanism, is synthesized by several cell types in response to cytokine release, and is an important factor in the body's response to parasite attack, bacterial infection, and tumor growth.

“iNOS produces large amounts of •NO as a defense mechanism and is synthesized by several cell types in response to cytokine release and is an important factor in the body’s response to parasite attack, bacterial infection, and tumor growth [109].”

• cites [109] Cronin, 2019, The role of iron regulation in immunometabolism and immune-related disease, Front. Mol. Biosci. sourceNot checked yet

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Localized ROS production drives Treg lineage commitment, while their removal decreases the balance of Treg/T effector cells.

“Additionally, localized ROS production drives Treg lineage commitment, while their removal decreases the balance of Treg/T effector cells [102].”

• cites [102] Nathan, 2013, Beyond oxidative stress: An immunologist’s guide to reactive oxygen species, Nat. Rev. Immunol. sourceNot checked yet

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iNOS is the cause of septic shock and plays a role in many diseases of autoimmune etiology.

“It is the cause of septic shock and plays a role in many diseases of autoimmune etiology [110].”

• cites [110] Delano, 2016, The immune system’s role in sepsis progression, resolution, and long-term outcome, Immunol. Rev. sourceNot checked yet

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Oxidative burst is the rapid release of ROS from different cell types, especially macrophages and neutrophils, and it requires a 10-to-20-fold increase in oxygen consumption through NOx activity.

“Oxidative burst is the rapid release of ROS from different cell types, macrophages and neutrophils are especially implicated, and it requires a 10-to-20-fold increase in oxygen consumption through NOx activity.”

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The central source of H2O2 is enzymatically catalyzed by superoxide dismutation through the enzyme superoxide dismutase SOD, and SOD is the only enzyme that can clear •O2− and is present at the mitochondrial level, in the cytoplasm and extracellular space.

“The central source of H2O2 is enzymatically catalyzed by superoxide dismutation through the enzyme superoxide dismutase SOD. SOD is the only enzyme that can clear •O2− and it is present at the mitochondrial level as well, in the cytoplasm and extracellular space [99].”

• cites [99] Fridovich, 1978, The biology of oxygen radicals: The superoxide radical is an agent of oxygen toxicity; superoxide dismutases provide an important defense, Science sourceNot checked yet

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Mycobacterium tuberculosis is killed by •NO produced by macrophages, and the acidic environment of alveolar phagosomes favors generation of RNS from •NO, causing oxidation of the methionine residue of enzymes present in the bacteria.

“Mycobacterium tuberculosis is killed by •NO produced by macrophages, the acidic environment of alveolar phagosomes favors the generation of RNS from •NO, causing oxidation of the methionine residue of enzymes present in the bacteria [131].”

• cites [131] Schnappinger, 2009, Acid-Susceptible Mutants of, J. BacteriolNot checked yet

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Endothelial eNOS and neuronal nNOS are controlled by calmodulin and, under stimulation, the inducible isoform iNOS is involved in the immune response, producing large amounts of •NO as an immune defense mechanism.

“Endothelial eNOS and neuronal nNOS are controlled by calmodulin and, under stimulation, the inducible isoform of iNOS is involved in the immune response, producing large amounts of -NO as an immune defense mechanism [105].”

• cites [105] Xue, Q., Yan, Y., Zhang, R., and Xiong, H. (2018). Regulation of iNOS on immune cells and its role in diseases. Int. J. Mol. Sci., 19. sourceNot checked yet

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During an infective process, macrophages and other innate immunity cells especially produce ROS and RNS (•O2−, •NO and ONOO-), but excessive production can cause injury and toxicity to host cells.

“During an infective process, macrophages and other innate immunity cells especially produce ROS and RNS (•O2−, •NO and ONOO—), but excessive production can cause injury and toxicity to host cells [121].”

• cites [121] Herb, M., and Schramm, M. (2021). Functions of ROS in macrophages and antimicrobial immunity. Antioxidants, 10. sourceNot checked yet

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In adaptive immune regulation, •NO inhibits T helper 1 lymphocytes and promotes Th2 lymphocytes, which leads to humoral immunity and allergic responses.

“In adaptative immune regulation, •NO inhibits the lymphocytes T helper 1 (Th1 is a population characterized by the release of IL-2 and IFN-γ) and promotes Th2 lymphocytes, which leads to humoral immunity and allergic responses [113].”

• cites [113] Viallard, 1999, Th1 (IL-2, interferon-gamma (IFN-γ)) and Th2 (IL-10, IL-4) cytokine production by peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus (SLE), Clin. Exp. Immunol. sourceNot checked yet

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Peroxynitrite is synthesized from the reaction of •NO with •O2−.

“Peroxynitrite is synthesized from the reaction of •NO with •O2−, Figure 5 up.”

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All NOS isoforms contain the cofactor tetrahydrobiopterin THB, and in its absence NOS produces superoxide •O2− instead of •NO.

“All NOS isoforms contain the important cofactor tetrahydrobiopterin THB, and in its absence, NOS produces superoxide •O2− instead of •NO [107].”

• cites [107] 2009, Tetrahydrobiopterin, superoxide, and vascular dysfunction, Free Radic. Biol. Med. sourceNot checked yet

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H2O2 is not a free radical, but it is a very important reactive form, generating the •OH radical in the presence of metals such as iron (Fenton reaction).

“It is not a free radical, but it is a very important reactive form, generating the •OH radical in the presence of metals such as iron (Fenton reaction).”

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In the skin, •NO provides a protective barrier against micro-organisms and regulates melanogenesis and the formation of erythema that can occur from exposure to ultraviolet UV light.

“In the skin, •NO provides a protective barrier against micro-organisms, and regulates melanogenesis and the formation of erythema that can occur from exposure to ultraviolet UV light [120].”

• cites [120] Adler, B.L., and Friedman, A.J. (2015). Nitric oxide therapy for dermatologic disease. Future Sci. OA, 1. sourceNot checked yet

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The role of •NO in macrophage reprogramming has been known for a long time, but current models greatly underestimate its importance.

“The role of •NO in macrophage reprogramming has been known for a long time, but current models greatly underestimate its importance [125].”

• cites [125] Palmieri, E.M., McGinity, C., Wink, D.A., and McVicar, D.W. (2020). Nitric Oxide in Macrophage Immunometabolism: Hiding in Plain Sight. Metabolites, 10. sourceNot checked yet

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SOD is composed of three isoforms: SOD1 (Cu/Zn-SOD, the predominant •O2− scavenger, localized in the cytoplasm), SOD2 (Mn-SOD, in the mitochondrial intermembrane space, nucleus, and lysosomes) and SOD3 (Cu/Zn-SOD, localized in the mitochondrion and extracellular matrix).

“It is composed of three isoforms, SOD1 (Cu/Zn-SOD is the predominant •O2− scavenger and is localized in the cytoplasm), SOD2 (Mn-SOD, in the mitochondrial intermembrane space, nucleus, and lysosomes) and SOD3 (Cu/Zn-SOD, is localized in the mitochondrion and extracellular matrix) [100].”

• cites [100] Trachootham, 2008, Redox regulation of cell survival, Antioxid. Redox Signal. sourceNot checked yet

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In lymphocytes, the half-life of H2O2 is 1 ms while that of the anion •O2− is 1 μs.

“It has been estimated that, in lymphocytes, the half-life of the H2O2 is 1 ms while that of the anion •O2− is 1 µs [98].”

• cites [98] Chen, X., Song, M., Zhang, B., and Zhang, Y. (2016). Reactive oxygen species regulate T cell immune response in the tumor microenvironment. Oxid. Med. Cell. Longev., 2016. sourceNot checked yet

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Alveolar macrophages typically produce lower levels of ROS than neutrophils and may require activation to exhibit their bactericidal properties.

“The oxidative burst in phagocytes is commonly associated with bacterial killing, but in the case of alveolar macrophages, they typically produce lower levels of ROS than neutrophils and may require their activation to exhibit their bactericidal properties.”

• cites [101] Forman, 2002, Reactive oxygen species and cell signaling: Respiratory burst in macrophage signaling, Am. J. Respir. Crit. Care Med. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

•NO synthesis has been identified in mammals, fish, birds, invertebrates, and bacteria, and there are several NOS isoenzymes.

“•NO synthesis has been identified in mammals, fish, birds, invertebrates, and bacteria and there are several NOS isoenzymes [104].”

• cites [104] Richard, 1994, Nitric oxide synthase in mammals, Biochem. J. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Nitric oxide synthases NOS are a family of enzymes that catalyze the production of nitric oxide radical •NO from the amino acid L-arginine.

“Nitric oxide synthases NOS are a family of enzymes that catalyze the production of nitric oxide radical •NO from the amino acid L-arginine [103].”

• cites [103] Sessa, 2012, Nitric oxide synthases: Regulation and function, Eur. Heart J. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The hydroxyl radical •OH, the most powerful ROS oxidant, is formed during the Haber-Weiss reaction, by the Fenton reaction or by decomposition of peroxynitrite, and has a very short half-life (10−9 s) and high reactivity.

“The hydroxyl radical •OH, the most powerful ROS oxidant, is formed during the Haber–Weiss reaction, by the Fenton reaction or by decomposition of peroxynitrite, and has a very short half-life (10−9 s) and high reactivity.”

May combine two claims.

Induction of iNOS usually occurs in the presence of an oxidative environment, which produces peroxynitrite when •NO reacts with superoxide, leading to cellular toxicity.

“Induction of iNOS usually occurs in the presence of an oxidative environment, which produces peroxynitrite when •NO reacts with superoxide [115], leading to cellular toxicity.”

• cites [115] Gerdes, 2020, Modulation of peroxynitrite produced via mitochondrial nitric oxide synthesis during Ca2+ and succinate-induced oxidative stress in cardiac isolated mitochondria, Biochim. Biophys. Acta Bioenerg. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Microbial clearance depends on •NO concentration, which in turn depends on NOS activity and the availability of arginine in phagosomes.

“Microbial clearance depends on •NO concentration [127], which in turn depends on NOS activity and the availability of arginine in phagosomes.”

• cites [127] Raulli, 2002, Antimicrobial properties of nitric oxide using diazeniumdiolates as the nitric oxide donor, Recent Res. Dev. MicrobiolNot checked yet

  Not checked in the free run.

May combine two claims.

•NO plays an important role during inflammation and is a potential target for therapeutic development in inflammatory diseases.

“In summary, •NO plays an important role during inflammation and is a potential target for therapeutic development in inflammatory diseases [124].”

• cites [124] Kobayashi, 2010, The regulatory role of nitric oxide in proinflammatory cytokine expression during the induction and resolution of inflammation, J. Leukoc. Biol. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The iNOS and nNOS isoforms are soluble and predominantly found in the cytosol, while eNOS is membrane-associated.

“The iNOS and nNOS isoforms are soluble and predominantly they are found in the cytosol, while eNOS is membrane-associated [108].”

• cites [108] Oess, 2006, Subcellular targeting and trafficking of nitric oxide synthases, Biochem. J. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

H2O2 forms naturally in living organisms and its attributed physiological role is the capability to induce bacterial killing.

“It is known that H2O2 forms naturally in living organisms and its attributed physiological role is the capability to induce bacterial killing.”

May combine two claims.

NADPH and superoxide act synergistically in phagosomes to scavenge •NO and increase peroxynitrite levels, which in an acidic environment contribute to the "cauldron effect".

“Nicotinamide adenine dinucleotide phosphate NADPH and superoxide act synergistically in phagosomes to scavenge •NO and increase peroxynitrite levels which, in an acidic environment, contribute to the “cauldron effect” [128].”

• cites [128] Shreshtha, 2018, Nitric Oxide: It’s Role in Immunity, J.Clin. Diagn. Res.Not checked yet

  Not checked in the free run.

May combine two claims.

Elevated levels of •NO cause bacterial lysis through nitrosation of thiol groups of proteins responsible for formation of pores in the cell membrane, preventing bacteria from leaving the infected cell and preventing spread of infection.

“Elevated levels of •NO cause bacterial lysis through nitrosation of the thiol groups of proteins responsible for the formation of pores in the cell membrane, thus preventing the bacteria from leaving the infected cell and preventing the spread of infection to other cells [132].”

• cites [132] Torres, 2004, Toll-like receptor 2 is required for optimal control of Listeria monocytogenes infection, Infect. Immun. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Nitrosated integrases and nucleocapsid proteins are unable to bind DNA and cannot function as topoisomerases, preventing integration of viral DNA into host cell DNA.

“Examples of these proteins are integrases and nucleocapsid proteins, and after being nitrosated they are unable to bind to DNA and cannot function as topoisomerases, thus preventing the integration of viral DNA into host cell DNA [128].”

• cites [128] Shreshtha, 2018, Nitric Oxide: It’s Role in Immunity, J.Clin. Diagn. Res.Not checked yet

  Not checked in the free run.

May combine two claims.

HOI formation is usually insignificant due to low plasma levels of I−, although it is generated rapidly and varies significantly with diet.

“HOI formation is usually insignificant due to the low plasma levels of I−, although it is generated rapidly, varying significantly with diet (lower levels are detected in vegans than in vegetarians).”

• cites [169] Leung, 2011, Iodine status and thyroid function of Boston-area vegetarians and vegans, J. Clin. Endocrinol. Metab. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

•NO is involved in immunity against Giardia intestinalis, and a strong increase in •NO and its derivatives was observed among patients infected with this parasite.

“•NO is also involved in the immunity provided against Giardia intestinalis, in the study by Zarebavani et al., 2017, a strong increase in •NO and its derivatives was observed among patients infected with this parasite [140].”

• cites [140] Zarebavani, 2017, Significance of nitric oxide level in giardiasis, Clin. Lab. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

In vitro, one million stimulated neutrophils can produce 0.1 μM of HOCl and this concentration can kill 15 million Escherichia coli bacteria in less than 5 min.

“It has been estimated that, in vitro, one million stimulated neutrophils can produce 0.1 μM of HOCl and this concentration can kill 15 million Escherichia coli bacteria in less than 5 min [151].”

• cites [151] McKenna, 1988, The inhibition of bacterial growth by hypochlorous acid. Possible role in the bactericidal activity of phagocytes, Biochem. J. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

HOCl/OCl− remains the preferred active microbicidal agent in pool disinfection.

“In recent years, the use of sodium dichloroisocyanurate as an organic precursor to HOCl has emerged, but HOCl/OCl− remains the preferred active microbicidal agent [166].”

• cites [166] Khazaei, 2020, Anchoring N-Halo (sodium dichloroisocyanurate) on the nano-Fe3O4 surface as “chlorine reservoir”: Antibacterial properties and wastewater treatment, Arab. J. Chem. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Neutrophil activation products myeloperoxidase, neutrophil elastase, and interleukin-8 were strongly elevated in the blood of patients with hantavirus HFRS and correlate positively with renal dysfunction.

“Tomas Strandin et al., in 2018, found that neutrophil activation products: myeloperoxidase, and neutrophil elastase, along with interleukin-8 (the major neutrophil chemotactic factor in humans), were strongly elevated in the blood of patients with hantavirus HFRS, factors that correlate positively with renal dysfunction [162].”

• cites [162] Strandin, 2018, Neutrophil activation in acute hemorrhagic fever with renal syndrome is mediated by hantavirus-infected microvascular endothelial cells, Front. Immunol. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

MPO is expressed in neutrophil granulocytes and produces hypohalous acids to carry out its antimicrobial activity.

“The enzyme myeloperoxidase MPO is expressed in neutrophil granulocytes (a subtype of white blood cells) and produces hypohalous acids to carry out its antimicrobial activity [146].”

• cites [146] Klebanoff, 2005, Myeloperoxidase: Friend and foe, J. Leukoc. Biol. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Reactive oxygen species and myeloperoxidase are implicated in clinical deterioration and mortality in COVID-19.

“A similar idea is maintained by Pravin T Goud et al., in developing an analysis implicating reactive oxygen species and myeloperoxidase in clinical deterioration and mortality in COVID-19 [164].”

• cites [164] Goud, 2021, A multiple-hit hypothesis involving reactive oxygen species and myeloperoxidase explains clinical deterioration and fatality in COVID-19, Int. J. Biol. Sci. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

•NO's dual action makes it a contributing player in pathophysiology and makes development of effective treatments for neurodegenerative diseases particularly difficult.

“This dual action makes it a contributing player in pathophysiology, but also makes the development of effective treatments for neurodegenerative diseases particularly difficult [141,142,143,144,145].”

• cites [141] Beal, 1997, Increased 3-nitrotyrosine in both sporadic and familial amyotrophic lateral sclerosis, Ann. Neurol. Off. J. Am. Neurol. Assoc. Child Neurol. Soc.Not checked yet

  Not checked in the free run.

• cites [142] Ferrante, 1997, Increased 3-nitrotyrosine and oxidative damage in mice with a human copper/zinc superoxide dismutase mutation, Ann. Neurol. Off. J. Am. Neurol. Assoc. Child Neurol. Soc.Not checked yet

  Not checked in the free run.

• cites [143] Liberatore, 1999, Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease, Nat. Med. sourceNot checked yet

  Not checked in the free run.

• cites [144] Schulz, 1995, Inhibition of neuronal nitric oxide synthase by 7-nitroindazole protects against MPTP-induced neurotoxicity in mice, J. Neurochem. sourceNot checked yet

  Not checked in the free run.

• cites [145] Yoshida, 1994, The NOS inhibitor, 7-nitroindazole, decreases focal infarct volume but not the response to topical acetylcholine in pial vessels, J. Cerebral Blood Flow Metab. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

•NO inhibits Toxoplasma infectivity and prevents disease progression to other systems, especially the central nervous system.

“as well as inhibiting Toxoplasma infectivity and preventing disease progression to other systems, especially the central nervous system CNS [139].”

• cites [139] Rozenfeld, 2003, Soluble factors released by Toxoplasma gondii-infected astrocytes down-modulate nitric oxide production by gamma interferon-activated microglia and prevent neuronal degeneration, Infect. Immun. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

During oxidative burst, cells convert O2 to •O2 using NOx and then to H2O2 through superoxide dismutase.

“During the oxidative burst process, cells utilize O2 and convert it to •O2 using the mitochondrial-membrane–bound enzyme NOx [148] and after to H2O2 through a family of enzymes called superoxide dismutase SOD [149].”

• cites [148] Panday, 2015, NADPH oxidases: An overview from structure to innate immunity-associated pathologies, Cell. Mol. Immunol. sourceNot checked yet

  Not checked in the free run.

• cites [149] Islam, 2021, Superoxide dismutase: An updated review on its health benefits and industrial applications, Crit. Rev. Food Sci. Nutr. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

The relative specificity constants for chloride, bromide, and thiocyanate are 1:60:730, respectively, with thiocyanate being the most favoured substrate for MPO.

“The relative specificity constants for chloride, bromide, and thiocyanate are 1:60:730, respectively, with thiocyanate being the most favoured substrate for MPO.”

• cites [170] Senthilmohan, 2006, Bromination and chlorination reactions of myeloperoxidase at physiological concentrations of bromide and chloride, Arch. Biochem. Biophys. sourceNot checked yet

  Not checked in the free run.

• cites [171] Whitehouse, 1997, Thiocyanate and chloride as competing substrates for myeloperoxidase, Biochem. J. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Thiocyanate is present at levels of 20-120 μM in serum and extracellular fluid and 800-806 mM in saliva, with the wide range attributed to smoking.

“Thiocyanate is present at levels of 20-120 µM in serum and extracellular fluid and 800–806 mM in saliva (the wide range is attributed to smoking) [167,168].”

• cites [167] Thomas, E., Pruitt, K., and Tenovuo, J. (1985). The Lactoperoxidase System, Chemsistry and Biological Significance, CRC Press.Not checked yet

  Not checked in the free run.

• cites [168] Klebanoff, 1980, Oxygen metabolism and the toxic properties of phagocytes, Ann. Intern. Med. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

HOBr is usually formed at low concentrations, is pH dependent, and can be improved by food supplement.

“HOBr is usually formed at low concentrations, it is pH dependent, and also can be improved by food supplement [169].”

• cites [169] Leung, 2011, Iodine status and thyroid function of Boston-area vegetarians and vegans, J. Clin. Endocrinol. Metab. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

HOCl is a weak halogen-based acid and a powerful chlorination agent, containing one labile proton (pKa = 7.46) that dictates co-existence between acid and conjugated base under physiological conditions at near equimolar ratio.

“HOCl is a weak halogen-based acid and a powerful chlorination agent, that contains one labile proton (pKa = 7.46) dictating the co-existence between acid and conjugated base under physiological conditions at near equimolar ratio.”

• cites [157] Snell, 2022, Hypochlorous Acid: From Innate Immune Factor and Environmental Toxicant to Chemopreventive Agent Targeting Solar UV-Induced Skin Cancer, Front. Oncol. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

At physiological pH, plasma ion concentrations are ~100 mM Cl−, 20-100 μM Br−, <1 μM I−, 20-100 μM SCN−, and MPO primarily generates HOCl and HOSCN.

“At physiological pH, plasma ion concentrations are ~100 mM Cl−, 20–100 μM Br−, <1 μM I−, 20–100 μM SCN−, and MPO primarily generates HOCl and HOSCN.”

• cites [169] Leung, 2011, Iodine status and thyroid function of Boston-area vegetarians and vegans, J. Clin. Endocrinol. Metab. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Taurine and HOCl form taurine chloramine, a more stable and weaker oxidant.

“Taurine present in human plasma and cells and HOCl form taurine chloramine (-O3SCH2CH2NHCl), a more stable and weaker oxidant [154].”

• cites [154] Park, 2004, Taurine and its chloramine: Modulators of immunity, Neurochem. Res. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

HOCl and its conjugated base HOCl/OCl− represent a potent oxidizing redox system under physiological conditions and serve as an endogenous microbicidal agent generated by myeloid lineage-derived effector cells.

“HOCl and its conjugated base HOCl/OCl− represent a potent oxidizing redox system [E0′ = +0.9 (OCl-); E0′ = +1.48 V (HOCl)] under physiological conditions, and serves as an endogenous microbicidal agent, generated by myeloid lineage-derived effector cells (including neutrophils) [157].”

• cites [157] Snell, 2022, Hypochlorous Acid: From Innate Immune Factor and Environmental Toxicant to Chemopreventive Agent Targeting Solar UV-Induced Skin Cancer, Front. Oncol. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

HOCl reacts rapidly with several biological molecules, particularly thiols, thioethers, heme proteins, and amino groups, and can cause tissue injury.

“HOCl reacts rapidly with several biological molecules, particularly those with thiols, thioethers, heme proteins, and amino groups, and can cause tissue injury [152].”

• cites [152] Storkey, 2014, Reevaluation of the rate constants for the reaction of hypochlorous acid (HOCl) with cysteine, methionine, and peptide derivatives using a new competition kinetic approach, Free Radic. Biol. Med. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Influenza virus was inactivated by MPO treatment of human polymorphonuclear leukocytes in the presence of H2O2, and viral protein modification occurred in all major proteins, including inner envelope proteins.

“On the treatment of viral infections, Yamamoto et al., 1991, show already at that time that the influenza virus IFV was inactivated by MPO-myeloperoxidase treatment of human polymorphonuclear leukocytes in the presence of H2O2 and that viral protein modification occurred in all major proteins, including the inner envelope proteins [161].”

• cites [161] Yamamoto, 1991, Virucidal activity and viral protein modification by myeloperoxidase: A candidate for defense factor of human polymorphonuclear leukocytes against influenza virus infection, J. Infect. Dis. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

OxyR contributes to the virulence of E. coli and P. aeruginosa.

“For instance, OxyR contributes to the virulence of E. coli and P. aeruginosa.”

• cites [196] Garai, 2011, Effectors of Salmonella pathogenicity island 2: An island crucial to the life of Salmonella, Virulence sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing). May combine two claims.

The human cathelicidin may activate ROS/NF-κβ/IL-6 and regulate oxidation signaling in cardiovascular diseases like atherosclerosis.

“Other authors have suggested the role of the human cathelicidin on the activation of ROS/NF-κβ/IL-6 and propose that it could regulate oxidation signaling in cardiovascular diseases like atherosclerosis [184].”

• cites [184] Dong, X., Wu, D., Zhang, Y., Jia, L., Pan, X., Sun, J., and Pan, L.-L. (2020). Cathelicidin modulates vascular smooth muscle cell phenotypic switching through ROS/IL-6 pathway. Antioxidants, 9. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

These peroxidases catalyze the oxidation of halides and pseudohalides by H2O2, resulting in potent oxidizing agents that exhibit antimicrobial activity in vitro and in vivo by damaging vital structural and functional components of microorganisms.

“These peroxidases catalyze the oxidation of halides (Cl−, Br−, I−) and pseudohalides (SCN−) by H2O2, resulting in potent oxidizing agents that exhibit antimicrobial activity in vitro and in vivo, as they damage vital structural and functional components of microorganisms.”

• cites [172] Zederbauer, 2006, Active site structure and catalytic mechanisms of human peroxidases, Arch. Biochem. Biophys. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

It has been proposed that the primary action of cathelicidins is to induce the production of ROS that damages bacterial molecules, resulting in slowed growth or cell death.

“It has been proposed that the primary action of cathelicidins is to induce the production of ROS that damages bacterial molecules, resulting in slowed growth or cell death [182].”

• cites [182] Kao, 2019, Cathelicidin peptides restrict bacterial growth via membrane perturbation and induction of reactive oxygen species, MBioNot checked yet

  Not checked in the free run.

May combine two claims.

The percentage of MPO-induced H2O2 loss in the presence of 100 mM Cl− doubled when 100 μM thiocyanate was added and was maximal at 1 mM thiocyanate.

“The percentage of MPO-induced H2O2 loss in the presence of 100 mM Cl− doubled when 100 µM thiocyanate was added and was maximal at 1 mM thiocyanate.”

• cites [170] Senthilmohan, 2006, Bromination and chlorination reactions of myeloperoxidase at physiological concentrations of bromide and chloride, Arch. Biochem. Biophys. sourceNot checked yet

  Not checked in the free run.

• cites [171] Whitehouse, 1997, Thiocyanate and chloride as competing substrates for myeloperoxidase, Biochem. J. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

LL-37 stimulates the generation of ROS in neutrophils, mediated by a flavoenzyme (most probably NOx) and via an increase in intracellular Ca2+ concentrations.

“LL-37 stimulates the generation of ROS in neutrophils and this process is mediated by a flavoenzyme (most probably NOx) and via an increase in intracellular Ca2+ concentrations [183].”

• cites [183] Yang, 2020, Significance of LL-37 on immunomodulation and disease outcome, BioMed Res. Int.Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

The lack of the LPO/H2O2/SCN− pathway in nasal and ocular human secretions may explain the survival, proliferation, and environmental dissemination of some bacteria and viruses.

“Several studies maintain that the lack of the LPO/H2O2/SCN− pathway in nasal and ocular human secretions may explain the survival, proliferation, and environmental dissemination of some bacteria and viruses [173].”

• cites [173] Cegolon, 2020, Nasal disinfection for the prevention and control of COVID-19: A scoping review on potential chemo-preventive agents, Int. J. Hyg. Environ. Health sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Coprisin, a defensin-like 43-mer peptide with three disulfide bonds, has been suggested to be a crucial participant in reactive oxygen species, especially hydroxyl radicals.

“Coprisin, a defensin-like 43-mer peptide with three disulfide bonds [187], has been suggested to be a crucial participant in reactive oxygen species (ROS), especially hydroxyl radicals (•OH) [188].”

• cites [187] Lee, 2014, Structure-activity relationships of the intramolecular disulfide bonds in coprisin, a defensin from the dung beetle, BMB Rep. sourceNot checked yet

  Not checked in the free run.

• cites [188] Lee, 2012, Coprisin-induced antifungal effects in Candida albicans correlate with apoptotic mechanisms, Free Radic. Biol. Med. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Cathelicidins are cationic and amphiphilic peptides consisting of 12-97 amino acids, found in humans, other vertebrates and some species of fish.

“Cathelicidins, first discovered in bovine neutrophils by Zanetti et al. in the early 1990s, are cationic and amphiphilic peptides consisting of 12–97 amino acids, found in humans, other vertebrates and some species of fish [179].”

• cites [179] Zanetti, 2002, Cathelicidin peptides as candidates for a novel class of antimicrobials, Curr. Pharm. Design sourceNot checked yet

  Not checked in the free run.

May combine two claims.

ROS response is under the control of master regulators and transcription factors such as OxyR, PerR, OhrR, and SoxRS, which can be stimulated by direct oxidation of their sensor proteins and then regulate the bacterial comeback appropriately.

“can be stimulated by direct oxidation of their sensor proteins and then regulating the bacterial comeback appropriately [192].”

• cites [191] Juttukonda, 2019, Acinetobacter baumannii OxyR Regulates the Transcriptional Response to Hydrogen Peroxide, Infect. Immun. sourceNot checked yet

  Not checked in the free run.

• cites [192] Chiang, 2012, Regulators of oxidative stress response genes in Escherichia coli and their functional conservation in bacteria, Arch. Biochem. Biophys. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Cathelicidins and defensins are a family of antimicrobial peptides that show a wide spectrum of antimicrobial activity against bacteria, enveloped viruses, and fungi.

“Cathelicidins and defensins are a family of antimicrobial peptides that show a wide spectrum of antimicrobial activity against bacteria, enveloped viruses, and fungi [176].”

• cites [176] Otazo-Pérez, A., Asensio-Calavia, P., González-Acosta, S., Baca-González, V., López, M.R., Morales-delaNuez, A., and Pérez de la Lastra, J.M. (2022). Antimicrobial Activity of Cathelicidin-Derived Peptide from the Iberian Mole Talpa occidentalis. Vaccines, 10. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Under non-lethal levels of ROS, certain pathogens have evolved mechanisms to adapt and thrive, and may even use ROS as a cornerstone for increasing tolerance and resistance to antibiotics.

“However, they are a double-edged sword and must be regulated with care, as under non-lethal levels of ROS, certain pathogens have evolved mechanisms to adapt and thrive, and may even use ROS as a cornerstone for increasing tolerance and resistance to antibiotics.”

• cites [5] Li, 2021, Reactive oxygen species in pathogen clearance: The killing mechanisms, the adaption response, and the side effects, Front. Microbiol. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

SCN− is not considered a biologically functional ion, but it plays an important role as a substrate for peroxidase enzymes, which form an essential part of innate defense, including LPO, SPO, MPO and EPO.

“In general, SCN− is not considered a biologically functional ion, but it plays an important role as a substrate for peroxidase enzymes, which form an essential part of innate defense, including lactoperoxidase LPO, salivary peroxidase SPO, myeloperoxidase MPO and eosinophilic peroxidase EPO [172].”

• cites [172] Zederbauer, 2006, Active site structure and catalytic mechanisms of human peroxidases, Arch. Biochem. Biophys. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

AMPs are an important component of the innate immune system in all organisms, including plants, animals, and humans, providing a rapid and non-specific response to pathogens.

“Antimicrobial peptides AMPs are an important component of the innate immune system in all organisms, including plants, animals, and humans, providing a rapid and non-specific response to pathogens [175].”

• cites [175] Boto, A., Pérez de la Lastra, J.M., and González, C.C. (2018). The road from host-defense peptides to a new generation of antimicrobial drugs. Molecules, 23. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

The cathelicidin family shares primary sequence homology with the cystatins, of the cysteine proteinase inhibitor family, although amino acid residues considered important in these cystatins are often missing.

“The cathelicidins family shares primary sequence homology with the cystatins, of the cysteine proteinase inhibitor family, although amino acid residues considered important in these cystatins are often missing [180,181].”

• cites [180] Shinnar, 2003, Cathelicidin family of antimicrobial peptides: Proteolytic processing and protease resistance, Bioorg. Chem. sourceNot checked yet

  Not checked in the free run.

• cites [181] Zaiou, 2003, Antimicrobial and protease inhibitory functions of the human cathelicidin (hCAP18/LL-37) prosequence, J. Investig. Dermatol. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Accumulation of ROS and mitochondrial membrane damage may be key for Papiliocin, a novel cecropin-like AMP able to induce fungal apoptosis.

“Similarly, it has also been suggested that accumulation of ROS and mitochondrial membrane damage may be key for Papiliocin, a novel cecropin-like AMP able to induce fungal apoptosis [186].”

• cites [186] Kim, 2021, Papiliocin, an antimicrobial peptide, rescues hyperoxia-induced intestinal injury, Int. J. Ind. Entomol.Not checked yet

  Not checked in the free run.

May combine two claims.

ROS generated by phagocytes converts thiosulphate to tetrathionate, which can be used as a respiratory electron sink by S. typhimurium, thus overcoming native microbiota.

“ROS generated by phagocytes converts thiosulphate to tetrathionate, which can be used as a respiratory electron sink by S. typhimurium, thus overcoming native microbiota [197].”

• cites [197] Sperandio, 2016, Interactions between the microbiota and pathogenic bacteria in the gut, Nature sourceNot checked yet

  Not checked in the free run.

May combine two claims.

At 100 μM thiocyanate, roughly 50% of peroxide is transformed into hypothiocyanite, and the quantity of hypohalogenic acid production was equal to the sum of the individual rates obtained when each negative ion was present alone.

“At 100 µM thiocyanate, roughly 50% of peroxide is transformed into hypothiocyanite, and the quantity of hypohalogenic acid production was equal to the sum of the individual rates obtained when each of these negative ions was present alone.”

• cites [170] Senthilmohan, 2006, Bromination and chlorination reactions of myeloperoxidase at physiological concentrations of bromide and chloride, Arch. Biochem. Biophys. sourceNot checked yet

  Not checked in the free run.

• cites [171] Whitehouse, 1997, Thiocyanate and chloride as competing substrates for myeloperoxidase, Biochem. J. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Ultimately, reactive species play an important and positive role in human health and innate immunity.

“Ultimately, reactive species play an important and positive role in human health and innate immunity.”

May combine two claims.

The innate immune system is the first line of defense against infection and is characterised by a rapid, non-specific response through the production of reactive species (oxygen, nitrogen, and chlorine), which are widely distributed in effector cells and are biocidal for pathogens.

“The innate immune system is the first line of defense against infection and is characterised by a rapid, non-specific response through the production of reactive species (oxygen, nitrogen, and chlorine), which are widely distributed in effector cells (neutrophils, macrophages, etc.) and are biocidal for pathogens.”

Probably not a substantial claim: may not pass S4 (based).

Deficiency of these antimicrobial agents is associated with severe recurrent infections and immunocompromised diseases, such as chronic granulomatous disease.

“Deficiency of these antimicrobial agents is associated with severe recurrent infections and immunocompromised diseases, such as chronic granulomatous disease.”