Adaptive Immune System – The adaptive immune system, also known as the acquired immune system or specific immune system, is a subsystem of the overall immune system that is composed of highly specialized, systemic cells and processes that eliminate pathogens or prevent their growth.
Advanced Glycation End-products / AGE’s – Advanced glycation end products (AGEs) are proteins or lipids that become glycated as a result of exposure to sugars. Sources of AGEs include high-temperature food processing and preparation, but also endogenous (internal) production caused by high dietary sugar intake, particularly from high fructose corn syrup. AGEs are toxic and have been shown to cause oxidative stress, mitochondrial dysfunction, insulin resistance, fibrosis, impairment of the transcriptional activity of the nuclear factor erythroid 2-related factor 2 (Nrf2) and organ damage.
Aldose Reductase In enzymology, aldose reductase (or aldehyde reductase) (EC 220.127.116.11) is a cytosolic NADPH-dependent oxidoreductase that catalyzes the reduction of a variety of aldehydes and carbonyls, including monosaccharides. It is primarily known for catalyzing the reduction of glucose to sorbitol, the first step in polyol pathway of glucose metabolism. Aldose Reductase is involved in dopamine synthesis. The reduction of aldose reductase has been linked to the downregulation of antioxidant enzymes leading to increase in oxidative stress.
Alpha Lipoic Acid – Lipoic acid (LA), also known as α-lipoic acid and alpha lipoic acid (ALA) and thioctic acid is an organosulfur compound derived from octanoic acid. Lipoic acid decreases lipid peroxidation and oxidative damage of proteins and is also responsible for improving non-enzymatic antioxidant capacity.
AMPK – 5′ AMP-activated protein kinase or AMPK or 5′ adenosine monophosphate-activated protein kinase is an enzyme (EC 18.104.22.168) that plays a role in cellular energy homeostasis. It belongs to a highly conserved eukaryotic protein family and its orthologues are SNF1 and SnRK1 in yeast and plants, respectively. AMPK is responsible for protecting the cells from oxidative stress as it elevates NAD+ intracellularly and through autophagic restoration.
Antioxidant Response Element / ARE – Hormone response element : 1- estrogen response elements (EREs) and 2- androgen response elements (AREs). Response elements are short sequences of DNA within a gene promoter region that are able to bind specific transcription factors and regulate transcription of genes. Under conditions of stress, a transcription activator protein binds to the response element and stimulates transcription. If the same response element sequence is located in the control regions of different genes, then these genes will be activated by the same stimuli, thus producing a coordinated response.
Advanced Oxidative Protein Products / AOPP’s. AOPPs are considered potential biomarkers for oxidative stress. They are oxidative byproducts produced during a state of redox imbalance.
Astaxanthin – Astaxanthin belongs to a larger class of chemical compounds known as terpenes (in Asthaxanthin’s case, a tetraterpenoid); terpenes are built from five carbon precursors; isopentenyl diphosphate (or IPP) and dimethylallyl diphosphate (or DMAPP)
Blood Brain Barrier / BBB hyperpermeability is a highly selective semipermeable membrane barrier that separates the circulating blood from the brain extracellular fluid in the central nervous system (CNS). The blood–brain barrier is formed by brain endothelial cells, which are connected by tight junctions. BBB hyperpermeability is a suspected pathomechanism in neurodegenerative disease, allowing both pathogens and immune system components to come in contact with the brain, resulting in increased inflammation and oxidative stress.
Calcium / Calcium Loading.
Calcium Channels – A calcium channel is an ion channel which displays selective permeability to calcium ions. It is sometimes synonymous as voltage-dependent calcium channel, although there are also ligand-gated calcium channels.
Complement System / Immune Complement System. The complement system is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promotes inflammation, and attacks the pathogen’s plasma membrane.
CoQ / CoQ10 / Ubiquinol. Ubiquinol is an electron-rich (reduced) form of coenzyme Q10.
Curcumin is a bright yellow chemical produced by some plants. It is the principal curcuminoid of turmeric (Curcuma longa), a member of the ginger family (Zingiberaceae). It is sold as an herbal supplement, cosmetics ingredient, food flavoring, and food coloring. As a food additive, its E number is E100.
Damage-associated molecular patterns (DAMPs), also known as danger-associated molecular patterns, danger signals, and alarmin, are host biomolecules that can initiate and perpetuate a noninfectious inflammatory response. In contrast, pathogen-associated molecular patterns (PAMPs) initiate and perpetuate the infectious pathogen-induced inflammatory response.
DNA damage is an alteration in the chemical structure of DNA, such as a break in a strand of DNA, a base missing from the backbone of DNA, or a chemically changed base as 8-OHdG. Damage to DNA that occurs naturally can result from metabolic or hydrolytic processes.
Electron Transport. An electron transport chain (ETC) is a series of complexes that transfer electrons from electron donors to electron acceptors via redox (both reduction and oxidation occurring simultaneously) reactions, and couples this electron transfer with the transfer of protons (H+ ions) across a membrane.
Endoplasmic Reticulum. The endoplasmic reticulum (ER) is a type of organelle in eukaryotic cells that forms an interconnected network of flattened, membrane-enclosed sacs or tube-like structures known as cisternae.
Endotoxin / Lipopolysaccharide. Lipopolysaccharides (LPS), also known as lipoglycans and endotoxins, are large molecules consisting of a lipid and a polysaccharide composed of O-antigen, outer core and inner core joined by a covalent bond; they are found in the outer membrane of Gram-negative bacteria, and elicit strong immune responses in animals.
Endothelial hyperpermeability or vascular permeability refers to the state endothelial tight junctions are relaxed, allowing larger molecules to pass through the vessel wall. This is useful for delivering immune components to cells beyond the reach of the vasculature
Feed Forward Loops. Feed-forward, sometimes written feedforward, is a term describing an element or pathway within a control system that passes a controlling signal from a source in its external environment, often a command signal from an external operator, to a load elsewhere in its external environment.
Flavonoids are a class of plant and fungal polyphenols
Gene Activation / Deactivation Epigenetic modification of a gene state.
Regulation of gene expression includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products (protein or RNA), and is informally termed gene regulation.
Glutathione. (GSH) is an important antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by reactive oxygen species such as free radicals, peroxides, lipid peroxides, and heavy metals.
Glutathione Peroxidase is the general name of an enzyme family with peroxidase activity whose main biological role is to protect the organism from oxidative damage. The biochemical function of glutathione peroxidase is to reduce lipid hydroperoxides to their corresponding alcohols and to reduce free hydrogen peroxide to water.
Gut-Vascular Barrier. First identified in 2015, the Gut-vascular barrier performs an analogous function to the Blood-brain barrier, which separates the brain pathogens and the immune system. A dysregulated gut-vascular barrier will allow larger molecules and even bacteria to pass from the intestine into the bloodstream.
Heavy Metal Toxicity. Heavy metals such as mercury and cobalt are potent oxidative stressors and are not easily broken down and removed from the system, making them a significant contributor to oxidative stress burden. Chelation, a process that binds and removes metals, is performed by glutathione, alpha lipoic acid amino acids such as Di mercapto succinic acid (DMSA).
Heat Shock Proteins. HSPs are a family of proteins produced as a part of the cellular stress response. While initially discovered as a response to heat, more recent research indicates that are produced under numerous stress conditions including cold and UV light. HSPs are generally considered to be protective and exhibit some overlapping functions with the unfolded protein response.
Heme Oxygenase / HO. Heme oxygenase or haem oxygenase (HO) is an enzyme that catalyzes the degradation of heme. This produces biliverdin, ferrous iron, and carbon monoxide. There is limited evidence that levels of heme oxygenase are positive predictors of metabolic disease, insulin resistance, and metaflammation.
HPA Axis. The hypothalamic–pituitary–adrenal axis (HPA axis or HTPA axis) is a complex set of direct influences and feedback interactions among three endocrine glands: the hypothalamus, the pituitary gland (a pea-shaped structure located below the thalamus), and the adrenal (also called “suprarenal”) glands (small, conical organs on top of the kidneys).
Hydrogen peroxide is a chemical compound with the formula H2O2. In its pure form, it is a colourless liquid, slightly more viscous than water. H2O2 is the most prominent redox signaling molecule due to its stability and ubiquity.
Hydoxyl Radical. The hydroxyl radical, •OH, is the neutral form of the hydroxide ion (OH−). Hydroxyl radicals are highly reactive (easily becoming hydroxyl groups) and consequently short-lived; however, they form an important part of radical chemistry.
Hyperaldosteronism, also aldosteronism, is a medical condition wherein too much aldosterone is produced by the adrenal glands, which can lead to lowered levels of potassium in the blood (hypokalemia) and increased hydrogen ion excretion (alkalosis).
Inflammation is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molecular mediators.
Inflammatory Cascade. Inflammation is triggered typically by a toxic or pathogenic insult followed by oxidative stress, NF-kB activation, TNF-alpha and IL-1B production and a cascade of additional inflammatory cytokines, hence the phrase ‘inflammatory cascade.’ This concept overlaps with the idea of feed-forward loops and pro-oxidant states.
Innate Immune System also known as the non-specific immune system or in-born immunity system, is an important subsystem of the overall immune system that comprises the cells and mechanisms that defend the host from infection by other organisms.
Intestinal Permeability is a term describing the control of material passing from inside the gastrointestinal tract through the cells lining the gut wall, into the rest of the body. The intestine normally exhibits some permeability, which allows nutrients to pass through the gut, while also maintaining a barrier function to keep potentially harmful substances (such as antigens) from leaving the intestine and migrating to the body more widely.
Iron is a necessary nutrient that needs to be maintained in balance. Low iron, anemia, is associated with fatigue and other symptoms including rapid heart rate, shortness of breath, pale skin, cold hands and feet, while oxidative stress and mitochondrial dysfunction are associated with both low and high iron levels.
Lectin Complement Pathway. The lectin pathway is a type of cascade reaction in the complement system, similar in structure to the classical complement pathway, in that, after activation, it proceeds through the action of C4 and C2 to produce activated complement proteins further down the cascade.
Leukocytes. White Blood cells
Magnesium / Magnesium Efflux. Magnesium is an essential element in biological systems. Magnesium occurs typically as the Mg2+ ion. It is an essential mineral nutrient (i.e., element) for life and is present in every cell type in every organism. For example, ATP (adenosine triphosphate), the main source of energy in cells, must be bound to a magnesium ion in order to be biologically active. What is called ATP is often actually Mg-ATP. As such, magnesium plays a role in the stability of all polyphosphate compounds in the cells, including those associated with the synthesis of DNA and RNA.
Mast Cell: a type of white blood cell. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a part of the immune and neuroimmune systems and contains many granules rich in histamine and heparin.
Metabolic Endotoxemia. Increased intestinal or gut-vascular permeability allows lipopolysaccharide (aka endotoxin) to pass from the gut lumen into the bloodstream causing a condition called metabolic endotoxemia. Elevated levels of LPS in the bloodstream are associated with most inflammatory diseases including diabetes, depression, anxiety, psychosis, osteoporosis, liver disease, etc.
Mitochondrial biogenesis is the process by which cells increase their individual mitochondrial mass and copy number to increase the production of ATP as a response to greater energy expenditure.
Mitochondrial Dysfunction. An early impact of oxidative stress, mitochondrial dysfunction can result from loss of antioxidant capacity, depletion of NAD+ and associated dysregulation of the electron transport chain. The end result is fewer, smaller and less healthy mitochondria, lowered energy production and increased mitochondrial ROS production due to decreased efficiency in the electron transport chain.
mTor pathway. The mechanistic target of rapamycin (mTOR), (formerly mammalian target of rapamycin before it was recognized to be highly conserved among eukaryotes.) also known as FK506-binding protein 12-rapamycin-associated protein 1 (FRAP1), is a kinase that in humans is encoded by the MTOR gene.[
N-acetylcysteine also known as N-acetylcysteine or N-acetyl-L-cysteine (NAC), is a medication used to treat paracetamol (acetaminophen) overdose and to loosen thick mucus such as in cystic fibrosis or chronic obstructive pulmonary disease.
NAD/NADH – The NAD redox couple includes NAD+ (the oxidized form) and NADH (the reduced from). NAD+ is notable for regulating metabolism and as a raw material for Sirtuin production and DNA repair (PARP).
NADP/NADPH – The NADP redox couple includes NADP (the oxidized form) and NADPH (the reduced form). For redox health, the NADP pool needs to be maintained in a reduced state. A higher NADP/NADPH ration will result in overproduction of Reactive Species.
Necrosis (from the Greek νέκρωσις “death, the stage of dying, the act of killing” from νεκρός “dead”) is a form of cell injury which results in the premature death of cells in living tissue by autolysis.
NRF2. Nuclear factor (erythroid-derived 2)-like 2, also known as NFE2L2 or Nrf2, is a transcription factor that in humans is encoded by the NFE2L2 gene. Nrf2 is a basic leucine zipper (bZIP) protein that regulates the expression of antioxidant proteins that protect against oxidative damage triggered by injury and inflammation.
Oxidative Damage. Reactive Oxygen and Nitrogen species cause oxidative damage to a variety of molecules including proteins, carbohydrates, fats and DNA. These oxidized molecules are useful biomarkers, evidence of oxidative stress.
Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system’s ability to readily detoxify the reactive intermediates or to repair the resulting damage.
Oxidative Stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system’s ability to readily detoxify the reactive intermediates or to repair the resulting damage.
PAMPs. Pathogen-associated molecular patterns, or PAMPs, are molecules associated with groups of pathogens, that are recognized by cells of the innate immune system. These molecules can be referred to as small molecular motifs conserved within a class of microbes.
Parathyroid Hormone also called parathormone or parathyrin, is a hormone secreted by the parathyroid glands that is important in bone remodeling, which is an ongoing process in which bone tissue is alternately resorbed and rebuilt over time.
Pathological Signaling is contrasted with physiological or normal signaling. Physiological redox signaling is generally understood in terms of H2O2 levels.
Peroxynitrite is an ion with the formula ONOO−. It is an unstable structural isomer of nitrate, NO−3. Although its conjugate acid is highly reactive, peroxynitrite is stable in basic solutions. It is prepared by the reaction of hydrogen peroxide with nitrite
Polyphenols (noun, pronunciation of the singular /pɒliˈfiːnəl/ or /pɒliˈfɛnəl/; also known as polyhydroxyphenols) are a structural class of mainly natural, but also synthetic or semisynthetic, organic chemicals characterized by the presence of large multiples of phenol structural units.
Protein folding is the physical process by which a protein chain acquires its native 3-dimensional structure, a conformation that is usually biologically functional, in an expeditious and reproducible manner.
Proteome. The proteome is the entire set of proteins expressed by a genome, cell, tissue, or organism at a certain time. More specifically, it is the set of expressed proteins in a given type of cell or organism, at a given time, under defined conditions. The term is a blend of proteins and genome. Proteomics is the study of the proteome.
Quercetin is a plant polyphenol from the flavonoid group, found in many fruits, vegetables, leaves, and grains. It can be used as an ingredient in supplements, beverages, or foods. Quercetin Decreases Oxidative Stress, NF-κB Activation, and iNOS Overexpression in Liver of Streptozotocin-Induced Diabetic Rats
Reactive nitrogen species (RNS) are a family of antimicrobial molecules derived from nitric oxide (•NO) and superoxide (O2•−) produced via the enzymatic activity of inducible nitric oxide synthase 2 (NOS2) and NADPH oxidase respectively. NOS2 is expressed primarily in macrophages after induction by cytokines and microbial products, notably interferon-gamma (IFN-γ) and lipopolysaccharide (LPS)
Renin Angiotensin Aldosterone System
Redox Imbalance Generally assumed to be elevated oxidative stress and reduced antioxidant capacity, though it also includes reductive stress, where antioxidants suppress physiological redox signaling.
Redox Signaling – In the past two decades, there is substantial evidence that ROS are essential second messengers in innate and adaptive immune cells [73, 74]. Yet, increased levels of ROS within immune cells can result in hyperactivation of inflammatory responses resulting in tissue damage and pathology .
Reductive stress is the counterpart to oxidative stress, where electron acceptors are expected to be mostly reduced. It can be caused by excess amounts of glutathione, and can contribute to cytotoxicity.
Resveratrol – Resveratrol is a stilbenoid, a type of natural phenol, and a phytoalexin produced by several plants in response to injury or, when the plant is under attack by pathogens such as bacteria or fungi.
Rutin. Rutin is a plant pigment (flavonoid) that is found in certain fruits and vegetables. Rutin is used to make medicine. The major sources of rutin for medical use include buckwheat, Japanese pagoda tree, and Eucalyptus macrorhyncha.
Senescence. Aging cells with shortened telomeres and no longer able divide are said to have reached a state of senescence. Senescent cells give off Damage-Associated Molecular Patterns (DAMPs) to alert the immune system. An aging immune system eventually fails to remove senescent cells with associated pathology in diseases like pulmonary fibrosis.
Static ORP (sORP): valuable “snapshot” of current redox balance, which appears to correlate with illness, injury severity and mortality. A higher sORP reading is indicative of oxidative stress
Superoxide Radical. The O2 radical is typically produce by mitochondria and quickly reduced to H2O2 by superoxide disumutase, and then
Superoxide Dismutase. One of the body’s primary endogenous antioxidant enzymes. Superoxide Dismutase reduces the Superoxide free radical into 2 HO2 → O2 + H2O2.
Sympathetic Nervous System activation. Oxidative stress leads to the activation of the Sympathetic Nervous system which regulates the body’s unconscious actions.
Telomere. A telomere is a region of repetitive nucleotide sequences at each end of a chromosome, which protects the end of the chromosome from deterioration or from fusion with neighboring chromosomes. “One important question is: what contributes to a persistent DDR during cellular senescence? Recent work has highlighted the importance of telomeres in the maintenance of senescence. It has been demonstrated that DNA damage at telomeres can occur as a consequence of genotoxic and oxidative stress, and that this damage is mostly irreparable”
TNF Tumor Necrosis Factor is a superfamily of proteins with diverse functions in cell cycle regulation including survival, proliferation, differentiation and death. TNF alpha is an inflammatory cytokine upregulated by NFkB and is associated with immune system activation and regulation.
Transcriptome. The sum total of all the messenger RNA molecules expressed from the genes of an organism.
Unfolded Protein Response
- The unfolded protein response (UPR) is a cellular stress response related to the endoplasmic reticulum (ER) stress. It is a stress response that has been found to be conserved between all mammalian species, as well as yeast and worms.
- Oxidative damage to proteins can take several forms. Oxidation of the protein backbone following H abstraction by OH• can result in protein fragmentation, as can oxidation of glutamyl, aspartyl, and prolyl side chains (Berlett and Stadtman, 1997). Sulfur-containing amino acids, cysteine, and methionine are particularly sensitive to oxidation (Berlett and Stadtman, 1997). These modifications can result in the loss of enzyme or protein function and the accumulation of unfolded proteins, which can impair cell function, leading to the UPR
- The UPR optimizes the ER to correctly manage protein folding and initiate apoptosis or autophagy in cells that are irreversibly damaged. UPR mediators and signaling proteins respond not only to exogenous toxicants that disturb ER function,
VEGF. Vascular endothelial growth factor (VEGF) is typically upregulated by oxidative stress and is Zinc – Zinc is an antioxidant metal with diverse roles, including 200 zinc enzymes and over 3,000 zinc proteins. Low zinc status increases oxidative stress in the body and negatively impacts immune status and DNA damage repair.