Types of flavonoids.
\\n\\n
Dr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\\n\\nSeeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\\n\\nOver these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\\n\\nWe are excited about the present, and we look forward to sharing many more successes in the future.
\\n\\nThank you all for being part of the journey. 5,000 times thank you!
\\n\\nNow with 5,000 titles available Open Access, which one will you read next?
\\n\\nRead, share and download for free: https://www.intechopen.com/books
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Preparation of Space Experiments edited by international leading expert Dr. Vladimir Pletser, Director of Space Training Operations at Blue Abyss is the 5,000th Open Access book published by IntechOpen and our milestone publication!
\n\n"This book presents some of the current trends in space microgravity research. The eleven chapters introduce various facets of space research in physical sciences, human physiology and technology developed using the microgravity environment not only to improve our fundamental understanding in these domains but also to adapt this new knowledge for application on earth." says the editor. Listen what else Dr. Pletser has to say...
\n\n\n\nDr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\n\nSeeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\n\nOver these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\n\nWe are excited about the present, and we look forward to sharing many more successes in the future.
\n\nThank you all for being part of the journey. 5,000 times thank you!
\n\nNow with 5,000 titles available Open Access, which one will you read next?
\n\nRead, share and download for free: https://www.intechopen.com/books
\n\n\n\n
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Free radicals are chemical species such as atoms or group of atoms with an odd (unpaired) number of electrons. They are produced due to splitting weak bonds. The biological free radicals, such as reactive oxygen species (ROS) and reactive nitrogen species (RNS), are usually produced in our bodies. It is known that free radicals are very reactive and may quickly react with other chemical entities (atoms or molecules) by capturing the required electron to gain stability. There are two types of biologically important reactive species. The first type contains oxygen and is known as reactive oxygen species (ROS), while the second type contains nitrogen and is known as reactive nitrogen species (RNS). Both ROS and RNS can be classified into radicals and non-radical species.
ROS can be classified into two types, radical species and non-radical species. The most important ROS radicals are: superoxide anion radical (O2.–), hydroxyl radical (.OH), alkoxyl radical (RO.), lipid peroxide radical (ROO.), and hydroperoxy radical (HOO.). While the non-radicals ROS are: hydrogen peroxide (H2O2), singlet oxygen (1O2), ozone (O3), organic peroxide (ROOH), and hypochlorous acid (HOCl).
It is important to emphasize that the mitochondria is the main source of the most active biological ROS [1, 2, 3, 4, 5] such as superoxide anion radical (O2.−), hydrogen peroxide (H2O2) and hydroxyl radical (.OH). Thus, the initial reactive oxygen species (O2.−) is produced due to the reduction of free oxygen by some electrons leaking out from the electron transport chain during the process of oxidative phosphorylation. This particle is relatively stable intermediate and considered as the precursor for most important ROS. The reduction of free oxygen by electrons in mitochondria can be illustrated as follows: O2 + e− → O2.−. In addition, the superoxide anion radical may be produced in a process of oxygen reduction by enzymatic systems in mammalian cells as follows [6]:
The superoxide anion radical and hydrogen peroxide are formed in vivo, in the brain, and the central nervous system (CNS). It is known that several areas in the brain contain high amount of iron which stimulates free radical reactions.
The superoxide anion and hydrogen peroxide can be converted rapidly to hydroxyl radical (.OH), which is known as the most reactive and destructive radical in biological system. This radical is quickly produced via Fenton [7] and Haber-Wiess reactions as follows [8, 9]:
The reaction of H2O2 with Fe+2 and Cu+ metal ions which are typically complexed with certain intracellular proteins such as ferritin and ceruloplasmin, respectively [7], occurs due to stress conditions, which means an excess of superoxide anion radical (O2.−). This phenomenon releases free ions (Fe+2) from ferritin which in turn reacts with H2O2 according to Fenton reaction to produce hydroxyl radical (.OH). This free radical can strongly react with biomolecules such as DNA, proteins, lipids, and carbohydrates and cause severe damage to the cells than any other ROS [10]. The. OH is the most destructive free radical and can more easily penetrate the phospholipid bilayer than O2.−, which is negatively charged. When ·OH is generated by Fenton reaction, the extent of its formation is largely determined by the availability and location of the metal ion catalyst. One feature of ·OH is that it leads to the generation of another radical, so when it reacts with a molecule, a new free radical is generated. However, the new free radical usually has lower reactivity than the hydroxyl radical (·OH). The ·OH attacks all proteins, DNA, polyunsaturated fatty acids (PUFA) in membranes, and almost any biological molecule it encounters [10]. The hydroxyl radical (·OH) can be obtained by another reaction in neutrophils, where HOCl reacts with superoxide anion radical [11, 12] as follows:
The hydroxyl radical (.OH) is the strongest oxidant produced in biological systems. It reacts very rapidly and indiscriminately with most biological targets present at its site of formation.
Peroxy radicals (ROO.) and alkoxy radicals (RO.) are moderately strong oxidants. Lipid peroxidation starts with abstraction of H-atom by .OH, or by RO. to form alkyl radical (R.), then oxygen (O2) is added to alkyl radical to generate peroxyl radical (ROO.). Lipid peroxidation or the oxidative destruction of PUFA containing methylene groups (-CH2-) comprise the main targets [13]. This process can be illustrated in three steps as follows:
Then, peroxyl radical reacts with another polyunsaturated fatty acid (RH) to remove H-atom:
Finally, to terminate lipid peroxidation, the following reaction takes place:
It is clear that lipid peroxidation leads to the formation of alkyl (R.), peroxyl (ROO.), and alkoxyl (RO.) radicals. Generally, lipid hydroperoxide (ROOH) is relatively stable, but in the presence of Fe and Cu ions, it causes the formation of alkoxy and peroxy radicals [14, 15].
The reactivity of RO. and ROO. is related to the presence of substituents at the α-carbon. As a result, the presence of an electron-withdrawing group increases the reactivity, while the presence of an electron-donating group decreases it. Thus, aromatic ROO. and RO. must be less reactive because of single electron delocalization. These free radicals react with biomolecules by abstracting H-atom [16, 17].
Hydroperoxyl radical, also known as perhydroxyl radical (HOO.), is formed due to the reversible reaction occurring between superoxide anion radical and proton. This reaction takes place in cells as follows:
The pKa of this radical is 4.88 [18]. At pH 7.2 in the cytoplasm, a small amount of this radical (1% of O2•−) exists as HOO. [19]. Perhaps for this reason, many researchers presumed that HOO• has little or no role in initiation of lipid peroxidation [20]. In comparison with other oxidants, HOO• shows high specificity in reaction with PUFA, linoleic (C18:2), and linolenic (C18:3) acids [21].
The singlet oxygen (1O2) is a potent oxidizing agent, because it can react with different macromolecules such as DNA [22], and is responsible for lipid peroxidation of membrane and other tissues [23]. It is generated in cells, specifically in neutrophils and eosinophils [24, 23]. In addition, this particle can be formed by enzymatic reactions [25, 26, 27]. This reactive particle is produced due to the activation of molecular oxygen to two excited states. In the first excited state, oxygen has two electrons with opposite spins in the same ᴨ* orbital, while in the second excited state oxygen has one electron in each of two degenerate ᴨ* orbitals. However, singlet oxygen in the first excited state is extremely reactive in comparison with other excited states like the triplet state. Allen [28] suggested the mechanism for the production of singlet oxygen from H2O2 and Cl− in the presence of the myeloperoxidase (MPO) enzyme as follows:
Hydrogen peroxide is generated via an enzymatic reaction where the reactive superoxide anion radical is rapidly converted by an antioxidant enzyme called superoxide dismutase (SOD). The new formed oxygen species H2O2 is less reactive. Thus, hydrogen peroxide is formed as follows by SOD:
It is clear that, in the dismutation reaction (an oxidation–reduction process), two superoxide anion radicals are involved. In this reaction, one superoxide anion radical is oxidized to oxygen while the other is reduced to hydrogen peroxide [29]. The latter (H2O2) is relatively stable and membrane permeable so this non-radical species can diffuse inside the cell and can be removed by mitochondrial antioxidant enzymatic systems such as catalase (CAT) and glutathione peroxidase (GPx) [30, 31].
As illustrated, glutathione peroxidase (GPx) removes hydrogen peroxide (H2O2) by oxidizing two glutathione molecules (GSH) to produce oxidized glutathione disulfide (GSSG). It is clear that the three SOD, CAT, and GPx enzymes show synergistic effect in the scavenging of superoxide anion radical (O2˙−). The in vivo destruction effects of hydrogen peroxide (H2O2) result due to the presence of transition metals or enzymes, such as heme-peroxidase. The destruction of H2O2 leads to the formation of other more reactive oxidants such as.OH, NO., and HOCl. Thus, reaction of hydrogen peroxide with Cu1+ and Fe2+ leads to the production of. OH. On the other hand, in phagocytic cells, myeloperoxidase uses its substrate H2O2 to generate HOCl. The release of MPO during phagocytosis may play an important role in microbial elimination [32].
Ozone gas (O3) exists in polluted atmosphere and the inhalation of this gas by human may lead to lung injury and inflammation. In living organisms, ozone is thought to be formed due to oxidation of H2O to H2O2 in the presence of antibodies [33]. Thus, antibodies use H2O as an electron source, facilitating its addition to 1O2 to generate dihydrogen trioxide (H2O3), which is converted to ozone [34].
Ozone reacts with fatty acids, cholesterol, amino acids and DNA. The lung is the most affected organ due to exposure to ozone. The effect of ozone on tissues occurs via free radical mechanisms [35, 36, 37]. The ozone radical anion then reacts with a proton to form the hydroxyl radical and oxygen as follows [36].
This species (HOCl) is generated in neutrophils by the reaction of Cl − with H2O2, which is catalyzed by the enzyme myeloperoxidase [38]. It is illustrated as follows:
The hypochlorous acid is considered to be a very reactive oxidizing agent. So, it may affect different biomolecules and may destroy phagocytized pathogens by causing oxidative damage to their biomolecules which include proteins [39], DNA [40], and lipids [41]. On the other hand, the overproduction of HOCl can lead to many health problems such as atherosclerosis and cancer [42, 38].
Reactive nitrogen species (RNS) can be found in biological systems as free radical species and non-radical species. However, the most common RNS radical is nitric oxide radical (NO.) and nitrogen dioxide (NO2). On the other side, the important non-radical RNS is peroxynitrite ion (ONOO−). Generations of these reactive species is discussed below.
Nitric oxide free radical (NO.) is an endogenous free radical synthesized in the presence of nitric oxide synthase (NOS) that oxidizes L-arginine to L-citrulline [43]. In this reaction, one of the guanidino nitrogen atoms is oxidized to form NO.. This process is shown below:
The NO. radical can diffuse easily and has the ability to reach many intracellular targets and cause biological damage [44]. The enzyme nitric oxide synthase (NOS) is found in different cells such as vascular endothelial cells, smooth muscle cells, platelets, neuronal cells, macrophages, and neutrophils [45]. In addition, this radical plays an important role in biological tissues such as vasodilation, memory, neuronal response, among others [46, 47, 48, 49, 50].
This nitrogenous species is generated due to reaction of superoxide anion radical (O2−.) with nitrogen oxide radical (NO.) radical as follows:
It is noted that at physiological pH (7.4), peroxynitrite exists in equilibrium with peroxynitrous acid, ONOOH [51].
Then, peroxynitrous acid (ONOOH) is subjected to homolysis to produce hydroxyl radical (OH•) and nitrogen dioxide radical (NO2.), which may rearrange to form nitrate (NO3−).
The ONOO− is a very reactive anion, even more so than the particle (NO. and O2•−) from which it is formed [52, 53, 54]. The peroxynitrite anion can cross biological membranes and interact with most critical biomolecules [55]. Thus, it can cause oxidation of lipids, and proteins via oxidation of methionine and tyrosine residues and can oxidize DNA to generate nitroguanine [56]. Under most biological conditions, ONOO- and ONOOH exist in equilibrium [57]:
Indeed, protonation weakens the O–O bond in ONOOH and leads to homolytic cleavage to generate hydroxyl radicals (.OH) and nitrogen dioxide (.NO2), two strongly oxidizing/hydroxylating and nitrating species, respectively.
As a nucleophile, a central reaction of peroxynitrite in biology is the addition of the anion to carbon dioxide (CO2) to yield a nitrosoperoxocarboxylate adduct (ONOOCO2) that undergoes fast homolysis to NO2 and [58, 59, 60].
An antioxidant is any substance that has the ability to prevent, inhibit, or delay the oxidation of other substances. In biological systems, antioxidants play a very important roles in removing free radicals such as ROS and RNS, and consequently reduce oxidative stress. Antioxidant molecules can be classified based on the type of mechanistic defense they offer:
These are endogenous antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). These enzymes efficiently suppress or prevent the formation of free radicals and other ROS in tissues. Thus, SOD removes superoxide anion radical as follows:
On the other hand, CAT reduces formed H2O2 to water and oxygen:
The GPx enzyme system detoxifies H2O2 by catalyzing its reduction using glutathione (GSH) as a sacrificial reductant to produce one molecule of oxidized glutathione (GSSG). Thus, the enzymes SOD, CAT, and GPx, work collectively to prevent the effect of O2˙−.
In addition, Fe and Cu ions are included to this type of defense, since these ions bind proteins such as transferrin and caeruloplasmin and prevent them from free radical formation. Generally, any chemical compound having two or more of the following functional groups: –OH, –SH, –COOH, –PO3H2, C=O, –NR2, –S– and –O– may have chelating activity [61]. The mechanism of metal ion chelation with some natural phenolics such as protocatechuic acid and anthocyanins is shown in Figure 1.
Mechanism of metal ion chelation with some natural phenolics.
Transition metal ions (Fe+2 and Cu+) make complex species with different types of phenolic compounds such as flavonoids containing multiple hydroxyl groups (polyhydroxylated). The involvement of these ions in the formation of complexes prevents the Fenton reaction which leads to the formation of hydroxyl radical (.OH) which is considered as the most dangerous ROS.
This type of antioxidants are enzymes which are involved in repairing damage due to the effects of free radicals on biomolecules (DNA, proteins, lipids and carbohydrates). These enzymes prevent the accumulation of toxic substances resulting from destruction of biomolecules in body tissues. Examples of this type of enzymatic antioxidants include the DNA repair enzyme systems (polymerases, glycosylases and nucleases), and proteolytic enzymes (proteinases, proteases and peptidases) located in both, cytosol and mitochondria of mammalian cells.
This type of antioxidants use the signals, which are required for the formation of free radicals. As a result, the signal generated from the formed free radical causes the formation and transport of the appropriate antioxidant to the appropriate and required site [62].
This type of scavenging antioxidants can directly neutralize free radicals by two mechanisms, either by donating a hydrogen free radical (H.) or donating an electron (e−). These mechanisms can be illustrated as follows:
In the preceding mechanism, the antioxidant donates a hydrogen free radical (H.) to scavenge free radicals, and the antioxidant (Ar-OH) itself becomes a free radical, though not as biologically harmful.
The second mechanism involves one-electron transfer where the antioxidant donates an electron to the free radical and becomes itself a radical cation. Generally, the new radicals are more stable and can be easily neutralized and made completely harmless and removed easily from biological systems. Many antioxidants such as ascorbic acid, uric acid, glutathione, vitamin E, and other natural compounds like polyhydroxyphenolic compounds belong to this class. This type of antioxidants are usually small molecules containing hydroxyl groups either of natural or synthetic origin. The importance of these compounds prompted us to review them in details.
There are many studies that have shown the biological effectiveness of phenolic compounds as natural antioxidants. They play very important roles in the prevention of dangerous diseases such as cancers, heart diseases, diabetes and others. There is a need for simple molecules capable of neutralizing free radicals responsible for what is known as oxidative stress, the lead cause of dangerous diseases like cancers, heart disease, diabetes and others. Antioxidants play a critical role in biological systems in getting rid of free radicals and work to prevent the phenomenon of oxidative stress. The most available natural antioxidants exist in plants such as fruits, vegetables, and medicinal plants. Herein, we present an overview of the natural and synthetic phenolic compounds acting as antioxidants.
Simple phenols are known as compounds containing at least one hydroxyl group attached to an aromatic ring which comprises the basic skeleton. The most important compounds under this class are: phenol, catechol, resorcinol, and phloroglucinol. Generally, phenols are widely distributed in plants and play very important roles in human health because of their ability to neutralize free radicals due to their hydroxyl groups. It is considered that these simple phenols along with other phenolic compounds can inhibit and prevent cancer diseases in humans (Figure 2) [63].
Natural phenolic antioxidants containing hydroxyl groups.
The study by Spiegel et al. [64] has shown that the most active of simple natural phenols as antioxidants were those containing more than one hydroxyl group in the
Mechanism of action of natural phenolic antioxidants by transfer of hydrogen free radical (H•).
Phenolic acids are also known as phenol carboxylic acids (Figure 4). There are two important groups of natural phenolic acids which are hydroxybenzoic acids and hydroxycinnamic acids. These are derived from benzoic and cinnamic acid, respectively. The molecular structural features of phenolic acids, such as the numbers and positions of the hydroxyl groups in relation to the carboxyl functional group, esterification, and glycosylation great impacts their antioxidant properties. Many studies [68, 69] have shown that the antioxidant activity of phenolic acids and their esters was enhanced substantially when the number of hydroxyl (-OH) and methoxy (-OCH3) groups increased. On the other hand, the carboxyl group has an electron withdrawing effect, making the H-atom less available to be donated. However, the antioxidant activity of hydroxylated cinnamates are greater than that of benzoates [70, 71, 72]. The antioxidant activities of different hydroxybenzoic acids such as 4-hydroxybenzoic acid, 3,4-dihydroxybenzoic acid, and 3,4,5-trihydroxybenzoic acid were shown to be dependent on the number and position of attached hydroxyl groups to the aromatic ring [73]. Based on bond dissociation energy of O-H group, the dihydroxybenzoic acid has greater antioxidant activity than monohydroxybenzoic acid. It was observed that the BDE for -OH at 3-position is greater than the BDE of -OH at 4-position, as a result the abstraction of H-atom from the 4-position becomes easier than abstraction from the 3-position. Thus, it can be concluded that in 3,4-dihydroxybenzoic acid, the ability to abstract H-atom from the 4-position is easier than the 3-position. On the other hand, gallic acid (3,4,5-trihydroxybenzoic acid) showed lower antioxidant activity than that of 3,4-dihydroxybenzoic acid. This phenomenon could be attributed to the formation of a weak intramolecular H-bond between the -OH at 4-position and -OH at 5-position [74]. The obtained theoretical BDE of the -OH groups in gallic acid were in the order 4-OH ≤ 5-OH ˂ 3-OH, which indicates that the removal of H-atom is easier from 4-OH and 5-OH. Both of these values in gallic acid become lower than that of 4-hydroxybenzoic acid. Thus, the introduction of two hydroxyl groups at 3-position and 5-position significantly increases the antioxidant activity [73].
Benzoic acid and the related hydroxybenzoic acids.
Similarly, the antioxidant activities of hydroxycinnamic acids (Figure 5) are related to their hydroxyl groups. The study of relationship between antioxidant activities and structures of hydroxycinnamic acids was carried out by Chen and Ho [74]. The BDE value of O-H group is a good indicator to evaluate the antioxidant activity of an antioxidant. Thus, the weaker the O-H bond, the greater the ability of an antioxidant to neutralize free radicals. In addition, phenolic molecules bearing two hydroxyl groups in
Cinnamic acid and hydroxycinnamic acids.
The flavonoids consist of a large group of low-molecular weight polyphenolic substances, benzo-γ-pyrone derivatives (Figure 5). The basic structural feature of all flavonoids is the flavane (2-phenyl-benzo-γ-pyran) nucleus, a system of two benzene rings (A and B) linked by an oxygen-containing pyran ring (C). According to the degree of oxidation of the C ring, the hydroxylation pattern of the nucleus, and the substituent at carbon 3, flavonoids can be categorized into the following subclasses: flavones, isoflavones, flavanols (catechins), flavonols, flavanones, anthocyanins, and proanthocyanidins. Flavonols differ from flavanones by a hydroxyl group at the C3 position and by a C2–C3 double bond. Anthocyanidins differ from the other flavonoids by possessing a charged oxygen atom in the C ring (Table 1).
Types of flavonoids.
Flavonoids are secondary metabolites and mainly distributed in the plant kingdom such as green and black tea, coffee, vegetables, fruits, olive oil, red wine, white wines, and chocolate [82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92]. They are consumed in milligrams per serving of these plant sources. Many researchers have shown that flavonoids possess different biological activities which include vasodilating, anti-allergenic, antiviral, and anti-inflammatory actions [93, 94, 95]. However, the antioxidant activity of these compounds attracted the most interest because, in addition to their ability to scavenge free radicals, they also reduce or prevent free radical formation.
The capability of antioxidant activities of flavonoids is mainly related to their chemical structures. Many previous investigations attributed the high antioxidant activities of these compounds to the presence and positions of hydroxyl groups attached to the A and B rings and/or to the C2 = C3 double bond in conjugation with the carbonyl group at 4-position, and the -OH group at 3-position [93, 94, 96]. On the other hand, the replacement of hydrogen atom by a saccharide at 3-position to form a glycosidic bond, the antioxidant activity decreases. The radical scavenging efficiency of flavonoids is related to their phenolic hydroxyl groups which follow the mechanism of H-atom transfer or the single electron transfer followed by sequential electron transfer-proton transfer (SETPT) [97, 98, 99, 100]. As in the case of phenolic acids, the antioxidant activity of flavonoids, is based on the value of the dissociation energy of the O-H bond [67, 97, 101]. The study by Quan et al. [102] showed that the dissociation energy of C-H at 3-position in some flavonoids appeared to be lower than that of the dissociation energy of O-H. As a result, the antioxidant activity might be due the donation of H-atom from C-H at 3-position. However, the mechanism of antioxidant activity via H-atom transfer from the -OH group appeared to be the most significant [102]. Generally, flavonoids as antioxidants may act by different mechanisms such as hydrogen atom transfer, single electron transfer, and transition metal chelation. These mechanisms are shown below in Figures 6–9. Figure 6 shows the proposed mechanism of radical scavenging activity of cyanidin by Nimse and Palb [103] following HAT mechanism.
Proposed mechanism of radical scavenging activity of cyanidin by Nimse and Palb [
Proposed mechanism of superoxide anion radical scavenging activity of quercetin by Nimse and Palb [
Proposed mechanism of single electron transfer by Leopoldini et al. [
Proposed metal–quercetin chelation by Leopoldinia et al. [
The flavonoid quercetin is found in many plants and foods and in notable quantities especially in onions, red wine, green tea, apples, berries, and others. The proposed mechanism of superoxide anion radical scavenging activity of quercetin by Nimse and Palb [103] is shown in Figure 7.
The proposed mechanism of single electron transfer by Leopoldini et al. [104] for single electron transfer (SET) and transition metal chelation (TMC) are shown in Figures 8 and 9.
Flavonoids with their multiple hydroxyl groups and the carbonyl group at the 4 position on ring C may offer several available sites for metal chelation. The ability of flavonoids to chelate Fe and Cu ions is related to their indirect antioxidant activities. This property of flavonoids is attributed to their multiple hydroxyl groups and the carbonyl group at 4-position [104].
The Stilbene family includes several compounds [105] among which resveratrol, pterostilbene, and piceatannol are the main representatives, characterized by a
Stilbene and its related polyphenolic derivatives.
Stilbene compounds are part of a group of natural polyphenols occurring in plant kingdom such as grapes [106], peanuts [107], and berries [108]. Resveratrol (3, 5, 4′-trihydroxy-trans-stilbene), which is found in grapes, showed different biological activities including antidiabetic, antiobesity, and neuroprotective properties against Alzheimer’s disease (AD) [109]. In addition, other stilbenes have shown additional activities as antimicrobials and antioxidants [110]. Different studies have shown that piceatannol (4′, 5′, 3, 5-tetrahydroxystilbene) expresses a wide spectrum of biological activities: anti-inflammatory, anticarcinogenic, antiviral, antioxidative, neuroprotective and estrogenic properties, and antioxidant activities [111, 112, 113, 114, 115, 116, 117]. A study by Hussein [118] demonstrated the strong ability of resveratrol to scavenge free radicals using different tests. The mechanism of antioxidant activity of resveratrol was proposed to be as follows (Figure 11).
Proposed mechanism of resveratrol antioxidant activity [
Synthetic antioxidants are usually used as food preservatives to prevent lipid oxidation [119]. The well-known synthetic antioxidants are butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and
Antioxidant action of
The progressively more sterically hindered BHT and the related BHA operated as radical terminators in a similar fashion to TBHQ (Figure 13).
Oxidation of BHT and BHA via donation of a hydrogen radical from a phenolic hydroxyl group.
Another type of radical quencher is shown in Figure 14 where the generated phenoxy radical is stabilized by intramolecular hydrogen bond.
Generation of a phenoxy radical with intramolecular hydrogen bond shown.
The presence of a bulky group introduces steric hindrance in proximity to the radical center, decreasing the rate of further propagation reactions. Another example which illustrates the increase in antioxidant activity is the presence of an extra hydroxyl group at the ortho or para position of the hydroxyl group of phenol. The stability of the phenoxy radical in this case is enhanced by the formation of an intramolecular hydrogen bond. Other studies [121, 122, 123] described the synthesis of different compounds like aromatic Schiff bases and aromatic hydrazones containing hydroxyl groups attached to different positions in the aromatic rings. These compounds were designed to mimic as much as possible natural phenolic compounds such as stilbene and chalcones. The number of hydroxyl groups and their locations in the aromatic rings play an important role in the antioxidant activity. The mechanism of antioxidant activity can be illustrated as follows and involves the donation of hydrogen radical (Figure 15).
Proposed mechanism for the action of aromatic hydrazones via H radical donation.
Oxidative stress is a phenomenon occurring in living systems and is related to the presence of free radicals (oxidants) and antioxidants (reductants). When we talk about free radicals in biological systems, we mean two types: reactive oxygen species (ROS) and reactive nitrogen species (RNS). Imbalance between free radicals and antioxidants (endogenous and exogenous) in biological systems creates a state know as oxidative stress. In this case, the present antioxidants cannot remove the ROS and RNS from living species. As a result, excess free radicals can negatively impact different biological processes, leading to the destruction of cell membrane, blocking pathways of major enzymes, stopping cell division, destruction of DNA, and halting energy production [124, 125, 126]. On the other hand, free radicals appear to be necessary for some processes in living organisms since they destroy bacteria by phagocytes (granulocytes and macrophages). In addition, ROS can be beneficial for the maintenance of homeostasis as well as other cellular functions [125, 127]. Again, it is important to remember that the primary free radicals are superoxide anion radicals O2. − and hydroxyl radical. OH which are derived from molecular oxygen (O2). High levels of these radicals may cause different biological problems which may lead to cancer, stroke (Reuter et al., 2010) [126], myocardial infarction, diabetes, and other significant conditions [128].
It is not easy to avoid the exposure of free radicals and consequently oxidative stress. However, the increase of consumption of natural antioxidants through diet may help to decrease the production of free radicals. In other words, to prevent oxidative stress, it is highly recommended to consume enough amounts of vegetables, fruits, medicinal plants, and honey to ensure sufficient supplementation of natural antioxidants [129, 130, 131, 132, 133].
To maintain normal health and avoid incurable diseases such as cardiovascular disease, cancer diseases, diabetes, among other, it is necessary to protect the existing balance between free radicals and antioxidants in biological systems. Naturally the human body has means of internal defense to neutralize free radicals. These means of defense are represented by a group of biological molecules known as antioxidant enzymes. In addition, there are a number of small molecules such as urea, bilirubin, vitamin E, vitamin A, and others. These simple molecules play a positive role in eliminating free radicals. However, when the internal system fails to get rid of free radicals, a supply of external antioxidants, especially those from natural sources, is needed to remove excess free radicals. There are many antioxidants in nature especially those that contain hydroxyl groups such as phenolic compounds, such as phenolic acids (derivatives of hydroxybenzoic and hydroxy cinnamic acids), flavonoids, stilbenes, chalcones and others. These compounds are found in fruits, vegetables and medicinal herbs. There are some chemically prepared antioxidants in laboratories which use is almost limited to the food and pharmaceutical industries. However, there are many attempts to manufacture antioxidants that mimic those found in nature, especially those containing hydroxyl groups, in the hope of obtaining compounds at the lowest cost, safe to use, and in large quantities.
Dr. Ziad Moussa is grateful to the United Arab Emirates University (UAEU) of Al-Ain and to the Research Office for supporting the research developed in his laboratory (Grant no. G00003291/Fund no.31S401/Project #852).
IntechOpen implements a robust policy to minimize and deal with instances of fraud or misconduct. As part of our general commitment to transparency and openness, and in order to maintain high scientific standards, we have a well-defined editorial policy regarding Retractions and Corrections.
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\\n\\n1. RETRACTIONS
\\n\\nA Retraction of a Chapter will be issued by the Academic Editor, either following an Author’s request to do so or when there is a 3rd party report of scientific misconduct. Upon receipt of a report by a 3rd party, the Academic Editor will investigate any allegations of scientific misconduct, working in cooperation with the Author(s) and their institution(s).
\\n\\nA formal Retraction will be issued when there is clear and conclusive evidence of any of the following:
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\\n\\n1.2. REMOVALS AND CANCELLATIONS
\\n\\n2. STATEMENTS OF CONCERN
\\n\\nA Statement of Concern detailing alleged misconduct will be issued by the Academic Editor or publisher following a 3rd party report of scientific misconduct when:
\\n\\nIntechOpen believes that the number of occasions on which a Statement of Concern is issued will be very few in number. In all cases when such a decision has been taken by the Academic Editor the decision will be reviewed by another editor to whom the author can make representations.
\\n\\n3. CORRECTIONS
\\n\\nA Correction will be issued by the Academic Editor when:
\\n\\n3.1. ERRATUM
\\n\\nAn Erratum will be issued by the Academic Editor when it is determined that a mistake in a Chapter originates from the production process handled by the publisher.
\\n\\nA published Erratum will adhere to the Retraction Notice publishing guidelines outlined above.
\\n\\n3.2. CORRIGENDUM
\\n\\nA Corrigendum will be issued by the Academic Editor when it is determined that a mistake in a Chapter is a result of an Author’s miscalculation or oversight. A published Corrigendum will adhere to the Retraction Notice publishing guidelines outlined above.
\\n\\n4. FINAL REMARKS
\\n\\nIntechOpen wishes to emphasize that the final decision on whether a Retraction, Statement of Concern, or a Correction will be issued rests with the Academic Editor. The publisher is obliged to act upon any reports of scientific misconduct in its publications and to make a reasonable effort to facilitate any subsequent investigation of such claims.
\\n\\nIn the case of Retraction or removal of the Work, the publisher will be under no obligation to refund the APC.
\\n\\nThe general principles set out above apply to Retractions and Corrections issued in all IntechOpen publications.
\\n\\nAny suggestions or comments on this Policy are welcome and may be sent to permissions@intechopen.com.
\\n\\nPolicy last updated: 2017-09-11
\\n"}]'},components:[{type:"htmlEditorComponent",content:'IntechOpen’s Retraction and Correction Policy has been developed in accordance with the Committee on Publication Ethics (COPE) publication guidelines relating to scientific misconduct and research ethics:
\n\n1. RETRACTIONS
\n\nA Retraction of a Chapter will be issued by the Academic Editor, either following an Author’s request to do so or when there is a 3rd party report of scientific misconduct. Upon receipt of a report by a 3rd party, the Academic Editor will investigate any allegations of scientific misconduct, working in cooperation with the Author(s) and their institution(s).
\n\nA formal Retraction will be issued when there is clear and conclusive evidence of any of the following:
\n\nPublishing of a Retraction Notice will adhere to the following guidelines:
\n\n1.2. REMOVALS AND CANCELLATIONS
\n\n2. STATEMENTS OF CONCERN
\n\nA Statement of Concern detailing alleged misconduct will be issued by the Academic Editor or publisher following a 3rd party report of scientific misconduct when:
\n\nIntechOpen believes that the number of occasions on which a Statement of Concern is issued will be very few in number. In all cases when such a decision has been taken by the Academic Editor the decision will be reviewed by another editor to whom the author can make representations.
\n\n3. CORRECTIONS
\n\nA Correction will be issued by the Academic Editor when:
\n\n3.1. ERRATUM
\n\nAn Erratum will be issued by the Academic Editor when it is determined that a mistake in a Chapter originates from the production process handled by the publisher.
\n\nA published Erratum will adhere to the Retraction Notice publishing guidelines outlined above.
\n\n3.2. CORRIGENDUM
\n\nA Corrigendum will be issued by the Academic Editor when it is determined that a mistake in a Chapter is a result of an Author’s miscalculation or oversight. A published Corrigendum will adhere to the Retraction Notice publishing guidelines outlined above.
\n\n4. FINAL REMARKS
\n\nIntechOpen wishes to emphasize that the final decision on whether a Retraction, Statement of Concern, or a Correction will be issued rests with the Academic Editor. The publisher is obliged to act upon any reports of scientific misconduct in its publications and to make a reasonable effort to facilitate any subsequent investigation of such claims.
\n\nIn the case of Retraction or removal of the Work, the publisher will be under no obligation to refund the APC.
\n\nThe general principles set out above apply to Retractions and Corrections issued in all IntechOpen publications.
\n\nAny suggestions or comments on this Policy are welcome and may be sent to permissions@intechopen.com.
\n\nPolicy last updated: 2017-09-11
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However, there has been a steadily growing clinical data revealing the active roles of erythrocytes in hemostasis. RBCs may contribute to thrombosis in several ways. In polycythemia, RBCs increase blood viscosity and marginate platelets toward the endothelium. The increased incidence of thrombosis is also associated with hemolytic anemia, especially with sickle cell disease and paroxysmal nocturnal hemoglobinuria. RBCs express phosphatidylserine and microparticles, supporting thrombin generation. They interact with platelets, endothelial cells, and fibrinogen, and these interactions lead their incorporation into the thrombi. The presence of RBCs in clots suppresses plasmin generation and reduces clot dissolution. Decreasing thrombus RBC content would accelerate thrombus resolution. In conclusion, RBCs are important complements of the complex reactions of clot formation.",book:{id:"5965",slug:"transfusion-medicine-and-scientific-developments",title:"Transfusion Medicine and Scientific Developments",fullTitle:"Transfusion Medicine and Scientific Developments"},signatures:"Anil Tombak",authors:[{id:"202814",title:"Associate Prof.",name:"Anil",middleName:null,surname:"Tombak",slug:"anil-tombak",fullName:"Anil Tombak"}]},{id:"70657",doi:"10.5772/intechopen.90372",title:"Distribution of Clinically Relevant Blood Group Antigens among Nigerians and the Management of Rhesus D Negative Pregnancies: Implications for Haemolytic Disease of the Foetus and Newborn and Haemolytic Transfusion Reactions",slug:"distribution-of-clinically-relevant-blood-group-antigens-among-nigerians-and-the-management-of-rhesu",totalDownloads:745,totalCrossrefCites:4,totalDimensionsCites:4,abstract:"The ABO and Rhesus blood group systems are the most clinically relevant blood group systems from haemolytic disease of the foetus and newborn (HDFN) and haemolytic transfusion reaction (HTR) perspectives. Other clinically relevant blood group systems include the Kell, Duffy, Kidd and MNSs blood group systems. The clinical relevance of a blood group system depends on the ability of antibodies of the system to cause HDFN and HTR. This chapter discusses the distribution of ABO, Rhesus and other clinically relevant red cell antigens among Nigerians and implications for HDFN and HTR. There are several challenges associated with the management of Rhesus negative pregnancies, pregnancies associated with clinically significant alloantibodies, implementation of policy on routine antenatal anti-D prophylaxis (RAADP), management of Rhesus negative women that require termination of pregnancy (TOP), provision of antigen negative blood for certain patient groups and the management of pregnant and non-pregnant patients with clinically significant alloantibodies. This chapter highlights the need for Nigeria and other African countries to implement best practices to optimize the care offered to pregnant women as well as patients in whom red cell transfusion is indicated.",book:{id:"9027",slug:"human-blood-group-systems-and-haemoglobinopathies",title:"Human Blood Group Systems and Haemoglobinopathies",fullTitle:"Human Blood Group Systems and Haemoglobinopathies"},signatures:"Osaro Erhabor, Tosan Erhabor, Teddy Charles Adias and Iwueke Ikechukwu Polycarp",authors:[{id:"35140",title:"Dr.",name:"Osaro",middleName:null,surname:"Erhabor",slug:"osaro-erhabor",fullName:"Osaro Erhabor"},{id:"35151",title:"Prof.",name:"Teddy",middleName:"Charles",surname:"Adias",slug:"teddy-adias",fullName:"Teddy Adias"},{id:"308337",title:"Dr.",name:"Tosan",middleName:null,surname:"Erhabor",slug:"tosan-erhabor",fullName:"Tosan Erhabor"},{id:"308338",title:"Dr.",name:"Iwueke",middleName:null,surname:"Ikechukwu",slug:"iwueke-ikechukwu",fullName:"Iwueke Ikechukwu"}]},{id:"70802",doi:"10.5772/intechopen.90995",title:"Sickle Cell Anemia, Representations and Care: Experience of a Brother of a Sick Child in Cameroon",slug:"sickle-cell-anemia-representations-and-care-experience-of-a-brother-of-a-sick-child-in-cameroon",totalDownloads:502,totalCrossrefCites:2,totalDimensionsCites:4,abstract:"In Africa, families often with more than one child consult with both modern and traditional African medicine to treat their child with sickle cell anemia. This research aimed to understand how a child experiences both the medical and traditional care of his sister. We collected data from an interview and family drawing of a young boy growing up with an affected sister in Cameroon. Results showed this child persisted to feel as though his sister had fallen victim to a sorcerer and that he was at risk of the same fate even after the two of them received traditional treatment. He also felt neglected about his suffering because of his sister’s disease by hospital professionals that were caring for her. It is therefore necessary to establish a support system for affected children and their family by providing a safe space in hospitals where they can express and contain their experiences with the disease.",book:{id:"9027",slug:"human-blood-group-systems-and-haemoglobinopathies",title:"Human Blood Group Systems and Haemoglobinopathies",fullTitle:"Human Blood Group Systems and Haemoglobinopathies"},signatures:"Hassan Njifon Nsangou and Régine Scelles",authors:[{id:"312724",title:"Ph.D.",name:"Hassan",middleName:null,surname:"Njifon Nsangou",slug:"hassan-njifon-nsangou",fullName:"Hassan Njifon Nsangou"},{id:"312830",title:"Prof.",name:"Régine",middleName:null,surname:"Scelles",slug:"regine-scelles",fullName:"Régine Scelles"}]},{id:"64280",doi:"10.5772/intechopen.81895",title:"Lymphocytes Studied by Raman Microspectroscopy",slug:"lymphocytes-studied-by-raman-microspectroscopy",totalDownloads:1013,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"The Raman spectroscopy detects the interaction of the incident light with the electrons in the illuminated molecule. The use of Raman spectroscopy to investigate biological molecular structures and the recognition of their particular functional groups have been growing rapidly, and nowadays the use of Raman spectroscopy has expanded toward the cellular level. The activation of lymphocytes occurs when they are exposed to viruses or other foreign antigens. We have observed that Raman spectroscopy can be used to screen the activation of lymphocytes during viral infection. We have indicated the bands that reveal differences between activated and intact cells. The most important marker of the lymphocyte activation process is the prominent 521 cm−1 disulfide band which marks the immunoglobulin formation. The blood from the patients with viral infections, e.g., mononucleosis, and from healthy volunteers was obtained by venipuncture during hospitalization in the University Hospital in Kraków.",book:{id:"6969",slug:"lymphocytes",title:"Lymphocytes",fullTitle:"Lymphocytes"},signatures:"Magdalena Pietruszewska, Grażyna Biesiada, Jacek Czepiel,\nMalwina Birczyńska, Paulina Moskal, Mateusz Kozicki, Emilia Hola,\nAleksander Garlicki and Aleksandra Wesełucha-Birczyńska",authors:null},{id:"69794",doi:"10.5772/intechopen.89952",title:"The Duffy Blood Group System",slug:"the-duffy-blood-group-system",totalDownloads:867,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"The Duffy group system includes six known antigens that reside on a glycoprotein which acts as a receptor for chemokines. It is also a receptor for some malaria species. There are significant racial variations in expression of Duffy antigens. Approximately 68% of Blacks lack both Fya and Fyb antigens. Individuals with this unique phenotype are resistant to two malaria species. Antibodies formed against the Duffy antigens are of IgG subclass and are clinically significant as they can be implicated in acute and delayed hemolytic transfusion reactions as well as hemolytic disease of fetus and newborn. Patients who form anti-Fya or anti-Fyb must receive antigen negative blood units in the future.",book:{id:"9027",slug:"human-blood-group-systems-and-haemoglobinopathies",title:"Human Blood Group Systems and Haemoglobinopathies",fullTitle:"Human Blood Group Systems and Haemoglobinopathies"},signatures:"Fatima A. Aldarweesh",authors:[{id:"307172",title:"Dr.",name:"Fatima A.",middleName:null,surname:"Aldarweesh",slug:"fatima-a.-aldarweesh",fullName:"Fatima A. Aldarweesh"}]}],mostDownloadedChaptersLast30Days:[{id:"73837",title:"Inherited Disorders of Hemoglobin and Plasmodium falciparum Malaria",slug:"inherited-disorders-of-hemoglobin-and-em-plasmodium-falciparum-em-malaria",totalDownloads:546,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"An estimated 300,000 babies are born each year with severe Inherited Disorders of Hemoglobin (IDH). Despite major advances in the understanding of the molecular pathology, control, and management of the IDH thousands of infants and children with these diseases are dying due to the accessibility to appropriate medical care. In addition, as malaria has been the principal cause of early mortality in several parts of the world for much of the last 5000 years, as a result, it is the strongest force for selective pressure on the human genome. That is why, in the world, there is an overlap of malaria endemicity and IDH. Over the past twenty years several studies have shown that IDH such us hemoglobin and/or red cell membrane abnormalities confer resistance to malaria reducing hence the mortality during the first years of life. This has led to the selection of populations with IDH in malaria-endemic areas. This may explain the overlap between these two pathologies. This chapter aims to present the relationship between IDH and malaria susceptibility, make an overview of the current state of knowledge and the burden of IDH, and highlight steps that require to be taken urgently to improve the situation.",book:{id:"9027",slug:"human-blood-group-systems-and-haemoglobinopathies",title:"Human Blood Group Systems and Haemoglobinopathies",fullTitle:"Human Blood Group Systems and Haemoglobinopathies"},signatures:"Edith Christiane Bougouma and Sodiomon Bienvenu Sirima",authors:[{id:"319317",title:"Dr.",name:"Edith Christiane",middleName:"Christianne",surname:"Bougouma",slug:"edith-christiane-bougouma",fullName:"Edith Christiane Bougouma"},{id:"319864",title:"Dr.",name:"Sodiomon Bienvenu",middleName:null,surname:"Sirima",slug:"sodiomon-bienvenu-sirima",fullName:"Sodiomon Bienvenu Sirima"}]},{id:"55676",title:"Transfusion in Transplantation",slug:"transfusion-in-transplantation",totalDownloads:1806,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Hematopoietic stem cell transplantation is increasingly performed in several diseases; majority of them are hematologic malignancies. Hematopoietic stem cell transplantation is not an instant procedure; contrarily, its unique clinical and laboratorial consequences may take life‐long time. Blood product transfusion is an inevitable and critical component for the management. Hematopoietic stem cell transplant patients have different requirements regarding blood products transfusion because of their immune status, long‐term cytopenias and especially HLA and ABO incompatibilities. Health‐care staff who take a part in the management of those patients should be aware of specific and specialized transfusion requirements.",book:{id:"5965",slug:"transfusion-medicine-and-scientific-developments",title:"Transfusion Medicine and Scientific Developments",fullTitle:"Transfusion Medicine and Scientific Developments"},signatures:"Eren Arslan Davulcu, Fahri Sahin and Güray Saydam",authors:[{id:"94230",title:"Prof.",name:"Guray",middleName:null,surname:"Saydam",slug:"guray-saydam",fullName:"Guray Saydam"},{id:"94231",title:"Prof.",name:"Fahri",middleName:null,surname:"Sahin",slug:"fahri-sahin",fullName:"Fahri Sahin"},{id:"202813",title:"M.D.",name:"Eren",middleName:null,surname:"Arslan Davulcu",slug:"eren-arslan-davulcu",fullName:"Eren Arslan Davulcu"}]},{id:"55954",title:"Red Blood Cells and Relation to Thrombosis",slug:"red-blood-cells-and-relation-to-thrombosis",totalDownloads:2030,totalCrossrefCites:4,totalDimensionsCites:4,abstract:"Blood coagulation and thrombin generation are primarily a function of platelets, coagulation factors, and endothelial cells. Red blood cells (RBCs) have generally been viewed as innocent bystanders in the clotting process. However, there has been a steadily growing clinical data revealing the active roles of erythrocytes in hemostasis. RBCs may contribute to thrombosis in several ways. In polycythemia, RBCs increase blood viscosity and marginate platelets toward the endothelium. The increased incidence of thrombosis is also associated with hemolytic anemia, especially with sickle cell disease and paroxysmal nocturnal hemoglobinuria. RBCs express phosphatidylserine and microparticles, supporting thrombin generation. They interact with platelets, endothelial cells, and fibrinogen, and these interactions lead their incorporation into the thrombi. The presence of RBCs in clots suppresses plasmin generation and reduces clot dissolution. Decreasing thrombus RBC content would accelerate thrombus resolution. In conclusion, RBCs are important complements of the complex reactions of clot formation.",book:{id:"5965",slug:"transfusion-medicine-and-scientific-developments",title:"Transfusion Medicine and Scientific Developments",fullTitle:"Transfusion Medicine and Scientific Developments"},signatures:"Anil Tombak",authors:[{id:"202814",title:"Associate Prof.",name:"Anil",middleName:null,surname:"Tombak",slug:"anil-tombak",fullName:"Anil Tombak"}]},{id:"70920",title:"Harmonized and Quality Sample Handling in Biobank-Supported Multicenter Prospective Studies",slug:"harmonized-and-quality-sample-handling-in-biobank-supported-multicenter-prospective-studies",totalDownloads:634,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"In the frame of multicenter research studies, biobanks ensure the harmonization and traceability of the prospective collection of quality samples. This is significant because pre-analytical variables must be carefully considered to guarantee the integrity of biomarkers to be tested and to avoid bias affecting the validity of the analytical results. According to a quality management system, biobanks contribute with documents and records; consumable preparation for collection, processing, and conservation; sample quality controls; and centralized management of sample handling, storage, and distribution. Traceability of samples is based on unique standard codes and the use of pre-assigned, pre-coded, and pre-labeled materials for sample collection, processing, and conservation. By using these supporting tools, quality derivatives are obtained based on common and evidence-based standard operating procedures (SOPs), with associated traceability information in relation with their collection, processing, conservation, and distribution. The biobank-supported workflow, specifically designed and implemented for each project, allows obtaining harmonized quality samples contributing to the quality of large and complex research projects and the corresponding validity of the analyses.",book:{id:"9027",slug:"human-blood-group-systems-and-haemoglobinopathies",title:"Human Blood Group Systems and Haemoglobinopathies",fullTitle:"Human Blood Group Systems and Haemoglobinopathies"},signatures:"Verónica Valdivieso-Gómez, Javier Garrancho-Pérez, Inés Aroca-Siendones and Rocío Aguilar-Quesada",authors:[{id:"217457",title:"Ph.D.",name:"Rocio",middleName:null,surname:"Aguilar-Quesada",slug:"rocio-aguilar-quesada",fullName:"Rocio Aguilar-Quesada"},{id:"217467",title:"Ms.",name:"Veronica",middleName:null,surname:"Valdivieso-Gomez",slug:"veronica-valdivieso-gomez",fullName:"Veronica Valdivieso-Gomez"},{id:"311385",title:"Mr.",name:"Javier",middleName:null,surname:"Garrancho-Pérez",slug:"javier-garrancho-perez",fullName:"Javier Garrancho-Pérez"},{id:"311386",title:"Ms.",name:"Inés",middleName:null,surname:"Aroca-Siendones",slug:"ines-aroca-siendones",fullName:"Inés Aroca-Siendones"}]},{id:"62616",title:"Understanding B Lymphocyte Development: A Long Way to Go",slug:"understanding-b-lymphocyte-development-a-long-way-to-go",totalDownloads:1695,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"B lymphocytes play a significant role in both antigen-dependent and antigen-independent pathways. Although significant progress has been made in context of delineating the pathways that lead to their development, maturity and differentiation, their detailed mechanisms are yet to be dissected out completely. This chapter is aimed towards summarising the knowledge that has been gained till date and identifying the areas that need to be addressed in future research work. Overall, the chapter is planned in a sequential way to guide the reader through the processes of B cell development and the various latest findings that have improved our understanding of this vital physiological system.",book:{id:"6969",slug:"lymphocytes",title:"Lymphocytes",fullTitle:"Lymphocytes"},signatures:"Malavika Bhattacharya",authors:null}],onlineFirstChaptersFilter:{topicId:"1030",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:99,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:289,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"10",title:"Physiology",doi:"10.5772/intechopen.72796",issn:"2631-8261",scope:"Modern physiology requires a comprehensive understanding of the integration of tissues and organs throughout the mammalian body, including the cooperation between structure and function at the cellular and molecular levels governed by gene and protein expression. While a daunting task, learning is facilitated by identifying common and effective signaling pathways mediated by a variety of factors employed by nature to preserve and sustain homeostatic life. \r\nAs a leading example, the cellular interaction between intracellular concentration of Ca+2 increases, and changes in plasma membrane potential is integral for coordinating blood flow, governing the exocytosis of neurotransmitters, and modulating gene expression and cell effector secretory functions. Furthermore, in this manner, understanding the systemic interaction between the cardiovascular and nervous systems has become more important than ever as human populations' life prolongation, aging and mechanisms of cellular oxidative signaling are utilised for sustaining life. \r\nAltogether, physiological research enables our identification of distinct and precise points of transition from health to the development of multimorbidity throughout the inevitable aging disorders (e.g., diabetes, hypertension, chronic kidney disease, heart failure, peptic ulcer, inflammatory bowel disease, age-related macular degeneration, cancer). 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He has published 290 original articles in some of the most prestigious scientific journals and seven book chapters on the pathophysiology of the GI tract, gastroprotection, ulcer healing, drug therapy of peptic ulcers, hormonal regulation of the gut, and inflammatory bowel disease.",institutionString:null,institution:{name:"Jagiellonian University",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"10",title:"Animal Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/10.jpg",isOpenForSubmission:!0,annualVolume:11406,editor:{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. 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From\r\n1964 to 1974, he worked as Assistant in Biochemistry at the School of MedicineUniversidad Nacional de La Plata, Argentina. From 1974 to 1976, he was a Fellowof the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor oBiochemistry at the Universidad Nacional de La Plata, Argentina. He is Member ofthe National Research Council (CONICET), Argentina, and Argentine Society foBiochemistry and Molecular Biology (SAIB). His laboratory has been interested for manyears in the lipid peroxidation of biological membranes from various tissues and different species. Professor Catalá has directed twelve doctoral theses, publishedover 100 papers in peer reviewed journals, several chapters in books andtwelve edited books. Angel Catalá received awards at the 40th InternationaConference Biochemistry of Lipids 1999: Dijon (France). W inner of the Bimbo PanAmerican Nutrition, Food Science and Technology Award 2006 and 2012, South AmericaHuman Nutrition, Professional Category. 2006 award in pharmacology, Bernardo\r\nHoussay, in recognition of his meritorious works of research. Angel Catalá belongto the Editorial Board of Journal of lipids, International Review of Biophysical ChemistryFrontiers in Membrane Physiology and Biophysics, World Journal oExperimental Medicine and Biochemistry Research International, W orld Journal oBiological Chemistry, Oxidative Medicine and Cellular Longevity, Diabetes and thePancreas, International Journal of Chronic Diseases & Therapy, International Journal oNutrition, Co-Editor of The Open Biology Journal.",institutionString:null,institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}},editorTwo:null,editorThree:null},{id:"12",title:"Human Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/12.jpg",isOpenForSubmission:!0,annualVolume:11408,editor:{id:"195829",title:"Prof.",name:"Kunihiro",middleName:null,surname:"Sakuma",slug:"kunihiro-sakuma",fullName:"Kunihiro Sakuma",profilePictureURL:"https://mts.intechopen.com/storage/users/195829/images/system/195829.jpg",biography:"Professor Kunihiro Sakuma, Ph.D., currently works in the Institute for Liberal Arts at the Tokyo Institute of Technology. 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His opinion is to attenuate sarcopenia by improving autophagic defects using nutrient- and pharmaceutical-based treatments.",institutionString:null,institution:{name:"Tokyo Institute of Technology",institutionURL:null,country:{name:"Japan"}}},editorTwo:null,editorThree:{id:"331519",title:"Dr.",name:"Kotomi",middleName:null,surname:"Sakai",slug:"kotomi-sakai",fullName:"Kotomi Sakai",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000031QtFXQA0/Profile_Picture_1637053227318",biography:"Senior researcher Kotomi Sakai, Ph.D., MPH, works at the Research Organization of Science and Technology in Ritsumeikan University. She is a researcher in the geriatric rehabilitation and public health field. She received Ph.D. from Nihon University and MPH from St.Luke’s International University. Her main research interest is sarcopenia in older adults, especially its association with nutritional status. Additionally, to understand how to maintain and improve physical function in older adults, to conduct studies about the mechanism of sarcopenia and determine when possible interventions are needed.",institutionString:null,institution:{name:"Ritsumeikan University",institutionURL:null,country:{name:"Japan"}}}},{id:"13",title:"Plant Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/13.jpg",isOpenForSubmission:!0,annualVolume:11409,editor:{id:"332229",title:"Prof.",name:"Jen-Tsung",middleName:null,surname:"Chen",slug:"jen-tsung-chen",fullName:"Jen-Tsung Chen",profilePictureURL:"https://mts.intechopen.com/storage/users/332229/images/system/332229.png",biography:"Dr. Jen-Tsung Chen is currently a professor at the National University of Kaohsiung, Taiwan. He teaches cell biology, genomics, proteomics, medicinal plant biotechnology, and plant tissue culture. Dr. Chen\\'s research interests include bioactive compounds, chromatography techniques, in vitro culture, medicinal plants, phytochemicals, and plant biotechnology. He has published more than ninety scientific papers and serves as an editorial board member for Plant Methods, Biomolecules, and International Journal of Molecular Sciences.",institutionString:"National University of Kaohsiung",institution:{name:"National University of Kaohsiung",institutionURL:null,country:{name:"Taiwan"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:17,paginationItems:[{id:"81791",title:"Self-Supervised Contrastive Representation Learning in Computer Vision",doi:"10.5772/intechopen.104785",signatures:"Yalin Bastanlar and Semih Orhan",slug:"self-supervised-contrastive-representation-learning-in-computer-vision",totalDownloads:12,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Pattern Recognition - New Insights",coverURL:"https://cdn.intechopen.com/books/images_new/11442.jpg",subseries:{id:"26",title:"Machine Learning and Data Mining"}}},{id:"79345",title:"Application of Jump Diffusion Models in Insurance Claim Estimation",doi:"10.5772/intechopen.99853",signatures:"Leonard Mushunje, Chiedza Elvina Mashiri, Edina Chandiwana and Maxwell Mashasha",slug:"application-of-jump-diffusion-models-in-insurance-claim-estimation-1",totalDownloads:2,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Data Clustering",coverURL:"https://cdn.intechopen.com/books/images_new/10820.jpg",subseries:{id:"26",title:"Machine Learning and Data Mining"}}},{id:"81557",title:"Object Tracking Using Adapted Optical Flow",doi:"10.5772/intechopen.102863",signatures:"Ronaldo Ferreira, Joaquim José de Castro Ferreira and António José Ribeiro Neves",slug:"object-tracking-using-adapted-optical-flow",totalDownloads:10,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Information Extraction and Object Tracking in Digital Video",coverURL:"https://cdn.intechopen.com/books/images_new/10652.jpg",subseries:{id:"24",title:"Computer Vision"}}},{id:"81558",title:"Thresholding Image Techniques for Plant Segmentation",doi:"10.5772/intechopen.104587",signatures:"Miguel Ángel Castillo-Martínez, Francisco Javier Gallegos-Funes, Blanca E. Carvajal-Gámez, Guillermo Urriolagoitia-Sosa and Alberto J. 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(Eng.) in Telematics from the Universidad de Colima, Mexico. He obtained both his M.Sc. and Ph.D. from the University of Liverpool, England, in the field of Intelligent Systems. He is a full professor at the Universidad Autonoma de Queretaro, Mexico, and a member of the National System of Researchers (SNI) since 2009. Dr. Aceves Fernandez has published more than 80 research papers as well as a number of book chapters and congress papers. He has contributed in more than 20 funded research projects, both academic and industrial, in the area of artificial intelligence, ranging from environmental, biomedical, automotive, aviation, consumer, and robotics to other applications. He is also a honorary president at the National Association of Embedded Systems (AMESE), a senior member of the IEEE, and a board member of many institutions. His research interests include intelligent and embedded systems.",institutionString:"Universidad Autonoma de Queretaro",institution:{name:"Autonomous University of Queretaro",institutionURL:null,country:{name:"Mexico"}}}]},{type:"book",id:"7726",title:"Swarm Intelligence",subtitle:"Recent Advances, New Perspectives and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/7726.jpg",slug:"swarm-intelligence-recent-advances-new-perspectives-and-applications",publishedDate:"December 4th 2019",editedByType:"Edited by",bookSignature:"Javier Del Ser, Esther Villar and Eneko Osaba",hash:"e7ea7e74ce7a7a8e5359629e07c68d31",volumeInSeries:2,fullTitle:"Swarm Intelligence - Recent Advances, New Perspectives and Applications",editors:[{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:null}]},{type:"book",id:"7656",title:"Fuzzy Logic",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7656.jpg",slug:"fuzzy-logic",publishedDate:"February 5th 2020",editedByType:"Edited by",bookSignature:"Constantin Volosencu",hash:"54f092d4ffe0abf5e4172a80025019bc",volumeInSeries:3,fullTitle:"Fuzzy Logic",editors:[{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. 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