Types of flavonoids.
\r\n\tThis book intends to provide the reader with a comprehensive overview of the current state-of-the-art on Theileriosis, Babesiosis, and Anaplasmosis, both in humans and domestic animals. Particularly this book aims to permit the researchers to enter into a critical focus on the biology of the parasites, eco-epidemiology of the diseases, clinical manifestations, risk factors, immunology, surveillance, diagnosis, identification, and management of risks as well as the potential economic impact on animal production.
",isbn:"978-1-80356-384-8",printIsbn:"978-1-80356-383-1",pdfIsbn:"978-1-80356-385-5",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"3d72ae651ee2a04b2368bf798a3183ca",bookSignature:"Prof. Elisa Pieragostini",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11577.jpg",keywords:"Zoonosis, Global Climate Change, Epidemiology, Risk Factors, Haemoparasites, Prevention & Control, Piroplasmosis, Anaplasmosis, Babesiosis, Theileriosis, Tick-Borne Diseases, Ticks",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 23rd 2022",dateEndSecondStepPublish:"April 29th 2022",dateEndThirdStepPublish:"June 28th 2022",dateEndFourthStepPublish:"September 16th 2022",dateEndFifthStepPublish:"November 15th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"3 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"Professor of Animal genetics and breeding at Bari University, a researcher in animal genetics related to the resilience of Apulian livestock to enzootic tick-borne haemoparasites and to the involved functional effect of hemoglobin variants. She is a member of national and international scientific associations.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"51521",title:"Prof.",name:"Elisa",middleName:null,surname:"Pieragostini",slug:"elisa-pieragostini",fullName:"Elisa Pieragostini",profilePictureURL:"https://mts.intechopen.com/storage/users/51521/images/system/51521.jpg",biography:"Dr. Pieragostini has a Degree in Biological Sciences, DPhil in Biochemistry received from Bologna University, Italy.\r\nShe was an Assistant professor of “Genetics” at the Faculty of Science of Bologna University, a Full professor of “Animal genetics and breeding” Bari University, Italy, and Elected President of course on “Agricultural Science and Technology” (2001-2010) Bari University.\r\nShe retired in 2015.\r\nFrom 1977 to 1984 she carried out intensive work on Drosophila investigating quantitative characters associated with biochemical markers. From the1985 onwards, she had been studying Apulian farm animals focusing on blood-based markers as well as on the structure-function relationship of the different hemoglobin variants come across and their relationship with the Apulian livestock resilience to the enzootic tick-borne diseases. \r\nShe was Project Director\r\nShe is a member of national and international scientific associations.",institutionString:"Independent Researcher",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Bari Aldo Moro",institutionURL:null,country:{name:"Italy"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"16",title:"Medicine",slug:"medicine"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"280415",firstName:"Josip",lastName:"Knapic",middleName:null,title:"Mr.",imageUrl:"https://mts.intechopen.com/storage/users/280415/images/8050_n.jpg",email:"josip@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copy-editing and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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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).
City councils in Chile have taken on an increasingly prominent role in the political-economic and public-media spheres, especially after the emergence of the unexpected outbreak of the pandemic and the social unrest prior to Covid-19. The analysis of these institutions becomes relevant, as well as the need to establish interdisciplinary and econometric instruments, that can provide public policies with better data, in order to optimize the perspectives of local government efficiency in situations of high instability and global-local complexity.
\nIn a country with a centralized administration system, the attributes of which intensified after the 1973 coup d’état and subsequent dictatorship of Augusto Pinochet, municipalities have since become bureaucratic units that are fundamental in the life and control of the population, due to a range of responsibilities assigned to them in their communal territories.
\nWith the arrival of democracy in 1990, a number of political and participative adjustments were implemented that impacted the municipalities. However, the challenges continued to multiply as social and cultural transformations were taking place in these territorial areas, all of a different nature and stretching across more than 4000 km on the mainland and islands of Chile.
\nNevertheless, the Chilean political system maintains its marked presidentialism and has not been able to move forward towards a decisive decentralization. High-ranking officials, such as regional and provincial governors, continue to be designated in accordance with criteria defined in the country’s capital or by elite groups.
\nThe OECD [1] points out that Chile has a long tradition of centralism, with an administration system associated with economic efficiency and political stability. However, there are discussions on the need to improve regional performance and competitiveness from a necessarily decentralizing role [2], capable of bringing the country, that received international recognition for its political and economic transition in the nineties, into line with the new challenges.
\nThe objective of the following research is to select municipalities that are regional capitals with over 50,000 inhabitants, in order to determine the factors that influence the efficiency of these city councils in Chile, based on the quality of life index of the districts. To do so, an econometric model was developed to explain the specific factors of the efficiency of city councils in Chile, as well as the variables with the greatest impact on such efficiency.
\nWe believe that this is a necessary yet seldom addressed dimension in Chile, in terms of the inputs that econometrics can provide, to move forward with better interdisciplinary perspectives in order to empower regional governments that promote human development in pursuit of sustainability and the best possible democratic and social conditions.
\nIn 2019, Chile experienced an outbreak of social unrest that began in October 2019, and was only interrupted by the arrival of the Covid-19 pandemic, in March 2020. This period of mobilization prior to the coronavirus, marked by ongoing protests throughout the country, demanded a new social and political pact, substantiated on the lost credibility of government institutions, politicians, business people and the clergy.
\nThe crisis was felt with unexpected force and presence in the streets and major public areas of the regional capitals, particularly in those with larger populations.
\nThe citizenry demanded better conditions for old-age pensions, access to healthcare, protection against market abuse and gender-based violence, among other things. These social causes have tended to come together under feelings of indignation that have sparked off a demand to end the most urgent inequalities and to bring greater dignity to the population. This has led to articulating the need for a more systematic change, driven by the demand for a new Political Constitution.
\nDuring the most critical times of the social unrest, between October and December 2019, with episodes of public violence and obvious problems of governance at the central level, the city councils proved to be a strategic political space by building bridges to address the citizens’ malaise. They showed a greater sensitivity and capacity for participation with different stakeholders and organizations of the local territories. The municipalities also made their resources available to help unblock the lack of social dialog and revert an increasing political polarization.
\nWith the onset of the health emergency in Chile in March 2020, the city councils once again became important spheres for social and political-media leadership, requesting the central government to implement quarantine measures, for greater coordination with the public health system, and urgent economic support plans for Covid-19, in response to public concern about the quick propagation of the virus. The city councils also focused their resources on meeting the people’s most immediate and actual demands, complementing the efforts of the ministries involved in managing the crisis.
\nDuring both of the episodes described (social unrest and Covid-19), that is, within the scope of a political and a health crisis, various surveys and public opinion polls showed that the Chilean city councils were among the most valued government institutions by the people.
\nIndeed, the potential that this kind of municipal organization has for future political, health or economic challenges could be crucial for the efficiency of the State and the identity of the territories. Therefore, we stress the need for a more in-depth study of the context and the variables that could improve the living conditions of the communities located within the municipalities.
\nAt present, there are 345 municipalities in Chile and they are defined in the Constitution as “autonomous public law corporations with legal status and their own assets. Their objective is to satisfy the needs of the local community and ensure their participation in the economic, cultural and social development” [3].
\nThe Constitutional Organic Law of Municipalities N°18.695 specifically regulates the most important aspects of the communal administration. For instance, it establishes the existence of a mayor and a city council, along with their respective functions and powers. However, there are numerous laws that regulate other aspects.
\nAccording to political theory, Chile’s municipalities constitute a public service that operate as a decentralized State body and are the State’s closest visible face for its citizens [4]. However, the concentration of the Chilean political system is evident in the difference established between the government and the administration.
\nThe government has the capacity for political decision-making, while the administration is a more limited concept and is further removed from political power. In fact, government powers in the territories are in the hands of the regional and provincial governors (chosen by the president in office) and those of the mayors are only for the municipal administration of their communes or cities [4].
\nA local government, as a political body of representation and not only of the administrative kind, is vested with the right of its municipalities to take certain decisions without the authorization or interference of the central government. In other words, [5] with its actions, a municipality can have independent effects on significant aspects of a specific community.
\nIn 2009, a process began to implement territorial decentralization through a series of legal changes, in pursuit of the election of regional counselors (regulated in 2013) and governors (suspended due to Covid-19, although regulated in 2018), along with establishing a system to transfer competences to regional governments (formalized in 2018). For some authors, this has meant progress, from a model of deconcentrated transiting towards one of territorial decentralization, as these laws would allegedly favor the modification of regional administration and the relationship of vertical political power [2, 6].
\nHowever, the Regional Authority Index [7], which compares the degree of decentralization between different countries, ranks us in 52nd place out of 63. This position is similar to nations of a smaller scale and population such as Ireland and Lithuania. Explanations could argue that Chile is compared with countries of a very different size and institutional regime. But if we limit the comparison to OECD unitary states with more than 3 million inhabitants, the results do not improve [8].
\nMaintaining a tendency towards centralization may bring about negative effects. For example, it creates administrative inefficiencies when requesting permits that need to be approved at the central level, hindering the possibility of innovation in public policies, due to the lack of competences and economic resources. It also limits economic growth and productivity, generating territorial imbalances and inequalities, where some regions are winners and others lag behind [8].
\nOne of the most specific aspects for true decentralization, that seeks to favor the power of municipalities, lies in transferring the competence and decision-making capacity, including, most notably, on budgetary matters, which “are fundamental and unavoidable” [9].
\nThe efficiency of the Chilean State’s resources should focus on a better connection with local spheres and study, in turn, what municipalities are doing with their administrations and how their decisions are impacting their respective communities. In fact, the OECD [1] pointed out that, in Chile, centralization hampers the development of the country.
\nAs for the economic situation, municipalities have several sources of income that can be differentiated between own funds and external funds [10]. While own funds consist of the Municipal Common Fund and Permanent Own-Source Income, external funds include those transferred to municipalities for programs or projects promoted by the central government and executed by local governments [11].
\nThe Municipal Common Fund (FCM) is regulated by Law N°20.237, the abovementioned Constitutional Organic Law of Municipalities (LOCM) and Decree N°1293 of the Ministry of the Interior of 2009. Law N°20.033 established that, as of 2005, a fixed monetary contribution from the central government for 218.000 UTM (approximately 11 billion Chilean pesos, or US$13.5 million) would be made to the FCM [11].
\nIt is worthwhile mentioning that the Municipal Common Fund is defined by the Political Constitution of the Republic (Article 122) as a “mechanism for the solidary redistribution of own incomes among the municipalities of the country” [11].
\nThe concept of efficiency applied to interdisciplinary dialog from the point of view of political and administrative theory, becomes especially important in times of crisis and empowerment of the people in their local setting.
\nPolitical efficiency is linked to “a government’s capability, competence or potential to establish guidelines that lead to objectives considered to be valid by a society at a specific time” [12]. City councils, on this level, are an institutional and operational power that, within their areas of impact, enables to achieve socially accepted and legally enshrined objectives.
\nAt the level of public management, administrative efficiency is legitimatized when it receives public recognition [13]. Citizen support of a State is largely the result of a performance that is perceived as efficient and effective, as for example, when it reduces poverty, unemployment or inequality. Hence, the democratic apparatus is strengthened and the people perceive that the performance of a municipality is coherent or fair. Public management creates a value [12], as long as there also is political communication that sets out these advances or achievements in a credible and plain way.
\nThe discussion between efficiency and democracy, under the perspective of legitimacy [14], understood as the capacity of political systems to generate, on the one hand, citizen representation and political responsibility (input-oriented legitimacy), and on the other, satisfactory results of public policies (output-oriented legitimacy) [15], is still valid in the current contexts we are analyzing.
\nIn fact, there is a third dimension of legitimacy that refers to the decision-making procedure (throughput legitimacy), given by transparency, the degree of openness and of inclusion [16]. The concept of representative democracy expands when examining in-depth analyses on how decisions are taken and whether they include deliberative democracy instruments that allow greater participation of all public and private stakeholders [17].
\nThis study determines the factors that influence the efficiency of city councils in Chile, in terms of the Quality of Life Index of the communities. To do so, an econometric model was developed to explain the determinants of the efficiency of city councils in Chile, and to identify the variables that have the greatest impact on such efficiency. Municipalities that are regional capitals, with over 50,000 inhabitants, were selected for this study.
\nThe efficiency model of the city councils demonstrates that, as described earlier, there is a growing interest in these entities in search of decentralization in Chile, as a way of strengthening the regions and to stop holding back the country’s development [18], which to a large extent could be carried out through efficient city councils. Therefore, arriving at the factors that determine the efficiency of the city council is of great importance, as it shows us the aspects that require special attention. New public policies focused on these aspects would increase the favorable perception of municipal management and, more importantly, the quality of life of the people.
\nFor the purposes of this research, a series of variables that are linked to the efficiency of Chilean municipalities will be included. Within this selection, variables stand out that have been a priority concern of citizens and that have tried to be incorporated into the country’s public policies. We refer, as shown in the final model (Table 1), to the Municipal Common Fund (FCM), Permanent Own-Source Income (IPP), rate of domestic violence, average University Selection Test (PSU) score, overcrowding and density.
Municipal Common Fund (FCM):
The FCM is the solidarity redistribution mechanism of own income in the municipalities of all Chile. In this regard, there is debate in political sectors of the country, about whether costs that are in line with resources would mean greater efficiency, since it would not translate into better provision of public services [19]. This is known in the literature as the “flypaper effect” [20], which could have a negative effect in the city councils of Chile.
Permanent Own-Source Income (IPP) [21]:
This is the budget of a city council, composed of the following accounts of the budget classifier: territorial tax, municipal benefit vehicle permits, municipal benefit licenses, sanitation taxes, other duties, property rentals, driver’s licenses and the like, fines and interests, concessions, aquaculture patents, mining patents and casinos. The probability that the inefficiency of public officials and local politicians increases, when there is a higher level of income that favors an increase in the fiscal capacity of the municipalities, is an aspect that the literature describes [22]. Meanwhile, the fiscal deficit could also have a negative impact on the efficiency of the city council as a variable of the IPP. If a municipality spends more than it can, it is exposed to financial vulnerability [23].
Overcrowding:
This variable is the result of the absence of urban development, both in infrastructure and housing. It affects the minimum conditions of people, integrated into a commune or political-administrative and territorial space. For the purposes of the study, it represents the average level of overcrowding in households, expressed as a percentage. It is a “different type of factor that influences the efficiency of the city council” [24], since it is associated with the characteristics of local residents and how these citizens coexist with their vital environments.
Population Density:
Population density considers, for these purposes, the number of inhabitants per km2. It has been shown [25] that a smaller number of inhabitants per square kilometer can increase the average cost of supplying goods and services, so that a municipality could be more efficient if its population density were higher.
Rate of Domestic Violence:
This is the rate of complaints of domestic violence reported per 100,000 inhabitants. According to studies on the subject, such violence ultimately harms an individual’s health and quality of life without distinction of gender, race or ethnicity around the world. This is supported by UNICEF’s definition of domestic violence, which includes that it is an affront to the quality of life [26].
Average University Selection Test (PSU) Score:
This is defined as the percentage of PSU scores equal to or greater than 450 points in municipal establishments. This score was defined, for the purpose of this research, under the assumption that each citizen who takes the University Selection Test (PSU) has a certain level of education and that he or she could potentially choose to improve that level. According to [25], it determined that the citizen participation variable, in relation with the educational level of the adult population, has a positive impact on the degree of city council efficiency. Along this same line are [23, 25, 26], which reinforce these results.
The research that explain the efficiency of the city councils, usually focus and limit themselves on socioeconomic, demographic and fiscal factors. In this sense, the literature is not abundant and tends to be obsolete, above all, because the local dimension in countries like Chile has undergone various changes in the last decade, being culturally and productively diverse.
\nThe models that are reiterated in the theme of the efficiency of city councils also present a special interest in resources. For example, there are authors [27] that maintain that the material well-being and the quality of life of a person do not have a direct correlation, varying this relationship by the level of income of citizens, the satisfaction or dissatisfaction of basic needs, as well as other factors [28]. According to [29] the interrelation between needs, satisfaction and economic goods, is of a permanent and dialectical nature. This can be explained, on the one hand, because economic goods can affect the efficiency of satisfaction; on the other, they are decisive in the generation and creation of these factors.
\nTherefore, taking into account that the municipalities are responsible for the administration of economic assets, obtained by the redistribution of resources, management has a direct impact on efficiency, as well as on factors that influence the quality of life in its set. Therefore, the planning and budget of each local reality is relevant.
\nDifferent authors point out that, as Chile is analyzed from North to South, the indicators improve [30]. However, the most prominent indicators are located in the central area of the country. Meanwhile, [19, 25, 31] consider that the higher the population density of the commune, the more efficient the city council will be.
\nThese hypotheses will be tested by the proposed final model, to determine the behavior of the Chilean municipalities and if it is related to what is presented in the literature.
\nThe research and analysis of efficiency in city councils in Chile, evidenced in the literature, is usually carried out from microeconomic theory, which evaluates two aspects of municipal efficiency: inputs and output.
\nIn fact, municipal efficiency is considered optimal when it reaches its maximum level of production, compared to certain inputs and the minimum level of inputs in a given product [24, 32].
\nIn the case of Chile, the studies and methodology applied to the efficiency of the city councils are few and focused on resources, not addressing other aspects of importance and complexity for the economic reality.
\nIn relation to the methodology, the analysis was applied to 93 communes in Chile, incorporating a diverse sample of the country, both in its political-administrative and geographical configuration. In other ways, the study integrates communes from the northern, central and southern macro-zones of the national territory. A cross-sectional econometric regression model was developed to explain and predict the effect over the municipal efficiency measured by Quality of Life Index (QLI) [33, 34, 35, 36]. This is validated by the assumptions of the residual before proceeding with the second objective, which is the estimation and interpretation of results [36, 37].
\nIn order to build the database to be used to forecast the efficiency of city councils in Chile [38], the National Municipal Information System was consulted, together with the Library of the National Congress of Chile (BCN), as well as an approximation based on the Urban Quality of Life Index (QLI) for the year 2018, while bearing in mind the different areas of the country. The model estimate specified in Eq. (1) is presented in the following Table 2.
\nVariable | \nCoefficient | \nStd. error | \nt-Statistic | \np-Value | \n
---|---|---|---|---|
RateDomesticViolence | \n−0.013222 | \n0.004051 | \n−3.263793 | \n0.0016 | \n
OwnIncomesIPP | \n1.12E-07 | \n3.26E-08 | \n3.433896 | \n0.0009 | \n
FCM | \n−2.15E-07 | \n7.71E-08 | \n−2.789977 | \n0.0065 | \n
Overcrowding | \n−79.50409 | \n17.53457 | \n−4.534135 | \n0.0000 | \n
Average PSU | \n16.36778 | \n4.456570 | \n3.672732 | \n0.0004 | \n
PopulationDensity | \n−0.000430 | \n0.000117 | \n−3.668260 | \n0.0004 | \n
C | \n59.43797 | \n4.688335 | \n12.67784 | \n0.0000 | \n
Final model parameter estimation.
Source: Own creation.
Variable | \nCoefficient | \nStd. error | \nt-Statistic | \np-Value | \n
---|---|---|---|---|
RateDomesticViolence | \n−0.012964 | \n0.004200 | \n−3.086408 | \n0.0028 | \n
Health Budget | \n0.076376 | \n0.053567 | \n1.425805 | \n0.1579 | \n
Scholarship | \n−0.000210 | \n8.57E-05 | \n−2.445162 | \n0.0167 | \n
OwnIncomesIPP | \n2.89E-07 | \n1.05E-07 | \n2.752694 | \n0.0073 | \n
Other Incomes | \n−3.70E-07 | \n2.59E-07 | \n−1.431423 | \n0.1563 | \n
FCM | \n1.64E-07 | \n2.15E-07 | \n0.762711 | \n0.4479 | \n
PopulationDensity | \n−0.000564 | \n0.000130 | \n−4.355540 | \n0.0000 | \n
Green Areas | \n1.84E-06 | \n1.15E-06 | \n1.598367 | \n0.1140 | \n
Average PSU | \n12.81732 | \n4.457474 | \n2.875466 | \n0.0052 | \n
Overcrowding | \n−57.43565 | \n18.52834 | \n−3.099881 | \n0.0027 | \n
Poverty | \n−22.91616 | \n13.88977 | \n−1.649859 | \n0.1030 | \n
C | \n59.64198 | \n4.667443 | \n12.77830 | \n0.0000 | \n
Estimation of general model parameters.
After estimating the tentative model using Stepwise Econometric Regression Models, and considering all of the variables studied to determine the quality of life of the inhabitants of a commune, the variables relevant to the determination of the study’s approach, such as municipal efficiency, were selected (see Table 1). The variables that were greater than the minimum level of confidence (p-value ≤0.05) adopted for this study were eliminated from the model. In addition to this method, what was stated in the literature and determination of the endogenous variable was also considered.
\nGiven the estimates of the variables described earlier in this chapter, a final econometric model was proposed that better and more up-to-date (Table 1) represents the factors that involve the efficiency of city councils in Chile.
\nAccording to the Quality of Life Index (QLI), the variability in the efficiency of Chilean municipalities is explained by 71% (R-squared) of the following variables: Municipal Common Fund (FCM), Permanent Income from own source (IPP), Overcrowding, PSU average, population density and rate of domestic violence. As for the hypotheses associated with the residues of the model, which can compare its behavior with Figure 1, they do not present problems of self-correlation of the residues, using the Breusch-Godfrey test1 (Table 3), nor problems of normality of the residues,2 nor problems of heteroscedasticity (Table 4) of the aforementioned.3\n
\nResidual from the final model. Source: Own creation by means of EViews statistical program.
F-statistic | \n0.391564 | \nProb. F(2.82) | \n0.6773 | \n
Obs*R-squared | \n0.860859 | \nProb. Chi-Square(2) | \n0.6502 | \n
Breusch-Godfrey serial correlation LM test.
Source: Own creation by means of EViews statistical program.
F-statistic | \n0.462869 | \nProb. F(27.63) | \n0.9852 | \n
Obs*R-squared | \n15.06367 | \nProb. Chi-Square(27) | \n0.9685 | \n
Scaled explained SS | \n15.65709 | \nProb. Chi-Square(27) | \n0.9592 | \n
Heteroscedasticity white test.
Source: Own creation by means of EViews statistical program.
As illustrated by Figure 1, we can see the distribution of the residuals, considering the data obtained through QLI, as the estimation of efficiency through the final model proposed, with the difference shown on the graph explained by the R2 adjusted for the 71.29% model. By the way, the final model for the Urban Quality of Life Index (QLI) is [Eq. (2)].
\nThis study provides us with contrasts between different municipalities that allow us to reach conclusions on the current situation in northern, central, and southern Chile. It also allows us to find and tear down certain prejudices, such as the centralization of the country, showing the variables that are influential to a greater degree, according to our econometric model, and raises new aspects to consider in municipal management.
\nAccording to the literature reviewed, there are references that indicate that the quality of life can be interpreted from economic growth, which in various studies is considered a factor in determining the efficiency of city councils. The authors also indicate that the quality of life must be decoded by development, from a necessary environmental and social efficiency. For this, he points out [39] it is important to consider the factors that allow a “greening” of the economy, but also a closer relationship with politics. In this way, a set of criteria oriented to equity and distribution can be determined, which would reduce interterritorial imbalances, considered elements of high entropy. In sum, for a better quality of life for the citizens of a territory in which the city council manages resources, social variables, such as domestic violence in a given commune, should be considered, along with economic variables such as the Municipal Common Fund (FCM) and the Permanent Income from own source (IPP).
\nTherefore, although any variable, from economic matters to population density, can increase the efficiency of city councils, when linked closer to the quality of life of the inhabitants belonging to a certain commune, this factor tends to slightly decrease that efficiency, counteracting to some level what was raised by the literature. Indeed [37] rectifies the fact that the changes produced through economic development and well-being or the structural transformation in human development, in a study on the quality of life and how the environment and, ultimately, the changes that occur in it, can contribute positively or negatively in each individual, that is, how the administration and management of resources are implemented. This contributes to the efficiency of city councils in Chile, which in turn affects the quality of life of the inhabitants in each of the communes under study, concluding that, according to the data, findings and the existing literature, both factors mentioned are very closely related.
\nRegarding the assumptions made, it can be concluded that they are acceptable. In other words, there are better indexes in the central zone of Chile and the rates improve when advancing from North to South of the country, according to what is observed in the graphs and as predicted by the model.
\nBased on this study, it was concluded that the characteristics of the people who inhabit the communes cannot be excluded from this type of analysis, due to the cultural transformations and political demands that are taking place in countries like Chile. The efficiency levels of city councils cannot be limited by the information available only on a group of economic factors, but must integrate other aspects of social sensitivity.
\nThe management of the social and economic crisis that the pandemic situation has generated, needs to integrate the reality of the territories, which is urgently demanded in Chile by civil society itself, which perceives imbalances in the responses provided by city councils. If the quality of life of individuals, as well as their characteristics, were taken into account, this would provide a more integrated and real result regarding the efficiency of city councils in Chile and their administration of resources. Therefore, based on the variables that make up the final model of this research, it can be shown that economic factors, typical of the management of resources that the network of city councils carries out throughout the country, as well as factors that characterize the population, are both a greater concern of those determinants that influence the quality of life of the inhabitants and their real impact on efficiency.
\nThe results described above, obtained through econometrics and interdisciplinary dialog, can contribute towards the design and improvement of political-administrative models being demanded by the Chilean population, insofar as decentralizing power and managing the crises that are currently creating tension and polarization, the likes of which the country has not experienced for decades.
\nClaudio Elórtegui Gómez and Hanns de la Fuente-Mella are supported by Grant NUCLEO DE INVESTIGACION EN DATA ANALYTICS/PUCV VRIEA/039.432/2020.
\nThe authors declare no conflict of interest.
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Throughout the life cycle, many of them thrive in pathogen-rich environments, manage harsh weathers, exposed to a number of allochemicals, and adapt well to both terrestrial and marine ecosystems. Their remarkable ability to cope up with the enormous oxidative stress generated in all these circumstances, make them attractive models in this field of research. Endocrine control of oxidative stress in insects is recently emerging. Adipokinetic hormone, glucagon, ecdysteroids and juvenile hormone have been implicated in antioxidative protective role in insects. Drosophila and Caenorhabditis elegans have provided the largest body of evidence addressing the free radical theory of ageing. Oxidative stress is also induced by pesticides/insecticides. In mollusks, pesticides exert their biological effects via generation of ROS. Oxidative stress has been shown to be associated with exposure to several organophosphorous compounds and different classes of pyrethroids. Malathion is a potential hazard to the environment. Adverse effects induced by malathion in earthworms and insects have been reported. Information is now available in great detail on the role of ROS in modulating insect immunity during parasite invasion and bacterial infection. In Drosophila melanogaster ROS are actively produced in the midgut at a basal level in the presence of commensal microbiota and highly generated upon bacterial challenge. The involvement of reactive oxygen species (ROS) in mosquito immunity against bacteria and Plasmodium was investigated in the malaria vector Anopheles gambiae. The concentration of ROS increased in sand fly midguts after they fed on the insect pathogen Serratia marcescens. Elevated oxidative stress was previously reported for a mosquito line experimentally infected with Wolbachia, indicating that oxidative stress may be important for Wolbachia-mediated antiviral protection. In a nutshell, this chapter highlights the current advances of oxidative stress in invertebrate model systems and its implications.",book:{id:"5121",slug:"free-radicals-and-diseases",title:"Free Radicals and Diseases",fullTitle:"Free Radicals and Diseases"},signatures:"R.K. Chaitanya, K. Shashank and P. Sridevi",authors:[{id:"178087",title:"Dr.",name:"Rk",middleName:null,surname:"Chaitanya",slug:"rk-chaitanya",fullName:"Rk Chaitanya"}]},{id:"51874",doi:"10.5772/64700",title:"Ovarian Cancer Metastasis: A Unique Mechanism of Dissemination",slug:"ovarian-cancer-metastasis-a-unique-mechanism-of-dissemination",totalDownloads:3109,totalCrossrefCites:12,totalDimensionsCites:23,abstract:"Ovarian cancer is the most lethal of all gynecologic malignancies and has witnessed minimal improvements in patient outcomes in the past three decades. About 70% of ovarian cancer patients present with disseminated disease at the time of diagnosis. The standard of care remains a combination of debulking surgery and platinum‐ and taxanes‐based cytotoxic chemotherapy. Even though metastasis is the leading cause of ovarian cancer related fatalities, our understanding of the process remains limited. Ovarian cancer has a unique pattern of metastasis where the hematogenous spread is less common. Ovarian cancer cells mainly metastasize within the peritoneal cavity, which involves exfoliation from the primary tumor, survival, and transport in the peritoneal fluid followed by metastatic colonization of the organs within the peritoneal cavity. A key step for successful metastasis is their attachment and productive interactions with the mesothelial cells covering the metastatic organs for the establishment of metastatic tumors. This chapter provides an overview of ovarian cancer metastasis highlighting the unique dissemination and the underlying mechanisms of regulation of the steps involved. The role of the microenvironment in the process of metastasis will also be reviewed.",book:{id:"5267",slug:"tumor-metastasis",title:"Tumor Metastasis",fullTitle:"Tumor Metastasis"},signatures:"Anirban K. Mitra",authors:[{id:"185152",title:"Dr.",name:"Anirban",middleName:"Kumar",surname:"Mitra",slug:"anirban-mitra",fullName:"Anirban Mitra"}]},{id:"51903",doi:"10.5772/64787",title:"Role of Oxygen Free Radicals in Cancer Development and Treatment",slug:"role-of-oxygen-free-radicals-in-cancer-development-and-treatment",totalDownloads:3627,totalCrossrefCites:14,totalDimensionsCites:17,abstract:"It is well known that species derived from oxygen are cytotoxic and are involved in the etiology of cancer. Several carcinogens during metabolism exert their effect by producing reactive oxygen species (ROS). One of the consequences of oxidative damage to cellular DNA is mutated. It plays a vital role in the process of carcinogenesis (especially in the initiation and progression). The alters, including rearrangement of DNA sequence, base modification, DNA miscoding lesions, gene amplification, and the activation of oncogenes, could be implicated in the initiation stage of several cancers. Mitochondrial changes in the cancer cells are well known and as a result are respiratory injured. Mitochondrial dysfunction could lead to a low coupling efficiency of the mitochondrial electron transport chain (mETC), raising electron leakage and increased ROS formation. It has been documented that by reducing and inactivation of antioxidant system, the oxidative stress (OS) in cancer cells is higher. Cancer cells exhibit a higher oxidative stress level compared to normal cells, rendering tumor cells more vulnerable to raise ROS levels. Therefore, increasing ROS levels through redox modulation can be a strategy to selectively kill cancer cells but not normal cells. A promising anti-cancer method named “oxidation therapy” has been developed by causing cytotoxic oxidative stress for cancer therapy. In this chapter, we described the role of ROS as a double-edged sword in cancer development and treatment.",book:{id:"5121",slug:"free-radicals-and-diseases",title:"Free Radicals and Diseases",fullTitle:"Free Radicals and Diseases"},signatures:"Jalal Pourahmad, Ahmad Salimi and Enaytollah Seydi",authors:[{id:"172672",title:"Prof.",name:"Jalal",middleName:null,surname:"Pourahmad",slug:"jalal-pourahmad",fullName:"Jalal Pourahmad"}]},{id:"44689",doi:"10.5772/55415",title:"Drug Resistance and Molecular Cancer Therapy: Apoptosis Versus Autophagy",slug:"drug-resistance-and-molecular-cancer-therapy-apoptosis-versus-autophagy",totalDownloads:4010,totalCrossrefCites:2,totalDimensionsCites:14,abstract:null,book:{id:"2857",slug:"apoptosis",title:"Apoptosis",fullTitle:"Apoptosis"},signatures:"Rebecca T. Marquez, Bryan W. Tsao, Nicholas F. Faust and Liang Xu",authors:[{id:"19713",title:"Dr.",name:"Liang",middleName:null,surname:"Xu",slug:"liang-xu",fullName:"Liang Xu"},{id:"149902",title:"Dr.",name:"Rebecca",middleName:null,surname:"Marquez",slug:"rebecca-marquez",fullName:"Rebecca Marquez"}]},{id:"51890",doi:"10.5772/64569",title:"Oxidative Stress and Autophagy",slug:"oxidative-stress-and-autophagy",totalDownloads:1964,totalCrossrefCites:6,totalDimensionsCites:13,abstract:"Free radical production related with many stress factors including radiation, drugs, ageing and trauma plays a key role in cell death. Notwithstanding, free radicals can cause pathology in a variety of diseases through oxidative stress: Under oxidative stress, excessive production of free radicals can trigger cell death by primarily DNA and all cellular macromolecule damages. Also, excessive free radicals have a role in early inducers of autophagy cell death upon nutrient deprivation. Autophagy is physiologic process of eukaryotic systems, which have significant role in adaptation to oxidative stress by degradation of metalloproteins and oxidatively damaged macromolecules. By oxidizing, membrane injuries allow the leakage of enzymes and contribute to cell damage. However, recent publications demonstrate the protecting role of lysosome system during excessive reactive oxygen species (ROS) production by the elimination of damaged proteins or organelles. Activation of autophagic or lysosomal system can eliminate the oxidizing components of cell in oxidative stress response. This chapter aims to provide the novel insight data for oxidative damage-mediated autophagy as well as their metabolic networks.",book:{id:"5121",slug:"free-radicals-and-diseases",title:"Free Radicals and Diseases",fullTitle:"Free Radicals and Diseases"},signatures:"Adem Kara, Semin Gedikli, Emin Sengul, Volkan Gelen and Seckin\nOzkanlar",authors:[{id:"177953",title:"Dr.",name:"Adem",middleName:null,surname:"Kara",slug:"adem-kara",fullName:"Adem Kara"},{id:"178363",title:"Dr.",name:"Emin",middleName:null,surname:"Sengul",slug:"emin-sengul",fullName:"Emin Sengul"},{id:"178365",title:"Dr.",name:"Semin",middleName:null,surname:"Gedikli",slug:"semin-gedikli",fullName:"Semin Gedikli"},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen"},{id:"178367",title:"Dr.",name:"Seckin",middleName:null,surname:"Ozkanlar",slug:"seckin-ozkanlar",fullName:"Seckin Ozkanlar"}]}],mostDownloadedChaptersLast30Days:[{id:"44699",title:"Apoptosis and Activation-Induced Cell Death",slug:"apoptosis-and-activation-induced-cell-death",totalDownloads:2949,totalCrossrefCites:0,totalDimensionsCites:0,abstract:null,book:{id:"2857",slug:"apoptosis",title:"Apoptosis",fullTitle:"Apoptosis"},signatures:"Joaquín H. Patarroyo S. and Marlene I. Vargas V",authors:[{id:"141183",title:"Prof.",name:"Joaquín",middleName:null,surname:"Patarroyo",slug:"joaquin-patarroyo",fullName:"Joaquín Patarroyo"},{id:"146188",title:"Prof.",name:"Marlene",middleName:null,surname:"Vargas",slug:"marlene-vargas",fullName:"Marlene Vargas"}]},{id:"44689",title:"Drug Resistance and Molecular Cancer Therapy: Apoptosis Versus Autophagy",slug:"drug-resistance-and-molecular-cancer-therapy-apoptosis-versus-autophagy",totalDownloads:4002,totalCrossrefCites:2,totalDimensionsCites:14,abstract:null,book:{id:"2857",slug:"apoptosis",title:"Apoptosis",fullTitle:"Apoptosis"},signatures:"Rebecca T. Marquez, Bryan W. Tsao, Nicholas F. Faust and Liang Xu",authors:[{id:"19713",title:"Dr.",name:"Liang",middleName:null,surname:"Xu",slug:"liang-xu",fullName:"Liang Xu"},{id:"149902",title:"Dr.",name:"Rebecca",middleName:null,surname:"Marquez",slug:"rebecca-marquez",fullName:"Rebecca Marquez"}]},{id:"51334",title:"Free Radicals and Biomarkers Related to the Diagnosis of Cardiorenal Syndrome",slug:"free-radicals-and-biomarkers-related-to-the-diagnosis-of-cardiorenal-syndrome",totalDownloads:3762,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"The National Heart, Lung, and Blood Institute Working Group has postulated the cardiorenal syndrome (CRS) as an interaction between the kidneys and the cardiovascular system in which therapy to relieve congestive heart failure (HF) symptoms is limited by the further worsening renal function. CRS is classified from type I to V, taking into account the progression of the symptoms in terms of mechanisms, clinical conditions, and biomarkers. Experimental and clinical studies have shown the kidney as both a trigger and a target to sympathetic nervous system (SNS) overactivity. Renal damage and ischemia, activation of the renin angiotensin aldosterone system (RAAS), and dysfunction of nitric oxide (NO) system are associated with kidney adrenergic activation. Indeed, the imbalances of RAAS and/or SNS share an important common process in CRS: the activation and production of free radicals, especially reactive oxygen species (ROS). The present chapter addresses connections of the free radicals as potential biomarkers as the imbalances in the RAAS and the SNS are developed. Understanding the involvement of free radicals in CRS may bring knowledge to design studies in order to develop accurate pharmacological interventions.",book:{id:"5121",slug:"free-radicals-and-diseases",title:"Free Radicals and Diseases",fullTitle:"Free Radicals and Diseases"},signatures:"Carolina B.A. Restini, Bruna F.M. Pereira and Tufik M. Geleilete",authors:[{id:"178144",title:"Dr.",name:"Carolina",middleName:null,surname:"Baraldi A. Restini",slug:"carolina-baraldi-a.-restini",fullName:"Carolina Baraldi A. Restini"},{id:"178387",title:"Ms.",name:"Bruna",middleName:null,surname:"Pereira",slug:"bruna-pereira",fullName:"Bruna Pereira"},{id:"184159",title:"Dr.",name:"Tufik",middleName:null,surname:"Geleilete",slug:"tufik-geleilete",fullName:"Tufik Geleilete"}]},{id:"52345",title:"Oxidative Stress in Invertebrate Systems",slug:"oxidative-stress-in-invertebrate-systems",totalDownloads:2474,totalCrossrefCites:8,totalDimensionsCites:23,abstract:"Invertebrates have been valuable research models in the discovery of many scientific principles owing to the numerous advantages they provide. Throughout the life cycle, many of them thrive in pathogen-rich environments, manage harsh weathers, exposed to a number of allochemicals, and adapt well to both terrestrial and marine ecosystems. Their remarkable ability to cope up with the enormous oxidative stress generated in all these circumstances, make them attractive models in this field of research. Endocrine control of oxidative stress in insects is recently emerging. Adipokinetic hormone, glucagon, ecdysteroids and juvenile hormone have been implicated in antioxidative protective role in insects. Drosophila and Caenorhabditis elegans have provided the largest body of evidence addressing the free radical theory of ageing. Oxidative stress is also induced by pesticides/insecticides. In mollusks, pesticides exert their biological effects via generation of ROS. Oxidative stress has been shown to be associated with exposure to several organophosphorous compounds and different classes of pyrethroids. Malathion is a potential hazard to the environment. Adverse effects induced by malathion in earthworms and insects have been reported. Information is now available in great detail on the role of ROS in modulating insect immunity during parasite invasion and bacterial infection. In Drosophila melanogaster ROS are actively produced in the midgut at a basal level in the presence of commensal microbiota and highly generated upon bacterial challenge. The involvement of reactive oxygen species (ROS) in mosquito immunity against bacteria and Plasmodium was investigated in the malaria vector Anopheles gambiae. The concentration of ROS increased in sand fly midguts after they fed on the insect pathogen Serratia marcescens. Elevated oxidative stress was previously reported for a mosquito line experimentally infected with Wolbachia, indicating that oxidative stress may be important for Wolbachia-mediated antiviral protection. In a nutshell, this chapter highlights the current advances of oxidative stress in invertebrate model systems and its implications.",book:{id:"5121",slug:"free-radicals-and-diseases",title:"Free Radicals and Diseases",fullTitle:"Free Radicals and Diseases"},signatures:"R.K. Chaitanya, K. Shashank and P. Sridevi",authors:[{id:"178087",title:"Dr.",name:"Rk",middleName:null,surname:"Chaitanya",slug:"rk-chaitanya",fullName:"Rk Chaitanya"}]},{id:"51782",title:"Is Extracellular Matrix a Castle Against to Invasion of Cancer Cells?",slug:"is-extracellular-matrix-a-castle-against-to-invasion-of-cancer-cells-",totalDownloads:2333,totalCrossrefCites:2,totalDimensionsCites:4,abstract:"Metastasis is a complicated course that involves the spread of a neoplasm to distant parts of the body from its original site. A cancer cell must complete a series of steps before it becomes a clinically detectable lesion for successful colonization in the body. These are separation from the primary tumor, invasion and penetration of their basement membranes, entry into the blood vessels and survival within blood, and entry into lymphatics. A major challenge in extracellular matrix (ECM) biology is to understand the roles of the ECM and how disruption of ECM dynamics may contribute to cancer. A noteworthy area of forthcoming cancer research will be to determine whether abnormal ECM could be an effective cancer therapeutic target. We should understand how ECM composition and organization are normally maintained and how they may be deregulated in cancer. So the aims of this chapter were to focus on extracellular matrix. Invasion and metastatic skills, properties and functions of the ECM, abnormal ECM dynamics, tumor microenvironment and ECM, details of ECM invasion, role of ECM and ECM‐associated proteins in metastasis, tumor dormant and metastatic process, essential component of the niches, role of the ECM in tumor angiogenesis and lymphangiogenesis are be briefly explained in this chapter.",book:{id:"5267",slug:"tumor-metastasis",title:"Tumor Metastasis",fullTitle:"Tumor Metastasis"},signatures:"Serdar Altınay",authors:[{id:"185324",title:"Associate Prof.",name:"Serdar",middleName:null,surname:"Altınay",slug:"serdar-altinay",fullName:"Serdar Altınay"}]}],onlineFirstChaptersFilter:{topicId:"411",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:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:18,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:139,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:122,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,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:21,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",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. 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Her focus is on quality, innovation, leadership, and personalised learning. She works primarily at the strategic and policy levels, both nationally and internationally, and with key international organisations. She is committed to promoting and improving OFDL in the context of SDG4 and the future of education. Ossiannilsson has more than 20 years of experience in her current field, but more than 40 years in the education sector. She works as a reviewer and expert for the European Commission and collaborates with the Joint Research Centre for Quality in Open Education. Ossiannilsson also collaborates with ITCILO and ICoBC (International Council on Badges and Credentials). She is a member of the ICDE Board of Directors and has previously served on the boards of EDEN and EUCEN. Ossiannilsson is a quality expert and reviewer for ICDE, EDEN and the EADTU. She chairs the ICDE OER Advocacy Committee and is a member of the ICDE Quality Network. 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He previously worked as a post-doctoral fellow at the Ben-Gurion University of Negev, Israel; University of the Free State, South Africa; and Central University of Technology Bloemfontein, South Africa. He obtained his Ph.D. in Organic Chemistry from Nagaoka University of Technology, Japan. He has published more than seventy-four journal articles and attended several national and international conferences as speaker and chair. Dr. Kendrekar has received many international awards. He has several funded projects, namely, anti-malaria drug development, MRSA, and SARS-CoV-2 activity of curcumin and its formulations. He has filed four patents in collaboration with the University of Central Lancashire and Mayo Clinic Infectious Diseases. His present research includes organic synthesis, drug discovery and development, biochemistry, nanoscience, and nanotechnology.",institutionString:"Visiting Scientist at Lipid Nanostructures Laboratory, Centre for Smart Materials, School of Natural Sciences, University of Central Lancashire",institution:null},{id:"428125",title:"Dr.",name:"Vinayak",middleName:null,surname:"Adimule",slug:"vinayak-adimule",fullName:"Vinayak Adimule",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/428125/images/system/428125.jpg",biography:"Dr. Vinayak Adimule, MSc, Ph.D., is a professor and dean of R&D, Angadi Institute of Technology and Management, India. He has 15 years of research experience as a senior research scientist and associate research scientist in R&D organizations. He has published more than fifty research articles as well as several book chapters. He has two Indian patents and two international patents to his credit. Dr. Adimule has attended, chaired, and presented papers at national and international conferences. He is a guest editor for Topics in Catalysis and other journals. He is also an editorial board member, life member, and associate member for many international societies and research institutions. His research interests include nanoelectronics, material chemistry, artificial intelligence, sensors and actuators, bio-nanomaterials, and medicinal chemistry.",institutionString:"Angadi Institute of Technology and Management",institution:null},{id:"284317",title:"Prof.",name:"Kantharaju",middleName:null,surname:"Kamanna",slug:"kantharaju-kamanna",fullName:"Kantharaju Kamanna",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284317/images/21050_n.jpg",biography:"Prof. K. Kantharaju has received Bachelor of science (PCM), master of science (Organic Chemistry) and Doctor of Philosophy in Chemistry from Bangalore University. He worked as a Executive Research & Development @ Cadila Pharmaceuticals Ltd, Ahmedabad. He received DBT-postdoc fellow @ Molecular Biophysics Unit, Indian Institute of Science, Bangalore under the supervision of Prof. P. Balaram, later he moved to NIH-postdoc researcher at Drexel University College of Medicine, Philadelphia, USA, after his return from postdoc joined NITK-Surthakal as a Adhoc faculty at department of chemistry. Since from August 2013 working as a Associate Professor, and in 2016 promoted to Profeesor in the School of Basic Sciences: Department of Chemistry and having 20 years of teaching and research experiences.",institutionString:null,institution:{name:"Rani Channamma University, Belagavi",country:{name:"India"}}},{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/158492/images/system/158492.jpeg",biography:"Prof. Dr. Yusuf Tutar conducts his research at the Hamidiye Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Division of Biochemistry, University of Health Sciences, Turkey. He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"94311",title:"Prof.",name:"Martins",middleName:"Ochubiojo",surname:"Ochubiojo Emeje",slug:"martins-ochubiojo-emeje",fullName:"Martins Ochubiojo Emeje",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94311/images/system/94311.jpeg",biography:"Martins Emeje obtained a BPharm with distinction from Ahmadu Bello University, Nigeria, and an MPharm and Ph.D. from the University of Nigeria (UNN), where he received the best Ph.D. award and was enlisted as UNN’s “Face of Research.” He established the first nanomedicine center in Nigeria and was the pioneer head of the intellectual property and technology transfer as well as the technology innovation and support center. Prof. Emeje’s several international fellowships include the prestigious Raman fellowship. He has published more than 150 articles and patents. He is also the head of R&D at NIPRD and holds a visiting professor position at Nnamdi Azikiwe University, Nigeria. He has a postgraduate certificate in Project Management from Walden University, Minnesota, as well as a professional teaching certificate and a World Bank certification in Public Procurement. Prof. Emeje was a national chairman of academic pharmacists in Nigeria and the 2021 winner of the May & Baker Nigeria Plc–sponsored prize for professional service in research and innovation.",institutionString:"National Institute for Pharmaceutical Research and Development",institution:{name:"National Institute for Pharmaceutical Research and Development",country:{name:"Nigeria"}}},{id:"436430",title:"Associate Prof.",name:"Mesut",middleName:null,surname:"Işık",slug:"mesut-isik",fullName:"Mesut Işık",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/436430/images/19686_n.jpg",biography:null,institutionString:null,institution:{name:"Bilecik University",country:{name:"Turkey"}}},{id:"268659",title:"Ms.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/268659/images/8143_n.jpg",biography:"Dr. Zhan received his undergraduate and graduate training in the fields of preventive medicine and epidemiology and statistics at the West China University of Medical Sciences in China during 1989 to 1999. He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. 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He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via machine-learning-based analyses of exosomal signatures. Dr. Paul has published in more than fifty peer-reviewed international journals and is highly cited. 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