\r\n\tmolecular and imaging methods for detection and identification of plant diseases have many limitations that will be discussed in this book. This sparked interest in the development of minimally invasive and substrate general spectroscopic \r\n\ttechniques that can be used directly in the field for confirmatory plant disease diagnostics.
\r\n
\r\n\tThis book will also discuss recent progress in development of reflectance, infrared, Raman and surface-enhanced Raman \r\n\tspectroscopy for detection and identification of plant diseases. It will also present advantages and disadvantages of these optical spectroscopy methods compared to the most common molecular and imaging techniques.
\r\n
\r\n\tThe book also aims to discuss specific plant diseases, their symptoms and available methods of treatment.
",isbn:"978-1-83962-516-9",printIsbn:"978-1-83962-515-2",pdfIsbn:"978-1-83962-517-6",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"daef7c0ea5e568cfc5ae1613a74634b3",bookSignature:"Dr. Dmitry Kurouski",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10113.jpg",keywords:"PCR, ELISA, UAV, Satellite, Spectroscopic Diagnostics, Wheat, Sorghum, Rice, Corn, Fungal Pathogens, Viral Pathogens, Bacterial Pathogens",numberOfDownloads:117,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 10th 2020",dateEndSecondStepPublish:"September 15th 2020",dateEndThirdStepPublish:"November 14th 2020",dateEndFourthStepPublish:"February 2nd 2021",dateEndFifthStepPublish:"April 3rd 2021",remainingDaysToSecondStep:"4 months",secondStepPassed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"Assistant Professor Kurouski obtained his Ph.D. at the State University of New York. He is an Assistant Professor at Texas A&M University. His experience includes working as a Senior Research Scientist at Boehringer-Ingelheim Pharmaceuticals and at Chemistry Department at Northwestern University, USA.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"264297",title:"Dr.",name:"Dmitry",middleName:null,surname:"Kurouski",slug:"dmitry-kurouski",fullName:"Dmitry Kurouski",profilePictureURL:"https://mts.intechopen.com/storage/users/264297/images/system/264297.jpeg",biography:"Dr. Dmitry Kurouski obtained his Ph.D. in Analytical/Physical Chemistry at State University of New York, Albany, USA. He is an Assistant Professor at Texas A&M University, at Department of Biochemistry & Biophysics. His experience includes working as a Senior Research Scientist at Boehringer-Ingelheim Pharmaceuticals and at Chemistry Department at Northwestern University, USA. He received numerous honors and awards for his continuous work in the field.",institutionString:"Texas A&M University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Texas A&M University",institutionURL:null,country:{name:"United States of America"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"5",title:"Agricultural and Biological Sciences",slug:"agricultural-and-biological-sciences"}],chapters:[{id:"74757",title:"The Trends in the Evaluation of Fusarium Wilt of Chickpea",slug:"the-trends-in-the-evaluation-of-fusarium-wilt-of-chickpea",totalDownloads:13,totalCrossrefCites:0,authors:[null]},{id:"74639",title:"Diagnosis of Fungal Plant Pathogens Using Conventional and Molecular Approaches",slug:"diagnosis-of-fungal-plant-pathogens-using-conventional-and-molecular-approaches",totalDownloads:41,totalCrossrefCites:0,authors:[null]},{id:"74600",title:"Blister Blight Disease of Tea: An Enigma",slug:"blister-blight-disease-of-tea-an-enigma",totalDownloads:65,totalCrossrefCites:0,authors:[null]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"184402",firstName:"Romina",lastName:"Rovan",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/184402/images/4747_n.jpg",email:"romina.r@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, copyediting 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. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"7059",title:"Amyloid Diseases",subtitle:null,isOpenForSubmission:!1,hash:"d9a197d34d3d6006af726d577060f928",slug:"amyloid-diseases",bookSignature:"Dmitry Kurouski",coverURL:"https://cdn.intechopen.com/books/images_new/7059.jpg",editedByType:"Edited by",editors:[{id:"264297",title:"Dr.",name:"Dmitry",surname:"Kurouski",slug:"dmitry-kurouski",fullName:"Dmitry Kurouski"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6418",title:"Hyperspectral Imaging in Agriculture, Food and Environment",subtitle:null,isOpenForSubmission:!1,hash:"9005c36534a5dc065577a011aea13d4d",slug:"hyperspectral-imaging-in-agriculture-food-and-environment",bookSignature:"Alejandro Isabel Luna Maldonado, Humberto Rodríguez Fuentes and Juan Antonio Vidales Contreras",coverURL:"https://cdn.intechopen.com/books/images_new/6418.jpg",editedByType:"Edited by",editors:[{id:"105774",title:"Prof.",name:"Alejandro Isabel",surname:"Luna Maldonado",slug:"alejandro-isabel-luna-maldonado",fullName:"Alejandro Isabel Luna Maldonado"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophanides",surname:"Theophile",slug:"theophanides-theophile",fullName:"Theophanides Theophile"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"878",title:"Phytochemicals",subtitle:"A Global Perspective of Their Role in Nutrition and Health",isOpenForSubmission:!1,hash:"ec77671f63975ef2d16192897deb6835",slug:"phytochemicals-a-global-perspective-of-their-role-in-nutrition-and-health",bookSignature:"Venketeshwer Rao",coverURL:"https://cdn.intechopen.com/books/images_new/878.jpg",editedByType:"Edited by",editors:[{id:"82663",title:"Dr.",name:"Venketeshwer",surname:"Rao",slug:"venketeshwer-rao",fullName:"Venketeshwer Rao"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"48720",title:"Oxidative Stress-Based Photodynamic Therapy with Synthetic Sensitizers and/or Natural Antioxidants",doi:"10.5772/60872",slug:"oxidative-stress-based-photodynamic-therapy-with-synthetic-sensitizers-and-or-natural-antioxidants",body:'
1. Introduction
Photodynamic therapy (PDT) (also known as photoirradiation therapy, phototherapy or photochemotherapy) is a new modality for cancer treatment and involves the combination of light with a photosensitizing drug in an oxygen-rich environment [1, 2]. The photodynamic therapy has been successfully used in the last decade for the therapy of solid malignant tumors and non-tumoral diseases such as psoriasis, age-related macular degeneration, actinic keratosis, ageing [3]. The PDT mechanism could be a direct one (by apoptosis and necrosis), or an indirect one (by immune response on tumor vasculature). An ideal sensitizer should have a defined pure chemical structure, a proper absorption in red/near-infrared region, and a good capacity of singlet oxygen generation. After irradiation, the photosensitizer (PS) passes into the singlet oxygen excited state and afterwards it can pass into the triplet state; in this state it can react with molecular oxygen, generating singlet oxygen or it can react with different molecules from the tissue generating radical forms of PS [4]. This final form can react with oxygen, leading to the formation of different reactive oxygen species such as the hydroxyl radical, hydrogen peroxide and the superoxide anion, which in their turn may oxidize the macromolecular cellular components, resulting in cellular death through either apoptosis or necrosis. PDT induces oxidative stress at specific subcellular sites through the light activation of organelle-associated photosensitizers, and is used in the destruction of tumor cells.
This chapter offers the most up-to-date results of photodynamic therapy with synthetic sensitizers and/or coupled with some natural antioxidants, by using our data correlated with literature reports.
2. General concept of photodynamic therapy
Photodynamic therapy (PDT) is a relatively new type of treatment for cancer, and makes use of a photosensitizer, visible light and molecular oxygen. Reactive oxygen species (ROS) are generated, causing the death of tumor cells by apoptosis or necrosis. Significant research efforts are nowadays focused on finding new photosensitizers with antineoplastic activity.
Over the last decade, there is an increasing interest in photosensitization mechanisms in biological systems, in relation to the therapeutic aspects of this phenomenon [5, 6]. The most used photosensitizers in photodynamic therapy are porphyrins, phthalocyanines and related compounds (Figure 1). These compounds are capable of generating a long-lived triplet excited state, responsible for facile energy transfer to molecular oxygen, leading to the formation of singlet oxygen. The photosensitization reactions include free radical reactions (type I) and singlet oxygen reactions (1O2) (type II) (Figure 2). The mechanism of PDT may lead to a direct tumor cell injury and also an indirect cell death via microcirculatory changes, resulting in reduced blood flow to the tumor [7-10].
Figure 1.
The structure of porphyrin (left) and phthalocyanine (right). (R=meso-substituent; M=central metal)
Figure 2.
The dual (up) and singlet mechanism (down) of PDT
The study of radical-induced damage in living systems is a topic of great interest in biology and medicine. Attention has been increasingly focused on the role of free radicals in normal physiological conditions and in different pathologies, with an essential role in cellular processes resulting in damages [11].
3. Mechanisms of photodynamic therapy
3.1. Photophysical and photochemical mechanism
Porphyrins are used in medical and biological applications as they can generate new sensitizer structures with extensive and versatile photophysical and photochemical properties. Synthetic porphyrins and phthalocyanines appear to be good models in order to create new efficient drugs for photodynamic therapy of cancer [12]. The photodynamic therapy of cancer is based on the ability of some sensitizers to be retained in larger amounts and longer time in neoplastic than in normal cells as well as on the possibility to generate singlet oxygen after the activation of the porphyrin with red light [13].
In our previous investigations on PDT sensitizers [14, 15], we have used several spectroscopic methods to evaluate the efficiency of triplet state generation of some sensitizers [16]. The absorption spectra of the dye incorporated into the cells provide information with low accuracy because of small absorption amplitudes and perturbation of the spectra by light scattering. Therefore fluorescence methods are widely used [17]. The fluorescence of photosensitizers observed under a confocal microscope enables to establish the localization of dye in the cells [18–20]. Changes in the fluorescence of cell material due to illumination of samples depend on the sensitizer localization in the cells, but for a group of similar dye molecules, the cells, stained to a higher degree, usually show higher fluorescence intensity [21].
3.2. Photobiological mechanism
Within PDT, a sensitizer, light and oxygen are used to cause photochemically induced cell death via apoptotic pathways. In vitro and in vivo photosensitizing efficacy of certain synthesized photosensitizers are usually investigated by their interaction with some proteins (human serum albumin (HSA) (Site II) for binding affinity, intracellular localization and DNA attack [22, 23].
The photobiological mechanisms by which some sensitizers induce tumor necrosis are very different: they strongly associate with serum albumins and it is assumed that they kill neoplastic cells indirectly by damaging blood vessels and interrupting the supply of oxygen [24]. A good example is water-soluble porphyrins, tetrakis (4-sulfonatophenyl) porphyrin (H2TSPP) as one of the best tumor localizer. It has a very low affinity for human plasma lipoproteins but binds strongly to human serum albumin (HSA), Figure 3. The association between H2TSPP and HSA has a spectacular effect on the singlet-state lifetime of porphyrins: it decreases from 5.2 ns to about 1.6 ns [25]. This marked decrease is due to the enhancement of one of the molecular processes involved in the deactivation of the singlet state. The shortening of the singlet state lifetime causes an important decrease of the quantum yield of triplet state (ϕT). This assumption is in agreement with the result of Davila and Harriman [26] that measured the ϕT of the complex H2TSPP–HSA and reported a value of 0.70. The shortening of the singlet state lifetime of this complex is compensated by a corresponding increase of the intersystem crossing rate. The photosensitizing efficiency of bound H2TSPP has a reduced mobility, characteristic of molecules bound deeply into the protein structure. Such molecule is expected to be less accessible by oxygen and thus less efficient in producing singlet oxygen. The number of binding sites per protein molecule is greater than unity (n=3 and k=1.5 × 106 M-1 for one binding site and k=2x105 M-1 for the other two). The binding of H2TSPP to HSA significantly modifies the photophysics of porphyrin.
Figure 3.
The changes of absorption spectra during the interaction between H2TSPP and HSA
On irradiation with light (laser), in the presence of a photosensitizer, DNA undergoes several modifications including chain breaks, DNA–protein cross-links, and basic sites changes coupled with oxidized DNA bases, which have been shown to be able to induce point mutations [27]. The single strand breaks (SSB) are mainly formed through the attack of OH radicals, where the hydrogen bonds between purine bases play an important role. OH radicals react with DNA to remove an H atom, leading to strand rupture. Mitochondria play a central role in the control of apoptosis induced by PDT, which through the mitochondrial permeability transition pore (PTP) lose the integrity of the outer mitochondrial membrane, thus releasing the intermembrane proteins, such as cytochrome c, into the cytosol to form the “apoptosome”. The apoptosome attacks procaspase-3 and cleaves it to form active caspase-3, which can lead to DNA breakage and nuclear chromatin condensation and cause cell death [28].
The porphyrins are able to induce changes of melting points and viscosity of DNA, which will be fragmented into small chains (Table 1). In this case, two modes of interaction between dye molecules and DNA are distinguished: a strong binding mode involving about 20-23% of the DNA phosphate groups and a weak binding mode involving the remaining phosphate groups.
\n\t\t
\n\t\t
\n\t\t\t
\n\t\t\t\t\n\t\t\t
\n\t\t
\n\t
Table 1.
The temperature and viscosity changes of DNA during the photodynamic process
An analysis on DNA degraded by sensitized attack of methylene blue (MB) showed that it had 80% of the guanine residues [29], and similar value for hematoporphyrins and furrocoumarins [30]. Apoptosis was evident in the post-PDT cells through the TdT-mediated dUTP nick end labeling (TUNEL) method and DNA fragmentation assay. Apoptosis was determined by cell morphology with light microscopy and transmission electron microscopy [31].
The two known modes of interaction between dye molecules and DNA are a strong binding mode involving about 20–23% of the DNA phosphate groups and a weak binding mode involving the remaining phosphate groups [32].
Based on the interaction sensitizer-DNA, three groups of porphyrins are known:
Group I porphyrins, which induce changes characteristic of intercalation in DNA samples with greater 40% GC base composition with an increasing of the linear viscosity of CT DNA, strongest intercalative binding in GC regions and the localization of AT regions only outside binding.
Group II porphyrins are believed to be outside binders, with an additional self-stacking features that induce DNA aggregation and a small viscosimetric changes of DNA with greater than 40% GC content.
Group III porphyrins give results characteristic of outside binding at both AT and GC sites, identified by the absence of an increasing of the solution viscosity for any of the linear or super helical DNA samples; they being able to bind with a preferential orientation.
Cationic porphyrins can interact with DNA either by intercalation between the G–C base-pairs or by outside binding in the minor groove with A–T sites selectively. An exemplification has been checked by personal data for cytosine (C) and guanine(G) by using as sensitizers methylene blue (MB), H2TSPP and Rhodamine (Rh) (Figure 4).
Figure 4.
Cytosine (C)- and guanine(G)-sensitized photooxidation by using as sensitizers MB, H2TSPP and Rh
The weakly bound dye molecules are identified to be attached to the helix exterior by means of electrostatic interaction with the phosphate groups. A red-shifted absorption is due to porphyrin–porphyrin interactions within long-range assemblies on the polymer in exterior. When the porphyrin is intercalated, a strong hypochromicity and a strong bathochromic shift for the absorption bands are observed. As a possibility of external association a small hypochromicity (or even a hyperchromicity) and a small batochromic shift are observed. If an external association is possible in concert with an aggregation process, only hypochromicity (or hyperchromicity) is important [28]. Some important conclusions had been stated: porphyrins intercalate in DNA with a binding constant of around 103–106 M-1; the porphyrin complex appears to be stabilized by extensive electrostatic interactions, especially in the minor groove; the porphyrin does not form van der Waals stacking contacts with adjacent bases; DNA may require conformational distortion reaching the limit of DNA melting; the resulting severe conformational distortion not resolved upon achievement of the ground-state complex; steric clashing between the DNA backbone and the porphyrin extending the DNA along its helical axis; and de-stacking the interior of the complex.
The aggregation process is very important in this interaction study. If the sensitizer is in a monomer form, the external association with DNA could be favored. The association process increases its rigidity and changes the distance between the bases creating the adequate distances unfavorable to the dimerization. The Soret band is batochromically shifted from 412 nm to 433 nm, and the Q-band decreases its intensity. New bands appear at 644 and 707 nm. Also, a new band appears at 490 nm (Figure 5). The band at 490 nm arises from the J-aggregate (edge-to-edge interaction) of porphyrin molecules [33]. Their structures have been identified by atomic force microscopy (AFM) (Figure 6). The porphyrins are externally bound when their planar structure fit into the major or minor groove and interact with DNA electrostatically. Also, hyperchromicity is observed (the greatest absorption value at 260 nm), which is similar with some mono- and di-catenare destructions. It could be presumed that during the laser irradiation support a photooxidation reaction takes place preferably at guanine site. By irradiation with DNA, an increase of viscosity is observed as an effect of a chain-breaks and helix destruction.
Figure 5.
The changes of absorption spectra during the interaction between H2TSPP and DNA
Figure 6.
The structure of H2TSPP in monomer (left) and J-aggregate (right) form
The fluorescence emission spectra of H2TSPP, DNA and their complex consist of two bands with maxima little affected by DNA; however, the emission intensity is markedly reduced (Figure 7). For H2TSPP, in the presence of DNA, the maxima from 605 and 640 nm increase simultaneously, as a proof for the external binding between both compounds. From the amplitude ration I604/I640, it was concluded that the porphyrin/DNA this ratio increases without irradiation and by irradiation with laser beam, this ratio registered a significant increase at the high time of irradiation. A spatial arrangement of porphyrin and DNA takes place on the DNA strand exterior based on electrostatic interaction between phosphate groups of DNA and positive charges of J-aggregated porphyrin. If H2TSPP has a J-aggregate form, it is possible to cover DNA molecule like two concentric bodies. DNA has a 20 Å diameter, while H2TSPP -J-aggregate has 0.35–0.40 Å interplanar distances and a 40 Å diameter [34].
Figure 7.
The fluorescence of H2TSPP and its mixture with DNA at different concentrations.
4. Photosensitizers
4.1. Conventional photosensitizers
The most used and most efficient sensitizers are synthetic compounds, as porphyrins (P) and phthalocyanines (Pc).
Porphyrins constitute a class of the molecules that contain four pyrrole rings linked by the methane carbon bridges. A large group of porphyrins can be chemically modified by introducing the metal at the center of the pyrrole rings or by attaching the peripheral groups to the outer rings of the methane bridges units, respectively. The main characteristic of free-base porphyrin consists in the absorption maxima: a Soret band around 400 nm and four Q-bands in the region of 500–700 nm. Although the porphyrins absorb light poorly in this wavelength region (650 nm, ε= 30000 M-1⋅∙ cm-1) [35], as a result of increased transparency of biological tissues at longer wavelength; red light is normally used for PDT. Some exemplification of porphyrins and phthalocyanines are shown in Figure 8.
Phthalocyanines (Pc)/naphthalocyanines (Nc) are molecules composed of four indole units: pyrrole rings linked by nitrogen atoms conjugated with benzene rings characterized by a strong, isolated Q band in the red region of the UV/Vis spectrum, while the less intense B band is found at higher energies (Figure 9). The Q band is characterized by a high molar absorptivity (ε = 105 M-1 ⋅ cm-1) [36], and it is accompanied by a series of vibrational bands. The B band is broad due to the super-positioning of B1 and B2 [37].
Figure 8.
The structure of some SiPc, SiNc and SiTPP
Porphyrins act as free bases and chelated with a variety of metals, the diamagnetic ones enhancing the phototoxicity. Paramagnetic metals shorten the lifetime of the triplet state and as result can make the dyes photoinactive [38]. The photosensitizing activity is quenched by the presence of transition metal ions (as central ions) with a d-electron configuration [39]. An exemplification is Si(enolate)2 5, 10, 15, 20-tetra-p-phenyl porphyrin (Si(enolate)2TPP) (Figure 8).
The presence of axial ligands to the centrally coordinated metal ion is often advantageous, since it generates some degree of steric hindrance to intermolecular aggregation, without impairing the photophysical properties of the dye. Several photophysical parameters for tetrasulfonated aluminum porphyrins (Table 2) have been evaluated by means of some in vitro experiments on EL-4 cells [40].
Figure 9.
The spectra of Pc as free base (a) and metallic complex (b)
Spectral properties and data for partitioning coefficients of some metallo-porphyrins
The quantum yield for singlet oxygen generation was evaluated in this experiments by using DPBF method [41], and an exemplification is shown in Table 3.
\n\t\t
\n\t\t
\n\t\t
\n\t\t
\n\t\t\t
\n\t\t\t\tPorphyrin\n\t\t\t
\n\t\t\t
\n\t\t\t\t\n\t\t\t\t\t1O2 quantum yield\n\t\t\t
\n\t\t\t
\n\t\t\t\tLifetime for singlet excited states of porphyrins (ps)\n\t\t\t
\n\t\t
\n\t\t
\n\t\t\t
C2AlTSPP
\n\t\t\t
0, 96
\n\t\t\t
5.03
\n\t\t
\n\t\t
\n\t\t\t
C4AlTSPP
\n\t\t\t
0.78
\n\t\t\t
40, 8
\n\t\t
\n\t\t
\n\t\t\t
C8AlTSPP
\n\t\t\t
0.83
\n\t\t\t
32, 9
\n\t\t
\n\t\t
\n\t\t\t
C12AlTSPP
\n\t\t\t
0.665
\n\t\t\t
47, 5
\n\t\t
\n\t
Table 3.
The singlet oxygen quantum yields and the lifetime values for the first excited states of Al porphyrins
The cellular uptake of different drugs seems to be correlated to their hydrophobicity only when the drugs are very closely related to chemical structure. Aluminum ion has a great influence on the sensitizer hydrophobicity without a corresponding effect on the cellular uptake (Table 4).
The data for cellular uptake of the aluminum porphyrins
Nevertheless, C2AlTSPP is not as well uptaken as H2TSPP, even in the studied series, porphyrin is the most reactive.The uptake ratio of porphyrins in vitro increases when increasing the lipophilic property of the drug. The uptake of aluminum porphyrins increases linearly with increasing lipophilicity. The inactivation kinetics for EL-4 cells is shown in Figure 10 and their microscopic aspects are shown in Figure 11.
Figure 10.
The inactivation diagram for EL-4 cells with aluminum porphyrins (1=AlC12TSPP; 2=AlC8TSPP; 3=AliBuTSPP; 4=AlC2TSPP; 5=Control
Figure 11.
The microscopic aspects of cells before (left) and after PDT (middle and right)
Apoptosis (type I cell death) is different from necrosis (type III cell death) [42, 45]. If apoptosis is a controlled suicide pathway, involving DNA breaks, membrane blebbing, cell shrinkage and phagocytosis, necrosis involves membrane damage, local inflammation and injury, which lead to oncosis. Except of these types, there is type II cell death, which is characterized by an enormous increase of two-membrane autophagic vacuoles in the cytoplasm, which are finally catalyzed by lysosomal hydrolases [43]. Autophagy is a convertible process, which can provoke both survival and death pathways, in contrast to the apoptotic irreversible process leading only to cell death. Apoptotic cell death is the most preferable effect of various anticancer therapies, which leads to destruction and elimination of pathological cells. Inflammation does not occur through apoptosis in cancer cells and surroundings tissue [44].
5. Concept of oxidative stress in photodynamic therapy
5.1. Types of Reactive Oxygen Species (ROS)
PDT is a concerted action of a sensitizer, a light source in the presence of oxygen, based on singlet oxygen and ROS production, leading to cell death by different mechanism [46].
Reactive oxygen species (ROS) is a collective term used for a group of oxidants, which are either free radicals or molecular species able to generate free radicals. The most important free radicals occurring in the human body are hydroxyl radical (*OH), singlet oxygen (1O2) and superoxide (O2*-). Except these species, the intracellular generation of ROS mainly comprises nitric oxide (NO•) radicals, which together with O2•− radicals, are converted to powerful oxidizing radicals like hydroxyl radical (•OH), alkoxy radicals (RO•), peroxyl radicals (ROO•), singlet oxygen (1O2) by complex transformation reactions. Some of the radical species are converted into molecular oxidants like hydrogen peroxide (H2O2), peroxynitrite (ONOO–) and hypochlorous acid (HOCl). The oxidative stress damage is targeted mainly at cellular macromolecules, such as lipids, nucleic acids and proteins. Hydrophobic photosensitizers accumulate mainly in cell membranes and they are primarily attacked by free radicals. These oxidizing agents can damage cells by starting chain reactions such as lipid peroxidation, or oxidation of proteins or DNA. Damage to DNA can cause mutations and even major diseases (cancer), while protein oxidation can lead to distortion and degradation. Oxidation or oxidative stress leads to the production of free radicals, for example the hydrogen and oxygen molecules, which are not related to other factors. In their free form these molecules react with other molecules, and contribute to oxidative stress [47-49].
Oxidative stress, arising as a result of an imbalance between free radical production and antioxidant defenses, is associated with damage to a wide range of molecular species including lipids, proteins, and nucleic acids. Oxidative stress is a factor that initiates cell death after photodynamic reaction [50–54]. The formation of reactive oxygen species (ROS) with cytotoxic effects is the key involved in the death of the tumor cells by PDT [55]. PDT may be considered an oxidative stress that induces apoptosis in different types of cancerous cells both in vitro and in vivo [56].
Cells have a highly developed and regulated antioxidant defense system to maintain appropriate intracellular ROS levels and prevent oxidative damage. This system includes antioxidant enzymes such as superoxide dismutase (SOD), catalase and various peroxidases and non-enzymatic systems (GSH, thioredoxin, uric acid, vitamins, coenzyme Q) that effectively remove ROS. Under normal conditions, antioxidant mechanisms scavenge ROS and protect the organism from the damaging effects of ROS. However, under conditions of excessive oxidative stress, cellular antioxidant mechanisms may be unable to prevent the adverse impact of ROS on critical cellular processes. ROS can interact with cellular macromolecules, including DNA, protein and lipids, and interfere with vital cellular functions [35]. Mutations caused by ROS can result in malignant transformation and the development of cancer [57].
To evaluate the presence of oxidative stress in the plasma, we used indirect methods. These quantify the lesions produced by the reactive oxygen species on the organism’s biomolecules.
To evaluate the presence of oxidative stress in PDT, some of the following methods could be used [58–64]:
Detection of malondialdehyde (MDA), the marker used most frequently for lipid peroxidation, using the fluorimetric method with 2-thiobarbituric acid (TBA);
The carbonylated proteins (CP) with 2, 4-dinitrophenylhydrazine using the Reznick method. To determine the level of proteins from the homogenate samples Bradford method was used.
The hydrogen-donating capacity (HDA) using the stable free radical: 1, 1 diphenyl-picrylhydrasyl (DPPH);
Detection of the –SH groups with 2, 2-dithiobisnitrobenzoic acid (Ellman’s reagent). The zymographic method was used to determine the MMPs activity.
Some synthetic PSs such as porphyrins have the capacity to generate reactive oxygen species with cytotoxic effects leading to the necrosis of tumor cells, and induced a significant oxidative stress response, with peak intensity at 24-hour post-exposure. The most significant responses were the increase of CP, MDA, MMP-2 (matrix metalloproteinase-2) activity and the decrease in HDA levels. The experiment also induced less significant, but present, reduction of the thiol groups.
As an exemplification, PDT with H2TSPP increases ROS production in plasma and tumor tissue and determines oxidative alterations of biomolecules (lipids, proteins) (Figure 12).
Oxidative stress, responsible for tissues injured in different pathologies, involves the nonequilibrium between the produced radical species and antioxidant defense agents.
There are some priority parameters which should be determined and evaluated:
Cell viability test measured by the lactate dehydrogenase release in the supernatant of cell culture as a marker of cell integrity. Viability results were expressed as % of live cells from the suspension subjected to 24 h incubation in the tested agents and/or irradiation.
Cell proliferation test measuring the number of viable cells as live cells reduce the kit reagent into a formazan compound that is colorimetric measured at 490 nm. From this point of view the test measures the quantity of viable cells in culture and thus the proliferative capacity of the tested cells.
RNA synthesis achieved by tritium-labeled uridine incorporation method, which involves beta-radioactivity measurement for radiolabeled cell cultures.
Total cellular RNA offer the concentration of total RNA, measured with SV total RNA isolation system.
TUNEL and immunofluorescence essential for apoptosis detection by observing the DNA fragmentation assay and TdT-mediated dUTP nick-end labeling (TUNEL) assay. TUNEL staining was performed to detect internal and end-strand breaks, which often occur in the early stages of apoptosis. TUNEL staining was carried out according to the manufacturer’s instructions (Promega, Madison, USA). The procedure is carried out as follows. Biotinylated nucleotide is incorporated at the 3\'-OH DNA ends using the terminal deoxynucleotidyl transferase (rTdT) recombinant enzyme. The apoptotic cells were counted under the microscope and photographed.
Analysis of genomic DNA fragmentation visualized by staining with ethidium bromide (0.5 µg/ml) and photographed under UV illumination. DNA was separated using standard 1.5% agarose (Bio-Rad) gel electrophoresis at 10 V/cm.
Cellular morphology visible by electron microscopy necessary for identifying the apoptotic cells. After PDT treatment, cells are developing morphological features characteristic of apoptosis: chromatin compaction into uniform electron-dense masses with nuclear margination, nuclear fragmentation, cellular shrinkage, cell membrane vacuolization and blebbing, and the increase in electron-density of the cytosol [63-65].
Photodegradation reaction of sensitizers, which are indicators for lifetime of the sensitizers, time efficiency and potential side effects of them (Figure 13).
Figure 12.
The oxidative stress parameters for PDT with H2TSPP. Adapted after [55]
Some of these parameters have been calculated for PDT with different sensitizers and for different cells; B16, K562, EL-4, etc. [64–69]. During irradiation, after the first 30 minutes, a strong cellular degradation, especially for TNP-loaded cells, is visible (Figure 14). The results indicate that a free-base porphyrin as 5, 10, 15, 20-tetra-p-naphthyl-porphyrin (TNP) induces apoptosis in K562 cells in a time-dependent manner. There were no changes in tail moment of K562 cells in the absence of light, whereas TNP (10 µg/mL) leads to DNA damage at different time incubation (1–4 h), light dose (0, 10 or 25 J/cm2) and time irradiation (5–50 minutes). Less genotoxicity will appear for higher light dose that for higher sensitizer concentration. Unloaded cells subjected to irradiation have a slightly higher LDH release, 56% proliferation capacity and 13% Urd incorporation compared to control cells. After 48 h of irradiation (Figure 14) cells have a high LDH release compared to control and a reduced proliferative capacity (100 %). After irradiation, the cells were subjected for 24 h, 48 h and 72 h to the LDH, MTS and uridine incorporation tests in order to study the capacity of remaining cells to proliferate after treatment. A significant reduction of RNA has been registered for TNP loaded and non-loaded cells (Figure 15). The viability of the irradiated K562 tumor cells was assessed by the increase of the LDH release and the associated decline of the MTS reduction (Figure 16). We also observed that cells that survive after the PDT procedure are more stable than the irradiated control.
Figure 13.
The photo degradation scheme of a sensitizer
Figure 14.
Time evolution of the cellular density for TNP-loaded K562 cells (10 µg/ml TNP)
After irradiation, the K562 cell viability is strongly affected both for TNP-loaded cells and for those unloaded. TNP activated increases the cell mortality by comparison with control cells (Mi) (Figure 15).
Figure 15.
The viability of K562 loaded with TNP after the first hours after irradiation
At different time post-irradiation, TNP intracellular loaded and activated shows a homogeneous effect on the cells’ capacity to deliver LDH (Figure 16).
Figure 16.
Time evolution of K562 cells viability after laser activation in the presence of TNP
RNA isolation from K562 cells has been achieved in the first 4 hours after irradiation. A 35% decrease of RNA content has been registered in the case of H2TSPP (Figure 17) [72], Also, there is a good correlation between uridine incorporation and number of live cells in 24 h post-irradiation in the presence of the same sensitizer, both of them decreading (Figure 18). Also, the amount of total cellular RNA isolated from the K562 cells drastically decreased after irradiation (Figure 19).
Figure 17.
The viability and multiplication rate of K562 tumor cells at 24h post-irradiation. C = nonirradiated unloaded cells; TSPP = nonirradiated loaded cells; Ci = irradiated unloaded cells; TSPPi = irradiated loaded cells.
At different time intervals after treatment, the cells were analyzed for caspase-3. At 4 h post-PDT, 100% of the cells displayed protease activities. After PDT, 30.6% of the cells showed total caspase activity. Thereafter, the fraction of cells with caspase activity increased to 48.6%.
When present in the cytoplasm, a number of caspases have been activated following PDT and responsible for the cleavage of multiple cellular proteins, DNA fragmentation, and cell death. Activation of procaspase-3 after PDT has been demonstrated in multiple experimental settings. The morphological manifestation of apoptosis (“execution” phase) can be ascribed as degradation of various structural proteins and DNA. After loading K562 cells with TNP, and irradiation, a strong decrease has been obtained for caspase-3 activity (Figure 20).
Figure 18.
Correlation between uridine incorporation and number of live cells in 24 h post-irradiation. C = non-irradiated unloaded cells; Ci = irradiated unloaded cells; H2TSPPi = irradiated loaded cells.
Figure 19.
The amount of total cellular RNA isolated from the K562 cells. C = unloaded non-irradiated cells; Ci = irradiated unloaded cells; TSPP = non-irradiated loaded cells; TSPPi = irradiated loaded cells.
Figure 20.
Caspase 3 activity in K562 cells loaded with 10 μg/ml TNP and activation by irradiation.
Induced apoptosis of K562 cells loaded with 10 μg/ml TNP and activated with laser (TUNEL) has been shown in Figure 21, as results of TUNEL test. Many apoptotic cells characterized with brown nuclei can be seen in the TNP-PDT groups.
The PDT efficacy relies on the concerted action of sensitizer and light, with none of them alone inducing apoptosis.
Figure 21.
Induced apoptosis of K562 cells loaded with 10 μg/ml TNP and activated with laser (TUNEL). Results of TUNEL. Many apoptotic cells characterized with brown nuclei can be seen in the TNP-PDT groups.
6. Natural products as antioxidants
An antioxidant is a molecule stable able to donate an electron to a free radical, neutralizing it, thus reducing its capacity to damage. The antioxidants delay or inhibit cellular damage mainly through their free radical scavenging property. A variety of dietary plants including grams, legumes, fruits, vegetables, tea, wine etc. contain antioxidants. The most important antioxidants seem to be nonenzymatic antioxidants derived from plant sources including vitamins (vitamin A, C, E, K), flavonoids (quercetin, catechin, epigallocatechin gallate, hesperidin, hesperetin, diosmin, and many others), phenolic acids (cinnamic acid derivatives, curcumin, caffeine, catechins, gallic acid derivatives, salicylic acid derivatives, chlorogenic acid, resveratrol, folate, anthocyanins and tannins) [74–80].
Carotenoids, known as naturally fat-soluble pigments and synthesized by vegetal organisms, are sources of different colors [81]. They could be classified into carotenes (beta-carotene and lycopene) and xanthophylls (lutein and zeaxanthin).Their structure is shown in Figure 22. Beta-carotene and lycopene are widely regarded as being effective antioxidants, with small sizes (nm), specific absorption and fluorescence spectra, and are easy to detect (Figures 23–25). The synergic antioxidant effect of the mixture lycopene-beta-carotene-vitamin E on some cellular systems (in vitro and in vivo), has been reported [82–84]. Some antioxidants with health-protective effects (lycopene, beta-carotene, vitamin C, quercetin-glycosides, naringenin-chalcone, chlorogenic acid) are seen in tomato plants.
From ancient times, plants have been used intuitively for medicinal purposes. A large number of plants have been investigated and various species have been reported to exhibit antioxidant activity, including Marigold flower (Calendula officinalis), belonging to the Asteraceae family, which is a medicinal plant which contains oleanolic acid and other compounds, which present considerable potential health benefits, protective effects against the development of cancer, adverse effects of chemotherapy and radiation therapy, inhibition of existing tumor cells, anti-inflammatory activity, antioxidant activity, protective cardiovascular and antiviral effects [85]. The medicinal plants contain many ingredients with antioxidant capacity, as the pigments: antocyanins, chlorophyll, carotenoids, flavonoids, and so on [86]. Reactive oxygen species (ROS) comprise singlet oxygen (SO) and a range of oxidizing free radicals. The interaction of carotenoids with such species is important for the understanding of many important aspects of life such as photosynthesis, vision, various medical treatments from dermatology to cancer, as well as understanding possible deleterious reactions affecting man and also for commercial reasons, such as, investigations into the stability of carotenoids used as food dyes [87-90].
Figure 22.
The transformation diagram of lycopene
Figure 23.
The DLS measurement of lycopene
Figure 24.
The absorption (left) and fluorescence (right) spectra of lycopene
Figure 25.
The absorption spectra of lycopene (- - -) and carotene (_____)
Many antioxidants could be identified in tea leaves and fruits. For example, green tea, produced from the leaves of the plant (Camellia sinensis) contains polyphenols, which are potent antioxidants and, based on studies in preclinical models, have several photoprotective properties. The most active constituents are polyphenolic catechins, of which epigallocatechin-3-gallate is the most potent. Tea polyphenols have been shown to inhibit carcinogenesis in many animal models, and the significance of catechins, the main constituents of green tea, has been increasingly recognized to play a role in cancer prevention. Green tea contains some catechins, such as (–)-epigallocatechin-3-gallate (EGCG), epicatechin (EC), epicatechin -3-gallate (ECG), and epigallocatechin (EGC) (Figure 26), the first one being recognized as an efficient anticancer agent. Except the catechins, tea polyphenols exhibit carcinogenesis effect [91–101].
Figure 26.
The chemical structure of the main epicatechin derivatives/polyphenols from green tea
The antioxidant activity (AA%) of the studied samples and their inhibitory effect against free radicals was evaluated using the DPPH method, by used the following formula:
AA% = [Acontrol-Asample/Acontrol]x 100
\n\t\t\t
where: Acontrol is the absorbance of a DPPH solution without sample, Asample is the absorbance of the sample mixed with DPPH solution.
Some citrus extracts are very important for their antioxidant activity such as hesperidin, hesperitin and diosmin (Figure 27). Among the flavonoids used in oral administration in chronic leg ulcer, hesperidin is a glucozid that is abundant in citrus fruits. Recently, formulating hesperidin in nanocrystals, has provided its dermatological application, assessing its antioxidant effect. In vitro studies have shown its clear antioxidant properties, and using them as nutrients has shown its vaso-protective action.
Figure 27.
The structure of hesperidin, diosmin and hesperetin
Among mostly exploited flavonoids in chronic venous condition, hesperidin (C28H34O15) [+/−-3, 5, 7-trihydroxy-4ʹ-methoxyflavanone 7-rhamnoglucoside] is a flavanone glycoside group of flavonoids found in large amounts in citrus fruits, grapefruit peels, lemon, oranges, blond grapefruit (Citrus paradisi), pummelo–blond grapefruit hybrid (Citrus paradisi var Jaffa Sweetie), or Chinese herbal medicine, with the highest concentration being found in the peel and the white parts of the fruit. Once formulated as nanocrystals, hesperidin also becomes dermally available and its antioxidant effect could be measured, a topic that is the subject of protected patents. In in vitro studies, this compound has a clear antioxidant action. In human nutrition, it contributes to maintenance of the integrity of blood vessels. Hesperidin has similar structure and properties with naringin, which is difficult to be separated from citrics [102]. In the same manner, diosmin is a hesperidin derivative, from the flavonoid family. As a synthetic drug, it is used for venous disease and for hemoroidal diseases [102]. Hesperetin, as a flavonoid from oranges and grapfruits, is a good protector of heart disease. It has antioxidant, anti-inflammatory, antiallergic and anticancer properties [103]. In spite of their structure differences, all of them show similar absorption spectra (Figure 28).
Figure 28.
The absorption spectra of hesperidin, hesperetin and diosmin
For all of them, total flavonoids content (TFC), total poliphenols content (TPC) and antioxidant activity (AA%) have been calculated following literature methods (Table 5) [103–105].
\n\t\t
\n\t\t
\n\t\t
\n\t\t
\n\t\t
\n\t\t\t
\n\t\t\t\tSample\n\t\t\t
\n\t\t\t
\n\t\t\t\tTFC (mg CE/L)\n\t\t\t
\n\t\t\t
\n\t\t\t\tTPC (mg GAE/L)\n\t\t\t
\n\t\t\t
\n\t\t\t\tAA (%)\n\t\t\t
\n\t\t
\n\t\t
\n\t\t\t
Diosmin etalon in MeOH
\n\t\t\t
85.53
\n\t\t\t
521.186
\n\t\t\t
55.79
\n\t\t
\n\t\t
\n\t\t\t
Hesperidin etalon in MeOH
\n\t\t\t
43.1
\n\t\t\t
466
\n\t\t\t
59.31
\n\t\t
\n\t\t
\n\t\t\t
Hesperetin etalon in MeOH
\n\t\t\t
169.16
\n\t\t\t
1814.406
\n\t\t\t
73.34
\n\t\t
\n\t
Table 5.
TFC, TPC and AA content
All the above measured parameters show very close values to the literature reports [106].
7. Conclusions
In spite of numerous advantages, the photodynamic therapy has a number of limitations. The light source should be close to the appropriate site in order to be effective before the diagnostic to be established. Persistent skin photosensitivity is observed some weeks after the treatment, which is considered as the main side effect. Also, this method is not possible without a light source and therefore entails high costs for the whole treatment. PDT acts both on ill cells and in a small manner on healthy cells. The intracellular Ca2+ from the cells induce low levels of shear stress on them, without any morphological changes [112]. The reactive oxygen species are localized to the cancer cells selectively destroying them and not the surrounding normal tissue. The presence of the lymphoid cells in tumor immunity has been demonstrated during PDT with various photosensitizers. The immunologic effects include the production of interleukin 1-beta, interleukin 2, tumor necrosis factor-alpha, and granulocyte colony-stimulating factor. PDT acts to induce oxidative stress by the generation of free radicals to damage DNA and proteins, and eventually cell death, by necrosis and apoptosis. The reactive oxygen species lead to the state called oxidative stress. The antioxidants offer protection against lipid oxidation, react and interfere with free radicals, reduce oxidative stress, and stop low-density lipoproteins from being oxidized. Also, they protect healthy tissues and lower the incidence of treatment-related side effects. In the context where many clinical studies with respect to the application of antioxidants as sensitizers are lacking, this chapter showed a systematic review by showing evidence of the antioxidant action in photochemotherapy and their comparison with synthetic sensitizers (porphyrins and phthalocyanines). Under such circumstances, PDT is extremely important for the treatment of different diseases: lung, bladder, and skin cancers (precancerous and even melanoma).
Acknowledgments
We have received the financial support of the project PNII 185/2014 to submit this book chapter.
\n',keywords:"photodynamic therapy, sensitizers, natural compounds, antioxidants",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/48720.pdf",chapterXML:"https://mts.intechopen.com/source/xml/48720.xml",downloadPdfUrl:"/chapter/pdf-download/48720",previewPdfUrl:"/chapter/pdf-preview/48720",totalDownloads:1425,totalViews:358,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,dateSubmitted:"October 11th 2014",dateReviewed:"May 21st 2015",datePrePublished:null,datePublished:"November 11th 2015",dateFinished:null,readingETA:"0",abstract:"Photodynamic therapy (also called PDT, photoirradiation therapy, phototherapy, or photochemotherapy) as a new modality for cancer treatment involves the combination of light with a photosensitizing drug in an oxygen-rich environment. PDT consists in the systemic administration of a photosensitizer (PS), which is selectively retained by tumor cells and the subsequent irradiation with visible light of the affected area. Basically two types of reactions can occur after photoactivation of the photosensitizer: the first involves the generation of free radicals (type-I photochemical reaction) and the other the production of singlet molecular oxygen, (type II) as the main species responsible for cell inactivation. The mechanism of PDT effects may involve a direct tumor cell injury and also an indirect cell killing via microcirculatory changes resulting in reduced blood flow in the tumor. Also, PDT may be considered an oxidative stress that induces cellular death in different types of cancerous cells both in vitro and in vivo. Oxidation or oxidative stress leads to the production of free radicals. Generated reactive oxygen species (ROS) cause oxidative stress in the cells targeting mainly at cellular macromolecules, such as lipids, nucleic acids and proteins. These oxidizing agents can damage cells by starting chain reactions such as lipid peroxidation, or oxidation of proteins or DNA, causing mutations and even major diseases, while protein oxidation can lead to distortion and degradation. To evaluate the presence of oxidative stress in PDT, some methods could be used: detection of malondialdehyde (MDA), the carbonylated proteins (CP), the hydrogen donating capacity (HDA), detection pf the -SH groups. By reducing basal levels of ROS in cells may facilitate the therapeutic effects of oxidative stress-based therapies. Natural antioxidants may also protect healthy tissues and lower the incidence of treatment-related side effects, and the chapter shows some results about hesperidin, hesperitine, diosmin and also, some tea rxtracts based on tea leaves and fruits. The Green tea polyphenols have been shown to have a protective effect in different forms of cancer in a variety of pre-clinical animal models. Green tea is composed of several catechins, including (-)-Epigallocatechin-3-gallate (EGCG), epicatechin (EC), epicatechin-3-gallate (ECG), and epigallocatechin (EGC). Among them, (-)-Epigallocatechin-3- gallate (EGCG), the major catechin found in green tea, has been recognized as a potential therapeutic agent. In the context where many clinical studies with respect to the application of antioxidants as sensitizers are lacking, this chapter shows a systematic review by putting into evidence the antioxidant action in photochemotherapy and their comparison with synthetic sensitizers (porphyrins and phthalocyanines). Some up-to-date results of photodynamic therapy with synthetic sensitizers and/or coupled with some natural antioxidants are shown and discussed.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/48720",risUrl:"/chapter/ris/48720",book:{slug:"basic-principles-and-clinical-significance-of-oxidative-stress"},signatures:"Rodica-Mariana Ion and Ioana-Raluca Şuică-Bunghez",authors:[{id:"171504",title:"Prof.",name:"Rodica-Mariana",middleName:null,surname:"Ion",fullName:"Rodica-Mariana Ion",slug:"rodica-mariana-ion",email:"rodica_ion2000@yahoo.co.uk",position:null,institution:{name:"Valahia University of Targoviste",institutionURL:null,country:{name:"Romania"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. General concept of photodynamic therapy",level:"1"},{id:"sec_3",title:"3. Mechanisms of photodynamic therapy",level:"1"},{id:"sec_3_2",title:"3.1. Photophysical and photochemical mechanism",level:"2"},{id:"sec_4_2",title:"3.2. Photobiological mechanism",level:"2"},{id:"sec_6",title:"4. Photosensitizers",level:"1"},{id:"sec_6_2",title:"4.1. Conventional photosensitizers",level:"2"},{id:"sec_8",title:"5. Concept of oxidative stress in photodynamic therapy",level:"1"},{id:"sec_8_2",title:"5.1. Types of Reactive Oxygen Species (ROS)",level:"2"},{id:"sec_10",title:"6. Natural products as antioxidants",level:"1"},{id:"sec_11",title:"7. Conclusions",level:"1"},{id:"sec_12",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'Ion R.M. The use of phthalocyanines and related complexes in photodynamic therapy. In Nyokong T., Ahsen V. (eds.); Photosensitizers in Medicine, Environment and Security. Springer, 2012, pp. 315–349.'},{id:"B2",body:'Ion R.M. Porphyrins for tumor destruction in photodynamic therapy. Current Topics on Biophysics 2000;24(1) 30–42.'},{id:"B3",body:'Ion R.M. Photodynamic Nanomedicine Strategies in Cancer Therapy and Drug Delivery. In Advances in Bioengineering, Intech, 2015.'},{id:"B4",body:'Ion R.M. Photodynamic therapy (PDT): A photochemical concept with medical applications, Revue Roumaine De Chimie 2007;52(12):1093–1102.'},{id:"B5",body:'Clichici S., Filip A., Daicoviciu D., Ion R.M., Mocan T., Tatomir C. The dynamics of reactive oxygen species in photodynamic therapy with tetra sulfophenyl-porphyrin. Acta Physiologica Hungarica 2010;97(1):41–51.'},{id:"B6",body:'Pushpan S.K., Venkatraman S., Anand V.G., Sankar J., Parmeswaran D., Ganesan S., Chandrashekar T.K. Porphyrins in photodynamic therapy—a search for ideal photosensitizers. Current Medicinal Chemistry Anti-Cancer Agents 2002;2(2):187–207.'},{id:"B7",body:'R.M. Ion, Nanomedicine between laboratory and clinical applications, in: Nanostructuring and Nanocharacterization, in Micro and Nanoengineering Series (eds. M. Zaharescu, M. Ciurea, D.Dascalu), Ed. Academiei, Bucharest, Romania (2010):241–256.'},{id:"B8",body:'Frackowiak D., Planner A., Waszkowiak A., Boguta A., Ion R.M., Wiktorowicz K. Yield of phthalocyanines intersystem (singlet-triplet) crossing evaluated on the basis of time resolved photothermal method. Journal Photochemistry and Photobiology A: Chemistry 2001;141(2–3):101–108.'},{id:"B9",body:'Frackowiak D., Waszkowiak A., Manikowski H., Ion R.M., Cofta J., Wiktorowicz K. The interactions of phtalocyanines with stimulated and resting human peripheral blood mononuclear cells. Acta Biochimica Polonica 2001;48(1) 257–269.'},{id:"B10",body:'Frąckowiak D., Planner A., Ion R.M., Wiktorowicz K. Incorporation of dye in resting and stimulated leukocytes: in: Near-Infrared Dyes for High Technology Applications. NATO ASI SERIES, (eds. S. Daehne, U. Resch-Genger, O. S. Wolfbeis), Kluwer Academic Publishers, Dordrecht, (1998):87–114.'},{id:"B11",body:'R.M. Ion, A.A. Sorescu, A. Nuta. New metallo-sensitizers in photodynamic therapy, in: Proceedings in Advanced Research in Scientific Areas, EDIS-Publishing Institution of the University of Zilina, Slovakia (2014) 223–228.'},{id:"B12",body:'Ion RM. Porphyrins and photodynamic therapy of cancer, Bucharest; FMR; 2003.'},{id:"B13",body:'Ochsner M. Photophysical and photobiological processes in the photodynamic therapy of tumours. Journal Photochemistry Photobiology B 1997;39(1):1–18.'},{id:"B14",body:'Foote C.S. Definition of type I and type II photosensitized oxidation. Photochemistry and Photobiology 1991;54(5):659.'},{id:"B15",body:'Bergamini C.M., Gambetti S., Dondi A., Cervellati C. Oxygen, reactive oxygen species and tissue damage. Current Pharmaceutical Design 2004;10(14):1611–1626.'},{id:"B16",body:'Sharman W.M., Allen C.M., van Lier J.E. Role of activated oxygen species in photodynamic therapy. Methods Enzymol 2000;319:376–400.'},{id:"B17",body:'Halliwell B. Oxygen radicals: a commonsense look at their nature and medical importance. Medical Biology 1984;62(2):71–77.'},{id:"B18",body:'Fernandez J.M., Bilgin M.D., Grossweiner L.I. Singlet oxygen generation by photodynamic agents, Journal of Photochemistry and Photobiology B:Biology 1997;37(1-2):131–140.'},{id:"B19",body:'Plaetzer K., Krammer B., Berlanda J., Berr F., Kiesslich T. Photophysics and photochemistry of photodynamic therapy: fundamental aspects. Lasers in Medical Science 2009;24(2):259–268.'},{id:"B20",body:'Bonnett R. Photosensitizers of the porphyrin and phthalocyanine series for photodynamic therapy. Chemical Society Reviews 1995;24:19–33.'},{id:"B21",body:'Boguta A., Wójcik A., Ion R.M., Wróbel, D. Photothermal methods as tools for investigation of weakly interacting non-fluorescent phthalocyanines. Journal of Photochemistry and Photobiology A: Chemistry, 2004;163(1-2):201–207.'},{id:"B22",body:'Ion R.M., Scarlat F., Gunaydin K.,.Niculescu V.I.R, Scarlat Fl. Radiation-induced degradation of DNA in photodynamic therapy of cancer. Studia Universitatis Babeş-Bolyai, Physica—Special Issue, 2001.'},{id:"B23",body:'Alarcon E., Edwards A.M., Aspee A., Moran F.E., Borsarelli C.D., Lissi E.A., Nilo D.G., Poblete H., Scaiano J.C.. Photophysics and photochemistry of dyes bound to human serum albumin are determined by the dye localization. Photochemical and Photobiological Sciences 2010;9(1):93–102.'},{id:"B24",body:'Ion R.M. Porphyrins for tumor destruction in photodynamic therapy. Current Topics on Biophysics 2000;24(1):30–42.'},{id:"B25",body:'Gunaydin K., Ion R.M., Scarlat F., Scarlat F.l., Niculescu V. I. R., Macau, C. (2004). Study of the fluorescence-quenching of Mg-TNP by anionic anthraquinones. Journal of Optoelectronics and Advanced Materials 2004;6(1):289–296.'},{id:"B26",body:'Davila J., Harriman A. Photoreactions of macrocyclic dyes bound to human serum albumin, Photochemistry and Photobiology 1990;51(1):9–19.'},{id:"B27",body:'Jasaitis A., Streckyte G., Rotomskis R. Spectroscopic studies of photosensitizer-human serum albumin complexes and their photostability, Proceedings of Photochemotherapy: Photodynamic Therapy and Other Modalities II, Vienna, 1996, SPIE, v.2924, 91–101.'},{id:"B28",body:'Ion R.M., Derivative UV-VIS spectrophotometry for porphyrins interactions in photodynamic therapy. Analytical Letters 2010;43(7):1277–1286.'},{id:"B29",body:'Chanon, M. Julliard M., Mehta G., Maiya B.G. Is 1O2 Alone sufficient for DNA cleavage? Possible involvement of paramagnetic intermediates, Research on Chemical Intermediates 1999; 25(7):633–644.'},{id:"B30",body:'Vedaldi D., Caffieri S., Miolo G., Dall\'Acqua F., Arslan P. Dark and photohemolysis of erythrocytes by furocoumarins. Zeitschrift für Naturforschung C. 1988; 43(11–12) 888–892.'},{id:"B31",body:'Ion R.M., Grigorescu M., Scarlat F., Niculescu V.I.R, Scarlat Fl., Porphyrins sensitization of DNA, Romain Journal of Physics 2001;46(9–10):637–646.'},{id:"B32",body:'Wang Q., Wang X., Yu Z., Yuan X., Jiao K. Spectroscopic and electrochemical studies on the binding mechanism of DNA with an anthraquinone biological dye, nuclear fast red, International Journal of Electrochemical Science 2011;6:5470–5481.'},{id:"B33",body:'Constantin C., Neagu M., Manda G., Ursaciuc C., Radu E., Ion R.M. Aspecte privind efectul terapiei fotodinamice cu porfirine de sinteza asupra continutului de acizi nucleici din celule tumorale, Proc. Al 35-lea simpozion de Imunologie, Timisoara, 2007, pp. 22.'},{id:"B34",body:'Ion R.M., Scarlat F., Niculescu V.I.R. Porphyrins as advanced materials in PDT. Romanian Journal of Physics 2003;48(1–2):339–346.'},{id:"B35",body:'Wróbel D., Hanyz I., Bartkowiak R., Ion R. M. Fluorescence and time-resolved delayed luminescence of porphyrins in organic solvents and polymer matrices. Journal of Fluorescence 1998;8(3):191–198.'},{id:"B36",body:'Lever A.B.P., The phthalocyanines, Advanced Inorganic Radiochemistry 1965;7:27–32.'},{id:"B37",body:'Stillman MJ., Nyokong T. In Phthalocyanines: Properties and Applications; New York; VCH; 1989.'},{id:"B38",body:'Frackowiak D., Planner A., Waszkowiak A., Boguta A., Ion R. M., Wiktorowicz K. Yield of intersystem (singlet-triplet) crossing in phthalocyanines evaluated on the basis of a time in resolved photothermal method. Journal of Photochemistry and Photobiology A: Chemistry 2001;141(2–3):101–108.'},{id:"B39",body:'Wróbel D., Goc J., Ion R. M. Photovoltaic and spectral properties of tetraphenyloporphyrin and metallotetraphenyloporphyrin dyes. Journal of Molecular Structure 1998;450(1–3):239–246.'},{id:"B40",body:'Ion R.M., Savi L., Savi G., Niculescu VIR. Photophysical parameters for EL-4 inactivation in PDT; Studia Universitatis Babes Bolyiai, Studia Physica 1 (2003).'},{id:"B41",body:'Ion R.M., Photochemical production and quenching of singlet oxygen by the porphyrins used in photodynamic therapy of cancer. Romanian Journal of Biophysics 1996;6(3–4):205–212.'},{id:"B42",body:'Kroemer G., Dallaporta B., Resche-Rigon M. The mitochondrial death/life regulator in apoptosis and necrosis. Annual Review of Physiology 1998;60:619–642.'},{id:"B43",body:'Kuwana, T., and Newmeyer, D.D. BCL-2-family proteins and the role of mitochondria in apoptosis. Current Opinion in Cell Biology. 2003;15(6);691–699.'},{id:"B44",body:'Kerr JF, Winterford CM, Harmon BV. Apoptosis. Its significance in cancer and cancer therapy. Cancer. 1994;73(8):2013–2026.'},{id:"B45",body:'Majno G, Joris I. Apoptosis, oncosis, and necrosis. An overview of cell death. The American Journal of Pathology 1995;146(1):3–15.'},{id:"B46",body:'Ion RM: Photodynamic therapy (PDT): a photochemical concept with medical applications. Revue Roumaine de Chemie. 2007;52(12):1093–1102.'},{id:"B47",body:'Pham-Huy L.A., He H., Pham-Huy C., Free Radicals, antioxidants in disease and health, International Journal of Biomedical Science 2008;4(2):89–96.'},{id:"B48",body:'Harman D. Role of free radicals in aging and disease. Annals of the New York Academy of Sciences 1992;673:126–141.'},{id:"B49",body:'Knight J. Free radicals: Their history and current status in aging and disease. Annals of Clinical & Laboratory Science 1998;28(6):331–346.'},{id:"B50",body:'Weishaupt. K.R., Gomer. C.J., Dougherty. T.J. Identification of singlet oxygen as the cytotoxic agent and photoinactivation of a murine tumor. Cancer Resources 1976;36(7PT1):2326–2329.'},{id:"B51",body:'Daicoviciu D., Filip A.G., Ion R.M., Clichici S., Decea N., Muresan A. Oxidative photodamage induced by photodynamic therapy with methoxyphenyl porphyrin derivatives in tumour-bearing rats. Folia Biologica 2011;57(1):12–19.'},{id:"B52",body:'Susan M., Baldea I., Senila S., Macovei V., Dreve S., Ion R. M., Cosgarea R. Photodamaging effects of porphyrins and chitosan on primary human keratinocytes and carcinoma cell cultures. International Journal of Dermatology 2011;50(3):280–286.'},{id:"B53",body:'Filip A.G., Clichici S., Daicoviciu D., Ion R.M., Tatomir C., Rogojan L., Opris I., Mocan T., Olteanu D., Muresan A. Possible in vivo mechanisms involved in photodynamic therapy using tetrapyrrolic macrocycles. Brazilian Journal of Medical and Biological Research 2011;44(1):53–61.'},{id:"B54",body:'Agarwal M.L., Larkin H., Zaidi S.I.A., Mukhtar H., Oleinick. N.L. Phospholipase activation triggers apoptosis in photosensitized mouse lymphoma cells. Cancer Resources 1993;53(24):5897–5902.'},{id:"B55",body:'Clichici S., Filip A., Daicoviciu D., Ion R.M., Mocan T., Tatomir C., Rogojan L, Olteanu D, Muresan A. The dynamics of reactive oxygen species in photodynamic therapy with tetra sulfophenyl-porphyrin. Acta Physiologica Hungarica, 2010;97(1):41–51.'},{id:"B56",body:'Matei C., Tampa M., Caruntu C., Ion R.M., Georgescu S.R., Dumitrascu G.R., Constantin C., Neagu M. Protein microarray for complex apoptosis monitoring of dysplastic oral keratinocytes in experimental photodynamic therapy, Biological Research 2014;47(1):33–42.'},{id:"B57",body:'Khaitan D., Dwarakanath B.S. Endogenous and induced oxidative stress in multi-cellular tumour spheroids: implications for improving tumour therapy, Indian Journal of Biochemistry & Biophysics 2009;46(1):16–24.'},{id:"B58",body:'Popescu T., Nenu I., Aldea M.D., Olteanu D., Gheban D., Tatomir C., Bolfa P., Muresan A., Ion R.M., Filip A.G. The effect of TSPP-mediated photodynamic therapy and Parecoxib in experimental tumours. Life Sciences 2014;117(2):75–83.'},{id:"B59",body:'Conti M, Moran PC, Levillain P. Improved fluorimetric determination of malondialdehyde. Clinical Chemistry. 1991;37(7):1273–1275.'},{id:"B60",body:'Ferrario A, Chantrain C, Von Tiehl K, Buckley S, Rucker N, Shalinsky D, Shimada H, DeClerck YA, Gomer J. The matrix metalloproteinase inhibitor Prinomastat enhances photodynamic therapy responsiveness in a mouse tumor model. Cancer Research 2004;64(7):2328–2332.'},{id:"B61",body:'Magi B, Ettorre A, Liberatori S, Bini L, Andreassi M, Frosali S, Neri P, Pallini V, Di Stefano A. Selectivity of protein carbonylation in the apoptotic response to oxidative stress associated with photodynamic therapy: a cell biochemical and proteomic investigation. Cell Death & Differentiation 2004;11(8):842–852.'},{id:"B62",body:'Reznick AZ, Packer L. Oxidative damage to proteins: spectrophotometric method for carbonyl assay. Methods in Enzymology. 1994;233:357–363.'},{id:"B63",body:'Saczko J, Kulbacka J, Chwilkowska A, Lugowski M, Banas T. Levels of lipid peroxidation in A549 cells after PDT in vitro. Rocz Akad Med Bialymst 2004;49(1):82–84.'},{id:"B64",body:'Mohammed AA, Ibrahim AA. Pathological roles of reactive oxygen species and their defence mechanism. Saudi Pharmaceutical Journal 2004;12:1–18.'},{id:"B65",body:'Nenu I., Popescu T., Aldea M.D., Craciun L., Olteanu D., Tatomir C., Bolfa P., Ion RM., Muresan A., Filip A.G. Metformin associated with photodynamic therapy—A novel oncological direction, Journal of Photochemistry and Photobiology B: Biology 2014;138: C80–91.'},{id:"B66",body:'Tampa M., Matei C., Popescu S., Georgescu S.R., Neagu M., Constantin, C., Ion, R.M. Zinc trisulphonated phthalocyanine used in photodynamic therapy of dysplastic oral keratinocytes, Revista de Chimie, 2013;64(6):639–645.'},{id:"B67",body:'Matei C., Tampa M., Ion R.M., Neagu M., Constantin C. Photodynamic properties of aluminium sulphonated phthalocyanines in human displazic oral keratinocytes experimental model, Digest Journal of Nanomaterials and Biostructures, 2012;7(4):1535–1547.'},{id:"B68",body:'Constantin C., Neagu M., Manda G., Ion R.M., Iordachescu D., The effects of laser activation of 5, 10, 15, 20-tetra-sulphophenyl-porphyrin loaded in K562 cells and human normal mononuclear cells. Romanian Archives of Microbiology and Immunology 2004;63(3-4):159–168.'},{id:"B69",body:'Pop S.F., Ion R.M., Neagu M., Constantin C., Photodynamic therapy on B16 cells with tetrasulphonated porphyrin and different light sources. Journal of Materials Science and Engineering 2010;4(3):10–16.'},{id:"B70",body:'Neagu M., Ion R.M., Manda G., Constantin C., Radu E., Cristu Z., Antitumoral effect of calixarenes in experimental photodynamic therapy with K562 tumor cell line, Romanian Journal of Biochemistry 2010;47(1):17–35.'},{id:"B71",body:'Ion, R.M., Neagu M., Manda G., Constantin C., Calin M. Mechanisms in photodynamic therapy photosensitizers and cellular localization on K562 cells, In Progress in Biomedical Optics and Imaging - Proceedings of SPIE, 2007, 6632, 17–21 June, 2007, Munich, Germany.'},{id:"B72",body:'Neagu M., Manda G., Constantin C., Radu E., Ion, R.M. Synthetic porphyrins in experimental photodynamic therapy induce a different antitumoral effect. Journal of Porphyrins and Phthalocyanines, 2007;11(1): 58–65.'},{id:"B73",body:'Stoykova E., Nedkova K., Sabotinov O., Ion, R.M., Alexandrova R. In vitro cytotoxicity assessment of second-generation photosensitizers for photodynamic therapy. Journal of Optoelectronics and Advanced Materials, 2007;9(2):490–493.'},{id:"B74",body:'Aruoma OI, Methodological consideration for characterization for potential antioxidant actions of bioactive components in plants foods. Mutation Research 2003;(523–524):9–20.'},{id:"B75",body:'López-Varela S, González-Gross M, Marcos A. Functional foods and the immune system: A review. European Journal of Clinical Nutrition 2002;56(3):S29–33.'},{id:"B76",body:'Han R.M., Zhang J.P., Skibsted L.H., Reaction dynamics of flavonoids and carotenoids as antioxidants. Molecules 2012;17 2140–2160.'},{id:"B77",body:'Vidya AD, Devasagayam TP. Current status of Herbal drug in India: An overview. Journal of Clinical Biochemistry and Nutrition 2007;41(1):1–11.'},{id:"B78",body:'Furuta S, Nishiba Y, Suda I. Fluorometric assay for screening antioxidative activities of vegetables. Journal of Food Science. 1997;62(3):526–528.'},{id:"B79",body:'Wang H, Cao G, Prior RL. Total antioxidant capacity of fruits. Journal of Agricultural and Food Chemistry 1996;44(3):701–705.'},{id:"B80",body:'Rao A.L., Bharani M., Pallavi V. Role of antioxidants and free radicals in health and disease. Advances in Pharmacology and Toxicology 2006;7:29–38.'},{id:"B81",body:'Holloway DE, Yang M, Paganga G, Rice-Evans CA, Bramley PM, Isomerization of dietary lycopene during assimiltion and transport in plasma, Free Radical Research 2000;32(1):93–102.'},{id:"B82",body:'Tapas AR, Sakarkar DM, Kakde RB. Flavonoids as nutraceuticals: A review. Tropical Journal of Pharmaceutical Research. 2008;7(3):1089–1099.'},{id:"B83",body:'Baranska M, Schütze W, Schulz H., Determination of lycopene and beta-carotene content in tomato fruits and related products: Comparison of FT-Raman, ATR-IR, and NIR spectroscopy, Analytical Chemistry. 2006;78(24):8456–8461.'},{id:"B84",body:'Bunghez I.R., Raduly M., Doncea S., Aksahin I., Ion R.M., Lycopene determination in tomatoes by different spectral techniques (UV-VIS, FTIR and HPLC), Digest Journal of Nanomaterials and Biostructures, 2011;6(3):1349–1356.'},{id:"B85",body:'Gupta V.K., Sharma S.K., Plants as natural antioxidants, Natural Product Radiance, 2006;5(4):326–334.'},{id:"B86",body:'Stoica R., Velea S., Ilie L., Calugareanu M., Ghimis S.B., Ion, R.M., The influence of ethanol concentration on the total phenolics and antioxidant activity of Scenedesmus Opoliensis algal biomass extracts, Revista de Chimie, 2013;64(3):304–306.'},{id:"B87",body:'Bensasson RV, Land EJ, Truscott TG. Excited States and Free Radicals in Biology and Medicine, Oxford University Press, Oxford, 1993, p. 195.'},{id:"B88",body:'Cantrell A, McGarvey DJ, Truscott TG, Rancan F, Boehm F., Singlet oxygen quenching by dietary carotenoids in a model membrane environment. Archives of Biochemistry and Biophysics. 2003;412(1):47–54.'},{id:"B89",body:'Edge R, Truscott TG. Properties of carotenoid radicals and excited states and their potential role in biological systems; in Carotenoids: Physical, Chemical and Biological Functions and Properties. Landrum JT (ed), Boca Raton; CRC Press, 2010, pp. 283–304.'},{id:"B90",body:'Edge R, McGarvey D, Truscott TG. The carotenoids as antioxidants—A review. Journal of Photochemistry and Photobiology B: Biology, 1997;41(3):189–200.'},{id:"B91",body:'Stoica, R., Pop, S.F., Ion, R.M., Evaluation of natural polyphenols entrapped in calcium alginate beads prepared by the ionotropic gelation method Journal of Optoelectronics and Advanced Materials, 2013;15(7-8):893–898.'},{id:"B92",body:'Wang Z, Agarwal R, Bickers D, Mukhtar H. Protection against ultraviolet B radiation-induced photocarcinogenesis in hairless mice by green tea polyphenols. Carcinogenesis 1991;12(8):1527–1530.'},{id:"B93",body:'Lin JK, Lin CH, Ling YC, Lin-Shian SY, Juan IM. Survey of catechins, gallic acid and methylxantines in green, oolong, pu-erh and black teas. Journal of Agricultural Food Chemistry. 1998;46(9):3635–3642.'},{id:"B94",body:'Ahn WS, Huh SW, Bae SM, Lee IP, Lee JM, Namkoong SE, Kim CK, Sin JI. A major constituent of green tea, EGCG, inhibits the growth of human cervical cancer cell lines, CaSKI cells, through apoptosis, G1 arrest and regulation of gene expression. DNA Cell Biology 2003;22(3):217–224.'},{id:"B95",body:'Taniguchi S, Fujiki H, Kobayashi H, Go H, Miyado K, Sadano H, Shimokawa R. Effect of (−)-epigallocatechin gallate, the main constituent of green tea, on lung metastasis with mouse B16 melanoma cell lines, Cancer Letters, 1991; 65(1):51–54.'},{id:"B96",body:'Nakazato T, Ito K, Ikeda Y, Kizaki M. Green tea component, catechin, induces apoptosis of human malignant B cells via production of reactive oxygen species. Clinical Cancer Research 2005;11(16):6040–6049.'},{id:"B97",body:'Fierascu I., Bunghez I.R., Fierascu R., Ion, R.M., Dinu-Pîrvu C.E., Nuţa, D., Characterization and antioxidant activity of phytosynthesised silver nanoparticles using Calendula officinalis extract, Farmacia, 2013;62(1):129–136.'},{id:"B98",body:'Mittal A, Piyathilake C, Hara Y, et al.: Exceptionally high protection of photocarcinogenesis by topical application of ()-epigallocatechin-3-gallate in hydrophilic cream in SKH-1 hairless mouse model: Relationship to inhibition of UVB-induced global DNA hypomethylation. Neoplasia 2003;5(6):555–565.'},{id:"B99",body:'Katiyar S, Matsui M, Elmets C, Mukhtar H. Polyphenolic antioxidant (–)-epigallocatechin-3-gallate from green tea reduces UVB-induced inflammatory responses and infiltration ofleukocytes in human skin. Photochemistry and Photobiology 1999;69(2):148–153.'},{id:"B100",body:'Katiyar S, Afaq F, Perez A, Mukhtar H. Green tea polyphenol(–)-epigallocatechin-3-gallate treatment of human skin inhibits ultraviolet radiation-induced oxidative stress. Carcinogenesis 2001;22(2):287–294.'},{id:"B101",body:'Otsuka T, Ogo T, Eto T, Asano Y, Suganuma M, Niho Y. Growth inhibition of leukemic cells by(–)-apigallocatechin-3-gallate, the main constituent of green tea. Life Sciences. 1998;63(16):1397–1403.'},{id:"B102",body:'Srilatha D., Nasare M., Nagasandhya B., Prasad V., Diwan P. Development and Validation of UV Spectrophotometric Method for Simultaneous Estimation of Hesperidin and Diosmin in the Pharmaceutical Dosage Form. Hindawi Publishing Corporation, ISRN Spectroscopy 2013, ID 534830, 4 pp.'},{id:"B103",body:'Erlund I., Review of the flavonoids quercetin, hesperetin and naringenin. Dietary sources, bioactivities, bioavailability, and epidemiology. Nutrition Research 2004;24(10):851–874.'},{id:"B104",body:'Biju J., Sulaiman C.T., Satheesh G., Reddy V.R.K., Total phenolics and flavonoids in selected medicinal plants from Kerala. International Journal of Pharmacy and Pharmaceutical Sciences, 2014;6(1):406–408.'},{id:"B105",body:'Zhishen J, Mengcheng T, Jianming W., The determination of flavonoid contents in mulberry and their scavenging effects on Superoxide radicals, Food Chemistry, 1999;64(4):555–559.'},{id:"B106",body:'Jakobek L., Seruga M., Medvidović-Kosanović M., Novak I. Antioxidant activity and polyphenols of aronia in comparison to other berry species, Agriculturae Conspectus Scientificus, 2007;72(4):301–306.'},{id:"B107",body:'Mosquera O.M., Correra Y.M., Nino J. Antioxidant activity of plant extracts from Colombian flora. Brazilian Journal of Pharmacognosy 2009;19(2A):382–387.'},{id:"B108",body:'Gurushankar K., Gohulkumar M., Rajendra Prasad N., Krishnakumar N. Synthesis, characterization and in vitro anti-cancer evaluation of hesperetin-loaded nanoparticles in human oral carcinoma (KB) cells, Advances in Natural Sciences: Nanoscience and Nanotechnology 2014;5(1):015006(10pp).'},{id:"B109",body:'Tsai T.H, Chen Y.F., Determination of unbound hesperetin in rat blood and brain by microdialysis coupled to microbore liquid chromatography, Journal of Food and Drug Analysis, 2000;8(4):331–336.'},{id:"B110",body:'Tsimogiannis D., Samiotaki M., Panayotou G., Oreopoulou V., Characterization of flavonoid subgroups and hydroxy substitution by HPLC-MS/MS, Molecules 2007;12(3) 593–606.'},{id:"B111",body:'Kuntic V., Pejic N., Svetlana Micic S., Direct spectrophotometric determination of hesperidin in pharmaceutical preparations, Acta Chimica Slovenica, 2012;59(2) 436–441.'},{id:"B112",body:'Yin H., Zhang X., Pattrick N., Klauke N., Cordingley H. C., Haswell S. J., Cooper J. M., Influence of hydrodynamic conditions on quantitative cellular assays in microfluidic systems. Anal. Chem. 2007; 79(18):7139–7144.'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Rodica-Mariana Ion",address:"rodica_ion2000@yahoo.co.uk",affiliation:'
ICECHIM, Nanomedicine Research Group, Bucharest, Romania
Valahia University, Nanomaterials Center, Targoviste, Romania
ICECHIM, Nanomedicine Research Group, Bucharest, Romania
'}],corrections:null},book:{id:"4597",title:"Basic Principles and Clinical Significance of Oxidative Stress",subtitle:null,fullTitle:"Basic Principles and Clinical Significance of Oxidative Stress",slug:"basic-principles-and-clinical-significance-of-oxidative-stress",publishedDate:"November 11th 2015",bookSignature:"Sivakumar Joghi Thatha Gowder",coverURL:"https://cdn.intechopen.com/books/images_new/4597.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"118572",title:"Dr.",name:"Sivakumar Joghi",middleName:null,surname:"Thatha Gowder",slug:"sivakumar-joghi-thatha-gowder",fullName:"Sivakumar Joghi Thatha Gowder"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},chapters:[{id:"49314",title:"Regulation of the Redox Environment",slug:"regulation-of-the-redox-environment",totalDownloads:1222,totalCrossrefCites:2,signatures:"Edgar Cano-Europa, Vanessa Blas-Valdivia, Margarita Franco-Colin\nand Rocio Ortiz-Butron",authors:[{id:"91909",title:"Prof.",name:"Edgar",middleName:null,surname:"Cano-Europa",fullName:"Edgar Cano-Europa",slug:"edgar-cano-europa"},{id:"102920",title:"Dr.",name:"Rocio",middleName:null,surname:"Ortiz-Butron",fullName:"Rocio Ortiz-Butron",slug:"rocio-ortiz-butron"},{id:"114464",title:"Prof.",name:"Margarita",middleName:null,surname:"Franco-Colin",fullName:"Margarita Franco-Colin",slug:"margarita-franco-colin"},{id:"129676",title:"Prof.",name:"Vanessa",middleName:null,surname:"Blas-Valdivia",fullName:"Vanessa Blas-Valdivia",slug:"vanessa-blas-valdivia"}]},{id:"49160",title:"Protein Oxidation and Redox Regulation of Proteolysis",slug:"protein-oxidation-and-redox-regulation-of-proteolysis",totalDownloads:1301,totalCrossrefCites:1,signatures:"Dominika Boguszewska-Mańkowska, Małgorzata Nykiel and\nBarbara Zagdańska",authors:[{id:"173803",title:"Dr.",name:"Dominika",middleName:null,surname:"Boguszewska",fullName:"Dominika Boguszewska",slug:"dominika-boguszewska"}]},{id:"48975",title:"Biochemistry of Reactive Oxygen and Nitrogen Species",slug:"biochemistry-of-reactive-oxygen-and-nitrogen-species",totalDownloads:4274,totalCrossrefCites:12,signatures:"Ayla Ozcan and Metin Ogun",authors:[{id:"95266",title:"Prof.",name:"Ayla",middleName:null,surname:"Özcan",fullName:"Ayla Özcan",slug:"ayla-ozcan"},{id:"177273",title:"Associate Prof.",name:"Metin",middleName:null,surname:"Öğün",fullName:"Metin Öğün",slug:"metin-ogun"}]},{id:"49498",title:"Members of Antioxidant Machinery and Their Functions",slug:"members-of-antioxidant-machinery-and-their-functions",totalDownloads:2767,totalCrossrefCites:7,signatures:"Shalini Kapoor Mehta and Sivakumar Joghi Thatha Gowder",authors:[{id:"118572",title:"Dr.",name:"Sivakumar Joghi",middleName:null,surname:"Thatha Gowder",fullName:"Sivakumar Joghi Thatha Gowder",slug:"sivakumar-joghi-thatha-gowder"}]},{id:"48813",title:"Antioxidants and Natural Compounds",slug:"antioxidants-and-natural-compounds",totalDownloads:1239,totalCrossrefCites:0,signatures:"Davood Maleki, Aziz Homayouni Rad, Leila Khalili and Baitullah\nAlipour",authors:[{id:"53877",title:"Dr.",name:"Aziz",middleName:null,surname:"Homayouni Rad",fullName:"Aziz Homayouni Rad",slug:"aziz-homayouni-rad"},{id:"91984",title:"Dr.",name:"Baitullah",middleName:null,surname:"Alipoor",fullName:"Baitullah Alipoor",slug:"baitullah-alipoor"},{id:"174038",title:"Ms.",name:"Leila",middleName:null,surname:"Khalili",fullName:"Leila Khalili",slug:"leila-khalili"},{id:"174039",title:"Dr.",name:"Davood",middleName:null,surname:"Maleki",fullName:"Davood Maleki",slug:"davood-maleki"}]},{id:"49495",title:"Antioxidants and Natural Compounds in Mexican Foods",slug:"antioxidants-and-natural-compounds-in-mexican-foods",totalDownloads:1192,totalCrossrefCites:0,signatures:"José Luis Silencio Barrita, Sara Montaño Benavides and Santiago\nSánchez",authors:[{id:"154175",title:"Dr",name:"Jose Luis",middleName:null,surname:"Silencio-Barrita",fullName:"Jose Luis Silencio-Barrita",slug:"jose-luis-silencio-barrita"}]},{id:"49269",title:"Rooibos (Aspalathus linearis) and its Major Flavonoids — Potential Against Oxidative Stress-Induced Conditions",slug:"rooibos-aspalathus-linearis-and-its-major-flavonoids-potential-against-oxidative-stress-induced-cond",totalDownloads:1677,totalCrossrefCites:5,signatures:"Olawale R. Ajuwon, Jeanine L. Marnewick and Lester M. Davids",authors:[{id:"156528",title:"Dr.",name:"Lester",middleName:null,surname:"Davids",fullName:"Lester Davids",slug:"lester-davids"},{id:"173313",title:"Dr.",name:"Olawale",middleName:null,surname:"Ajuwon",fullName:"Olawale Ajuwon",slug:"olawale-ajuwon"},{id:"173509",title:"Prof.",name:"Jeanine",middleName:null,surname:"Marnewick",fullName:"Jeanine Marnewick",slug:"jeanine-marnewick"}]},{id:"49357",title:"Oxidative Stress and Antioxidant Defenses Induced by Physical Exercise",slug:"oxidative-stress-and-antioxidant-defenses-induced-by-physical-exercise",totalDownloads:1395,totalCrossrefCites:3,signatures:"Juana M. Morillas-Ruiz and Pilar Hernández-Sánchez",authors:[{id:"173469",title:"Dr.",name:"Juana",middleName:null,surname:"Morillas-Ruiz",fullName:"Juana Morillas-Ruiz",slug:"juana-morillas-ruiz"},{id:"175442",title:"Dr.",name:"Pilar",middleName:null,surname:"Hernandez-Sanchez",fullName:"Pilar Hernandez-Sanchez",slug:"pilar-hernandez-sanchez"}]},{id:"48812",title:"Antioxidant Status and Sex Hormones in Women with Simple Endometrial Hyperplasia",slug:"antioxidant-status-and-sex-hormones-in-women-with-simple-endometrial-hyperplasia",totalDownloads:853,totalCrossrefCites:0,signatures:"Snežana Pejić, Ana Todorović, Vesna Stojiljković, Ivan Pavlović,\nLjubica Gavrilović, Nataša Popović and Snežana B. Pajović",authors:[{id:"81583",title:"Dr.",name:"Vesna",middleName:null,surname:"Stojiljković",fullName:"Vesna Stojiljković",slug:"vesna-stojiljkovic"},{id:"123496",title:"Dr.",name:"Ljubica",middleName:null,surname:"Gavrilović",fullName:"Ljubica Gavrilović",slug:"ljubica-gavrilovic"},{id:"173330",title:"Dr.",name:"Snezana",middleName:null,surname:"Pejic",fullName:"Snezana Pejic",slug:"snezana-pejic"},{id:"173513",title:"Dr.",name:"Ana",middleName:null,surname:"Todorovic",fullName:"Ana Todorovic",slug:"ana-todorovic"},{id:"173514",title:"MSc.",name:"Ivan",middleName:null,surname:"Pavlovic",fullName:"Ivan Pavlovic",slug:"ivan-pavlovic"},{id:"173515",title:"MSc.",name:"Natasa",middleName:null,surname:"Popovic",fullName:"Natasa Popovic",slug:"natasa-popovic"},{id:"173516",title:"Dr.",name:"Snezana",middleName:null,surname:"Pajovic",fullName:"Snezana Pajovic",slug:"snezana-pajovic"}]},{id:"48720",title:"Oxidative Stress-Based Photodynamic Therapy with Synthetic Sensitizers and/or Natural Antioxidants",slug:"oxidative-stress-based-photodynamic-therapy-with-synthetic-sensitizers-and-or-natural-antioxidants",totalDownloads:1425,totalCrossrefCites:1,signatures:"Rodica-Mariana Ion and Ioana-Raluca Şuică-Bunghez",authors:[{id:"171504",title:"Prof.",name:"Rodica-Mariana",middleName:null,surname:"Ion",fullName:"Rodica-Mariana Ion",slug:"rodica-mariana-ion"}]}]},relatedBooks:[{type:"book",id:"3408",title:"New Insights into Toxicity and Drug Testing",subtitle:null,isOpenForSubmission:!1,hash:"71cbc4a6caf1e19add9556925b6d2974",slug:"new-insights-into-toxicity-and-drug-testing",bookSignature:"Sivakumar Gowder",coverURL:"https://cdn.intechopen.com/books/images_new/3408.jpg",editedByType:"Edited by",editors:[{id:"118572",title:"Dr.",name:"Sivakumar Joghi",surname:"Thatha Gowder",slug:"sivakumar-joghi-thatha-gowder",fullName:"Sivakumar Joghi Thatha Gowder"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"},chapters:[{id:"41961",title:"Pre-Clinical Assessment of the Potential Intrinsic Hepatotoxicity of Candidate Drugs",slug:"pre-clinical-assessment-of-the-potential-intrinsic-hepatotoxicity-of-candidate-drugs",signatures:"Jacob John van Tonder, Vanessa Steenkamp and Mary Gulumian",authors:[{id:"160968",title:"Dr.",name:"Jacob",middleName:"John",surname:"Van Tonder",fullName:"Jacob Van Tonder",slug:"jacob-van-tonder"},{id:"162430",title:"Dr.",name:"Mary",middleName:null,surname:"Gulumian",fullName:"Mary Gulumian",slug:"mary-gulumian"},{id:"162431",title:"Prof.",name:"Vanessa",middleName:null,surname:"Steenkamp",fullName:"Vanessa Steenkamp",slug:"vanessa-steenkamp"}]},{id:"41968",title:"The Kidney Vero-E6 Cell Line: A Suitable Model to Study the Toxicity of Microcystins",slug:"the-kidney-vero-e6-cell-line-a-suitable-model-to-study-the-toxicity-of-microcystins",signatures:"Carina Menezes, Elisabete Valério and Elsa Dias",authors:[{id:"86640",title:"Dr",name:"Elsa",middleName:null,surname:"Dias",fullName:"Elsa Dias",slug:"elsa-dias"},{id:"160227",title:"MSc.",name:"Carina",middleName:null,surname:"Menezes",fullName:"Carina Menezes",slug:"carina-menezes"},{id:"160228",title:"Dr.",name:"Elisabete",middleName:null,surname:"Valério",fullName:"Elisabete Valério",slug:"elisabete-valerio"}]},{id:"42016",title:"Why are Early Life Stages of Aquatic Organisms more Sensitive to Toxicants than Adults?",slug:"why-are-early-life-stages-of-aquatic-organisms-more-sensitive-to-toxicants-than-adults-",signatures:"Azad Mohammed",authors:[{id:"147061",title:"Dr.",name:"Azad",middleName:null,surname:"Mohammed",fullName:"Azad Mohammed",slug:"azad-mohammed"}]},{id:"42020",title:"Screening of Herbal Medicines for Potential Toxicities",slug:"screening-of-herbal-medicines-for-potential-toxicities",signatures:"Obidike Ifeoma and Salawu Oluwakanyinsola",authors:[{id:"142730",title:"Dr.",name:"Ifeoma",middleName:null,surname:"Ezenyi",fullName:"Ifeoma Ezenyi",slug:"ifeoma-ezenyi"}]},{id:"42021",title:"Retracted: New Trends in Genotoxicity Testing of Herbal Medicinal Plants",slug:"new-trends-in-genotoxicity-testing-of-herbal-medicinal-plants",signatures:"Hala M. Abdelmigid",authors:[{id:"159676",title:"Dr.",name:"Hala M.",middleName:null,surname:"Abdelmigid",fullName:"Hala M. Abdelmigid",slug:"hala-m.-abdelmigid"}]},{id:"42018",title:"Animal Models in Drug Development",slug:"animal-models-in-drug-development",signatures:"Ray Greek",authors:[{id:"159530",title:"M.D.",name:"Ray",middleName:null,surname:"Greek",fullName:"Ray Greek",slug:"ray-greek"}]},{id:"42070",title:"Renal Transporters and Biomarkers in Safety Assessment",slug:"renal-transporters-and-biomarkers-in-safety-assessment",signatures:"P.D. Ward, D. La and J.E. McDuffie",authors:[{id:"80588",title:"Dr.",name:"Peter",middleName:null,surname:"Ward",fullName:"Peter Ward",slug:"peter-ward"},{id:"161244",title:"Dr.",name:"David",middleName:null,surname:"La",fullName:"David La",slug:"david-la"},{id:"161246",title:"Dr.",name:"J. Eric",middleName:null,surname:"McDuffie",fullName:"J. Eric McDuffie",slug:"j.-eric-mcduffie"},{id:"161247",title:"Dr.",name:"Sandra",middleName:null,surname:"Snook",fullName:"Sandra Snook",slug:"sandra-snook"}]},{id:"42072",title:"Autophagy: A Possible Defense Mechanism in Parkinson's Disease?",slug:"autophagy-a-possible-defense-mechanism-in-parkinson-s-disease-",signatures:"Rosa A. González-Polo, Rubén Gómez-Sánchez, Lydia Sánchez- Erviti, José M Bravo-San Pedro, Elisa Pizarro-Estrella, Mireia Niso- Santano and José M. Fuentes",authors:[{id:"82741",title:"Prof.",name:"Jose M",middleName:null,surname:"Fuentes",fullName:"Jose M Fuentes",slug:"jose-m-fuentes"}]},{id:"42073",title:"Physiologically Based Pharmacokinetic Modeling: A Tool for Understanding ADMET Properties and Extrapolating to Human",slug:"physiologically-based-pharmacokinetic-modeling-a-tool-for-understanding-admet-properties-and-extrapo",signatures:"Micaela B. Reddy, Harvey J. Clewell III, Thierry Lave and Melvin E. Andersen",authors:[{id:"159458",title:"Dr",name:"Michaela",middleName:null,surname:"Reddy",fullName:"Michaela Reddy",slug:"michaela-reddy"},{id:"161273",title:"Dr.",name:"Harvey",middleName:null,surname:"Clewell",fullName:"Harvey Clewell",slug:"harvey-clewell"},{id:"161274",title:"Dr.",name:"Thierry",middleName:null,surname:"Lave",fullName:"Thierry Lave",slug:"thierry-lave"},{id:"161275",title:"Dr.",name:"Melvin",middleName:null,surname:"Andersen",fullName:"Melvin Andersen",slug:"melvin-andersen"}]},{id:"42074",title:"Plasma Methadone Level Monitoring in Methadone Maintenance Therapy: A Personalised Methadone Therapy",slug:"plasma-methadone-level-monitoring-in-methadone-maintenance-therapy-a-personalised-methadone-therapy",signatures:"Nasir Mohamad, Roslanuddin Mohd Salehuddin, Basyirah Ghazali, Nor Hidayah Abu Bakar, Nurfadhlina Musa, Muslih Abdulkarim Ibrahim, Liyana Hazwani Mohd Adnan, Ahmad Rashidi and Rusli Ismail",authors:[{id:"78599",title:"Associate Prof.",name:"Nasir",middleName:null,surname:"Mohamad",fullName:"Nasir Mohamad",slug:"nasir-mohamad"}]}]}]},onlineFirst:{chapter:{type:"chapter",id:"72624",title:"Detection of Nutrient-Related SNP to Reveal Individual Malnutrition Risk",doi:"10.5772/intechopen.92458",slug:"detection-of-nutrient-related-snp-to-reveal-individual-malnutrition-risk",body:'\n
\n
1. Introduction
\n
Malnutrition is a state of disordered nutrition, in which a combination of varying degrees of over- or undernutrition and inflammatory activity has led to a change in body composition, diminished function, and outcome [1]. Malnutrition, including undernutrition, micronutrient deficiencies, and overweight and obesity, not only affects the people’s health and well-being by impacting negatively on human physical and cognitive development, compromising the immune system, increasing susceptibility to communicable and noncommunicable diseases, restricting the attainment of human potential, and reducing productivity but also poses a high burden in the form of negative social and economic consequences to individuals, families, communities, and states [2].
\n
Currently, more than 810 million people worldwide are hungry, mainly in poor, natural disaster-destroyed and war-torn countries. About 2 billion people are suffering from micronutrient deficiencies, which is called hidden hunger, and about 2 billion adults are affected by overweight and obesity, with one in 12 adults suffering from diabetes and one in two with cardiovascular diseases [3]. Developmental Origins of Health and Disease (DoHaD theory) considers that adult disease stems from malnutrition in the fetus and early childhood. More evidence accumulated that malnutrition would result in adverse consequences to the later life cycle and should be addressed in the whole life cycle [4].
\n
Malnutrition is a result of complicated reasons from diet and food behavior and also related to genetic background which has been revealed by studies in recent decades. Traditionally, nutrition status are measured and expressed with indexes of anthropometric, diet survey, clinical symptom, biochemistry, behavior, etc. [5]. These measurement has been used in national nutrition monitoring, clinic nutrition therapy, mother and children nutrition care, nutrition intervention projects, and scientific studies. However, genetic and epigenetic information on nutrition explain malnutrition in a genetic view that would supply additional new theory and methodology for the growing requirement in terms of personalized and precise nutrition. In this chapter, an introduction on detection of nutrient-related SNP to reveal individual malnutrition risk is discussed.
\n
\n
\n
2. Malnutrition related to inheritance
\n
Following the restrictive enzyme cut technology on fragment length polymorphisms and short series repeat sequences, single nucleotide polymorphisms (SNP) became the third-generation polymorphism marker with the characteristics of high genetic marker density, high stability, and high feasibility of automation detection, which showed a strong application prospect in human genomics research, such as genetic diagnosis, genetic risk assessment, chain imbalance map, and genetic association analysis. Severe malnutrition such as iron deficiency anemia, xerophthalmia and nyctalopia, pellagra, scurvy, rickets, beriberi, and other nutrient deficiency diseases was caused by the combined impact of environment and genetic factors. And the Human Genome Project study showed that 99.9% of DNA sequences were consistent among different individuals, with only small genetic differences in the sequence. 0.1% of DNA sequence differences may vary the level of risk of malnutrition and diseases such as non-chronic diseases. Single nucleotide polymorphism could be measureable markers to reveal the genetic differences.
\n
\n
2.1 Iron deficiency-related genes
\n
The discovery of polymorphisms on DNA sequences associated with common diseases was an important way to understand the risk of nutritional deficiency from genetic perspective. Iron deficiency was one of the most important nutritional problems in the world, especially in developing countries. Iron deficiency not only leads to anemia but also causes the body’s immune function, work performance, and damage of adolescent’s psychological behavior and mental development. With the deepening of research on nutritional genomics, genetic polymorphisms associated with iron nutrition status have been found. A study reported by Mclaren et al. [6] showed that rs2111833 and rs1121312 in TMPRSS6 gene with iron biochemical indicators showed that rs2111833 is associated with serum iron and log-to-ferritin saturation in the Caucasian population and shows total iron binding force, unsaturated iron binding force, and serum iron in the Asian population. Rs1421312 sites were associated with serum iron and log-to-ferritin saturation in the Caucasian population and serum iron and log-ferritin saturation in the Afro-American population. The study found that rs2111833 and rs1421312 had an impact on iron nutrition in different races.
\n
\n
\n
\n
3. Folic acid deficiency genes
\n
Folic acid was a cofactor that interacted with a variety of enzymes in many intercellular reactions, with methionine enzymes acting as coenzymes when isocysteine was converted to cystic thiopental. The extent to which the body absorbed folic acid and vitamin B6 and B12 is influenced by environmental and genetic factors. In 1964, Smithells et al. [7] showed that women with reproductive neural tube malformations (neural tube defect, NTD) had micronutrient deficiencies, especially folic acid. NTDs were congenital malformations of the brain and spinal cord that occurred within pregnancy from 21 to 28 days, including spina bifida, anencephaly, and brain bulging, which could lead to infant death and child disability. NTDs had the epidemiological characteristics of environmental and genetic factors. In 1995, a variant of MTHFR enzyme was identified which causes a substitution of C to T at nucleotide 677 [8]. The MTHFR C677T homozygous variant (TT genotype) is thermolabile, and its activity is reduced by 70% compared to the wild type (CC genotype). This reduced enzyme activity causes an accumulation of plasma homocysteine and higher rates of thymidylate synthesis. It is well established that B vitamin status is affected by genotype, particularly the C677T polymorphism in MTHFR, with the T allele being associated with higher circulating concentrations of homocysteine and lower circulating concentrations of plasma and erythrocyte folate. In 2018, Zhang et al. [9, 10] explored the association between maternal methylenetetrahydrofolate reductase (MTHFR) C677T, methionine synthase reductase (MTRR) A66G, and methionine synthase (MTR) A2756G which effects on absorption and utilization of folate, B6 and B12, and neural tube defects in offspring through meta-analysis, which showed that these SNPs were significantly associated with NTDs in offspring. A cross-sectional study of dietary and genetic predictors of blood folate levels in a large racial healthy young adults group by Daniel et al. in 2017 [11] showed that the interactive effect of the genotype with naturally occurring food folate intake on RBC folate levels occurred in the anticipated stronger individuals that is homozygous for the T allele. This pattern suggests that polyglutamated folic acid (naturally occurring food folate) is less well absorbed among C allele carriers. This interpretation is consistent with the results from previous research, which found that those with hypofunctional FOLH1 484 variants had lower RBC folate levels despite equivalent dietary folate intake. Understanding why circulating folate levels vary from person to person is critical to ensuring adequate bioavailability, especially among women of childbearing age.
\n
\n
3.1 Genes of other nutrients deficiency
\n
In recent years, the levels of folic acid; vitamin B2, B3, B6, and B12; and homocysteine (HCY) in pregnant women, as well as enzymes in folic acid and HCY pathways such as methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase (MTRR), and gene polymorphism sites associated with methionine synostic ingendraase (MTR) have been explored as potential causes of NTDs. Wilcken et al. [12] showed that the frequency of the homozygous C677T genotype (TT) was highest among individuals of Hispanic ethnicity, followed by whites, with the lowest frequency found in blacks. There were geographical and racial differences in gene polymorphisms, so future studies should conduct large samples and cross-regional surveys and established a database of gene polymorphisms in different regions and populations to provide a scientific basis for precise nutrition guidance and intervention.
\n
\n
\n
3.2 Measurement of malnutrition-related SNPs
\n
Nutrigenomics studies have sufficiently accumulated data in the last two decades to reveal phenotypes of SNPs between health and micronutrient deficiency population [13]. Zhang et al. [9, 10] explored that the genes of MTHFR C677T, MTRR A66G, and MTR A2756G were genetic factors for low absorption and bioavailability of folate, B6, B12, etc. Those nutrients are closely related with the prevalence of neural tube defects (NTDs) in newborn infants. Daniel et al. [11] reported that mutant genotype of a C allele SNP of individuals predicted lower RBC folate concentration than that of T allele SNP of individuals with the same diet folate intake level. Studies have reported numbers of micronutrient deficiency-related SNPs (MD-SNPs) of vitamins A, D, E, B6, and B12, folate, calcium, iron, zinc, selenium, etc. [14, 15, 16, 17, 18, 19, 20, 21, 22]. It is assumed that MD-SNPs based on high -quality observations in large population could be used as biomarkers for assessing genetic potential risk of micronutrient deficiency. The sequencing of the human genome has catalyzed efforts to search for disease genes by the strategy of associating sequence variants with measurable phenotypes. In particular, the Human Genome Project and follow-on efforts to characterize genetic variation have resulted in the discovery of millions of SNPs, which have emerged as genetic markers of choice because of their high-density and relatively even distribution in the human genomes. When one nutrient deficiency risk-related gene has been mapped to a chromosomal region, a high-density SNP mapping or candidate gene association studies are logical steps to follow.
\n
\n
\n
3.3 Gene sequencing
\n
The first-generation sequencing technology, also known as Sanger sequencing method, is based on the sequencing of DNA polymerase synthesis reaction. The basic principle is that the test DNA template, desired DNA synthase, deoxynucleoside triphosphates (dNTPs), reaction buffer, primers, and other components of DNA synthesis reaction and a small amount of four kinds of radioisotope dideoxynucleoside triphosphates (ddATP, ddTTP, ddCTP, and ddGTP) were added to the reaction system. Because the ddNTP dideoxyribose connected on the 3-carbon atom is not a hydroxyl group (-OH) but the hydrogen (H) after deoxidation, the ddNTP is added to the DNA strand being synthesized, the system subsequent to dNTP no longer be bound to this DNA strand, and the synthesis of this DNA strand was randomly terminated at the base of the ddNTP. Thus, after several cycles, a group is formed from short to long DNA fragments; these fragments can be directly length difference of one nucleotide, and the 3‘end nucleotide is radiolabelled with A, T, C, or G. The product was divided into A, T, C, and G, the four electrophoresis lanes; the base can be read in the order to be synthesized, thereby obtaining the DNA sequence to be tested. Thereafter, on the basis of “the Sanger sequencing method,” the automatic detection and fluorescence techniques, isotopically labeled with a fluorescent label in place of the four fluorophores, four bases were replaced and automatically detected by imaging techniques, no longer subjected to electrophoresis separately read sequences, greatly improving the speed and accuracy of DNA sequencing. Generation sequencing technology to ensure smooth implementation of Human Genome Project can be obtained secret of human health and disease at the molecular level. However, first-generation sequencing technology has considerable limitations, namely, low throughput, high cost, and long time. Further, since test DNA Sanger sequencing is applied to the support, and cloned in E. coli and other bacteria, therefore, it could not be cloned fragments of harmful bacteria, and, in some regions of the genome, such as the centromere and terminal area around the particles is difficult to be cloned, leading to deletion of part of gene sequence. Additionally, the method of analysis is limited ability alleles, SNP detection is very difficult, which facilitates the birth of a new generation of genome sequencing technology.
\n
\n
\n
3.4 Methods detecting SNP
\n
Some technologies such as mass spectrometry, electrophoresis, and microarray hybridization are much more dependent on PCR multiplexing than others to reach their throughput potential [23, 24, 25]. However, the efficiency of these technologies was constricted by cross impact in the PCR of primers and DNA samples in one reaction tube. It is evidenced that less than 20 primer pairs could be amplified together that could not support large numbers of SNP measurement. And when multiple SNPs are amplified together in a reaction chamber, only 50–70% SNPs can be amplified successfully, and the amount of products varies greatly from 10 to 1000 folds, what leads to the cooling rate for samples which decreases dramatically—some SNPs that are scored for sample A may not be scored for sample B or C [26, 27, 28]. Single-base extension based on multiplexing PCR like mass spectrometry assay is expensive and requires well-trained personnel for performing the various steps of the analysis with a lengthy protocol. For most homogenous detection formats like fluorescence resonance energy transfer and fluorescent polarization, because their testing equipment have very limited capacity of multiplex recently, some technologies such as TaqMan 5′-nuclease assay, DNA hybridization, could not rely on multiplexing PCR to increase their throughput. Genotyping technologies have become a significant bottleneck for these applications despite rapid progress in the field. Exploring fast, accurate, high-throughput SNP genotyping, new technology is particularly urgent. Microfluidics chip is composed of microdroplets, microchannels, and microchambers [29, 30, 31, 32, 33, 34]. Each microchamber could be used to amplify only one primer pair. A number of microchambers can be designed to meet the requirement. The physical isolation of different primer pairs is a simple and effective strategy to avoid the drawbacks of conventional multiplex PCR. In order to overcome the SNP genotyping error @caused by different amplification efficiency, chambers and channels with special structures have also been designed for primer storage and allocation of reaction mixtures. The characteristics of smaller reaction volumes, high-throughput capacity, ease of integration, and portability compared to traditional PCR endow microfluidics (microdroplets, microchannels, and microchambers) with the potential to be a powerful technology to meet SNP genotyping demands. For example, 116-plex PCR designed by Li et al. can be accomplished using a hydrophobically patterned microarray [35]. However, it requires precise operations, and the amplification is performed in an open environment, which risks contamination. Microdroplets (e.g., digital PCR) are also a potential technology for multiplex PCR, but barcoding technology is essential but challenging for multiplex digital PCR. The OpenArray® platform from Applied Biosystems, which was the commercial products for multiplex PCR, is rather expensive and sophisticated, and costly instruments are also required. In brief, these methods for multiplex PCR are effective, but complications in chip processing and/or their high associated costs hinder their wide use.
\n
\n
\n
3.5 Measurement malnutrition-related SNPs and their genotypes
\n
SNP genotype measurement has been widely studied in the risk screen and diagnosis for genetic diseases and chronic diseases, but few studies for nutrient deficiency risk determination. It is agreed that the body micronutrient diagnosis or evaluation is the bottleneck technology barrier since there are numbers of indexes for varieties of micronutrients; in addition, there seems even difficulty to know the genetic information related with micronutrient deficiency. Nutritional genotype studies have facilitated to use MD-SNPs (malnutrition-related SNPs) as risk biomarkers, i.e., vitamins A, D, E, and B12, folate, calcium, iron, zinc, and selenium.
\n
\n
3.5.1 Microfluidic chip designed for malnutrition-related SNPs
\n
Microfluidic chip as high-throughput technology could amplify large numbers of target DNA fragments at the same time in a chip, and the physical isolation of different primer pairs is a simple and effective strategy to avoid the drawbacks of conventional multiplex PCR. Xu et al. took this advantage to reduce the mutual interference and competition among different primers in one tube for multiple PCR [36]. They adopted a modified method with a blocking step, which had showed less contamination than that without blocking method. A study reported by Zhang et al. showed that MD-SNPs were extracted from published studies of GWAS, reviews, and meta-analysis, which epidemically related with micronutrient deficiency, and a method was established by modified microfluidic chip for MD-SNPs measurement by Xu et al. The study would explore possibility to describe MD potential risk from genetic point of view for an individual.
\n
\n
\n
3.5.2 Primer design of nutrition-related SNPs
\n
Primer mix contained three primers, common reverse primer, tailed allele primer 1 and tailed allele primer 2, in a ratio of 5:2:2. Primer mix (0.14 μl, 2 μM for each forward and reverse primers) was preloaded in a reaction chamber. Master mix containing FRET cassette plus enzymes with high-fidelity activity in an optimized buffer solution was stored at −20°C in the refrigerator, kept cool with ice when taken out from refrigerator, and vortex shocked before use (Figure 1).
\n
Figure 1.
Steps and principle of allele-specific extension on primer arrays. (A), primer pairs mix containing two different, allele-specific, competing forward primers with unique tail sequences and one reverse primer. Master mix containing FRET cassette plus enzymes with high-fidelity activity in an optimized buffer solution. Test DNA with the SNP of interest. (B), in the first round of PCR, one of the allele-specific primers matches the target SNP and, with the common reverse primer, amplifies the target region; (C), in the second round of PCR, reverse primer binds, elongates, and makes a complement copy of allele-1 tail; (D), in the third round of PCR, FAM-labeled oligo binds to new complementary tail sequence and is no longer quenched; in further rounds of PCR, the levels of allele-specific tail increase. The fluorescent substance-labeled part of the FRET cassette is complementary to new tail sequences and binds, releasing the fluorescent substance from the quencher to generate a fluorescent signal.
\n
\n
\n
3.5.3 MD-SNP measurement process
\n
The material of the chip was polymethylmethacrylate (PMMA) and was fabricated by machining to final dimensions of 7.5 cm (length) × 2.5 cm (width) × 2 mm (thickness). There were 28 microchambers in a column and 4 parallel columns in a chip that supported for simultaneously testing of 112 SNPs in 3 genotypes of wild type, hybrid type, and mutant type. Each column consisted of a circular inlet and outlet, a “sine-shaped” sample infusing channel, 28 linking channels, and 28 circular reaction chambers. A modified method has been established to prepare the microfluidic chip. Prior to use, the chip was washed with ethanol and ultrapure water and dried with nitrogen gas. Then, the primer pairs were pipetted into different reaction chambers and allowed to dry at room temperature for 30 min. A piece of single-sided, PCR-compatible adhesive tape was used to seal the top side of the chip at 175°C for 1 min. After sealing, the primer-loaded chip was stored at 4°C before use. An aqueous PCR mixture containing PCR master mix and DNA template was loaded into infusing channels by pipetting from the inlets. Outlets and inlets on the bottom side were sealed with adhesive tape to achieve a fully hermetic system. Then, the chip was centrifuged at 4000 rpm for 1 min so that the PCR mixture was uniformly transferred into reaction chambers and thoroughly mixed with the preloaded primers mix, and the final reaction volume was 0.8 μl. Each linking channel was blocked at 150°C for 1 min. Then, the chip was placed on a MasterCycler Nexus flat and pressed with a PMMA block to ensure tight contact and avoid distortion of the chip under high temperature (Figure 2).
\n
Figure 2.
Workflow protocol of the chip.
\n
The temperature program of PCR in the chip was set as follows (Figure 2): hot-start activation at 94°C for 15 min, followed by 10 touchdown cycles (94°C for 20 s; touchdown 61–55°C, dropping 0.6°C per cycle), and then followed by 26 cycles of amplification (94°C 20 s; 55°C 60 s). After thermal cycling for 100 min, the amplified products were detected by LuxScan-10 K/A scanner at 40°C or below for 15 min. The fluorescence intensity values (FIVs) were used to identify three distinct genotypes of wild type, hybrid type, and mutant type.
\n
\n
\n
3.5.4 Cross-contamination test
\n
Odd-numbered chambers in a column of a chip were preloaded primer mix, while even-numbered chambers were not. In addition, gel electrophoresis was observed with solutions from the corresponding reaction chambers. For specificity of primer mix and accuracy, each primer pair preloaded chamber loaded different template DNAs in a concentration of 10 ng/μl with master mix pipetted into infusing channels. The results were compared with the expected results obtained by next-generation sequencing (NGS). For the selection of appropriate DNA reaction concentration, 52 difficult DNA templates were diluted to 1 ng/μl, 5 ng/μl, 10 ng/μl, and 15 ng/μl to test appropriate DNA reaction concentration, respectively. The repeatability of multiplexed SNPs is observed with four repeats of 52 MD-SNPs in one DNA template. All these experiments were repeated six times. The established method was used to measure DNA templates from six different samples to evaluate the possible MD risk of vitamin A, D, E, and B12, folate, calcium, iron, zinc, and selenium (Figure 3).
\n
Figure 3.
The cross-contamination testing of adjacent reaction chambers. Odd number and even number represented reaction chambers with and without preloaded primers, respectively. (A) is the fluorescence pseudo-color image; (B) is the corresponding gray scale image; (C) is the electrophoretogram of the amplicons in each reaction chamber which corresponded to the product in the chamber of (A) or (B) above. The lane marked with M represents the DNA marker. The molecular weights of the bands from the top to bottom were 1200, 900, 700, 500, 300, and 100 bps.
\n
\n
\n
3.5.5 Multiplex PCR in MD-SNP measurement
\n
Multiplex PCR is a promising method for multiple nucleic acid analysis and detection. Several primers involved in a single tube behaves as multiplex PCR, in which one allele sequence is often preferentially amplified, resulting in the scarcity of other allele sequences, so it is very tedious to establish an optimized multiplex PCR protocol. Most chip-based multiplexed genotyping platforms are suitable for large-scale studies requiring genotypic data with thousands of SNPs. Although multiplexing offers greater throughput with less reagent consumption, it restricts the use which require low to medium marker density, for example, Illumina company requires a minimum number of plates ordered in order to develop specific assays, and this requirement was much higher than individual needs. So Xu et al. developed an innovative microfluidic chip to be the most convenient and cost-effective option for genotyping various individuals, which physically isolates the primer pairs in a reaction chamber. Fifty-two SNPs demonstrated the effectiveness of our strategy by multiplex PCRs and further illustrated its clinical applicability with blood and saliva samples. As a qualitative method, primer pairs of MD-SNPs designed in this study could be successfully amplified in the given conditions and replicated target DNA fragments with additional florescence carriers of FAM and HEX. Three genotypes of mutant type, hybrid type, and wild type could be identified specifically and accurately by the measurement. The sample chambers showed averagely at least two times higher FIV than that of NTCs. 5 ng/μl or higher suggested the suitable DNA concentration for the selected 52 MD-SNPs, although the optimal concentration for each primer pair may be different. The method showed high repeatability in both inner chips and among chips. The results of 52 MD-SNPs determined by MD-chips and NGS were completely the same, suggesting a high accuracy of the method.
\n
There are several advantages of the microfluidic chip multiplex PCR: (1) the generality of the primer design principle which was adopted by this microfluidic chip assays. The principle is developed for common use in all genotyping assays to stringently target the two alleles with standard PCR conditions and similar amplification efficiencies and significantly decreases the cost in PCR reagents and labors. (2) It is more specific. The microfluidic chip genotyping results were completely coincident with next-generation sequencing results. (3) It is easier. All the primer pairs are physically isolated; deleting or adding one or a few primer pairs from a multiplex PCR primer panel will not alter the performance of the other primer pairs with standard PCR conditions; almost no additional optimization is required. So, the universal protocol is viable for developing diverse multiplex PCR applications. (4) Its throughput is flexible. The selection of a technique has to weigh factors of instrument, throughput, technical support, and cost. Because of its unprecedented specificity, simplicity, and flexibility of throughout, the chip could serve as a powerful tool in clinical individual nutriment deficiency risk diagnostics for multiplexed detection of nutriments. The results of the analysis performed using the chip may provide early and crucial information for physicians to prevent nutriment deficiency risk and conduct appropriate nutritional intervention.
\n
\n
\n
\n
\n
4. Malnutrition risk evaluated by personal SNPs
\n
\n
4.1 Expression of malnutrition risk with MD-SNPs
\n
The MD-SNP chip method was used to measure MD risk of six students which showed distinguished differences of genetic potentials. The MD risk of six students was shown in a colored image in a pattern of SNP genotypes in three colors. The wild type was in red, hybrid type in orange, and mutant type in green. The risk of individuals in a micronutrient deficiency could be identified by the differences of red color areas. The genotype for each SNP of micronutrients in a person could be presented with the image (Figure 4).
\n
Figure 4.
The color grade of nine MD-SNPs in six measured individual samples. S, sample.
\n
\n
\n
4.2 Guiding on nutrient intake with MD-SNP
\n
The combination of this method with present laboratory measurement might comprehensively explain individual MD risk in both genetic and diet environmental conditions, thus facilitating with precise nutrition intervention. For example, MTHFR-C677T polymorphism has been extensively studied, and the association between the TT genotype and low folate status is well documented. Individuals with the TT genotype seem to be particularly susceptible to insufficient status of several B vitamins, and they may need to consume more folate to maintain serum folate levels similar to those found in individuals with the CC/CT genotypes. A study by Crider et al. reported that daily 0.8 mg folic acid may be necessary to lower homocysteine concentration for Chinese hypertensive subjects with CT or TT genotype, which have important clinical and public health implications [37]. The Centers for Disease Control and Prevention in the United States showed in 1992 that women who have previously suffered a NTD-affected pregnancy are advised to take 4 mg of folic acid daily before conception and during the first months of pregnancy [38]. Then we could calculate the required amount of an individual micronutrients according to SNPs.
\n
In the real world, the body’s nutritional status is regulated by multiple genes and nutrients. For example, homocysteine (Hcy) is a precursor of methionine and cysteine. Methionine converts into S-adenosyl methionine, which acts as a universal methyl donor. These multistep reactions involve various enzymes and cofactors in the form of essential micronutrients, which include vitamin B complex family (B2, B6, B9, and B12). Therefore, in measuring tHcy, folic acid and vitamin B12, vis-a`-vis the genotypes of the Hcy-pathway genes, Zhang et al. evaluated contribution of the individual variables (SNPs of Hcy-pathway genes) in the development of the phenotype (Hcy level) and get an estimate of the relative contribution of the environment (vitamins) in modulating the effect of genotypes in this region. Hyperhomocysteinemia is a result of either reduced enzymatic activity in the enzymes that participate in homocysteine metabolism and/or a reduction in the concentrations of plasma B vitamins, particularly, folate. Dietary intake of folate or folic acid supplementation can lower the concentration of p-tHcy. The establishment of gender and age as covariates is associated with SNP HCY polygenic risk score model (PRS), PRS = −0.024802rs2274976 + 0.025011rs1801131 + 0.205567rs1801133–0.025646rs1805087–0.025047rs2118981 + 0.340703rs492602–0.448651rs602662 + 0.067954sex + 0.060073 age+1.553543; sex, female 0, male 1; age, Year (R2 = 0.4084, p < 2.2e-16).
\n
The incidence of early detection, prevention, and intervention was the fundamental goal of promoting human health; predicting the probability of an individual assessment of the risk of susceptibility to disease was the core clinical decision-making, especially for the detection and prevention of common diseases. The current clinical data for common adult disease risk often relied on basic human indicators, such as age, gender and ethnicity, lifestyle, and basic health indicators, such as body mass index, smoking status, alcohol use, and physical activity habits; suffering disease relevant to the biomarkers like blood pressure level and biochemical indexes; analysis of environmental exposure, such as air pollution, heavy metals, and other environmental toxins; and family history. Many recent studies have begun to demonstrate the utility of gene association analysis and access to individual genetic susceptibility to a disease useful for the guidance of information from the probability of large population data. In theory, gene mapping could be considered a useful part of a healthy management.
\n
\n
\n\n',keywords:"SNP, nutrients, malnutrition",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/72624.pdf",chapterXML:"https://mts.intechopen.com/source/xml/72624.xml",downloadPdfUrl:"/chapter/pdf-download/72624",previewPdfUrl:"/chapter/pdf-preview/72624",totalDownloads:128,totalViews:0,totalCrossrefCites:0,dateSubmitted:"October 20th 2019",dateReviewed:"April 13th 2020",datePrePublished:"June 26th 2020",datePublished:"November 11th 2020",dateFinished:null,readingETA:"0",abstract:"Malnutrition is a result of complicated reasons from diet and food behavior and also related to genetic background which has been revealed by studies in recent decades. Traditionally, nutrition status are measured and expressed with indexes of anthropometric, diet survey, clinical symptom, biochemistry, behavior, etc. These measurement has been used in national nutrition monitoring, clinic nutrition therapy, mother and children nutrition care, nutrition intervention projects, and scientific studies. However, genetic and epigenetic information on nutrition explain malnutrition in a genetic view that would supply additional new theory and methodology for the growing requirement in terms of personalized and precise nutrition. In this chapter, an introduction on the detection of nutrient-related SNP to reveal individual malnutrition risk is discussed.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/72624",risUrl:"/chapter/ris/72624",signatures:"Junsheng Huo and Chunhong Zhang",book:{id:"8030",title:"Malnutrition",subtitle:null,fullTitle:"Malnutrition",slug:"malnutrition",publishedDate:"November 11th 2020",bookSignature:"Muhammad Imran and Ali Imran",coverURL:"https://cdn.intechopen.com/books/images_new/8030.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"194146",title:"Dr.",name:"Muhammad",middleName:null,surname:"Imran",slug:"muhammad-imran",fullName:"Muhammad Imran"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"313851",title:"Prof.",name:"Junsheng",middleName:null,surname:"Huo",fullName:"Junsheng Huo",slug:"junsheng-huo",email:"huojs@ninh.chinacdc.cn",position:null,institution:null},{id:"313864",title:"Dr.",name:"Chunhong",middleName:null,surname:"Zhang",fullName:"Chunhong Zhang",slug:"chunhong-zhang",email:"956308151@qq.com",position:null,institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Malnutrition related to inheritance",level:"1"},{id:"sec_2_2",title:"2.1 Iron deficiency-related genes",level:"2"},{id:"sec_4",title:"3. Folic acid deficiency genes",level:"1"},{id:"sec_4_2",title:"3.1 Genes of other nutrients deficiency",level:"2"},{id:"sec_5_2",title:"3.2 Measurement of malnutrition-related SNPs",level:"2"},{id:"sec_6_2",title:"3.3 Gene sequencing",level:"2"},{id:"sec_7_2",title:"3.4 Methods detecting SNP",level:"2"},{id:"sec_8_2",title:"3.5 Measurement malnutrition-related SNPs and their genotypes",level:"2"},{id:"sec_8_3",title:"3.5.1 Microfluidic chip designed for malnutrition-related SNPs",level:"3"},{id:"sec_9_3",title:"3.5.2 Primer design of nutrition-related SNPs",level:"3"},{id:"sec_10_3",title:"3.5.3 MD-SNP measurement process",level:"3"},{id:"sec_11_3",title:"3.5.4 Cross-contamination test",level:"3"},{id:"sec_12_3",title:"3.5.5 Multiplex PCR in MD-SNP measurement",level:"3"},{id:"sec_15",title:"4. Malnutrition risk evaluated by personal SNPs",level:"1"},{id:"sec_15_2",title:"4.1 Expression of malnutrition risk with MD-SNPs",level:"2"},{id:"sec_16_2",title:"4.2 Guiding on nutrient intake with MD-SNP",level:"2"}],chapterReferences:[{id:"B1",body:'\nSoeters P, Bozzetti F, Cynober L, Forbes A, Shenkin A, Sobotka L. Defining malnutrition: A plea to rethink. Clinical Nutrition. 2016;S0261-5614(16):31272-31279. DOI: 10.1016/j.clnu.2016.09.032\n'},{id:"B2",body:'\nDraft of the Rome Declaration on Nutrition. https://www.who.int/nutrition/events/icn2_draft_RomeDeclaration_Nutrition_en.pdf\n\n'},{id:"B3",body:'\nInitiatives D. 2018 Global Nutrition Report: Shining a Light to Spur Action on Nutrition. Bristol, UK: Development Initiatives; 2018\n'},{id:"B4",body:'\nYang YX, Ge KY. Encyclopedia of Nutrition Science. Beijing: People’s medical publishing house; 2019\n'},{id:"B5",body:'\nHaugen AC, Schug TT, Collman G, Heinder JJ. Evolution of DOHaD: The impact of environmental health sciences. Journal of Developmental Origins of Health and Disease. 2015;6(2):55-64. DOI: 10.1017/s2040174414000580\n'},{id:"B6",body:'\nMcLaren Christine E, Stela ML, Garner Chad P, et al. Associations between single nucleotide polymorphisms in iron-related genes and iron status in multiethnic populations. PLoS One. 2012;7(6):e38339\n'},{id:"B7",body:'\nSmithells RW, Chinn ER. Meclozine and Fetal malformations: A prospective study. British Medical Journal. 1964;1(5377):217-218\n'},{id:"B8",body:'\nFrosst P, Blom HJ, Milos R, et al. A candidate genetic risk factor for vascular disease: A common mutation in methylenetetrahydrofolate reductase. Nature Genetics. 1995;10(1):111-113\n'},{id:"B9",body:'\nChunhong Z, Junsheng H, Jing S, et al. The association of maternal MTR and MTRR polymorphisms with neural tube defect of offspring: Meta-analysis. The Journal of Chinese Preventive Medicine. 2018;19:726-733 (In Chinese)\n'},{id:"B10",body:'\nChunhong Z, Junsheng H, Jing S, et al. Meta-analysis on relationship between the Chinese maternal MTHFR gene polymorphism (C677T) and neural tube defects in offspring. The Journal of Hygiene Research. 2018;47:312-317 (In Chinese)\n'},{id:"B11",body:'\nDaniel C, Kevin D, Noah S, et al. A cross-sectional study of dietary and genetic predictors of blood Folate levels in healthy young adults. Nutrients. 2017;9(9):994\n'},{id:"B12",body:'\nWilcken B. Geographical and ethnic variation of the 677C>T allele of 5,10 methylene tetrahydrofolate reductase (MTHFR): Findings from over 7000 newborns from 16 areas worldwide. Journal of Medical Genetics. 2003;40(8):619-625\n'},{id:"B13",body:'\nClifford AJ, Chen K, McWade L, et al. Gender and single nucleotide polymorphisms in MTHFR, BHMT, SPTLC1, CRBP2, CETP, and SCARB1 are significant predictors of plasma homocysteine normalized by RBC folate in healthy adults. The Journal of Nutrition. 2012;142:1764-1771\n'},{id:"B14",body:'\nJacobsen N. LNA-enhanced detection of single nucleotide polymorphisms in the apolipoprotein E. Nucleic Acids Research. 2002;30:100e-1100e\n'},{id:"B15",body:'\nMajor JM, Yu K, Chung CC, et al. Genome-wide association study identifies three common variants associated with serologic response to vitamin E supplementation in men. The Journal of Nutrition. 2012;142:866-871\n'},{id:"B16",body:'\nO’Seaghdha CM, Wu H, Yang Q , et al. Meta-analysis of genome-wide association studies identifies six new loci for serum calcium concentrations. PLoS Genetics. 2013;9:e1003796\n'},{id:"B17",body:'\nMcLaren CE, McLachlan S, Garner CP, et al. Associations between single nucleotide polymorphisms in iron-related genes and iron status in multiethnic populations. PLoS One. 2012;7:e38339\n'},{id:"B18",body:'\nFredriksen A, Meyer K, Ueland PM, et al. Large-scale population-based metabolic phenotyping of thirteen genetic polymorphisms related to one-carbon metabolism. Human Mutation. 2007;28:856-865\n'},{id:"B19",body:'\nLi WX, Dai SX, Zheng JJ, et al. Homocysteine metabolism gene polymorphisms (MTHFR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) jointly elevate the risk of folate deficiency. Nutrients. 2015;7:6670-6687\n'},{id:"B20",body:'\nLiang S, Zhou Y, Wang H, et al. The effect of multiple single nucleotide polymorphisms in the folic acid pathway genes on homocysteine metabolism. BioMed Research International. 2014;2014:560183\n'},{id:"B21",body:'\nTanaka T, Scheet P, Giusti B, et al. Genome-wide association study of vitamin B6, vitamin B12, folate, and homocysteine blood concentrations. American Journal of Human Genetics. 2009;84:477-482\n'},{id:"B22",body:'\nAhn J, Yu K, Stolzenberg-Solomon R, et al. Genome-wide association study of circulating vitamin D levels. Human Molecular Genetics. 2010;19:2739-2745\n'},{id:"B23",body:'\nSteluti J, Carvalho AM, Carioca AAF, et al. Genetic variants involved in one-carbon metabolism: Polymorphism frequencies and differences in homocysteine concentrations in the folic acid fortification era. Nutrients. 2017;9:539-550\n'},{id:"B24",body:'\nSexton TR, Henry RJ, McManus LJ, et al. Capture of assay template by multiplex PCR of long amplicons for genotyping SNPs and indels with MALDI-TOF mass spectrometry. Molecular Breeding. 2009;25:471-480\n'},{id:"B25",body:'\nTajadini M, Panjehpour M, Javanmard SH. Comparison of SYBR green and Taqman methods in quantitative real-time polymerase chain reaction analysis of four adenosine receptor subtypes. Advances in Biology Research. 2014;3:85\n'},{id:"B26",body:'\nFan JB, Oliphant A, Shen R, et al. Highly parallel SNP genotyping. Cold Spring Harbor Symposia on Quantitative Biology. 2003;68:69\n'},{id:"B27",body:'\nHindson BJ, Ness KD, Masquelier DA, et al. High-throughput droplet digital PCR system for absolute quantitation of DNA copy number. Analytical Chemistry. 2011;83:8604-8610\n'},{id:"B28",body:'\nMorrison T, Hurley J, Garcia J, et al. Nanoliter high throughput quantitative PCR. Nucleic Acids Research. 2006;34:e123\n'},{id:"B29",body:'\nShen F, Du W, Davydova EK, et al. Nanoliter multiplex PCR arrays on a slipChip. Analytical Chemistry. 2010;82:4606-4612\n'},{id:"B30",body:'\nChen X, Sullivan PF. Single nucleotide polymorphism genotyping: Biochemistry, protocol, cost and throughput. The Pharmacogenomics Journal. 2003;3:77-96\n'},{id:"B31",body:'\nSundberg SO, Wittwer CT, Chao G, et al. Spinning disk platform for microfluidic digital polymerase chain reaction. Analytical Chemistry. 2010;82:1546-1550\n'},{id:"B32",body:'\nTomi Pastinen MR, Lindroos K, Tainola P, et al. A system for specific, high-throughput genotyping by allele-specific primer extension on microarrays. Genome Research. 2000;10:1031-1042\n'},{id:"B33",body:'\nYan H, Zhu Y, Zhang Y, et al. Multiplex detection of bacteria on an integrated centrifugal disk using bead-beating lysis and loop-mediated amplification. Scientific Reports. 2017;7:1-12\n'},{id:"B34",body:'\nPalani K, Chaoyong James Y, Cronier SA, et al. High-throughput single copy DNA amplification and cell analysis in engineered Nanoliter droplets. Analytical Chemistry. 2008;80:3522-3529\n'},{id:"B35",body:'\nLi Y, Guo SJ, Shao N, Tu S, et al. A universal multiplex PCR strategy for 100-plex amplification using a hydrophobically patterned microarray. Lab on a Chip. 2011;11:3609-3618\n'},{id:"B36",body:'\nXu Y, Yan H, Zhang Y, et al. A fully sealed plastic chip for multiplex PCR and its application in bacteria identification. Lab on a Chip. 2015;15:2826-2834\n'},{id:"B37",body:'\nCrider KS, Zhu JH, Hao L, et al. MTHFR 677C->T genotype is associated with folate and homocysteine concentrations in a large, population-based, double-blind trial of folic acid supplementation. American Journal of Clinical Nutrition. 2011;93(6):1365-1372\n'},{id:"B38",body:'\nCDC (Centers for Disease Control and Prevention). Recommendations for the use of folic acid to reduce the number of cases of spina bifida and other neural tube defects. MMWR. Morbidity and Mortality Weekly Report. 1992;41(RR-14):001\n'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Junsheng Huo",address:"huojs@ninh.chinacdc.cn",affiliation:'
Institute of Nutrition and Health of China’s Center for Disease Control and Prevention, China
Institute of Nutrition and Health of China’s Center for Disease Control and Prevention, China
'}],corrections:null},book:{id:"8030",title:"Malnutrition",subtitle:null,fullTitle:"Malnutrition",slug:"malnutrition",publishedDate:"November 11th 2020",bookSignature:"Muhammad Imran and Ali Imran",coverURL:"https://cdn.intechopen.com/books/images_new/8030.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"194146",title:"Dr.",name:"Muhammad",middleName:null,surname:"Imran",slug:"muhammad-imran",fullName:"Muhammad Imran"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},profile:{item:{id:"129566",title:"Prof.",name:"Mazlin",middleName:null,surname:"Mokhtar",email:"mazlin@ukm.my",fullName:"Mazlin Mokhtar",slug:"mazlin-mokhtar",position:null,biography:null,institutionString:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",totalCites:0,totalChapterViews:"0",outsideEditionCount:0,totalAuthoredChapters:"1",totalEditedBooks:"0",personalWebsiteURL:null,twitterURL:null,linkedinURL:null,institution:{name:"National University of Malaysia",institutionURL:null,country:{name:"Malaysia"}}},booksEdited:[],chaptersAuthored:[{title:"Irrigation: Types, Sources and Problems in Malaysia",slug:"irrigation-types-sources-and-problems-in-malaysia",abstract:null,signatures:"M. E. Toriman and M. Mokhtar",authors:[{id:"79054",title:"Dr.",name:"Mohd Ekhwan",surname:"Toriman",fullName:"Mohd Ekhwan Toriman",slug:"mohd-ekhwan-toriman",email:"ikhwan@ukm.my"},{id:"129566",title:"Prof.",name:"Mazlin",surname:"Mokhtar",fullName:"Mazlin Mokhtar",slug:"mazlin-mokhtar",email:"mazlin@ukm.my"}],book:{title:"Irrigation Systems and Practices in Challenging Environments",slug:"irrigation-systems-and-practices-in-challenging-environments",productType:{id:"1",title:"Edited Volume"}}}],collaborators:[{id:"77140",title:"Prof.",name:"Zorica",surname:"Jovanovic",slug:"zorica-jovanovic",fullName:"Zorica Jovanovic",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"78156",title:"Dr.",name:"Saeideh",surname:"Maleki Farahani",slug:"saeideh-maleki-farahani",fullName:"Saeideh Maleki Farahani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Shahed University",institutionURL:null,country:{name:"Iran"}}},{id:"79271",title:"Ph.D.",name:"Bergson",surname:"Bezerra",slug:"bergson-bezerra",fullName:"Bergson Bezerra",position:"Researcher",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"80212",title:"Dr.",name:"Kamel",surname:"Ben Mbarek",slug:"kamel-ben-mbarek",fullName:"Kamel Ben Mbarek",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"80319",title:"Prof.",name:"Radmila",surname:"Stikic",slug:"radmila-stikic",fullName:"Radmila Stikic",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Belgrade",institutionURL:null,country:{name:"Serbia"}}},{id:"83537",title:"Dr.",name:"Ramesh",surname:"Thatikunta",slug:"ramesh-thatikunta",fullName:"Ramesh Thatikunta",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/83537/images/571_n.jpg",biography:"Dr. Ramesh Thatikunta has seventeen years of experience as a Plant Physiologist in Acharya N G Ranga Agricultural University, India. Graduated from the premier Indian Agricultural Research Institute and carried out post doctoral research work. Presented paper in ASA meeting in Denver. Published forty research papers and two lab manuals. Worked in projects on environment and pollution.",institutionString:null,institution:{name:"Acharya N. G. Ranga Agricultural University",institutionURL:null,country:{name:"India"}}},{id:"83625",title:"Dr.",name:"Ana",surname:"Quinones",slug:"ana-quinones",fullName:"Ana Quinones",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Instituto Valenciano de Investigaciones Agrarias",institutionURL:null,country:{name:"Spain"}}},{id:"83808",title:"Dr",name:"Arvind",surname:"Kumar",slug:"arvind-kumar",fullName:"Arvind Kumar",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"87392",title:"Dr.",name:"Rita",surname:"Linke",slug:"rita-linke",fullName:"Rita Linke",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"129155",title:"Dr.",name:"Mohammad Reza",surname:"Chaichi",slug:"mohammad-reza-chaichi",fullName:"Mohammad Reza Chaichi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null}]},generic:{page:{slug:"open-access-funding-funders-list",title:"List of Funders by Country",intro:"
If your research is financed through any of the below-mentioned funders, please consult their Open Access policies or grant ‘terms and conditions’ to explore ways to cover your publication costs (also accessible by clicking on the link in their title).
\n\n
IMPORTANT: You must be a member or grantee of the listed funders in order to apply for their Open Access publication funds. Do not attempt to contact the funders if this is not the case.
",metaTitle:"List of Funders by Country",metaDescription:"If your research is financed through any of the below-mentioned funders, please consult their Open Access policies or grant ‘terms and conditions’ to explore ways to cover your publication costs (also accessible by clicking on the link in their title).",metaKeywords:null,canonicalURL:"/page/open-access-funding-funders-list",contentRaw:'[{"type":"htmlEditorComponent","content":"
UK Research and Innovation (former Research Councils UK (RCUK) - including AHRC, BBSRC, ESRC, EPSRC, MRC, NERC, STFC.) Processing charges for books/book chapters can be covered through RCUK block grants which are allocated to most universities in the UK, which then handle the OA publication funding requests. It is at the discretion of the university whether it will approve the request.)
UK Research and Innovation (former Research Councils UK (RCUK) - including AHRC, BBSRC, ESRC, EPSRC, MRC, NERC, STFC.) Processing charges for books/book chapters can be covered through RCUK block grants which are allocated to most universities in the UK, which then handle the OA publication funding requests. It is at the discretion of the university whether it will approve the request.)
Wellcome Trust (Funding available only to Wellcome-funded researchers/grantees)
\n
\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{sort:"featured,name"},profiles:[{id:"6700",title:"Dr.",name:"Abbass A.",middleName:null,surname:"Hashim",slug:"abbass-a.-hashim",fullName:"Abbass A. Hashim",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/6700/images/1864_n.jpg",biography:"Currently I am carrying out research in several areas of interest, mainly covering work on chemical and bio-sensors, semiconductor thin film device fabrication and characterisation.\nAt the moment I have very strong interest in radiation environmental pollution and bacteriology treatment. The teams of researchers are working very hard to bring novel results in this field. I am also a member of the team in charge for the supervision of Ph.D. students in the fields of development of silicon based planar waveguide sensor devices, study of inelastic electron tunnelling in planar tunnelling nanostructures for sensing applications and development of organotellurium(IV) compounds for semiconductor applications. I am a specialist in data analysis techniques and nanosurface structure. I have served as the editor for many books, been a member of the editorial board in science journals, have published many papers and hold many patents.",institutionString:null,institution:{name:"Sheffield Hallam University",country:{name:"United Kingdom"}}},{id:"54525",title:"Prof.",name:"Abdul Latif",middleName:null,surname:"Ahmad",slug:"abdul-latif-ahmad",fullName:"Abdul Latif Ahmad",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"20567",title:"Prof.",name:"Ado",middleName:null,surname:"Jorio",slug:"ado-jorio",fullName:"Ado Jorio",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidade Federal de Minas Gerais",country:{name:"Brazil"}}},{id:"47940",title:"Dr.",name:"Alberto",middleName:null,surname:"Mantovani",slug:"alberto-mantovani",fullName:"Alberto Mantovani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"12392",title:"Mr.",name:"Alex",middleName:null,surname:"Lazinica",slug:"alex-lazinica",fullName:"Alex Lazinica",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/12392/images/7282_n.png",biography:"Alex Lazinica is the founder and CEO of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his PhD studies in Robotics at the Vienna University of Technology. Here he worked as a robotic researcher with the university's Intelligent Manufacturing Systems Group as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and most importantly he co-founded and built the International Journal of Advanced Robotic Systems- world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career, since it was a pathway to founding IntechOpen - Open Access publisher focused on addressing academic researchers needs. Alex is a personification of IntechOpen key values being trusted, open and entrepreneurial. Today his focus is on defining the growth and development strategy for the company.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"19816",title:"Prof.",name:"Alexander",middleName:null,surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/19816/images/1607_n.jpg",biography:"Alexander I. Kokorin: born: 1947, Moscow; DSc., PhD; Principal Research Fellow (Research Professor) of Department of Kinetics and Catalysis, N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow.\r\nArea of research interests: physical chemistry of complex-organized molecular and nanosized systems, including polymer-metal complexes; the surface of doped oxide semiconductors. He is an expert in structural, absorptive, catalytic and photocatalytic properties, in structural organization and dynamic features of ionic liquids, in magnetic interactions between paramagnetic centers. The author or co-author of 3 books, over 200 articles and reviews in scientific journals and books. He is an actual member of the International EPR/ESR Society, European Society on Quantum Solar Energy Conversion, Moscow House of Scientists, of the Board of Moscow Physical Society.",institutionString:null,institution:{name:"Semenov Institute of Chemical Physics",country:{name:"Russia"}}},{id:"62389",title:"PhD.",name:"Ali Demir",middleName:null,surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62389/images/3413_n.jpg",biography:"Dr. Ali Demir Sezer has a Ph.D. from Pharmaceutical Biotechnology at the Faculty of Pharmacy, University of Marmara (Turkey). He is the member of many Pharmaceutical Associations and acts as a reviewer of scientific journals and European projects under different research areas such as: drug delivery systems, nanotechnology and pharmaceutical biotechnology. Dr. Sezer is the author of many scientific publications in peer-reviewed journals and poster communications. Focus of his research activity is drug delivery, physico-chemical characterization and biological evaluation of biopolymers micro and nanoparticles as modified drug delivery system, and colloidal drug carriers (liposomes, nanoparticles etc.).",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"61051",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"100762",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"St David's Medical Center",country:{name:"United States of America"}}},{id:"107416",title:"Dr.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Texas Cardiac Arrhythmia",country:{name:"United States of America"}}},{id:"64434",title:"Dr.",name:"Angkoon",middleName:null,surname:"Phinyomark",slug:"angkoon-phinyomark",fullName:"Angkoon Phinyomark",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/64434/images/2619_n.jpg",biography:"My name is Angkoon Phinyomark. I received a B.Eng. degree in Computer Engineering with First Class Honors in 2008 from Prince of Songkla University, Songkhla, Thailand, where I received a Ph.D. degree in Electrical Engineering. My research interests are primarily in the area of biomedical signal processing and classification notably EMG (electromyography signal), EOG (electrooculography signal), and EEG (electroencephalography signal), image analysis notably breast cancer analysis and optical coherence tomography, and rehabilitation engineering. I became a student member of IEEE in 2008. During October 2011-March 2012, I had worked at School of Computer Science and Electronic Engineering, University of Essex, Colchester, Essex, United Kingdom. In addition, during a B.Eng. I had been a visiting research student at Faculty of Computer Science, University of Murcia, Murcia, Spain for three months.\n\nI have published over 40 papers during 5 years in refereed journals, books, and conference proceedings in the areas of electro-physiological signals processing and classification, notably EMG and EOG signals, fractal analysis, wavelet analysis, texture analysis, feature extraction and machine learning algorithms, and assistive and rehabilitative devices. I have several computer programming language certificates, i.e. Sun Certified Programmer for the Java 2 Platform 1.4 (SCJP), Microsoft Certified Professional Developer, Web Developer (MCPD), Microsoft Certified Technology Specialist, .NET Framework 2.0 Web (MCTS). I am a Reviewer for several refereed journals and international conferences, such as IEEE Transactions on Biomedical Engineering, IEEE Transactions on Industrial Electronics, Optic Letters, Measurement Science Review, and also a member of the International Advisory Committee for 2012 IEEE Business Engineering and Industrial Applications and 2012 IEEE Symposium on Business, Engineering and Industrial Applications.",institutionString:null,institution:{name:"Joseph Fourier University",country:{name:"France"}}},{id:"55578",title:"Dr.",name:"Antonio",middleName:null,surname:"Jurado-Navas",slug:"antonio-jurado-navas",fullName:"Antonio Jurado-Navas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/55578/images/4574_n.png",biography:"Antonio Jurado-Navas received the M.S. degree (2002) and the Ph.D. degree (2009) in Telecommunication Engineering, both from the University of Málaga (Spain). He first worked as a consultant at Vodafone-Spain. From 2004 to 2011, he was a Research Assistant with the Communications Engineering Department at the University of Málaga. In 2011, he became an Assistant Professor in the same department. From 2012 to 2015, he was with Ericsson Spain, where he was working on geo-location\ntools for third generation mobile networks. Since 2015, he is a Marie-Curie fellow at the Denmark Technical University. His current research interests include the areas of mobile communication systems and channel modeling in addition to atmospheric optical communications, adaptive optics and statistics",institutionString:null,institution:{name:"University of Malaga",country:{name:"Spain"}}}],filtersByRegion:[{group:"region",caption:"North America",value:1,count:5681},{group:"region",caption:"Middle and South America",value:2,count:5161},{group:"region",caption:"Africa",value:3,count:1683},{group:"region",caption:"Asia",value:4,count:10200},{group:"region",caption:"Australia and Oceania",value:5,count:886},{group:"region",caption:"Europe",value:6,count:15610}],offset:12,limit:12,total:117095},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{sort:"dateEndThirdStepPublish",topicId:"16"},books:[{type:"book",id:"10231",title:"Proton Therapy",subtitle:null,isOpenForSubmission:!0,hash:"f4a9009287953c8d1d89f0fa9b7597b0",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10231.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10331",title:"Salmonella - a Challenge From Farm to Fork",subtitle:null,isOpenForSubmission:!0,hash:"131535f5d2ebf6c7cfd85fd229bbfd0e",slug:null,bookSignature:"Dr. Alexandre Lamas, Ms. Patricia Regal and Dr. Carlos Franco",coverURL:"https://cdn.intechopen.com/books/images_new/10331.jpg",editedByType:null,editors:[{id:"194841",title:"Dr.",name:"Alexandre",surname:"Lamas",slug:"alexandre-lamas",fullName:"Alexandre Lamas"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10348",title:"Addictions - Diagnosis and Treatment",subtitle:null,isOpenForSubmission:!0,hash:"4b66187e9866019abbb18183e4364d2b",slug:null,bookSignature:"Dr. William Meil and Dr. John Mills",coverURL:"https://cdn.intechopen.com/books/images_new/10348.jpg",editedByType:null,editors:[{id:"87876",title:"Dr.",name:"William",surname:"Meil",slug:"william-meil",fullName:"William Meil"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10721",title:"Preeclampsia",subtitle:null,isOpenForSubmission:!0,hash:"d23fca4321fbc65c3e5c3e0d377c6e1f",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10721.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10729",title:"Sepsis",subtitle:null,isOpenForSubmission:!0,hash:"3981e82a4ab305272c07784a8f7298fb",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10729.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10708",title:"Regional Anesthesia",subtitle:null,isOpenForSubmission:!0,hash:"b481b3c45dfcce8c4f048ce08f520763",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10708.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10717",title:"Gestational Diabetes",subtitle:null,isOpenForSubmission:!0,hash:"9e38724c0e4f2bd852444e9b6f0facc8",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10717.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10725",title:"Paranasal Sinuses Anatomy and Conditions",subtitle:null,isOpenForSubmission:!0,hash:"7373bad684eb0c956ad2725227cd7227",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10725.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10703",title:"Cardiovascular Risk Factors",subtitle:null,isOpenForSubmission:!0,hash:"74951b49bbb62ec0de58ef39b777256b",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10703.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10714",title:"Decompression",subtitle:null,isOpenForSubmission:!0,hash:"bc40028a7727e796398dccca1b24e866",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10714.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10722",title:"Pelvic Floor Disorders",subtitle:null,isOpenForSubmission:!0,hash:"aa5c089f92b3aad8316c96cbb5ba106c",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10722.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10730",title:"Extracorporeal Membrane Oxygenation",subtitle:null,isOpenForSubmission:!0,hash:"2ac3ed12d9db14ee4bc66d7808c82295",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10730.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:9},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:18},{group:"topic",caption:"Business, Management and Economics",value:7,count:2},{group:"topic",caption:"Chemistry",value:8,count:7},{group:"topic",caption:"Computer and Information Science",value:9,count:10},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:5},{group:"topic",caption:"Engineering",value:11,count:14},{group:"topic",caption:"Environmental Sciences",value:12,count:2},{group:"topic",caption:"Immunology and Microbiology",value:13,count:5},{group:"topic",caption:"Materials Science",value:14,count:4},{group:"topic",caption:"Mathematics",value:15,count:1},{group:"topic",caption:"Medicine",value:16,count:62},{group:"topic",caption:"Nanotechnology and Nanomaterials",value:17,count:1},{group:"topic",caption:"Neuroscience",value:18,count:1},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:6},{group:"topic",caption:"Physics",value:20,count:2},{group:"topic",caption:"Psychology",value:21,count:3},{group:"topic",caption:"Robotics",value:22,count:1},{group:"topic",caption:"Social Sciences",value:23,count:3},{group:"topic",caption:"Technology",value:24,count:1},{group:"topic",caption:"Veterinary Medicine and Science",value:25,count:2}],offset:12,limit:12,total:107},popularBooks:{featuredBooks:[{type:"book",id:"9208",title:"Welding",subtitle:"Modern Topics",isOpenForSubmission:!1,hash:"7d6be076ccf3a3f8bd2ca52d86d4506b",slug:"welding-modern-topics",bookSignature:"Sadek Crisóstomo Absi Alfaro, Wojciech Borek and Błażej Tomiczek",coverURL:"https://cdn.intechopen.com/books/images_new/9208.jpg",editors:[{id:"65292",title:"Prof.",name:"Sadek Crisostomo Absi",middleName:"C. Absi",surname:"Alfaro",slug:"sadek-crisostomo-absi-alfaro",fullName:"Sadek Crisostomo Absi Alfaro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9139",title:"Topics in Primary Care Medicine",subtitle:null,isOpenForSubmission:!1,hash:"ea774a4d4c1179da92a782e0ae9cde92",slug:"topics-in-primary-care-medicine",bookSignature:"Thomas F. Heston",coverURL:"https://cdn.intechopen.com/books/images_new/9139.jpg",editors:[{id:"217926",title:"Dr.",name:"Thomas F.",middleName:null,surname:"Heston",slug:"thomas-f.-heston",fullName:"Thomas F. Heston"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8697",title:"Virtual Reality and Its Application in Education",subtitle:null,isOpenForSubmission:!1,hash:"ee01b5e387ba0062c6b0d1e9227bda05",slug:"virtual-reality-and-its-application-in-education",bookSignature:"Dragan Cvetković",coverURL:"https://cdn.intechopen.com/books/images_new/8697.jpg",editors:[{id:"101330",title:"Dr.",name:"Dragan",middleName:"Mladen",surname:"Cvetković",slug:"dragan-cvetkovic",fullName:"Dragan Cvetković"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9785",title:"Endometriosis",subtitle:null,isOpenForSubmission:!1,hash:"f457ca61f29cf7e8bc191732c50bb0ce",slug:"endometriosis",bookSignature:"Courtney Marsh",coverURL:"https://cdn.intechopen.com/books/images_new/9785.jpg",editors:[{id:"255491",title:"Dr.",name:"Courtney",middleName:null,surname:"Marsh",slug:"courtney-marsh",fullName:"Courtney Marsh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9343",title:"Trace Metals in the Environment",subtitle:"New Approaches and Recent Advances",isOpenForSubmission:!1,hash:"ae07e345bc2ce1ebbda9f70c5cd12141",slug:"trace-metals-in-the-environment-new-approaches-and-recent-advances",bookSignature:"Mario Alfonso Murillo-Tovar, Hugo Saldarriaga-Noreña and Agnieszka Saeid",coverURL:"https://cdn.intechopen.com/books/images_new/9343.jpg",editors:[{id:"255959",title:"Dr.",name:"Mario Alfonso",middleName:null,surname:"Murillo-Tovar",slug:"mario-alfonso-murillo-tovar",fullName:"Mario Alfonso Murillo-Tovar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7831",title:"Sustainability in Urban Planning and Design",subtitle:null,isOpenForSubmission:!1,hash:"c924420492c8c2c9751e178d025f4066",slug:"sustainability-in-urban-planning-and-design",bookSignature:"Amjad Almusaed, Asaad Almssad and Linh Truong - Hong",coverURL:"https://cdn.intechopen.com/books/images_new/7831.jpg",editors:[{id:"110471",title:"Dr.",name:"Amjad",middleName:"Zaki",surname:"Almusaed",slug:"amjad-almusaed",fullName:"Amjad Almusaed"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8468",title:"Sheep Farming",subtitle:"An Approach to Feed, Growth and Sanity",isOpenForSubmission:!1,hash:"838f08594850bc04aa14ec873ed1b96f",slug:"sheep-farming-an-approach-to-feed-growth-and-sanity",bookSignature:"António Monteiro",coverURL:"https://cdn.intechopen.com/books/images_new/8468.jpg",editors:[{id:"190314",title:"Prof.",name:"António",middleName:"Cardoso",surname:"Monteiro",slug:"antonio-monteiro",fullName:"António Monteiro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8816",title:"Financial Crises",subtitle:"A Selection of Readings",isOpenForSubmission:!1,hash:"6f2f49fb903656e4e54280c79fabd10c",slug:"financial-crises-a-selection-of-readings",bookSignature:"Stelios Markoulis",coverURL:"https://cdn.intechopen.com/books/images_new/8816.jpg",editors:[{id:"237863",title:"Dr.",name:"Stelios",middleName:null,surname:"Markoulis",slug:"stelios-markoulis",fullName:"Stelios Markoulis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9376",title:"Contemporary Developments and Perspectives in International Health Security",subtitle:"Volume 1",isOpenForSubmission:!1,hash:"b9a00b84cd04aae458fb1d6c65795601",slug:"contemporary-developments-and-perspectives-in-international-health-security-volume-1",bookSignature:"Stanislaw P. Stawicki, Michael S. Firstenberg, Sagar C. Galwankar, Ricardo Izurieta and Thomas Papadimos",coverURL:"https://cdn.intechopen.com/books/images_new/9376.jpg",editors:[{id:"181694",title:"Dr.",name:"Stanislaw P.",middleName:null,surname:"Stawicki",slug:"stanislaw-p.-stawicki",fullName:"Stanislaw P. Stawicki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7769",title:"Medical Isotopes",subtitle:null,isOpenForSubmission:!1,hash:"f8d3c5a6c9a42398e56b4e82264753f7",slug:"medical-isotopes",bookSignature:"Syed Ali Raza Naqvi and Muhammad Babar Imrani",coverURL:"https://cdn.intechopen.com/books/images_new/7769.jpg",editors:[{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9279",title:"Concepts, Applications and Emerging Opportunities in Industrial Engineering",subtitle:null,isOpenForSubmission:!1,hash:"9bfa87f9b627a5468b7c1e30b0eea07a",slug:"concepts-applications-and-emerging-opportunities-in-industrial-engineering",bookSignature:"Gary Moynihan",coverURL:"https://cdn.intechopen.com/books/images_new/9279.jpg",editors:[{id:"16974",title:"Dr.",name:"Gary",middleName:null,surname:"Moynihan",slug:"gary-moynihan",fullName:"Gary Moynihan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7807",title:"A Closer Look at Organizational Culture in Action",subtitle:null,isOpenForSubmission:!1,hash:"05c608b9271cc2bc711f4b28748b247b",slug:"a-closer-look-at-organizational-culture-in-action",bookSignature:"Süleyman Davut Göker",coverURL:"https://cdn.intechopen.com/books/images_new/7807.jpg",editors:[{id:"190035",title:"Associate Prof.",name:"Süleyman Davut",middleName:null,surname:"Göker",slug:"suleyman-davut-goker",fullName:"Süleyman Davut Göker"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:12,limit:12,total:5126},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"9208",title:"Welding",subtitle:"Modern Topics",isOpenForSubmission:!1,hash:"7d6be076ccf3a3f8bd2ca52d86d4506b",slug:"welding-modern-topics",bookSignature:"Sadek Crisóstomo Absi Alfaro, Wojciech Borek and Błażej Tomiczek",coverURL:"https://cdn.intechopen.com/books/images_new/9208.jpg",editors:[{id:"65292",title:"Prof.",name:"Sadek Crisostomo Absi",middleName:"C. Absi",surname:"Alfaro",slug:"sadek-crisostomo-absi-alfaro",fullName:"Sadek Crisostomo Absi Alfaro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9139",title:"Topics in Primary Care Medicine",subtitle:null,isOpenForSubmission:!1,hash:"ea774a4d4c1179da92a782e0ae9cde92",slug:"topics-in-primary-care-medicine",bookSignature:"Thomas F. Heston",coverURL:"https://cdn.intechopen.com/books/images_new/9139.jpg",editors:[{id:"217926",title:"Dr.",name:"Thomas F.",middleName:null,surname:"Heston",slug:"thomas-f.-heston",fullName:"Thomas F. Heston"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8697",title:"Virtual Reality and Its Application in Education",subtitle:null,isOpenForSubmission:!1,hash:"ee01b5e387ba0062c6b0d1e9227bda05",slug:"virtual-reality-and-its-application-in-education",bookSignature:"Dragan Cvetković",coverURL:"https://cdn.intechopen.com/books/images_new/8697.jpg",editors:[{id:"101330",title:"Dr.",name:"Dragan",middleName:"Mladen",surname:"Cvetković",slug:"dragan-cvetkovic",fullName:"Dragan Cvetković"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9785",title:"Endometriosis",subtitle:null,isOpenForSubmission:!1,hash:"f457ca61f29cf7e8bc191732c50bb0ce",slug:"endometriosis",bookSignature:"Courtney Marsh",coverURL:"https://cdn.intechopen.com/books/images_new/9785.jpg",editors:[{id:"255491",title:"Dr.",name:"Courtney",middleName:null,surname:"Marsh",slug:"courtney-marsh",fullName:"Courtney Marsh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9343",title:"Trace Metals in the Environment",subtitle:"New Approaches and Recent Advances",isOpenForSubmission:!1,hash:"ae07e345bc2ce1ebbda9f70c5cd12141",slug:"trace-metals-in-the-environment-new-approaches-and-recent-advances",bookSignature:"Mario Alfonso Murillo-Tovar, Hugo Saldarriaga-Noreña and Agnieszka Saeid",coverURL:"https://cdn.intechopen.com/books/images_new/9343.jpg",editors:[{id:"255959",title:"Dr.",name:"Mario Alfonso",middleName:null,surname:"Murillo-Tovar",slug:"mario-alfonso-murillo-tovar",fullName:"Mario Alfonso Murillo-Tovar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8468",title:"Sheep Farming",subtitle:"An Approach to Feed, Growth and Sanity",isOpenForSubmission:!1,hash:"838f08594850bc04aa14ec873ed1b96f",slug:"sheep-farming-an-approach-to-feed-growth-and-sanity",bookSignature:"António Monteiro",coverURL:"https://cdn.intechopen.com/books/images_new/8468.jpg",editors:[{id:"190314",title:"Prof.",name:"António",middleName:"Cardoso",surname:"Monteiro",slug:"antonio-monteiro",fullName:"António Monteiro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8816",title:"Financial Crises",subtitle:"A Selection of Readings",isOpenForSubmission:!1,hash:"6f2f49fb903656e4e54280c79fabd10c",slug:"financial-crises-a-selection-of-readings",bookSignature:"Stelios Markoulis",coverURL:"https://cdn.intechopen.com/books/images_new/8816.jpg",editors:[{id:"237863",title:"Dr.",name:"Stelios",middleName:null,surname:"Markoulis",slug:"stelios-markoulis",fullName:"Stelios Markoulis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7831",title:"Sustainability in Urban Planning and Design",subtitle:null,isOpenForSubmission:!1,hash:"c924420492c8c2c9751e178d025f4066",slug:"sustainability-in-urban-planning-and-design",bookSignature:"Amjad Almusaed, Asaad Almssad and Linh Truong - Hong",coverURL:"https://cdn.intechopen.com/books/images_new/7831.jpg",editors:[{id:"110471",title:"Dr.",name:"Amjad",middleName:"Zaki",surname:"Almusaed",slug:"amjad-almusaed",fullName:"Amjad Almusaed"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9376",title:"Contemporary Developments and Perspectives in International Health Security",subtitle:"Volume 1",isOpenForSubmission:!1,hash:"b9a00b84cd04aae458fb1d6c65795601",slug:"contemporary-developments-and-perspectives-in-international-health-security-volume-1",bookSignature:"Stanislaw P. Stawicki, Michael S. Firstenberg, Sagar C. Galwankar, Ricardo Izurieta and Thomas Papadimos",coverURL:"https://cdn.intechopen.com/books/images_new/9376.jpg",editors:[{id:"181694",title:"Dr.",name:"Stanislaw P.",middleName:null,surname:"Stawicki",slug:"stanislaw-p.-stawicki",fullName:"Stanislaw P. Stawicki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7769",title:"Medical Isotopes",subtitle:null,isOpenForSubmission:!1,hash:"f8d3c5a6c9a42398e56b4e82264753f7",slug:"medical-isotopes",bookSignature:"Syed Ali Raza Naqvi and Muhammad Babar Imrani",coverURL:"https://cdn.intechopen.com/books/images_new/7769.jpg",editors:[{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"8468",title:"Sheep Farming",subtitle:"An Approach to Feed, Growth and Sanity",isOpenForSubmission:!1,hash:"838f08594850bc04aa14ec873ed1b96f",slug:"sheep-farming-an-approach-to-feed-growth-and-sanity",bookSignature:"António Monteiro",coverURL:"https://cdn.intechopen.com/books/images_new/8468.jpg",editedByType:"Edited by",editors:[{id:"190314",title:"Prof.",name:"António",middleName:"Cardoso",surname:"Monteiro",slug:"antonio-monteiro",fullName:"António Monteiro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9523",title:"Oral and Maxillofacial Surgery",subtitle:null,isOpenForSubmission:!1,hash:"5eb6ec2db961a6c8965d11180a58d5c1",slug:"oral-and-maxillofacial-surgery",bookSignature:"Gokul Sridharan",coverURL:"https://cdn.intechopen.com/books/images_new/9523.jpg",editedByType:"Edited by",editors:[{id:"82453",title:"Dr.",name:"Gokul",middleName:null,surname:"Sridharan",slug:"gokul-sridharan",fullName:"Gokul Sridharan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9785",title:"Endometriosis",subtitle:null,isOpenForSubmission:!1,hash:"f457ca61f29cf7e8bc191732c50bb0ce",slug:"endometriosis",bookSignature:"Courtney Marsh",coverURL:"https://cdn.intechopen.com/books/images_new/9785.jpg",editedByType:"Edited by",editors:[{id:"255491",title:"Dr.",name:"Courtney",middleName:null,surname:"Marsh",slug:"courtney-marsh",fullName:"Courtney Marsh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9018",title:"Some RNA Viruses",subtitle:null,isOpenForSubmission:!1,hash:"a5cae846dbe3692495fc4add2f60fd84",slug:"some-rna-viruses",bookSignature:"Yogendra Shah and Eltayb Abuelzein",coverURL:"https://cdn.intechopen.com/books/images_new/9018.jpg",editedByType:"Edited by",editors:[{id:"278914",title:"Ph.D.",name:"Yogendra",middleName:null,surname:"Shah",slug:"yogendra-shah",fullName:"Yogendra Shah"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8816",title:"Financial Crises",subtitle:"A Selection of Readings",isOpenForSubmission:!1,hash:"6f2f49fb903656e4e54280c79fabd10c",slug:"financial-crises-a-selection-of-readings",bookSignature:"Stelios Markoulis",coverURL:"https://cdn.intechopen.com/books/images_new/8816.jpg",editedByType:"Edited by",editors:[{id:"237863",title:"Dr.",name:"Stelios",middleName:null,surname:"Markoulis",slug:"stelios-markoulis",fullName:"Stelios Markoulis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9585",title:"Advances in Complex Valvular Disease",subtitle:null,isOpenForSubmission:!1,hash:"ef64f11e211621ecfe69c46e60e7ca3d",slug:"advances-in-complex-valvular-disease",bookSignature:"Michael S. Firstenberg and Imran Khan",coverURL:"https://cdn.intechopen.com/books/images_new/9585.jpg",editedByType:"Edited by",editors:[{id:"64343",title:null,name:"Michael S.",middleName:"S",surname:"Firstenberg",slug:"michael-s.-firstenberg",fullName:"Michael S. Firstenberg"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10150",title:"Smart Manufacturing",subtitle:"When Artificial Intelligence Meets the Internet of Things",isOpenForSubmission:!1,hash:"87004a19de13702d042f8ff96d454698",slug:"smart-manufacturing-when-artificial-intelligence-meets-the-internet-of-things",bookSignature:"Tan Yen Kheng",coverURL:"https://cdn.intechopen.com/books/images_new/10150.jpg",editedByType:"Edited by",editors:[{id:"78857",title:"Dr.",name:"Tan Yen",middleName:null,surname:"Kheng",slug:"tan-yen-kheng",fullName:"Tan Yen Kheng"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9386",title:"Direct Numerical Simulations",subtitle:"An Introduction and Applications",isOpenForSubmission:!1,hash:"158a3a0fdba295d21ff23326f5a072d5",slug:"direct-numerical-simulations-an-introduction-and-applications",bookSignature:"Srinivasa Rao",coverURL:"https://cdn.intechopen.com/books/images_new/9386.jpg",editedByType:"Edited by",editors:[{id:"6897",title:"Dr.",name:"Srinivasa",middleName:"P",surname:"Rao",slug:"srinivasa-rao",fullName:"Srinivasa Rao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9139",title:"Topics in Primary Care Medicine",subtitle:null,isOpenForSubmission:!1,hash:"ea774a4d4c1179da92a782e0ae9cde92",slug:"topics-in-primary-care-medicine",bookSignature:"Thomas F. Heston",coverURL:"https://cdn.intechopen.com/books/images_new/9139.jpg",editedByType:"Edited by",editors:[{id:"217926",title:"Dr.",name:"Thomas F.",middleName:null,surname:"Heston",slug:"thomas-f.-heston",fullName:"Thomas F. Heston"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9208",title:"Welding",subtitle:"Modern Topics",isOpenForSubmission:!1,hash:"7d6be076ccf3a3f8bd2ca52d86d4506b",slug:"welding-modern-topics",bookSignature:"Sadek Crisóstomo Absi Alfaro, Wojciech Borek and Błażej Tomiczek",coverURL:"https://cdn.intechopen.com/books/images_new/9208.jpg",editedByType:"Edited by",editors:[{id:"65292",title:"Prof.",name:"Sadek Crisostomo Absi",middleName:"C. Absi",surname:"Alfaro",slug:"sadek-crisostomo-absi-alfaro",fullName:"Sadek Crisostomo Absi Alfaro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"1262",title:"Mobile Robot",slug:"psychology-artificial-intelligence-mobile-robot",parent:{title:"Artificial Intelligence",slug:"physical-sciences-engineering-and-technology-robotics-artificial-intelligence"},numberOfBooks:4,numberOfAuthorsAndEditors:76,numberOfWosCitations:151,numberOfCrossrefCitations:120,numberOfDimensionsCitations:226,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicSlug:"psychology-artificial-intelligence-mobile-robot",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"7227",title:"Applications of Mobile Robots",subtitle:null,isOpenForSubmission:!1,hash:"b4993517c29aed9abd474e362370e28a",slug:"applications-of-mobile-robots",bookSignature:"Efren Gorrostieta Hurtado",coverURL:"https://cdn.intechopen.com/books/images_new/7227.jpg",editedByType:"Edited by",editors:[{id:"38850",title:"Dr.",name:"Efren",middleName:null,surname:"Gorrostieta Hurtado",slug:"efren-gorrostieta-hurtado",fullName:"Efren Gorrostieta Hurtado"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"857",title:"Recent Advances in Mobile Robotics",subtitle:null,isOpenForSubmission:!1,hash:"f0d60714b266e84fd76fd0f18ebeebae",slug:"recent-advances-in-mobile-robotics",bookSignature:"Andon Venelinov Topalov",coverURL:"https://cdn.intechopen.com/books/images_new/857.jpg",editedByType:"Edited by",editors:[{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3689",title:"Robot Manipulators",subtitle:null,isOpenForSubmission:!1,hash:null,slug:"robot_manipulators",bookSignature:"Marco Ceccarelli",coverURL:"https://cdn.intechopen.com/books/images_new/3689.jpg",editedByType:"Edited by",editors:[{id:"5828",title:"Prof.",name:"Marco",middleName:null,surname:"Ceccarelli",slug:"marco-ceccarelli",fullName:"Marco Ceccarelli"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6105",title:"Mobile Robotics, Moving Intelligence",subtitle:null,isOpenForSubmission:!1,hash:"5a118a7f27c5c73a4bc8a955ae7e2efb",slug:"mobile_robotics_moving_intelligence",bookSignature:"Jonas Buchli",coverURL:"https://cdn.intechopen.com/books/images_new/6105.jpg",editedByType:"Edited by",editors:[{id:"144262",title:"Dr.",name:"Jonas",middleName:null,surname:"Buchli",slug:"jonas-buchli",fullName:"Jonas Buchli"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:4,mostCitedChapters:[{id:"24924",doi:"10.5772/17790",title:"Motion Planning for Mobile Robots Via Sampling-Based Model Predictive Optimization",slug:"motion-planning-for-mobile-robots-via-sampling-based-model-predictive-optimization",totalDownloads:2906,totalCrossrefCites:3,totalDimensionsCites:19,book:{slug:"recent-advances-in-mobile-robotics",title:"Recent Advances in Mobile Robotics",fullTitle:"Recent Advances in Mobile Robotics"},signatures:"Damion D. Dunlap, Charmane V. Caldwell, Emmanuel G. Collins, Jr. and Oscar Chuy",authors:[{id:"29474",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Collins",slug:"emmanuel-collins",fullName:"Emmanuel Collins"},{id:"39955",title:"Dr.",name:"Damion",middleName:null,surname:"Dunlap",slug:"damion-dunlap",fullName:"Damion Dunlap"},{id:"39956",title:"Dr.",name:"Charmane",middleName:null,surname:"Caldwell",slug:"charmane-caldwell",fullName:"Charmane Caldwell"},{id:"39957",title:"Dr.",name:"Oscar",middleName:null,surname:"Chuy",slug:"oscar-chuy",fullName:"Oscar Chuy"}]},{id:"5579",doi:"10.5772/6197",title:"Unit Quaternions: A Mathematical Tool for Modeling, Path Planning and Control of Robot Manipulators",slug:"unit_quaternions__a_mathematical_tool_for_modeling__path_planning_and_control_of_robot_manipulators",totalDownloads:4370,totalCrossrefCites:15,totalDimensionsCites:17,book:{slug:"robot_manipulators",title:"Robot Manipulators",fullTitle:"Robot Manipulators"},signatures:"Ricardo Campa and Karla Camarillo",authors:null},{id:"24926",doi:"10.5772/25621",title:"Fuzzy Logic Based Navigation of Mobile Robots",slug:"fuzzy-logic-based-navigation-of-mobile-robots",totalDownloads:3370,totalCrossrefCites:8,totalDimensionsCites:11,book:{slug:"recent-advances-in-mobile-robotics",title:"Recent Advances in Mobile Robotics",fullTitle:"Recent Advances in Mobile Robotics"},signatures:"Amur S. Al Yahmedi and Muhammed A. Fatmi",authors:[{id:"63929",title:"Prof.",name:"Amur",middleName:null,surname:"Al-Yahmedi",slug:"amur-al-yahmedi",fullName:"Amur Al-Yahmedi"}]}],mostDownloadedChaptersLast30Days:[{id:"62563",title:"Online Mapping-Based Navigation System for Wheeled Mobile Robot in Road Following and Roundabout",slug:"online-mapping-based-navigation-system-for-wheeled-mobile-robot-in-road-following-and-roundabout",totalDownloads:759,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"applications-of-mobile-robots",title:"Applications of Mobile Robots",fullTitle:"Applications of Mobile Robots"},signatures:"Mohammed A. H. Ali and Musa Mailah",authors:[{id:"32016",title:"Prof.",name:"Musa",middleName:null,surname:"Mailah",slug:"musa-mailah",fullName:"Musa Mailah"},{id:"243606",title:"Dr.",name:"Mohammed A. H",middleName:null,surname:"Ali",slug:"mohammed-a.-h-ali",fullName:"Mohammed A. H Ali"}]},{id:"62978",title:"Intelligent Robotic Perception Systems",slug:"intelligent-robotic-perception-systems",totalDownloads:1219,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"applications-of-mobile-robots",title:"Applications of Mobile Robots",fullTitle:"Applications of Mobile Robots"},signatures:"Cristiano Premebida, Rares Ambrus and Zoltan-Csaba Marton",authors:[{id:"203409",title:"Ph.D.",name:"Cristiano",middleName:null,surname:"Premebida",slug:"cristiano-premebida",fullName:"Cristiano Premebida"},{id:"254880",title:"Dr.",name:"Rares",middleName:null,surname:"Ambrus",slug:"rares-ambrus",fullName:"Rares Ambrus"},{id:"254881",title:"Dr.",name:"Zoltan-Csaba",middleName:null,surname:"Marton",slug:"zoltan-csaba-marton",fullName:"Zoltan-Csaba Marton"}]},{id:"63854",title:"A Survey and Analysis of Cooperative Multi-Agent Robot Systems: Challenges and Directions",slug:"a-survey-and-analysis-of-cooperative-multi-agent-robot-systems-challenges-and-directions",totalDownloads:1547,totalCrossrefCites:4,totalDimensionsCites:8,book:{slug:"applications-of-mobile-robots",title:"Applications of Mobile Robots",fullTitle:"Applications of Mobile Robots"},signatures:"Zool Hilmi Ismail and Nohaidda Sariff",authors:[{id:"91546",title:"MSc.",name:"Nohaidda Binti Sariff",middleName:null,surname:"Sariff",slug:"nohaidda-binti-sariff-sariff",fullName:"Nohaidda Binti Sariff Sariff"},{id:"135439",title:"Dr.",name:"Zool",middleName:"H",surname:"Ismail",slug:"zool-ismail",fullName:"Zool Ismail"}]},{id:"64100",title:"Mobile Robot Feature-Based SLAM Behavior Learning, and Navigation in Complex Spaces",slug:"mobile-robot-feature-based-slam-behavior-learning-and-navigation-in-complex-spaces",totalDownloads:423,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"applications-of-mobile-robots",title:"Applications of Mobile Robots",fullTitle:"Applications of Mobile Robots"},signatures:"Ebrahim A. Mattar",authors:[{id:"216016",title:"Dr.",name:"Ebrahim",middleName:"A.",surname:"Mattar",slug:"ebrahim-mattar",fullName:"Ebrahim Mattar"}]},{id:"62387",title:"IntelliSoC: A System Level Design and Conception of a System- on-a-Chip (SoC) to Cognitive Agents Architecture",slug:"intellisoc-a-system-level-design-and-conception-of-a-system-on-a-chip-soc-to-cognitive-agents-archit",totalDownloads:384,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"applications-of-mobile-robots",title:"Applications of Mobile Robots",fullTitle:"Applications of Mobile Robots"},signatures:"Diego Ferreira, Augusto Loureiro da Costa and Wagner Luiz Alves\nDe Oliveira",authors:[{id:"246122",title:"Prof.",name:"Augusto",middleName:null,surname:"Loureiro Da Costa",slug:"augusto-loureiro-da-costa",fullName:"Augusto Loureiro Da Costa"},{id:"247158",title:"M.Sc.",name:"Diego",middleName:"Stéfano",surname:"Fonseca Ferreira",slug:"diego-fonseca-ferreira",fullName:"Diego Fonseca Ferreira"},{id:"247159",title:"Prof.",name:"Wagner Luiz",middleName:null,surname:"Alves De Oliveira",slug:"wagner-luiz-alves-de-oliveira",fullName:"Wagner Luiz Alves De Oliveira"}]},{id:"24924",title:"Motion Planning for Mobile Robots Via Sampling-Based Model Predictive Optimization",slug:"motion-planning-for-mobile-robots-via-sampling-based-model-predictive-optimization",totalDownloads:2906,totalCrossrefCites:3,totalDimensionsCites:19,book:{slug:"recent-advances-in-mobile-robotics",title:"Recent Advances in Mobile Robotics",fullTitle:"Recent Advances in Mobile Robotics"},signatures:"Damion D. Dunlap, Charmane V. Caldwell, Emmanuel G. Collins, Jr. and Oscar Chuy",authors:[{id:"29474",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Collins",slug:"emmanuel-collins",fullName:"Emmanuel Collins"},{id:"39955",title:"Dr.",name:"Damion",middleName:null,surname:"Dunlap",slug:"damion-dunlap",fullName:"Damion Dunlap"},{id:"39956",title:"Dr.",name:"Charmane",middleName:null,surname:"Caldwell",slug:"charmane-caldwell",fullName:"Charmane Caldwell"},{id:"39957",title:"Dr.",name:"Oscar",middleName:null,surname:"Chuy",slug:"oscar-chuy",fullName:"Oscar Chuy"}]},{id:"62939",title:"Path Tracking of a Wheeled Mobile Manipulator through Improved Localization and Calibration",slug:"path-tracking-of-a-wheeled-mobile-manipulator-through-improved-localization-and-calibration",totalDownloads:485,totalCrossrefCites:0,totalDimensionsCites:1,book:{slug:"applications-of-mobile-robots",title:"Applications of Mobile Robots",fullTitle:"Applications of Mobile Robots"},signatures:"Tao Song, Fengfeng (Jeff) Xi and Shuai Guo",authors:[{id:"65530",title:"Prof.",name:"Guo",middleName:null,surname:"Shuai",slug:"guo-shuai",fullName:"Guo Shuai"},{id:"133537",title:"Prof.",name:"Fengfeng",middleName:null,surname:"Xi",slug:"fengfeng-xi",fullName:"Fengfeng Xi"},{id:"244038",title:"Dr.",name:"Tao",middleName:null,surname:"Song",slug:"tao-song",fullName:"Tao Song"}]},{id:"24916",title:"Three-Dimensional Environment Modeling Based on Structure from Motion with Point and Line Features by Using Omnidirectional Camera",slug:"three-dimensional-environment-modeling-based-on-structure-from-motion-with-point-and-line-features-b",totalDownloads:1849,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"recent-advances-in-mobile-robotics",title:"Recent Advances in Mobile Robotics",fullTitle:"Recent Advances in Mobile Robotics"},signatures:"Ryosuke Kawanishi, Atsushi Yamashita and Toru Kaneko",authors:[{id:"2556",title:"Dr.",name:"Atsushi",middleName:null,surname:"Yamashita",slug:"atsushi-yamashita",fullName:"Atsushi Yamashita"},{id:"64426",title:"Dr.",name:"Ryosuke",middleName:null,surname:"Kawanishi",slug:"ryosuke-kawanishi",fullName:"Ryosuke Kawanishi"},{id:"64431",title:"Prof.",name:"Toru",middleName:null,surname:"Kaneko",slug:"toru-kaneko",fullName:"Toru Kaneko"}]},{id:"63790",title:"Mobile Robot Navigation in Indoor Environments: Geometric, Topological, and Semantic Navigation",slug:"mobile-robot-navigation-in-indoor-environments-geometric-topological-and-semantic-navigation",totalDownloads:805,totalCrossrefCites:0,totalDimensionsCites:3,book:{slug:"applications-of-mobile-robots",title:"Applications of Mobile Robots",fullTitle:"Applications of Mobile Robots"},signatures:"Ramón Barber, Jonathan Crespo, Clara Gómez, Alejandra C.\nHernámdez and Marina Galli",authors:[{id:"158703",title:"Dr.",name:"Ramon",middleName:null,surname:"Barber",slug:"ramon-barber",fullName:"Ramon Barber"},{id:"260264",title:"Dr.",name:"Jonathan",middleName:null,surname:"Crespo",slug:"jonathan-crespo",fullName:"Jonathan Crespo"},{id:"260265",title:"Ms.",name:"Clara",middleName:null,surname:"Gomez",slug:"clara-gomez",fullName:"Clara Gomez"},{id:"260266",title:"Ms.",name:"Alejandra C.",middleName:null,surname:"Hernandez",slug:"alejandra-c.-hernandez",fullName:"Alejandra C. Hernandez"},{id:"260267",title:"Ms.",name:"Marina",middleName:null,surname:"Galli",slug:"marina-galli",fullName:"Marina Galli"}]},{id:"24932",title:"Feedback Equivalence and Control of Mobile Robots Through a Scalable FPGA Architecture",slug:"feedback-equivalence-and-control-of-mobile-robots-through-a-scalable-fpga-architecture",totalDownloads:2737,totalCrossrefCites:6,totalDimensionsCites:7,book:{slug:"recent-advances-in-mobile-robotics",title:"Recent Advances in Mobile Robotics",fullTitle:"Recent Advances in Mobile Robotics"},signatures:"G.P. Moustris, K.M. Deliparaschos and S.G. Tzafestas",authors:[{id:"67849",title:"Dr.",name:"George",middleName:"P.",surname:"Moustris",slug:"george-moustris",fullName:"George Moustris"},{id:"81032",title:"Dr.",name:"Kyriakos",middleName:"M",surname:"Deliparaschos",slug:"kyriakos-deliparaschos",fullName:"Kyriakos Deliparaschos"},{id:"81034",title:"Prof.",name:"Spyros",middleName:null,surname:"Tzafestas",slug:"spyros-tzafestas",fullName:"Spyros Tzafestas"}]}],onlineFirstChaptersFilter:{topicSlug:"psychology-artificial-intelligence-mobile-robot",limit:3,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[{type:"book",id:"10176",title:"Microgrids and Local Energy Systems",subtitle:null,isOpenForSubmission:!0,hash:"c32b4a5351a88f263074b0d0ca813a9c",slug:null,bookSignature:"Prof. Nick Jenkins",coverURL:"https://cdn.intechopen.com/books/images_new/10176.jpg",editedByType:null,editors:[{id:"55219",title:"Prof.",name:"Nick",middleName:null,surname:"Jenkins",slug:"nick-jenkins",fullName:"Nick Jenkins"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:8,limit:8,total:1},route:{name:"profile.detail",path:"/profiles/129566/mazlin-mokhtar",hash:"",query:{},params:{id:"129566",slug:"mazlin-mokhtar"},fullPath:"/profiles/129566/mazlin-mokhtar",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()