Summary of miRNAs bioactive compounds and miRNAs expression in human pathology.
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
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In this respect, the chapters cover the following topics: chemical structure and phase transitions in bent-core liquid crystals, phase and structural behavior of liquid crystals used to align carbon nanotubes, molecular alignment, and photorefractive effect in the ferroelectric phase, which has the potential to be used as transistors, for image storage, and in optical signal processing. 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Her areas of research\ninterest include synthesis and characterization of liquid crystals\nwith applications in opto-electronics, azobenzene compounds,\nglycoconjugates and ferrocene derivatives. She is a reviewer for\nLiquid Crystals, Crystals, Molecules and Medicinal Chemistry Research. She is also co-author of twenty-seven articles in peer-reviewed journals, h-index = 8.",institutionString:"Gheorghe Asachi Technical University of Iași",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Gheorghe Asachi Technical University of Iași",institutionURL:null,country:{name:"Romania"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1169",title:"Condensed Matter Physics",slug:"nanotechnology-and-nanomaterials-material-science-condensed-matter-physics"}],chapters:[{id:"64523",title:"Introductory Chapter: Liquid Crystals",doi:"10.5772/intechopen.82296",slug:"introductory-chapter-liquid-crystals",totalDownloads:1130,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:null,signatures:"Irina Carlescu",downloadPdfUrl:"/chapter/pdf-download/64523",previewPdfUrl:"/chapter/pdf-preview/64523",authors:[{id:"258032",title:"Prof.",name:"Irina",surname:"Carlescu",slug:"irina-carlescu",fullName:"Irina Carlescu"}],corrections:null},{id:"64291",title:"Bent-Core Liquid Crystals: Structures and Mesomorphic Properties",doi:"10.5772/intechopen.81704",slug:"bent-core-liquid-crystals-structures-and-mesomorphic-properties",totalDownloads:1345,totalCrossrefCites:1,totalDimensionsCites:3,hasAltmetrics:1,abstract:"Bent-core (BC) molecules became an attractive liquid crystal class due to their potential use in smart displays and photonic devices. 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A more comprehensive study is still required, and such type of smectic liquid crystal panel provides unique electro-optic properties that have not been reported.",signatures:"Akihiro Mochizuki",downloadPdfUrl:"/chapter/pdf-download/63828",previewPdfUrl:"/chapter/pdf-preview/63828",authors:[{id:"255297",title:"Dr.",name:"Akihiro",surname:"Mochizuki",slug:"akihiro-mochizuki",fullName:"Akihiro Mochizuki"}],corrections:null},{id:"64051",title:"The Photorefractive Effect in Liquid Crystals",doi:"10.5772/intechopen.81573",slug:"the-photorefractive-effect-in-liquid-crystals",totalDownloads:1049,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This chapter summarizes the state of the art of research regarding photorefractive liquid crystals. Photorefractive effect is of interest because it can be used to obtain dynamic holograms, based on interference between dual laser beams within a liquid crystal to generate a refractive index grating. This technique can be employed in numerous diffraction optics applications, such as optical amplifiers, phase-conjugate wave generators, 3D displays, novelty filters, and optical tomography. The photorefractive effect in liquid crystals is especially pronounced, and both ferroelectric and nematic liquid crystals have been researched for this purpose, with the former showing special promise in practical applications. 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His research interest is ionizing radiation metrology, especially ionization chambers, EPR, and thermoluminescence dosimetry (TLD). He is a reviewer for several peer-reviewed journals and has supervised a number of master’s and Ph.D. theses, and was elected as the vice president of the National Committee of Physics (NPC) in Egypt.",institutionString:"National Institute of Standards",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"3",institution:null}],coeditorOne:{id:"259474",title:"Prof.",name:"Basim",middleName:"A.",surname:"Almayyahi",slug:"basim-almayyahi",fullName:"Basim Almayyahi",profilePictureURL:"https://mts.intechopen.com/storage/users/259474/images/system/259474.jpg",biography:"Dr. Basim Almayahi is currently a professor in the College of Science, University of Kufa, Iraq. His fields of interest include radiation biophysics; radiation medical physics; the natural radioactivity of the environment; treatment of prostate cancer using gold nanoparticles; synthesis and applications of silver nanoparticles on bacterial pathogens; biosensors for detecting radon and lead; the natural radioactivity of gamma rays, radon, and alpha particles in tissue, blood, teeth, bones, soil, water, air, food, fertilizer, and building materials; radiation detection and measurements (scintillation detector (Na I (Tl)); high-purity Germanium (HPGe) detector, Exploranium GR-135; 1029 Continuous Radon Monitor; RAD 7 System; SSNTDs CR-39; radiation protection; statistical physics; and environmental statistics (GenStat, SPSS, OrginLab, Sigmaplot). He was a lecturer in the Department of Physics at Babylon University, Iraq, from 2001 to 2004, before taking up a post as a teacher in the Atomic and Nuclear Lab at the University of Kufa from 2005 to 2008. He is Head of the Department of Environment and Director of Scientific Affairs and Cultural Relations at the College of Science, University of Kufa. He has mentored four master’s theses and one Ph.D. dissertation. He is the editor and author of three books and a reviewer for more than 200 journals. He is an editorial board member of twenty-three boards, and a member of various institutions. He has published ninety-five scientific papers in domestic and international journals and participated in forty-three scientific congresses and conferences.",institutionString:"University of Kufa",position:null,outsideEditionCount:null,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"1",institution:null},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"227",title:"Nuclear Physics",slug:"nuclear-physics"}],chapters:[{id:"74233",title:"Relative Biological Effectiveness Studies Using 3 MeV Proton Beam from Folded Tandem Ion Accelerator: An Experimental and Theoretical Approach",slug:"relative-biological-effectiveness-studies-using-3-mev-proton-beam-from-folded-tandem-ion-accelerator",totalDownloads:346,totalCrossrefCites:0,authors:[{id:"325101",title:"Dr.",name:"Rajesha",surname:"Nairy",slug:"rajesha-nairy",fullName:"Rajesha Nairy"},{id:"326238",title:"Dr.",name:"Nagesh N",surname:"Bhat",slug:"nagesh-n-bhat",fullName:"Nagesh N Bhat"},{id:"326239",title:"Dr.",name:"K B",surname:"Anjaria",slug:"k-b-anjaria",fullName:"K B Anjaria"},{id:"326240",title:"Mrs.",name:"Usha",surname:"Yadav",slug:"usha-yadav",fullName:"Usha Yadav"},{id:"326241",title:"Mr.",name:"Rajesh",surname:"Chaurasia",slug:"rajesh-chaurasia",fullName:"Rajesh Chaurasia"},{id:"326242",title:"Mr.",name:"Kapil",surname:"Shirsath",slug:"kapil-shirsath",fullName:"Kapil Shirsath"},{id:"326243",title:"Ms.",name:"Utkarsha",surname:"Desai",slug:"utkarsha-desai",fullName:"Utkarsha Desai"},{id:"326244",title:"Dr.",name:"S.K",surname:"Gupta",slug:"s.k-gupta",fullName:"S.K Gupta"},{id:"326246",title:"Dr.",name:"B K",surname:"Sapra",slug:"b-k-sapra",fullName:"B K Sapra"},{id:"326247",title:"Dr.",name:"Narayana",surname:"Yerol",slug:"narayana-yerol",fullName:"Narayana Yerol"}]},{id:"72256",title:"Biologically Effective Dose (BED) or Radiation Biological Effect (RBEf)?",slug:"biologically-effective-dose-bed-or-radiation-biological-effect-rbef-",totalDownloads:844,totalCrossrefCites:2,authors:[{id:"315306",title:"B.Sc.",name:"Terman",surname:"Frometa-Castillo",slug:"terman-frometa-castillo",fullName:"Terman Frometa-Castillo"}]},{id:"71680",title:"State of Radiation Protection in Bulgaria",slug:"state-of-radiation-protection-in-bulgaria",totalDownloads:549,totalCrossrefCites:0,authors:[{id:"314874",title:"Ph.D.",name:"Nikolay",surname:"Dolchinkov Todorov",slug:"nikolay-dolchinkov-todorov",fullName:"Nikolay Dolchinkov Todorov"}]},{id:"71613",title:"Natural Radioactive Decay",slug:"natural-radioactive-decay",totalDownloads:532,totalCrossrefCites:0,authors:[{id:"313923",title:"Dr.",name:"Entesar H.",surname:"Elaraby",slug:"entesar-h.-elaraby",fullName:"Entesar H. 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There is neither an accurate early diagnosis nor an effective treatment that allows the patients to have better life expectancies [1]. Perhaps one of the most important problems to solve is understand that when the diagnosis is made, the symptoms and the signs of Alzheimer\'s disease are the result of a long chain of events that took place during an extended period of time and that such symptoms and signs change with time [2].
\nOne can assume that intracellular signaling and metabolic changes found during the early stages of the disease are not the same as the ones found at more advanced stages. For this reason, recent postmortem studies fail to completely clarify the physiopathology of this disease.
\nAcute oxidative stress is reversible and it is present in a number of physiological and pathological mechanisms that are reversible as well. These mechanisms play a defensive role in the organism during respiratory burst [3]. However, the chronic oxidative stress state is an epiphenomenon that affects the organism and the brain tissue at different levels. It is involved in the maintenance and advance of the chronic degenerative disease that is usually irreversible [4].
\nIt has been widely demonstrated that in redox balance, the rise in reactive species induces an increase in the production of antioxidant enzymes. In turn, the enzymes rapidly compensate the free radicals, allowing the system to return to redox balance [5]. During this state, free radicals also play a central role signaling the different intracellular cascades related to cell cycle and antioxidant response. The latter is associated to repair mechanisms and cell survival, regulation of inflammatory response, signaling of intracellular metabolic pathways, maintenance of energetic metabolism, and the efficient system of protein degradation by the proteasome [6].
\nIn the brain, insulin signaling over its receptors is crucial to survival maintenance of neural metabolism. Similarly, the correct functioning of phosphorylation and dephosphorylation pathways that takes place during redox balance promotes an efficient functioning of the signaling pathways [7]. We must also include low‐density lipoprotein (LDL) receptors, cholesterol, and receptors for advanced glycation end products [8–10].
\nNevertheless, the loss of redox balance causes disturbances in the pathways mentioned above changing the signaling and the normal metabolism needed to maintain cell function.
\nIt has been reported that the excess of free radicals formed during normal metabolism is able to produce oxidation in proteins, DNA, and RNA. It also causes lipid peroxidation and sugar modification, thus inducing changes that lead to catastrophic neuronal death in the hippocampus, including neocortex regions [11]. Furthermore, free radicals are chemical species that have one or more unpaired electrons, which can act as acceptors of other electrons belonging to other molecules. As a result, they produce oxidation and cause a chain of molecular damage [12]. Free radicals come from sources that are endogenous (the own metabolism of the cell, mainly carried out during the respiratory chain in the internal membrane of the mitochondria) and exogenous (environmental pollution, tobacco, smoke, drugs, xenobiotics, or radiation) [13]. Despite the deleterious effects of oxidative stress, aerobic organisms have developed a wide variety of mechanisms to maintain genomic stability. These mechanisms include endogenous and exogenous antioxidants that can be divided into enzymatic and nonenzymatic antioxidants [14].
\nThe enzymatic antioxidants are genetically codificated, for example, superoxide dismutase (SOD) cupper/zinc, manganese, glutathion peroxidase, glutathion reductase, and catalase [15]. The nonenzymatic antioxidants such as thioredoxin, vitamin C, vitamin A, and vitamin E have a strong role as scavengers [16].
\nThe free radicals are metabolized in the biological systems leading to the formation of reactive species that, depending on the radical (oxygen, nitrogen, iron, copper, etc.), receive their denomination. For example, the metabolism of the superoxide radical generates the reactive oxygen species (ROS), whereas the metabolism of the nitric oxide radical generates reactive nitrogen species (RNS) [17].
\nThe increase of ROS together with the deficit of antioxidant systems causes a chronic oxidative stress state. It is interesting to point out that an acute increase of the ROS causes a stimulation of the antioxidant systems depending on the antioxidant capability of the organism; this is the basis of ozone therapy [18]. However, the production or the exposure chronic, whether by environmental pollutants or metabolic disorders, to low or moderate ROS concentrations in the organism induces a chronic oxidative stress state. Such state is found in several chronic degenerative diseases among which neurodegenerative diseases as Parkinson\'s and Alzheimer\'s are included [19].
\nThe chronic oxidative stress state is an epiphenomenon that affects cell functions at different levels. They go from changes in signaling of the cell cycle [20], response to endogenous antioxidant systems [21], loss of repair and cell function mechanisms [22], and regulation of the dynamic of the cytoskeleton [23]. They also include protein misfolding and oxidation [24], alterations in function and signaling of the endoplasmic reticulum (ER) during protein synthesis and chaperone signaling [25], alteration and loss of cell receptor functionality [26, 27], and mitochondrial damage leading to a deficit of energy [28]. In addition, there is loss of the regulation and selectivity of the cell membrane [29], stimulation of phosphorylation pathways and inhibition of dephosphorylation pathways, which alter intracellular signaling [30, 31], and finally, the loss of regulation of inflammatory response [32], as is shown in Figure 1.
Effect of chronic oxidative stress on intracellular changes present during the development of Alzheimer\'s disease.
The presence of an oxidative stress state has been associated with an aberrant reentry into the cell cycle, a phenomenon associated with the death of terminally differentiated neurons. This mechanism has been observed in samples from Alzheimer\'s disease and Down syndrome patients [33, 34]. It has been proven that the increase in the cyclin D2 levels due to the loss of FoxO 1a downregulation on this cyclin may take part of the aberrant reentry into cell cycle. In consequence, the mature neurons do not divide activating cell death mechanisms by apoptosis where caspase‐3 might play an important role [35].
\nThe increase of free radicals acts upon a series of pathways that lead to transcription of antioxidant enzymes. Transcription factors within these pathways allow the activation of antioxidant response elements (AREs) in the nucleus [36]. The AREs cause the raise in messenger RNA transcription for the increase in antioxidant enzyme synthesis. For instance, FoxO 3a activation stimulates the signaling pathway for the increase in the synthesis of superoxide dismutase enzymes, particularly the manganese superoxide dismutase, MnSOD [35]. The signaling pathway regulated by the transcription factor Nrf2 is also activated by the presence of ROS. Under oxidative stress conditions, Nrf2 transactivates the synthesis of hundreds of antioxidant genes such as HMOX‐1, NQO‐1, GCS, and GSTM1, among others [37]. In humans, the insufficient activation of this transcription factor has been related to chronic diseases as Parkinson\'s, Alzheimer\'s, and amyotrophic lateral sclerosis [38]. In brains of Alzheimer\'s patients, studies have also proven a reduction in the Nrf2 protein levels in hippocampus astrocytes. This is one of the key areas where ROS causes neurodegeneration in this disease [39]. In addition, some target genes of this transcription factor have been found to be reduced in the frontal cortex, as is the case of the protein p62 [40].
\nThe neuronal cytoskeleton consists of microtubules, actin filaments, and neurofilaments (intermediate filaments). All these components are regulated through the changes in the levels of expression of the genes that code, posttranslational changes, and the set of proteins with which they interact. Oxidative stress affects the regulation mechanisms of the neuronal cytoskeleton when acting over its components. Because all the components are interconnected and regulate each other, the damage caused by oxidative stress affects the whole cytoskeleton network [41]. The microtubules are particularly susceptible to oxidative stress that causes its depolymerization [42]. Furthermore, oxidative stress affects the tubulin through aberrant posttranslational modifications [43]. For their part, actin filaments are less susceptible to the negative effects of oxidative stress because they use ROS for their reorganization [44]. Finally, neurofilaments are phosphorylated in the presence of reactive species, which causes the formation of protein aggregates as the ones found in neurodegenerative diseases like Alzheimer\'s [45].
\nOxidation can affect protein structure because the endoplasmic reticulum responds to oxidative stress by affecting chaperons and producing protein misfolding altering their spatial structure. This causes negative effects on the functionality of the proteins and makes them susceptible to aggregation, inducing to cell toxicity [46].
\nThe disassembly in the ubiquitin‐proteasome proteins is a protection mechanism to avoid the damages caused by oxidative stress [47]. A number of studies have reported that from the 26S proteasome complex, the 20S subunit is more resistant to the damage caused by ROS compared to the 19S subunit. It may bind and degrade misfolded oxidized proteins without the need of ubiquitination and ATP expenditure [48]. However, during a chronic oxidative stress state, proteasomal proteins are also modified by oxidation, thus altering their function and causing intracellular and extracellular protein accumulation [49].
\nThe endoplasmic reticulum is the organelle that within their functions include the calcium (Ca2+) storage and protein folding with the participation of different enzymes and chaperones [50]. The redox state inside the ER lumen is highly oxidant and the changes caused by the presence of ROS affect the correct protein folding. It contributes to the breaking of the disulphide bonds by the binding of reactive species to thiol groups [51]. Misfolded proteins that are formed in the ER cause Ca2+ release in the cytoplasmic space. When the mitochondria capture excessive amounts of calcium, it loses the regulation of its membrane, creating a mitochondrial transition pore. This results in ATP deficit and ROS increase which induce, in turn, ER Ca2+ release; thus, a vicious cycle in the intracellular regulation of Ca2+ levels is created [52]. Studies performed with cerebral samples from Alzheimer\'s patients have demonstrated that the redox modifications caused by oxidative stress inhibit the function of chaperones and the correct folding proteins, causing protein misfolding and ER stress [53]. In Alzheimer\'s pathology, β‐protein has been reported to induce stress in the ER and change the morphology of the ER and also of the mitochondria. This results in the loss of the mitochondrial membrane potential and the consequent production of ROS [54].
\nThe mitochondria play a number of cell functions, such as ATP synthesis, calcium homeostasis, and processes of cell survival and death. Additionally, this organelle is the main source of endogenous ROS; therefore, it is constantly exposed to oxidative stress [55]. Several metabolic and mitochondrial abnormalities have been found in hippocampal neurons of patients with Alzheimer\'s. Mitochondria of AD patients show a reduction in size, DNA alterations, and mitochondrial proteins in vacuoles, suggesting mitochondrial degradation by autophagy [56]. Studies have also observed deficiencies in the production of antioxidant enzymes that play a protective role protecting the mitochondria from the damage caused by ROS; for example, there are the cytochrome oxidase complex IV, MnSOD, and uncoupling proteins [57].
\nThe immune defense of the central nervous system (CNS) is composed of a number of small cells known as microglia, astrocytes, and an effective blood‐brain barrier [58]. The presence of an oxidative stress state causes the activation of the microglia and the astrocytes. As a result, inflammatory and neurotoxic factors are released increasing the levels of oxidative stress and causing a chronic neuroinflammatory response. Depending on its duration, the response may cause damage in the brain tissue [59]. Neurodegenerative diseases are characterized by a chronic dysregulation of the inflammatory response that involves glial alteration. This produces alterations in the neuronal metabolism, neuronal survival, and repair that progress to neuronal death and memory disturbances [4].
\nThe chronic oxidative stress state causes alterations in dendritic spines. These alterations consist of a reduction in the size of the spines as well as a decrease in their number. This phenomenon is present in neurodegenerative diseases and in chronic diseases as alcoholism [60, 61]. An explanation of this histologic alteration found in the hippocampus of the patients is the loss of the existing regulation in calcium metabolism during oxidative stress state. There is an increase of extracellular Ca2+ entry, which tries to be regulated by the cells; they send Ca2+ to the ER or the mitochondria to avoid the alteration Ca2+‐dependent cell functions [62]. In addition, some studies have proposed a neuronal defense mechanism in which the cell tries to decrease the membrane surface exposed to free radicals, with the final purpose to try to control the balance in the intraneuronal medium [63]. All these changes affect the number of synapses and the metabolic interaction between astrocytes and neurons.
\nThe signaling and metabolic changes that occur in the presence of oxidative stress affect the interaction between neurons and astrocytes, and cause the activation of the microglia, inducing and maintaining the loss of regulation of the inflammatory response [64]. Among these alterations, we find the loss of regulation in neurotransmitter metabolism as glutamate, dopamine, as well as alterations in the metabolism of antioxidant systems like glutathione [65, 66]. On the other hand, the changes in the expression of inducible nitric oxide synthase and in the extracellular Ca2+ levels cause the release of proinflammatory cytokines as interleukin (IL)‐1, IL‐3, IL‐6, interferon (IFN)‐α, IFN‐β, and tumor necrosis factor (TNF)‐α by the astrocytes (Figure 2). This promotes the maintenance of the inflammatory response and the stimulation of the glia, creating a vicious cycle consisting of oxidative stress, cytokine release, inflammatory response, and increase of oxidative stress [67].
Microphotography that shows the chronic effect of oxidative stress in hippocampal astrocytes from rats exposed to low doses of ozone (40×). There are changes in the astrocytes in the samples from animals exposed to ozone.
The blood‐brain barrier finely regulates the entry of substances into the brain. Among its functions is the capability of changing the affinity of the transporters according to the necessities of the nervous tissue [68]. This barrier is created by a close relationship between neurons, astrocytes, and endothelial cells; the microglia is involved as well [69]. The barrier creates a neurovascular unit that promotes neuronal homeostasis maintenance. Nevertheless, in neurodegenerative diseases and during inflammatory processes, this barrier is broken down and loses its selectivity [70]. We have proven that the blood‐brain barrier is broken and there are changes in the morphology of the end feet of astrocytes in animal models of neurodegeneration caused by oxidative stress in the hippocampus of rats exposed to ozone [71]. Finally, this break is followed by endothelial cell edema, changes in the processes and in astrocytic feet, and an increase of the proinflammatory factors. It promotes the exacerbation of the neurodegenerative process [72]. Oligomer production of β‐amyloid increases oxidative damage of the blood‐brain barrier, attracting astrocytes, glia, and activated microglia [73].
\nThe break of the amyloid precursor protein (APP) has two phases: a nonamyloidogenic pathway and an amyloidogenic pathway. The amino acid 83 is cleaved by the α‐secretase on the carboxyl‐terminal, producing a long amino N‐terminal ectodomain (sAPPα). The result of this process is the formation of C83, which is retained by the membrane to be cleaved by gamma secretase, creating short p3 fragments. The break down by α‐secretase occurs within the β‐amyloid region, preventing the formation of β‐amyloid [74].
\nOn the other hand, the amyloidogenic pathway is an alternative APP breakdown which leads to the creation of β‐amyloids. This pathway is created by the β‐secretase cleaving in the amino acid 99, allowing sAPPβ release in the extracellular space [75]. In consequence, the breakdown of this fragment between the 38 and 43 residues by the γ‐secretase releases an intact Aβ peptide [76]. The complete β‐amyloid peptide is 40 residues long (Aβ40) and 10% is a 42‐residue variant (Aβ42). This variant is more hydrophobic and easily induces the formation of fibrils. It is also the largest form of this peptides prevailing the β‐amyloid plaques [77].
\nThere is a variety of assembly forms in which the β‐amyloid peptide can be found. This peptide can carry out different physiological or pathological functions depending on the assembly pathway [78]. The β‐amyloid can be deposited in specific brain regions forming amyloid plaques [79, 80].
\nAmong the different hypotheses explaining the possible causes intervening in the development of the disease, the participation of oxidative stress is nowadays widely accepted. Results obtained in our laboratory show that oxidative stress in healthy animals is per se capable of producing hyperphosphorylated tau protein and the formation of isoforms of β‐amyloids 1‐42 in hippocampal neurons of rats chronically exposes to low doses of ozone [81] (Figure 3).
\nThe formation of senile plaques is due to intracellular and extracellular accumulation of insoluble β‐amyloids in the brain. The β‐amyloid peptide is generated by APP cleavage where the enzymes α, β, and γ secretases are involved as previously indicated [82]. Both the enzymes of the amyloidogenic pathway as the enzymes of the nonamyloidogenic pathway are altered by a chronic oxidative stress state. Experiments performed in our laboratory demonstrate that chronic oxidative stress, caused by exposure to low doses of ozone, is capable of inhibiting the enzymes involved in the nonamyloidogenic pathway. It also increases the enzymes in the amyloidogenic pathway in the hippocampus of rats which were exposed to this gas for 4 hours during 60 and 90 days (Figures 4 and 5).
\nMicrography that shows the chronic effect of oxidative stress on the formation of β‐amyloid 1‐42 in rat hippocampus exposed to low doses of ozone for 90 days (100×). Note changes in intracellular accumulation of β‐amyloid 1‐42 in neurons of the dentate gyrus.
Micrography that shows the chronic effect of oxidative stress on the enzymes of the nonamyloidogenic pathway (A: ADAM 9; B: ADAM 10) in dentate gyrus of rat hippocampus exposed to low doses of ozone (40×). Note the decrease in immunoreactivity after 90 days of exposure to ozone compared to the control.
Micrography that shows the chronic effect of oxidative stress on the amyloidogenic pathway enzymes (A: presenilin 1; B: presenilin 2) in the dentate gyrus of rat hippocampus exposed to low doses of ozone (40×). Note the increase in immunoreactivity at 90 days for presenilin 1 and presenilin 2 to 60 days in the brains of animals exposed to ozone compared to the control.
The β‐amyloid accumulation in specific compartments of the neuron causes an energy deficit and alterations in protein folding [83, 84]. For its part, the intracellular increase of these oligomers causes the inhibition of the proteasome activity, lowering the possibility of processing misfolded proteins and causing their accumulation buildup within the cell [85].
\nThe β‐amyloid accumulation attracts immune system cells such as astrocytes, activated microglia, and macrophages, among others. Glial cells maintain the loss of regulation of the inflammatory response, the inflammation, and the oxidative stress state, creating a vicious cycle that is maintained in time [86].
\nWhen the levels of the intracellular β‐amyloid peptide decrease, the internalization of APP is induced. The internalization is mediated by the low density lipoprotein receptor‐related protein 1B (LRP1B), one of the members of the LDL family. This receptor usually binds APP to the plasmatic membrane to prevent the internalization of the β‐amyloid peptide, reducing its production [87]. The failure of these mechanisms by the effect of oxidative stress and the hyperphosphorylation of tau protein induced a disturbance in the formation of microtubules, producing neurofibrillary tangles [88]. Furthermore, tau protein associates with β‐amyloids that might be involved in the internalization of the extracellular protein into the neurons. This produces and externalizes the insoluble isoform of β‐amyloid [89]. During this phase, the synthesis of soluble β‐amyloid is decreased while the synthesis of misfolded insoluble β‐amyloids is increased. It forms part of the insoluble β‐amyloid plaques [90].
\nFinally, our laboratory has developed a noninvasive model of oxidative stress using the exposure to low doses of ozone to that effect. Using this model, we have proven that oxidative stress per se is capable of producing progressive neurodegeneration in the hippocampus together with the formation of insoluble β‐amyloid 1‐42 and the accumulation of such peptides.
\nThe loss of redox homeostasis accelerates ageing and plays a fundamental role in the pathogeny and development of Alzheimer\'s disease. It alters the cell signaling mechanisms of an important number of metabolic pathways, promotes epigenetic alterations, and alters the posttranslational mechanisms. Finally, the chronic alteration of the redox balance induces the misfolding of proteins by oxidative stress in ER, cholesterol oxidation, and alterations in insulin receptors that lead to changes in neuronal metabolism and survival.
\nWe can infer that Alzheimer\'s disease is the final manifestation of a series of oxidative alterations of the metabolism. There is a slow involvement of different biomolecules during the development of the disease. The loss of redox balance plays a crucial role in the formation of hyperphosphorylated tau protein, insoluble β‐amyloids, and the loss of regulation of the immune system.
\nThis work was supported by CONACYT under grant 219703 to S. R‐A.
\nMicroRNAs or miRNAs are a class of small non-coding RNA approximately 21–25 nucleotides that modulate on gene expression post-transcriptionally via binding to the 3′ untranslated region (3′-UTR) of the target messenger RNA (mRNA), resulting in mRNA degradation or translational repression. The first miRNA, lin-4, was discovered by Ambro and his research group in 1993 and it was found to be related with larva development in
miRNAs are normally transcribed by RNA polymerase II from miRNA genes. This transcription leads to generate a primary miRNA transcript (pri-miRNA). Then, pri-miRNA is further cleaved by a microprocessor complex, which consists of Drosha, the double-stranded RNase III enzyme and DiGeorge syndrome critical region 8 (DGCR8), important cofactor, into a hairpin structure precursor miRNA (pre-miRNA) in the nucleus (Figure 1). The double strand pre-miRNAs with 70 nucleotides are then exported to the cytoplasm by the process of nuclear export factor exportin-5. The pre-miRNA is then processed by RNase III, Dicer, thereby generating a mature miRNA:miRNA duplex approximately 22 nucleotides in length and without a hairpin structure. The helicase enzyme cleaves miRNA duplexes into single-stranded miRNAs and incorporated into the Argonaute (AGO), TRBP and PACT proteins to form the RNA-induced silencing complex (RISC). Usually, other single strand called passenger strand or the star (*) strand will be degraded, while single strand mature miRNA is able to bind with its target mRNA and mediating translational inhibition or mRNA degradation, along with their sequence complementarity to the target [1, 3]. In plants, target mRNA will be degraded if miRNA has perfect or near-perfect complementarity to its target. In contrast to mammal, miRNAs bind to partially complementary sites in the 3′-UTRs of target mRNA, which leading to translational repression [4]. the target mRNA is either blocked (imperfect complementary) or degraded (perfect complementary) of the ribosomal translation, which sequentially impacts the cellular functions.
miRNA biogenesis. miRNA gene is transcribed by RNA polymerase II and then forming the primary miRNA transcript (pri-miRNA), which is further cleaved by the Drosha/DGCR8 complex to generate the precursor miRNA (pre-miRNA). Pre-miRNA is then exported into the cytoplasm by exportin 5/RAN-GTP and further processed by dicer to create the mature miRNA, which is loaded into RISC, which contains AGO, PACT and TRBP proteins. Mature miRNA that binding to its target mRNA by perfect complementary binding and resulting in gene suppression by mRNA degradation. The partially complementary binding of miRNA and its target mRNA, which in turn inhibit the protein translation.
Phytochemicals are major plant-derived compounds that naturally found in vegetables, fruits, medicinal plants or other plants with medicinal properties including antioxidant, anti-diabetic, anti-inflammatory, antimicrobial, antidepressant, anticancer and prevention in other chronic non-communicable diseases [5, 6, 7]. Phenolic and flavonoid compounds are the most important group of bioactive compounds and second metabolites in plants which comprise of essential molecules of human diet [6, 8]. It has been shown that bioactive compounds can modulate the endogenous miRNAs expression [1, 9, 10, 11, 12]. Recently, some studies have revealed that plant-derived miRNAs (dietary miRNAs) as new bioactive compounds in plants can affect the synthesis of endogenous miRNAs [13, 14, 15]. Strikingly, miRNAs do not function only their origins but they are able to regulate the gene expression in cross-kingdom. Therefore, bioactive compounds present in functional foods are potentially regulate endogenous miRNAs expression.
Extensive studies have been performed to understand the molecular mechanism of bioactive compounds with a positive effect on chronic diseases or non-communicable diseases such as arthritis, cancer, cardiovascular diseases, diabetes and obesity [1, 16]. Emerging evidences confirm that alteration of endogenous miRNAs expression can be influenced by bioactive compounds in functional foods [16, 17] (Figure 2 and Table 1).
Influences of bioactive compounds and dietary miRNAs on human non-communicable diseases. Ascending arrows represent up-regulated miRNAs and descending arrows represent down-regulated miRNAs by bioactive compounds. The green triangles show the positive impact of dietary miRNAs on human health.
Dietary compound | miRNA expression | Target of miRNA | Diseases | References | |
---|---|---|---|---|---|
Up-regulation | Down-regulation | ||||
Acetyl-11-Keto-β-Boswellic Acid | miR-27a miR-34a | Unknown | Colorectal cancer | [23] | |
miR-155 | SOCS-1 | Neuroinflammation | [21] | ||
miR-206 | ER-α | Breast cancer | [22] | ||
Arctigenin | miR-16 miR-199a | Unknown | Neuroinflammation | [28] | |
miR-21 miR-19b miR-148a | Unknown | Prostate cancer | [29] | ||
Cinnamic acid derivatives | miR-143 | MAPK/Erk5 | Colon cancer | [31] | |
miR-145 | Unknown | Gastric cancer | [33] | ||
Curcumin | miR-15a, miR-16, miR-34a, miR-146b-5p miR-181b | miR-19a miR-19b | Unknown | Breast cancer | [38] |
miR-101, miR-200b, miR-200c, miR-141 miR-429 | miR-21 | Unknown | Colorectal cancer | [39, 40] | |
miR-21 | Gastric cancer | [41] | |||
miR-145 miR-1275 miR-1908 miR-3127 miR-3178 miR-3198 | miR-23b*, miR-183 miR-193b* miR-210 miR-222* miR-494 miR-664* miR-671-5p | Oct4 | Prostate cancer | [42] | |
miR-181b | CXCL1 CXCL2 | Breast cancer | [43] | ||
miR-378 | p38 | glioblastoma | [44] | ||
miR-124 miR-155 | Unknown | Neurodegenerative disorder | [45] | ||
3,3′-Diindolyl-methane | let-7 miR-34a miR-150-5p | EZH2, Notch1 AR Ahr | Prostate cancer | [46] | |
miR-200 | FoxM1 | Breast cancer | [47] | ||
miR-212/132 cluster miR-21 | Sox4 Cdc25A | Breast cancer | [48, 49] | ||
let-7b, let-7c, let-7d, let-7e, and miR-200b/c | ZEB-1, E-cadherin | Pancreatic cancer | [50] | ||
miR-146a | Unknown | Pancreatic cancer | [51] | ||
(−)-Epigallocatechin-3-Gallate | miR-296 | STAT3 | Nasopharyngeal carcinoma | [57] | |
let-7a miR34a | c-Myc | Hepatocellular carcinoma | [58] | ||
miR-34a | miR-93 | Unknown | Prostate cancer | [59] | |
miR-29 miR-210 | miR-125b miR-203 | Unknown | Cervical cancer | [60] | |
let-7 | HMGA2 | Melanoma cell | [61] | ||
miR-384 | Beclin-1 | Myocardial ischemia/ reperfusion | [62] | ||
miR-140-3p | Unknown | Osteoarthritis | [63] | ||
miR-10b miR-181a miR-221 | Unknown | Liver fibrosis | [64] | ||
Genistein | miR-23b | Unknown | Breast cancer | [66] | |
miR-1260b | sRRP1 Smad4 | Prostate cancer | [67] | ||
miR-1260b | sFRP1, Dkk2, Smad4 | Renal cancer | [68] | ||
miR-27a | Unknown | Lung cancer | [69] | ||
miR-29b | Unknown | Lung cancer | [70] | ||
miR-451 | Unknown | Chronic liver disease | [72] | ||
Quercetin | miR-200b-3p | Notch1 | Pancreatic cancer | [75] | |
miR-146a | EGFR | Breast cancer | [76] | ||
miR-16 | HOXA10 | Oral cancer | [77] | ||
miR-22 | WNT1/β-catenin | Oral cancer | [78] | ||
miR-97 miR-298 miR-2218 miR-1502 miR-2117 | Unknown | Oxidative stress in pheochromocytoma | [79] | ||
miR-503-5p miR-1283, miR-3714 miR-6867-5p | CCND1 | Endometriosis | [80] | ||
miR-122 | miR-21 | Unknown | Liver fibrosis | [81] | |
miR-199 | Sert1 | Hypoxia | [82] | ||
Silymarin | miR-203 | class 1 HDAC proteins and ZEB1 | Lung cancer | [84] | |
miR-155 | Unknown | Rheumatoid arthritis | [85] | ||
miR-122 | Unknown | Liver damage | [86] | ||
miR-122 miR-192 miR-194 | Unknown | Liver damage | [87] | ||
β-Sitosterol-d-glucoside | miR-10a | Unknown | Breast cancer | [89] | |
Sulforaphane | miR-23b miR-92b miR-381 miR-382 | Unknown | Breast cancer | [92] | |
miR-616-5p | GSK3β/β-catenin | Lung cancer | [93] | ||
miR-135b-5p | miR-30a-3p | RASAL2 Cx43 | Pancreatic cancer | [94] | |
miR-200c | Unknown | Oral cancer | [96] | ||
miR-9 miR-326 | Unknown | Gastric cancer | [97] | ||
miR-124-3p | STAT3 | Nasopharyngeal cancer | [98] | ||
miR-423-5p | Unknown | Liver fibrosis | [99] | ||
miR-155 | Unknown | Neuroinflammation | [100] |
Summary of miRNAs bioactive compounds and miRNAs expression in human pathology.
3-acetyl-11-keto- β -boswellic acid (AKBA) is pentacyclic triterpene acids that mainly found in
Arctigenin (AR) is a phenylpropanoid dizbenzylbutyrolactone lignin and was first identified in
Cinnamic acid derivatives can occur naturally in plants and their structure composing of benzene ring and acrylic acid group. Several compounds of cinnamic acid derivatives have been identified including artepilin C, baccharin, drupanin, ferulic acid, curcumin, caffeic acid, p-hydroxycinnamic acid, coumaric and chlorogenic acids, etc. [30, 31]. Medicinal activities of cinnamic acid derivatives have been reported such as anti-inflammatory, anti-oxidant, anti-viral, anti-microbial, anti-diabetic, neuroprotective and anti-tumor activities [30, 31, 32]. Cinnamic acid derivatives from propolis significantly induced colon cancer cell apoptosis through TRAIL/DR4/5 and/or FasL/Fas death-signaling pathways and via the upregulated miR-143 expression, resulting in decreased the target gene MAPK/Erk5 expression and its downstream target c-Myc [31]. Moreover, Li et al. demonstrated that cinnamic acid derivatives decreased gastric cancer cell proliferation through the up-regulation of miR-145 and down-regulation P13K/Akt signaling pathway [33]. Therefore, cinnamic acid derivatives have a potential as therapeutic agents for cancer.
Curcumin[(1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptane-3,5-dione] is well known as natural polyphenol and derived from the rhizome of turmeric or
3,3′-diindolylmethane (DIM) is a naturally active compound found in stomach, which derived from indole-3-carbinol (I3C) that present in cruciferous vegetables. DIM has been reported to regulate several miRNAs expression in cancer. Tumor suppressor miRNAs was upregulated by DIM in prostate cancer cells including let-7, miR-34a and miR-150-5p by targeting EZH2, Notch1 and AR and Ahr, respectively [46]. DIM also upregulated tumor suppressor miR-200, which led to inhibit the expression of FoxM1 in breast cancer cells [47]. miR-212/132 cluster and miR-21 were upregulated by DIM, which downregulated the expression of Sox4 and Cdc25A, respectively in breast cancer [48, 49]. Moreover, DIM upregulated let-7b, let-7c, let-7d, let-7e, and miR-200b/c expression, which led to inhibit the expression of ZEB-1, E-cadherin in pancreatic cancer cells [50]. It has been reported miR-146a was upregulated upon treated with DIM and suppressed the expression of MTA2, NF-κB, IRAK1, EGFR in pancreatic cancer cells [51].
DIM showed the modulation of miRNAs expression in other inflammatory diseases. The expression of miR-106a, miR-20b, and miR-125b-5p were increased after treatment with DIM and suppressed the expression of IRAK4 and TNF-α to limit responses to TLRs activated by LPS in acute liver failure (ALF) animal model [52]. DIM significantly upregulated miR-200c, miR-146a, miR-16, miR-93, and miR-22 in brain CD4+ T cells and inhibited the expression of cyclin E1 and B-cell lymphoma-2 in experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis [53].
(−)-Epigallocatechin-3-Gallate or EGCG is a major polyphenol compound in green tea (
EGCG showed the protective effect against myocardial ischemia/reperfusion (I/R) injury through up-regulation of miR-384-mediated autophagy by targeting Beclin-1 via activating the PI3K/Akt signaling pathway [62]. EGCG also demonstrated the anti-arthritic effects by inhibited IL-1β-induced ADAMTS5 expression and up-regulated the expression of miR-140-3p in osteoarthritis chondrocytes [63]. EGCG treatment has potential role of preventing toxin-induced fibrosis by suppression of osteopontin expression and up-regulation of miR-10b, miR-181a and miR-221 in liver hepatocellular carcinoma cells [64].
Genistein belongs to isoflavone family and presents in soybeans with antiangiogenic, anti-metastasis, anti-inflammatory, anti-oxidant, cell cycle arrest and induction of apoptosis effects [65]. Genistein can regulate the expression of miRNAs in several call types [65]. It has been reported that treatment of genistein up-regulated miR-23b and inhibited breast cancer cell growth [66]. Genistein also exhibited anti-tumor effect by down-regulated miR-1260b and targeting sRRP1 and Smad4 through DNA methylation or histone modifications in prostate cancer cells [67]. The same research group reported that miR-1260b was highly expressed in renal cancer cells and miR-1260b was down-regulated in genistein treated renal cancer cells [68]. The treatment of miR-1260b inhibitor inhibited the expression of its target genes, sFRP1, Dkk2, Smad4 [68]. Treatment with genistein induced non-small lung cancer cell apoptosis, caspase-3/9 activation and inhibited cell proliferation via up-regulation of miR-27a -mediated MET signaling [69]. Co-encapsulate miR-29b with genistein in hybrid nanoparticles (GMLHN) has been studied to treat effectively in non-small lung cancer cell and GMLHN showed the anti-proliferative effect by down-regulation of phosphorylated AKT (pAKT) and phosphorylated phosphoinositide-3 kinase (p-PI3K) [70].
Genistein promoted myoblast proliferation and differentiation through down-regulated miR-222 expression, resulting in increased expression of its target genes, MyoG, MyoD, and ERα [71]. Interestingly, genistein up-regulated miR-451 expression and inhibited IL1β expression and inflammation in chronic liver disease nonalcoholic steatohepatitis (NASH) mice model [72].
Quercetin is bioactive flavonoids that can be found in fruits and vegetables including onion, kale, apple, many berries, citrus fruits and tea [73]. Anti-cancer, anti-inflammatory, antioxidant, anti-diabetes, anti-atherosclerosis and anti-viral effects have been reported in different in vitro studies for quercetin [74]. Several studies have focused on quercetin and miRNAs modulation for therapeutic approaches. miR-200b-3p was up-regulated in pancreatic cancer cells when treated with quercetin, resulting in inhibition of self-renewal and decrease of proliferation through Notch1 signaling pathway [75]. Quercetin significantly inhibited breast cancer cell proliferation and invasion via up-regulated miR-146a expression and targeting EGFR [76]. Quercetin inhibited cell viability, migration and invasion by up-regulated miR-16 and targeting HOXA10 in oral cancer cells [77]. In addition, quercetin decreased oral cancer cell viability and increased cell apoptosis via miR-22/WNT1/β-catenin pathway [78].
Recently, quercetin modulated 34 miRNAs expression (5 upregulated and 29 downregulated) and novel miR-97, miR-298, miR-2218, miR-1502, and miR-2117 were identified in pheochromocytoma of the rat adrenal medulla that responded for protective effect against oxidative stress through PI3K-AKT signaling pathway [79]. Treatment of quercetin inhibited proliferation of endometriosis through up-regulated miR-503-5p, miR-1283, miR-3714 and miR-6867-5p by targeting CCND1 [80]. TGFβ1 is a fibrosis inducer and quercetin significantly down-regulated miR-21 and TGFβ1 and up-regulated miR-122 in liver fibrosis [81]. Protection of cardiomyocyte against hypoxia caused insults of quercetin has been reported by up-regulation of miR-199 mediated sirt1 expression and AMPK phosphorylation [82].
Silymarin is a flavonolignans extracted from the milk thistle
β-Sitosterol-d-glucoside is bioactive compounds that has been isolated from
Sulforaphane is dietary compounds in broccoli (
Sulforaphane has potential to inhibit hepatic fibrosis by downregulating miR-423-5p in hepatic stellate cell [99]. Sulforaphane showed the protective effect in microglia-mediated neurotoxicity by inhibited LPS-induced expression of inflammatory miRNA, miR-155 [100].
Several evidences demonstrated the direct modulation of cellular signaling pathways by dietary compounds could decrease the risk of chronic diseases [101]. Interestingly, it has been reported that small non-coding RNA including miRNAs can be transferred across Kingdoms, for example dietary miRNAs have been found in human body fluids and these circulating miRNAs are likely to regulate human gene expression [15, 102, 103, 104, 105, 106, 107]. The uptake of plant derived miRNAs could be in the form of raw and cooked plants in capable of stability forms [107, 108]. Due to high temperature cooking process, low pH and enzymes in digestive tract as well as enzymes in blood circulation, miRNAs might be destroyed before their functions with target mRNAs [15]. Strikingly, GC base content, 2’-O-methylation on the 3′-terminal, unique nucleotide sequence of dietary miRNAs and extracellular vesicles (exosome and microvesicle) are preventive features of plant derived miRNAs in harmful conditions [109, 110, 111, 112, 113, 114].
There are numerous studies to support the functional roles of dietary miRNAs in cross kingdom gene regulation. Rice miR156a and miR168a were detected in human serum and miR168a down-regulated low-density lipoprotein receptor adapter protein 1 (LDLRAP1) expression, resulted in an increase of plasma LDL cholesterol level, Table 2 [105]. miR2910 from
Plants | Plant derived-miRNAs | Human target gene/ Disease | References |
---|---|---|---|
osa-miR156a osa-miR166a osa-miR168a | LDLRAP1 | [105] | |
peu-miR2910 | JAK–STAT pathway | [115] | |
14 miRNAs | Cancer (breast, lung and leukemia) | [116] | |
miR156 miR531 miR160 miR529b miR1118 | Ras-MAPK signaling pathway, Alzheimer disease, breast cancer, cardiomyopathy, HIV, lung cancer, several neurological disorders | [117] | |
miR14 | Rheumatoid arthritis | [120] | |
cabbage, spinach and lettuce | miR156a | Cardiovascular disease | [118] |
miR156-5p miR164-5p miR168-5p miR395-3p miR396-3p miR396-5p miR444-3p miR529-3p miR1846-3p miR2907-3p | Cancer, cardiovascular and neurodegenerative diseases | [119] |
Dietary miRNAs and human gene regulation.
The abundantly expressed miRNA in dietary green vegetable, miR156a which was detected in human serum and targeted the junction adhesion molecule-A (JAM-A) [118]. The JAM-A was up-regulated in atherosclerotic lesions from cardiovascular disease patients and miR156a could suppressed inflammatory cytokine-induced monocytes adhesion by targeting JAM-A [118]. The very recently report using a computational approach to predict the potential target of rice miRNAs including miR156-5p, miR164-5p, miR168-5p, miR395-3p, miR396-3p, miR396-5p, miR444-3p, miR529-3p, miR1846-3p, miR2907-3p, which can bind to the human mRNA [119]. Most of these target genes were associated with cancer, cardiovascular and neurodegenerative diseases [119]. miR14 derived from
It has been widely known that functional foods and their bioactive compounds have the capacity for human health benefits. To date, miRNAs have been shown a significant effect on gene expression and modulate the cellular biological functions in physiological and pathological conditions. There is emerging evidence suggesting that dietary bioactive compounds can be effective in human diseases as a result of altering miRNAs expression levels, resulting in modulation of cellular signaling pathway. Additional research the possibility of bioactive compounds for developing as novel drugs with less side effects is required
This study has been supported by University of Phayao Research Grant (Grant no. FF64-RIM037) and School of Medical Sciences Research Grant (Grant no. MS 632001), University of Phayao.
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On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. 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Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,annualVolume:11411,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. 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He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. 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He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. 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He has both an MS and Ph.D. in Biomedical Engineering. He was previously a research scientist at the University of California Los Angeles (UCLA) and visiting professor and researcher at the University of North Dakota. He is currently working in artificial intelligence and its applications in medical signal processing. In addition, he is using digital signal processing in medical imaging and speech processing. Dr. Asadpour has developed brain-computer interfacing algorithms and has published books, book chapters, and several journal and conference papers in this field and other areas of intelligent signal processing. 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Dr. Gaiceanu is a member of the National Council for Attesting Titles, Diplomas and Certificates, an expert of the Executive Agency for Higher Education, Research Funding, and a member of the Senate of the Dunarea de Jos University of Galati. He has been the head of the Integrated Energy Conversion Systems and Advanced Control of Complex Processes Research Center, Romania, since 2016. He has conducted several projects in power converter systems for electrical drives, power quality, PEM and SOFC fuel cell power converters for utilities, electric vehicles, and marine applications with the Department of Regulation and Control, SIEI S.pA. (2002–2004) and the Polytechnic University of Turin, Italy (2002–2004, 2006–2007). He is a member of the Institute of Electrical and Electronics Engineers (IEEE) and cofounder-member of the IEEE Power Electronics Romanian Chapter. He is a guest editor at Energies and an academic book editor for IntechOpen. He is also a member of the editorial boards of the Journal of Electrical Engineering, Electronics, Control and Computer Science and Sustainability. Dr. Gaiceanu has been General Chairman of the IEEE International Symposium on Electrical and Electronics Engineering in the last six editions.",institutionString:'"Dunarea de Jos" University of Galati',institution:{name:'"Dunarea de Jos" University of Galati',country:{name:"Romania"}}},{id:"4519",title:"Prof.",name:"Jaydip",middleName:null,surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4519/images/system/4519.jpeg",biography:"Jaydip Sen is associated with Praxis Business School, Kolkata, India, as a professor in the Department of Data Science. His research areas include security and privacy issues in computing and communication, intrusion detection systems, machine learning, deep learning, and artificial intelligence in the financial domain. 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He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:null},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). He leads the working group of experts representing Brazil in the Global Partnership on Artificial Intelligence (GPAI), on the theme \"AI and the Pandemic Response\".",institutionString:"Manufacturing and Technology Integrated Campus – SENAI CIMATEC",institution:null},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:"Polytechnic University of Timişoara",institution:{name:"Polytechnic University of Timişoara",country:{name:"Romania"}}},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:null},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"414880",title:"Dr.",name:"Maryam",middleName:null,surname:"Vatankhah",slug:"maryam-vatankhah",fullName:"Maryam Vatankhah",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Borough of Manhattan Community College",country:{name:"United States of America"}}},{id:"414879",title:"Prof.",name:"Mohammad-Reza",middleName:null,surname:"Akbarzadeh-Totonchi",slug:"mohammad-reza-akbarzadeh-totonchi",fullName:"Mohammad-Reza Akbarzadeh-Totonchi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ferdowsi University of Mashhad",country:{name:"Iran"}}},{id:"414878",title:"Prof.",name:"Reza",middleName:null,surname:"Fazel-Rezai",slug:"reza-fazel-rezai",fullName:"Reza Fazel-Rezai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"American Public University System",country:{name:"United States of America"}}},{id:"302698",title:"Dr.",name:"Yao",middleName:null,surname:"Shan",slug:"yao-shan",fullName:"Yao Shan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Dalian University of Technology",country:{name:"China"}}},{id:"125911",title:"Prof.",name:"Jia-Ching",middleName:null,surname:"Wang",slug:"jia-ching-wang",fullName:"Jia-Ching Wang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Central University",country:{name:"Taiwan"}}},{id:"357085",title:"Mr.",name:"P. Mohan",middleName:null,surname:"Anand",slug:"p.-mohan-anand",fullName:"P. Mohan Anand",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356696",title:"Ph.D. Student",name:"P.V.",middleName:null,surname:"Sai Charan",slug:"p.v.-sai-charan",fullName:"P.V. Sai Charan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"357086",title:"Prof.",name:"Sandeep K.",middleName:null,surname:"Shukla",slug:"sandeep-k.-shukla",fullName:"Sandeep K. Shukla",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356823",title:"MSc.",name:"Seonghee",middleName:null,surname:"Min",slug:"seonghee-min",fullName:"Seonghee Min",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Daegu University",country:{name:"Korea, South"}}},{id:"353307",title:"Prof.",name:"Yoosoo",middleName:null,surname:"Oh",slug:"yoosoo-oh",fullName:"Yoosoo Oh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:"Yoosoo Oh received his Bachelor's degree in the Department of Electronics and Engineering from Kyungpook National University in 2002. He obtained his Master’s degree in the Department of Information and Communications from Gwangju Institute of Science and Technology (GIST) in 2003. In 2010, he received his Ph.D. degree in the School of Information and Mechatronics from GIST. In the meantime, he was an executed team leader at Culture Technology Institute, GIST, 2010-2012. In 2011, he worked at Lancaster University, the UK as a visiting scholar. In September 2012, he joined Daegu University, where he is currently an associate professor in the School of ICT Conver, Daegu University. Also, he served as the Board of Directors of KSIIS since 2019, and HCI Korea since 2016. From 2017~2019, he worked as a center director of the Mixed Reality Convergence Research Center at Daegu University. From 2015-2017, He worked as a director in the Enterprise Supporting Office of LINC Project Group, Daegu University. His research interests include Activity Fusion & Reasoning, Machine Learning, Context-aware Middleware, Human-Computer Interaction, etc.",institutionString:null,institution:{name:"Daegu Gyeongbuk Institute of Science and Technology",country:{name:"Korea, South"}}},{id:"262719",title:"Dr.",name:"Esma",middleName:null,surname:"Ergüner Özkoç",slug:"esma-erguner-ozkoc",fullName:"Esma Ergüner Özkoç",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Başkent University",country:{name:"Turkey"}}},{id:"346530",title:"Dr.",name:"Ibrahim",middleName:null,surname:"Kaya",slug:"ibrahim-kaya",fullName:"Ibrahim Kaya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"419199",title:"Dr.",name:"Qun",middleName:null,surname:"Yang",slug:"qun-yang",fullName:"Qun Yang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Auckland",country:{name:"New Zealand"}}}]}},subseries:{item:{id:"22",type:"subseries",title:"Applied Intelligence",keywords:"Machine Learning, Intelligence Algorithms, Data Science, Artificial Intelligence, Applications on Applied Intelligence",scope:"This field is the key in the current industrial revolution (Industry 4.0), where the new models and developments are based on the knowledge generation on applied intelligence. The motor of the society is the industry and the research of this topic has to be empowered in order to increase and improve the quality of our lives.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/22.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11418,editor:{id:"27170",title:"Prof.",name:"Carlos",middleName:"M.",surname:"Travieso-Gonzalez",slug:"carlos-travieso-gonzalez",fullName:"Carlos Travieso-Gonzalez",profilePictureURL:"https://mts.intechopen.com/storage/users/27170/images/system/27170.jpeg",biography:"Carlos M. Travieso-González received his MSc degree in Telecommunication Engineering at Polytechnic University of Catalonia (UPC), Spain in 1997, and his Ph.D. degree in 2002 at the University of Las Palmas de Gran Canaria (ULPGC-Spain). He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). 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This topic will closely deal with all emerging trends in this discipline.",annualVolume:11411,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null,editorialBoard:[{id:"241413",title:"Dr.",name:"Azhar",middleName:null,surname:"Rasul",fullName:"Azhar Rasul",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRT1oQAG/Profile_Picture_1635251978933",institutionString:null,institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",fullName:"Sergey Sedykh",profilePictureURL:"https://mts.intechopen.com/storage/users/178316/images/system/178316.jfif",institutionString:null,institution:{name:"Novosibirsk State University",institutionURL:null,country:{name:"Russia"}}}]},{id:"17",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",annualVolume:11413,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",fullName:"Anca Pantea Stoian",profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"203824",title:"Dr.",name:"Attilio",middleName:null,surname:"Rigotti",fullName:"Attilio Rigotti",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"Pontifical Catholic University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"300470",title:"Dr.",name:"Yanfei (Jacob)",middleName:null,surname:"Qi",fullName:"Yanfei (Jacob) Qi",profilePictureURL:"https://mts.intechopen.com/storage/users/300470/images/system/300470.jpg",institutionString:null,institution:{name:"Centenary Institute of Cancer Medicine and Cell Biology",institutionURL:null,country:{name:"Australia"}}}]},{id:"18",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",annualVolume:11414,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life Sciences",institutionURL:null,country:{name:"Indonesia"}}},{id:"40928",title:"Dr.",name:"Cesar",middleName:null,surname:"Lopez-Camarillo",fullName:"Cesar Lopez-Camarillo",profilePictureURL:"https://mts.intechopen.com/storage/users/40928/images/3884_n.png",institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",institutionURL:null,country:{name:"Mexico"}}},{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",fullName:"Shymaa Enany",profilePictureURL:"https://mts.intechopen.com/storage/users/81926/images/system/81926.png",institutionString:"Suez Canal University",institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/100305",hash:"",query:{},params:{id:"100305"},fullPath:"/profiles/100305",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)}()