Graphene quantum dots for cancer-targeted drug delivery.
\\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
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"5540",leadTitle:null,fullTitle:"Enzyme Inhibitors and Activators",title:"Enzyme Inhibitors and Activators",subtitle:null,reviewType:"peer-reviewed",abstract:"Over the recent years, medicinal chemistry has become responsible for explaining interactions of chemical molecule processes such that many scientists in the life sciences from agronomy to medicine are engaged in medicinal research. This book contains an overview focusing on the research area of enzyme inhibitor and activator, enzyme-catalyzed biotransformation, usage of microbial enzymes, enzymes associated with programmed cell death, natural products as potential enzyme inhibitors, protease inhibitors from plants in insect pest management, peptidases, and renin-angiotensin system. The book provides an overview on basic issues and some of the recent developments in medicinal science and technology. Especially, emphasis is devoted to both experimental and theoretical aspect of modern medicine. The primary target audience for the book includes students, researchers, chemists, molecular biologists, medical doctors, pharmacologists, and professionals who are interested in associated areas. The textbook is written by international scientists with expertise in biochemistry, enzymology, molecular biology, and genetics, many of which are active in biochemical and pharmacological research. I would like to acknowledge the authors for their contribution to the book. We hope that the textbook will enhance the knowledge of scientists in the complexities of some medical approaches; it will stimulate both professionals and students to dedicate part of their future research in understanding relevant mechanisms and applications of pharmacology.",isbn:"978-953-51-3058-1",printIsbn:"978-953-51-3057-4",pdfIsbn:"978-953-51-4887-6",doi:"10.5772/63325",price:119,priceEur:129,priceUsd:155,slug:"enzyme-inhibitors-and-activators",numberOfPages:268,isOpenForSubmission:!1,isInWos:1,isInBkci:!1,hash:"5f1fa8db9cc4553ea23e011e520e689c",bookSignature:"Murat Senturk",publishedDate:"March 29th 2017",coverURL:"https://cdn.intechopen.com/books/images_new/5540.jpg",numberOfDownloads:32020,numberOfWosCitations:98,numberOfCrossrefCitations:72,numberOfCrossrefCitationsByBook:1,numberOfDimensionsCitations:181,numberOfDimensionsCitationsByBook:1,hasAltmetrics:1,numberOfTotalCitations:351,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 19th 2016",dateEndSecondStepPublish:"June 9th 2016",dateEndThirdStepPublish:"September 5th 2016",dateEndFourthStepPublish:"November 4th 2016",dateEndFifthStepPublish:"December 4th 2016",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"14794",title:"Prof.",name:"Murat",middleName:null,surname:"Şentürk",slug:"murat-senturk",fullName:"Murat Şentürk",profilePictureURL:"https://mts.intechopen.com/storage/users/14794/images/system/14794.jpeg",biography:"Dr. Murat Şentürk obtained a baccalaureate degree in Chemistry in 2002, a master’s degree in Biochemistry in 2006, and a doctorate degree in Biochemistry in 2009 from Atatürk University, Turkey. Dr. Şentürk currently works as an professor of Biochemistry in the Department of Basic Pharmacy Sciences, Faculty of Pharmacy, Ağri Ibrahim Cecen University, Turkey. \nDr. Şentürk published over 120 scientific papers, reviews, and book chapters and presented several conferences to scientists. \nHis research interests span enzyme inhibitor or activator, protein expression, purification and characterization, drug design and synthesis, toxicology, and pharmacology. \nHis research work has focused on neurodegenerative diseases and cancer treatment. Dr. Şentürk serves as the editorial board member of several international journals.",institutionString:"Ağrı İbrahim Çeçen University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Ağrı İbrahim Çeçen University",institutionURL:null,country:{name:"Turkey"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"393",title:"Applied Microbiology",slug:"biochemistry-genetics-and-molecular-biology-enzymology-applied-microbiology"}],chapters:[{id:"52854",title:"Peptidases and the Renin-Angiotensin System: The Alternative Angiotensin-(1-7) Cascade",doi:"10.5772/65949",slug:"peptidases-and-the-renin-angiotensin-system-the-alternative-angiotensin-1-7-cascade",totalDownloads:1787,totalCrossrefCites:3,totalDimensionsCites:4,hasAltmetrics:1,abstract:"The renin-angiotensin system (RAS) constitutes a key hormonal system in the physiological regulation of blood pressure via peripheral and central mechanisms. Dysregulation of the RAS is considered a major factor in the development of cardiovascular pathologies, and pharmacologic blockades of this system by the inhibition of angiotensin-converting enzyme (ACE) or antagonism of the angiotensin type 1 receptor (AT1R) are effective therapeutic regimens. The RAS is now defined as a system composed of different angiotensin peptides with diverse biological actions mediated by distinct receptor subtypes. The classic RAS comprises the ACE-Ang II-AT1R axis that promotes vasoconstriction, water intake, sodium retention and increased oxidative stress, fibrosis, cellular growth, and inflammation. The nonclassical or alternative RAS is composed primarily of the ACE2-Ang-(1-7)-AT7R pathway that opposes the Ang II-AT1R axis. In lieu of the complex aspects of this system, the current review assesses the enzymatic cascade of the alternative Ang-(1-7) axis of the RAS.",signatures:"Nildris Cruz-Diaz, Bryan A. Wilson and Mark C. Chappell",downloadPdfUrl:"/chapter/pdf-download/52854",previewPdfUrl:"/chapter/pdf-preview/52854",authors:[{id:"120145",title:"Dr.",name:"Brian",surname:"Rybarczyk",slug:"brian-rybarczyk",fullName:"Brian Rybarczyk"},{id:"191435",title:"Prof.",name:"Mark",surname:"Chappell",slug:"mark-chappell",fullName:"Mark Chappell"},{id:"195179",title:"Dr.",name:"Nildris",surname:"Cruz-Diaz",slug:"nildris-cruz-diaz",fullName:"Nildris Cruz-Diaz"}],corrections:null},{id:"52789",title:"Programmed Cell Death-Related Proteases in Plants",doi:"10.5772/65938",slug:"programmed-cell-death-related-proteases-in-plants",totalDownloads:1712,totalCrossrefCites:2,totalDimensionsCites:8,hasAltmetrics:0,abstract:"From an ancient Greek term related to the “leavening of bread” (en, in; zyme, leaven), an enzyme can be defined as a substance showing the properties of a catalyst that is produced as a result of cellular activity. Every proteinaceous enzyme that performs hydrolysis of peptide bonds is appropriately termed “protease” (peptidase). All of them share aspects of catalytic strategy, but with some variation. As a result, the proteases are grouped into six different catalytic families: serine, threonine, cysteine, aspartic, glutamic and metallopeptidases (http://merops.sanger.ac.uk/). The larger families (cysteine, serine, aspartic and metallopeptidases) have a wide range of distribution on living organism groups, and are also present in the “controversial” viruses. As a well‐represented family, the cysteine proteases play important roles in events such as signalling pathways, programmed cell death (PCD), nutrient mobilization, protein maturing, hormone synthesis and degradation. In the past two decades, an increased interest was driven to the study of the programmed cell death (PCD), mainly after the discovery of caspase‐related proteins and caspase‐like activities in organisms not metazoan. Caspases are cysteine proteases that cleave their substrate after aspartate residues and are part of signalling cascades of the apoptotic PCD process (also in inflammatory process), unique of metazoan. The caspase‐related proteins are named paracaspases and metacaspases. Paracaspases are found on metazoan and Dictyostelium, whereas the metacaspases are present on plants, fungi and groups of protozoan. On plants, PCD has features that are distinct from that of animals and is an important pathway on developmental events, defensive and stress response (biotic and abiotic). All these events have their own particularities, but the participation of proteases seems to be universal with those responsible for caspase‐like activities and metacaspases having an increasing number of reports that put them as important for plant PCD. In this chapter, we tackle important aspects of the proteases, in special that involved in plant PDC, as well as their specific regulators. Aspects of function, catalytic mechanisms and interaction with ligands will be on focus.",signatures:"Gustavo Lemos Rocha, Jorge Hernandez Fernandez, Antônia Elenir\nAmâncio Oliveira and Kátia Valevski Sales Fernandes",downloadPdfUrl:"/chapter/pdf-download/52789",previewPdfUrl:"/chapter/pdf-preview/52789",authors:[{id:"193467",title:"Ph.D.",name:"Katia",surname:"Fernandes",slug:"katia-fernandes",fullName:"Katia Fernandes"},{id:"193476",title:"Dr.",name:"Jorge H.",surname:"Fernandez",slug:"jorge-h.-fernandez",fullName:"Jorge H. Fernandez"},{id:"193477",title:"MSc.",name:"Gustavo L.",surname:"Rocha",slug:"gustavo-l.-rocha",fullName:"Gustavo L. Rocha"},{id:"193478",title:"Dr.",name:"Antonia E.A.",surname:"Oliveira",slug:"antonia-e.a.-oliveira",fullName:"Antonia E.A. Oliveira"}],corrections:null},{id:"53230",title:"Effect of High-Pressure Technologies on Enzymes Applied in Food Processing",doi:"10.5772/66629",slug:"effect-of-high-pressure-technologies-on-enzymes-applied-in-food-processing",totalDownloads:2069,totalCrossrefCites:5,totalDimensionsCites:7,hasAltmetrics:0,abstract:"High isostatic pressure (HIP) and high-pressure homogenization (HPH) are considered important physical technologies that able to induce changes on enzymes. HIP and HPH are emerging food processing technologies that involve the use of ultra high pressures (up to 1200 MPa for HIP and up to 400 MPa for HPH), where the first process is based on the principle that the maintenance of a product inside vessels at high pressures induces changes in the molecules conformation and, consequently, in the functionality of polysaccharides, proteins and enzymes. To the contrary, for HPH process, the high shear and sudden pressure drop are the responsible phenomena for the changes on the processed product. This chapter aims to evaluate comparatively the effects of HIP and HPH on the activity of enzymes currently applied in food industry and to identify the main structural changes induced by each process. The overall evaluation of the results shows that mild conditions of both processes were recently highlighted as able to improve the activity and the stability of several enzymes, whereas extreme process conditions (pressure, time and temperature) induce enzyme denaturation with consequent reduction of biological activity. Considering the complexity and diversity involved in the enzyme structure and its ability to react, it is not possible to determine specific conditions that each process is able to promote increase or reduction of enzyme activity, being necessary to evaluate HIP and HPH for each enzyme. Finally, in terms of molecular structure, the effect of HIP and HPH on enzymes can be explained by the alterations in the quaternary, tertiary and secondary structures of enzymes, which directly affects its active site configuration.",signatures:"Bruno Ricardo de Castro Leite Júnior, Alline Artigiani Lima Tribst\nand Marcelo Cristianini",downloadPdfUrl:"/chapter/pdf-download/53230",previewPdfUrl:"/chapter/pdf-preview/53230",authors:[{id:"178295",title:"Dr.",name:"Bruno Ricardo",surname:"Leite Júnior",slug:"bruno-ricardo-leite-junior",fullName:"Bruno Ricardo Leite Júnior"},{id:"193474",title:"Prof.",name:"Alline Artigiani Lima",surname:"Tribst",slug:"alline-artigiani-lima-tribst",fullName:"Alline Artigiani Lima Tribst"},{id:"193475",title:"Prof.",name:"Marcelo",surname:"Cristianini",slug:"marcelo-cristianini",fullName:"Marcelo Cristianini"}],corrections:null},{id:"54515",title:"Kinetic Modelling of Enzyme Catalyzed Biotransformation Involving Activations and Inhibitions",doi:"10.5772/67692",slug:"kinetic-modelling-of-enzyme-catalyzed-biotransformation-involving-activations-and-inhibitions",totalDownloads:4314,totalCrossrefCites:1,totalDimensionsCites:6,hasAltmetrics:0,abstract:"To achieve transition from lab scale enzyme studies to industrial applications, understanding of enzyme kinetics plays a critical role. The widely applied Michaelis Menten equation of the single substrate kinetics, sequential and double replacement mechanism of bisubstrate reaction and the relevant kinetics, inhibition and activation of enzyme are all integral parts of this discussion. In this chapter, we have discussed different types of inhibition and kinetic modelling. Systematic approach to generate data and its interpretation as well as designing of inhibitors is also explained.",signatures:"Ganapati D. Yadav and Deepali B. Magadum",downloadPdfUrl:"/chapter/pdf-download/54515",previewPdfUrl:"/chapter/pdf-preview/54515",authors:[{id:"49324",title:"Prof.",name:"Ganapati",surname:"Yadav",slug:"ganapati-yadav",fullName:"Ganapati Yadav"},{id:"193953",title:"Ms.",name:"Deepali",surname:"Magadum",slug:"deepali-magadum",fullName:"Deepali Magadum"}],corrections:null},{id:"52721",title:"Telomerase Inhibitors and Activators: Pharmaceutical Importance",doi:"10.5772/65933",slug:"telomerase-inhibitors-and-activators-pharmaceutical-importance",totalDownloads:2836,totalCrossrefCites:1,totalDimensionsCites:3,hasAltmetrics:1,abstract:"Telomeres are specialized functional complexes that protect the ends of eukaryotic chromosomes. The telomeric DNA sequences are tandem repeats of a short hexameric sequence unit. The inability to DNA polymerase to replicate the end of the chromosome during lagging strand synthesis results in the loss of telomeric repeats when cell divides. Telomere shortening provides a barrier to cancer progression and the majority of the cancer cells depend on the activation of telomerase to gain proliferative immortality. Thus, telomerase is a molecular target for diseases since its discovery. Telomerase inhibition enables more specific ground for cancer therapy because the telomerase is not detected in most normal tissues. Some of the synthetic and natural telomerase inhibitors were tried on various cancer cells and there was a decrease in the number of cancer cells. But on the other hand, telomere shortening correlates with cellular aging. Some evidence suggests that the progressive loss of telomeric repeats of chromosomes may function as a molecular clock that triggers senescence. Telomerase-related gene mutations also result in some diseases. Because of this, telomerase activators are important for antiaging and telomerase-dependent disease treatments. This chapter summarizes the pharmaceutical importance of telomeres, telomerase structure, telomerase activators, and inhibitors.",signatures:"Ayse Gul Mutlu",downloadPdfUrl:"/chapter/pdf-download/52721",previewPdfUrl:"/chapter/pdf-preview/52721",authors:[{id:"115828",title:"Dr.",name:"Ayse Gul",surname:"Mutlu",slug:"ayse-gul-mutlu",fullName:"Ayse Gul Mutlu"}],corrections:null},{id:"52798",title:"Effect of Metal Ions, Chemical Agents and Organic Compounds on Lignocellulolytic Enzymes Activities",doi:"10.5772/65934",slug:"effect-of-metal-ions-chemical-agents-and-organic-compounds-on-lignocellulolytic-enzymes-activities",totalDownloads:2774,totalCrossrefCites:14,totalDimensionsCites:46,hasAltmetrics:0,abstract:"Lignocellulolytic enzymes have been extensively studied due to their potential for industrial applications such as food, textile, pharmaceutical, paper, and, more recently, energy. The influence of metal ions, chemical agents, and organic compounds on these enzyme activities are addressed in this chapter, based on data available in the scientific literature.",signatures:"Josiani de Cassia Pereira, Ellen Cristine Giese, Marcia Maria de Souza\nMoretti, Ana Carolina dos Santos Gomes, Olavo Micali Perrone,\nMaurício Boscolo, Roberto da Silva, Eleni Gomes and Daniela\nAlonso Bocchini Martins",downloadPdfUrl:"/chapter/pdf-download/52798",previewPdfUrl:"/chapter/pdf-preview/52798",authors:[{id:"58745",title:"Prof.",name:"Eleni",surname:"Gomes",slug:"eleni-gomes",fullName:"Eleni Gomes"},{id:"126536",title:"Dr.",name:"Marcia Maria de Souza",surname:"Moretti",slug:"marcia-maria-de-souza-moretti",fullName:"Marcia Maria de Souza Moretti"},{id:"139595",title:"Dr.",name:"Ellen",surname:"Giese",slug:"ellen-giese",fullName:"Ellen Giese"},{id:"192443",title:"Ph.D. Student",name:"Josiani",surname:"De Cassia Pereira",slug:"josiani-de-cassia-pereira",fullName:"Josiani De Cassia Pereira"},{id:"193381",title:"MSc.",name:"Ana Carolina",surname:"Dos Santos Gomes",slug:"ana-carolina-dos-santos-gomes",fullName:"Ana Carolina Dos Santos Gomes"},{id:"193382",title:"Dr.",name:"Daniela",surname:"Alonso Bocchini Martins",slug:"daniela-alonso-bocchini-martins",fullName:"Daniela Alonso Bocchini Martins"},{id:"195332",title:"Dr.",name:"Olavo",surname:"Micali Perrone",slug:"olavo-micali-perrone",fullName:"Olavo Micali Perrone"}],corrections:null},{id:"54038",title:"Natural Products as a Potential Enzyme Inhibitors from Medicinal Plants",doi:"10.5772/67376",slug:"natural-products-as-a-potential-enzyme-inhibitors-from-medicinal-plants",totalDownloads:2498,totalCrossrefCites:13,totalDimensionsCites:44,hasAltmetrics:0,abstract:"Enzyme inhibitory agents are attractive because of their application in treating different ailments. The absence of enzymes produce a number of diseases. Medicinal plants are a rich source of producing secondary metabolites which showed broad-spectrum enzyme inhibitory potential. The position of enzyme inhibitors as new drugs is vast since these compounds have been used for the treatment of various physiological disorders. Bioactive secondary metabolites can deliver excellent pharmacophore patterns for drugs related to numerous illnesses. This book chapter is planned to document the enzyme inhibitory potential of natural compounds, medicinal plant extract, and its isolated compounds.",signatures:"Abdur Rauf and Noor Jehan",downloadPdfUrl:"/chapter/pdf-download/54038",previewPdfUrl:"/chapter/pdf-preview/54038",authors:[{id:"192295",title:"Dr.",name:"Abdur",surname:"Rauf",slug:"abdur-rauf",fullName:"Abdur Rauf"}],corrections:null},{id:"52729",title:"Microbial Glycosidases for Nondigestible Oligosaccharides Production",doi:"10.5772/65935",slug:"microbial-glycosidases-for-nondigestible-oligosaccharides-production",totalDownloads:1716,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"There is much interest in the study and production of nondigestible oligosaccharides (NDOs), due to their bioactivities and beneficial effects to the human health. The main approach in the production of NDOs relies on the action of glycosidases performing hydrolysis or transglycosylation of polysaccharides and sugars. In this chapter, a description of the main microbial glycosidases used for NDOs production, their sources, their principal properties, and a description of the production processes with the better results obtained are discussed.",signatures:"Thais Bezerra, Rubens Monti, Egon B. Hansen and Jonas Contiero",downloadPdfUrl:"/chapter/pdf-download/52729",previewPdfUrl:"/chapter/pdf-preview/52729",authors:[{id:"193454",title:"Prof.",name:"Jonas",surname:"Contiero",slug:"jonas-contiero",fullName:"Jonas Contiero"}],corrections:null},{id:"52877",title:"Inhibitors and Activators of SOD, GSH‐Px, and CAT",doi:"10.5772/65936",slug:"inhibitors-and-activators-of-sod-gsh-px-and-cat",totalDownloads:3683,totalCrossrefCites:18,totalDimensionsCites:42,hasAltmetrics:0,abstract:"Reactive oxygen species (ROS) is harmful to our health, and SOD, CAT, and GPX are the major antioxidant enzymes that defend us from effects of ROS. In medicine, food, and dairy industries, antioxidant enzymes often surround complex environments. For better utilization of these enzymes, the inhibitors (including competitive inhibitors and noncompetitive inhibitors) and activators of SOD, CAT, and GPX are descripted in detail in this chapter. Also, the structure and catalytic mechanism of these antioxidants are summarized.",signatures:"Xianyong Ma, Dun Deng and Weidong Chen",downloadPdfUrl:"/chapter/pdf-download/52877",previewPdfUrl:"/chapter/pdf-preview/52877",authors:[{id:"193346",title:"Prof.",name:"Xianyong",surname:"Ma",slug:"xianyong-ma",fullName:"Xianyong Ma"},{id:"193352",title:"Dr.",name:"Dun",surname:"Deng",slug:"dun-deng",fullName:"Dun Deng"}],corrections:null},{id:"54207",title:"Enzyme Dynamic in Plant Nutrition Uptake and Plant Nutrition",doi:"10.5772/66938",slug:"enzyme-dynamic-in-plant-nutrition-uptake-and-plant-nutrition",totalDownloads:2533,totalCrossrefCites:1,totalDimensionsCites:3,hasAltmetrics:1,abstract:"Soil contains enzymes, constantly interacting with soil constituents, e.g. minerals, rhizosphere and numerous nutrients. Enzymes, in turn, catalyse important biochemical reactions for rhizobacteria and plants, stabilize the soil by degrading wastes and mediate nutrient recycling.The available enzymes inside soil could originate from plants, animals or microbes. The enzymes that are produced from these organism could exhibit intracellular activities, at the cell membrane, interacting therefore with soil and its constituents, or extracellularly (so freely available). Therefore, vis-à-vis to plant nutrition, the (extra or sub) cellular localization has a key role. Typical major enzymes available in soil can be listed as dehydrogenases, hydrogenases, oxidases, catalases, peroxidases, phenol o-hydroxylase, dextransucrase, aminotransferase, rhodanese, carboxylesterase, lipase, phosphatase, nuclease, phytase, arylsulphatase, amylase, cellulase, inulase, xylanase, dextranase, levanase, poly-galacturonase, glucosidase, galactosidase, invertase, peptidase, asparaginase, glutaminase, amidase, urease, aspartate decarboxylase, glutamate decarboxylase and aromatic amino acid decarboxylase. An interesting strategy for improving the nutritional quality of the soil would be to inoculate microorganism to soil while giving attention to mineral or other compounds that affect enzyme activity in soil. Since, some elements or compounds could show both activation and inhibitory effect, such as Fe, Na, etc. metals, the regulation of their bioavailability is crucial.",signatures:"Metin Turan, Emrah Nikerel, Kerem Kaya, Nurgul Kitir, Adem Gunes,\nNegar Ebrahim Pour Mokhtari, Şefik Tüfenkçi, M. Rüştü Karaman\nand K. Mesut ÇİMRİN",downloadPdfUrl:"/chapter/pdf-download/54207",previewPdfUrl:"/chapter/pdf-preview/54207",authors:[{id:"140612",title:"Prof.",name:"Metin",surname:"Turan",slug:"metin-turan",fullName:"Metin Turan"},{id:"186637",title:"Dr.",name:"Nurgül",surname:"Kıtır",slug:"nurgul-kitir",fullName:"Nurgül Kıtır"},{id:"186638",title:"Dr.",name:"Emrah",surname:"Nikerel",slug:"emrah-nikerel",fullName:"Emrah Nikerel"},{id:"186643",title:"Dr.",name:"Adem",surname:"Güneş",slug:"adem-gunes",fullName:"Adem Güneş"},{id:"194478",title:"Dr.",name:"Leyla",surname:"Tarhan",slug:"leyla-tarhan",fullName:"Leyla Tarhan"},{id:"199306",title:"Dr.",name:"Bahar",surname:"Soğutmaz",slug:"bahar-sogutmaz",fullName:"Bahar Soğutmaz"},{id:"199307",title:"Dr.",name:"Negar Ebrahim Pour",surname:"Mokhtari",slug:"negar-ebrahim-pour-mokhtari",fullName:"Negar Ebrahim Pour Mokhtari"}],corrections:null},{id:"54390",title:"Enzyme Inhibitors and Activators",doi:"10.5772/67248",slug:"enzyme-inhibitors-and-activators",totalDownloads:6102,totalCrossrefCites:13,totalDimensionsCites:17,hasAltmetrics:0,abstract:"Enzymes are very effective biological catalysts that accelerate almost all metabolic reactions in living organisms. Enzyme inhibitors and activators that modulate the velocity of enzymatic reactions play an important role in the regulation of metabolism. Enzyme inhibitors are also useful tool for study of enzymatic reaction as well as for design of new medicine drugs. In this chapter, we focused on the properties of enzyme inhibitors and activators. Here we present canonical inhibitor classification based on their kinetic behavior and mechanism of action. We also considered enzyme inhibitors that were used for design of various types of pharmacological drugs and natural inhibitors as a plausible source for design of future drugs. Mechanisms of action of enzyme activators and some features of allosteric modulators are considered.",signatures:"Olga D. 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Cell Applications",slug:"graphene-supported-platinum-and-platinum-ruthenium-nanoparticles-for-fuel-cell-applications",signatures:"Lifeng Dong, Qianqian Liu, Li Wang and Kezheng Chen",authors:[{id:"15985",title:"Prof.",name:"Lifeng",middleName:null,surname:"Dong",fullName:"Lifeng Dong",slug:"lifeng-dong"},{id:"24405",title:"Ms.",name:"Qianqian",middleName:null,surname:"Liu",fullName:"Qianqian Liu",slug:"qianqian-liu"},{id:"24406",title:"Ms.",name:"Li",middleName:null,surname:"Wang",fullName:"Li Wang",slug:"li-wang"},{id:"24407",title:"Prof.",name:"Kezheng",middleName:null,surname:"Chen",fullName:"Kezheng Chen",slug:"kezheng-chen"}]}]}],publishedBooks:[{type:"book",id:"180",title:"Carbon Nanotubes",subtitle:"Growth and Applications",isOpenForSubmission:!1,hash:"32865140876c21193ac4e9b1f5d95d2d",slug:"carbon-nanotubes-growth-and-applications",bookSignature:"Dr. Mohammad Naraghi",coverURL:"https://cdn.intechopen.com/books/images_new/180.jpg",editedByType:"Edited by",editors:[{id:"67361",title:"Dr.",name:"Mohammad",surname:"Naraghi",slug:"mohammad-naraghi",fullName:"Mohammad Naraghi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"328",title:"Graphene Simulation",subtitle:null,isOpenForSubmission:!1,hash:"26044659f984fbaeac93a996ab1d4995",slug:"graphene-simulation",bookSignature:"Jian Ru Gong",coverURL:"https://cdn.intechopen.com/books/images_new/328.jpg",editedByType:"Edited by",editors:[{id:"61172",title:"Prof.",name:"Jian Ru",surname:"Gong",slug:"jian-ru-gong",fullName:"Jian Ru Gong"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"465",title:"Carbon Nanotubes",subtitle:"Applications on Electron Devices",isOpenForSubmission:!1,hash:null,slug:"carbon-nanotubes-applications-on-electron-devices",bookSignature:"Jose Mauricio 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Nanotubes",subtitle:"From Research to Applications",isOpenForSubmission:!1,hash:null,slug:"carbon-nanotubes-from-research-to-applications",bookSignature:"Stefano Bianco",coverURL:"https://cdn.intechopen.com/books/images_new/469.jpg",editedByType:"Edited by",editors:[{id:"32081",title:"Dr.",name:"Stefano",surname:"Bianco",slug:"stefano-bianco",fullName:"Stefano Bianco"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],publishedBooksByAuthor:[{type:"book",id:"469",title:"Carbon Nanotubes",subtitle:"From Research to Applications",isOpenForSubmission:!1,hash:null,slug:"carbon-nanotubes-from-research-to-applications",bookSignature:"Stefano Bianco",coverURL:"https://cdn.intechopen.com/books/images_new/469.jpg",editedByType:"Edited by",editors:[{id:"32081",title:"Dr.",name:"Stefano",surname:"Bianco",slug:"stefano-bianco",fullName:"Stefano Bianco"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},onlineFirst:{chapter:{type:"chapter",id:"81256",title:"Advances in Graphene Platforms for Drug Delivery in Cancer and Its Biocompatibility",doi:"10.5772/intechopen.103688",slug:"advances-in-graphene-platforms-for-drug-delivery-in-cancer-and-its-biocompatibility",body:'The major health problems currently afflicting the world population have spurred both research and the development of several medicines meant to treat historical diseases as well as more recent ones, such as the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The range of systems and approaches that can be used to deliver therapies is therefore growing and advancing at an accelerated rate. However, the development of any drug involves a research phase, during which several iterative tests and trials provide important information on the characteristics of the therapeutic target, the biological context, and possible physiological implications [1, 2]. These types of studies provide information on the formulation, efficacy, dosage, and safety of drugs. Products obtained from nanobiotechnology require very rigorous studies due to the great chemical diversity and toxicity said products can produce. These studies must be designed to provide detailed information on the biocompatibility of the nanomaterial and reveal any functional effect on the main physiological systems in order to decide whether a nanobiotechnological product should be tested in humans [3, 4].
The incorporation of nanomaterials into biological systems requires strategies for manipulating the ligands bound to the surface to make them more polar and biocompatible [5]. Nanomaterials must be soluble to have the biological application, and this is achieved by adding functional groups (functionalization). An ideal ligand must meet the following requirements: (1) provide stability and solubility to the nanomaterial in biological buffers; (2) maintain high resistance to photobleaching and other photophysical properties in aqueous media; (3) have functional groups that can conjugate biomolecules (conjugation), and (4) minimize the overall hydrodynamic size [6, 7]. Quantum dots (QDs) are among the most popular nanomaterials: they are semiconductor nanoparticles with photoluminescent properties and a wide variety of applications.
Functionalized QDs are very useful in biomedicine because they can be modified with a great variety of molecules and small biological polymers, which help improve their bioactivity and reduce their toxic effects [8, 9, 10]. Thanks to these characteristics, QDs can bind effectively to cell membranes, meaning they can be employed as excellent probes for cell detection, diagnosis, imaging, and delivery of therapeutic agents. Due to the great coupling achieved between QDs and biomolecules, today these are used as a tool for biological goals, to improve the efficacy of drug release control and significantly reduce toxicity [11, 12, 13]. At present, a wide range of studies on GQD platforms are mainly focused on cancer treatment (Table 1 and Figure 1). This chapter will review the advances in all these areas, as well as aspects related to the toxicity and biocompatibility of GQDs.
Model | Target | Result | References |
---|---|---|---|
MDAMB-231 cells | Genes | Suppression of gene expression and the reduction of the metastatic potential | Huang et al., [14] |
MCF-7 and MDA-MB-231 cells | Genes | Induction of cell death | Imani et al., [15] Liyanage et al., [16] |
MCF-7, MDA-MB-231 and MCF-10 cells | Genes | Induction of apoptosis and inhibition of the growth | Assali et al., [17] |
MCF-7, MDA-MB-231 and MCF-10 cells | siRNA and pDNA | Protection of enzymatic degradation | Cheang et al., [18] |
MCF-7 and MDA-MB-231 cells | P-gp/MDR-1 | Reversal of multidrug resistance (MDR), anticancer drugs mediated by ATP-binding cassette (ABC) transporters | Luo et al., [19] |
Huh-7 hepatocarcinoma cells | mRNA | Delivery intact mRNA | Liu et al., [20] |
HeLa cells | miRNAs | Regulation of miRNAs | Dong et al., [21] |
Myeloma cells and ovarian cancer cells | Enzymes | For the delivery of enzyme inhibitors to the nucleus for inducing cytotoxicity and cell death | Felix et al., [22] |
4T1 cells, MFC7/ADR cells | miRNA-21 | Reversal of multidrug resistance (MDR) | Tian et al., [23] Bukowski et al., [24] |
Colorectal carcinoma cells | Mitochondria | Cellular stress and apoptosis | Ruan et al., [25] |
Oral squamous cell carcinoma | Cytotoxic effect | Zhang et al., [26] | |
A549 cells | DNA | Cytotoxicity induced by doxorubicin | Iannazzo et al., [27] |
Leukemia cells | DNA | Cytotoxicity induced by daunorubicin | Sinha et al., [28] |
A549 cells | DNA | Cytotoxicity induced by doxorubicin | Ko et al., [29] |
Mice/BALBc | DNA | Apoptosis of tumor cells and antitumoral effect induced by doxorubicin | Zhu et al., [30] |
Breast tumor-bearing mice | Immune cells | Elimination of the tumor mass in a subcutaneous mammary tumor | Li et al., [31] |
A549 tumor xenografts. | Tumor cells | Ablation of tumor | Gazzi et al., [32] |
MDA-MB-231 triple-negative breast cancer (TNBC) model | miRNA-21i | Phototherapeutic efficiency of indocyanine green | Wu et al., [33] |
Graphene quantum dots for cancer-targeted drug delivery.
Application of GQDs platforms for cancer treatment. Cellular targets and effects of GQDs platforms in cell lines and experimental animals.
GQDs are carbon-based nanomaterials. Their structure consists of one or more graphene sheets with lateral dimensions of 10 nm [34]. GQDs have a large π-conjugated aromatic structure and a large surface area that allows them to be easily conjugated with various molecules to generate hybrid nanomaterials, but they can also be conjugated with antibodies, proteins, and nucleic acids due to their dimensional similarity with these molecules [35, 36, 37, 38]. They also have a high capacity for loading drugs containing aromatic groups, such as camptothecin, paclitaxel, and doxorubicin through π -π stacking interactions between layers of GQDs and drug molecules. Currently, a variety of synthesis methods allow for size, structure, and optical profile design, depending on the intended application. Even green synthesis has been used to protect the environment [39]. Given the properties of GQDs, the biomedical sector has found several applications in the prevention, diagnosis, and treatment of diseases. Recent studies report that GQDs are less toxic, show greater biocompatibility than other nanomaterials, and also have stable and strong fluorescence. All these characteristics make these nanomaterials ideal for use in cancer treatment.
Targeted therapy is a cancer treatment employing drugs that target specific genes and proteins involved in the growth and survival of cancer cells. Targeted therapy can affect tissue conditions that help cancer grow and survive, or it can target cells related to cancer growth, such as cells in blood vessels. To develop targeted therapies, researchers first identify the genetic changes that contribute to a tumor’s growth and change [40]. A possible target can be a protein present in cancer cells but not healthy ones. Specificity is required. Targeted therapies are a rapidly growing field of cancer research, and researchers are studying many new targets and drugs in clinical trials. Hence, multifunctional nanoparticles directed at specific targets of the tumor cell are also being developed in the field of nanobiotechnology. GQD platforms have been studied in gene-based therapies across various breast cell lines, where a variety of effects have been discovered. These include the suppression of gene expression and the reduction of the metastatic potential of MDAMB-231 cells [14]; induction of cell death in MCF-7 and MDA cells [15, 16]; the induction of apoptosis and inhibition of the growth of MCF-7, MDA-MB-231, and MCF-10 cells [17]; protection of small interference RNA (siRNA) and DNA plasmids (pDNA) from enzymatic degradation [18]; and reversal of multidrug resistance (MDR) [19]. These same methodologies have been studied in animal models with good results. For example, in mice/BALBc, GQD platforms can induce apoptosis of tumor cells and have an antitumoral effect [30]. Furthermore, it has been observed that they can eliminate the tumor mass in a subcutaneous mammary tumor model [31].
Messenger ribonucleic acid (mRNA) delivery systems are another type of targeted therapy having a recent boom because of advantages such as biocompatibility and low genotoxicity. Stable graphene platforms functionalized with polyethyleneimine were used in one study, achieving successful delivery of intact mRNA to hepatocarcinoma cells [20]. Let us remember that mRNA has been widely used in the study of gene function and has become popular in the development of new therapeutic strategies for cancer immunotherapy and vaccines. GQDs have also been used as platforms for the delivery of nucleic acids for the regulation of microRNA (miRNAs), negative regulators of gene expression, with great therapeutic effectiveness in HeLa cells [21]. Various investigations indicate that the expression of some miRNAs is altered in some cancers; achieving their regulation would be useful in oncology. And while one would expect targeted cancer therapy to be less toxic than traditional chemotherapy drugs because tumor cells are more dependent on targets than normal cells, this is not the case. Clinical observation indicates that targeted therapies can also produce significant side effects.
Another approach to targeted therapy is for the delivery of enzyme inhibitors to the nucleus. For example, in one study, GQDs were conjugated to imatinib, successfully achieving cytotoxicity and apoptotic cell death in myeloma cells and ovarian cancer cells [22]; imatinib is an inhibitor of the protein tyrosine kinase, which potently and specifically inhibits breakpoint cluster region-Abelson (bcr-abl) tyrosine kinase. However, genetic manipulation and treatments directed at nuclear targets have numerous technical difficulties that are not yet fully resolved. Targeted therapy is complex and does not always work. One of the limitations of this type of therapy is that the drugs for some identified targets are difficult to formulate due to the structure of the target or the way its function is regulated in the cell. An example of this is Ras, a signaling protein that has mutations in up to a quarter of all cancers, but for this type of therapy to work, one would have to know what mutation the gene has [41]. In short, using nanotechnological platforms does not guarantee patient safety, given that side effects of drugs as well as those of the nanomaterial have yet to be assessed.
The lack of response to treatment and the recurrence of initially chemosensitive tumors are responsible for a significant number of deaths in cancer patients. Treatment options used as salvage, such as alternating chemotherapy, dose-escalation, or regional chemotherapy, have yet to yield the expected results. Most cancer patients who initially respond to chemotherapy have relapses because of the so-called acquired resistance to multiple antineoplastic drugs (MDR) [24]. Today, combination therapies seek to address different therapeutic targets using nanobiotechnology. GQD platforms can exhibit all the desirable characteristics of a combination therapy since, as previously mentioned, their surface can be conjugated with different molecules. Their physical, chemical, electrical, and optical properties, however, confer additional functions. As shown, GQDs have a high photothermal modification power under near-infrared radiation (NIR), which allows for their use as photothermal therapy [42, 43, 44]. Graphene platforms can also be employed for photodynamic therapy, the goal of which is to generate highly cytotoxic reactive oxygen species (ROS) [45]. A great variety of experimental studies involving different types of cancer have been carried out on animals, in most cases resulting in complete ablation of the tumor [32]. Both photothermic and photodynamic therapy show selectivity toward hyperthermic processes typical of cancer cells, but this is rare with normal cells. GQD platforms with more than one therapeutic effect have been used for the treatment of breast cancer; these include chemothermal therapy [46], chemogenic therapy [23, 47], chemo-photothermal therapy [33], and gene therapy [48]. With these platforms, it has been possible to induce greater cytotoxicity, apoptosis, and reverse drug resistance in breast cancer cells. Moreover, inhibition of tumor growth in an animal model of breast cancer MDA-MB-231 triple-negative has been achieved. Graphene platforms have also been employed as nano radiosensitizers to improve the effectiveness of radiotherapy. Oxidized GOQDs with high phototoxicity has been built to induce a cellular stress response via the production of the reactive oxygen species that would be generated during a tumor’s exposure to radiation [49]. Important effects, such as mitochondrial damage and apoptotic death have been observed in colorectal carcinoma cells treated with graphene platforms and radiation therapy [25]. Based on this same principle and thanks to their photodynamic properties, GQDs have also been employed to induce phototoxicity and synergize the cytotoxic effect of radiation in oral squamous cell carcinoma [26].
In addition to these novel uses, GQD platforms are good for the delivery of multiple antineoplastic drugs. A multifunctional platform of GQDs for synergistic breast cancer therapy with controlled release of doxorubicin, methotrexate, and paclitaxel, showed a significant synergistic effect in killing tumor cells with improved efficacy [50]. The advantage of combination therapies is that a therapeutic effect is achieved while reducing drug resistance. On some occasions, however, and as happens in the clinic, the side effects could be considerable. Another method that has been tried for therapeutic efficacy is the conjugation of GQD with a ligand that directs it toward the therapeutic target while additionally carrying the antineoplastic drug. This methodology has been carried out in A549 cells treated with GQDs-biotin-doxorubicin and demonstrates GQDs may have multifunctional effects for cancer treatment [27].
As previously noted, graphene platforms can be built according to the needs of cancer therapy. The construction of ultra-small QDs makes them ideal for achieving not only cell penetration and drug delivery to target sites, but also visualization within the cell. Recently, a graphene platform was used in microspheres with daunorubicin. The small size allowed to monitor drug delivery and the intercalation of daunorubicin in DNA, exerting a better pharmacological effect [28]. Several studies have taken advantage of the fluorescence emitted by QDs to image neoplastic tissues so that, at the same time, drug delivery can be tracked and controlled [51]. In this sense, GQD platforms have become ideal candidates for such purposes due to the high quality of image formation obtained thanks to their fluorescence emission [52]. Additionally, drug/gene delivery in tumor cells has been achieved with greater efficiency both
The growth of solid tumors is characterized not only by the uncontrolled proliferation of cells but also by changes in the tumoral microenvironment. In solid tumors, hypoxic areas generally have a low pH. There may be low levels of glucose and other nutrients, as well as changes in temperature, all associated with various alterations in tumor cell metabolism [60]. While the heterogeneity of the tumor microenvironment sometimes makes it difficult to adequately characterize tumors [61], this has spawned interest in developing new nanotechnology therapeutic strategies to improve not only drug delivery conditions and directly destroy tumor cells, but also alter the balance between neoplastic cells and their microenvironment. Therefore, intelligent systems have been developed for the administration of drugs that respond to stimuli, and therapeutic agents can be activated by endogenous or exogenous stimuli [62, 63]. Platforms based on graphene have proven excellent due to their physicochemical properties since, according to the functional groups that are attached to them, they can be sensitive to changes in the tumor microenvironment or to intracellular signals in response to physical stimulus factors. Graphene platforms have been conjugated with functional chemical groups that allow the drug to be released when there are changes in pH and temperature [64]. For example, it has been observed that when pH-sensitive functional groups (COOH, ▬NH2, and SO3H) are added to graphene platforms, controlled drug release can be achieved in tumor areas [65]. The functionalization allows the pH of the platform to change in the bloodstream and, with this, remain in circulation for longer and favor the delivery and effectiveness of the treatment. This same effect has been achieved by changes in the loading of the platform. This was the case with the construction of the graphene platform with polymers such as polyethylene glycol and doxorubicin, where it was observed that the release of the drug is accelerated in an acidic environment [66]. Or with the construction of graphene microspheres conjugated with a dendrimer and maltose (Fe3O4@C@TDG) as a potential transporter to promote the release of doxorubicin and improve its therapeutic efficacy at specific pH [67]. Polymer aggregation has also served to make photoluminescence more stable at different pH for imaging tumor cells, which, as already mentioned, is part of the multifunctionality of the graphene platform.
The available literature indicates that research on GQDs has grown widely in relation to their uses, and that is why we now know their biomedical applications include the elimination of bacteria, the administration of drugs, the development of nanocarriers, cancer therapy, and tissue engineering [35, 36, 37, 68]. The therapeutic applications of nanomaterials remain quite limited, and there is no safe and effective formulation yet that can be administered in humans [69, 70, 71]. While QDs produce a series of morphological and functional alterations that lead to tumor cell death, what happens to healthy cells is unknown [72]. Therefore, the toxicological profile of each nanomaterial is needed to make decisions regarding potential risks vs. benefits. However, what is known about the biocompatibility of GQDs and what evidence is there of the toxicity of drug delivery platforms?
GQDs and their derivatives have variable toxicity in biological systems ranging from prokaryotic to eukaryotic, depending on the dose and the functional groups with which they are coated [34]. They have also been evaluated in a series of human cell lines. For example, studies carried out on leukocytes showed that there was significant uptake of GQDs in monocytic and granulocytic cells, suggesting that phagocytic cells can incorporate GQDs. The toxicity observed in this study was relatively low (10%) after a 36-hour exposure period at concentrations of 500 μg/mL [73]. In another study using GQDs functionalized with NH2, COOH, and CO▬N(CH3)2 it was observed that A549 and C6 cells showed a slight increase in their proliferation at concentrations of 200 μg/mL, but no death due to apoptosis [74]. GQDs have also produced toxic effects on mesenchymal stem cell self-renewal and differentiation [75]. Several studies have pointed to the toxic effects of graphene derivatives [76, 77, 78, 79, 80, 81]. These functionalized QDs can produce a variety of toxic effects at the cellular level and in vivo due to the series of impurities produced during the oxidation process. The same happens in the coating process with other molecules [82]. However, when GQDs are coated with polyethylene glycol at concentrations of 320 μg/mL, they do not affect the viability and differentiation capacity of neural stem/progenitor cells (NSPCs) [83]. Also, reduced toxicity, absence of ROS production, absence of apoptosis, and lack of morphological changes have been observed in HeLa and A549 tumor cells under concentrations of 100 μg/mL [84, 85].
The cellular and nuclear effects that GQDs produce are due to their high permeability in biological membranes. It is known that the uptake and localization of GQDs are highly dependent on size, shape, coating, and pH, among other factors. Previous studies have shown that GQDs use membrane lipid rafts for their transport across the cell membrane. This process is better, the smaller the QDs are [86]. However, protein-coated GQDs enter mainly by phagocytosis and with smaller coatings by clathrin-mediated endocytosis [87, 88]. GQDs with amide groups enter the cell through energy-dependent mechanisms by endocytosis, mediated by caveolae and phagocytosis [89]. Within the cell, GQDs are distributed in different organelles producing a variety of cellular effects. They are later distributed through endosomal trafficking and reach lysosomes, mitochondria, and the nucleus, and can produce autophagy, apoptosis, and DNA damage [90, 91, 92]. At the nuclear level, the NPC Kap2 and Nup98 genes can participate in the uptake of GQDs and can produce morphological and functional alterations associated with genotoxicity, including oxidative stress and DNA damage [93, 94].
There are many reports in the literature regarding the toxic effects of both GQDs and their derivatives in a variety of human cell lines and it is impossible to mention them all in this chapter. What is evident is the ease with which they penetrate cells, position themselves and participate in strategic cellular processes, thus potentially affecting cell functionality and leading to cell death. However, of the studies reviewed so far, most were done in tumor cell lines where physiological processes are altered and there are specific survival and adaptation mechanisms. To date, there are no studies carried out on cell lines from healthy tissue, so we cannot rule out the fact that GQDs could produce morphological and functional modifications associated with toxicity in healthy cells.
What effects do they produce in higher organisms and experimental animals? What is known about the processes of absorption, distribution, metabolism, and excretion (ADME) of GQDs? The information so far is limited. Previous studies in nematodes have shown that nitrogen-bound GQDs (N-GQDs) produce degeneration of dopaminergic and glutamatergic neurons at concentrations of 100 μg/mL [95]. A series of studies on the biocompatibility and biodistribution of GQDs in adult and embryonic zebrafish have been reported and provide important information on embryos’ developmental delays, pigmentation inhibition, pericardial edema, and delayed hatching among other things. In adults, GQDs showed high biocompatibility and accumulation in the digestive tract [96]. Apparently, the accumulation of QDs depends on the stage of development of the zebrafish (embryo, larva, adult). Studies in adult zebrafish using GQDs at different concentrations (0.1 ng/mL to 100 μg/mL) and exposure times (8 h to 6 days) showed distribution in the heart, blood vessels, brain, intestine, head, and tail [97, 98, 99, 100, 101]. The effects that have been found in zebrafish are morphological and functional alterations, while mortality is attributed to the generation of ROS, oxidative stress, and, finally, apoptosis [102]. On the other hand, studies carried out in chicken embryos have also shown evidence of GQDs-induced toxicity. It was found this affected survival but did not produce morphological or biochemical alterations in the embryo [103]. However, another study found morphological alterations and hemolysis of erythrocytes [104], as well as ultrastructural alterations of the brain, suggesting neurotoxicity [105]. These results suggest that GQDs can alter key processes, not only in adulthood but also during embryonic development.
Biodistribution studies in rodents have shown that GQDs are distributed in various tissues and produce certain toxic effects as well. For example, in mice that received GQDs in a single dose of 10 mg/kg intravenously, it was found that 6 hours after inoculation the QDs were distributed in several organs. Clearance began after 3 days and, at 14 days, the QDs had been completely removed. Histological and biochemical studies did not reveal alterations, only weight loss [106]. However, in another biodistribution study carried out in rodents treated with a single dose of 5 and 15 mg/kg of GQDs intravenously, they produced morphological alterations compatible with inflammation and biochemical damage in the lungs after 7 days of exposure [107]. Additionally, yet another study using repeated doses of 5, 10, and 15 mg/kg every third day for 30 days, showed a reduction in blood cells, morphological alterations in the liver, lipofuscin deposits in the kidney, and the presence of inflammatory infiltrate in the lungs. These alterations were dose-dependent [108]. Taken together, these data suggest that GQDs produce acute toxicity at both single and repeated doses in mammals.
Today there are no reports of long-term studies (chronic toxicity), studies on reproduction and development, or of any other type that allow a general overview of the toxicological profile of GQDs. However, there is experimental evidence showing that other materials derived from graphene can produce a series of toxic effects that must be considered. For example, studies of the distribution of graphene and its derivatives after aerial exposure showed toxic effects in the lungs of rodents [109, 110]. In a chronic inhalation toxicity study of graphene nanoplates, deposits of the nanomaterial were observed in the lungs and pulmonary lymph nodes in mice [111]. In a distribution study in rats using doses of 10, 20, and 40 mg/kg of graphene oxide orally, it was found that it produced nephrotoxic effects due to oxidative stress [112]. While in another study, the administration of multiple doses of oxidized graphene (4 mg/kg) for 4 weeks showed deposits of the material in different tissues in rats [113]. Mutagenic effects have been observed in rats when exposed to graphene oxide at a dose of 4 mg/kg for 4 weeks [114]. Likewise, toxic effects on the reproductive capacity and development of offspring have also been reported after the administration of oxidized graphene to mice with doses from 6.25 mg/kg [115]. Unfortunately, when reviewing the subject, we noted there are no toxicity studies regarding the GQDs platforms employed for drug delivery in cancer research. In fact, all the studies have focused on evaluating its efficiency and specificity toward the tumor cell. That is, what has mattered so far is to demonstrate their possible therapeutic applications in cancer, but not the possible toxic effects they may produce. Therefore, we could say that biosafety studies on GQDs platforms are null.
To date, GQDs have been widely studied as carriers with a large surface area favoring drug transport and particular interest has been placed on characterizing their therapeutic bio properties
Concern regarding the toxicity of graphene not only stems from the findings mentioned above, but also from the long-standing concern about environmental and occupational exposure to graphene [116]. Inhalation toxicity data of graphene analyzed in experimental animals suggest that acute exposure by repeated inhalation to graphene-derived materials could induce inflammatory/fibrotic reactions, suggesting that it could also induce fibrotic disease in humans [117, 118]. Hence the importance of conducting preclinical biosafety studies of graphene nanomaterials and their derivatives using specific criteria, for these are not necessarily the same as those used for chemical products. The toxicological evaluation must be extrapolated with special care due to the size of the nanomaterials and the chemical groups they contain. If there is no complete toxicological profile that meets the standards required by the guidelines of administrative agencies such as the US Food and Drug Administration (FDA), the European Medicines Agency (EMA) or the European Medicines Evaluation Agency (EMEA), and the Japanese Agency for Pharmaceutical and Medical Devices Agency (PMDA), the research will not leave the laboratory.
Drug delivery through nanocarriers has been used successfully in recent years; however, there are still certain challenges that must be addressed to achieve successful drug delivery to target sites. Each of these nanocarrier drug systems has its own chemical, physical and morphological characteristics, and may have an affinity for the different polarities of drugs through chemical or physical interactions, in addition to its own toxicity [119, 120, 121, 122, 123]. One of the goals of using GQDs platforms is to transport and deliver ligands to specific tumor targets and improve antitumor therapy by taking advantage of the supposedly low toxicity of this nanomaterial. However, and as was discussed above, one of the main problems with GQDs and GQD platforms is the lack of toxicological studies that effectively demonstrate their safety and biocompatibility. We have nothing to indicate that they have low toxicity, if there is no evidence to prove this. Additionally, there are several issues inherent to GQDs, the therapeutic targets to be reached and the drugs to be delivered that we must take into consideration.
One of the main problems with small nanomaterials, including GQDs, is the tendency toward aggregation. The lack of dispersion of a nanomaterial can result in transportation problems through the blood, the binding to the plasma protein corona, and the deposition of QDs in biological fluids and tissues [124]. Due to their size, they can go undetected by the immune system and, if they are not biocompatible, could induce toxicity. The dispersion of these QDs has been achieved with the use of some polymers. However, this can sometimes make the QDs larger and thus recognizable by the immune system [125]. Covalent functionalization of GQDs platforms is easy and simple, given their properties and the high surface area for their functionalization. On the other hand, the binding of non-covalent GQDs is more complicated and unstable and can lead to loss of important functional groups that can, in turn, lead to loss of electronic properties. It is also possible to obtain a wide area of functionalization [126] but the presence of a large, functionalized surface area can have adverse consequences, especially if it is a biologically active ligand that can impact cellular physiological processes. There are currently no studies on real-time monitoring and distribution of GQDs in animal models, so the effect of these platforms remains unknown.
If we want to direct GQD platforms toward specific tumor targets, we must know the molecular biology of the tumor. That is, where they need to be directed and with what do we intend them to interact. To achieve this, we require platforms that can specifically locate and access the tumor and not reach healthy tissue. Unfortunately, as we saw in the previous section, very few of the studies on animal models provide any information on this, since the studies only focus on the effects of GQD platforms at the tumor site but do not mention whether neighboring or distant tissues were affected, if systemic toxic effects were observed, or if there was mortality. The great disadvantage of most nanomaterial platforms, including GQDs, animal models have not yielded enough information about them. All nanomaterials are widely known to be cytotoxic, and so not a single one has been identified as harmless. Therefore, it is important that we obtain detailed information regarding the effects they produce
Furthermore, all drugs used in clinical oncology are in themselves toxic and produce a variety of adverse effects. While GQD platforms have been used to target specific cells and molecules, most of the studies have been carried out using cells cultured
GQDs hold great promise as a platform for multifunctional drug/gene delivery as well as an excellent tool for quality bioimaging. Current studies of drug delivery systems based on nanotechnology are expected to facilitate advanced forms of this kind of delivery. However, they are currently limited by the lack of preclinical pharmacological and toxicological studies, and their unknown biosafety and biocompatibility. A detailed understanding of how GQDs interact with blood components, the immune system, and aspects related to ADME processes is of vital importance. If the regulatory requirements requested by pharmacovigilance agencies are not addressed and resolved, the biotechnological and biomedical potential of GQDs cannot be employed in clinical studies. There is no doubt that, in the past decade, there have been great advances in drug delivery methods. GQD platforms have advantages over other platforms, including their surface area, size variability, their ability to functionalize with different ligands, and their photothermal and photodynamic properties. All these features make these platforms into ideal tools, not only as intelligent and multifunctional platforms for cancer therapy but also to monitor drug delivery and therapeutic effectiveness via their fluorescent emission. All these qualities could open up new pathways toward improved technological knowledge on nanoparticle-based therapies, particularly those aimed at a variety of cancers currently affecting the human population.
This work was supported by the Universidad Nacional Autónoma de México (UNAM) project DGAPA-PAPIIT-IG100920; as well as by the Consejo Nacional de Ciencia y Tecnología (CONACYT) México through grant FORDECYT-PRONACES No. Project 74884.
The authors declare no conflict of interest.
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Cárdenas-Aguayo, M. del C. Silva-Lucero, M. Cortes-Ortiz,\nB. Jiménez-Ramos, L. Gómez-Virgilio, G. Ramírez-Rodríguez, E. Vera-\nArroyo, R. Fiorentino-Pérez, U. García, J. 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MRI is commonly used once treating brain, prostate cancers, ankle and foot. The Magnetic Resonance Imaging (MRI) images are usually liable to suffer from noises such as Gaussian noise, salt and pepper noise and speckle noise. So getting of brain image with accuracy is very extremely task. An accurate brain image is very necessary for further diagnosis process. During this chapter, a median filter algorithm will be modified. Gaussian noise and Salt and pepper noise will be added to MRI image. A proposed Median filter (MF), Adaptive Median filter (AMF) and Adaptive Wiener filter (AWF) will be implemented. The filters will be used to remove the additive noises present in the MRI images. The noise density will be added gradually to MRI image to compare performance of the filters evaluation. The performance of these filters will be compared exploitation the applied mathematics parameter Peak Signal-to-Noise Ratio (PSNR).",book:{id:"6144",slug:"high-resolution-neuroimaging-basic-physical-principles-and-clinical-applications",title:"High-Resolution Neuroimaging",fullTitle:"High-Resolution Neuroimaging - Basic Physical Principles and Clinical Applications"},signatures:"Hanafy M. Ali",authors:[{id:"213318",title:"Dr.",name:"Hanafy",middleName:"M.",surname:"Ali",slug:"hanafy-ali",fullName:"Hanafy Ali"}]},{id:"41589",doi:"10.5772/50323",title:"The Role of the Amygdala in Anxiety Disorders",slug:"the-role-of-the-amygdala-in-anxiety-disorders",totalDownloads:9671,totalCrossrefCites:4,totalDimensionsCites:28,abstract:null,book:{id:"2599",slug:"the-amygdala-a-discrete-multitasking-manager",title:"The Amygdala",fullTitle:"The Amygdala - A Discrete Multitasking Manager"},signatures:"Gina L. Forster, Andrew M. Novick, Jamie L. Scholl and Michael J. 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Particularly in the case of motor imagery BCIs, users may need several training sessions before they learn how to generate desired brain activity and reach an acceptable performance. A typical training protocol for such BCIs includes execution of a motor imagery task by the user, followed by presentation of an extending bar or a moving object on a computer screen. In this chapter, we discuss the importance of a visual feedback that resembles human actions, the effect of human factors such as confidence and motivation, and the role of embodiment in the learning process of a motor imagery task. Our results from a series of experiments in which users BCI-operated a humanlike android robot confirm that realistic visual feedback can induce a sense of embodiment, which promotes a significant learning of the motor imagery task in a short amount of time. We review the impact of humanlike visual feedback in optimized modulation of brain activity by the BCI users.",book:{id:"6610",slug:"evolving-bci-therapy-engaging-brain-state-dynamics",title:"Evolving BCI Therapy",fullTitle:"Evolving BCI Therapy - Engaging Brain State Dynamics"},signatures:"Maryam Alimardani, Shuichi Nishio and Hiroshi Ishiguro",authors:[{id:"11981",title:"Prof.",name:"Hiroshi",middleName:null,surname:"Ishiguro",slug:"hiroshi-ishiguro",fullName:"Hiroshi Ishiguro"},{id:"231131",title:"Dr.",name:"Maryam",middleName:null,surname:"Alimardani",slug:"maryam-alimardani",fullName:"Maryam Alimardani"},{id:"231134",title:"Dr.",name:"Shuichi",middleName:null,surname:"Nishio",slug:"shuichi-nishio",fullName:"Shuichi Nishio"}]}],mostDownloadedChaptersLast30Days:[{id:"29764",title:"Underlying Causes of Paresthesia",slug:"underlying-causes-of-paresthesia",totalDownloads:192666,totalCrossrefCites:3,totalDimensionsCites:7,abstract:null,book:{id:"1069",slug:"paresthesia",title:"Paresthesia",fullTitle:"Paresthesia"},signatures:"Mahdi Sharif-Alhoseini, Vafa Rahimi-Movaghar and Alexander R. 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Precise anatomical description along with a correct characterization of the component structures is essential for understanding its functions.",book:{id:"6331",slug:"hypothalamus-in-health-and-diseases",title:"Hypothalamus in Health and Diseases",fullTitle:"Hypothalamus in Health and Diseases"},signatures:"Miana Gabriela Pop, Carmen Crivii and Iulian Opincariu",authors:null},{id:"57103",title:"GABA and Glutamate: Their Transmitter Role in the CNS and Pancreatic Islets",slug:"gaba-and-glutamate-their-transmitter-role-in-the-cns-and-pancreatic-islets",totalDownloads:3478,totalCrossrefCites:3,totalDimensionsCites:9,abstract:"Glutamate and gamma-aminobutyric acid (GABA) are the major neurotransmitters in the mammalian brain. Inhibitory GABA and excitatory glutamate work together to control many processes, including the brain’s overall level of excitation. The contributions of GABA and glutamate in extra-neuronal signaling are by far less widely recognized. In this chapter, we first discuss the role of both neurotransmitters during development, emphasizing the importance of the shift from excitatory to inhibitory GABAergic neurotransmission. The second part summarizes the biosynthesis and role of GABA and glutamate in neurotransmission in the mature brain, and major neurological disorders associated with glutamate and GABA receptors and GABA release mechanisms. The final part focuses on extra-neuronal glutamatergic and GABAergic signaling in pancreatic islets of Langerhans, and possible associations with type 1 diabetes mellitus.",book:{id:"6237",slug:"gaba-and-glutamate-new-developments-in-neurotransmission-research",title:"GABA And Glutamate",fullTitle:"GABA And Glutamate - New Developments In Neurotransmission Research"},signatures:"Christiane S. Hampe, Hiroshi Mitoma and Mario Manto",authors:[{id:"210220",title:"Prof.",name:"Christiane",middleName:null,surname:"Hampe",slug:"christiane-hampe",fullName:"Christiane Hampe"},{id:"210485",title:"Prof.",name:"Mario",middleName:null,surname:"Manto",slug:"mario-manto",fullName:"Mario Manto"},{id:"210486",title:"Prof.",name:"Hiroshi",middleName:null,surname:"Mitoma",slug:"hiroshi-mitoma",fullName:"Hiroshi Mitoma"}]},{id:"35802",title:"Cross-Cultural/Linguistic Differences in the Prevalence of Developmental Dyslexia and the Hypothesis of Granularity and Transparency",slug:"cross-cultural-linguistic-differences-in-the-prevalence-of-developmental-dyslexia-and-the-hypothesis",totalDownloads:3601,totalCrossrefCites:2,totalDimensionsCites:7,abstract:null,book:{id:"673",slug:"dyslexia-a-comprehensive-and-international-approach",title:"Dyslexia",fullTitle:"Dyslexia - A Comprehensive and International Approach"},signatures:"Taeko N. Wydell",authors:[{id:"87489",title:"Prof.",name:"Taeko",middleName:"N.",surname:"Wydell",slug:"taeko-wydell",fullName:"Taeko Wydell"}]},{id:"58597",title:"Testosterone and Erectile Function: A Review of Evidence from Basic Research",slug:"testosterone-and-erectile-function-a-review-of-evidence-from-basic-research",totalDownloads:1331,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Androgens are essential for male physical activity and normal erectile function. Hence, age-related testosterone deficiency, known as late-onset hypogonadism (LOH), is considered a risk factor for erectile dysfunction (ED). This chapter summarizes relevant basic research reports examining the effects of testosterone on erectile function. Testosterone affects several organs and is especially active on the erectile tissue. The mechanism of testosterone deficiency effects on erectile function and the results of testosterone replacement therapy (TRT) have been well studied. Testosterone affects nitric oxide (NO) production and phosphodiesterase type 5 (PDE-5) expression in the corpus cavernosum through molecular pathways, preserves smooth muscle contractility by regulating both contraction and relaxation, and maintains the structure of the corpus cavernosum. Interestingly, testosterone deficiency has relationship to neurological diseases, which leads to ED. Testosterone replacement therapy is widely used to treat patients with testosterone deficiency; however, this treatment might also induce some problems. Basic research suggests that PDE-5 inhibitors, L-citrulline, and/or resveratrol therapy might be effective therapeutic options for testosterone deficiency-induced ED. Future research should confirm these findings through more specific experiments using molecular tools and may shed more light on endocrine-related ED and its possible treatments.",book:{id:"5994",slug:"sex-hormones-in-neurodegenerative-processes-and-diseases",title:"Sex Hormones in Neurodegenerative Processes and Diseases",fullTitle:"Sex Hormones in Neurodegenerative Processes and Diseases"},signatures:"Tomoya Kataoka and Kazunori Kimura",authors:[{id:"219042",title:"Ph.D.",name:"Tomoya",middleName:null,surname:"Kataoka",slug:"tomoya-kataoka",fullName:"Tomoya Kataoka"},{id:"229066",title:"Prof.",name:"Kazunori",middleName:null,surname:"Kimura",slug:"kazunori-kimura",fullName:"Kazunori Kimura"}]}],onlineFirstChaptersFilter:{topicId:"18",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81646",title:"Cortical Plasticity under Ketamine: From Synapse to Map",slug:"cortical-plasticity-under-ketamine-from-synapse-to-map",totalDownloads:14,totalDimensionsCites:0,doi:"10.5772/intechopen.104787",abstract:"Sensory systems need to process signals in a highly dynamic way to efficiently respond to variations in the animal’s environment. For instance, several studies showed that the visual system is subject to neuroplasticity since the neurons’ firing changes according to stimulus properties. This dynamic information processing might be supported by a network reorganization. Since antidepressants influence neurotransmission, they can be used to explore synaptic plasticity sustaining cortical map reorganization. To this goal, we investigated in the primary visual cortex (V1 of mouse and cat), the impact of ketamine on neuroplasticity through changes in neuronal orientation selectivity and the functional connectivity between V1 cells, using cross correlation analyses. We found that ketamine affects cortical orientation selectivity and alters the functional connectivity within an assembly. These data clearly highlight the role of the antidepressant drugs in inducing or modeling short-term plasticity in V1 which suggests that cortical processing is optimized and adapted to the properties of the stimulus.",book:{id:"11374",title:"Sensory Nervous System - Computational Neuroimaging Investigations of Topographical Organization in Human Sensory Cortex",coverURL:"https://cdn.intechopen.com/books/images_new/11374.jpg"},signatures:"Ouelhazi Afef, Rudy Lussiez and Molotchnikoff Stephane"},{id:"81582",title:"The Role of Cognitive Reserve in Executive Functioning and Its Relationship to Cognitive Decline and Dementia",slug:"the-role-of-cognitive-reserve-in-executive-functioning-and-its-relationship-to-cognitive-decline-and",totalDownloads:22,totalDimensionsCites:0,doi:"10.5772/intechopen.104646",abstract:"In this chapter, we explore how cognitive reserve is implicated in coping with the negative consequences of brain pathology and age-related cognitive decline. Individual differences in cognitive performance are based on different brain mechanisms (neural reserve and neural compensation), and reflect, among others, the effect of education, occupational attainment, leisure activities, and social involvement. These cognitive reserve proxies have been extensively associated with efficient executive functioning. We discuss and focus particularly on the compensation mechanisms related to the frontal lobe and its protective role, in maintaining cognitive performance in old age or even mitigating the clinical expression of dementia.",book:{id:"11742",title:"Neurophysiology",coverURL:"https://cdn.intechopen.com/books/images_new/11742.jpg"},signatures:"Gabriela Álvares-Pereira, Carolina Maruta and Maria Vânia Silva-Nunes"},{id:"81488",title:"Aggression and Sexual Behavior: Overlapping or Distinct Roles of 5-HT1A and 5-HT1B Receptors",slug:"aggression-and-sexual-behavior-overlapping-or-distinct-roles-of-5-ht1a-and-5-ht1b-receptors",totalDownloads:19,totalDimensionsCites:0,doi:"10.5772/intechopen.104872",abstract:"Distinct brain mechanisms for male aggressive and sexual behavior are present in mammalian species, including man. However, recent evidence suggests a strong connection and even overlap in the central nervous system (CNS) circuitry involved in aggressive and sexual behavior. The serotonergic system in the CNS is strongly involved in male aggressive and sexual behavior. In particular, 5-HT1A and 5-HT1B receptors seem to play a critical role in the modulation of these behaviors. The present chapter focuses on the effects of 5-HT1A- and 5-HT1B-receptor ligands in male rodent aggression and sexual behavior. Results indicate that 5-HT1B-heteroreceptors play a critical role in the modulation of male offensive behavior, although a definite role of 5-HT1A-auto- or heteroreceptors cannot be ruled out. 5-HT1A receptors are clearly involved in male sexual behavior, although it has to be yet unraveled whether 5-HT1A-auto- or heteroreceptors are important. Although several key nodes in the complex circuitry of aggression and sexual behavior are known, in particular in the medial hypothalamus, a clear link or connection to these critical structures and the serotonergic key receptors is yet to be determined. This information is urgently needed to detect and develop new selective anti-aggressive (serenic) and pro-sexual drugs for human applications.",book:{id:"10195",title:"Serotonin and the CNS - New Developments in Pharmacology and Therapeutics",coverURL:"https://cdn.intechopen.com/books/images_new/10195.jpg"},signatures:"Berend Olivier and Jocelien D.A. Olivier"},{id:"81093",title:"Prehospital and Emergency Room Airway Management in Traumatic Brain Injury",slug:"prehospital-and-emergency-room-airway-management-in-traumatic-brain-injury",totalDownloads:49,totalDimensionsCites:0,doi:"10.5772/intechopen.104173",abstract:"Airway management in trauma is critical and may impact patient outcomes. Particularly in traumatic brain injury (TBI), depressed level of consciousness may be associated with compromised protective airway reflexes or apnea, which can increase the risk of aspiration or result in hypoxemia and worsen the secondary brain damage. Therefore, patients with TBI and Glasgow Coma Scale (GCS) ≤ 8 have been traditionally managed by prehospital or emergency room (ER) endotracheal intubation. However, recent evidence challenged this practice and even suggested that routine intubation may be harmful. This chapter will address the indications and optimal method of securing the airway, prehospital and in the ER, in patients with traumatic brain injury.",book:{id:"11367",title:"Traumatic Brain Injury",coverURL:"https://cdn.intechopen.com/books/images_new/11367.jpg"},signatures:"Dominik A. Jakob, Jean-Cyrille Pitteloud and Demetrios Demetriades"},{id:"81011",title:"Amino Acids as Neurotransmitters. The Balance between Excitation and Inhibition as a Background for Future Clinical Applications",slug:"amino-acids-as-neurotransmitters-the-balance-between-excitation-and-inhibition-as-a-background-for-f",totalDownloads:19,totalDimensionsCites:0,doi:"10.5772/intechopen.103760",abstract:"For more than 30 years, amino acids have been well-known (and essential) participants in neurotransmission. They act as both neuromediators and metabolites in nervous tissue. Glycine and glutamic acid (glutamate) are prominent examples. These amino acids are agonists of inhibitory and excitatory membrane receptors, respectively. Moreover, they play essential roles in metabolic pathways and energy transformation in neurons and astrocytes. Despite their obvious effects on the brain, their potential role in therapeutic methods remains uncertain in clinical practice. In the current chapter, a comparison of the crosstalk between these two systems, which are responsible for excitation and inhibition in neurons, is presented. The interactions are discussed at the metabolic, receptor, and transport levels. Reaction-diffusion and a convectional flow into the interstitial fluid create a balanced distribution of glycine and glutamate. Indeed, the neurons’ final physiological state is a result of a balance between the excitatory and inhibitory influences. However, changes to the glycine and/or glutamate pools under pathological conditions can alter the state of nervous tissue. Thus, new therapies for various diseases may be developed on the basis of amino acid medication.",book:{id:"10890",title:"Recent Advances in Neurochemistry",coverURL:"https://cdn.intechopen.com/books/images_new/10890.jpg"},signatures:"Yaroslav R. Nartsissov"},{id:"80821",title:"Neuroimmunology and Neurological Manifestations of COVID-19",slug:"neuroimmunology-and-neurological-manifestations-of-covid-19",totalDownloads:41,totalDimensionsCites:0,doi:"10.5772/intechopen.103026",abstract:"Infection with SARS-CoV-2 is causing coronavirus disease in 2019 (COVID-19). Besides respiratory symptoms due to an attack on the broncho-alveolar system, COVID-19, among others, can be accompanied by neurological symptoms because of the affection of the nervous system. These can be caused by intrusion by SARS-CoV-2 of the central nervous system (CNS) and peripheral nervous system (PNS) and direct infection of local cells. In addition, neurological deterioration mediated by molecular mimicry to virus antigens or bystander activation in the context of immunological anti-virus defense can lead to tissue damage in the CNS and PNS. In addition, cytokine storm caused by SARS-CoV-2 infection in COVID-19 can lead to nervous system related symptoms. Endotheliitis of CNS vessels can lead to vessel occlusion and stroke. COVID-19 can also result in cerebral hemorrhage and sinus thrombosis possibly related to changes in clotting behavior. Vaccination is most important to prevent COVID-19 in the nervous system. There are symptomatic or/and curative therapeutic approaches to combat COVID-19 related nervous system damage that are partly still under study.",book:{id:"10890",title:"Recent Advances in Neurochemistry",coverURL:"https://cdn.intechopen.com/books/images_new/10890.jpg"},signatures:"Robert Weissert"}],onlineFirstChaptersTotal:17},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:288,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"13",title:"Veterinary Medicine and Science",doi:"10.5772/intechopen.73681",issn:"2632-0517",scope:"Paralleling similar advances in the medical field, astounding advances occurred in Veterinary Medicine and Science in recent decades. These advances have helped foster better support for animal health, more humane animal production, and a better understanding of the physiology of endangered species to improve the assisted reproductive technologies or the pathogenesis of certain diseases, where animals can be used as models for human diseases (like cancer, degenerative diseases or fertility), and even as a guarantee of public health. Bridging Human, Animal, and Environmental health, the holistic and integrative “One Health” concept intimately associates the developments within those fields, projecting its advancements into practice. This book series aims to tackle various animal-related medicine and sciences fields, providing thematic volumes consisting of high-quality significant research directed to researchers and postgraduates. It aims to give us a glimpse into the new accomplishments in the Veterinary Medicine and Science field. By addressing hot topics in veterinary sciences, we aim to gather authoritative texts within each issue of this series, providing in-depth overviews and analysis for graduates, academics, and practitioners and foreseeing a deeper understanding of the subject. Forthcoming texts, written and edited by experienced researchers from both industry and academia, will also discuss scientific challenges faced today in Veterinary Medicine and Science. In brief, we hope that books in this series will provide accessible references for those interested or working in this field and encourage learning in a range of different topics.",coverUrl:"https://cdn.intechopen.com/series/covers/13.jpg",latestPublicationDate:"May 18th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:10,editor:{id:"38652",title:"Prof.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",biography:"Rita Payan Carreira earned her Veterinary Degree from the Faculty of Veterinary Medicine in Lisbon, Portugal, in 1985. She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",institutionURL:null,country:{name:"Portugal"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:5,paginationItems:[{id:"19",title:"Animal Science",coverUrl:"https://cdn.intechopen.com/series_topics/covers/19.jpg",editor:{id:"259298",title:"Dr.",name:"Edward",middleName:null,surname:"Narayan",slug:"edward-narayan",fullName:"Edward Narayan",profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",biography:"Dr. Edward Narayan graduated with Ph.D. degree in Biology from the University of the South Pacific and pioneered non-invasive reproductive and stress endocrinology tools for amphibians - the novel development and validation of non-invasive enzyme immunoassays for the evaluation of reproductive hormonal cycle and stress hormone responses to environmental stressors. \nDr. Narayan leads the Stress Lab (Comparative Physiology and Endocrinology) at the University of Queensland. A dynamic career research platform which is based on the thematic areas of comparative vertebrate physiology, stress endocrinology, reproductive endocrinology, animal health and welfare, and conservation biology. \nEdward has supervised 40 research students and published over 60 peer reviewed research.",institutionString:null,institution:{name:"University of Queensland",institutionURL:null,country:{name:"Australia"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"258334",title:"Dr.",name:"Carlos Eduardo",middleName:null,surname:"Fonseca-Alves",slug:"carlos-eduardo-fonseca-alves",fullName:"Carlos Eduardo Fonseca-Alves",profilePictureURL:"https://mts.intechopen.com/storage/users/258334/images/system/258334.jpg",institutionString:null,institution:{name:"Universidade Paulista",institutionURL:null,country:{name:"Brazil"}}},{id:"191123",title:"Dr.",name:"Juan José",middleName:null,surname:"Valdez-Alarcón",slug:"juan-jose-valdez-alarcon",fullName:"Juan José Valdez-Alarcón",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBfcQAG/Profile_Picture_1631354558068",institutionString:"Universidad Michoacana de San Nicolás de Hidalgo",institution:{name:"Universidad Michoacana de San Nicolás de Hidalgo",institutionURL:null,country:{name:"Mexico"}}},{id:"161556",title:"Dr.",name:"Maria Dos Anjos",middleName:null,surname:"Pires",slug:"maria-dos-anjos-pires",fullName:"Maria Dos Anjos Pires",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS8q2QAC/Profile_Picture_1633432838418",institutionString:null,institution:{name:"University of Trás-os-Montes and Alto Douro",institutionURL:null,country:{name:"Portugal"}}},{id:"209839",title:"Dr.",name:"Marina",middleName:null,surname:"Spinu",slug:"marina-spinu",fullName:"Marina Spinu",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRLXpQAO/Profile_Picture_1630044895475",institutionString:null,institution:{name:"University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca",institutionURL:null,country:{name:"Romania"}}},{id:"92185",title:"Dr.",name:"Sara",middleName:null,surname:"Savic",slug:"sara-savic",fullName:"Sara Savic",profilePictureURL:"https://mts.intechopen.com/storage/users/92185/images/system/92185.jfif",institutionString:'Scientific Veterinary Institute "Novi Sad"',institution:{name:'Scientific Veterinary Institute "Novi Sad"',institutionURL:null,country:{name:"Serbia"}}}]},{id:"20",title:"Animal Nutrition",coverUrl:"https://cdn.intechopen.com/series_topics/covers/20.jpg",editor:{id:"175967",title:"Dr.",name:"Manuel",middleName:null,surname:"Gonzalez Ronquillo",slug:"manuel-gonzalez-ronquillo",fullName:"Manuel Gonzalez Ronquillo",profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",biography:"Dr. Manuel González Ronquillo obtained his doctorate degree from the University of Zaragoza, Spain, in 2001. He is a research professor at the Faculty of Veterinary Medicine and Animal Husbandry, Autonomous University of the State of Mexico. He is also a level-2 researcher. He received a Fulbright-Garcia Robles fellowship for a postdoctoral stay at the US Dairy Forage Research Center, Madison, Wisconsin, USA in 2008–2009. He received grants from Alianza del Pacifico for a stay at the University of Magallanes, Chile, in 2014, and from Consejo Nacional de Ciencia y Tecnología (CONACyT) to work in the Food and Agriculture Organization’s Animal Production and Health Division (AGA), Rome, Italy, in 2014–2015. He has collaborated with researchers from different countries and published ninety-eight journal articles. He teaches various degree courses in zootechnics, sheep production, and agricultural sciences and natural resources.\n\nDr. Ronquillo’s research focuses on the evaluation of sustainable animal diets (StAnD), using native resources of the region, decreasing carbon footprint, and applying meta-analysis and mathematical models for a better understanding of animal production.",institutionString:null,institution:{name:"Universidad Autónoma del Estado de México",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"175762",title:"Dr.",name:"Alfredo J.",middleName:null,surname:"Escribano",slug:"alfredo-j.-escribano",fullName:"Alfredo J. 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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:"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"}}},{id:"351158",title:"Prof.",name:"David W.",middleName:null,surname:"Anderson",slug:"david-w.-anderson",fullName:"David W. Anderson",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Calgary",country:{name:"Canada"}}}]}},subseries:{item:{id:"14",type:"subseries",title:"Cell and Molecular Biology",keywords:"Omics (Transcriptomics; Proteomics; Metabolomics), Molecular Biology, Cell Biology, Signal Transduction and Regulation, Cell Growth and Differentiation, Apoptosis, Necroptosis, Ferroptosis, Autophagy, Cell Cycle, Macromolecules and Complexes, Gene Expression",scope:"The Cell and Molecular Biology topic within the IntechOpen Biochemistry Series aims to rapidly publish contributions on all aspects of cell and molecular biology, including aspects related to biochemical and genetic research (not only in humans but all living beings). We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics include, but are not limited to: Advanced techniques of cellular and molecular biology (Molecular methodologies, imaging techniques, and bioinformatics); Biological activities at the molecular level; Biological processes of cell functions, cell division, senescence, maintenance, and cell death; Biomolecules interactions; Cancer; Cell biology; Chemical biology; Computational biology; Cytochemistry; Developmental biology; Disease mechanisms and therapeutics; DNA, and RNA metabolism; Gene functions, genetics, and genomics; Genetics; Immunology; Medical microbiology; Molecular biology; Molecular genetics; Molecular processes of cell and organelle dynamics; Neuroscience; Protein biosynthesis, degradation, and functions; Regulation of molecular interactions in a cell; Signalling networks and system biology; Structural biology; Virology and microbiology.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11410,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. 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,series:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983"},editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",slug:"ana-isabel-flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",slug:"christian-palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",slug:"francisco-javier-martin-romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},onlineFirstChapters:{paginationCount:17,paginationItems:[{id:"81647",title:"Diabetes and Epigenetics",doi:"10.5772/intechopen.104653",signatures:"Rasha A. 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