List of putative genes/transcription factors and functional genomics tools involved in regulating biosynthesis of secondary metabolites in legumes.
\\n\\n
IntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\\n\\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
\\n\\nLaunching 2021
\\n\\nArtificial Intelligence, ISSN 2633-1403
\\n\\nVeterinary Medicine and Science, ISSN 2632-0517
\\n\\nBiochemistry, ISSN 2632-0983
\\n\\nBiomedical Engineering, ISSN 2631-5343
\\n\\nInfectious Diseases, ISSN 2631-6188
\\n\\nPhysiology (Coming Soon)
\\n\\nDentistry (Coming Soon)
\\n\\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\\n\\nNote: Edited in October 2021
\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/132"}},components:[{type:"htmlEditorComponent",content:'With the desire to make book publishing more relevant for the digital age and offer innovative Open Access publishing options, we are thrilled to announce the launch of our new publishing format: IntechOpen Book Series.
\n\nDesigned to cover fast-moving research fields in rapidly expanding areas, our Book Series feature a Topic structure allowing us to present the most relevant sub-disciplines. Book Series are headed by Series Editors, and a team of Topic Editors supported by international Editorial Board members. Topics are always open for submissions, with an Annual Volume published each calendar year.
\n\nAfter a robust peer-review process, accepted works are published quickly, thanks to Online First, ensuring research is made available to the scientific community without delay.
\n\nOur innovative Book Series format brings you:
\n\nIntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\n\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
\n\nLaunching 2021
\n\nArtificial Intelligence, ISSN 2633-1403
\n\nVeterinary Medicine and Science, ISSN 2632-0517
\n\nBiochemistry, ISSN 2632-0983
\n\nBiomedical Engineering, ISSN 2631-5343
\n\nInfectious Diseases, ISSN 2631-6188
\n\nPhysiology (Coming Soon)
\n\nDentistry (Coming Soon)
\n\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\n\nNote: Edited in October 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:"4637",leadTitle:null,fullTitle:"Toxicity and Hazard of Agrochemicals",title:"Toxicity and Hazard of Agrochemicals",subtitle:null,reviewType:"peer-reviewed",abstract:"This edited book, Toxicity and Hazard of Agrochemicals, is intended to provide an overview of toxicology that examines the hazardous effects of common agrochemicals employed every day in our agricultural practices. Furthermore, it is hoped that the information in the present book will be of value to those directly engaged in the handling and use of agrochemicals and that this book will continue to meet the expectations and needs of all interested in the different aspects of human and environmental risk toxicities.",isbn:null,printIsbn:"978-953-51-2145-9",pdfIsbn:"978-953-51-5403-7",doi:"10.5772/59450",price:119,priceEur:129,priceUsd:155,slug:"toxicity-and-hazard-of-agrochemicals",numberOfPages:170,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"6aff74df1ea32df7f1e20e29c8363ff5",bookSignature:"Marcelo L. Larramendy and Sonia Soloneski",publishedDate:"July 22nd 2015",coverURL:"https://cdn.intechopen.com/books/images_new/4637.jpg",numberOfDownloads:15210,numberOfWosCitations:64,numberOfCrossrefCitations:52,numberOfCrossrefCitationsByBook:4,numberOfDimensionsCitations:88,numberOfDimensionsCitationsByBook:5,hasAltmetrics:1,numberOfTotalCitations:204,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 13th 2014",dateEndSecondStepPublish:"November 3rd 2014",dateEndThirdStepPublish:"February 7th 2015",dateEndFourthStepPublish:"May 8th 2015",dateEndFifthStepPublish:"June 7th 2015",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"14764",title:"Dr.",name:"Marcelo L.",middleName:null,surname:"Larramendy",slug:"marcelo-l.-larramendy",fullName:"Marcelo L. Larramendy",profilePictureURL:"https://mts.intechopen.com/storage/users/14764/images/system/14764.jpg",biography:"Marcelo L. Larramendy, Ph.D., serves as Professor of Molecular Cell Biology at the School of Natural Sciences and Museum (National University of La Plata, Argentina). Appointed Senior Researcher of the National Scientific and Technological Research Council of Argentina. Former Member of the Executive Committee of the Latin American Association of Environmental Mutagenesis, Teratogenesis and Carcinogenesis. Author of more than 450 contributions, including scientific publications, research communications and conferences worldwide. Recipient of several national and international awards. Prof. Larramendy is a regular Lecturer at the international A. Hollaender Courses organized by the IAEMS and former guest scientist at NIH (USA) and the University of Helsinki, (Finland). He is an expert in Genetic Toxicology and is, or has been, referee for more than 20 international scientific journals. Member of the International Panel of Experts at the International Agency for Research on Cancer (IARC, WHO, Lyon, France) in 2015 for the evaluation of DDT, 2,4-D and Lindane. Presently, Prof. Dr. Larramendy is Head of the Laboratory of Molecular Cytogenetics and Genotoxicology at the UNLP.",institutionString:"National University of La Plata",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"20",institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"14863",title:"Dr.",name:"Sonia",middleName:null,surname:"Soloneski",slug:"sonia-soloneski",fullName:"Sonia Soloneski",profilePictureURL:"https://mts.intechopen.com/storage/users/14863/images/system/14863.jpg",biography:"Sonia Soloneski has a Ph.D. in Natural Sciences and is Assistant Professor of Molecular Cell Biology at the School of Natural Sciences and Museum of La Plata, National University of La Plata, Argentina. She is a member of the National Scientific and Technological Research Council (CONICET) of Argentina in the Genetic Toxicology field, the Latin American Association of Environmental Mutagenesis, Teratogenesis and Carcinogenesis (ALAMCTA), the Argentinean Society of Toxicology (ATA), the Argentinean Society of Biology (SAB) and the Society of Environmental Toxicology and Chemistry (SETAC). She has authored more than 380 contributions in the field, including scientific publications in peer-reviewed journals and research communications. She has served as a review member for more than 30 scientific international journals. She has been a plenary speaker in scientific conferences and a member of scientific committees. She is a specialist in issues related to Genetic Toxicology, Mutagenesis, and Ecotoxicology.",institutionString:"National University of La Plata",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"7",institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"306",title:"Pesticides",slug:"pesticides"}],chapters:[{id:"48545",title:"Environmental Risk Assessment of Agrochemicals — A Critical Appraisal of Current Approaches",doi:"10.5772/60739",slug:"environmental-risk-assessment-of-agrochemicals-a-critical-appraisal-of-current-approaches",totalDownloads:2561,totalCrossrefCites:9,totalDimensionsCites:14,hasAltmetrics:0,abstract:"This chapter provides insights into the difficulties and challenges of performing risk evaluations of agrochemicals. It is a critical review of the current methodologies used in ecological risk assessment of these chemicals, not their risks to humans. After an introduction to the topic, the current framework for ecological risk assessment is outlined. Two types of assessments are typically carried out depending on the purpose: i) regulatory assessments for registration of a chemical product; and ii) ecological assessments, for the protection of both terrestrial and aquatic ecosystems, which are usually site-specific. Although the general framework is well established, the methodologies used in each of the steps of the assessment are fraught with a number of shortcomings. Notwithstanding the subjectivity implicit in the evaluation of risks, there is scepticism in scientific circles about the appropriateness of the current methodologies because, after so many years of evaluations, we are still incapable of foreseeing the negative consequences that some agrochemicals have in the environment. A critical appraisal of such methodologies is imperative if we are to improve the current assessment process and fix the problems we face today. The chapter reviews first the toxicity assessment methods, pointing to the gaps in knowledge about this essential part of the process and suggesting avenues for further improvement. Deficiencies in the current regulations regarding toxicity testing are discussed, in particular the effect of the time factor on toxicity and the issue of complex mixtures. Other matters of concern are the extrapolation of toxicity data from the individual to the population and community levels, and the sub-lethal effects. The exposure assessment methods are dealt with in a second place. These rely on modelling and actual measurements of chemical residues in the environment. Various techniques employed to determine to exposure and bioavailability of agrochemicals to the various organisms in both aquatic and terrestrial ecosystems are reviewed. Again, the shortcomings and gaps in knowledge are addressed and suggestions for improvement are pointed out. Then, the process of putting together the information from the toxicity and exposure assessments to evaluate risks is discussed. Tiers I and II of the risk assessment are reviewed. The challenge here is to keep objectivity in the evaluations; this may require the introduction of new methods of risk assessment. Finally, the risk assessment implies establishing a management strategy that aims at reducing or minimising the impacts of agrochemicals under normal agricultural scenarios. Recommendations are often case-specific and need to be based on sound science as well as common sense principles. The chapter concludes with a summary of issues that need to be considered for improving risk assessments of agrochemicals.",signatures:"Francisco Sánchez-Bayo and Henk A. Tennekes",downloadPdfUrl:"/chapter/pdf-download/48545",previewPdfUrl:"/chapter/pdf-preview/48545",authors:[{id:"74970",title:"Dr.",name:"Francisco",surname:"Sánchez-Bayo",slug:"francisco-sanchez-bayo",fullName:"Francisco Sánchez-Bayo"},{id:"173845",title:"Dr.",name:"Henk",surname:"Tennekes",slug:"henk-tennekes",fullName:"Henk Tennekes"}],corrections:null},{id:"48552",title:"Environmental Pesticides and Heavy Metals — Role in Breast Cancer",doi:"10.5772/60779",slug:"environmental-pesticides-and-heavy-metals-role-in-breast-cancer",totalDownloads:2239,totalCrossrefCites:4,totalDimensionsCites:7,hasAltmetrics:0,abstract:"The intent of this chapter is to provide an overview to the current thoughts and ideals regarding the involvement of pesticides and heavy metals in the progress of breast cancer. The history of pesticides encompasses a few millennia, but our understanding of the pesticide action and the health consequences has only begun to develop in the last 30-40 years. Interestingly, many of these pesticides have estrogen-like activity and may be involved in the development of breast cancer. A new category of estrogen-like compounds has been identified and studied in the last 30 years, the ‘metalloestrogens’. Heavy metals, such as cadmium, which have estrogen like activity will be discussed. Finally, we will attempt to pull together the actions of pesticides and metalloestrogens as a possible synergistic mechanism by which these toxins may work to promote breast cancer development.",signatures:"David R. Wallace",downloadPdfUrl:"/chapter/pdf-download/48552",previewPdfUrl:"/chapter/pdf-preview/48552",authors:[{id:"173819",title:"Dr.",name:"David",surname:"Wallace",slug:"david-wallace",fullName:"David Wallace"}],corrections:null},{id:"48594",title:"Environmental Exposure and Health Effects Associated with Malathion Toxicity",doi:"10.5772/60911",slug:"environmental-exposure-and-health-effects-associated-with-malathion-toxicity",totalDownloads:2699,totalCrossrefCites:17,totalDimensionsCites:34,hasAltmetrics:1,abstract:"Malathion (O,O-dimethyl-S-1,2-bis ethoxy carbonyl ethyl phosphorodithionate) is a non-systemic, wide-spectrum pesticide. It is widely used throughout the world for agricultural, residential, and public health purposes, mainly to enhance food production and to provide protection from disease vectors. Malathion preference over other organophosphate pesticides relates to its low persistence in the environment as it is highly susceptible to hydrolysis, photolysis, and biodegradation. However, numerous malathion poisoning incidents including acute and chronic cases have been reported among pesticide workers and small children through accidental exposure. Malathion toxicity is compounded by its reactive metabolites and also depends upon the product purity, route of exposure, nutritional status, and gender of exposed individuals. Its metabolic oxidation in mammals, insects, and plants leads to the formation of malaoxon which appears to be several times more acutely toxic and represents the primary cause of malathion’s toxicity. Depending on the level of exposure, several signs and symptoms of toxicity including numbness, tingling sensation, headache, dizziness, difficulty breathing, weakness, irritation of skin, exacerbation of asthma, abdominal cramps, and death have been reported. Similar to other organophosphate pesticides, malathion exerts it toxic action by binding to acetylcholinesterase enzyme and inhibiting its activity, leading to accumulation of acetylcholine in synaptic junctions, which in turn results in overstimulation of cholinergic, muscarinic, and nicotinic receptors, and subsequent induction of adverse biologic effects. This chapter provides an update and analysis of the production and use, environmental occurrence, molecular mechanisms of toxicity, genotoxicity and carcinogenicity, and adverse human health effects associated with malathion exposure.",signatures:"Paul B. Tchounwou, Anita K. Patlolla, Clement G. Yedjou and\nPamela D. Moore",downloadPdfUrl:"/chapter/pdf-download/48594",previewPdfUrl:"/chapter/pdf-preview/48594",authors:[{id:"113353",title:"Prof.",name:"Paul",surname:"Tchounwou",slug:"paul-tchounwou",fullName:"Paul Tchounwou"}],corrections:null},{id:"48553",title:"Ecotoxicology of Glyphosate and Glyphosate-Based Herbicides — Toxicity to Wildlife and Humans",doi:"10.5772/60767",slug:"ecotoxicology-of-glyphosate-and-glyphosate-based-herbicides-toxicity-to-wildlife-and-humans",totalDownloads:2596,totalCrossrefCites:10,totalDimensionsCites:19,hasAltmetrics:1,abstract:"The use of agrochemicals, especially herbicides, is necessary to control pests in order to produce adequate food for the global population (estimated at 7 billion). Glyphosate and glyphosate-based herbicides have been used extensively for this purpose but recent studies have reported these chemical substances to be found in aquatic ecosystems, wildlife and humans in various quantities. In this chapter, we reviewed the impacts of glyphosate and glyphosate-based herbicides on wildlife and humans using measured endpoint effects caused by genotoxicity, cytotoxicity and reproductive toxicity. We used findings from different current investigations to demonstrate adverse effects, or otherwise, of glyphosate exposure to wildlife and humans. Our review reveals that glyphosate and its formulations may not only be considered as having genotoxic, cytotoxic or endocrine disrupting properties but they may also be causative agents of reproduction abnormalities in both wildlife and humans. Furthermore, the extensive use of glyphosate-based herbicides in genetically modified glyphosate-resistant plants grown for food and feed should be of grave concern since they can be sources of genotoxicity, cytotoxicity, and reproductive toxicity in wildlife and humans.",signatures:"Paul K. Mensah, Carolyn G. Palmer and Oghenekaro N. Odume",downloadPdfUrl:"/chapter/pdf-download/48553",previewPdfUrl:"/chapter/pdf-preview/48553",authors:[{id:"169135",title:"Dr.",name:"Paul",surname:"Mensah",slug:"paul-mensah",fullName:"Paul Mensah"},{id:"173888",title:"Prof.",name:"Carolyn",surname:"Palmer",slug:"carolyn-palmer",fullName:"Carolyn Palmer"},{id:"175580",title:"Dr.",name:"Oghenekaro Nelson",surname:"Odume",slug:"oghenekaro-nelson-odume",fullName:"Oghenekaro Nelson Odume"}],corrections:null},{id:"48784",title:"Genotoxicity of the Neonicotinoid Insecticide Poncho (Clothianidin) on CD1 Mice Based on Alkaline Comet and Micronucleus Assays",doi:"10.5772/61174",slug:"genotoxicity-of-the-neonicotinoid-insecticide-poncho-clothianidin-on-cd1-mice-based-on-alkaline-come",totalDownloads:1796,totalCrossrefCites:8,totalDimensionsCites:8,hasAltmetrics:0,abstract:"Poncho is a commercial formulation of neonicotinoid insecticides and a new agrochemical in Mexico, and it has the active ingredient clothianidin. The genotoxic effects of this commercial formulation of clothianidin on CD1 male mice were analyzed using micronucleus and comet alkaline assays. Three concentrations of clothianidin (20, 40, and 80 mg/kg/body weight) as well as negative (deionized water) and positive controls (cyclophosphamide 40 mg/g/body weight) were intraperitoneally injected into groups of mice every 3 days for 21 days. Peripheral blood samples were drawn from the caudal vein and divided to carry out the comet alkaline and micronuclei assays. DNA damage was evaluated using three genotoxicity parameters: the comet frequency, the tail length, and the moment from 100 nuclei. Additionally, the micronuclei frequency was quantified in 2000 peripheral blood erythrocytes using Giemsa stain. The results of the comet assay showed that the neonicotinoid insecticide Poncho leads to a significant increase in these three genotoxic parameters and in micronuclei frequency in the peripheral blood erythrocytes of mice treated with either concentration as compared with negative controls. At 80 mg/kg/body weight of Poncho, higher micronuclei frequencies and many more DNA strand breaks were observed compared with the negative controls. This study demonstrates that the commercial neonicotinoid insecticide Poncho induces genotoxic effects in CD1 male mice.",signatures:"María Elena Calderón-Segura, José Arturo Marcial Rojas, María de\nGuadalupe Mézquita Brito, Manuel TecCab, María del Carmen\nCalderón-Ezquerro and Sandra Gómez-Arroyo",downloadPdfUrl:"/chapter/pdf-download/48784",previewPdfUrl:"/chapter/pdf-preview/48784",authors:[{id:"174590",title:"Dr.",name:"María Elena",surname:"Calderón Segura",slug:"maria-elena-calderon-segura",fullName:"María Elena Calderón Segura"},{id:"175532",title:"Prof.",name:"Jose Arturo",surname:"Marcial-Rojas",slug:"jose-arturo-marcial-rojas",fullName:"Jose Arturo Marcial-Rojas"},{id:"175533",title:"Dr.",name:"María De Guadalupe",surname:"Mezquita-Brito",slug:"maria-de-guadalupe-mezquita-brito",fullName:"María De Guadalupe Mezquita-Brito"},{id:"175534",title:"BSc.",name:"Manuel",surname:"TecCab",slug:"manuel-teccab",fullName:"Manuel TecCab"},{id:"175535",title:"Dr.",name:"María Del Carmen",surname:"Calderón-Esquerro",slug:"maria-del-carmen-calderon-esquerro",fullName:"María Del Carmen Calderón-Esquerro"}],corrections:null},{id:"48760",title:"The Ecotoxicity of Pyrimethanil for Aquatic Biota",doi:"10.5772/60708",slug:"the-ecotoxicity-of-pyrimethanil-for-aquatic-biota",totalDownloads:1551,totalCrossrefCites:2,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Via the application of agrochemicals, farmers currently guarantee high productivity of fruit and vegetable crops. However, pest reduction using excessive amounts of such chemicals has a negative effect on aquatic organisms. The spray-drift, leaching, run-off or accidental spills occurring during or after application has become a serious and increasing problem for aquatic ecosystems. Pyrimethanil (PYR) is one of the most used fungicides. Such increase has heightened the interest in studying the potential risk and influence of PYR on the environment. In this chapter information on the PYR environmental risks for aquatic organisms was divided into three different approaches: (i) assessment of toxic effects of the pure active ingredient or the commercial formulation on primary producers, (ii) assessment of toxic effects of the pure active ingredient and PYR formulation on aquatic animals, and (iii) estimation of the role of PYR as an environmental disturber by triggering avoidance response. The available data provide evidences that PYR is potentially toxic for many aquatic species, affecting survival, reproduction, feeding, growth, and that it can disturb the environmental quality with no direct effect at the individual level by inducing organisms to migrate to less impacted areas.",signatures:"Cristiano V.M. Araújo, Cândida Shinn, Ruth Müller, Matilde Moreira-\nSantos, Evaldo L.G. Espíndola and Rui Ribeiro",downloadPdfUrl:"/chapter/pdf-download/48760",previewPdfUrl:"/chapter/pdf-preview/48760",authors:[{id:"173959",title:"Dr.",name:"Cristiano",surname:"Araújo",slug:"cristiano-araujo",fullName:"Cristiano Araújo"},{id:"174319",title:"Dr.",name:"Cândida",surname:"Shinn",slug:"candida-shinn",fullName:"Cândida Shinn"},{id:"174320",title:"Dr.",name:"Matilde",surname:"Moreira-Santos",slug:"matilde-moreira-santos",fullName:"Matilde Moreira-Santos"},{id:"174321",title:"Dr.",name:"Ruth",surname:"Müller",slug:"ruth-muller",fullName:"Ruth Müller"},{id:"174322",title:"Dr.",name:"Evaldo",surname:"Espíndola",slug:"evaldo-espindola",fullName:"Evaldo Espíndola"},{id:"174323",title:"Dr.",name:"Rui",surname:"Ribeiro",slug:"rui-ribeiro",fullName:"Rui Ribeiro"}],corrections:null},{id:"48539",title:"Toxicity of Agrochemicals on Freshwater Invertebrates — A Short Review",doi:"10.5772/60762",slug:"toxicity-of-agrochemicals-on-freshwater-invertebrates-a-short-review",totalDownloads:1771,totalCrossrefCites:2,totalDimensionsCites:3,hasAltmetrics:0,abstract:"The increase of worldwide population and the need to control pests are some of the factors that have led to the application of agrochemicals on agricultural areas to protect and increase crop production. Nevertheless, these substances are of environmental concern since they can reach water reservoirs and act on non-target organisms. Therefore, different aquatic species have been tested to evaluate their sensitivity to different toxicants, including pesticides, so as to elucidate the secondary effects of these chemicals to estimate “safe levels” in aquatic media. A wide variety of toxicity tests can be found in literature to evaluate the toxicity of xenobiotics in the environment at organismal and sub-organismal levels under different regimes. This chapter focuses on those tests performed with some freshwater invertebrates (cladocerans and rotifers) to study the toxicity of four important classes of pesticides.",signatures:"Daniel Robles-Vargas",downloadPdfUrl:"/chapter/pdf-download/48539",previewPdfUrl:"/chapter/pdf-preview/48539",authors:[{id:"173830",title:"Dr.",name:"Daniel",surname:"Robles-Vargas",slug:"daniel-robles-vargas",fullName:"Daniel Robles-Vargas"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"8533",title:"Pesticides",subtitle:"Use and Misuse and Their Impact in the Environment",isOpenForSubmission:!1,hash:"420a19fa07c8510eeb08decebed430cc",slug:"pesticides-use-and-misuse-and-their-impact-in-the-environment",bookSignature:"Marcelo Larramendy and Sonia Soloneski",coverURL:"https://cdn.intechopen.com/books/images_new/8533.jpg",editedByType:"Edited by",editors:[{id:"14764",title:"Dr.",name:"Marcelo L.",surname:"Larramendy",slug:"marcelo-l.-larramendy",fullName:"Marcelo L. 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Patients may present with malignant arrhythmias and hemodynamic collapse, and may require transport to a center offering extracorporeal life support. In this chapter we aim to provide a brief overview of pediatric myocarditis, with a particular focus on considerations for stabilization and transport in acute fulminant myocarditis. These considerations include intubation and ventilation, hemodynamic support, induction of anesthesia and pharmacological considerations for sedation, patient triage, and choice of an appropriate receiving center.
Myocarditis is an acute inflammatory disease of the myocardium, classically characterized by myocyte necrosis [1], which leads to ventricular dysfunction. There are several possible causes of myocarditis including infectious (viral, bacterial, fungal, yeast, parasitic, and protozoan) and non-infectious (immune mediated reactions, toxins, and other disorders). In many cases there is no identified cause. Most cases of pediatric myocarditis with a known etiology are caused by infections, in particular by viral infections [2]- [4], however a viral etiology may be difficult to detect. In a recent autopsy series examining 28 cases of myocarditis, viral analysis was done in 25 cases and was only positive in 9 of those. [5]
It has been estimated that pediatric cardiomyopathy occurs in between 1.13 and 1.24 per 100,000 patients, and more than 14% of these patients likely have cardiomyopathy from an infectious cause. [6]- [8] Klugman et al identified 216 cases of pediatric myocarditis over a one-year period in 35 different children’s hospitals, making up 0.05% of all patients seen. This group concluded that pediatric patients with myocarditis have considerable variability in their outcomes, use more intensive care unit (ICU) resources, and die more often than children with other diagnoses. [9] There is a broad range of clinical presentation ranging from asymptomatic to fulminant and symptoms are often non-specific. Some patients present with constitutional symptoms, and complaints of chest pain and fatigue are common. Additionally there may be large variability between presentations in different age groups. Patients with cardiac dysfunction may have syncope, heart failure, arrhythmias, or shock. [1] Fulminant myocarditis occurs in approximately 20–30% of all cases, and clinically presents with severe hemodynamic deterioration, cardiogenic shock, severe ventricular dysfunction, and possibly life-threatening arrhythmias. [10] Unlike adult patients, children more commonly present with fulminant myocarditis. [11] Myocarditis is a significant cause of sudden death and may result in the development of cardiomyopathy in some affected children. [12], [13]
The diagnosis of myocarditis is often difficult. In one series of 31 cases of myocarditis in a pediatric emergency department, 57% of patients had been previously evaluated by a physician and diagnosed with pneumonia or asthma. [14] The less controversial diagnostic modalities include chest x-ray, electrocardiogram (EKG) and echocardiogram. Sinus tachycardia on EKG with low-voltage QRS complexes is described as a classic finding. Beyond that there may be a variety of changes seen on EKG, including widened QRS complexes, non-specific ST changes, axis deviation, and/or Q waves. Patients may also present with arrhythmias including ventricular tachycardia, supraventricular tachycardia, and varying degrees of heart block.
EKG of a 12 year old patient with myocarditis, atrioventricular block [
EKG (rhythm strip) of the same patient, who had ongoing severe ventricular dysfunction and developed intermittent episodes of wide-complex tachycardia [
EKG (rhythm strip) of a 7 year old patient with myocarditis; wide-complex tachycardia [
Chest x-ray findings tend to be consistent with congestive heart failure, including cardiomegaly and increased pulmonary markings suggestive of pulmonary edema. Echocardiography is a useful adjunct to assess ventricular dimensions, function, and presence of atrioventricular valve regurgitation or pericardial effusion.
A recent review of diagnostic strategies for myocarditis concluded that enlarged ventricular dimensions on echocardiography and elevated cardiac troponin levels were the most common findings. [16] Troponin I has high specificity but limited sensitivity in the diagnosis of myocarditis, despite the fact that it is otherwise a reliable and commonly available biomarker of myocardial injury. [17] In children, cardiac troponin T has been reported to have a sensitivity of 71% in myocarditis. [18] Other common laboratory studies include general markers of inflammation or infection, such as complete blood count with differential, C-reactive protein and erythrocyte sedimentation rate. It is also useful to examine markers of end organ perfusion including lactate, liver function tests and creatinine. These studies may help understand the etiology and impact of the disease process, but none are specific for myocarditis.
More controversial diagnostic modalities include cardiac magnetic resonance (CMR) imaging and endomyocardial biopsy (EMB). In general these techniques would not be employed in an acute setting in a non-tertiary care center. CMR has the advantage of being non-invasive it requires specialty equipment and radiologists familiar with the interpretation of findings. EMB is controversial for a variety of reasons, especially since it is invasive and carries a risk of adverse events. Also, myocardial inflammation tends to be patchy and may be missed by biopsy. A recent consensus statement by the American College of Cardiology and the European Society of Cardiology made a class IIa recommendation for EMB in cases of unexplained cardiomyopathy in children. [19]
Pediatric patients with symptomatic myocarditis should be admitted to a pediatric tertiary care center. Klugman et al. reported that in their cohort of pediatric myocarditis patients 45% of patients required milrinone, 35% needed epinephrine, and 25% were supported with mechanical ventilation. Extracorporeal membrane oxygenation was needed in 7% of patients, and cardiac transplantation in 5%. [9] When triaging the patient, consideration should be given to the fact that any patient requiring the use of blood pressure support in the setting of acute myocarditis may quickly deteriorate and need mechanical cardiovascular support. Extracorporeal membrane oxygenation (ECMO) support is now increasingly viewed as optimal supportive therapy in anticipation of full cardiac recovery. [20] In larger children, a ventricular assist device (VAD) has also been used to support ventricular function during acute illness. In a previously published paper reporting the transport a series of children with myocarditis, there were five out of ten patients who required ECMO. Among those five patients there were three survivors. [15] In another retrospective review of 36 cases of histologically confirmed myocarditis ECMO was used in 4 patients (11%). [21]
It has been estimated that fewer than ten percent of hospitals with intensive care unit beds have pediatric critical care beds. [22], [23] Therefore, pediatric admission to a tertiary intensive care unit frequently requires patient transport. Though emergency medical service teams are trained in basic pediatric resuscitation and stabilization, often times they do not have the breadth of experience or advanced training which would provide for the safest transport of the critically ill child. The use of a critical care transport teams on the other hand is strongly associated with decreased complication rates. [24]- [27] In particular for pediatric patients, the chance of an unplanned airway or cardiovascular event was 22 times greater when a critical care transport team was not used. [24] In any population of patients with a high risk for cardiopulmonary deterioration, consideration must be given to balancing the potential benefit of using a critical care transport team and the risk of holding the patient in the emergency department for a longer time period until the specialty team is available.
For the above reasons, patients who present with symptomatic myocarditis are best transported to a tertiary care center with a critical care transport team. These patients are at high risk for deteriorating during transport, and often require urgent interventions upon arrival at the receiving hospital. Helicopter transport may be faster than ground transport, although this is not always true in urban environments or if the involved facilities do not have an on-site helipad. [28] Helicopter transport guidelines have identified pediatric patients with symptomatic myocarditis as appropriate candidates for helicopter transport. [29] While an efficient mode of transport, medical helicopters have maximum distance limitations. There are also strict weather and altitude limitations to helicopter transport, which may affect ground and fixed wing transport to a lesser degree. A patient requiring frequent assessment or interventions may be challenging to care for in a helicopter due to noise, lack of space making access to the patient challenging and turbulence in flight. Additionally in a helicopter, and certainly in a fixed wing vehicle, it may be more difficult to divert to a different receiving facility should the patient become acutely unstable for transport. There is no evidence looking at pediatric myocarditis and ideal modes of transport. Data from adult patients shows that there are conflicting reports about the efficacy of different modes of transport, specifically helicopter versus ground transport. In 2012 a retrospective cohort study showed that among patients with major trauma admitted to level I or level II trauma centers, transport by helicopter compared with ground services was associated with improved survival to hospital discharge. [30] While there are earlier studies in agreement with these findings, other studies in the adult population have failed to show a benefit of helicopter transport. [31]- [34]
In summary, choosing a team and mode of transport for a patient is complex. There are many factors influencing decision-making surrounding patient transport. The medical team should consider the patient’s anticipated medical needs and the risks of destabilization during transport, the urgency of the treatments needed at the receiving facility, transport logistics such as altitude, weather and distance, and the team availability and experience. [35]
There are currently no specific therapies for acute fulminant myocarditis. The mainstay of therapy is supportive care to maintain cardiac output including mechanical ventilation, inotropic support and, if tolerated, afterload reduction and diuresis. For transport purposes intubation, ventilation and inotropic support play a larger role than other support strategies. In adult populations there have historically been more options for ventricular assist devices. However, pediatric assist devices have been successfully developed. In a recent study of the Excor Pediatric ventricular assist device (Berlin Heart), Fraser et al demonstrated that survival rates for patients awaiting heart transplant were significantly higher with the ventricular assist device than with ECMO. [36] This data is not specific for myocarditis, but is promising that assist devices can be effectively used in the pediatric population. Currently, the majority of patients with refractory cardiogenic shock and/or severe respiratory failure will likely require ECMO for ongoing support.
In patients with evidence of pulmonary edema the risk of worsening hypoxemia and potential for respiratory acidosis is concerning, as neither would be well tolerated from a cardiac standpoint. As respiratory demands increase to compensate for these issues, the oxygen consumption of the respiratory muscles can increase up to eightfold. [37] Intubation and mechanical ventilation will reduce respiratory muscle oxygen consumption, and thus overall myocardial oxygen demand. [37] The risks of the induction for intubation should be carefully weighed against these benefits, but declining status may force a clinician to proceed with endotracheal intubation prior to transport.
In general, positive pressure ventilation reduces left ventricular wall tension and left ventricular afterload, and therefore may improve cardiac output by this mechanism. However, other cardiopulmonary interactions associated with intubation and positive pressure ventilation may precipitate low cardiac output or cardiac arrest in a patient with biventricular failure. Those potentially harmful interactions include cessation of right sided venous return during the transition from spontaneous breathing to positive pressure ventilation, and systemic vasodilation and negative inotropy induced by medication used for induction of anesthesia. If possible, it is important to ensure that the patient is euvolemic prior to induction to preserve right ventricular preload upon initiation of positive pressure ventilation. It is also advisable to have an inotropic agent either initiated or prepared to infuse to support biventricular function. [38]The choice of specific induction agents is less important than recognizing that patients in failure will likely have limited contractile reserve, will be relatively preload dependent and will not respond well to rapid changes in afterload. [39] The choice of the appropriate medication for induction of anesthesia for intubation is important. Any agent may precipitate vasodilation and cardiac depression. Etomidate is well-known for a low rate of adverse hemodynamic effects, and the direct sympathomimetic effects of ketamine may be particularly beneficial in shock states. [40] Carefully titrated low-dose fentanyl may also provide appropriate levels of sedation and analgesia with a more favorable cardiac profile. Midazolam, propofol, and barbiturates are all likely to trigger hypotension at induction doses and should therefore be avoided. Atropine premedication may be considered in pediatric patients with bradycardia, though many patients with myocarditis are tachycardic on presentation. [38]
The adverse hemodynamic effects of positive pressure ventilation on right sided venous return may be ameliorated by using a strategy to minimize mean airway pressure, thus reducing intrathoracic pressure. This includes avoiding lung hyperinflation, minimizing peak inspiratory pressures, the use of short inspiratory times and adequate expiratory times and conservative use of positive end-expiratory pressure (PEEP). While PEEP may be helpful in managing pulmonary edema and hypoxemia, it should be used with caution as it may lead to decreased right ventricular preload and increased right ventricular afterload.
Both tachycardia and bradycardia can pose risks to a pediatric patient in acute heart failure. Arrhythmias must be quickly recognized and treated. Transcutaneous pacing has been recognized as an easy, safe, and effective temporary measure of rate control but may require sedation and likely requires analgesia in the pediatric patient. [41]- [44] As mentioned, administering sedation in a pediatric patient with myocarditis and cardiovascular compromise could lead to further hemodynamic instability. Initiation of catecholamines such as dopamine may provide benefit in patients with complete heart block by increasing the ventricular escape rate to improve systemic perfusion in transport and should be considered before initiation of transcutaneous pacing in hemodynamically stable patients. However, when using such agents care should be taken not to acutely increase left ventricular afterload.
Management of heart failure should be employed if the patient can tolerate diuresis and afterload reduction, but is probably not advisable in the acute setting. Ideally this management would include diuretics to lower filling pressures and angiotensin-converting enzyme (ACE) inhibitors to reduce systemic vascular resistance and left ventricular afterload. Beta-blockade may be used as well, however the only randomized controlled trial of beta-blockade for treatment of pediatric heart failure failed to demonstrate a benefit. [45] Furthermore using a beta-blocker in the acute setting may complicate resuscitation efforts should a patient have critically compromised output or lose circulation altogether. In patients with significant dysfunction and diminished cardiac output systemic inodilators such as milrinone, are often useful if tolerated. Due to the risk of systemic hypotension and some risk of worsening myocardial dysfunction these interventions are best started in a tertiary care setting, not during transport.
Levosimendan is a positive ionotrope and functions by binding to cardiac troponin C to increase calcium sensitivity of myocytes. It also has vasodilatory effects in arterial, venous and coronary vasculature, which leads to afterload reduction and better matching of myocardial oxygen demand. [46]- [49] Therefore despite improving ventricular function, levosimendan does not significantly increase myocardial oxygen demand. Levosimendan is currently not FDA approved, so there is no collective experience with it the US centers. There are case reports of levosimendan being used successfully in both adult and pediatric myocarditis. [50]- [52] However, there are no larger, prospective studies to provide adequate evidence for routine use at this point. It remains unclear what potential benefit this drug would have in critical care transport.
The benefit of immune modulation remains controversial, and is not usually an adjunct to consider during acute transport management. Intravenous immunoglobulins (IVIG) are the most commonly used immune modulator in myocarditis. Drucker et al. showed a statistically significant improvement in survival in pediatric patients treated with IVIG. [53] However McNamara conducted a randomized control trial in adults and failed to show any difference in survival among those treated with IVIG. [54] The data on the use of immunosuppressive agents such as prednisone, azathioprine and cyclosporine is not yet convincing. When the existing data was examined in a meta-analysis, Hia et al were not able to find statistical significance for improved outcomes. [55] That said, many centers currently use IVIG in the treatment of myocarditis and in certain cases immunosuppressive therapy may improve outcomes. [9], [56]
In severe cases of cardiogenic shock patients may require rescue with veno-arterial (VA) ECMO or ventricular assist devices (VADs). Veno-venous (VV) ECMO is typically reserved for patients with predominant pulmonary failure. Whether requiring ECMO or VAD support, patients are best cared for in tertiary care centers with established ECMO programs.
VA-ECMO should be considered in patients with myocarditis only once routine supportive therapies have failed. [57], [58] While potentially life-sustaining in these cases, ECMO is not without risk. There is significant chance for hemorrhage, infectious complications and vascular injury during cannulation. There is also a risk of cerebral and coronary hypoxia and stroke. Less common, but potentially life-threatening are thrombotic events. Another complicating issue, which may ultimately compromise ventricular recovery, is left atrial hypertension secondary to poor ventricular function and decreased ejection while on ECMO. Left atrial hypertension can result in increased left ventricular end-diastolic pressure, subendocardial ischemia and pulmonary edema. There is no consensus on indications or technique for left atrial decompression, but it has been shown to relieve pulmonary edema and improve hemodynamics in one study. [59]
In experienced centers, ECMO is often successfully employed as a short-term rescue therapy for refractory cardiopulmonary failure. Though there is extensive experience with pediatric ECMO, in addition to potential complications there are also other significant limitations: need for sedation, lack of mobility, and relatively short lifespan of the circuit. In cases where failure is more chronic, or transplant is needed, a VAD may be a more appropriate intervention. VADs are available as right (RVAD), left (LVAD) and bi-ventricular (BiVAD) devices. They have been used for ventricular recovery, destination devices and as bridges to heart transplant. A recent prospective, single-group pediatric trial showed that survival rates to transplant were significantly higher with the ventricular assist device than with ECMO. [36] Complications of assist devices are significant and similar to ECMO, including bleeding, stroke, infection and thrombotic events.
Pediatric ECMO is offered in many centers worldwide [60], and increasingly ECMO centers are confronted with the request to transport a patient on ECMO. A few centers in the United States and in Europe reported these transports in the literature. [61]- [67] One group reported the successful transport of 68 children on ECMO, traveling a distance between eight and 7500 miles. Overall ECMO survival was comparable with in-house survival on ECMO at the same institution. More importantly, no deaths occurred during ECMO transport. [66]
Bringing an ECMO team to a referring facility to place an unstable patient on extracorporeal support and then transport the patient back to a tertiary care center on ECMO has been suggested and, in a few cases, successfully completed. The logistics of providing such a service are very complicated. Based on military data, Coppola and colleagues reported that the ECMO transport team consists of 10-15 staff members, including a mission commander, a pediatric intensivist, a pediatric cardiologist, a pediatric surgeon, two to three ECMO specialists, nurses and respiratory therapists [66]. A civilian team reported using a team consisting of two nurses, two ECLS specialists, an attending physician, and a resident. [67] ECMO transports to date have been completed in ground, fixed-wing, and rotor-wing vehicles. The complexity of ECMO transport warrants careful discussion about feasibility and resource utilization, but may be successfully accomplished. That said, early referral to an ECMO center while the patient may be safely transported without ECMO is the preferred option.
Myocarditis presents with a broad range of relatively non-specific symptoms and for that reason is difficult to diagnose, but must remain on the list of differential diagnoses for any child presenting with acute heart failure or other signs of cardiac deterioration. Acute fulminant myocarditis is life-threatening and requires careful, proactive management. When treating the pediatric patient with acute fulminant myocarditis clinicians should consider the benefits of intubation, inotropic infusions, and transcutaneous pacing as temporizing measures especially during the transport phase, recognizing that any of those interventions can lead to further deterioration of the patient if not performed with great caution. Prompt and safe transport to a pediatric tertiary care center should be ensured. The option of early management with ECMO or other assist devices seems beneficial and should be considered when making triage decisions.
Evolution, expansion and transformation of several wild crops via domestication and breeding have blessed the humans and animals with never ending wide varieties of plant-based foods around the globe [1]. Nevertheless, ~ 1 billion population around the world combat with hunger and malnutrition as they are unable to consume important vitamins/minerals thus affecting food and nutritional security in many developing countries [2]. These nutritional deficiencies could be due to the increased inclination towards consumption of specific crops as majority of the peoples relies on wheat, rice and maize for their food [1]. Several lines of literatures have documented that around 50% of total world population relies on above crops for catering while other crops like legumes are cultivated and consumed by marginal communities [3]. The crops cultivated by marginal communities are referred as neglected and underutilised crop species (NUCS) and rich source of vitamins, minerals and secondary metabolites having pharmaceutical properties [4]. These NUCS have the potential to counteract malnutrition by ensuring health/nutritional security, alleviate poverty by increasing resilience and sustainability to the farming systems [1]. However, compare to mainstream crops, less focused have been given towards the genetic improvement of NUCS.
Hyacinth bean (
Furthermore, the seeds of hyacinth bean are also abundant in carbohydrate myoinositol that are exceptional in ovarian function in women by controlling oligomenorrhea and polycystic syndrome [8]. Additionally, the seeds also contain brassinolide which is a steroid which is clinically proven to cure prostate cancer in humans. The alkaloid spermidine found in hyacinth bean seeds is comprehensively used as a biomarker for the perception of skin cancer where as another alkaloid spermine is commonly used in the treatment of cancer/tumours [9]. Trigonelline another alkaloid found in its seed has demonstrated its role in the treatment of diabetes mellitus and also possess antimicrobial property against
Despite of its pharmaceutical/therapeutic importance and catering food requirements of both humans and animals, hyacinth bean still lack focused research for its genomic improvement as compared to other mainstream crops (wheat, rice maize etc.). The genomic improvement through state-of -the art tools and techniques will not only reform its architectural growth but will also pave the way for rewiring the biosynthesis of imperative metabolites which will significantly impact its growth, yield and therapeutic potential. Therefore, this chapter provides valuable insights about the different state-of -the art tools and techniques that can be employed for the genetic improvement of hyacinth bean and how they can be exploited to inspire its therapeutic potential. Further, role of biotic and abiotic elicitors in stimulating the production of important metabolites in hyacinth bean has also been critically reviewed.
Being sessile in nature, plants have to withstand against various adverse climatic conditions to maintain their growth and developmental architecture. The plants are able to survive stressful conditions by synthesising diverse range of secondary metabolites and protease inhibitors that improve their adaptability [13]. Hyacinth bean for example, produces higher level of trypsin inhibitor (14–27 unit/mg) which is a unique property of this orphan legume crop compared to any other major legumes [14]. Like other serine inhibitors, trypsin inhibitor could also function as antifeedant or could also be responsible for strengthening growth, development and productivity by efficiently modulating proteolytic events with in hyacinth bean, mechanism of which has yet to be revealed [15]. Besides this, hyacinth bean also contains wide range of alkaloids, phenols and flavonoids which can be used in treatment of various chronic diseases essentially arthritis, nephritis sepsis as well as skin diseases thus significantly contributing towards human and animal health. All these nutritional and therapeutic properties make hyacinth bean a prime source of food, forage and cash crop in arid and semi-arid areas. However, till date the genes encoding these secondary metabolites are still ambiguous as the crop it self is considered as “orphan crop” for its genome revolution [1]. Further, both conventional and molecular breeding techniques also have been futile in the identification/linking of quantitative trait loci (QTLs) with production of these imperative secondary metabolites [4]. Therefore, all the above information’s have reinstated the need to implement advance omics technology for unleashing the genetic constituent of hyacinth bean and to identify genes/proteins involved in the biosynthesis of important secondary metabolites.
The phytochemicals or secondary metabolites synthesised by various under-utilised crops have the potential to boost innate immune response in humans as well as in animals thus providing immunity against infection, injury and irritation [7]. Several lines of literatures have strongly substantiated that various fruits, vegetables and food legumes synthesise various phytochemicals which are effectively exploited for the treatment of anti-inflammatory disorders, however their mechanism of action is still vague and needs to explored [13]. Various legumes such as soybean, mung bean, moth bean including hyacinth bean have diverted the attention of plant science community due to the presence of functional biological compounds which not only have health benefits and can also be simultaneously used for the treatment of various chronic diseases [8]. Researchers have analysed, tested and confirmed that the crude extracts of mung bean, hyacinth bean and soybean checks the synthesis of nitric oxide (NO) which is an inflammatory mediator thus significantly reducing the ear edema in mice caused by up-accumulation of arachidonic acid [16]. Likewise, another researcher evaluated crude extract of
The phenols present in the dry seeds of legumes such as hyacinth bean have also been implicated to exaggerate anti-inflammatory response upon their adequate consumption [18]. A plethora of research have well indicated that seed and other ethanolic extract of food legumes is rich source of polyphenols and natural antioxidants capable of stimulating anti-inflammatory activity by suppressing the expression of 15-LOX as well as modulating the expression of cyclooxygenase −1 (COX-1) and COX-2 [19]. Similar findings have also been reported by Zhu et al. [16] in pinto bean, black bean and common bean where seed extract was effective in regulating the expression of interlukin-6 (IL-6), interferon-γ (IFN- γ) and IL-17A thus effectively ameliorating acute colitis in mice. In addition to phenolic compounds, these legumes also contain lectins which is protein capable of showing anti-inflammatory response after binding reversibly to carbohydrates [20]. For example, lectins isolated and purified from
The flavonoids such as flavanones, flavanols, anthocyanidins, flavones and isoflavones present in fruits and vegetables have delineated themselves as key players in the treatment of cardiovascular diseases, diabetes and cancers [22]. Various legumes are also a rich source of dietary flavonoids that can regulate carbohydrate digestion, glucose uptake and insulin signalling via various signalling pathways [23]. Among all the flavonoids, dietary isoflavones
Some researchers have also reported neutral to moderate effect of soy food and methanolic extract of hyacinth bean rich in isoflavones in controlling plasma lipid profile thereby confirming anti-diabetic effect of isoflavones could act differentially under
Genistein have also been documented to stimulate the expression of protein kinase A and cAMP cascade which play important role in the proliferation of INS1 and pancreatic β-cells thus efficiently regulating glucose metabolism in mice [31]. However, in addition to isoflavones, anthocyanidin found in soybean seeds rich in cyanidin, delphinidin and petunidin have also demonstrated anti-diabetic effect in streptozotocin induced diabetic rats [32]. Researchers have used methanolic extract of anthocyanidin to diabetic mice and observed that the anthocyanidin effectively raised serum insulin concentration and glucose metabolism in rats. The possible reason behind the anti-diabetic effect of anthocyanidin could be due to the enhance translocation of GLUT4 (glucose transporter) which in turn have stimulated glucose uptake or anthocyanidin could have improved insulin signalling by causing phosphorylation of insulin receptor [33]. Similarly, in another study, researchers have also documented the beneficial effect of anthocyanidin by analysing it on diabetic animal model where they observe that diabetic animal treated with soybean anthocyanidin showed enhanced plasma insulin levels and low triglyceride content [34]. Furthermore, researchers continued their observation up to 12 weeks and observed that the diabetic mice exhibited reduced body weight, blood glucose level, triglyceride levels as revealed by lower expression of lipogenic gene expression in liver and fat [35]. Although, various studies have demonstrated the anti-diabetic effect of both isoflavones and anthocyanidin on animal system, there effect on controlling diabetes in humans are still limited. Therefore, efforts are needed to expand the dimension of research involving structural, biochemical and molecular characterisation of important therapeutic compounds obtained from underutilised legume crops for their efficient use in the human and animal welfare.
The bioactive peptides found in certain legumes and cereals crops has been implicated to regulate growth and development of crops plants by imparting biotic and abiotic stress tolerance [36]. Further, researchers have also isolated and purified some of the plant bioactive peptides and demonstrated their pivotal impact on human health and immune response [37]. Lunasin, a 43 amino acid peptide initially identified and isolated from soybean has shown its tremendous competency in inhibiting cell division in tumour/cancer cells and protect DNA damage by delaying histone acetylation in mammalian cells under oxidative stress [38]. Later, lunasin was also identified in cereals and pseudo-cereals such as rice, wheat, barley and amaranth, however, its present in extremely low quantity as compared to soybean [39]. Being a rich source of lunasin, soybean has been extensively investigated in order to get valuable insight into its structure and function properties, mode action in preventing cancer and the ecological factors that can influence its biosynthesis and transport [37]. Initially, lunasin was identified as chemo-preventive agent but in-depth investigations by several researchers demonstrated that lunasin can effectively suppress skin tumorigenesis in mouse by delaying foci formation in DMBA NIH/3 T3 cells [40].
In addition, researchers have also well documented the chemo-preventive property of lunasin in breast cancer affected mice where they observed significant reduction (30–40%) in tumour cells after treating the mice with lunasin for two months [37]. However, not much research has been focused on lunasin therapeutic properties in soybean as well as in other underutilised legumes still researchers have hypothesised its broad-spectrum role in the treatment of lung cancer, colon cancer and leukaemia [36]. One of the possible mechanisms by which lunasin block cell division in cancer cells could be due to its ability inhibits cell cycle at G2 phase thereby inducing apoptosis in the affected cells [40]. Initial studies on lunasin’s mode of action revealed that it can bind to hypoacetylated histone cores in cancer cells and inhibit acetylation in breast cancer cells and prostrate cancer cells [37]. Recently, researchers have made striking discovery claiming that lunasin binding can suppress the integrin signalling in cancer/tumour cells thereby inhibiting focal adhesion kinase/protein kinase B (FAK/AKT) and extracellular signal-regulated kinase 1 (ERK1) signalling in cancer cells [41]. Certain plant protease inhibitors such as Bowman-Birk inhibitors and flavonoids such as flavon-3-ols found in soybean and other legumes have also demonstrated their role in controlling breast and colon cancer [41]. However, detailed characterisation of their structural and functional properties in many legume crops is still ambiguous and need extensive research by employing advance omics technology for their potential application.
Hypertension is one of the most important factors (apart from diabetes and high cholesterol level) causing cardiovascular disease in humans which is characterised by the increase in systolic/diastolic arterial pressure [42]. Studies have well documented that healthy diet/lifestyle i.e. reduce sodium intake and physical exercise are important factors controlling blood pressure, hypertension and ultimately risk of cardiovascular disease [42]. Various major and underutilised legumes are rich source of secondary metabolites, fibres and micronutrients thus forming an important framework of plant’s bioactive compounds for healthy diet [43]. For example, some bioactive peptides from food as well as grain legumes have demonstrated their potential to combat both hyper and hypotensive effects. Peptides having Glu-Phe, Ile-Arg and Lys-Phe dipeptides identified form legume crops have shown anti-hypertensive effect by inhibiting the activity of Angiotensin-I- Converting Enzyme (ACE) [36, 44]. Similarly, proteins like tyrosinase and lupin present in legume crops have also shown their remarkable ability control both systolic/diastolic blood pressure in peoples suffering from hypertensive disorder [44].
The hypertensive property of both lupin and tyrosinase have also been extensively investigated under in vivo conditions in Goto-Kakizaki rats suffering from hypertension due to excessive consumption of Na rich diet. The researchers fed the hypertensive rats with both lupin and tyrosinase for two weeks and then observed significant reduction in the systolic/diastolic pressure in both the groups [45]. However, lupin treatment also significantly improved endothelium-dependent vasodilation in hypertensive rats more efficiently as compared to tyrosinase [45]. A large body of literatures have also indicated that these bioactive peptides/proteins do not only possess hypertensive and ACE inhibitory effect but are also actively involved in lowering cholesterol and lipid levels [44]. Researchers have also extensively studied hypocholesterolaemia by using bioactive peptides and proteins and identified that the peptide Ile-Ala-Val-Pro-Gly-Glu-Val-Ala was compellingly involved in lowering cholesterol and triglycerides levels by stimulating the activity of bile salts [46]. Furthermore, other studies have also well documented the role of soybean peptides/proteins in efficiently controlling high cholesterol and lipid levels by efficiently modulating ratio of low density/high density lipo-proteins and expression of beta-very-low-density lipoprotein (β-VLDL) receptors thus minimising risk factors for cardiovascular disease [46]. Researchers have identified and evaluated several of these bioactive peptides from other legumes crops as well, however efforts are needed for in-depth characterisation of their function and mode of action in other underutilised legumes such as in hyacinth bean.
Reactive oxygen species (ROS) generated as a consequence of oxidative stress are concomitantly involved in the onset and progression of various chronic diseases. Increased level of ROS has been shown to instigate severe damage to nucleic acids, cause membrane damage via lipid peroxidation and inhibit protein synthesis thus causing cell death or apoptosis [47]. Several crop plants including legumes contains various bioactive compounds such as flavonoids, phenols and some peptides that can efficiently scavenge ROS thus ameliorating stress induced oxidative damages [48]. Flavonoids such as flavanones and flavon-3-ols present in the seeds of certain leguminous plants such soybean and hyacinth bean have been reported to have antioxidative effect as demonstrated by both animal and cell culture studies [49]. In a study conducted by Babu et al. [50] oral infusion of flavanones and flavon-3-ols to an alloxan induced insulin dependent diabetic mouse, significantly enhanced the activity of hepatic catalase, superoxide dismutase and glutathione reductase enzymes thereby confirming their function as antioxidants. Similarly, in another study, researchers orally administered a flavonoid rich compound apigenin to streptozotocin-induced diabetic rats that significant reduction in the triglyceride levels which could be due the antioxidative effect of apigenin that effectively maintained ion/osmotic homeostasis [51]. Moreover, like apigenin, researchers also used anthocyanidin and luteolin treatment to diabetic rats which ultimately protected rat cells from oxidative damage via controlling the synthesis of iterlukin-1β and interferon-γ [52]. Like other flavonoids, anthocyanidin is also extensively present in legume plants which have received significant recognition owing to their health benefits and potential antioxidative properties [52].
Antioxidant peptides like His-Trp-Tyr-Lys have demonstrated to play exceptional role in ameliorating stress induce oxidative damage by efficiently regulating the scavenging of ROS [53]. Moreover, several studies have shown that thiol group of Cys residue can efficiently chelate metallic ions thus lowering the effect of oxidative stress and minimising the onset of chronic disease [53]. A study conducted by Morales-Medina et al. [54] reported that Val and Leu residues present at N-terminus of a peptide and Tyr and Trp residues present at C-terminus of same peptide have antioxidative properties that were effective in minimising lipid peroxidation and strengthening ion homeostasis. Furthermore, it is also well documented that seeds and leaves of legume plants are rich source of other bioactive compounds such as anthocyanins, polyphenols with antioxidative properties and are also capable of performing metal sequestration and stimulate the expression of other stress responsive genes [55]. Additionally, Zhu et al. [56] evaluated various other peptides from soybean and wheat having Leu-Leu-Pro-His-His repeat for its antioxidative activity by using distinct experimental procedure and conditions. The results indicated that the peptide was effective in stimulating 1,1-diphenyl-2-picrylhydrazyl (DPPH) activity, expression of enzymatic and non-enzymatic antioxidants such as catalase, superoxide dismutase, peroxidase and ascorbate thus controlling the level of ROS generation and minimising the chance of severe disease. Lunasin peptide found in soybean and other legume has also been extensively investigated for its antioxidative properties where the researchers documented that lunasin was effective in scavenging both hydrogen peroxide and superoxide anion thereby protecting cell from oxidative damage [42].
Since ancient times legumes have been ascribed to have pharmaceutical/therapeutic values far beyond than providing essential nutrition in the form of amino acids [57]. In recent years, various proteins/peptides form several legume species have been included in the category of nutraceuticals i.e., food or products derived from them having medicinal or therapeutic role in the prevention of disease along with nutritional benefits [57]. Various legume-based bioactive proteins/peptides have been isolated and characterised for their functional role such as Bowman-Birk inhibitors (BBIs), Kunitz inhibitors (KIs) and alpha amylase inhibitors (AAIs) which are also commonly known as anti-nutritional compounds [58]. Several researchers during their early epidemiological studies observed that the protease such as Bowman-Birk inhibitors isolated from soybean seeds were highly effective in the counteracting tumour growth under both
Furthermore, AAIs have demonstrated themselves has a suitable candidate for controlling triglyceride levels thus keeping obesity under check whereas lectins obtained from the seeds of legumes have also shown immense therapeutic potential displaying cytotoxic and anti-cancer activity [60]. For example, concanavalin lectin obtained from the seeds of
Several major and underutilised legumes are rich source of bioactive phenolic compounds or polyhydroxylated compounds with immense anti-nutritional and therapeutic potential [46]. These phenolic compounds also play significant role in the stimulation of immune response, protect cells from oxidative damage and other pathogenic diseases [64]. Several studies have documented that some phenolic compounds isolated from seeds of legume crops are indispensably involved in the treatment of cancer disease, microbial/pathogenic attack, inflammatory disease thus providing potential health benefits [46]. Phenolic compounds are large group of compounds comprising phenolic acids, flavonoids, tannins and stilbenes [64]. Several recent studies have well documented the anti-microbial activity of phenolic compounds obtained from Faba bean, broad bean, adzuki bean and Dolichos bean in their crude methanolic extract of leaf and seeds [65]. The total antioxidant activity (TAA) of methanolic extract of various phenolic compounds and tannins obtained from adzuki bean and lectins have been shown to exhibit anti-microbial activity against several bacterial strains showing average zone of inhibition of 8–20 mm [66]. In addition, these methanolic extract have also shown potential anti-fungal activity against
In addition to phenolic compounds, several bioactive peptides have also been instigated to play important role in regulating various biological activities along with antimicrobial and anti-inflammatory effects [57]. Studies have well reported that several of the ACE-inhibitory peptides containing Arg-Lys residues at C-terminus have shown enhanced anti-microbial activities against pathogenic microorganism [44]. Similarly, peptide containing Leu-Leu-His-His residues also have been shown to posses anti-microbial and anti-oxidative properties. Moreover, a group of researchers working on legume bioactive proteins attempted to used bioactive peptides in conjunction with phenolic compounds and ascertain that the amalgamation of both stimulate the defence mechanisms of plants against pathogenic attack [44]. Similarly, a protein dolichin extracted from hyacinth bean exhibited strong anti-microbial activity against
Plants act as factories that synthesises wide array of nutritional and secondary metabolites with complex structure and functions. Essentially, therapeutic/pharmaceutical secondary metabolites are often extensively isolated and purified from wild plant species or under-utilised crops as compared to cultivated species. However, the chemical synthesis of these medicinally important metabolites is a daunting challenge and is not economically feasible. Recent advancement in the system biology tools have pave the way to exaggerate their synthesis in tissue culture plants, but still their applications are limited to certain plant species because of the complex nature of technological standardisation in respective crops and lack of proper understanding of biosynthetic pathway. In this section, we will be discussing recent advancements made in the system and synthetic biology tools to provide detailed glimpse of the biosynthetic pathways and to explore the unprecedented possibilities of their application for the human welfare. These cutting-edged technologies can be successfully exploited for the improvement/enhancement of secondary metabolites production or could also help in the identification of novel metabolites in cultivated plants as well.
The phenotype exhibited by plants at certain stages of growth/developments are the function of gene × environment interaction that govern a peculiar trait of interest expressed from the plant’s genome [67]. The term “phenotype” corresponds to precise and rigorous recording of the distinct phenotypic parameters from single cell to whole plant level, which if conducted explicitly can help facilitate identification/classification of novel traits in several plant species. Phenomics is a sub-discipline of plant biology that deals with phenotyping under controlled green-house conditions as well as field experimentation using advanced imaging technologies and imaging tools [67]. Phenomics study is a three-step process involving (i) setting up experimental plot, light intensities, nutrition acquisition and temperature (ii) rigorous monitoring/phenotyping such as growth, stress response, photosynthesis, chlorophyll and secondary metabolite contents etc. using advanced imaging tools and (iii) computer-assisted data visualisation, interpretation and storage [68]. Recent technological advancements have paved the way for the development of high-resolution imaging platforms aided with advanced bio-informatic tools for the phenotyping several important traits in plants for cellular and functional analysis [69]. Therefore, phenomics has now been recognised as an indispensable tool that can provide valuable insights into plant’s morphology and physiology which can be further integrated with functional genomics data for analysing key traits such as secondary metabolites production and other economically important traits [68].
Several informatorily databases and analytical toolkits have been developed to facilitate phenomics and taxonomic studies in various cultivated and under-utilised crops at a greater pace. For example., PlantCLEF (2019) is an online repository that contain wide variety of images of plant’s organs with the sole purpose to facilitate identification and classification of underutilised crop plants having distinct features [70]. PlantCLEF act like a real-life computerised program that can identify and classify plant species using raw images by extracting similar traits/characteristics and matching them defined plant species and family [70]. Similarly, MPID (Medicinal plant images database) which is a premium database maintained by Hong Kong Baptist University that is known to accommodate vast range of phenotypic data related to medicinal and therapeutically important plants [71]. Furthermore, in addition to phenotypic data, it also acts as a repertoire of scientific/botanical names, therapeutic values, physiological and ecological parameters of more than 1000 medicinal plants. Likewise, MPDB (Medicinal plant database of Bangladesh) database is also specifically dedicated to store phenotypic and physiological data associated with medicinal and aromatic plants found in Bangladesh [72].
Apart from databases, several computer-based analytical tools and techniques have also been developed and implemented for recording high-resolution images and morpho-physiological parameters in selected plants [70]. Plant computer vision (PlantCV) is a freeware software package written explicitly in python language that provide valuable algorithms for analysing phenotypic data [71]. It can analyse phenotypic data for multiple plant species and compare them with in the database for identification of novel traits/characteristics in genetically un-explored crops [67]. Similarly, ImageJ is a Java based program equipped with various algorithms such as image enhancer, graphic correction, segmentation and measurement to facilitate accurate phenotyping of plant species [73]. HTPheno is an algorithm of ImageJ that allows monitoring of plant’s growth and development in terms colour spectrum. It captures image related to growth and fitness by various angles, time period and temperature/light conditions in the form high-resolution images [74]. However, despite of these technological breakthroughs, the implantation of these state-of-the art techniques are limited certain plant species. Therefore, efforts are needed to establish, standardise and implement these advanced phenomics techniques in various under-utilised medicinally important crops in order to facilitate comprehensive analysis of their physiological, morphological and cellular functions.
Identification of hereditary determinants governing morphological, physiological and biochemical properties are of astute importance to uncover genetic potential of plant species. With the advent of next-generation sequencing techniques it has now become possible to perform in-depth studies on economically/therapeutically important under-utilised crops [75]. Till date whole genome sequencing projects has led to the development of draft genomes and chloroplast genomes of various medicinally important plants which can be efficiently exploited in-conjunction with advanced bio-informatic tools to obtain information about gene families, gene regulatory networks, miRNA and non-coding RNAs involved in gene regulation in those plants whose genome sequence is not available [76]. Furthermore, it can also result in the development of DNA markers for DNA fingerprinting and DNA barcoding to facilitate efficient taxonomic identification of plant under study using specific region of DNA [77]. Several DNA fingerprinting/barcoding primers such as 18-S-rRNA, 5S-rRNA, rupture of the cranial cruciate ligament (rccl), maturase K (matK), internal transcribed spacer (ITS), intergenic spacer (trnH-psbA) have been successfully implemented for identification and classification of medicinal plants. In addition, several dominant and co-dominant markers such as single nucleotide polymorphism (SNP), sequence characterised amplified region (SCAR), amplified fragment length polymorphism (AFLP), inter simple-sequence repeat (ISSR) and random amplified polymorphic DNA (RAPD) have also facilitated identification and authentication of medicinal plants [76].
Transcriptome-wide profiling of genes of regulatory pathways can help researchers gain valuable insight into the functional mechanisms of plant’s biosynthetic pathways. In the recent years, researchers have exploited expressed sequence tags (ESTs) for transcriptome wide analysis of important medicinal plants [77]. Later, the scientists began to use microarray which is probe hybridization-based technique for studying regulation of gene expression and candidate gene discovery [78]. Recently, various transcriptome-wide analysis studies have been conducted in several medicinally important plants and their sequencing and expression profiling data are available in various online databases such as GarlicESTdb (garlic EST database), GEO (gene expression omnibus), ArrayExpress, RASP (RNA atlas of structure probing), AgriSeqDB (RNA sequence database), EGENES (EST database) that can help expedite transcriptomic research in those plants in which transcriptome wide analysis has yet not been completed [79]. Likewise, several toolkits have also been designed that explicitly analyse microarray data and can also be used in conjunction with other phenomics, transcriptomics, proteomics and epigenomics for the identification of functional biological pathways liked with secondary metabolite synthesis [79]. Notably used toolkits are iArray, BRB-Arraytools, KEGG (Kyoto encyclopaedia for genes and genomes), GENEVESTIGATOR, PLEXdb, ExPath are the ones which offers various features for microarray data analysis, visualisation, interpretation and annotation in the form of heat map, graph and tables [80].
In addition, few databases have also been developed such as CroFGD (
Several protein-coding genes have also been qualitatively and quantitatively analysed for their corresponding products to generate a profile of their proteome to help researchers gain valuable insights into the mechanisms underlying cellular and metabolic pathways in medicinal plants [86]. Fewer studies have been conducted to develop a complete proteome map in the medicinal plants describing the proteins involved in the regulation of secondary metabolite synthesis. For example, a study conducted by Jacobs et al. [87] identified various proteins involved in alkaloid biosynthesis in
S. No | Legumes | Genes/Transcription factors (TFs) | Secondary metabolites | Pathway involved | Technique used | References |
---|---|---|---|---|---|---|
1. | Fatty acid desaturase 2 (FAD2) | Linoleic acid | Octadecanoid pathway | Generation of mutant followed by LC–MS analysis | Liu et al. [89] | |
2. | Cytochrome 72A67 (CYP72A67), lateral organ boundaries domain TFs | Saponins | Isoprenoid pathway | Generation of mutant followed by GC–MS | Biazzi et al. [90] | |
3. | Apetella 2/ ethylene responsive factor (AP2/ERF TF) | Quinolizidine alkaloids | Decarboxylation of lysine | Transcriptome de-novo assembly and QTL mapping | Kroc et al. [91] | |
4. | 13-hydroxylupanine O-tigloyltransferase (HMT/HLT), Lysine/ornithine decarboxylase (LDC) and 4-hydroxy-tetrahydrodipicolinate synthase (DHDPS) | Quinolizidine alkaloids | Decarboxylation of lysine | Transcriptome de-novo assembly and QTL mapping | Kroc et al. [91] | |
5. | R2R3-MYB TF (TaMYB14) | Proanthocyanidin | Flavonoid biosynthetic pathway | Gene silencing followed by LC–MS analysis | Hancock et al. [92] | |
6. | MYB TF and MtLAR and MtANR | Proanthocyanidin | Flavonoid biosynthetic pathway | Targeted mutagenesis by HPLC analysis | Cañas and Beltrán [93] | |
7. | Uridine diphosphate glucosyltransferases (UGT73K1 and UGT71G1) | Saponins and isoflavonoids | Triterpenoid saponins biosynthetic pathway | Localization through prokaryotic expression system followed by microarray analysis | Achnine et al. [94] | |
8. | Hyp 1 – Hyp 7 | β-amyrin and mimosine | Triterpenoid saponins biosynthetic pathway | Microarray analysis | Honda and Borthakur [95] | |
9. | TM1624.23 | Phenylpropanoid derivatives and pro-anthocyanidin metabolism | Phenylpropanoid pathway | Gas chromatography coupled to electron impact ionisation/time-of-flight mass spectrometry | Sanchez et al. [96] | |
10. | CaUGT | Isoflavonoids | methylerythritol phosphate pathway | Next generation sequencing followed by marker assisted breeding | Jha et al. [97] | |
11. | Trc genes | Trigonelline, | Tryptophane-kynurenine pathway. | Gene cloning and mutagenesis | Boivin et al. [98] | |
12. | mtPAR, isoflavone synthase (IFS), mtTT8 and mtWD40 1 | proanthocyanidin | Flavonoid biosynthetic pathway | Cloning, gene expression and microarray analysis | Li et al. [99] | |
13. | GmF3H1, GmF3H2 and GmFNSII-1 | Isoflavones | Flavonoid biosynthetic pathway | CRISPR/Cas9-mediated metabolic engineering | Zhang et al. [82, 83] | |
14. | No apical meristem-Arabidopsis transcription activator factor-Cup shaped cotyledon (NAC TF) NAC 4, NAC 29, NAC 25 and NAC 72 | Abscisic acid and secondary metabolite synthesis | Biosynthetic pathway | Multi-OMICS platform | Jha et al. [100] | |
15. | GmCHS1–GmCHS9 | Flavonoids and isoflavonoids | Flavonoid biosynthetic pathway | Cloning, gene expression and microarray analysis | Dastmalchi and Dhaubhadel [101] | |
16. | 2-hydroxyisoflavanone synthase (CYP93C), 2,7,4 0-trihydroxyisoflavanone 4 0-O-methyltransferase/isoflavone 4 0-O-methyltransferase (HI4OMT) and isoflavone-7-O-methyltransferase (7-IOMT) | Flavonoids and isoflavonoids | Flavonoid biosynthetic pathway | Whole genome sequencing, assembly and gene expression | Mochida et al. [102] |
List of putative genes/transcription factors and functional genomics tools involved in regulating biosynthesis of secondary metabolites in legumes.
Metabolomics is also a functional genomics tool with the sole purpose to provide in-depth understanding of different cellular and metabolic pathways in various organisms. Metabolomics is an advanced system biology tool with improved analytical methodologies, sensitivity and resolution that has been successfully exploited to understand biosynthesis of important metabolites in various plant species [103]. Several researchers have used this technique to discover candidate genes/proteins involved biosynthesis of specialised metabolites [104]. Furthermore, it has also provided great depth of understanding about the structural properties and diversity that exists among different metabolites as well as has facilitated to gain valuable insight into the type active ingredients that gives each metabolites its specific nutritional and medicinal properties [103]. Recent decades have witnessed the detailed characterisation of various medicinally important metabolites such as paclitaxel, artemisinin, vincristine, vinblastine, camptothecin and accuminata etc. from Pacific yew tree,
Several metabolomic studies have been conducted in model as well as crop legumes such as
Systemic workflow depicting the application of integrated OMICS tools as well as role of different biotic/abiotic elicitors for improving the biosynthesis known bioactive compounds and identification of novel therapeutic metabolites in legume crops. In this process, tissue culture plants or plants grown in field are treated with different biotic or abiotic elicitors either independently of in combination. The plants are then analysed for the differential expression of genes involved in the regulation of secondary metabolites using integrated OMICS techniques. Candidate genes are discovered using various techniques such as cDNA-AFLP, SAGE, analysed by bioinformatics tools and are rewired using synthetic biology tool. The transformed plants are then exploited for sustainable production of important bioactive metabolites. GWAS: Genome wide association studies; MAS: Marker assisted selection; SNP: Single nucleotide polymorphism; QTLs: Quantitative trait loci’s; miRNA: microRNA; siRNA: Small interfering RNA; NMR: Nuclear magnetic resonance; HPLC: High performance liquid chromatography; GC: Gas chromatography; LC: Liquid chromatography; MALDI-TOF-MS: Matrix assisted laser desorption ionisation-time of flight-mass spectrometry; cDNA AFLP: Complementary DNA amplified fragment length polymorphism (RNA finger printing technique); SAGE: Serial analysis of gene expression; DdPCR: Differential display PCR; SM: Secondary metabolites; CRISPR-CAS 9: Clustered regulatory interspaced short palindromic repeat, CRISPR associated protein 9; TFs: Transcription factors.
In plants, increase synthesis and accumulation of secondary metabolites occur upon their exposure to adverse climatic conditions which not only strengthen their growth but also revamp their innate immune response [107]. Several studies have indicated that distinct physical, chemical and microbial factors could act as abiotic/biotic elicitors for stimulating genes of metabolic pathways which will in turn result in the increase production important/specialised metabolites [108]. Now a day’s elicitation is extensively used as a biotechnological tool to induce the biosynthesis of medicinally important metabolites in various tissues and organs of tissue cultured plants. The functional mechanism behind elicitor’s elicitation involves signal perception by the receptors designed specifically to initiate signal transduction of the genes/transcription factor involved in the biosynthetic pathway (Figure 2) which in turn enhance the production and accumulation of different metabolites [107]. This section briefly describes different biotic/abiotic elicitors that can be employed for enhancing the production of secondary metabolites in medicinal as well as crop plants. A list of different biotic/abiotic elicitors involved in the regulation of bioactive metabolites in legumes are presented in Table 2.
Schematic representation of mechanisms by which biotic/abiotic elicitors signalling pathways involved in the biosynthesis of important bioactive metabolites in plants. The elicitors are perceived by the receptors which then interacts with various components of signal atransduction pathway. This interaction activates certain transcription factors which in turn regulate the expression of various biosynthetic genes/proteins thus stimulating enhanced production of important therapeutic metabolites. SA: Salicylic acid; NO: Nitric oxide; MeJA: Methyl jasmonate; ROS: Reactive oxygen species; CDPKs: Calcium dependent protein kinases; MAPKs: Mitogen activated protein kinases; IP3: Inositol triphosphate; DAG: Diacyglycerol; TFs: Transcription factors.
S. No. | Legumes | Abiotic/biotic elicitor used | Secondary metabolite elicited | Pathway involved | Probable role | References |
---|---|---|---|---|---|---|
1. | Chitosan (0.12%), Salicylic acid (800 μM) and potassium cyanide (400 μM) | Isoflavonoid genistein | Phenylpropanoid pathway | Treatment of cancer, osteoporosis, and ischemic heart disease | Kneer et al. [109] | |
2. | UV light (30-50 W for 5, 10 and 15 hr) | Phenolics and L-Dopamine | Pentose phosphate pathway | Act as neuromodulator and used for treatment of Parkinson’s disease | Shetty et al. [110] | |
3. | UV light (5.5 min at 8000 J m−2), Methyl jasmonate (50 mM), Yeast | Triterpene saponins and other primary metabolites | Phenylpropanoid pathway | Act as anti-tumour, anti-mutagenic, anti-inflammatory, anti-viral and cardiac activities | Broeckling et al. [111] | |
4. | Methyl jasmonate (at 0.1 kg/m3) | Genistein and Daidzein, and β-glycosidic type isoflavonoids | Phenylpropanoid pathway | Treatment of cancer, osteoporosis, and ischemic heart disease | Gueven and Knorr [112] | |
5. | cadmium (at 10 mg/l) and lead (at 150 mg/l) | 2′-hydroxygenistein glucoside and 2′-hydroxygenistein 7-O-glucoside | Phenylpropanoid pathway | Treatment of cancer, osteoporosis, and ischemic heart disease | Pawlak-Sprada et al. [113] | |
6. | Fungal spore suspension (2 × 106 spores/ml, approximately 5 ml/plant) | Isoflavone phytoalexins or their precursors | Phenylpropanoid pathway | Treatment of cardiovascular disease, osteoporosis, hormone-dependent cancer and loss of cognitive function | Wojakowska et al. [114] | |
7. | Ascorbic acid (500 μM) Folic acid (50 μM) and glutamic acid (5 mM) | Phenolic composition and angiotensin I converting enzyme (ACE) | — | Treatment of hypertension and cardiovascular disease, inhibition of cholesterol synthesis | Dueñas et al. [115] | |
8. | Sucrose, gibberellins and proline | Quercetin-3O-glucoside, malvidin-3O-glucoside, and soyasaponins | Phenylpropanoid pathway | Act as anti-tumour, anti-mutagenic, anti-inflammatory, anti-viral and cardiac activities | Díaz-Sánchez et al. [116] | |
9. | AgNO3 and H2O2 | Glyceollin and Isoflavones | Phenylpropanoid pathway | Act as anti-tumour, treatment of cardiovascular disease and other chronic diseases | Kalli et al. [117] | |
10. | 6-Prenyl daidzein and phaseol | Phenylpropanoid pathway | Menopausal relief, treatment of osteoporosis, blood cholesterol, and lowering the risk of some hormone-related cancers, and heart disease | Kalli et al. [117] | ||
11. | Arbuscular mycorrhizal fungal inoculum and exogenous methyl jasmonate | Trigonelline and diosgenin | Acetyl coenzyme A through the mevalonate pathway | A novel multitarget based chemo-preventive or therapeutic agent neuroprotective, anti-diabetic | Irankhah et al. [118] | |
12. | Sodium silicate | Flavonoids and phenolic acids | Phenylpropanoid and shikimic acid pathway | Act as anti-tumour, anti-mutagenic, anti-inflammatory, anti-viral and cardiac activities | Dębski et al. [119] | |
13. | Sodium silicate + Fe EDTA | Flavonoids and phenolic acids | Phenylpropanoid and shikimic acid pathway | Act as anti-tumour, treatment of cardiovascular disease and other chronic diseases | Dębski et al. [119] | |
14. | Sodium silicate | Flavonoids and phenolic acids | Phenylpropanoid and shikimic acid pathway | Act as anti-tumour, anti-mutagenic, anti-inflammatory, anti-viral and cardiac activities | Dębski et al. [119] |
List of different abiotic/biotic elicitors used for eliciting secondary metabolites production in legume crops.
Biological materials such as proteins, carbohydrates, inactivated enzymes, and polysaccharides etc. whether of plant, fungi or bacterial origin either in crude or purified form is used to induce the synthesis of secondary metabolites are termed as biotic elicitors [120]. Researchers have well indicated that proteins/enzymes are being explicitly used to stimulate the defence system of plants by increasing the synthesis of secondary metabolites involved in the regulation of stress responsive genes [121]. In tissue culture generated plants, several glycoprotein elicitors have been shown to elicit the production of phytoalexin, lectins and agglutinins that tremendously ameliorate the stress-induced oxidative damage [122]. Similarly, various fungal elicitor proteins such as PebC and PevD1 from
Polysaccharides such as xyloglucans, oligogalacturonides, hemicellulose and pectin derived from plant, bacterial or fungal cell wall could also be exploited as an elicitor to stimulate secondary metabolite synthesis in plants [124]. For instance, a polysaccharide derived from
Various phytohormones/signalling molecules such as salicylic acid (SA), nitric oxide (NO) jasmonic acid (JA), ethylene (ET) and abscisic acid (ABA) which can serve as an elicitor to elicit secondary metabolites production and stress-induced defence response in various plant species [127]. Among all, the role of SA, NO and JA have been extensively investigated for the elicitation of secondary metabolites synthesis and imparting resistance against biotic/abiotic stress induced oxidative damage in plants [128]. Methyl-jasmonate a derivative of jasmomic acid precisely activated the production of indole glucosinolate, β-thujaplicin and terpenes indole alkaloids in
Various plant growth promoting rhizobacteria (PGPR) and arbuscular mycorrhizal fungal inoculum in conjunction with methyl jasmonate have been shown to enhance production of various secondary metabolites in
Elicitation of secondary metabolite synthesis by using substance of non-biological such as inorganic salts of heavy metals (VOSO4, NiSO4, CdCl2, AgNO3, CuCl2), UV-radiation, heat, light etc. is known as abiotic elicitation and the substance used are known as abiotic elicitors. Abiotic elicitors such as high temperature, salt, drought, light and heavy metals etc. have also been successfully used as physical and chemical stimuli to elicit the biosynthesis of medicinally important metabolites in various plants [122]. These abiotic elicitors have been successfully used either independently or in combination either by foliar spray, irrigation or as hydroponics under both open field or controlled conditions for secondary metabolite production in medicinally important plants [122]. Present section deciphers the functional mechanism by which these different abiotic based elicitors elicit the production of therapeutically important compounds.
Drought is one of the most prevalent abiotic stress that alter plant growth and productivity around the globe [108]. Researchers have also indicated that in order to cope up with drought induced oxidative stress, plants synthesise certain metabolites such as glycine betaine and proline as mean to strengthen their defence system [122]. Based on this notion, researchers are using mannitol, calcium chloride and polyvinyl pyrrolidone (chemical which are used to induce drought stress) as a physical elicitor to induce the production of terpene indole alkaloids up to 2-fold in treated
Salinity is also known to affect wide array of physiological and biochemical properties in plants thus affecting their growth and development [137]. Prolong exposure to salinity stress causes cellular dehydration and generation of oxidative stress in plants thus limiting their ion/osmotic homeostasis [122]. However, in order to withstand to salinity stress, plants synthesised various secondary metabolites like phenols, alkaloids and terpenes as an ameliorative mechanism to overcome oxidative damage. For instance, researchers observed significant increase in the biosynthesis of terpene indole alkaloids (TIAs) in
High light intensity and temperature are also able to alter the course of secondary metabolites production in plants [138]. Prolong exposure of both high light and temperature can induce oxidative stress in plants that can have adverse effect growth, ontology and development. High temperature can also lead to the induction of premature leaf senescence, stomatal closure and can stimulate transpiration rate to a greater extent [137]. Nonetheless, despite affecting plant’s growth these physical factors have also been reported to stimulate the biosynthesis of important secondary metabolites in the root of
Increasing bioaccumulation of heavy metals such as As, Cd, Cu, Ni, Co and Ag have significantly impacted the agricultural lands and productivity. These heavy metals when presence in excess amount adversely affects plant growth and development [137]. However, at low levels these heavy metals act as co-enzymes/co-factors in various cellular and metabolic pathways thus stimulating secondary metabolite production in plants [122]. Several researchers have well documented the role of heavy metals in stimulating oil content, shikonin/digitalin levels in
In the present era, hyacinth bean has been recognised as an omnipotent legume crop which has the ability to conquer malnutrition, food/hunger index and several chronic diseases all around the globe. Being rich source of genetic and genome resources, the information’s reviewed here can significantly contributes towards unravelling its structural, biochemical and molecular genomics which can lead to the identification of signalling pathways involve in the biosynthesis of important therapeutic metabolites/compounds. Furthermore, the implementation of multi “OMICS” techniques are the need of the hour which can transform hyacinth bean and other underutilised legume crops from being “orphan” to “model crop” by exploiting them in the breeding programs. These underutilised legumes hold the potential for developing sustainable agriculture which can lead to hunger and disease-free world in the era of global warming/pandemic. Therefore, synergistic use of multi OMICS tools are of ultimate requirement for expanding the current horizons of underutilised legume crops to address important problems relevant to Nations be it on health, nutrition and environment.
The authors are also thankful to DST (Department of Science and Technology), and DBT-ISLS facility, BHU, Govt. of India (Grant No. DST/BHU/PURSE 2017-2018 and DST/BHU/FIST 2016-2017) for financial support. KKR is also thankful for financial support in the form of Research Associate by National Academy of Sciences India, Prayagraj is gratefully acknowledged.
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Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:null},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). He leads the working group of experts representing Brazil in the Global Partnership on Artificial Intelligence (GPAI), on the theme \"AI and the Pandemic Response\".",institutionString:"Manufacturing and Technology Integrated Campus – SENAI CIMATEC",institution:null},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:"Polytechnic University of Timişoara",institution:{name:"Polytechnic University of Timişoara",country:{name:"Romania"}}},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:null},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"414880",title:"Dr.",name:"Maryam",middleName:null,surname:"Vatankhah",slug:"maryam-vatankhah",fullName:"Maryam Vatankhah",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Borough of Manhattan Community College",country:{name:"United States of America"}}},{id:"414879",title:"Prof.",name:"Mohammad-Reza",middleName:null,surname:"Akbarzadeh-Totonchi",slug:"mohammad-reza-akbarzadeh-totonchi",fullName:"Mohammad-Reza Akbarzadeh-Totonchi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ferdowsi University of Mashhad",country:{name:"Iran"}}},{id:"414878",title:"Prof.",name:"Reza",middleName:null,surname:"Fazel-Rezai",slug:"reza-fazel-rezai",fullName:"Reza Fazel-Rezai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"American Public University System",country:{name:"United States of America"}}},{id:"302698",title:"Dr.",name:"Yao",middleName:null,surname:"Shan",slug:"yao-shan",fullName:"Yao Shan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Dalian University of Technology",country:{name:"China"}}},{id:"125911",title:"Prof.",name:"Jia-Ching",middleName:null,surname:"Wang",slug:"jia-ching-wang",fullName:"Jia-Ching Wang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Central University",country:{name:"Taiwan"}}},{id:"357085",title:"Mr.",name:"P. Mohan",middleName:null,surname:"Anand",slug:"p.-mohan-anand",fullName:"P. Mohan Anand",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356696",title:"Ph.D. Student",name:"P.V.",middleName:null,surname:"Sai Charan",slug:"p.v.-sai-charan",fullName:"P.V. Sai Charan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"357086",title:"Prof.",name:"Sandeep K.",middleName:null,surname:"Shukla",slug:"sandeep-k.-shukla",fullName:"Sandeep K. Shukla",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356823",title:"MSc.",name:"Seonghee",middleName:null,surname:"Min",slug:"seonghee-min",fullName:"Seonghee Min",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Daegu University",country:{name:"Korea, South"}}},{id:"353307",title:"Prof.",name:"Yoosoo",middleName:null,surname:"Oh",slug:"yoosoo-oh",fullName:"Yoosoo Oh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:"Yoosoo Oh received his Bachelor's degree in the Department of Electronics and Engineering from Kyungpook National University in 2002. He obtained his Master’s degree in the Department of Information and Communications from Gwangju Institute of Science and Technology (GIST) in 2003. In 2010, he received his Ph.D. degree in the School of Information and Mechatronics from GIST. In the meantime, he was an executed team leader at Culture Technology Institute, GIST, 2010-2012. In 2011, he worked at Lancaster University, the UK as a visiting scholar. In September 2012, he joined Daegu University, where he is currently an associate professor in the School of ICT Conver, Daegu University. Also, he served as the Board of Directors of KSIIS since 2019, and HCI Korea since 2016. From 2017~2019, he worked as a center director of the Mixed Reality Convergence Research Center at Daegu University. From 2015-2017, He worked as a director in the Enterprise Supporting Office of LINC Project Group, Daegu University. His research interests include Activity Fusion & Reasoning, Machine Learning, Context-aware Middleware, Human-Computer Interaction, etc.",institutionString:null,institution:{name:"Daegu Gyeongbuk Institute of Science and Technology",country:{name:"Korea, South"}}},{id:"262719",title:"Dr.",name:"Esma",middleName:null,surname:"Ergüner Özkoç",slug:"esma-erguner-ozkoc",fullName:"Esma Ergüner Özkoç",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Başkent University",country:{name:"Turkey"}}},{id:"346530",title:"Dr.",name:"Ibrahim",middleName:null,surname:"Kaya",slug:"ibrahim-kaya",fullName:"Ibrahim Kaya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"419199",title:"Dr.",name:"Qun",middleName:null,surname:"Yang",slug:"qun-yang",fullName:"Qun Yang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Auckland",country:{name:"New Zealand"}}}]}},subseries:{item:{id:"6",type:"subseries",title:"Viral Infectious Diseases",keywords:"Novel Viruses, Virus Transmission, Virus Evolution, Molecular Virology, Control and Prevention, Virus-host Interaction",scope:"The Viral Infectious Diseases Book Series aims to provide a comprehensive overview of recent research trends and discoveries in various viral infectious diseases emerging around the globe. The emergence of any viral disease is hard to anticipate, which often contributes to death. A viral disease can be defined as an infectious disease that has recently appeared within a population or exists in nature with the rapid expansion of incident or geographic range. This series will focus on various crucial factors related to emerging viral infectious diseases, including epidemiology, pathogenesis, host immune response, clinical manifestations, diagnosis, treatment, and clinical recommendations for managing viral infectious diseases, highlighting the recent issues with future directions for effective therapeutic strategies.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/6.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11402,editor:{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. 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Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. 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