Biological effect of various terpyridine isosteres with four aryl groups.
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{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"}]},book:{item:{type:"book",id:"7728",leadTitle:null,fullTitle:"Synthetic Biology - New Interdisciplinary Science",title:"Synthetic Biology",subtitle:"New Interdisciplinary Science",reviewType:"peer-reviewed",abstract:"Synthetic biology gives us a new hope because it combines various disciplines, such as genetics, chemistry, biology, molecular sciences, and other disciplines, and gives rise to a novel interdisciplinary science. We can foresee the creation of the new world of vegetation, animals, and humans with the interdisciplinary system of biological sciences. These articles are contributed by renowned experts in their fields. The field of synthetic biology is growing exponentially and opening up new avenues in multidisciplinary approaches by bringing together theoretical and applied aspects of science.",isbn:"978-1-78984-090-2",printIsbn:"978-1-78984-089-6",pdfIsbn:"978-1-78985-329-2",doi:"10.5772/intechopen.77541",price:119,priceEur:129,priceUsd:155,slug:"synthetic-biology-new-interdisciplinary-science",numberOfPages:206,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"cc50b31cb749d94a5aa38999a712ae2f",bookSignature:"Madan L. Nagpal, Oana-Maria Boldura, Cornel Baltă and Shymaa Enany",publishedDate:"February 12th 2020",coverURL:"https://cdn.intechopen.com/books/images_new/7728.jpg",numberOfDownloads:21976,numberOfWosCitations:7,numberOfCrossrefCitations:13,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:32,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:52,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"September 12th 2018",dateEndSecondStepPublish:"March 15th 2019",dateEndThirdStepPublish:"May 14th 2019",dateEndFourthStepPublish:"August 2nd 2019",dateEndFifthStepPublish:"October 1st 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"182681",title:"Dr.",name:"Madan L.",middleName:null,surname:"Nagpal",slug:"madan-l.-nagpal",fullName:"Madan L. Nagpal",profilePictureURL:"https://mts.intechopen.com/storage/users/182681/images/system/182681.png",biography:"Research Associate Professor at the Department of Microbiology and Immunology, University of South Carolina, Columbia, SC, and Research Chemist at the Dorn Veterans Medical Center, Columbia, SC, USA for 10 plus years. He has published 40 research articles, 38 Abstracts and Presentations, a Book Chapter and edited a book. He was awarded Research & Productive Scholarship 1990 by the Univ. South Carolina. He was funded by the grants as Co-Investigator by National Institutes of Health (NIH) and the VA Merit Review grants. His contributions include gene regulation in steroid hormone biosynthesis and the characterization of Bacillus species. He is a member of American Society of Cell Biology, American Association of Advancement of Science, The Endocrine Society, Fellow Linnean Society of London, American Association for Laboratory Animal Science, International Who’s Who Professionals, and Marquis Who’s Who in America.",institutionString:"University of South Carolina",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"University of South Carolina",institutionURL:null,country:{name:"United States of America"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"189429",title:"Prof.",name:"Oana-Maria",middleName:null,surname:"Boldura",slug:"oana-maria-boldura",fullName:"Oana-Maria Boldura",profilePictureURL:"https://mts.intechopen.com/storage/users/189429/images/system/189429.jpg",biography:"Oana-Maria Boldura is licensed in Genetic Engineering with specialization in Molecular Biology (2005), Master\\'s Degree in Genetic Manipulation (2007) and Pharmacy (2014), and PhD in Biotechnology field (2010). From 2015 she has been an Assistant Professor at Banat University of Agricultural Sciences and Veterinary Medicine 'King Michael I of Romania” Timisoara, Faculty of Veterinary Medicine, Department of Chemistry, Biochemistry and Molecular Biology and researcher at ,,Horia Cernescu” Research Unit. Her main scientific competences are in the field of Molecular Biology, Biotechnology, Genomics and Biosecurity with technical aptitudes in manipulation and experimentation with nucleic acid and proteins (purification, sequencing, gene expression studies, SDS-PAGE analysis of proteins fractions, ,,Lab-on-chip” electrophoresis, Immunological Testing). Her areas of interest are Molecular Forensic Methods and Apoptotic Process Pathways.",institutionString:"Banat’s University of Agricultural Sciences and Veterinary Medicine",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Banat University of Agricultural Sciences and Veterinary Medicine",institutionURL:null,country:{name:"Romania"}}},coeditorTwo:{id:"222863",title:"Dr.",name:"Cornel",middleName:null,surname:"Balta",slug:"cornel-balta",fullName:"Cornel Balta",profilePictureURL:"https://mts.intechopen.com/storage/users/222863/images/system/222863.jpg",biography:"Dr. Cornel Baltă, MD, DVM, is a licensed veterinarian with both\na PhD and MD in Veterinary Medicine. He is a researcher at the\nInstitute of Life Sciences, at “Vasile Goldis” Western University\nArad, Romania. Dr. Baltă’s main scientific competences are in\nthe fields of laboratory animals, molecular biology, physiology,\nhistology, and clinical Laboratory. He has technical aptitudes in\nnucleic acid examination by electrophoresis techniques, PCR and\nqPCR, and qualitative and quantitative determination of proteins by Western Blot\nand microelectrophoresis. His areas of interest include molecular mechanisms involved in the evolution of liver and gastrointestinal diseases, and bone regeneration\nand remodeling using different types of polymers.",institutionString:'"Vasile Goldis" Western University of Arad',position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Vasile Goldis Western University of Arad",institutionURL:null,country:{name:"Romania"}}},coeditorThree:{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",slug:"shymaa-enany",fullName:"Shymaa Enany",profilePictureURL:"https://mts.intechopen.com/storage/users/81926/images/system/81926.png",biography:"Dr. Shymaa Enany is an Associate Professor of Microbiology, at Suez Canal University, Egypt, and is currently working at Armed Forces College of Medicine, Egypt. She received her Ph.D. from the School of Medical Sciences, Niigata University, Japan. She completed her post-doctoral studies in the United States and Japan. Dr. Enany was one of the first Arab scientists to apply bacterial proteomic techniques to reveal good markers for microbes spreading in the community. She has received many awards for her scientific contributions, including the 2021 International Science Council Award for Early Career Scientist in Africa, the 2019 Egyptian state encouragement prize for women in the field of health and pharmaceutical sciences, and the 2018 World Academy of Sciences Young Arab Scientist Prize in Medical Sciences.",institutionString:"Suez Canal University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"6",institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}},coeditorFour:null,coeditorFive:null,topics:[{id:"694",title:"Genetic Engineering",slug:"engineering-biomedical-engineering-genetic-engineering"}],chapters:[{id:"70481",title:"Introductory Chapter: The Role of Genetic Engineering Technology in the Manipulation of Genetics of Organisms and Synthetic Biology",doi:"10.5772/intechopen.90549",slug:"introductory-chapter-the-role-of-genetic-engineering-technology-in-the-manipulation-of-genetics-of-o",totalDownloads:647,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Madan L. Nagpal",downloadPdfUrl:"/chapter/pdf-download/70481",previewPdfUrl:"/chapter/pdf-preview/70481",authors:[{id:"182681",title:"Dr.",name:"Madan L.",surname:"Nagpal",slug:"madan-l.-nagpal",fullName:"Madan L. Nagpal"}],corrections:null},{id:"65149",title:"Synthetic Biology, Artificial Intelligence, and Quantum Computing",doi:"10.5772/intechopen.83434",slug:"synthetic-biology-artificial-intelligence-and-quantum-computing",totalDownloads:2150,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:1,abstract:"We envisage a world where genetic engineering, artificial intelligence (AI), and quantum computing (QC) will coalesce to bring about a forced speciation of the Homo sapiens. A forced speciation will drastically reduce the emergence time for a new species to a few years compared to Nature’s hundreds of millennia. In this chapter, we explain the basic concepts that would allow a forced speciation of the Homo sapiens to occur and its consequences on life on Earth thereafter. Accelerating speciation mediated by Homo sapiens via domestication, gene splicing, and gene drive mechanisms is now scientifically well understood. Synthetic biology can advance speciation far more rapidly using a combination of clustered regularly interspaced short palindromic repeats (CRISPR) technology, advanced computing technologies, and knowledge creation using AI. The day is perhaps not far off when Homo sapiens itself will initiate its own speciation once it advances synthetic biology to a level where it can safely modify the brain to temper emotion and enhance rational thinking as a means of competing against AI-embedded machines guided by quantum algorithms.",signatures:"Rajendra K. Bera",downloadPdfUrl:"/chapter/pdf-download/65149",previewPdfUrl:"/chapter/pdf-preview/65149",authors:[{id:"77013",title:"Prof.",name:"Rajendra",surname:"Bera",slug:"rajendra-bera",fullName:"Rajendra Bera"}],corrections:null},{id:"68797",title:"Construction and Analysis of Metagenome Library from Bacterial Community Associated with Toxic Dinoflagellate Alexandrium tamiyavanichii",doi:"10.5772/intechopen.88751",slug:"construction-and-analysis-of-metagenome-library-from-bacterial-community-associated-with-toxic-dinof",totalDownloads:675,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Previous studies have suggested that a specific community of bacteria coexists within the phycosphere of marine dinoflagellates. In order to better understand the dinoflagellate-bacteria relationships, a fosmid clone library was constructed from the metagenome DNA and analyzed. Some of the fosmid clones were end-sequenced. A total of 1501 fosmid clones with insert sizes of 30–40 Kbp were produced. End sequencing of 238 clones showed that 55% of the genes had known functions, 11% were of putative function and 34% were genes of unknown function or had no match in Genbank. There were approximately 14% sequences with no classification and could potentially represent novel genes. Analysis of these partial sequences also revealed some promising enzymes that possess various potential industrial applications such as chitinases, kinases, agarases and oxygenases. The results also showed that the bacterial flora of the Alexandrium tamiyavanichii culture was dominated by the Alpha-proteobacteria, followed by Bacteroidetes and Gamma-proteobacteria. The findings in this study suggested that the bacterial community may play various role in the association with dinoflagellate. This study had also shown that dinoflagellate-associated bacterial community is a valuable source for discovery of novel genes and gene products.",signatures:"Muhd Danish-Daniel, Mohd Ezhar Mohd Noor, Yik Sung Yeong, Tan Min Pau and Gires Usup",downloadPdfUrl:"/chapter/pdf-download/68797",previewPdfUrl:"/chapter/pdf-preview/68797",authors:[{id:"253550",title:"Associate Prof.",name:"Muhd",surname:"Danish-Daniel",slug:"muhd-danish-daniel",fullName:"Muhd Danish-Daniel"},{id:"309693",title:"MSc.",name:"Mohd Ezhar",surname:"Mohd Noor",slug:"mohd-ezhar-mohd-noor",fullName:"Mohd Ezhar Mohd Noor"},{id:"309694",title:"Prof.",name:"Yik Sung",surname:"Yeong",slug:"yik-sung-yeong",fullName:"Yik Sung Yeong"},{id:"309695",title:"Dr.",name:"Tan",surname:"Min Pau",slug:"tan-min-pau",fullName:"Tan Min Pau"},{id:"309696",title:"Prof.",name:"Gires",surname:"Usup",slug:"gires-usup",fullName:"Gires Usup"}],corrections:null},{id:"68217",title:"Applied Molecular Cloning: Present and Future for Aquaculture",doi:"10.5772/intechopen.88197",slug:"applied-molecular-cloning-present-and-future-for-aquaculture",totalDownloads:1088,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"With the grim picture of millions of people living in poverty and hunger, there is also an international alarm over future world food supply. This global concern of food scarcity has established the need to not only increase the production of traditional staples but also fisheries and aquaculture. Genetically, physiologically and phenotypically, fish are the most diverse group of livings. Similar to mammals, molecular biology is being extensively used in aquaculture, be it in disease management, or growth and reproduction enhancement. In this chapter we aim to discuss the molecular methodologies applied to uplift and attain sustainability in aqua farming.",signatures:"Tapas Chakraborty, Sipra Mohapatra, Chimwar Wanglar and Dipak Pandey",downloadPdfUrl:"/chapter/pdf-download/68217",previewPdfUrl:"/chapter/pdf-preview/68217",authors:[{id:"295354",title:"Dr.",name:"Tapas",surname:"Chakraborty",slug:"tapas-chakraborty",fullName:"Tapas Chakraborty"},{id:"301450",title:"Dr.",name:"Sipra",surname:"Mohapatra",slug:"sipra-mohapatra",fullName:"Sipra Mohapatra"},{id:"301567",title:"Dr.",name:"Dipak",surname:"Pandey",slug:"dipak-pandey",fullName:"Dipak Pandey"},{id:"301568",title:"Dr.",name:"Chimwar",surname:"Wanglar",slug:"chimwar-wanglar",fullName:"Chimwar Wanglar"}],corrections:null},{id:"67662",title:"Molecular Cloning of Genic Male-Sterility Genes and Their Applications for Plant Heterosis via Biotechnology-based Male-sterility Systems",doi:"10.5772/intechopen.86976",slug:"molecular-cloning-of-genic-male-sterility-genes-and-their-applications-for-plant-heterosis-via-biote",totalDownloads:1064,totalCrossrefCites:1,totalDimensionsCites:4,hasAltmetrics:0,abstract:"In this chapter, we summarize the strategies about molecular cloning and functional confirmation of plant genic male-sterility (GMS) genes and their applications for hybrid breeding and seed production via biotechnology-based male-sterility (BMS) systems in crop plants. The main content includes four sections: (1) GMS gene cloning strategies, including forward genetic approaches (e.g., map-based cloning, T-DNA or transposon tagging, and MutMap method) and reverse genetic approaches (e.g., homology-based cloning, anther-specific expression gene screening, and other reverse genetic methods); (2) functional confirmation methods of GMS genes, including transgenic complementation, targeted mutagenesis, allelic mutant test and sequencing, anther spatiotemporal expression analysis, and cytological observation; (3) application value assessment of GMS genes and mutants, such as genetic stability analysis of male sterility controlled by GMS genes under different genetic backgrounds and multiple environments, and genetic effects driven by GMS genes on plant heterosis and analysis of potential linkage with bad traits; (4) development and application of BMS systems based on GMS genes and/or their mutants, including transgenic construct-driven non-transgenic seed systems (e.g., seed production technology (SPT) and multi-control sterility (MCS)), and transgenic male-sterility systems (e.g., roundup hybridization systems (RHS1 and RHS2) and Barnase/Barstar system). Finally, we summarize and provide our perspectives on the studies of GMS genes and development of cost-effective and environment-friendly BMS systems in crop plants.",signatures:"Xiangyuan Wan and Suowei Wu",downloadPdfUrl:"/chapter/pdf-download/67662",previewPdfUrl:"/chapter/pdf-preview/67662",authors:[{id:"299083",title:"Prof.",name:"Xiangyuan",surname:"Wan",slug:"xiangyuan-wan",fullName:"Xiangyuan Wan"},{id:"299450",title:"Dr.",name:"Suowei",surname:"Wu",slug:"suowei-wu",fullName:"Suowei Wu"}],corrections:null},{id:"68741",title:"Silencing of Peroxiredoxin-4 in Anticancer Activity of Gamma-Tocotrienol",doi:"10.5772/intechopen.88813",slug:"silencing-of-peroxiredoxin-4-in-anticancer-activity-of-gamma-tocotrienol",totalDownloads:688,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Peroxiredoxin-4 (PRDX4) is known to have a role in protecting cells from oxidative stress. It has been previously reported to increase in HepG2 liver cancer cells treated with gamma-tocotrienol (GTT). As GTT treatment potentially kills the cancer cell by regulating multiple signaling pathways, this study aims to determine the involvement of PRDX4 in GTT anticancer activity by silencing the PRDX4 gene. The efficiency of PRDX4 silencing is achieved by optimizing HepG2 cell density, effect of serum presence in transduction media, incubation time of the cells with lentivirus, polybrene concentration, puromycin dose, functional titer, and multiplicity of infection (MOI) of the lentivirus. Silenced HepG2-PRDX4 cells (HepG2-shRNA-PRDX4) were treated with 70 μM of GTT for 48 h. GTT treatment significantly decreased the HepG2-shRNA-PRDX4 cell viability, increased apoptosis rate, and reduced free radical production compared to untreated HepG2-shRNA-PRDX4 cells. These findings are further supported by proteomic analysis, which showed that pro-apoptotic and DNA damage proteins were upregulated, and proteins involved in cell cycle arrest, carcinogenesis, and anti-apoptotic signaling pathways were downregulated in HepG2-shRNA-PRDX4 cells treated with GTT compared to control. In conclusion, PRDX4 plays a role in GTT anticancer activity by increasing free radical production and oxidative damage to induce apoptosis in HepG2 cell.",signatures:"Afiah Nasuha Aznan and Zakiah Jubri",downloadPdfUrl:"/chapter/pdf-download/68741",previewPdfUrl:"/chapter/pdf-preview/68741",authors:[{id:"296821",title:"Associate Prof.",name:"Zakiah",surname:"Jubri",slug:"zakiah-jubri",fullName:"Zakiah Jubri"},{id:"296847",title:"BSc.",name:"Afiah Nasuha",surname:"Aznan",slug:"afiah-nasuha-aznan",fullName:"Afiah Nasuha Aznan"}],corrections:null},{id:"67615",title:"A Noninvasive, Orally Stable, Mucosa-Penetrating Polyvalent Vaccine Platform Based on Hepatitis E Virus Nanoparticle",doi:"10.5772/intechopen.86830",slug:"a-noninvasive-orally-stable-mucosa-penetrating-polyvalent-vaccine-platform-based-on-hepatitis-e-viru",totalDownloads:767,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Hepatitis E virus nanoparticle (HEVNP) is an orally stable, mucosa-penetrating delivery platform for noninvasive, targeted delivery of therapeutic and diagnostic agents. HEVNP does not carry HEV genomic RNA and is incapable of replication. The key characteristics that make HEVNP an ideal and unique vehicle for diagnostic and therapeutic delivery include surface plasticity, resistance to the harsh environment of the gastrointestinal (GI) tract, significant payload capacity, platform sustainability, and safety. Furthermore, HEVNP is easily produced using currently available expression/purification technologies; can be easily formulated as a liquid, powder, or solid; and can be distributed (and stored) without the need for a temperature-controlled supply chain.",signatures:"Shizuo G. Kamita, Mo A. Baikoghli, Luis M. de la Maza and R. Holland Cheng",downloadPdfUrl:"/chapter/pdf-download/67615",previewPdfUrl:"/chapter/pdf-preview/67615",authors:[{id:"242476",title:"Distinguished Prof.",name:"R. Holland",surname:"Cheng",slug:"r.-holland-cheng",fullName:"R. Holland Cheng"},{id:"258461",title:"Dr.",name:"Mo",surname:"Baikoghli",slug:"mo-baikoghli",fullName:"Mo Baikoghli"},{id:"304542",title:"Dr.",name:"Shizuo",surname:"Kamita",slug:"shizuo-kamita",fullName:"Shizuo Kamita"},{id:"304543",title:"Prof.",name:"Luis",surname:"De La Maza",slug:"luis-de-la-maza",fullName:"Luis De La Maza"}],corrections:null},{id:"66383",title:"PCR and Infectious Diseases",doi:"10.5772/intechopen.85630",slug:"pcr-and-infectious-diseases",totalDownloads:1654,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:1,abstract:"Since the 1950s, the medical community has been faced with infectious diseases, which have brought significant public health and financial challenges. Currently, routine testing for the laboratory diagnosis for infectious agents is based on cell culture, serological, and molecular methods. However, cell culture-based methods are used mainly in research laboratories and are less sensitive methods when compared with serological and molecular methods. The diagnosis of infectious diseases has been revolutionized by the development of molecular techniques, mainly with the applications of polymerase chain reaction (PCR). The high sensitivity, specificity, and ease with which the PCR can be used to detect genetic sequences known have led to your wide application in science. A great number of qualitative and quantitative molecular assays are mostly based on what have been described such as real-time PCR, multiplex PCR, LAMP-PCR, and digital PCR. These assays could identify active infection by detecting infectious agents and nucleic acid in various clinical conditions including arboviruses, sexually transmitted infections, and bacterial infections. Further advancement of molecular technology is needed to improve the capacity to detect infectious agents in order to control the spread of infectious diseases and lead to appropriate actions which help to benefit patients and health-care workers themselves.",signatures:"Danielle Alves Gomes Zauli",downloadPdfUrl:"/chapter/pdf-download/66383",previewPdfUrl:"/chapter/pdf-preview/66383",authors:[{id:"282969",title:"Ph.D.",name:"Danielle",surname:"Zauli",slug:"danielle-zauli",fullName:"Danielle Zauli"}],corrections:null},{id:"67558",title:"Polymerase Chain Reaction (PCR): Principle and Applications",doi:"10.5772/intechopen.86491",slug:"polymerase-chain-reaction-pcr-principle-and-applications",totalDownloads:10686,totalCrossrefCites:8,totalDimensionsCites:18,hasAltmetrics:1,abstract:"The characterization of the diversity of species living within ecosystems is of major scientific interest to understand the functioning of these ecosystems. It is also becoming a societal issue since it is necessary to implement the conservation or even the restoration of biodiversity. Historically, species have been described and characterized on the basis of morphological criteria, which are closely linked by environmental conditions or which find their limits especially in groups where they are difficult to access, as is the case for many species of microorganisms. The need to understand the molecular mechanisms in species has made the PCR an indispensable tool for understanding the functioning of these biological systems. A number of markers are now available to detect nuclear DNA polymorphisms. In genetic diversity studies, the most frequently used markers are microsatellites. The study of biological complexity is a new frontier that requires high-throughput molecular technology, high speed computer memory, new approaches to data analysis, and the integration of interdisciplinary skills.",signatures:"Karim Kadri",downloadPdfUrl:"/chapter/pdf-download/67558",previewPdfUrl:"/chapter/pdf-preview/67558",authors:[{id:"290766",title:"Dr.",name:"Kadri",surname:"Karim",slug:"kadri-karim",fullName:"Kadri Karim"}],corrections:null},{id:"66513",title:"Annealing Temperature of 55°C and Specificity of Primer Binding in PCR Reactions",doi:"10.5772/intechopen.85164",slug:"annealing-temperature-of-55-c-and-specificity-of-primer-binding-in-pcr-reactions",totalDownloads:1548,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"In our study, we used PCR to clone papA, papEF, papG and F17G genes of Escherichia coli isolated from faecal samples of dogs with diarrhoea. Annealing temperature of 55°C was used in the PCR. Nucleotide sequence analysis of 26 cloned PCR products showed that in PCRs with papA primers, six out of eight obtained PCR products were false due to non-specific binding of the forward primer on both DNA strands; in PCRs with the papEF primers, all seven obtained PCR products originated from specific binding of the forward primer on the 3′ → 5′ DNA strand and non-specific binding of the forward primed on the 5′ → 3′ DNA strand; and in PCRs with the F17G primers, four out of eight obtained PCR products were false due to non-specific binding of forward and reverse primer. The anticipated annealing sites for non-specific primer binding in analysed nucleotide sequences are presented. In the case of PCR products obtained with papG-specific primers, all PCR products were amplifications of the papG sequence. When the annealing temperature of papA PCRs was raised to 60°C, all obtained PCR products were amplifications of the correct DNA sequences.",signatures:"Marjanca Starčič Erjavec",downloadPdfUrl:"/chapter/pdf-download/66513",previewPdfUrl:"/chapter/pdf-preview/66513",authors:[{id:"58980",title:"Dr.",name:"Marjanca",surname:"Starčič Erjavec",slug:"marjanca-starcic-erjavec",fullName:"Marjanca Starčič Erjavec"}],corrections:null},{id:"66117",title:"Real-Time Quantitative PCR as a Tool for Monitoring Microbiological Quality of Food",doi:"10.5772/intechopen.84532",slug:"real-time-quantitative-pcr-as-a-tool-for-monitoring-microbiological-quality-of-food",totalDownloads:1010,totalCrossrefCites:1,totalDimensionsCites:4,hasAltmetrics:1,abstract:"Microbiological parameters of food provide quality information regarding the processing, storage, and distribution conditions, shelf life, as well as whether the food poses a health risk to the population. In this context, the concern with food safety is a competitive advantage, as the pressure of consumers, who are increasingly interested and concerned about what they are consuming, directs the trade to reach the quality of products and services offered. With regard to microbiological analyses, researchers have been developing sensitive techniques to produce rapid results, since traditional methods of microbiological culture are time-consuming and very laborious. Thus, the real-time quantitative PCR technique (qPCR) offers the possibility of quantifying the total bacterial DNA in a food sample without the need of the microbial growth step. That is, the result can be expressed on the same day, and it is possible to perform a simultaneous quantification of more than one pathogen in a single assay. Therefore, it can be a useful tool for monitoring microbiological quality in food industries. In this chapter, we will present the advantages and disadvantages of this methodology for food microbiology emphasizing the challenge of differentiating viable cells from nonviable cells.",signatures:"Amanda Teixeira Sampaio Lopes and Bianca Mendes Maciel",downloadPdfUrl:"/chapter/pdf-download/66117",previewPdfUrl:"/chapter/pdf-preview/66117",authors:[{id:"284957",title:"Prof.",name:"Bianca",surname:"Mendes Maciel",slug:"bianca-mendes-maciel",fullName:"Bianca Mendes Maciel"},{id:"284958",title:"MSc.",name:"Amanda",surname:"Teixeira Sampaio Lopes",slug:"amanda-teixeira-sampaio-lopes",fullName:"Amanda Teixeira Sampaio Lopes"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"6752",title:"Cholesterol",subtitle:"Good, Bad and the Heart",isOpenForSubmission:!1,hash:"599b1f8bc760449a4ee6ecd816a1df93",slug:"cholesterol-good-bad-and-the-heart",bookSignature:"Madan L. 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Ever since then, the clinical use of echocardiography has steadily increased. Echocardiography is an attractive imaging modality for several reasons. It is highly available, relatively inexpensive, it does not involve ionising radiation, and images are displayed in realtime allowing prompt diagnosis. However, despite a staggering technical progress in echocardiography, regional myocardial function was, until recently, still assessed by visual analysis of wall motion, a relatively inaccurate and poorly reproducible manner.
During the last 10 years, tissue Doppler imaging has been developed to quantify regional myocardial function [1]. Initially formatted as a one-dimensional method for measurement of regional longitudinal myocardial velocity profiles, tissue Doppler imaging has been further developed to allow measurements of one-dimensional regional strain [2]. This index measures local deformation as opposed to (passive and active) motion and thereby better reflects regional myocardial function. However, tissue Doppler imaging is inextricably limited by the angle-dependency of the technique. Because of this limitation, it is not clinically feasible to measure myocardial deformation in directions not parallel to the direction of the Doppler beam, such as left ventricular rotation. Although some have tried to override this limitation by applying complex algorithms [3], measurement of left ventricular rotation by echocardiography has only recently become clinically feasible by the development of speckle tracking echocardiography.
In the 16th century, Leonardo daVinci already described the rotational motion of the left ventricle [4,5] and in 1669, Richard Lower observed that myocardial contraction could be compared with ‘the wringing of a linen cloth to squeeze out the water’ [6]. The mechanistic basis for this wringing motion or twist lies in the complex spiral architecture of the left ventricle as revealed by the anatomical studies of Streeter et al. [7] and Greenbaum et al. [8] The left ventricle consists of obliquely oriented muscle fibres that vary from a smaller-radius, right-handed helix at the subendocardium to a larger-radius, left-handed helix at the subepicardium. The functional consequence of this three-dimensional helical structure is a cyclic systolic twisting deformation, resulting from clockwise basal rotation and counterclockwise apical rotation (as seen from the apex). Left ventricular twist plays a pivotal role in the mechanical efficiency of the heart, making it possible that only 15% fibre shortening results in a 60% reduction in left ventricular volume [9]. Moreover, diastolic untwisting of the left ventricle plays a crucial role in diastolic suction [10]. In the last decades, left ventricular twist has mainly been studied with tagged magnetic resonance imaging (MRI). However, lack of availability, limited temporal resolution, and the time-consuming and complex data analysis have precluded its use in routine clinical practice. More recently, it became possible to study left ventricular twist with tissue Doppler techniques and two-dimensional speckle tracking echocardiography. As mentioned before, this latter technique offers the opportunity to track myocardial deformation independently of both cardiac translation and the insonation angle.
Ever since the description of the rotational motion of the left ventricle by Leonardo da Vinci [4,5] in the 16th century, left ventricular twist has intrigued clinicians and researchers in their quest to understand the performance of the human heart. In the early 1960s, Harrison et al. [11] developed a method to measure external ventricular wall dimensions during the cardiac cycle. Silver tantalum clips were sutured into the human epicardium during cardiac surgery and these markers were viewed by calibrated cineradiographs. Ingels et al. [12] further developed this technique and studies of left ventricular twist continued throughout the 1980s. Unfortunately, progress was limited due to the invasive nature of the technique with its inherent limitations; the surgical implantation of the clips frequently led to local inflammation, hemorrhage and fibrosis, possibly affecting left ventricular twist. In addition, implantation of the clips could only be done in surgically accessible areas, which limited the left ventricular areas studied. In 1990, Buchalter et al. [13] described for the first time the non-invasive assessment of left ventricular twist with MRI. A tagging technique was employed to label specific areas of the myocardium prior to image acquisition. Tagging is achieved by selective radio-frequency excitation of narrow planes and appears as black lines on the image acquisition. Using dedicated software, displacement of these tagging lines can be monitored, allowing quantification of left ventricular deformation. However, the limited availability, the poor temporal resolution, and the time-consuming and complex data analysis have precluded its use in routine clinical practice.
More recently, assessment of left ventricular twist by speckle tracking echocardiography has become available. The fundamental principle of deformation imaging by speckle tracking echocardiography is simple. A certain segment of myocardial tissue is shown in an ultrasound image as a pattern of gray values caused by the interference of ultrasound reflected by the tissue. Such a pattern, resulting from the spatial distribution of the gray values, is commonly referred to as a speckle pattern. If the position of the myocardial segment within the ultrasound image changes, one can presume that the position of the speckle pattern will change accordingly. Since each region of the myocardium has its own rather unique speckle pattern, the speckle pattern can serve as a fingerprint of the region of interest of the myocardium. Furthermore, given a sufficiently high frame rate, it can be assumed that particular speckle patterns are preserved between subsequent image frames [14]. Thus, tracking of the speckle pattern during the cardiac cycle allows one to follow the motion of this myocardial segment within the two-dimensional ultrasound image. Several studies have shown [15,16] that twist data derived from commercially available speckle tracking software correlated well with tagged MRI. To be able to evaluate serial studies of left ventricular twist by speckle tracking echocardiography in the same patient, the technique needs to be reproducible as well. Van Dalen et al. [17] studied the feasibility and variability of left ventricular twist measurement and found that the method is feasible in approximately two thirds of subjects and has good intraobserver, interobserver and temporal reproducibility, allowing to study changes over time in left ventricular twist in an individual patient.
In this chapter, the important physiological role of left ventricular twist and untwist will be explained. Furthermore, cardiomyopathies may show striking alterations of left ventricular twist. The pathophysiological background and potential clinical role of these changes is discussed.
According to the Hippocratic treatise “On the Heart”, the heart is shaped like a pyramid, has a deep crimson colour, and is an extremely strong muscle. From the top of the heart, rivers that irrigate the “mortal habitation” flow into the body. If these rivers dry up, then the person dies [18]. Leonardo da Vinci’s investigations of the heart and circulation began nearly 18 centuries later, in the 1490s. Da Vinci made a number of advances in the understanding of the heart and blood flow. For example, he showed that the heart is indeed a muscle, that it has four chambers an he linked the pulse in the wrist with left ventricular contraction. Furthermore, as mentioned before, Da Vinci was the first to describe the rotational motion of the left ventricle [4,5]. However, it lasted until the late 1960s before left ventricular twist was described in more detail by Streeter et al. [7] following a study of post-mortem canine hearts. Using a rapid method of fixation, they were able to analyze these hearts in either systole, begin diastole or end-diastole. Fibre angle, representing the angle between the myofibres as projected onto the circumferential-longitudinal plane and the circumferential axis, was introduced for quantification of fibre orientation. This angle changed continuously from the subendocardium to the subepicardium, typically ranging from +60 degrees at the subendocardium to –60 degrees at the subepicardium. Left ventricular twist is supposed to originate from the dynamic interaction between these oppositely wound subepicardial and subendocardial myocardial fibre helices, whereby the direction of left ventricular twist is governed by the subepicardial fibres, mainly owing to their longer arm of movement [19]. Left ventricular twist plays a pivotal role in the mechanical efficiency of the heart, making it possible that only 15% fibre shortening results in a 60% reduction in left ventricular volume [20]. Furthermore, mathematical models have shown that the counterdirectional arrangement of muscle fibres in the heart is energetically efficient and important for equal redistribution of stresses and strain in the heart [21]. However, controversy remains present. The group of Buckberg published in 2005 a comprehensive compendium, “Rethinking the cardiac helix; a structure function journey”, of the Liverpool meeting: “New concepts of cardiac anatomy & physiology” [22]. Buckberg et al. believe that, based on anatomical studies by Torrent-Guasp [23] the heart is a helix that contains an apex, and that sequential contraction of the basal, descending, and ascending loop of the helix leads to the physiological pattern of myocardial contraction [24]. Although interesting, other anatomical studies have failed to reproduce the findings of Torrent-Guasp, and during the past few years this latter theory seems to gradually lose appreciation as compared to the theory of dynamic interaction between oppositely wound subepicardial and subendocardial myocardial fibres [25]. Taber et al. [19] used a theoretical model to underscore the importance of the arrangement of myocardial fibres for left ventricular function. Peak systolic twist approximately doubled with a change in de epicardial / endocardial fibre angles from +90 degrees / –90 degrees to +60 degrees / –60 degrees. The importance of fibre orientation for left ventricular twist was highlighted in clinical context as well [26]. Left ventricular sphericity index was found to have an independent positive linear relation with peak systolic twist in dilated cardiomyopathy patients. Even in dilated cardiomyopathy patient with similar left ventricular ejection fraction, left ventricular sphericity index remained positively correlated to left ventricular twist. Interestingly, in normal hearts the left ventricular sphericity index had a parabolic relation with apical peak systolic rotation and peak systolic twist. A left ventricular sphericity index of about 2.1 was associated with the highest peak systolic twist, lower and higher sphericity indices were associated with less peak systolic twist. The findings of this study seem to support the hypothesis by Taber et al. that alterations in fibre-orientation influence left ventricular peak systolic twist. Furthermore, the curvature of the left ventricular wall is related to wall tension. Since deformation of myocardial fibres is known to be inversely related to wall tension, changes in cardiac shape may also lead to changes in left ventricular twist by means of alterations in wall tension [21].
In 1995, Moon et al. [27] investigated the effects of load and inotropic state on left ventricular twist. They studied 6 cardiac transplant recipients 1 year after heart transplantation. At the time of surgery 12 radiopaque midwall left ventricular myocardial markers were implanted. The authors claimed that pressure and volume loading did not affect left ventricular twist. However, in more recent tagged MRI studies by MacGowan et al. [28] and Dong et al. [29] it has been shown that afterload changes do affect left ventricular twist. Dong et al. also investigated the influence of preload and contractility. An isolated increase in preload resulted in an increase in left ventricular twist. From a multiple linear regression analysis, they concluded that the effect of preload on left ventricular twist was about two-thirds as great as that of afterload. Since left ventricular twist is critically dependent on the arrangement of fibres in the myocardium, the dependence of left ventricular twist on pre- and afterload-induced changes in left ventricular volumes is intuitive. Dong et al. also observed that dobutamine increased left ventricular twist, even at identical pre- and afterload, indicating that there is a direct inotropic effect on left ventricular twist that is not mediated through changes in volume, but through changes in force.
Finally, several groups investigated the influence of aging on left ventricular twist [30-32]. Nakai et al. [30] and Takeuchi et al. [31] reported increased left ventricular twist with aging. Because left venticular peak systolic twist is calculated as the maximal value of
Untwisting starts after the peak of left ventricular twist, just before the end of systole. The twisting deformation of the left ventricle during systole results not only in ejection of blood but also in storage of potential energy. During the isovolumic relaxation period the twisted fibres behave like a compressed coil that springs open while abruptly releasing the potential energy. This process may be actively supported by still depolarized subendocardial fibres that are – in contrast to the systolic period – now not opposed by active contraction of the subepicardial fibres [38]. However, the effective force of contraction of myocardial fibres is expected to be minimal during this part of the cardiac cycle. Nevertheless, dissimilarities of apparent stiffness of the endocardium and epicardium caused by differences in breakdown of actin-myosin cross-bridges may be of influence. The group of Shapiro and Rademakers was one of the first to investigate the physiology of left ventricular untwisting in more detail with MRI [39]. They found, in an open-chest canine model, that left ventricular untwisting and filling are dissociated in time. In the normal resting heart about 40% of left ventricular untwisting occurs during isovolumic relaxation. Dobutamine enhanced the extent of left ventricular untwisting before mitral valve opening and further accentuated the dissociation between left ventricular untwisting and filling. The untwisting rate, the mean left ventricular untwisting velocity during the isovolumic relaxation phase, is proportional to the rate of isovolumic pressure decay [40]. In addition, left ventricular untwisting precedes and is a strong predictor of the intraventricular pressure gradient, a marker of diastolic suction during early left ventricular filling. This may be caused by a temporal dispersion between basal and apical de-rotation, the diastolic reversal of systolic rotation [41]. At the left ventricular apical level there is faster de-rotation, as compared to the basal level, which may be explained by the relatively increased systolic apical rotation, and thus stored potential energy. Interestingly, at the left ventricular basal level there is still a profound de-rotation from mitral valve opening until the peak of early left ventricular filling velocity. This may be explained by the temporal dispersion in basal and apical repolarization. Since the basal endocardial fibres are the latest to be repolarized (repolarization progresses from the apex to the base of the heart and from the epicardium to the endocardium, and takes approximately 150ms), an extra de-rotating force may still be present during this period at the basal level. Furthermore, there is a brief episode of re-rotation at the basal level from the peak to the end of the early left ventricular filling velocity that may partially be explained by the sudden omission of the de-rotational forces of the endocardial fibres, at the moment of complete cardiac repolarization. In contrast, during this period continuing de-rotation is seen at the left ventricular apical level. Since rotation is related to an increase and de-rotation to a decrease in left ventricular pressure, this phenomenon may facilitate blood flow all the way to the apex. Thus, left ventricular untwisting provides a temporal link between two crucial diastolic phenomena, relaxation and diastolic suction.
In adolescents and young adults, there may be a marked contribution of active left ventricular relaxation to left ventricular filling, resulting in an accentuated early diastolic filling velocity with a short deceleration time, resembling restrictive left ventricular filling at Doppler echocardiography (‘pseudo-restrictive’ left ventricular filling pattern). Very rapid left ventricular untwisting plays a pivotal role in this physiological rapid early diastolic filling [42]. In contrast, in dilated cardiomyopathy patients, untwisting is delayed and this impairment to utilize suction may impair left ventricular filling [42].
Marked changes in left ventricular diastolic function are known to occur in healthy elderly [43,44]. As described before, with advancing age left ventricular twist increases, probably due to both a decrease in rotational deformation delay and subendocardial dysfunction leading to loss of the counteraction of the subendocardial fibre helix. The early diastolic release of increased potential energy stored during this augmented systolic twisting deformation may be the cause of preserved peak diastolic untwisting velocity and untwisting rate with aging. A strong age-independent relation between left ventricular peak systolic twist and peak diastolic untwisting velocity and untwisting rate supports this hypothesis. Nevertheless, although peak diastolic untwisting velocity and untwisting rate do not change significantly with advancing age, both parameters are significantly impaired when normalized for the increased extent of left ventricular twist. This results in a progressive delay in relative left ventricular untwisting and in the time-to-peak diastolic untwisting velocity with aging. This may reflect the increased stiffness known to occur in aging. In addition, the same subendocardial dysfunction that is supposed to lead to increased left ventricular twist with aging, may also lead to loss of the active part of untwisting normally caused by in early diastole still depolarized subendocardial fibres. Relatively reduced and delayed left ventricular untwisting may help to explain the increased duration of isovolumic relaxation in the elderly. Because left ventricular untwisting generates the left ventricular pressure gradient that helps filling the left ventricle [10], impediment of left ventricular untwisting may lead to delayed generation of this pressure gradient, and thereby to delayed opening of the mitral valve.
As mentioned before, left ventricular twist originates from the dynamic interaction between oppositely wound subepicardial and subendocardial myocardial fibres. The direction of left ventricular twist is governed by the subepicardial fibres, mainly owing to their longer arm of movement. Subendocardial ischemia with loss of contraction of the counteracting subendocardial fibres will lead to increased left ventricular twist. Therefore, left ventricular twist, and in particular changes within one patient, may provide an easily assessable marker of subendocardial ischemia. Increased left ventricular twist has been described in aging healthy subjects (as discussed previously), and in patients with hypertrophic cardiomyopathy (HCM), aortic stenosis (AS), or diabetes.
In HCM patients, left ventricular twist is increased [45,46]. Actually, in particular left ventricular basal rotation is augmented [46]. The increased basal rotation may be explained by loss of counteraction of the subendocardial fibre helix, caused by endocardial ischemia due to microvascular dysfunction [47,48]. Also, larger radius differences between the subepicardium and subendocardium in hypertrophic muscle may increase the dominant action of the subepicardial fibres and increase basal rotation. Interestingly, left ventricular apical rotation and twist are dependent on the pattern of left ventricular hypertrophy. In patients with a sigmoidal septal curvature, left ventricular apical rotation and twist are increased as compared to patients with a reverse septal curvature. This may be partly explained by the degree of subendocardial ischemia, since patients with a sigmoidal septal curvature more often have left ventricular outflow tract obstruction. The extravascular compressive forces caused by gradients due to the outflow obstruction may lead to more extensive microvascular dysfunction and subendocardial ischemia.
AS patients are consistently found to have increased left ventricular twist, mainly due to increased left ventricular apical rotation [49-51]. Furthermore, left ventricular apical rotation and twist correlate positively to the severity of AS. This underlines the potential role of subendocardial ischemia as the cause of increased left ventricular apical rotation and twist in AS since the severity of subendocardial ischemia is known to be related to the severity of AS [52]. In addition, left ventricular apical rotation and twist are highest in AS patients with symptoms (angina) or electrocardiographic signs (strain) compatible with subendocardial ischemia [53]. However, deformation of myocardial fibres is known to be inversely related to wall tension. Since increased afterload in AS leads to increased endocardial wall tension, increased left ventricular twist in AS may also be caused by decreased endocardial deformation as a result of increased endocardial wall tension, independently of ischemia.
Increased left ventricular twist was also described in diabetics with a normal left ventricular ejection fraction [54-56]. Several potential mechanisms for the supposed loss of counteraction of the subendocardial fibres have been mentioned, including metabolic disturbances triggered by hyperglycemia, increased free fatty acid oxidation, altered calcium homeostasis, myocyte death, fibrosis, small-vessel diseases, and cardiac autonomic neuropathy.
In all the above mentioned examples, increased left ventricular twist may serve as a compensatory mechanism to balance loss of left ventricular myocardial contraction in other directions, which with subendocardial dysfunction is usually a loss of contraction in the longitudinal direction, and thereby preserve left ventricular ejection fraction.
The need for objective evidence of left ventricular diastolic dysfunction has led to an extensive search for accurate, noninvasive, load-independent methods to quantify its severity. Takeuchi et al. [57] examined whether left ventricular hypertrophy adversely affects left ventricular untwisting in hypertension patients. Patients with moderate to severe left ventricular hypertrophy had reduced and delayed left ventricular untwisting as compared to patients without left ventricular hypertrophy, which may contribute to the left ventricular relaxation abnormality seen in these patients.
In both HCM [58] and AS [51], the untwisting rate, the mean untwisting velocity during the isovolumic relaxation phase, is decreased and untwisting is delayed. Subendocardial ischemia may lead to loss of active untwisting normally caused by the subendocardial fibres during early diastole. In addition, the impaired compliance of the left ventricles of these patients will prevent optimal transformation of the potential energy stored in systolic left ventricular twisting into kinetic energy. However,
Noncompaction cardiomyopathy (NCCM) is a myocardial disorder characterized by excessive and prominent trabeculations associated with deep recesses that communicate with the ventricular cavity but not the coronary circulation [59]. Although NCCM was included in the 2006 World Health Organization classification of cardiomyopathies [60], it remains subject to controversy owing to lack of consensus on its aetiology, pathogenesis, diagnosis, and management [61]. The final stage of the development of myocardial architecture is characterized by the formation of compact myocardium and development of oppositely wound epicardial and endocardial myocardial fibre helices [62,63]. Since NCCM is probably caused by intrauterine arrest of this final stage of cardiac embryogenesis [64], it may be anticipated that left ventricular twist characteristics are altered, beyond that seen in patients with impaired left ventricular function and normal compaction. This has been confirmed in a clinical study. NCCM patients were found to show left ventricular rigid body rotation, that is predominantly instantaneous rotation at the basal and apical level in the same direction, with near absent left ventricular twist. In a subsequent, larger study left ventricular rigid body rotation was confirmed to be an objective, quantitative, and reproducible criterion with a good predictive value for the diagnosis of NCCM as established by expert opinion [65]. Interestingly, all familial NCCM patients showed rigid body rotation. Since the diagnosis of NCCM seems most certain in patients with familial NCCM, this finding underscores the excellent sensitivity of solid body rotation for NCCM. Of additional interest was the finding that NCCM patients who were first-degree relatives from one family had identical left ventricular rotation patterns, suggesting a genetic-functional relationship in NCCM.
Although a significant reduction of left ventricular twist was observed in patients with advanced heart failure, left ventricular twist did not improve after resynchronization therapy, despite significant gains in left ventricular global and short-axis function in responders. In fact, non-responders showed further reduction of left ventricular twist [66]. However, in a more recent study, subendocardial and subepicardial left ventricular twist were investigated separately, which did lead to identification of prognostic value of left ventricular twist in the population undergoing resynchronization [67]. At 6-month follow-up, 53% of the patients showed favorable outcomes after resynchronization therapy. In a multivariate logistic regression analysis, only the immediate improvement of subepicardial left ventricular twist was independently related to favorable outcomes. Furthermore, the immediate improvement of subepicardial left ventricular twist had incremental value over established parameters. Several reasons may explain this finding. First, subepicardial left ventricular twist may reflect the positive effects of cardiac resynchronization therapy better than subendocardial left ventricular twist, because the subepicardial layer is the major determinant of left ventricular twist. Second, left ventricular pacing in cardiac resynchronization therapy is applied from the epicardial surface, which may be more closely related to mechanical changes in the subepicardial than the subendocardial left ventricular layer.
Sun et al. [68] subjected 7 pigs to myocardial infarction by occlusion of the left anterior descending coronary artery. After 8 weeks, left ventricular twist was decreased significantly in the left anterior descending coronary artery territory areas, whereas there was no change in twist in adjacent and remote left ventricular areas. Therefore, the authors proposed that left ventricular twist may be suitable for noninvasive quantification of left ventricular regional function in ischemic heart disease. Kroeker et al. [69], using an optical device coupled to the left ventricular apex in 16 open-chest dogs, also found a decrease of left ventricular apical rotation with ischemia caused by occlusion of the left anterior descending coronary artery. Interestingly, in the first 10 seconds of occlusion, there was a paradoxical increase in left ventricular apical rotation, which was attributed to isolated subendocardial ischemia leading to loss of the counteractive action of the subendocardial helix of myofibres.
In clinical studies in patients with a prior anterior myocardial infarction it was found that, although left ventricular basal rotation was preserved, left ventricular apical rotation was decreased, leading to decreased left ventricular twist [70]. In patients with a left ventricular aneurysm, left ventricular apical rotation was nonexistent or even inverted, leading to severely decreased left ventricular twist.
In the majority of left ventricular twist studies in congenital heart disease, investigators focused on patients with a congenital transposition of the great arteries. In patients operated with atrial switch, the systemic right ventricle shows absence of twist, whereas the subpulmonary left ventricle shows reduced twist [71,72]. Furthermore, there are regional differences of apical rotation of the subpulmonary left ventricular, whereas apical rotation is homogeneous in a normal left ventricle [73,74]. In a theoretical model of situs inversus totalis, and in 8 patients with this condition [75,76] it was shown that, although gross anatomy is mirror imaged, this is not the case for left ventricular systolic deformation. Both the left ventricular base and apex rotated in a counterclockwise direction, whereas the midventricular section exhibited hardly any rotation. These findings may be explained by the arrangement of myofibres in these patients. Anatomical studies have revealed that in situs inversus totalis arrangement of myofibres is normal in the apical regions leading to normal counterclockwise rotation, whereas at the basal level a partly mirror-imaged pattern of the normal transmural change in fibre angle is seen.
Even though left ventricular twist is indispensable for proper left ventricular function, little is known about it in “the cardiology community”. Mainly due to the development of speckle tracking echocardiography, allowing accurate, reproducible and rapid bedside assessment of left ventricular twist, interest in this important mechanical aspect of left ventricular deformation has been rapidly increasing.
Although the vital physiological role of left ventricular twist is indisputable, the clinical relevance of assessment of left ventricular twist in cardiomyopathies still needs to be confirmed. Nonetheless, left ventricular twist evaluation has already provided significant pathophysiological insight in a broad variety of cardiomyopathies. It has become clear that increased left ventricular twist in for example HCM, AS, and diabetics, but also in a healthy ageing population, may serve as a compensatory mechanism to preserve ejection fraction. Furthermore, demonstration of left ventricular rigid body rotation in NCCM may provide a unique way to objectively confirm this difficult diagnosis. Diastolic left ventricular untwisting represents the elastic recoil caused by the release of restoring forces that have been generated during the preceding systolic left ventricular twist and has an important contribution in left ventricular filling through suction generation. Measurement of left ventricular untwisting may become an important element of diastolic function evaluation in cardiomyopathies in the future.
Oncological diseases pose a major problem worldwide in terms of societal, healthcare, financial, and economic impact with the number of cancer cases continually rising. The research for novel anticancer drugs comprises a significant portion of contemporary research and development in the field of medicine and pharmacy. Nitrogen heterocycles are a component of 59% of FDA-registered drugs [1] as of 2014. Among them, pyridine is the second most commonly incorporated nitrogen heterocycle. Pyridine-containing drugs are quite heterogeneous in terms of chemical structure, pharmacokinetics and pharmacodynamics – antihistamines (chlorpheniramine, brompheniramine), antiarrhythmic (disopyramide), antihypercholesterolaemic (cerivastatin), antitubercular (isoniazid, ethionamide), antibiotic (telithromycin), antiretroviral for AIDS treatment (indinavir), and anticancer (crizotinib, abiraterone) to name a few.
A multitude of natural substances contains pyridine. They tend to be involved in a number of physiological processes, among which is cancer pathogenesis. The pyridine ring is a chemically stable heterocyclic structure. Its nitrogen atom is able to participate in hydrogen bonding, which allows pyridines to bind to DNA and exhibit anticancer effects [2]. Pyridine can play the role of pharmacophore and can also serve as a stable basis for the synthesis of novel anticancer drugs. The present chapter aims to inform the reader in a brief and concise manner on the latest developments in the search for pyridine-based anticancer drugs, their mechanisms of action, and the most utilized synthetic approaches. Herein are included the most common types of novel, pyridine-based compounds, found in the scientific literature that do not involve fused ring structures. They are represented by molecular hybrids that the authors have classified into the following groups in terms of structure:
Coumarin-pyridine hybrids
Chalcone-pyridine hybrids
Combretastatin-pyridine hybrids
Terpyridines and terpyridines isosteres
Additionally, the authors are also presenting data on biological activity, types of cancer cell lines being suppressed, and pharmacodynamic action of the molecules discussed, should such information be available.
A number of pyridines have recently been registered for anticancer treatment [3]. The list predominantly includes kinase inhibitors (apalutamide, pexidartinib, lorlatinib, acalabrutinib, abemaciclib, neratinib, and alpelisib) – drugs that inhibit cellular kinases. Kinases are a family of enzymes that participate in cellular metabolism, signaling, replication, and survival. Inhibiting them suppresses vital cellular functions, therefore, targeting cancer-specific kinases suppresses tumor growth. Ivosidenib and enasidenib serve as isocitrate dehydrogenase (IDH) inhibitors. IDH is involved in energy production and includes two subtypes (IDH1 and IDH2). Mutations in IDH1 and IDH2 can cause changes in DNA gene expression including expression of oncogenes [4]. Inhibition of these enzymes could impair cancer growth. Benetoclax is a Bcl-2 inhibitor. Bcl-2 is a protein that suppresses cell death (apoptosis) [4]. Overexpression of Bcl-2 can prevent or significantly delay cell death – a typical characteristic of cancer. These drugs have been approved by FDA within the period 2017–2019. Considering the extremely stringent approval process of novel medicinal molecules, such a large number of newly-approved anticancer agents underscores both the extreme intensity of scientific exploration for novel anticancer treatments as well as the important role of the pyridine structure plays in drug research.
The coumarin (benzopyran-2-on) structure (Figure 1) is considered an important bioactive scaffold, included in numerous drugs currently in use [5].
Chemical structure of coumarin.
Coumarins are derived both naturally and synthetically. The specific structure of the coumarin scaffold allows coumarin derivatives to interact with a large variety of receptors and enzymes. They are currently being clinically utilized as anticoagulants and antithrombotic agents with relatively low toxicity. Naturally occurring and synthetic derivatives have shown promise as antimicrobial, anti-inflammatory, anticancer, antioxidant, and MAO-B inhibitory agents [6]. They can exhibit cytostatic and cytotoxic activities against a significant number of cancer cell lines [7]. Adding a variety of functional groups and creating molecular hybrids is a promising direction for the development of novel medicinal molecules, aimed at alleviating a wide variety of maladies. Hybridization of coumarin derivatives with pyridines is a field of intense study in anticancer drug research [8, 9, 10].
4-Arylcoumarins are known for their cytotoxic and antiproliferative properties [11]. They can be viewed as structural analogs of the promising antiproliferative molecule combretastatin A-4 (CA-4), yielding very similar effects. For more information on CA-4 and its characteristics, please see Section 5. Pyridine isosteres of that class of compounds have been synthesized and tested for antiproliferative activity (Figure 2).
Structure of the 4-arylcoumarin isosteres.
Pyridine derivatives manifest moderate activity against the A549 lung adenocarcinoma cell line [12]. Variants a and b significantly disrupt microtubule formation. Adding an electron-donating group in 6th place of ring A increases antiproliferative activity (Figure 2). Substituting with an electron-withdrawing group, such as a fluorine atom, in that same place decreases biological activity. Substituting the para-situated methoxy group in ring B only decreases the effect (Figure 2). The basics of the synthetic approach to yield 4-arylcoumarins are schematically presented in Figure 3.
Brief representation of the synthesis of 4-arylcoumarines.
Research and development of novel anticancer drugs are most often targeted toward a specific mechanism of action. A number of potential PI3K lipid kinase inhibitors have been synthesized by hybridization of coumarins and pyridines.
PI3K are enzymes, involved in the regulation of cellular growth, replication, and survival, as well as the mediation of protein kinase B (universally known as Akt). Upregulation of PI3K and Akt signaling is associated with tumor growth and tumor cell migration. The aforementioned substances have been tested for PI3K and Akt inhibition as well as antiproliferative activity against K562 (myelogenous leukemia), HeLa (cervical carcinoma), A549, and MCF-7 (adenocarcinoma) cancer strains [13]. A brief schematic of the synthesis is presented in Figure 4.
Synthetic approach for generating some PI3K kinase inhibitors.
The member with difluoro-substituted phenyl ring (Figure 5) has the strongest effect on all observed cell lines.
The most active PI3K inhibitors against various cancer cell lines.
All 3,4-disubstituted members exhibit a similar degree of antiproliferative effect. Another member, with monochloro substituted phenyl ring (Figure 5) has been found to significantly inhibit both PI3K and Akt and to initiate apoptosis in the K562 cell line.
A number of hybrid molecules have been synthesized using a novel approach [14]. The final step of the synthesis is conducted in two different media – in refluxing ethanol or under microwave heating. Microwave heating proves to be more energy-efficient, quicker, and produces significantly higher yields. Figure 6 represents the basic synthesis of the most potent substance which exhibits promising activity against HCT-116 (colorectal carcinoma) and MCF-7 cell lines.
Novel synthesis of coumarin-pyridine hybrid compounds.
Chalcones are natural products from the flavonoid family, found in abundance in plants. Chalcone (Figure 7) is a molecular scaffold, characterized by uncomplicated chemistry, easy synthesis, and a large number of hydrogen atoms that, when substituted, can yield a huge selection of derivatives, exhibiting multiple physiological effects – antioxidant [15], antidiabetic [16], antihypertensive [17], anticancer [18], and many others.
The chalcone molecular scaffold.
They are known to inhibit cell proliferation, acting as antitumor agents both in vitro and in vivo. The antiproliferative properties of chalcones have been known for more than two decades [19]. Chalcones tend to bind to the so-called colchicine binding site in tubulin – a building block of microtubules. Microtubules are essential structures in all eukaryotic cells, responsible for keeping the structural integrity of cells, cell division, and many others [20]. Disrupting their synthesis is the mechanism of action of a number of antineoplastic drugs [21]. Attaching a pyridine moiety to the chalcone skeleton would be a way to complement the observed anticancer activity.
A promising design approach for the synthesis of chalcone-pyridine derivatives would be replacing one of the benzene rings with pyridine. A number of such molecules have been generated and then tested for antiproliferative activities and tubulin polymerization suppression [22]. α-(4-pyridyl) ketones and the necessary aldehydes undergo an aldol reaction to yield a number of chalcone-pyridine hybrids. The aforementioned step in the synthesis of the most potent member is presented in Figure 8.
Chalcone synthesis via aldol condensation.
All generated substances prove to be effective against K652 cells. The most potent one (Figure 8) is almost as effective as combretastatin A-4. It acts as a microtubule-destabilizing agent with an IC50 lower than that of CA-4. It connects with the colchicine binding site with 88% potency at 5 μM concentration, arresting the cell cycle of K562 at the G2/M phase and inducing apoptosis in a concentration-dependent manner.
The α-positioned methyl moiety to the carbonyl group tends to improve activity. The exposed hydroxyl at the meta-position of ring B (R3) is important for the biological activity – changing it to methoxy decreases the observed effect. Adding electron-donating groups to ring A increases the effect, while adding electron-withdrawing groups (such as chlorine atoms) decreases the activity.
Aldol condensation has also been applied to generate a number of pyridinium bromide salts that have manifested promising antiproliferative activity against MCF-7, HeLa, U-87MG (malignant glioblastoma), and HEK293 (kidney) cell lines [23]. A brief summary of the synthesis of the two most active members is presented in Figure 9.
Pyridinium bromide salts’ synthesis.
In terms of the structure-activity relationship, adding a strongly electron-donating functional group at the para-position of the phenyl radical R increases biological activity. Interestingly, adding the strongly electron-withdrawing nitro group also improves the antiproliferative properties. Replacing the radical R with a coumarin substituent (potentially anticancer-bearing) nullifies the anticancer effect.
Another class of substances that have been synthesized incorporates pyridine nucleus not as a substitute of one of the chalcone phenyl rings, but as a substituent [24]. They have been tested for their antiproliferative effect and colchicine-binding ability. The synthesis of the most active compounds is shown in Figure 10.
Synthesis of pyridine substituted chalcones.
As in the previous case, adding electron-withdrawing groups, particularly in para-position, to the chalcone phenyl ring increases biological activity. Adding electron-donating groups (methoxy) to the same position has the same effect on ACHN (renal adenocarcinoma), MCF-7, and A549 cancer cell lines. The novel compounds have been docked in silico to the tubulin receptor, yielding promising results in terms of microtubule disruption.
Combretastatins are a family of stilbenes, derived from the bark of the African Willow tree [25]. Combretastatin A-4 (Figure 11) in particular is an effective, selective inhibitor of tubulin polymerization by binding to the colchicine binding site. Thus it inhibits microtubule growth and acts as an antivascular and antimitotic agent, preventing cellular multiplication, changing endothelial cell structure, and resulting in tumor necrosis [26].
Structure of combretastatin A4.
The cis-orientation of rings A and B is crucial for combretastatin A-4’s cytotoxicity [27]. CA-4’s application has been limited by its low solubility in aqueous media. Modification of its molecular structure (changing the aromatic rings and replacing the stilbene bridge) to increase its bioavailability, while maintaining its physiological effect has been a source of numerous investigations [28, 29, 30].
A number of combretastatin A-4 analogs with pyridine aromatic rings as a linker have been synthesized [31]. Two examples are presented in Figure 12.
CA-4 analogs − 2,4-diphenyl-substituted pyridines.
Compound 1 manifests moderate cytotoxicity against MCF-7 cancer cells. Replacing the methyl group in its pyridine cycle with a hydroxyl group causes negation of the observed effect (compound 2). The antiproliferative effect associated with these 2,4-diphenyl-substituted pyridine structures is not very clearly manifested.
Interesting observations have been made with similar compounds, utilizing a pyridine linker between the two phenyl rings [32]. Among dozens of substances, three exhibit notable anticancer activity (Figure 13).
CA-4 analogs - 2,6-diphenylsubstitited pyridines.
In terms of the structure-activity relationship, when the phenyl rings are at a para position from each other in the pyridine linker, cytotoxicity is low. Meta-position improves biological activity. The best results are observed with a 2,6-diphenyl substituted pyridine linker. 3,4,5-trimetoxy substituted ring A does not contribute significantly to biological activity. Compound 3 is the only one from a multitude of members, bearing such substituent, that yields promising results. It is an almost full analog of CA-4 − the stilbene linker is replaced with a 2,6-disubstituted pyridine. On the other hand, a 2,4-dimethoxy substituted ring A causes significant suppression against several cell lines − MDA-MB-231 (breast cancer), A549, and HeLa. Any other type of dimethoxy substitution (e.g., 3,4-; 2,5-, etc.) decreases the antiproliferative effect. 3,4,5-trimethoxy substitution in ring B also weakens the biological effect. With 2,4-dimethoxysusbtituted ring A, 3-monomethoxy and 4-monomethoxy substituted ring B offer high antiproliferative effect, while 2-monomethoxy offers lesser activity. Thus, compounds 1, 2, and 3 potently inhibit cell survival and growth, arrest the cell division cycle and bind to the colchicine site to a degree, similar to combretastatin A4.
Terpyridine is a known ligand in a variety of complexes [33]. Its structural analogs tend to bind to and intercalate in nucleic acids [34, 35]. α-Terpyridine (Figure 14) and its isosteres have manifested significant topoisomerase I and II inhibitory activity as well as notable cytotoxicity against a variety of cancer cell lines [36, 37]. Topoisomerases are a family of enzymes that catalyze changes in the topological state of the DNA double helix. They are involved in DNA replication and transcription, hence impairment of their function inhibits cellular replication – a way to suppress rapid tumor growth.
Chemical structure of α-terpyridine.
Terpyridines can be derived by way of the Kröhnke pyridine synthesis [38], represented in Figure 15.
Schematic representation of the synthesis of terpyridines and their isosteres.
Two families of terpyridine isosteres have been synthesized and tested for topoisomerase inhibitory activity and cytotoxicity – molecules with four aryl groups (furyl, thienyl, and pyridyl) and molecules with three aryl groups (Figure 16).
Structures of the investigated terpyridines.
Three-ringed terpyridine members manifest low topoisomerase inhibitory activity and cytotoxicity. Some 2,4,6-trisubstituted members exhibit significant biological activity (listed in Table 1).
Biological effect of various terpyridine isosteres with four aryl groups.
Notably, topoisomerase I inhibiting substances do not suppress topoisomerase II and topoisomerase II inhibiting substances do not suppress topoisomerase I. Interestingly, topoisomerase inhibitors manifest low toxicity toward a variety of cancer cell lines – MCF-7, HeLa, DU145 (prostate cancer), and HCT15 (colorectal cancer). At the same time, some trisubstituted terpyridines did not behave as enzyme inhibitors but despite that are highly cytotoxic. In terms of molecular structure 2-furyl and 2-thienyl moieties in 2nd place, 4-pyridyl in 6th place, and 2/3-thienyl in 4th place seem to have the greatest impact on biological activity.
Terpyridines are being intensely studied in the field of oncology not so much for their intrinsic antiproliferative properties but for their ability to chelate metal ions. Recent data show that chelating copper ions with terpyridine ligands produce coordination compounds with high cytotoxicity and G0/G1 cell cycle phase inhibitory activity [39]. Experiments have demonstrated that complexes of terpyridines manifest antiproliferative activity in the nanomolar range against a large variety of cancer cell lines – MCF-7, A549, HCT-116, U-251 (glioblastoma), and PANC-1 (pancreatic carcinoma). At the same time, the observed IC50 doses against normal human fibroblasts (NHDF) are about 10−15 times higher, demonstrating good selectivity and potentially lower toxicity toward healthy human tissues. Numerous terpyridine complexes with platinum (Figure 17), palladium, and lanthanides have also recently been synthesized [40, 41, 42, 43], bearing promising protein-binding, DNA-binding, and antiproliferative activities.
An example of terpyridine-platinum complex. The ligand incorporates a “nitrogen mustard” moiety (in red), linked to the central pyridine ring. That molecular “tail” increases antiproliferative activity and DNA-binding of both the ligand itself and its platinum complex.
The pyridine heterocycle is an important chemical structure, ubiquitously utilized within the field of modern pharmaceutical science, research, and development. Its characteristic physicochemical properties (chemical stability, participation in hydrogen bonding, and numerous hydrogen atoms that can be substituted) make it an attractive molecular basis for synthesis of medicinal substances. Its nitrogen atom makes it a useful pharmacophore, imbuing potential drug molecules with novel pharmacological effects. Attaching it to extant compounds can modify their pharmacokinetics, pharmacodynamics, and physiological effect. The authors’ aim is that the present chapter reveals to the reader the important role pyridine chemistry plays in the field of oncology. Pyridine-based compounds are being intensely researched in the hope of inventing novel oncological drugs that combine significant anticancer cytotoxicity with an improved safety profile and a targeted mechanism of action. Within the past several years a large number of novel pyridine anticancer molecules have been synthesized, yielding some very promising results. Substances of both natural and synthetic origin have been generated and/or modified, synthetic approaches have been refined and interesting and potentially important structure-activity relationships have been revealed. Hopefully, the authors have been able to present the subject of pyridines in oncology to the reader’s satisfaction, both informing them as well as sparking an interest in this rapidly evolving area of research.
The authors declare no conflict of interest.
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The tissue and cell deformations caused by shear forces are the most common pathological features in TBI and lead to long-term symptoms. Our current understanding of TBI derives mainly from in vivo studies of poststimulus pathology and the effects on brain function. Little is known about the early responses of brain cells during mechanical stimuli. In this chapter, we evaluate the early cell response to the rapid shear forces in vitro. We introduce advanced technologies capable of generating fast shear stimuli mimicking forces occurring in TBI and reporting internal forces in specific proteins at the time of injury. We define the threshold shear forces for calcium influx using an astrocyte model. We describe the spatiotemporal distribution of cytoskeletal forces and correlate them with variations in cell membrane tension. This chapter makes a strong argument that cells’ response to external forces is nonlinear. 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Then it introduces the basic concepts of kinematics, kinetics, and anthropometry and discusses in detail the muscle mechanics and electromyography. The muscle is the actuator of the human body, especially the skeletal muscles which are attached with the skeleton play an important role in defining the movements of the human body. The human body controls the muscle through the nervous system, and this nervous system generates signals called electroencephalogram (EEG) which upon leaving the nerves excites the muscle and converted into muscle signals usually called electromyogram (EMG). In this chapter, we will discuss the mechanics of the muscle in conjunction with the EMG. 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Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:6,paginationItems:[{id:"22",title:"Applied Intelligence",coverUrl:"https://cdn.intechopen.com/series_topics/covers/22.jpg",isOpenForSubmission:!0,editor:{id:"27170",title:"Prof.",name:"Carlos",middleName:"M.",surname:"Travieso-Gonzalez",slug:"carlos-travieso-gonzalez",fullName:"Carlos Travieso-Gonzalez",profilePictureURL:"https://mts.intechopen.com/storage/users/27170/images/system/27170.jpeg",biography:"Carlos M. Travieso-González received his MSc degree in Telecommunication Engineering at Polytechnic University of Catalonia (UPC), Spain in 1997, and his Ph.D. degree in 2002 at the University of Las Palmas de Gran Canaria (ULPGC-Spain). He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. 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His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. 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His present research includes organic synthesis, drug discovery and development, biochemistry, nanoscience, and nanotechnology.",institutionString:"Visiting Scientist at Lipid Nanostructures Laboratory, Centre for Smart Materials, School of Natural Sciences, University of Central Lancashire",institution:null},{id:"428125",title:"Dr.",name:"Vinayak",middleName:null,surname:"Adimule",slug:"vinayak-adimule",fullName:"Vinayak Adimule",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/428125/images/system/428125.jpg",biography:"Dr. Vinayak Adimule, MSc, Ph.D., is a professor and dean of R&D, Angadi Institute of Technology and Management, India. He has 15 years of research experience as a senior research scientist and associate research scientist in R&D organizations. He has published more than fifty research articles as well as several book chapters. He has two Indian patents and two international patents to his credit. Dr. Adimule has attended, chaired, and presented papers at national and international conferences. He is a guest editor for Topics in Catalysis and other journals. He is also an editorial board member, life member, and associate member for many international societies and research institutions. His research interests include nanoelectronics, material chemistry, artificial intelligence, sensors and actuators, bio-nanomaterials, and medicinal chemistry.",institutionString:"Angadi Institute of Technology and Management",institution:null},{id:"284317",title:"Prof.",name:"Kantharaju",middleName:null,surname:"Kamanna",slug:"kantharaju-kamanna",fullName:"Kantharaju Kamanna",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284317/images/21050_n.jpg",biography:"Prof. K. Kantharaju has received Bachelor of science (PCM), master of science (Organic Chemistry) and Doctor of Philosophy in Chemistry from Bangalore University. He worked as a Executive Research & Development @ Cadila Pharmaceuticals Ltd, Ahmedabad. He received DBT-postdoc fellow @ Molecular Biophysics Unit, Indian Institute of Science, Bangalore under the supervision of Prof. P. Balaram, later he moved to NIH-postdoc researcher at Drexel University College of Medicine, Philadelphia, USA, after his return from postdoc joined NITK-Surthakal as a Adhoc faculty at department of chemistry. Since from August 2013 working as a Associate Professor, and in 2016 promoted to Profeesor in the School of Basic Sciences: Department of Chemistry and having 20 years of teaching and research experiences.",institutionString:null,institution:{name:"Rani Channamma University, Belagavi",country:{name:"India"}}},{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/158492/images/system/158492.jpeg",biography:"Prof. Dr. Yusuf Tutar conducts his research at the Hamidiye Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Division of Biochemistry, University of Health Sciences, Turkey. He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"94311",title:"Prof.",name:"Martins",middleName:"Ochubiojo",surname:"Ochubiojo Emeje",slug:"martins-ochubiojo-emeje",fullName:"Martins Ochubiojo Emeje",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94311/images/system/94311.jpeg",biography:"Martins Emeje obtained a BPharm with distinction from Ahmadu Bello University, Nigeria, and an MPharm and Ph.D. from the University of Nigeria (UNN), where he received the best Ph.D. award and was enlisted as UNN’s “Face of Research.” He established the first nanomedicine center in Nigeria and was the pioneer head of the intellectual property and technology transfer as well as the technology innovation and support center. Prof. Emeje’s several international fellowships include the prestigious Raman fellowship. He has published more than 150 articles and patents. He is also the head of R&D at NIPRD and holds a visiting professor position at Nnamdi Azikiwe University, Nigeria. He has a postgraduate certificate in Project Management from Walden University, Minnesota, as well as a professional teaching certificate and a World Bank certification in Public Procurement. Prof. Emeje was a national chairman of academic pharmacists in Nigeria and the 2021 winner of the May & Baker Nigeria Plc–sponsored prize for professional service in research and innovation.",institutionString:"National Institute for Pharmaceutical Research and Development",institution:{name:"National Institute for Pharmaceutical Research and Development",country:{name:"Nigeria"}}},{id:"436430",title:"Associate Prof.",name:"Mesut",middleName:null,surname:"Işık",slug:"mesut-isik",fullName:"Mesut Işık",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/436430/images/19686_n.jpg",biography:null,institutionString:null,institution:{name:"Bilecik University",country:{name:"Turkey"}}},{id:"268659",title:"Ms.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/268659/images/8143_n.jpg",biography:"Dr. Zhan received his undergraduate and graduate training in the fields of preventive medicine and epidemiology and statistics at the West China University of Medical Sciences in China during 1989 to 1999. He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a scientist and Principal Investigator at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering the lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via artificial intelligence-based analyses of exosomal Raman signatures. Dr. Paul also works on spatial multiplex immunofluorescence-based tissue mapping to understand the immune repertoire in lung cancer. Dr. Paul has published in more than sixty-five peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award and the 2022 AAISCR-R Vijayalaxmi Award for Innovative Cancer Research. He is a senior member of the Institute of Electrical and Electronics Engineers (IEEE) and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. He is currently working on the protective activity of phenolic compounds in disorders associated with oxidative stress and inflammation.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329248",title:"Dr.",name:"Md. Faheem",middleName:null,surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329248/images/system/329248.jpg",biography:"Dr. Md. Faheem Haider completed his BPharm in 2012 at Integral University, Lucknow, India. In 2014, he completed his MPharm with specialization in Pharmaceutics at Babasaheb Bhimrao Ambedkar University, Lucknow, India. He received his Ph.D. degree from Jamia Hamdard University, New Delhi, India, in 2018. He was selected for the GPAT six times and his best All India Rank was 34. Currently, he is an assistant professor at Integral University. Previously he was an assistant professor at IIMT University, Meerut, India. 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