\\n\\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\\n\\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\\n\\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\\n\\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\\n\\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\\n\\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\\n\\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\\n\\nFeel free to share this news on social media and help us mark this memorable moment!
\\n\\n\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/237"}},components:[{type:"htmlEditorComponent",content:'
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\nIntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\n\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\nFeel free to share this news on social media and help us mark this memorable moment!
\n\n\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:"9744",leadTitle:null,fullTitle:"DNA - Damages and Repair Mechanisms",title:"DNA",subtitle:"Damages and Repair Mechanisms",reviewType:"peer-reviewed",abstract:"DNA is the most important biomolecule ever discovered. Indeed, this molecule bears genetic information from one generation to another. In this regard, DNA bases have a key role in transferring genetic information and data safely. However, there are cellular, genetic, and environmental factors that may damage the different parts of DNA molecules. These damages may result in mutations and cell death. As such, several DNA repair mechanisms have evolved. Over three sections, this book examines many of these mechanisms.",isbn:"978-1-83881-094-8",printIsbn:"978-1-83881-093-1",pdfIsbn:"978-1-83881-095-5",doi:"10.5772/intechopen.87549",price:119,priceEur:129,priceUsd:155,slug:"dna-damages-and-repair-mechanisms",numberOfPages:234,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"470a5da792f88551c8380519604524a5",bookSignature:"Payam Behzadi",publishedDate:"May 19th 2021",coverURL:"https://cdn.intechopen.com/books/images_new/9744.jpg",numberOfDownloads:4053,numberOfWosCitations:2,numberOfCrossrefCitations:9,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:9,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:20,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 27th 2020",dateEndSecondStepPublish:"September 15th 2020",dateEndThirdStepPublish:"November 14th 2020",dateEndFourthStepPublish:"February 2nd 2021",dateEndFifthStepPublish:"April 3rd 2021",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"45803",title:"Ph.D.",name:"Payam",middleName:null,surname:"Behzadi",slug:"payam-behzadi",fullName:"Payam Behzadi",profilePictureURL:"https://mts.intechopen.com/storage/users/45803/images/system/45803.jpg",biography:"Dr. Payam Behzadi was born in Tehran, Iran, in 1973. He began his collaboration with the Department of Microbiology, College of Basic Sciences, Shahr-e-Qods Branch, Islamic Azad University as a faculty member in 2004. He has a BSc and MSc in Microbiology and a Ph.D. in Molecular Biology and now continues his scientific activities in the position of assistant professor at Islamic Azad University. He has authored and edited more than twenty chapters and academic books and more than seventy original and review articles. His scientific research interests include urinary tract infections, antibiotics, bioinformatics, genetics, gene profiling, molecular biology, and cellular and molecular immunology. Dr. Behzadi trains as an ice skater in his free time.",institutionString:"Islamic Azad University, Tehran",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"6",totalChapterViews:"0",totalEditedBooks:"6",institution:{name:"Islamic Azad University, Tehran",institutionURL:null,country:{name:"Iran"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"396",title:"Molecular Genetics",slug:"genomics-molecular-genetics"}],chapters:[{id:"74145",title:"Where Quantum Biochemistry Meets Structural Bioinformatics: Excited Conformationally-Tautomeric States of the Classical A·T DNA Base Pair",doi:"10.5772/intechopen.94565",slug:"where-quantum-biochemistry-meets-structural-bioinformatics-excited-conformationally-tautomeric-state",totalDownloads:284,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"This Chapter summarizes recent quantum-chemical (QM) investigations of the novel conformational and tautomeric states on the potential energy hypersurface of the classical A·T/A·U nucleobase pairs. For the first time, it was observed 28 local minima for each base pair excluding enantiomers - planar, non-planar base pairs and structures with wobble geometry. Considered excited conformationally-tautomeric states of the classical A·T DNA base pair have been revealed in the Nucleic Acid Database by structural bioinformatics. These data shed light on the biological significance of the unusual A·T/A·U nucleobase pairs for the functioning of the nucleic acids at the quantum level.",signatures:"Ol’ha O. Brovarets’, Kostiantyn S. Tsiupa and Dmytro M. Hovorun",downloadPdfUrl:"/chapter/pdf-download/74145",previewPdfUrl:"/chapter/pdf-preview/74145",authors:[{id:"212824",title:"Prof.",name:"Dmytro M.",surname:"Hovorun",slug:"dmytro-m.-hovorun",fullName:"Dmytro M. Hovorun"},{id:"329397",title:"Prof.",name:"Ol’ha O.",surname:"Brovarets’",slug:"ol'ha-o.-brovarets'",fullName:"Ol’ha O. Brovarets’"}],corrections:null},{id:"73555",title:"Origin of DNA Repair in the RNA World",doi:"10.5772/intechopen.93822",slug:"origin-of-dna-repair-in-the-rna-world",totalDownloads:425,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The early history of life on Earth likely included a stage in which life existed as self-replicating protocells with single-stranded RNA (ssRNA) genomes. In this RNA world, genome damage from a variety of sources (spontaneous hydrolysis, UV, etc.) would have been a problem for survival. Selection pressure for dealing with genome damage would have led to adaptive strategies for mitigating the damage. In today’s world, RNA viruses with ssRNA genomes are common, and these viruses similarly need to cope with genome damage. Thus ssRNA viruses can serve as models for understanding the early evolution of genome repair. As the ssRNA protocells in the early RNA world evolved, the RNA genome likely gave rise, through a series of evolutionary stages, to the double-stranded DNA (dsDNA) genome. In ssRNA to dsDNA evolution, genome repair processes also likely evolved to accommodate this transition. Some of the basic features of ssRNA genome repair appear to have been retained in descendants with dsDNA genomes. In particular, a type of strand-switching recombination occurs when ssRNA replication is blocked by a damage in the template strand. Elements of this process appear to have a central role in recombinational repair processes during meiosis and mitosis of descendant dsDNA organisms.",signatures:"Harris Bernstein and Carol Bernstein",downloadPdfUrl:"/chapter/pdf-download/73555",previewPdfUrl:"/chapter/pdf-preview/73555",authors:[{id:"61946",title:"Dr.",name:"Carol",surname:"Bernstein",slug:"carol-bernstein",fullName:"Carol Bernstein"},{id:"172285",title:"Dr.",name:"Harris",surname:"Bernstein",slug:"harris-bernstein",fullName:"Harris Bernstein"}],corrections:null},{id:"74873",title:"Super-Resolution Radiation Biology: From Bio-Dosimetry towards Nano-Studies of DNA Repair Mechanisms",doi:"10.5772/intechopen.95597",slug:"super-resolution-radiation-biology-from-bio-dosimetry-towards-nano-studies-of-dna-repair-mechanisms",totalDownloads:394,totalCrossrefCites:3,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Past efforts in radiobiology, radio-biophysics, epidemiology and clinical research strongly contributed to the current understanding of ionizing radiation effects on biological materials like cells and tissues. It is well accepted that the most dangerous, radiation induced damages of DNA in the cell nucleus are double strand breaks, as their false rearrangements cause dysfunction and tumor cell proliferation. Therefore, cells have developed highly efficient and adapted ways to repair lesions of the DNA double strand. To better understand the mechanisms behind DNA strand repair, a variety of fluorescence microscopy based approaches are routinely used to study radiation responses at the organ, tissue and cellular level. Meanwhile, novel super-resolution fluorescence microscopy techniques have rapidly evolved and become powerful tools to study biological structures and bio-molecular (re-)arrangements at the nano-scale. In fact, recent investigations have increasingly demonstrated how super-resolution microscopy can be applied to the analysis of radiation damage induced chromatin arrangements and DNA repair protein recruitment in order to elucidate how spatial organization of damage sites and repair proteins contribute to the control of repair processes. In this chapter, we would like to start with some fundamental aspects of ionizing radiation, their impact on biological materials, and some standard radiobiology assays. We conclude by introducing the concept behind super-resolution radiobiology using single molecule localization microscopy (SMLM) and present promising results from recent studies that show an organized architecture of damage sites and their environment. Persistent homologies of repair clusters indicate a correlation between repair cluster topology and repair pathway at a given damage locus. This overview over recent investigations may motivate radiobiologists to consider chromatin architecture and spatial repair protein organization for the understanding of DNA repair processes.",signatures:"Jin-Ho Lee and Michael Hausmann",downloadPdfUrl:"/chapter/pdf-download/74873",previewPdfUrl:"/chapter/pdf-preview/74873",authors:[{id:"117296",title:"Prof.",name:"Michael",surname:"Hausmann",slug:"michael-hausmann",fullName:"Michael Hausmann"},{id:"343438",title:"MSc.",name:"Jin-Ho",surname:"Lee",slug:"jin-ho-lee",fullName:"Jin-Ho Lee"}],corrections:null},{id:"74778",title:"DNA Damage and Repair Mechanisms Triggered by Exposure to Bioflavonoids and Natural Compounds",doi:"10.5772/intechopen.95453",slug:"dna-damage-and-repair-mechanisms-triggered-by-exposure-to-bioflavonoids-and-natural-compounds",totalDownloads:462,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:1,abstract:"Eukaryotic cells use homologous recombination (HR), classical end-joining (C-NHEJ), and alternative end-joining (Alt-EJ) to repair DNA double-strand breaks (DSBs). Repair pathway choice is controlled by the activation and activity of pathways specific proteins in eukaryotes. Activity may be regulated by cell cycle stage, tissue type, and differentiation status. Bioflavonoids and other environmental agents such as pesticides have been shown to biochemically act as inhibitors of topoisomerase II (Top2). In cells, bioflavonoids directly lead to DNA double-strand breaks through both Top2-dependent and independent mechanisms, as well as induce DNA damage response (DDR) signaling, and promote alternative end-joining and chromosome alterations. This chapter will present differences in expression and activity of proteins in major DNA repair pathways, findings of Top2 inhibition by bioflavonoids and cellular response, discuss how these compounds trigger alternative end-joining, and conclude with implications for genome instability and human disease.",signatures:"Donna Goodenow, Kiran Lalwani and Christine Richardson",downloadPdfUrl:"/chapter/pdf-download/74778",previewPdfUrl:"/chapter/pdf-preview/74778",authors:[{id:"322325",title:"Prof.",name:"Christine",surname:"Richardson",slug:"christine-richardson",fullName:"Christine Richardson"},{id:"322328",title:"Dr.",name:"Donna",surname:"Goodenow",slug:"donna-goodenow",fullName:"Donna Goodenow"},{id:"324559",title:"Ms.",name:"Kiran",surname:"Lalwani",slug:"kiran-lalwani",fullName:"Kiran Lalwani"}],corrections:null},{id:"76472",title:"Recent Perspectives in Radiation-Mediated DNA Damage and Repair: Role of NHEJ and Alternative Pathways",doi:"10.5772/intechopen.96374",slug:"recent-perspectives-in-radiation-mediated-dna-damage-and-repair-role-of-nhej-and-alternative-pathway",totalDownloads:364,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Radiation is one of the causative agents for the induction of DNA damage in biological systems. There is various possibility of radiation exposure that might be natural, man-made, intentional, or non-intentional. Published literature indicates that radiation mediated cell death is primarily due to DNA damage that could be a single-strand break, double-strand breaks, base modification, DNA protein cross-links. The double-strand breaks are lethal damage due to the breakage of both strands of DNA. Mammalian cells are equipped with strong DNA repair pathways that cover all types of DNA damage. One of the predominant pathways that operate DNA repair is a non-homologous end-joining pathway (NHEJ) that has various integrated molecules that sense, detect, mediate, and repair the double-strand breaks. Even after a well-coordinated mechanism, there is a strong possibility of mutation due to the flexible nature in joining the DNA strands. There are alternatives to NHEJ pathways that can repair DNA damage. These pathways are alternative NHEJ pathways and single-strand annealing pathways that also displayed a role in DNA repair. These pathways are not studied extensively, and many reports are showing the relevance of these pathways in human diseases. The chapter will very briefly cover the radiation, DNA repair, and Alternative repair pathways in the mammalian system. The chapter will help the readers to understand the basic and applied knowledge of radiation mediated DNA damage and its repair in the context of extensively studied NHEJ pathways and unexplored alternative NHEJ pathways.",signatures:"Ajay Kumar Sharma, Priyanka Shaw, Aman Kalonia, M.H. Yashavarddhan, Pankaj Chaudhary, Arpana Vibhuti and Sandeep Kumar Shukla",downloadPdfUrl:"/chapter/pdf-download/76472",previewPdfUrl:"/chapter/pdf-preview/76472",authors:[{id:"262210",title:"Ph.D.",name:"Sandeep",surname:"Shukla",slug:"sandeep-shukla",fullName:"Sandeep Shukla"},{id:"340535",title:"Dr.",name:"Ajay",surname:"Sharma",slug:"ajay-sharma",fullName:"Ajay Sharma"},{id:"340537",title:"MSc.",name:"Priyanka",surname:"Shaw",slug:"priyanka-shaw",fullName:"Priyanka Shaw"},{id:"340539",title:"MSc.",name:"Aman",surname:"Kalonia",slug:"aman-kalonia",fullName:"Aman Kalonia"},{id:"340541",title:"Dr.",name:"M. H.",surname:"Yashavarddhan",slug:"m.-h.-yashavarddhan",fullName:"M. H. Yashavarddhan"},{id:"340543",title:"Dr.",name:"Pankaj",surname:"Chaudhary",slug:"pankaj-chaudhary",fullName:"Pankaj Chaudhary"},{id:"340544",title:"Prof.",name:"Arpana",surname:"Vibhuti",slug:"arpana-vibhuti",fullName:"Arpana Vibhuti"}],corrections:null},{id:"76434",title:"Interstrand Crosslink Repair: New Horizons of DNA Damage Repair",doi:"10.5772/intechopen.97551",slug:"interstrand-crosslink-repair-new-horizons-of-dna-damage-repair",totalDownloads:338,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Since the dawn of civilization, living organisms are unceasingly exposed to myriads of DNA damaging agents that can temper the ailments and negatively influence the well-being. DNA interstrand crosslinks (ICLs) are spawned by various endogenous and chemotherapeutic agents, thus posing a somber menace to genome solidity and cell endurance. However, the robust techniques of damage repair including Fanconi anemia pathway, translesion synthesis, nucleotide excision and homologous recombination repair faithfully protect the DNA by removing or tolerating damage to ensure the overall survival. Aberrations in such repair mechanisms adverse the pathophysiological states of several hereditary disorders i.e. Fanconi Anemia, xeroderma pigmentosum, cerebro-oculo-facio-skeletal syndrome and cockayne syndrome etc. Although, the recognition of ICL lesions during interphase have opened the new horizons of research in the field of genetics but still the detailed analysis of conditions in which repair should occur is largely elusive.",signatures:"Amna Aqeel, Javaria Zafar, Naureen Ehsan, Qurat-Ul-Ain, Mahnoor Tariq and Abdul Hannan",downloadPdfUrl:"/chapter/pdf-download/76434",previewPdfUrl:"/chapter/pdf-preview/76434",authors:[{id:"339017",title:"M.Sc.",name:"Amna",surname:"Aqeel",slug:"amna-aqeel",fullName:"Amna Aqeel"},{id:"346638",title:"MSc.",name:"Javaria",surname:"Zafar",slug:"javaria-zafar",fullName:"Javaria Zafar"},{id:"346641",title:"Ms.",name:"Qurat Ul Ain",surname:"Aqeel",slug:"qurat-ul-ain-aqeel",fullName:"Qurat Ul Ain Aqeel"},{id:"346642",title:"Ms.",name:"Noreen",surname:"Ehsan",slug:"noreen-ehsan",fullName:"Noreen Ehsan"},{id:"346644",title:"BSc.",name:"Abdul",surname:"Hannan",slug:"abdul-hannan",fullName:"Abdul Hannan"},{id:"346645",title:"Ms.",name:"Mahnoor",surname:"Tariq",slug:"mahnoor-tariq",fullName:"Mahnoor Tariq"}],corrections:null},{id:"74418",title:"DNA Repair Defects in Sarcomas",doi:"10.5772/intechopen.94881",slug:"dna-repair-defects-in-sarcomas",totalDownloads:338,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"DNA repair pathway is considered to be one of the most important mechanisms that protect cells from intrinsic and extrinsic stresses. It has been established that DNA repair activity has a crucial role in the way that cancer cells respond to treatment. Sarcomas are a group of tumors with mesenchymal origin in which their association with DNA repair aberrations has been reported in numerous studies. Special attention has been focused on exploiting these alterations to improve the patient’s overall survival and overcome drug resistance in cancer. While there is a large degree of heterogeneity among different types of sarcomas, DNA repair alteration is found to be a common defect in the majority of patients. In this chapter, we will introduce and review some of the most important dysregulated components involved in the DNA repair system, and discuss their association with tumorigenesis, cancer aggressiveness, drug resistance, and overall prognosis in the patients with sarcomas.",signatures:"Niknam Riyahi, M. Reza Saadatzadeh, Khadijeh Bijangi-Vishehsaraei, Farinaz Barghi, Pankita H. Pandya and Karen E. Pollok",downloadPdfUrl:"/chapter/pdf-download/74418",previewPdfUrl:"/chapter/pdf-preview/74418",authors:[{id:"194099",title:"Dr.",name:"Karen",surname:"Pollok",slug:"karen-pollok",fullName:"Karen Pollok"},{id:"326911",title:"Dr.",name:"Niknam",surname:"Riyahi",slug:"niknam-riyahi",fullName:"Niknam Riyahi"},{id:"334990",title:"Dr.",name:"M. Reza",surname:"Saadatzadeh",slug:"m.-reza-saadatzadeh",fullName:"M. Reza Saadatzadeh"},{id:"334991",title:"Dr.",name:"Khadijeh",surname:"Bijangi-Vishehsaraei",slug:"khadijeh-bijangi-vishehsaraei",fullName:"Khadijeh Bijangi-Vishehsaraei"},{id:"334993",title:"MSc.",name:"Farinaz",surname:"Barghi",slug:"farinaz-barghi",fullName:"Farinaz Barghi"},{id:"334994",title:"Dr.",name:"Pankita",surname:"Pandya",slug:"pankita-pandya",fullName:"Pankita Pandya"}],corrections:null},{id:"73467",title:"Epigenetics and DNA Repair in Cancer",doi:"10.5772/intechopen.94030",slug:"epigenetics-and-dna-repair-in-cancer",totalDownloads:429,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Cells can use chemical modifications in chromatin to regulate accessibility to DNA to the repair complexes and to prevent transcription in case of damage. We analyzed the relationship between repair systems and epigenetic mechanisms in DNA and RNA. We searched the PubMed database for genes involved in DNA damage response (DDR) and methylation in mRNA and DNA repair, in cancer. Epigenetic modifications, particularly histone modifications and nucleosome remodeling, trigger a signaling cascade of kinases in DNA damage response (DDR) toward efficient repair. SWI/SNF remodelers promote the recruitment of repair factors in DNA, such as DNA double-strand breaks (DSBs) that activate kinases in DDR. RNA methylation via m6A has recently attracted attention as a possible alternative pathway for repairing DNA damage. m6A is a dynamic methylation mark on mRNA that accumulates after UV irradiation and regulates transcription to facilitate DNA repair. Currently, studies seek to understand how signaling pathways activate proteins in the early response to damage. The repair maintains DNA integrity, which is a challenge in cancer because this process also represents a potential barrier to anticancer agents. The impact that epigenetic regulation can have on DNA repair is beginning to be understood.",signatures:"María José López-Ibarra and Marta Elena Hernández-Caballero",downloadPdfUrl:"/chapter/pdf-download/73467",previewPdfUrl:"/chapter/pdf-preview/73467",authors:[{id:"100782",title:"Dr.",name:"Elena",surname:"Hernández-Caballero",slug:"elena-hernandez-caballero",fullName:"Elena Hernández-Caballero"},{id:"329688",title:"Dr.",name:"Maria Jose",surname:"Lopez-Ibarra",slug:"maria-jose-lopez-ibarra",fullName:"Maria Jose Lopez-Ibarra"}],corrections:null},{id:"74923",title:"Genomic Instability and DNA Repair in Cancer",doi:"10.5772/intechopen.95736",slug:"genomic-instability-and-dna-repair-in-cancer",totalDownloads:413,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:1,abstract:"Mutations in genome are essential for evolution but if the frequency of mutation increases it can evince to be detrimental, for a steady maintenance there exist a detailed complex system of surveillance and repair of DNA defects. Therefore, fault in DNA repair processes raises the probability of genomic instability and cancer in organisms. Genome instability encompasses various aspects of mutations from indels to various somatic variants. The chapter tries to present an overview of how cancer puts up several ways to ensure suppression of the fidelity in our DNA repair system. Cancer cells assure failure of efficient DNA repair mechanisms by innumerous ways, by mutation and epigenetic modifications in repair genes themselves or genes controlling their expression and functions, other by some catastrophic events like kataegis, chromothripsis and chromoplexy. These are clustered mutations taking place at a particular genomic locus which deluge the repair process. Cancer generation and evolution is dependent largely on genome instability, so it applies many strategies to overcome one of its basic obstacles that is DNA repair, targeting these DNA repair genes has also demonstrated to be helpful in cancer therapy; but an intricate understanding of recalcitrant process and mechanisms of drug resistant in cancer will further enhance the potential in them.",signatures:"Bhaswatee Das, Bipasha Choudhury, Aditya Kumar and Vishwa Jyoti Baruah",downloadPdfUrl:"/chapter/pdf-download/74923",previewPdfUrl:"/chapter/pdf-preview/74923",authors:[{id:"247053",title:"Dr.",name:"Aditya",surname:"Kumar",slug:"aditya-kumar",fullName:"Aditya Kumar"},{id:"330958",title:null,name:"Vishwa Jyoti",surname:"Baruah",slug:"vishwa-jyoti-baruah",fullName:"Vishwa Jyoti Baruah"},{id:"343519",title:"Ms.",name:"Bhaswatee",surname:"Das",slug:"bhaswatee-das",fullName:"Bhaswatee Das"},{id:"343520",title:"Ms.",name:"Bipasha",surname:"Choudhury",slug:"bipasha-choudhury",fullName:"Bipasha Choudhury"}],corrections:null},{id:"73335",title:"The Striatal DNA Damage and Neurodegenerations",doi:"10.5772/intechopen.93706",slug:"the-striatal-dna-damage-and-neurodegenerations",totalDownloads:606,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Reactive oxygen species (ROS) are produced during normal metabolic reactions in living cells. ROS causes oxidative damage to many types of biomolecules. An age-related increase in oxidative damage to DNA and RNA has been described in the human neurons, which play a vital role in the progression of age-associated neurodegeneration. As dopamine metabolism is believed to be the primary source of ROS, oxidative insults correlate with dopamine levels in the striatum during the progression of neurodegenerative diseases. Parallel changes in dopamine concentrations and vesicular monoamine transporter 2 (VMAT2) binding densities in the striatum were observed. Besides Fenton oxidation taking place, the packing of cytosolic dopamine into synaptic vesicles by VMAT2 inhibits its autoxidation and subsequent decay of dopaminergic neurons. The female bias in the DNA damage in the late-stage Parkinson disease (PD) patients suggests that the sex-determining region of the Y chromosome (SRY) genes are critically involved. ROS are involved in regulating the rate of the aging procession in healthy cohorts and an increased life span of patients with neurodegenerative diseases via stimulation of protective stress responses. Moreover, the DNA repair pathway’s mechanism, as genetic modifiers determine the age at onset through a ROS-inducing mutation.",signatures:"Huifangjie Li and Jinbin Xu",downloadPdfUrl:"/chapter/pdf-download/73335",previewPdfUrl:"/chapter/pdf-preview/73335",authors:[{id:"322747",title:"Prof.",name:"Jinbin",surname:"Xu",slug:"jinbin-xu",fullName:"Jinbin Xu"},{id:"322748",title:"Dr.",name:"Huifangjie",surname:"Li",slug:"huifangjie-li",fullName:"Huifangjie Li"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"7452",title:"Microbiology of Urinary Tract Infections",subtitle:"Microbial Agents and Predisposing Factors",isOpenForSubmission:!1,hash:"e99363f3cb1fe89c406f4934a23033d0",slug:"microbiology-of-urinary-tract-infections-microbial-agents-and-predisposing-factors",bookSignature:"Payam 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\r\n\tThe goal of this book is to give the reader an overview of a field related to various applications in chemistry, chemical engineering, and nanotechnology. This book aims to provide information about the design of ion exchangers, their application in environmental technologies, and in biotechnology and pharmaceutical applications. This book will be written by authors in the field of experimental methods and critical reviews from multi-disciplines such as chemistry, membranes, and materials science. Among others, some of the topics covered will be Structure of ion exchangers, Synthesis of ion exchangers, Synthesis of inorganic ion exchangers, Properties of ion exchangers, Ion exchange voltammetry, Ion exchange as a separations method, Ion exchange in analytical chemistry, Ion exchange and extraction, Ion exchange membranes, Preparation of organic-inorganic hybrid ion exchangers, Application in environmental technologies, Application in biotechnology and pharmaceutical applications.
\r\n\r\n\tIn this book, the authors will focus on recent studies, applications, and new technological developments on the fundamental properties of ion exchangers.
",isbn:"978-1-83768-391-8",printIsbn:"978-1-83768-390-1",pdfIsbn:"978-1-83768-392-5",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"8dd8a87a8e42422ab2f346d7d33f2f18",bookSignature:"Dr. Selcan Karakuş",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/12301.jpg",keywords:"Selectivity, Diffusion, Isotherm, Electrodialyzer, Computer Simulation, Activity Coefficients, Thermodynamic, Kinetic Model, Semiempirical Models, Ion Exchange Resins, Ion Exchange Composites, Biosorbents",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 10th 2022",dateEndSecondStepPublish:"July 8th 2022",dateEndThirdStepPublish:"September 6th 2022",dateEndFourthStepPublish:"November 25th 2022",dateEndFifthStepPublish:"January 24th 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"a month",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Multidisciplinary Nanoscience Technology Research Group Leader from Istanbul University (Cerrahpasa) and holder of three registered patents on advanced metal/ metal oxide-based nanostructures. Assoc. Prof. Selcan Karakuş has research experience in nanoparticles, nanocomposites, nanoemulsions, metal oxide nanostructures, and sensors.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"206110",title:"Dr.",name:"Selcan",middleName:null,surname:"Karakuş",slug:"selcan-karakus",fullName:"Selcan Karakuş",profilePictureURL:"https://mts.intechopen.com/storage/users/206110/images/system/206110.jpeg",biography:"Assoc. Prof. Selcan Karakuş is currently working at the Department of Chemistry, Istanbul University - Cerrahpasa, Turkey. She obtained her Master of Science degree in Physical Chemistry from Istanbul University (IU) in 2006. She obtained her Doctor of Philosophy degree in Physical Chemistry from IU in 2011. She has worked as a visiting researcher at the University of Massachusetts, Department of Polymer Science and Engineering. She has research experience in nanoparticles, nanocomposites, nanoemulsions, metal oxide nanostructures, and sensors. She has worked on different projects funded by Istanbul University - Cerrahpasa and has published several research articles and book chapters in her area of interest.",institutionString:"Istanbul University Cerrahpaşa",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"4",institution:{name:"Istanbul University Cerrahpaşa",institutionURL:null,country:{name:"Turkey"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"8",title:"Chemistry",slug:"chemistry"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"429341",firstName:"Paula",lastName:"Gavran",middleName:null,title:"Ms.",imageUrl:"//cdnintech.com/web/frontend/www/assets/author.svg",email:"paula@intechopen.com",biography:null}},relatedBooks:[{type:"book",id:"6519",title:"Science and Technology Behind Nanoemulsions",subtitle:null,isOpenForSubmission:!1,hash:"f4dd10764e9841064827609a62952748",slug:"science-and-technology-behind-nanoemulsions",bookSignature:"Selcan Karakuş",coverURL:"https://cdn.intechopen.com/books/images_new/6519.jpg",editedByType:"Edited by",editors:[{id:"206110",title:"Dr.",name:"Selcan",surname:"Karakuş",slug:"selcan-karakus",fullName:"Selcan Karakuş"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9199",title:"Sonochemical Reactions",subtitle:null,isOpenForSubmission:!1,hash:"72f3010437d022fd2a932421ff4a9200",slug:"sonochemical-reactions",bookSignature:"Selcan Karakuş",coverURL:"https://cdn.intechopen.com/books/images_new/9199.jpg",editedByType:"Edited by",editors:[{id:"206110",title:"Dr.",name:"Selcan",surname:"Karakuş",slug:"selcan-karakus",fullName:"Selcan Karakuş"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6694",title:"New Trends in Ion Exchange Studies",subtitle:null,isOpenForSubmission:!1,hash:"3de8c8b090fd8faa7c11ec5b387c486a",slug:"new-trends-in-ion-exchange-studies",bookSignature:"Selcan Karakuş",coverURL:"https://cdn.intechopen.com/books/images_new/6694.jpg",editedByType:"Edited by",editors:[{id:"206110",title:"Dr.",name:"Selcan",surname:"Karakuş",slug:"selcan-karakus",fullName:"Selcan Karakuş"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7604",title:"Colloid Science in Pharmaceutical Nanotechnology",subtitle:null,isOpenForSubmission:!1,hash:"f3940914be015381c3928eae31c2457e",slug:"colloid-science-in-pharmaceutical-nanotechnology",bookSignature:"Selcan Karakuş",coverURL:"https://cdn.intechopen.com/books/images_new/7604.jpg",editedByType:"Edited by",editors:[{id:"206110",title:"Dr.",name:"Selcan",surname:"Karakuş",slug:"selcan-karakus",fullName:"Selcan Karakuş"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2270",title:"Fourier Transform",subtitle:"Materials Analysis",isOpenForSubmission:!1,hash:"5e094b066da527193e878e160b4772af",slug:"fourier-transform-materials-analysis",bookSignature:"Salih Mohammed Salih",coverURL:"https://cdn.intechopen.com/books/images_new/2270.jpg",editedByType:"Edited by",editors:[{id:"111691",title:"Dr.Ing.",name:"Salih",surname:"Salih",slug:"salih-salih",fullName:"Salih Salih"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"76015",title:"Cardiomyopathy in Duchenne Muscular Distrophy: Clinical Insights and Therapeutic Implications",doi:"10.5772/intechopen.97022",slug:"cardiomyopathy-in-duchenne-muscular-distrophy-clinical-insights-and-therapeutic-implications",body:'Duchenne muscular dystrophy (DMD) is an X-linked degenerative neuromuscular disease that affects the skeletal muscles and the heart and over time leads to loss of walking, severe respiratory complications and progressive cardiac dilation and dysfunction.
It is caused by a mutation of the DMD gene, the largest gene in the human genome, mapped on the X-chromosome that codes for dystrophin, an essential protein for the stability of the myocyte membranes. The type of mutation and the degree of reduced expression of this structural protein influences the degree of muscle and cardiac impairment and especially the speed of myopathy progression. The milder forms are generally identified with the term Becker’s muscular dystrophy (BMD) while the most severe and rapidly evolving forms, due to a severe reduction or total absence of dystrophin, are properly defined as DMD. Due to the X-linked recessive inheritance, the condition of female carriers must also be considered; they have a second normally functioning allele of dystrophin gene, thus they are generally characterized by a completely normal muscular and cardiac phenotype but may also present a mild/variable expression of the disease [1].
The incidence of DMD is approximately 1 in 5000 live male births, with 2/3 of the cases due to the transmission of the X-chromosome containing the mutated gene from a carrier female to male offspring and the remaining 1/3 of cases consequent to de novo mutations.
Generally the first manifestation of the DMD is muscle weakness that begins around the age of four and worsens quickly, leading to the loss of independent walking by the age of ten and to respiratory dysfunction around the second decade of life. The cardiac involvement begins around 6–10 years of age [2, 3] while cardiovascular symptoms are rare before the age of twenty and often appear when the degree of cardiac dysfunction is severe [4].
In last decades, the life expectancy of patients with DMD has grown considerably as a result of advances in the prevention and management of respiratory complications. As a result, there has been a significant increase in manifestations of advanced cardiomyopathy that is becoming the main cause of morbidity and mortality for these patients. This has led to a growing interest in the prevention and management of DMD-DCM [5, 6, 7].
While some aspects of DMD-DCM assessment and therapy are well defined by current guidelines [8], such as the need of routine cardiac evaluation and the indication to start prophylactic cardio-protective therapy from the age of ten in all patients, many other aspects remain under investigation, especially at end stage phase.
The DMD gene, encoded on the X chromosome, is the longest gene of our genome; it contains long introns with many “hotspots” susceptible to a high rate of mutations which can lead to the deletion (60–65% of all DMD mutations) or duplication (10%) of one or many exons. Shorter mutations such as point mutations are responsible for the remaining 25% of DMD cases. One third of DMD cases are due to de novo mutations while two third are inherited. The mutations resulting in the production of a truncated protein or of a dystrophin lacking in structural domains necessary for interaction with other proteins, are responsible for the most severe forms of the disease [9].
Dystrophin is a long intracellular protein of 3685 aminoacids and a molecular weight of 427 kDa. It is composed by four domains: an
The dystrophin- associated protein complex (DAPC). Dystrophin and DAPC plays an essential structural role in linking the actin of cytoskeleton to the extracellular matrix. The subunits of the DAPC, such as the sarcoglycans, have a vital role in the maintenance of muscle integrity. Dystrophin, a flexible rod-like cytoplasmic protein, directly interacts with the actin polymers of the cytoskeleton and with a complex of transmembrane glico-proteins composed by sarcoglycans, beta- and alpha-dystroglycan that creates a connection with the extracellular matrix by its linking with laminin-2.
Fibrosis, abnormal Ca2+ homeostasis and elevated reactive oxygen species are also predisposing factor to the onset of ventricular arrhythmias in DMD-DCM. Recently, a predisposition to pacing induced ventricular arrhythmias was demonstrated in an animal model of DMD. In this model, the aberrant Ca2+ release through RyR2, which leads to delayed after depolarizations (DADs) and triggered ventricular arrhythmias, was related to the oxidated Ca2+/calmodulin-dependent protein kinase II, Ox-CaMKII. Genetic inhibition of Ox-CaMKII normalized intracellular Ca2+ and prevented ventricular arrhythmias in this model [12]. Another interesting study suggested that arrhythmias could also result from an alteration of the components of the cardiac gap junction; in particular it has been proposed that the dislocation and anomalous S-nitrosylation of connexin 43 (Cx43) lead to the early depolarization of the cytoplasmic membrane and the consequent generation of action potentials. Then, these channels can be therapeutic targets to prevent fatal arrhythmias in patients with DMD [13].
The diagnosis of DMD may occur around 4 yo for difficulty in gait, calf hypertrophy, delayed speech, inability to jump or stand without using the arms for assistance (Gower maneuver), toe walking and difficulty in climbing stairs. Over the time the progressive muscle waste leads to loss of ambulatory capacity and to decline of respiratory and cardiac functions [14].
Literature reports the beginning of ongoing cardiac disease processes as around 6–10 years of age. Echocardiographic abnormalities and clinical DCM can occur at any age but often appear around 14–15 yo and are common over 18 years of age [15]. Symptoms are mild or completely absent up to the most advanced stages of cardiomyopathy, and this is mainly due to the significant reduction in oxygen consumption and in energy expenditure consequent to muscle weakness. It is remarkable that often the severity of cardiomyopathy does not correlate with the degree of skeletal muscle weakness, thus regular cardiac evaluation is very important also in patients with mild motility impairment and it is required before any invasive diagnostic procedure or surgery.
In the last decade, the increase in life expectancy, deriving from the better management of the respiratory involvement and the improved supportive cares, have resulted in a sharp increase in the number of patients with severe cardiomyopathy, and to date, end-stage HF has becoming one of the leading causes of morbidity and mortality in DMD [6].
Data from a multicentre Pediatric Cardiomyopathy Registry (PCMR) show a high prevalence of DCM also in milder forms of dystrophinopathies as in BMD (up to 90% of cases). Interestingly, in these patients, detection of cardiomyopathy often occurs at a more advanced stage and the progression of the LV dysfunction and dilation may be more rapid than in patients with DMD. Despite this, mortality rate for DMD patients with DCM is significantly worse than that of BMD patients, who can undergo heart transplant [16].
From the time of DMD diagnosis, every effort should be focused to detect early the onset and the progression of DCM. Early recognition and periodic re-evaluation are essential to guide therapy and to identify patients at increased risk of progression of cardiomyopathy and major cardiac events. Clinical evaluation remains challenging because most of these patients have often low blood pressure values and cool extremities because of reduced skeletal muscular mass even in the presence of hemodynamic compensation. Therefore, multiparametric evaluation is crucial to correctly recognize the progression of cardiac impairment [8].
Serum biomarkers are often very useful for the diagnosis and monitoring heart disease. In particular, serum levels of cardiac troponin I/T are known to be associated to the extension of myocardial damage, but there are conflicting results about their diagnostic and prognostic implications in the DMD-DCM. Actually, only troponin I showed to be reliable in patients with neuromuscular disorder [17]. Troponin I levels seem to be significantly elevated in patients with initial myocardial fibrosis expressed by mild late gadolinium enhancement (LGE) at the cardiac magnetic resonance (CMR) compared to those without LGE. Interestingly, this positive association between troponin levels and myocardial fibrosis is lost when LGE degree becomes moderate-to-severe, probably because at advanced stage of cardiomyopathy most of myocardium is already substituted by fibro-fatty tissue, therefore the release of myocardio-necrosis enzymes is reduced [18].
Natriuretic peptides are well established markers of HF and congestion in DCM. In DMD, pulmonary hypertension caused by impairment of the respiratory muscles and restrictive physiopathology are considered to be involved in the mechanism of increased values of plasma natriuretic peptide. In addition to the more commonly used brain natriuretic peptide (BNP), a significant elevation in plasma alpha-atrial natriuretic peptide (alphaANP) levels is found as a sign of a poor prognosis and may be a useful index for the management of patients with DMD-DCM [19].
In the management of HF is very important to assess renal function. In DMD serum creatinine values are generally very low as a consequence of their reduced muscle mass and therefore creatinine cannot be considered a good marker of renal function. In these patients, serum values of cystatin C, a protein produced by all cells, not only by muscle cells, are a good parameter for assessing renal function, because they better correlate with glomerular filtration rate (GFR) and cardiac dysfunction. Furthermore, it is reported a significant correlation between Cystatin C and cardiac dysfunction, providing for the first time a novel marker to identify cardio-renal syndrome in patients with DMD [20].
Electrocardiogram and transthoracic echocardiogram are the two fundamental exams advised to establish baseline cardiac involvement and they are recommended annually in all patients since the diagnosis of DMD. After the age of ten, cardiac assessment should have been
For earlier detection of LV impairment, speckle tracking echocardiography is also very useful, as it is a technique able to evaluate subclinical LV dysfunction before development of overt LVEF reduction. Global longitudinal strain (GLS), obtained by 2D speckle tracking echocardiography is abnormal in nearly 50% of DMD patients with a normal LVEF, and a decrease of 0,34% per year of GLS in DMD patients according to age has been recently reported [24]. The lowest values of strain is often observed in the inferolateral and anterolateral mid-basal segments. However, speckle tracking analysis is often limited in DMD because echocardiographic image quality is poor in these patients and declines by 2,5% for each 1 year increase in age because of chest deformities, lung hyperinflation, and limited mobility [25].
CMR can be useful also to evaluate more precisely the severity of myocardial dysfunction and fibrosis in further stages, to assess the efficacy of anti-remodeling therapy, to screen asymptomatic DMD female carriers. However, the high costs, patient’s claustrophobia and the technical difficulties to obtain the exam in patients with home ventilator may limit its use in this group of patients.
In the clinical course of DMD-DCM three stages of DCM can be distinguished: a
Cardiac magnetic resonance (CMR), electrocardiographic (EKG) features and clinical status at different stages of the DMD-DCM progression. In the pre-clinical stage left ventricular (LV) function is still preserved, CMR may identify initial fibrosis, at the EKG some alterations such as QRS fragmentation, rsr’ complexes in V1 and alterations of ventricular repolarization may appear, and blood levels of troponin T (TnT) may be slightly or moderately high while NTproBNP is normal. The clinical stage is characterized by a certain degree of LV dysfunction and dilation, inflammation and fibrotic replacement of the heart muscle are extended, as shown by the wide distribution of late gadolinium enhancement (LGE) areas at CMR imagines, abnormal Q waves appear at the ECG, and the values of TnT and NTpro BNP are usually very high and moderately high respectively. In the end-stage, LV dilation and dysfunction are severe, much of the heart muscle is replaced by fibrous tissue, filling pressure increases, and episodes of acute heart failure and ventricular arrhythmias become frequent, NTproBNP values are very high while TnT values may not be particularly high due to reduced total cardiac muscle mass.
The
At this stage of the DMD-DCM, the aim will be to delay the onset of ventricular contractile dysfunction. Current recommendation advices to start angiotensin converting enzyme inhibitor (ACE- I) as preventive strategy. Perindopril 2–4 mg/die, [28] or an angiotensin receptor blocker (ARB) can be prescribed in all DMD patients from the age of ten. The indication to start therapy earlier, in patients with initial signs of cardiac involvement (such as the presence of mild LGE) but with preserved contractile function is still under debate and investigation [8].
At this early phase of DCM, when LV is mildly dilated, the use of mineralocorticoid receptor antagonist (MRA), such as eplerenone or spironolactone, may slow the rate of decline of LV function. Further studies are needed to determine the effect of combined cardioprotective therapy on event-free survival in these patients [29, 30].
The
The
In end-stage CMD signs and symptoms of systemic or pulmonary congestion may be clinically evident and loop diuretics are indicated. For chronic use furosemide 1 to 6 mg/kg/die is generally effective, but in some cases the addiction of Metolazone, a thiazide-like diuretic, is required. It is important to underline that there is no evidence of the effectiveness of loop diuretics in improving survival, so they are to be considered only for relieving symptoms [38].
In patients with severe LV dysfunction an antithrombotic therapy should be considered in the primary prevention of thromboembolic events, although not routinely recommended [39].
As mentioned above, DMD patients are at risk of arrhythmias such as atrial fibrillation, atrial flutter and ventricular tachycardia and this risk increases as cardiomyopathy progresses. To date, the management of arrhythmias, with drugs and devices, in DMD-DCM is based on general international guidelines, as there are no specific recommendations for DMD. Implantable cardioverter defibrillator (ICD) has gained acceptance in selected patients [40]. The effectiveness of cardiac resynchronization therapy (CRT) in these patients seems to be poor probably due to the presence of the extensive postero-lateral fibrosis and poorly explored.
Patients with DMD are generally not considered suitable for cardiac transplant candidacy due to early walking impairment, predisposition to respiratory complications, and their short life expectancy. Heart transplant (HTx) has been considered in few highly selected cases in which respiratory compromise was not relevant and reported [40]. In BMD, HTx is considered in end stage phase of CMP.
Few cases of patients with end-stage DMD-DCM and preserved or only mild reduced respiratory function, left ventricle assist device (LVAD) has been considered as a destination therapy [41, 42]. To date, the international literature about LVAD in DMD patients is poor and proper selection of patient and ethical aspect should be accurately evaluated case by case. Share decision making process is also crucial and exploratory dialog with patients and caregivers should be routinely carried out during follow up, not only in urgent situation [43].
Recently, a retrospective study on DMD patients evaluated the effects of advanced cardiac therapies (i.e. ICD, LVAD, HTx) on large DMD population. Out of 436 DMD patients, 9 had ICD placed, 4 had LVAD and 1 HTx. The authors concluded that advanced HF therapies may be used effectively in select subjects with DMD but further studies are needed to stratify the risk and select patients [40].
In the process of choosing about advanced cardiac therapies for end-stage DMD-DCM an in-depth personalized assessment is crucial, and involves the collaboration of the patient and his family with a team of experts composed of cardiologists, cardiac surgeons, neuromuscular specialists, anesthetists, pneumologists, bioethics experts and psychologists.
Given their effectiveness in slowing the progression of muscle damage and in prolonging the ability to walk and the life-expectancy, corticosteroids such as prednisone and deflazacort have become the standard basic treatment of patients with DMD from the moment of diagnosis or, in any case, by the age of five [44]. While some preclinical studies have suggested that corticosteroids can accelerate cardiomyopathy, subsequent clinical studies have supported their beneficial role in preserving ventricular function and delaying the progression of heart disease, especially by slowing down the inflammation and the fibrotic process and by increasing myogenic repair and myoblast proliferation [45].
Schram et al. [46] showed that steroid therapy was associated with a significantly lower all-cause mortality rate, due to a substantial reduction in HF–related deaths. In this observational study, patients treated with combination of steroid and ACE-I, experienced a much lower incidence of new-onset cardiomyopathy than those treated without steroid.
In recent years a new MRA, called Vamorolone, has been discovered. This new MRA is able to mimic the anti-inflammatory effects of glucocorticoids and it could represent, in the near future, an alternative to the others. It has been reported it seems to have less side effects and greater antifibrotic effect thanks to the inhibition of the aldosterone pathway [47].
Moreover, several other new therapeutic strategies are under investigation, focused to mitigate inflammation and fibrosis or to restore the dystrophin expression. These last strategy includes:
t
Most of these gene-targeted therapies are still under study and the evaluation of their efficacy is mainly based on the increased expression of dystrophin in skeletal myocytes and on the slowing of the myopathy progression. Whether these therapies are able to increase dystrophin expression equally in skeletal muscle cells and in cardiomyocytes is still unclear since the heart cannot be routinely biopsied. This is a crucial point as isolated improvement in muscle function would lead to increased demand on a weak heart, accelerating the progression of cardiomyopathy. In particular, Ataluren has shown a modest increase in dystrophin expression in mouse heart, while in a small cohort of humans neither measurable improvement nor deterioration in heart function were observed during 24 months of treatment. Instead, there are strong evidences regarding the benefit on heart function from gene therapies that use micro-dystrophin genes. In preclinical studies a robust expression of micro-dystrophin in cardiomyocytes has been proved, but the high dose required may be burdened significant side effects and the presence of micro-dystrophin instead of wild-type dystrophin can still lead to the development of a BMD-like cardiomyopathy. Further studies are needed to better understand the long-term effects of these therapies on the heart [48].
Most women carrying the DMD mutation in one of the two X chromosomes are asymptomatic for life due to the presence of sufficient normal dystrophin produced by the unchanged allele of the gene. Some of these women, called “manifesting carriers”, may have mild or moderate forms of myopathy and cardiomyopathy; this is probably due to a mosaic inactivation of the healthy allele in skeletal and heart muscles, or simply to the reduced total amount of normal dystrophin in the cells. In particular, cardiomyopathy can occur in up to 8% of cases and symptoms can appear from adolescence to late adulthood even without any correlation with musculoskeletal manifestations [49]. Therefore, current guidelines recommend to perform echocardiography every 5 years in all adult dystrophinopathy carriers [14]. The severity of disease can vary widely and can worsen during concomitant events such as pregnancy and childbirth. It is interesting to note that in 45% of DMD carriers, subepicardial LGE in the inferolateral free LV wall is detectable at CMR as well as in the initial forms of cardiomyopathy in DMD male patients and this is associated with myocardial enzyme release and with a greater probability of progression of the cardiomyopathy [50].
Given the primary role of cardiomyopathy in determining the prognosis of DMD patients, every effort should be focused on preventing or slowing the progression of their cardiac dysfunction. Many drugs commonly used for HF have proven to be quite effective, especially if used from the very early stages of the disease, before heart dysfunction becomes evident. So current recommendations underline the importance of routinely cardiac evaluation since the diagnosis of DMD to early recognize heart abnormalities and start ACE-I. In this preclinical stage of DMD-DCM, CMR plays a substantial role due to its sensitivity in identifying initial areas of fibrotic replacement of the heart muscle. Because of the lack of specific DMD-DCM therapies, current drugs used for HF might be used and further studies are required to address their efficacy, especially at end-stage DCM. To date some new target therapies are available and many others are under evaluation, so that in the near future we will be able to count on a much wider range of specific therapeutic possibilities than now. Moreover, in the end-of- life management, ethical issues are still a matter of intense debate in order to identify potential advanced cardiac therapies candidates. Surely, in this challenging course of treatment, sharing decisions with the patient and his caregivers and the support of a multidisciplinary team are crucial cornerstones for obtaining the best possible results.
The authors declare no conflict of interest.
Glioblastoma multiforme (GBM), classified as grade IV glioma, is highly invasive, heterogeneous, and malignant primary brain tumor. It accounts for ~57% of all gliomas and ~ 48% of all primary malignant central nervous system (CNS) tumors [1, 2]. Such tumors are associated with poor quality of life of the patient due to progressive decline in neurologic function, thus making a huge impact on the patients, care givers, and their families. The standard treatment includes multimodal approach involving maximal surgical resection followed by radiotherapy, systemic therapy (chemotherapy, targeted therapy), and supportive care; however, long-term survival is exceptional. Despite the treatment, these tumors regrow and that too with aggressive phenotype, which worsen the symptoms leading to prognosis with average overall survival time < 14.6 months for primary GBM patients and < 6.9 months for recurrent GBM patients [3]. Understanding the molecular mechanism involved in therapeutic resistance and tumor regrowth despite standard treatment is imperative.
In this regard, researchers have identified existence of cancer stem cells (CSCs) in a variety of cancers that play crucial role in tumor initiation, maintenance, resistance to therapy, recurrence, metastasis, and generation of more aggressive phenotype [4]. These properties of CSC are manifested by their potential to self-renew, proliferate, ability to differentiate in multiple phenotypes, plasticity, quiescence, and dormancy. It is suggested that these CSCs originate either from normal stem cells that were already present in tissue or can be generated from dedifferentiation of somatic cells from bulk of tumor. Based on the properties of CSCs, they pose not only a barrier for anticancer therapy but also are responsible for recurrence into more aggressive phenotype. Various researchers have shown that CSC escape anticancer therapy due to their ability to enter dormancy, plasticity, renewal, and regrowth into heterogeneous group of tumor cells. Of interest, recent evidences have suggested that these CSCs are further enriched in response to standard radio-chemotherapy, which may be responsible for tumor regrowth and aggressive phenotype. These enriched CSCs might be result from the existing population of CSCs that evades the therapy or as per recent evidences, can be generated from non-CSCs from the bulk of tumor in response to therapy. Of note, CSCs have been identified in HGG cases also known as glioma stem cells (GSCs) that contribute to tumor heterogeneity and resistance to therapies, thus a major contributor of tumor recurrence. These GSCs are considered as a potential therapeutic target, therefore understanding the molecular pathways that drive GSCs becomes imperative [5]. In this book chapter, we have discussed about the properties of cancer stem cells, cell surface markers, signaling pathways, and mechanism of resistance to therapies and ways by which these pathways can be targeted using different chemotherapeutic agents.
Stem cells are specialized cells present in our body that possess properties such as capacity to self-renew, proliferate, and differentiate into multiple cell types. This quality of self-renewal along with associated signaling pathways is shared between both stem cells and cancer stem cells with added feature of oncogenicity in CSCs. The most common pathways that drive multipotency and self-renewal of stem cells include the Notch, Sonic hedgehog (Shh), and Wnt signaling pathways [4]. Due to activation of oncogenic pathways, CSCs can give rise to tumor mass consisting of heterogeneous cell population. Initially, Bonnet and Dick characterized CSCs in acute myeloid leukemia as leukemia-initiating cell that possessed properties of leukemia stem cell [6]. Later, such cells were also identified in a variety of solid tumors, including prostate [7], colon [8], lung [9], ovarian [10], and brain [11] tumors. It is hypothesized that CSCs are the seed of a tumor that are responsible for tumorigenesis by initiation, maintenance, propagation, resistance to therapy, recurrence as well as progression of the tumor [12].
In brain tumors, presence of CSC has been identified and characterized by various groups and are defined as GSCs or glioma initiating cells [11]. When cultured, these cells grown into neurospheres that constitute of cells that express SC markers including Nestin and CD133. When these cells are injected into nude mice, they lead to tumor formation due to their SC properties [13]. To add further, various groups have utilized properties of stem cells that are present in brain predominantly in subventricular zone (SVZ) to initiate tumor by exposure to chemicals (ethylnitrosourea) or viruses (avian sarcoma virus) in animals that strongly support the importance of stem cells in tumor formation [7, 14, 15]. These cells contribute to tumor heterogeneity and plasticity and have shown resistance to therapies and thus have emerged as a major contributor of tumor recurrence [5, 16, 17]. These CSCs are also influenced by micro environmental conditions such as nutrient deprivation, hypoxia, pH, vasculature, radiation, and chemotherapeutic treatment (explained in detail in coming sections) [16, 17, 18, 19].
Several putative GSC surface markers, such as CD133, CD15, and CD44, and GSC transcription factors, such as SRY-box transcription factor 2 (SOX2), octamer-binding transcription factor 4 (OCT4), and NANOG, have been discovered [20, 21]. However, before its clinical implication, higher sensitivity and specificity of these GSC markers need to be established [21, 22].
In order to maintain stemness properties, GSCs depend upon number of signaling pathways that also support them to sustain under adverse conditions during tumorigenesis [23, 24, 25]. To understand the process of stemness in GSC, the signaling pathways that are also a part of normal neuronal stem cells are discussed. These pathways mainly include Notch, bone morphogenic proteins (BMPs), NF-
Notch signaling pathway is crucial in developmental process and plays a major role during embryonic development. This pathway regulates cellular proliferation, differentiation, apoptosis, and cell lineage decisions. In GSCs, Notch signaling pathways are highly active, which in turn maintain stemness by inhibiting differentiation. Notch signaling is also involved in oncogenic transformation. It has been identified that inhibition of Notch signaling decreases oncogenic potential of GSCs [26, 27].
BMP group of molecules belongs to the transforming growth factor-β (TGF-β) superfamily of proteins. BMPs plays role during embryogenesis, development as well as adult tissue homeostasis. It interacts with different signaling molecules including Wnt/
Wnt/β-catenin signaling is a highly conserved pathway that regulates cellular proliferation, differentiation, migration, genetic stability, apoptosis, and stem cell renewal. This pathway also regulates NSC expansion and promotes astroglial lineage differentiation during neural development [33, 34]. In GSC,
The EGFR pathway is one of the most crucial pathways involved in cellular processes including proliferation, differentiation, migration, and apoptosis in a variety of cells including stem cells. Dysregulation of this pathway has been linked to cancer. Critical role of EGFR has been identified in NSCs as well [40, 41, 42]. In GSC EGFR works through activation of
The Shh signaling pathway is crucial for proper embryonic development as it governs tissue polarity, patterning maintenance, cellular proliferation, intercellular communication, and differentiation [44, 45]. Persistent Shh pathway signaling has been observed in the subventricular zone of adult brain where it plays a critical role in regional specification and maintenance of NSCs [46]. Aberrant regulation of the Shh pathway due to mutation has been identified to cause tumorigenesis in a wide variety of cancer tissues including gliomas and GSCs. This pathway is highly active in GSCs where it regulates stemness genes and thus maintains self-renewal of GSC and promotes tumorigenesis and inhibition of Shh signaling reduces both stemness as well as
Resistance of CSCs toward therapies resulting in their enrichment and regrowth of tumor due to proliferation of these cells has been suggested by various researchers [48, 49, 50]. In HGG, despite the effectiveness of TMZ in removing the bulk tumor cells, regrowth with a more aggressive phenotype is inevitable, and researchers have identified critical role of CSCs in such regrowth. For instance, in HGG, treatment with therapeutic doses of temozolomide (TMZ) leads to expansion of GSCs pool in both patient-derived and established glioma cell lines. Such expansions are reported not only due to enrichment and proliferation of existing CSCs but also due to interconversion between differentiated tumor cells and GSCs [18]. Similarly, bevacizumab (VEGF antibody) although reduces GBM tumor growth, it is followed by tumor regrowth where the role of autocrine signaling through the VEGF-VEGFR2-Neuropilin-1 (NRP1) axis leads to enrichment of active VEGFR2 GSC subset in human GBM cells [51]. It is evident that the therapeutics evoke enrichment of CSCs involving multiple mechanisms. Thus, understanding various ways by which CSCs escape the radio- and chemotherapy, more effective treatment modalities can be developed. Broadly, in CSCs various different mechanism such as epithelial-mesenchymal transition (EMT), multiple drug resistance (MDR) dormancy, tumor environment contribute to resistance toward therapeutics and other adverse conditions faced by them in tumor microenvironment and are discussed as follows.
GSCs possess better DNA repair capacity as compared with bulk tumor cells [52]. These cells express higher levels of DNA repair enzymes such as O6-methylguanine-methyltransferase (MGMT), which are responsible for therapy resistance against DNA alkylating agents such as TMZ [53, 54, 55, 56]. However, there are contradictory studies that also suggest that TMZ resistance in GSCs is independent of MGMT status and alternate pathways might be involved [57, 58]. Further, preferential expression of DNA checkpoint kinases 1 (Chk1) and 2 (Chk2) lead to more efficient repair of DNA damage in CD133-positive glioma cells than CD133-negative glioma cells [54]. Other transcriptional regulators such as BMI, DNA-PK, poly (ADP-ribose) polymerase-1, hnRNP U, and histone H1, which play a role in DNA double-strand break repair, are highly expressed in CD133-positive GBM cells and play pivotal role in GSCs’ functions [59, 60].
EMT involves phenotypic changes in cells from epithelial to mesenchymal type involving high expression of markers such as N-cadherin and vimentin under various physiological as well as pathological conditions including cancer [61]. Interestingly, CSCs also share the EMT-like cell features [62], and it is believed that the link between EMT and CSCs might be responsible for cancer drug resistance acquisition and plasticity resulting in cancer cells transformation into the malignant cells and
As the understanding of CSC biology has improved, it has been identified that CSCs can exist in proliferative or dormant state. Dormant CSCs maintain a low metabolic activity, however, show similarities with the normal proliferative counterpart in terms of stemness and other signaling pathways. For instance, dormant stem cells are low in metabolic activity that preferentially utilize the glycolytic pathway and produce low levels of levels of reactive oxygen species (ROS) [68]. However, these dormant/quiescent cells demonstrate high plasticity and can be reactivated to reenter proliferative stage and lead to tumor formation. Such dormant cells are also chemoresistant due to their dormant nature; interestingly, proliferative CSC can also enter dormancy in response to chemotherapeutics agents. In GBM, existence of a relatively quiescent subset of GSCs has been observed, which is responsible for maintaining the long-term tumor growth and responsible for recurrence by entering into highly proliferative cells upon receiving proper signals [69].
Various anti-apoptotic protein such as B-cell lymphoma-2 (BCL-2), BCL2 like 1 (BCL2L1), myeloid cell leukemia-1, MCL1 and BCL-xL are highly expressed in GSCs than differentiated bulk tumor cells. These proteins not only play role in GSCs maintenance but also provide survival advantage to these cells against various chemotherapeutic agents [70]. Other mediator of GSCs resistance includes BMI1, a GSC-enriched protein that inhibits p53-mediated apoptosis against TMZ [71]. Inhibition of such anti-apoptotic pathways can increase sensitivity of GSCs against different therapeutic agents.
Stem cells express higher levels of several ATP-binding cassette (ABC) transporters resulting in efflux ability for various antineoplastic drugs [72]. In GSCs, increased
GSCs show metabolic adaptations to survive adverse conditions of tumor microenvironment that includes low pH, hypoxia, and low nutrient supply; at the same time they proliferate at a high rate to maintain their stemness [16, 17]. Majority of GSCs rely on glucose uptake via high-affinity glucose transporter 3 (GLUT3) to provide carbon source for nucleotide biosynthesis for rapid proliferating cells along with high energy demands [78, 79, 80]. These cells also highly express glutamine synthetase as compared with differentiated glioma cells for higher glutamine uptake, which acts as preferential source for
Autophagy is a catabolic pathway which is a cellular stress response under physiological as well as pathological conditions. This pathways acts by removal of damaged macromolecules such as proteins, nucleic acid, and lipids and recycles them for cellular processes and thus promotes cell survival; however, defect or dysregulation of such pathway may lead to cell death [84]. Role of autophagy is well established in a variety of cancers including GBM where it can play a role in cell survival or cell death [84, 85]. Autophagy also contributes to the maintenance of stemness characteristics of GSCs as well as provides chemoresistance to CSC against therapeutic agents [19, 86]. Inhibition of autophagy sensitizes GSCs towards a variety of therapeutic agents [19, 87, 88, 89]. Interestingly, other studies demonstrated that induction of autophagy by mammalian target of rapamycin (mTOR) inhibitors as well as curcumin-induced autophagy shows anti proliferative effect, induces differentiation and also improves sensitivity of GSC towards DNA damaging agents [90, 91, 92]. Together, these results suggest that GSCs require a balanced level of autophagy, too much or too little can significantly affect their stemness potential and resistance toward therapeutics. Further, role of autophagy has also been shown to support motility/migration capacity of GSCs [93]. However, role of autophagy in suppression of the self-renewal ability and tumorigenicity of GSCs has also been demonstrated where autophagy mediates Notch1 degradation [94]. Thus, role of autophagy in GSCs is crucial for maintenance of stemness as well as chemotherapeutic agents; targeting such pathway appears as a p These cells also highly express glutamine synthetase otential strategy to make the existing treatment more effective.
Besides the signaling pathways and genetic signature of GSCs, extracellular environment also called as microenvironment in which these cells resides also plays crucial role in its functions and determines response towards therapeutic agents [95]. It has been identified that GSCs reside in inner tumor mass where rapid growth and high energy requirement of these cells along with neovasculature result in hypoxic conditions as well as low pH [29, 96]. These adverse conditions further promote expression of GSC markers and associated phenotype [97]. Various hypoxia and acidic pH-induced genes such as hypoxia-inducible factor (HIF) 1 and 2alpha and vascular endothelial growth factor (VEGF) are highly expressed in GSCs that contribute to GSC functions [98, 99]. It has been shown that in GSCs Notch signaling and MGMT expression are also regulated by HIF-1α, resulting in GSC stemness and also resistance toward TMZ [100, 101]. Further, hypoxic GSCs release extracellular vesicles that deliver HIF-1α induced miR-30b-3p that further activates STAT3 pathway and promotes TMZ resistance [102]. Further, it has been identified that TMZ increases the GSC pool in non-GSC subpopulations, indicating that non-GSC shows plasticity and can be converted to GSCs that might be responsible for resistance as well as regrowth of the tumor [18, 19]. Together, these findings suggest that
Various signaling pathways such as Notch and SHH are active in GSCs compared with bulk tumor cells [103]. Further, in response to TMZ treatment of GSCs from primary GBM cells resulted in upregulation of
Despite extensive research in oncology, the target is being missed leading to recurrence in a variety of high-grade tumors including malignant gliomas. With advancement in understanding of GSCs and its capacity of initiation, progression, resistance as well as recurrence of tumor, they appear as most promising target to treat cancers such as HGG. The drugs that can target GSC are being developed using multiple strategist including molecular targeting, autophagy inhibition, drug repositioning, and indirect targeting of GSC niches [17, 21, 106].
GSCs are regulated by various pathways involving differential expression of epidermal growth factor receptor (EGFR), Notch1, sonic hedgehog (Shh), and STAT3, as well as related signaling pathways.
As discussed earlier, CD133 is the most well-characterized cell surface marker for GSCs, which has become a potential target for antibody-based therapy. Different immunotherapeutic approaches such use of synthetic monoclonal antibody, dual-antigen T cell engager, and chimeric antigen receptor (CAR) T cell have been utilized to target CD133+ GSCs. RW03 (anti-CD133 antibody) targets self-renewal ability of GSCs without effecting its proliferative capacity and could be a promising strategy in targeting GSCs [107]. Further, photothermal therapy has also shown selective efficacy in diminishing CD133-positive cells both
EGFR, a receptor tyrosine kinase, which is highly expressed in GSCs, is crucial for its survival, self-renewal, and tumorigenicity. Of importance, EGFR variant III (EGFRvIII) mutation is most commonly detectable (25–33%) in GBM cases [109]. Thus, EGFR inhibition becomes a potential target to inhibit GSCs proliferation, self-renewal, and induction of apoptosis [110]. EGFR inhibition in fact enhanced chemo- and radio-sensitivity of human glioma CSCs. Various reversible and irreversible inhibits of EGFR are available that can bind EGFR alone or along with its co-receptor HER2 [111, 112]. First-generation EGFR TKIs include gefitinib and erlotinib that can reversibly bind EGFR along with HER2; however, less than 20% of patients presented a response to these treatments [112, 113]. Irreversible inhibitor of EGFR, osimertinib, has shown efficiency in crossing the blood-brain barrier (BBB) and significantly inhibits GBM tumorigenesis
Various signaling pathways such as Notch and SHH are active in GSCs compared with bulk tumor cells [114]. Further, in response to TMZ treatment of GSCs from primary GBM cells resulted in upregulation of
Shh/Gli signaling that regulates GSCs cell proliferation, stem cell fate determination, and differentiation has also appeared as potential target for GSCs therapeutics [124]. Inhibition of hedgehog pathway by LDE225 induces autophagic cell death in GSCs with higher sensitivity of CD133-positive cells than CD133-negative cells [125]. LDE225 inhibits expression and nuclear translocation of Gli proteins, a transcriptional effectors of the Shh signaling pathway [126]. Casein kinase 2 (CK2) is another target to inhibit Shh/Gli signaling via transcriptional activation of β-catenin [127] and inhibition of CK2 by, CX-4945 (silmitasertib), reduces MGMT expression and sensitized tumor cells to TMZ [128].
Signal transducer and activator of transcription 3 (STAT3) that regulates multiple processes such as cell cycle and survival, regulation, immune response, and differentiation, tumorigenic transformation has also been implicated in GSC maintenance [129, 130]. Resveratrol (RV), a polyphenol present in grapes, a tumor preventive agent targets STAT3 signaling. In glioma, RV has shown antineoplastic actions by apoptosis induction and improving radio sensitivity of GSCs CD133+ cell population along with reducing of tumorigenic potential. Furthermore, RV also modulates Wnt signaling pathway and EMT activators, thereby regulating stemness of GSCs and reducing cellular motility [131, 132]. Another molecule that inhibits STAT pathway is WP1066, which is an analog of the natural product caffeic acid benzyl ester and targets GSCs. This molecule has shown promising results in clinical trial for patients with recurrent malignant glioma [133]. Other STAT3 inhibitors, STX-0119 and WP1066 have shown ability to suppress GSC proliferation
GSCs are localized in specific niches, which have been identified as protective microenvironments in GBM. Five types of GSC niches have been identified where different cell types exists and have specific singling pathways: peri-vascular, peri-arteriolar, peri-hypoxic, peri-immune, and extracellular matrix out of which peri-vascular niche is the most frequently described GSC [135]. GSC microenvironment lacks organizations and has compromised BBB, higher levels of hypoxia, and excessive angiogenesis making it a target for anti-angiogenic therapy [136, 137].
Drug repositioning also called as repurpose drugs is a growing concept that explores pre-existing a well-established drug to treat diseases aside from the intended ones. This concept results in lowering the overall developmental cost, time and risk assessments, as the efficacy and safety of the original drug have already been well accessed and approved by regulatory authorities [138]. In case of GSCs, repurpose drugs are being tested and have shown encouraging results. Especially, anti-diabetes drugs have been most well studied with promising results in GSCs targeting. Metformin, successfully used for type 2 diabetes mellitus, has entered phase I clinical trial for GBM in combination with TMZ [139]. Metformin preferentially acts in GSCs by inhibiting Akt activation and also induces conversion on GSCs to non-GSCs [140, 141]. Similarly glimepiride, another anti-diabetes drug, impairs GSCs by targeting glycolytic flux and increases its radio sensitivity to GBM [791]. Further, more repurpose drugs need to be identified that can effectively target GSCs along with its associated mechanism before it can be used in clinical application [138].
Autophagy is a cellular stress response, which can either promote survival or cell death. Our laboratory along with others has identified that autophagy is required for maintenance of GSCs and also plays a role in resistance of GSCs toward chemotherapy [19, 142, 143]. Targeting autophagy by commonly used agent chloroquine (CQ), which blocks the fusion of autophagosomes with lysosomes, has been shown to inhibit GSCs as well as sensitized them toward chemotherapeutic agents [19, 144]. This drug has also entered multiple clinical trials as an adjuvant treatment for GBM; where its antitumor effects of CQ are not limited to GSCs [145]. Further, combination of autophagy inhibitors with radiation effectively induced apoptosis and inhibited tumorosphere formation in GSCs [146, 147]. More selective autophagy inhibitor NSC185058, antagonist of autophagy-related 4B, inhibits tumorigenic potential of GSCs and enhances GBM sensitivity to radiotherapy in xenograft mouse models [148].
Treatment of HGG remains challenging. With identification of GSCs and their properties to resist treatment and repopulate the original tumor, a big momentum has been created in the development of novel therapeutics. Such therapeutic will involve a combination of drugs that controls the bulk tumor mass along with CSCs-directed agents. It has been identified that GSCs are responsible for tumorigenesis, therapeutic resistance, and tumor recurrence, and thus GSC-targeting drugs are being developed for improvement of treatment regime. These GSCs can survive cancer treatment by activating multiple mechanisms such as EMT, signaling pathways to regulate self-renewal, its interaction with tumor microenvironment, higher expression of drug transporters or detoxification proteins, plasticity, autophagy induction, anti-apoptotic mechanism, induction of dormant phenotype, and many others to overcome the toxic effects of therapeutics. With knowledge of these pathways, anticancer therapeutics are targeted against GSCs, which includes directing specific and pathways that regulate GSCs and protect them from therapeutic stress. Such GSC-directed drugs can be combined with agents that are currently in use to achieve better survival rates of cancer patients.
Identification of bioactive products and their molecular mechanisms that can modulate GSCs needs to be incorporated in treatment regime of HGG patients. With recent advancements in the field of high-throughput screening and genetic and epigenetic signatures, specific targeted drugs that can target bulk tumor with minimal generation of induced GSCs along with combination of drug that can target GSCs can be developed. Furthermore, tumor microenvironment that significantly regulates GSCs is also a potential target to prevent rate of dedifferentiation. It is important to consider that current therapeutic can result in conversion of non-GSC to GSCs; therefore, newer drugs or combinations need to be developed that can prevent this detrimental conversion. More stringent strategies involving GSC-targeted therapy along with glioma molecular subtypes need to be designed for selective and effective clinical trials.
However, most therapeutic agents have failed to be approved for clinical application or during clinical trials due to lack of understanding of the underlying mechanisms or failure to consider individual characteristics of the tumor. Further investigation of the molecular pathways that drive GSCs and make them resistant to therapies along with subtype-specific pathways of GSCs is required. Such studies will significantly improve not only the understanding of disease but will also direct the development of highly specific drugs with minimal side effects along with improved patient outcome.
The authors would like to acknowledge the funding support from Department of Biotechnology Bio-CARe grant, Govt. of India (BT/P19357/BIC/101/927/2016 to M.T.) and Intramural Research Grant by SGPGIMS (PGI/DIR/RC/36/2021) to LKS.
The authors declare that they have no conflict of interest.
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",metaTitle:"IntechOpen events",metaDescription:"In our mission to support the dissemination of knowledge, we travel worldwide to present our publications, authors and editors at international symposia, conferences, and workshops, as well as attend business meetings with science, academia and publishing professionals. We are always happy to host our scientists in our office to discuss further collaborations. Take a look at where we’ve been, who we’ve met and where we’re going.",metaKeywords:null,canonicalURL:"/page/events",contentRaw:'[{"type":"htmlEditorComponent","content":"May 18, 2022 | 1:00 PM - 2:00 PM CEST
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May 18, 2022 | 1:00 PM - 2:00 PM CEST
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The aim of the review article was to determine the comprehensive physical motor function assessment. Muscle function was assessed with the grip strength. Gait function was assessed with walking time tests conducted at a normal pace. Balance function was assessed with one‐legged standing time. The 6‐min walking distance test (6MD) was performed in a 10‐m, straight corridor. Walking efficiency during the 6MD trials was measured using the Cosmed K4b2 (Rome, Italy), an indirect calorimetry system specifically designed to measure energy expenditure in nonlaboratory settings. The center of pressure was recorded using a balance board (Wii; Nintendo Co., Ltd., Kyoto, Japan). A vibratory stimulus was applied alternately to two muscles by fixing two vibrators from the vibration device onto the participant’s gastrocnemius and lumbar multifidus muscle. These findings show that an assessment affecting postural control under proprioceptive stimulation might be a good indicator of elderly people. Also, the objective assessment of walking efficiency might be important for identifying the risk of external activity limitation or functional limitations among the late elderly.",book:{id:"5782",slug:"clinical-physical-therapy",title:"Clinical Physical Therapy",fullTitle:"Clinical Physical Therapy"},signatures:"Tadashi Ito",authors:[{id:"196581",title:"Ph.D.",name:"Tadashi",middleName:null,surname:"Ito",slug:"tadashi-ito",fullName:"Tadashi Ito"}]},{id:"55041",doi:"10.5772/67901",title:"Manual Lymphatic Drainage in the Treatment of Chronic Venous Disease",slug:"manual-lymphatic-drainage-in-the-treatment-of-chronic-venous-disease",totalDownloads:1889,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Chronic venous disease (CVD) is a chronic condition that is associated with venous hypertension, vein’s valves damage, venous obstruction, and calf muscle pump impairment. This blood circulatory condition is also characterized by important inflammatory changes affecting the skin, the subcutaneous tissue and the muscles, which are probably triggered by blood stasis and venous edema. With disease progression, severe ulcerative skin damage might occur, which when present represent the more severe stage of this condition. CVD has a significant economic, social and health impact, mostly due to raised morbidity and chronicity.",book:{id:"5782",slug:"clinical-physical-therapy",title:"Clinical Physical Therapy",fullTitle:"Clinical Physical Therapy"},signatures:"Rute S.S. Crisóstomo and Paulo A.S. Armada-da-Silva",authors:[{id:"197861",title:"Ph.D.",name:"Rute",middleName:null,surname:"Crisóstomo",slug:"rute-crisostomo",fullName:"Rute Crisóstomo"},{id:"205140",title:"Prof.",name:"Paulo A. S.",middleName:null,surname:"Armada-Da-Silva",slug:"paulo-a.-s.-armada-da-silva",fullName:"Paulo A. S. Armada-Da-Silva"}]}],mostDownloadedChaptersLast30Days:[{id:"54472",title:"Physiotherapy and Mental Health",slug:"physiotherapy-and-mental-health",totalDownloads:8634,totalCrossrefCites:8,totalDimensionsCites:12,abstract:"Physiotherapy in mental health care and psychiatry is a recognized specialty within physiotherapy. It offers a rich variety of observational and evaluation tools as well as a range of interventions that are related to the patient's physical and mental health problems based on evidence‐based literature and a 50‐year history. Physiotherapy in mental health care addresses human movement, function, physical activity and exercise in individual and group therapeutic settings. Additionally, it connects the physical and mental health needs of humans. This chapter offers general reflections on mental health, the scope of physiotherapy in mental health care and physiotherapy research. Physiotherapy in mental health care and psychiatry can offer added and beneficial value to the treatment of people with mental health problems.",book:{id:"5782",slug:"clinical-physical-therapy",title:"Clinical Physical Therapy",fullTitle:"Clinical Physical Therapy"},signatures:"Michel Probst",authors:[{id:"186905",title:"Prof.",name:"Michel",middleName:null,surname:"Probst",slug:"michel-probst",fullName:"Michel Probst"}]},{id:"53866",title:"Physical Therapy in Patients with Cancer",slug:"physical-therapy-in-patients-with-cancer",totalDownloads:4830,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Physical therapists often treat cancer patients. Cancer treatment includes chemotherapy, radiotherapy, and surgery, which are being continuously developed and thus increase survival of patients with each cancer diagnosis. More specifically, 5-year survival rates increase with each cancer diagnosis. Cancer patients have many problems including muscle weakness, pulmonary dysfunction, fatigue, and pain. In the end, patients with cancer tend to have a decline in activities of daily living (ADL) and quality of life (QOL). Additionally, cancer patients often have progressive disease, depression, and anxiety. Physical therapy often helps patients regain strength and physical function and improve their QOL and independence of daily living that they may have lost due to cancer or its treatment. Physical therapy has an important role in increasing physical function of cancer patients, cancer survivors, and children with cancer. In the future, physical therapy may be progressively needed for management of cancer patients.",book:{id:"5782",slug:"clinical-physical-therapy",title:"Clinical Physical Therapy",fullTitle:"Clinical Physical Therapy"},signatures:"Shinichiro Morishita and Atsuhiro Tsubaki",authors:[{id:"139514",title:"Ph.D.",name:"Shinichiro",middleName:null,surname:"Morishita",slug:"shinichiro-morishita",fullName:"Shinichiro Morishita"},{id:"202889",title:"Dr.",name:"Atsuhiro",middleName:null,surname:"Tsubaki",slug:"atsuhiro-tsubaki",fullName:"Atsuhiro Tsubaki"}]},{id:"55065",title:"Exercise Therapy for Physical Therapist",slug:"exercise-therapy-for-physical-therapist",totalDownloads:2451,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"This chapter describes exercise therapy in terms of definition, objectives, concept, techniques, mechanisms, and equipment. Mechanisms explaining the effect of exercise training on treatments for other diseases are included. In addition, new biomarkers capable of evaluating exercise performance capacity and progress in training and early detection of overtraining are provided. Very promising are mainly small non‐coding microRNAs (miRNAs). Important background knowledge for exercise therapy is also provided. The knowledge covers the exercise for healthy and unhealthy people. The former includes sedentary and sport player. The latter includes patients with various diseases, for example, metabolic diseases, cardiovascular disease, orthopedics, etc. Importantly, all the knowledge was presented in latest information.",book:{id:"5782",slug:"clinical-physical-therapy",title:"Clinical Physical Therapy",fullTitle:"Clinical Physical Therapy"},signatures:"Naruemon Leelayuwat",authors:[{id:"196387",title:"Associate Prof.",name:"Naruemon",middleName:null,surname:"Leelayuwat",slug:"naruemon-leelayuwat",fullName:"Naruemon Leelayuwat"}]},{id:"54293",title:"The Function of Scapular Muscle",slug:"the-function-of-scapular-muscle",totalDownloads:2266,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"In shoulder rehabilitation, it is important to evaluate scapular stability. However, it is not revealed how the mechanism runs for scapular stability. Additionally, the contribution of scapular muscles for scapular stability remains a matter of debate. Wherefore, I suggest some studies in this section to understand the function of scapulothoracic joint and the mechanism of scapular stability in detail. In the results of these studies, it was revealed that each scapular muscle activation is different for shoulder isometric contraction, and the exercise for a scapular muscle increases only the shoulder muscle strength of specific movement direction. If we can consider each scapular muscle individually by utilizing these results, we can provide more effective rehabilitation program.",book:{id:"5782",slug:"clinical-physical-therapy",title:"Clinical Physical Therapy",fullTitle:"Clinical Physical Therapy"},signatures:"Tomohito Ijiri",authors:[{id:"197891",title:"M.Sc.",name:"Tomohito",middleName:null,surname:"Ijiri",slug:"tomohito-ijiri",fullName:"Tomohito Ijiri"}]},{id:"54689",title:"Pelvic Movement in Aging Individuals and Stroke Patients",slug:"pelvic-movement-in-aging-individuals-and-stroke-patients",totalDownloads:1450,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The mobility of the lumbar spine (anteversion and retroversion) may be reflected in seated pelvic mobility. When sitting with the soles of the feet in contact with the floor, friction may restrict the flexion of the knees and, consequently, the pelvic anteversion. In general, joint mobility declines with advancing age. Lumbar spine mobility in anteversion and retroversion also decreases with advancing age. The first half of this chapter is based on a study that investigated the relationship between age and the maximum pelvic anteversion and the retroversion angles in healthy volunteers. The measurements were performed with the subject in a sitting position with free knee movement. On the other hand, the sit-to-stand movement is one of the most mechanically demanding tasks undertaken during daily activity. The sacral sitting posture, which is a characteristic posture of stroke patients, is not ideal for smoothly executing the sit-to-stand movement. Stroke patients may adopt this posture due to the need to increase sitting stability. The second half of this chapter discusses a study that investigated the relationship between the pelvic anteversion and retroversion angles and the ability of stroke patients to perform the sit-to-stand movement.",book:{id:"5782",slug:"clinical-physical-therapy",title:"Clinical Physical Therapy",fullTitle:"Clinical Physical Therapy"},signatures:"Hitoshi Asai",authors:[{id:"198129",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Asai",slug:"hitoshi-asai",fullName:"Hitoshi Asai"}]}],onlineFirstChaptersFilter:{topicId:"1118",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:141,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:124,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:22,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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\r\n\tEducation and Human Development is an interdisciplinary research area that aims to shed light on topics related to both learning and development. This Series is intended for researchers, practitioners, and students who are interested in understanding more about these fields and their applications.
",coverUrl:"https://cdn.intechopen.com/series/covers/23.jpg",latestPublicationDate:"August 12th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:0,editor:{id:"280770",title:"Dr.",name:"Katherine K.M.",middleName:null,surname:"Stavropoulos",slug:"katherine-k.m.-stavropoulos",fullName:"Katherine K.M. Stavropoulos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRdFuQAK/Profile_Picture_2022-05-24T09:03:48.jpg",biography:"Katherine Stavropoulos received her BA in Psychology from Trinity College, in Connecticut, USA and her Ph.D. in Experimental Psychology from the University of California, San Diego. She completed her postdoctoral work at the Yale Child Study Center with Dr. James McPartland. Dr. Stavropoulos’ doctoral dissertation explored neural correlates of reward anticipation to social versus nonsocial stimuli in children with and without autism spectrum disorders (ASD). She has been a faculty member at the University of California, Riverside in the School of Education since 2016. Her research focuses on translational studies to explore the reward system in ASD, as well as how anxiety contributes to social challenges in ASD. She also investigates how behavioral interventions affect neural activity, behavior, and school performance in children with ASD. She is also involved in the diagnosis of children with ASD and is a licensed clinical psychologist in California. She is the Assistant Director of the SEARCH Center at UCR and is a faculty member in the Graduate Program in Neuroscience.",institutionString:null,institution:{name:"University of California, Riverside",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:2,paginationItems:[{id:"89",title:"Education",coverUrl:"https://cdn.intechopen.com/series_topics/covers/89.jpg",isOpenForSubmission:!1,editor:{id:"260066",title:"Associate Prof.",name:"Michail",middleName:null,surname:"Kalogiannakis",slug:"michail-kalogiannakis",fullName:"Michail Kalogiannakis",profilePictureURL:"https://mts.intechopen.com/storage/users/260066/images/system/260066.jpg",biography:"Michail Kalogiannakis is an Associate Professor of the Department of Preschool Education, University of Crete, and an Associate Tutor at School of Humanities at the Hellenic Open University. He graduated from the Physics Department of the University of Crete and continued his post-graduate studies at the University Paris 7-Denis Diderot (D.E.A. in Didactic of Physics), University Paris 5-René Descartes-Sorbonne (D.E.A. in Science Education) and received his Ph.D. degree at the University Paris 5-René Descartes-Sorbonne (PhD in Science Education). His research interests include science education in early childhood, science teaching and learning, e-learning, the use of ICT in science education, games simulations, and mobile learning. He has published over 120 articles in international conferences and journals and has served on the program committees of numerous international conferences.",institutionString:"University of Crete",institution:{name:"University of Crete",institutionURL:null,country:{name:"Greece"}}},editorTwo:{id:"422488",title:"Dr.",name:"Maria",middleName:null,surname:"Ampartzaki",slug:"maria-ampartzaki",fullName:"Maria Ampartzaki",profilePictureURL:"https://mts.intechopen.com/storage/users/422488/images/system/422488.jpg",biography:"Dr Maria Ampartzaki is an Assistant Professor in Early Childhood Education in the Department of Preschool Education at the University of Crete. Her research interests include ICT in education, science education in the early years, inquiry-based and art-based learning, teachers’ professional development, action research, and the Pedagogy of Multiliteracies, among others. She has run and participated in several funded and non-funded projects on the teaching of Science, Social Sciences, and ICT in education. She also has the experience of participating in five Erasmus+ projects.",institutionString:"University of Crete",institution:{name:"University of Crete",institutionURL:null,country:{name:"Greece"}}},editorThree:null},{id:"90",title:"Human Development",coverUrl:"https://cdn.intechopen.com/series_topics/covers/90.jpg",isOpenForSubmission:!0,editor:{id:"191040",title:"Dr.",name:"Tal",middleName:null,surname:"Dotan Ben-Soussan",slug:"tal-dotan-ben-soussan",fullName:"Tal Dotan Ben-Soussan",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBf1QAG/Profile_Picture_2022-03-18T07:56:11.jpg",biography:"Tal Dotan Ben-Soussan, Ph.D., is the director of the Research Institute for Neuroscience, Education and Didactics (RINED) – Paoletti Foundation. Ben-Soussan leads international studies on training and neuroplasticity from neurophysiological and psychobiological perspectives. As a neuroscientist and bio-psychologist, she has published numerous articles on neuroplasticity, movement and meditation. She acts as an editor and reviewer in several renowned journals and coordinates international conferences integrating theoretical, methodological and practical approaches on various topics, such as silence, logics and neuro-education. She lives in Assisi, Italy.",institutionString:"Research Institute for Neuroscience, Education and Didactics, Patrizio Paoletti Foundation",institution:null},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:11,paginationItems:[{id:"83053",title:"Apologies in L2 French in Canadian Context",doi:"10.5772/intechopen.106557",signatures:"Bernard Mulo Farenkia",slug:"apologies-in-l2-french-in-canadian-context",totalDownloads:0,totalCrossrefCites:0,totalDimensionsCites:0,authors:[{name:"Bernard",surname:"Mulo Farenkia"}],book:{title:"Second Language Acquisition - Learning Theories and Recent Approaches",coverURL:"https://cdn.intechopen.com/books/images_new/11480.jpg",subseries:{id:"89",title:"Education"}}},{id:"82903",title:"Walking Accessibility to Primary Healthcare Services: An Inequity Factor for Olders in the Lisbon Metropolitan Area (Portugal)",doi:"10.5772/intechopen.106265",signatures:"Eduarda Marques da Costa, Ana Louro, Nuno Marques da Costa, Mariana Dias and Marcela Barata",slug:"walking-accessibility-to-primary-healthcare-services-an-inequity-factor-for-olders-in-the-lisbon-met",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Social Aspects of Ageing - Selected Challenges, Analyses, and Solutions",coverURL:"https://cdn.intechopen.com/books/images_new/11479.jpg",subseries:{id:"90",title:"Human Development"}}},{id:"82622",title:"Contemporary Geographical Gerontology: Reconciling Space and Place in Population Ageing",doi:"10.5772/intechopen.105863",signatures:"Hamish Robertson",slug:"contemporary-geographical-gerontology-reconciling-space-and-place-in-population-ageing",totalDownloads:13,totalCrossrefCites:0,totalDimensionsCites:0,authors:[{name:"Hamish",surname:"Robertson"}],book:{title:"Social Aspects of Ageing - Selected Challenges, Analyses, and Solutions",coverURL:"https://cdn.intechopen.com/books/images_new/11479.jpg",subseries:{id:"90",title:"Human Development"}}},{id:"82610",title:"Perspective Chapter: The Role of Learning Styles in Active Learning",doi:"10.5772/intechopen.105964",signatures:"Armando Lozano-Rodríguez, Fernanda Inez García-Vázquez and José Luis García-Cué",slug:"perspective-chapter-the-role-of-learning-styles-in-active-learning",totalDownloads:11,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Active Learning - Research and Practice",coverURL:"https://cdn.intechopen.com/books/images_new/11481.jpg",subseries:{id:"89",title:"Education"}}}]},overviewPagePublishedBooks:{paginationCount:0,paginationItems:[]},openForSubmissionBooks:{paginationCount:2,paginationItems:[{id:"11474",title:"Quality of Life Interventions - Magnitude of Effect and Transferability",coverURL:"https://cdn.intechopen.com/books/images_new/11474.jpg",hash:"5a6bcdaf5ee144d043bcdab893ff9e1c",secondStepPassed:!0,currentStepOfPublishingProcess:3,submissionDeadline:"July 7th 2022",isOpenForSubmission:!0,editors:[{id:"245319",title:"Ph.D.",name:"Sage",surname:"Arbor",slug:"sage-arbor",fullName:"Sage Arbor"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{id:"11473",title:"Social Inequality - Structure and Social Processes",coverURL:"https://cdn.intechopen.com/books/images_new/11473.jpg",hash:"cefab077e403fd1695fb2946e7914942",secondStepPassed:!0,currentStepOfPublishingProcess:3,submissionDeadline:"July 13th 2022",isOpenForSubmission:!0,editors:[{id:"313341",title:"Ph.D.",name:"Yaroslava",surname:"Robles-Bykbaev",slug:"yaroslava-robles-bykbaev",fullName:"Yaroslava Robles-Bykbaev"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},onlineFirstChapters:{paginationCount:21,paginationItems:[{id:"83000",title:"Purine and Pyrimidine Pathways as Antimalarial Targets",doi:"10.5772/intechopen.106468",signatures:"Yacoba V.T. 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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 Principal Investigator and Scientist 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 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 machine-learning-based analyses of exosomal signatures. Dr. Paul has published in more than fifty peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award, 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. He has experience teaching DPharm, Pharm.D, BPharm, and MPharm students. He has more than five publications in reputed journals to his credit. Dr. Faheem’s research area is the development and characterization of nanoformulation for the delivery of drugs to various organs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/system/329795.png",biography:"Dr. Mohd Aftab Siddiqui is an assistant professor in the Faculty of Pharmacy, Integral University, Lucknow, India, where he obtained a Ph.D. in Pharmacology in 2020. He also obtained a BPharm and MPharm from the same university in 2013 and 2015, respectively. His area of research is the pharmacological screening of herbal drugs/natural products in liver cancer and cardiac diseases. He is a member of many professional bodies and has guided many MPharm and PharmD research projects. Dr. Siddiqui has many national and international publications and one German patent to his credit.",institutionString:"Integral University",institution:null}]}},subseries:{item:{id:"10",type:"subseries",title:"Animal Physiology",keywords:"Physiology, Comparative, Evolution, Biomolecules, Organ, Homeostasis, Anatomy, Pathology, Medical, Cell Division, Cell Signaling, Cell Growth, Cell Metabolism, Endocrine, Neuroscience, Cardiovascular, Development, Aging, Development",scope:"Physiology, the scientific study of functions and mechanisms of living systems, is an essential area of research in its own right, but also in relation to medicine and health sciences. The scope of this topic will range from molecular, biochemical, cellular, and physiological processes in all animal species. Work pertaining to the whole organism, organ systems, individual organs and tissues, cells, and biomolecules will be included. Medical, animal, cell, and comparative physiology and allied fields such as anatomy, histology, and pathology with physiology links will be covered in this topic. Physiology research may be linked to development, aging, environment, regular and pathological processes, adaptation and evolution, exercise, or several other factors affecting, or involved with, animal physiology.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/10.jpg",hasOnlineFirst:!1,hasPublishedBooks:!1,annualVolume:11406,editor:{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. 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