",isbn:"978-1-80356-966-6",printIsbn:"978-1-80356-965-9",pdfIsbn:"978-1-80356-967-3",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"f86a9f720cc3ac0f1c385d0367ea89b9",bookSignature:"Dr. Fiaz Ahmad and Prof. Muhammad Sultan",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11624.jpg",keywords:"Agricultural Waste, Reuse, Reduction, Soil Health, Recycling, Agriculture and Environment, Modelling and Simulation, Agro-Industrial Waste, Bioresource Processing, Processing and Management, Crop Residue, Forest Waste",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 8th 2022",dateEndSecondStepPublish:"June 16th 2022",dateEndThirdStepPublish:"August 15th 2022",dateEndFourthStepPublish:"November 3rd 2022",dateEndFifthStepPublish:"January 2nd 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"2 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"Dr. Fiaz Ahmad is a researcher in the field of Agricultural Engineering with fifteen years of field and academic experience, currently in charge of the Agricultural Machinery Design Laboratory at Bahauddin Zakariya University. He applied for two patents at the national level.",coeditorOneBiosketch:"A renowned researcher in the field of Agricultural Engineering with 14 years of academic experience at Bahauddin Zakariya University. Winner of various prestigious fellowships, awards, and research grants. Published 250+ articles along with several books and chapters. Guest editor of seven ISI-SCI journals for publishers like SAGE, MDPI, and Frontiers.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"338219",title:"Dr.",name:"Fiaz",middleName:null,surname:"Ahmad",slug:"fiaz-ahmad",fullName:"Fiaz Ahmad",profilePictureURL:"https://mts.intechopen.com/storage/users/338219/images/system/338219.png",biography:"Dr. Fiaz Ahmad is an assistant professor and lecturer at the Department of Agricultural Engineering, Bahauddin Zakariya University, Multan, Pakistan. He obtained his Ph.D. in Agricultural Bioenvironmental and Energy Engineering from Nanjing Agriculture University, China, in 2015, and completed his postdoctorate in Agricultural Engineering from Jiangsu University, Zhenjiang, China, in 2020. He was awarded a fellowship from the Higher Education Commission of Pakistan for Ph.D. studies and from the Chinese Government for post-doctoral studies. He earned a BSc and MSc (Hons) in Agricultural Engineering from the University of Agriculture, Faisalabad, Pakistan, in 2004 and 2007, respectively. He is the author of more than fifty journal and conference articles. He has supervised six master’s students to date, and is currently supervising six master and two doctoral students. Dr. Ahmad has completed three research projects with his research interest focusing on the design of agricultural machinery, agricultural waste management, artificial intelligence (AI), and agricultural bioenvironment.",institutionString:"Bahauddin Zakariya University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Bahauddin Zakariya University",institutionURL:null,country:{name:"Pakistan"}}}],coeditorOne:{id:"199381",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sultan",slug:"muhammad-sultan",fullName:"Muhammad Sultan",profilePictureURL:"https://mts.intechopen.com/storage/users/199381/images/system/199381.png",biography:"Muhammad Sultan is an Assistant Professor at the Department of Agricultural\r\nEngineering, Bahauddin Zakariya University, Multan (Pakistan). He completed his Ph.D.\r\nand Postdoc from Kyushu University (Japan) in the field of Energy & Environmental\r\nEngineering. He was an awardee of MEXT and JASSO fellowships (from the Japanese\r\nGovernment) during Ph.D. and Postdoc studies, respectively. He also did a Postdoc as\r\na Canadian Queen Elizabeth Advance Scholar at Simon Fraser University (Canada) in\r\nthe field of Mechatronic Systems Engineering. He worked for Kyushu University\r\nInternational Institute for Carbon-Neutral Energy Research (WPI-I2CNER) for two years.\r\nCurrently, he is working on 4 research projects funded by the Higher Education\r\nCommission (HEC) of Pakistan. He has completed six projects in past in the field of\r\nagricultural engineering. He has supervised 10+ M.Eng. and Ph.D. thesis and 10+\r\nstudents are currently working under his supervision. He has published 120+ journal\r\narticles, 100+ conference articles, 13 book chapters, and 6 books. He is serving as guest\r\neditor for the journals like Sustainability (MDPI), Agriculture (MDPI), Energies (MDPI),\r\nAdvances in Mechanical Engineering (SAGE), Frontiers in Mechanical Engineering, and\r\nEvergreen Journal of Kyushu University. His research is focused on developing energy-\r\nefficient temperature and humidity control systems for agricultural storage, greenhouse,\r\nlivestock, and poultry applications. His research keywords include desiccant air-\r\nconditioning, evaporative cooling, adsorption heat pump, Maisotsenko cycle (M-cycle),\r\nenergy recovery ventilators; adsorption desalination; wastewater treatment.",institutionString:"Bahauddin Zakariya University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"5",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Bahauddin Zakariya University",institutionURL:null,country:{name:"Pakistan"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"5",title:"Agricultural and Biological Sciences",slug:"agricultural-and-biological-sciences"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"440212",firstName:"Elena",lastName:"Vracaric",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/440212/images/20007_n.jpg",email:"elena@intechopen.com",biography:"As an Author Service Manager, my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"10454",title:"Technology in Agriculture",subtitle:null,isOpenForSubmission:!1,hash:"dcfc52d92f694b0848977a3c11c13d00",slug:"technology-in-agriculture",bookSignature:"Fiaz Ahmad and Muhammad Sultan",coverURL:"https://cdn.intechopen.com/books/images_new/10454.jpg",editedByType:"Edited by",editors:[{id:"338219",title:"Dr.",name:"Fiaz",surname:"Ahmad",slug:"fiaz-ahmad",fullName:"Fiaz Ahmad"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6418",title:"Hyperspectral Imaging in Agriculture, Food and Environment",subtitle:null,isOpenForSubmission:!1,hash:"9005c36534a5dc065577a011aea13d4d",slug:"hyperspectral-imaging-in-agriculture-food-and-environment",bookSignature:"Alejandro Isabel Luna Maldonado, Humberto Rodríguez Fuentes and Juan Antonio Vidales Contreras",coverURL:"https://cdn.intechopen.com/books/images_new/6418.jpg",editedByType:"Edited by",editors:[{id:"105774",title:"Prof.",name:"Alejandro Isabel",surname:"Luna Maldonado",slug:"alejandro-isabel-luna-maldonado",fullName:"Alejandro Isabel Luna Maldonado"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10359",title:"Landraces",subtitle:"Traditional Variety and Natural Breed",isOpenForSubmission:!1,hash:"0600836fb2c422f7b624363d1e854f68",slug:"landraces-traditional-variety-and-natural-breed",bookSignature:"Amr Elkelish",coverURL:"https://cdn.intechopen.com/books/images_new/10359.jpg",editedByType:"Edited by",editors:[{id:"231337",title:"Dr.",name:"Amr",surname:"Elkelish",slug:"amr-elkelish",fullName:"Amr Elkelish"}],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. 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1. Introduction
Eukaryotic DNA is tightly packaged into nucleosome repeats, which form the basic unit of cellular chromatin. The nucleosome consists of an octamer core wrapped with a segment of 146 base pairs of double stranded DNA. Each octamer core is composed of two molecules of each core histone proteins H2A, H2B, H3 and H4 (Figure 1). A fifth histone protein, linker H1, binds to the nucleosomal core particle and assists in further compaction of the chromatin into higher-order structure(Lusser and Kadonaga, 2003;Roberts and Orkin, 2004). This compaction of genomic DNA into chromatin restricts access of a variety of DNA regulatory proteins to the DNA strand, which are involved in the processes of transcription, replication, DNA repair and recombination machinery. To overcome these barriers, eukaryotic cells possess a number of multi-protein complexes which can alter the chromatin structure and make DNA more accessible. These complexes can be divided into two groups, histone-modifying enzymes and ATP-dependent chromatin remodelling complexes. The histone-modifying enzymes post-translationally modify the N-terminal tails of histone proteins through acetylation, phosphorylation, ubiquitination, ADP-ribosylation and methylation. On the other hand, ATP-dependent chromatin remodelling complexes use the energy of ATP hydrolysis to disrupt the contact between DNA and histones, move nucleosomes along DNA, and remove or exchange nucleosomes(Kallin and Zhang, 2004;Lusser and Kadonaga, 2003;Roberts and Orkin, 2004). The importance of chromatin structure and its functional role in genome regulation and development is becoming increasingly evident, especially in diseases such as cancer.
Figure 1.
Schematic representation of a nucleosome (A) and major histone modifications (B). Modifications on histones are described in text. The major modifications shown include acetylation (A), methylation (M), phosphorylation (P) and ubiquitination (U). Histone modifications mainly occur on the N-terminal tails of histones but also on the C-terminal tails and globular domains, for example, ubiquitination of the C-terminal tails of H2A and H2B and acetylation and methylation of the globular domain of H3 at K56 and K79, respectively.
Intracellular pathogens, through a long-standing coexistence with host cells, have evolved mechanisms that provide pathogens with the amazing capacity to adapt and survive in the variable and often hostile environments of their hosts (Galan and Cossart, 2005). The concept of chromatin modification as a mechanism by which pathogens affect host immune responses to facilitate infection has emerged in recent years. For example, listeriolysin O (LLO), secreted by Listeria monocytogenes, induces a dramatic dephosphorylation of histone H3 at serine 10 and deacetylation of histone H4, and these modifications are associated with changes in host gene expression during early stages of infection (Hamon et al., 2007). Arbibe and colleagues also indicate that Shigella flexneri effector OspF dephosphorylates ERK and p38 mitogen-activated protein kinase (MAPK) in the nucleus; this subsequently prevents histone H3 phosphorylation at Ser10 at the promoters of a specific subset of genes, which blocks the activation of nuclear factor –κB (NF-κB)- responsive genes leading to a compromised inflammation in the infected tissue(Arbibe et al., 2007). These results suggest a strategy developed by microbial pathogens to manipulate the host cellular function through histone modification and subversion of host innate immune responses for their survival or to infect the host.
Histone acetylation/deacetylation is a key epigenetic regulator of chromatin structure and gene expression, in combination with other posttranslational modifications. These patterns of histone modification are maintained by histone modifying enzymes such as histone acetyltransferases (HATs) and histone deacetylases (HDACs). While HATs acetylate histones, conferring an ‘’open” chromatin structure that allows transcriptional activation, HDACs have the opposite effect resulting in transcriptional repression by closing chromatin structure. Global HDAC-mediated transcriptional changes can have a concomitant effect on cell function – an epigenetic mechanism often exploited by viruses to promote infection (Punga and Akusjarvi, 2000;Radkov et al., 1999;Valls et al., 2007). Recent reports also show that intracellular bacteria manipulate host cell epigenetics to facilitate infection (Arbibe et al., 2007;Hamon et al., 2007;Hamon and Cossart, 2008). Disruption of HDAC activity with inhibitors or by siRNA affects gene expression profilling in different cell types (Glaser et al., 2003a;Glaser et al., 2003b;Lee et al., 2004;Zupkovitz et al., 2006). The potential of HDAC inhibitors in treatment of infection has being studied.
In this chapter, the chromatin modifications in host cells induced by bacterial pathogens and their effects on host gene expression and infection will be reviewed. Furthermore, the potential role of HDAC inhibitors, as a therapeutic immunomodulator, in treatment of infections will also be discussed.
2. Chromatin structure in transcription regulation
The packaging of DNA into chromatin does not only simply facilitate the compaction of eukaryotic DNA genomes into the cell nucleus but also plays a profound and ubiquitous roles in almost all DNA-related cellular processes such as DNA replication, repair, recombination and transcription (Clapier and Cairns, 2009;Li et al., 2007a). Chromatin structure is not a simple static unit. It possesses dynamic properties that are orchestrated by ATP-dependent chromatin-remodeling complexes and histone-modifying enzymes. In conjunction with other co-regulators, these chromatin remodelers modify histone-DNA interaction and regulate transcription at specific genomic loci.
2.1. Histone modifications and transcription
Histone sequences are highly conserved. A core histone protein typically consists of an unstructured N-terminal tail, a globular core including a central histone-fold domain, and a conformationally mobile C-terminal tail (Garcia et al., 2007b;Mersfelder and Parthun, 2006). Both N-terminal tails and globular domains are subject to a variety of posttranslational modifications (Kouzarides T, Cell, 2007, 128:693-705) (Figure 1). At least fourteen different types of posttranslational (or covalent) modifications involving more than 60 different residues on histones have been reported to date including acetylation, methylation, phosphorylation, ubiquitination, poly-ADP ribosylation, sumoylation, butyrylation, formylation, deimination, citrullination, isomerisation, O-GlcNAcylation, crotonylation and hydroxylation (Martin and Zhang, 2007;Ruthenburg et al., 2007;Sakabe et al., 2010;Tan et al., 2011). The majority of known histone modifications are located within the N-terminal tails of core histones. These modifications play an important role in the control of chromatin dynamics and its availability for transcription (Kouzarides, 2007). It has been suggested that all these modifications are combinatorial and interdependent and therefore may constitute a ``histone code`` (Jenuwein and Allis, 2001;Strahl and Allis, 2000). According to this hypothesis, the “histone code” is read by effector proteins (readers) which recognize and bind to modifications via specific domains and result in distinct and consistent cellular processes, such as replication, transcription, DNA repair and chromosome condensation (Kouzarides, 2007;Shi and Whetstine, 2007). Specific histone modifications are essential for partitioning the genome into functional domains, such as transcriptionally silent heterochromatin and transcriptionally active euchromatin (Martin and Zhang, 2005).
There are two major mechanisms underlying the function of histone modifications (Kouzarides, 2007;Ruthenburg et al., 2007). The first is the modulation of chromatin structure either by altering DNA-nucleosome interaction or by altering nucleosome-nucleosome interactions via changing the histone charges or by addition of physical entities. For example, histone acetylation, a modification associated with transcriptional activation, has been proposed to unfold chromatin structure via neutralization of the basic charges of lysines (Kouzarides, 2007). Indeed, in vitro studies using recombinant nucleosomal arrays have demonstrated that acetylation of H4K16 restricts the formation of a 30-nanometer fiber and the generation of higher-order structures (Shogren-Knaak et al., 2006;Shogren-Knaak and Peterson, 2006). Secondly, histone modifications provide docking sites for the recruitment of specific binding proteins, which recognize and interact with modified histones via specialized domains such as bromo-, chromo- and PHD (plant homeodomain) domains, thereby influence chromatin dynamics and function (Wysocka et al., 2005;Wysocka et al., 2006b;Zeng and Zhou, 2002). A number of proteins have been identified that are recruited to specific modifications. For example, methylation of H3K4, H3K9 and H3K27 can be recognized by inhibitor of growth (ING) proteins, heterochromatin protein 1 (HP1) and polycomb proteins, respectively. It has been shown that histone modification binding proteins can tether, directly or indirectly, an enzyme to chromatin. The activity of this recruited enzyme can be regulated (Pena et al., 2006;Shi et al., 2006;Wysocka et al., 2006b). BPTF, a component of the NURF chromatin remodelling complex, binds to H3K4me3 via a PHD domain and tethers the SNF2L ATPase to H0XC8 gene and activates the expression of the latter (Wysocka et al., 2006b). JMJD2A and CHD1, two other H3K4me-binding proteins, possess enzymatic activities themselves and can directly deliver enzymatic activities to chromatin when recruited (Huang et al., 2006;Pray-Grant et al., 2005;Sims, III et al., 2005).
The link between histone modifications and transcriptional regulation has been widely studied. It has been found that a specific modification can be associated with transcriptional activation or repression. Among the histone modifications, methylation and acetylation of H3 and H4 play a major role in the regulation of transcriptional activity (Berger, 2007;Jenuwein and Allis, 2001;Li et al., 2007a;Shahbazian and Grunstein, 2007). Methylation, which occurs on either a lysine or an arginine residue, is catalyzed by three different classes of methyltransferases: SET domain-containing histone methyltransferases (HMTs), non-SET domain-containing lysine methyltransferases as well as protein arginine methyltransferase (PRMT). Methylation is implicated in both activation and repression of transcription depending on the methylation site and the type of methyltransferase involved (Shilatifard, 2006;Wysocka et al., 2006a). For example, methylation of lysine 4, 36 or 79 of H3 correlates with activation of transcription whereas methylation of lysine 9, 27 of H3 or lysine 20 of H4 is usually linked to transcriptional repression (Pawlak and Deckert, 2007). Type I PRMT, such as CARM1 (cofactor associated arginine methyltransferase 1), PRMT1 and PRMT2, catalyze the formation of monomethyl- and asymmetric dimethyl-arginine derivatives and is involved in transcriptional activation. Type II PRMT, such as PRMT5, catalyzes the formation of monomethyl- and symmetric dimethyl-arginine derivatives and is involved in transcriptional repression. In addition, a lysine can be mono-, di- or trimethylated with different effect on gene transcription (Santos-Rosa et al., 2002;Schneider et al., 2005). Both lysine and arginine methylations can be reversed by histone demethylases, which had been discovered many years after the discovery of HMTs. LSD1 was the first histone demethylase discovered in 2004 and was shown to demethylate H3K4 and to repress transcription (Shi et al., 2004). However, LSD1 was also shown to demethylate H3K9 and activate transcription when present in a complex with the androgen receptor (Metzger et al., 2005). Following the discovery of LSD1, a number of other related enzymes were subsequently discovered. Among them, Jumonji domain–containing 6 protein (JMJD6) is the only direct arginine demethylase reported to date shown to demethylate H3 at arginine 2 and H4 at arginine 3 (Chang et al., 2007). In addition, human peptidylarginine deiminase 4 protein (Pad4) can regulate histone arginine methylation by converting mono-methylated arginine into citrulline via demethylimination or deimination (Cuthbert et al., 2004;Wang et al., 2004). Histone methylation may affect the binding of other histone-modifying enzymes to the chromatin, which then mediates other posttranscriptional modifications, such as histone phosphorylation and DNA methylation (Mosammaparast and Shi, 2010;Pedersen and Helin, 2010).
Acetylation, another well-characterized modification, occurs on lysine residues mainly in the N-terminal tail of core histones. However, a lysine 56 within the globular domain of H3 (H3K56) has been found to be acetylated in yeast. Yeast protein SPT10, a putative histone acetyltransferase (HAT), was shown to mediate the H3K56 acetylation of histone genes at their promoter regions. H3K56 acetylation allows the recruitment of Snf5, an essential component of SWI/SNF chromatin remodeling complex and subsequently regulating transcription (Xu et al., 2005). Compared with the SPT10, the Rtt109 acetyltransferase mediates H3K56 acetylation more globally (Driscoll et al., 2007;Han et al., 2007;Schneider et al., 2006). The acetylation level correlates with transcriptional activation (Davie, 2003;Legube and Trouche, 2003). The level of acetylation is balanced by HATs and HDACs. Generally, increased levels of histone acetylation by HATs enhance chromatin decondensation and DNA accessibility for transcription factors to activate gene expression. In contrast to acetylation, deacetylation of histones catalyzed by HDACs leads to chromatin condensation and gene silencing (Berger, 2007;Li et al., 2007a). The relationship between histone acetylation and gene expression has been well documented (Verdone et al., 2006). HATs can also acetylate non-histone proteins, such as transcription factors and nuclear receptors to facilitate gene expression (Bannister and Miska, 2000;Masumi, 2011)
Other histone modifications, such as phosphorylation, ubiquitylation and sumoylation, have also been shown to be involved in transcriptional regulation. For example, H3S10 phosphorylation has been demonstrated to be involved in the activation of NF-κB-regulated genes as well as “immediate early” genes, such as c-fos and c-jun (Macdonald et al., 2005). Ubiquitination of H2AK119 and H2BK120 are associated with transcriptional repression and activation, respectively (Wang et al., 2006;Zhu et al., 2005).
2.2. Chromatin remodelling complex and transcription
The second major class of chromatin-modifying factors are the protein complexes that use energy from ATP hydrolysis to alter nucleosomal structure and DNA accessibility and hence are generally referred to as chromatin remodeling complex (Flaus and Owen-Hughes, 2004;Saha et al., 2006). Each ATP-dependent chromatin-remodeling complex characterized to date contains a highly conserved ATPase subunit that belongs to the SNF2 ATPase superfamily (Marfella CGA, Mutate Res, 2007). Based on the similarities of their ATPase subunits and the presence of other conserved domains, these complexes can be classified into at least four different families (Figure 2): the SWI/SNF (mating type switching /sucrose non-fermenting) family; the ISWI (imitation switch) family; the NuRD/Mi-2/CHD (chromodomain helicase DNA-binding) family and INO80 (inositol requiring 80) family (Farrants, 2008;Saha et al., 2006). The ATPase subunits of the SWI/SNF family members, including yeast Snf2 and Sth1, Drosophila\n\t\t\t\t\tmelangaster brahma (BRM) and mammalian BRM and BRG1 (brahma-related gene 1), contain an C-terminal bromodomains which recognize and binds to acetylated histone tails (Hassan et al., 2002;Marfella and Imbalzano, 2007). The members of ISWI family, such as yeast homologues ISW1 and ISW2, and mammalian homologues SNF2H and SNF2L, each contains an ATPase subunit with homology to Drosophila ISWI protein and has nucleosome-stimulated ATPase activity. These enzymes are characterized by the presence of a SANT (SWI3-ADA2-NCoR-TFIIIB) domain, which functions as a histone-tail-binding module (Boyer et al., 2004;de la Serna et al., 2006). SANT domain has been found in a number of transcriptional regulatory proteins and is therefore thought to play a role in transcriptional regulation (Aasland et al., 1996;Boyer et al., 2002). The NuRD/Mi-2/CHD family members include a number of proteins that are highly conserved from yeast to humans and are characterized by the presence of two N-terminal chromodomains involved in the remodeling of chromatin structure and regulation of transcription (Brehm et al., 2004;Eissenberg, 2001;Jones et al., 2000). The INO80 family contains the INO80 remodeling complex (INO80.com) and the SWR1 remodeling complex (SWR1.com), which are distinguished by the split ATPase domains and the presence of two RuvB-like proteins, Rvb1 and Rvb2 (Bao and Shen, 2007).
Figure 2.
ATPase subunits of the four main families of ATP-dependent chromatin remodeling complexes. The ATPase subunit of each ATP-dependent chromatin-remodeling complex belongs to the SNF2 ATPase superfamily, whose ATPase domain comprises an N-terminal DExx and a C-terminal HELICc subdomain, separated by an insert region. The SWI/SNF family contains an HSA domain for actin binding, and a bromodomain which recognizes and binds to the acetylated histone tails. The ISWI family contains the SANT and SLIDE domains, important for histone binding. The CHD/NURD/Mi-2 family is characterized by the presence of two N-terminal chromodomains that is involved in the remodeling of chromatin structure and the transcriptional regulation of genes. The INO80 family, like the SWI/SNF family, also contains an HSA domain, however the insert region between the DExx and the HELICc subdomains is three times longer than that of other three families.
ATP-dependent chromatin remodelers can reposition (slide, twist, or loop) nucleosomes along the DNA, evict histones from DNA or facilitate exchange of histone variants, and thus creating nucleosome-free regions for gene activation (Figure 3) (Wang et al., 2007).
Figure 3.
Mechanisms of ATP-dependent chromatin remodeling activity to alter the accessibility of nucleosomal DNA. Upon utilization of the energy from ATP hydrolysis, the nucleosomal structure is altered to make protected region of chromatin available to DNA binding protein complexes, such as transcription factors, which involves mobilization of nucleosome position(sliding), dissociation of DNA-histone contact (unwrapping), and eviction of histones (histone eviction). In some cases ATP dependent remodeling complexes can use the energy from ATP hydrolysis to introduce histone variants into the nucleosome (exchange of histone variants), such as H2A–H2B or H2A variants (H2Avar)–H2B dimers.
3. The role of chromatin remodelling in the regulation of inflammatory gene expression
The inflammatory response is a defense mechanism developed in higher organisms to protect themselves from infection with pathogens. It demands rapid and coordinated regulation of expression of multiple inflammatory genes in immune cells, including macrophages. It has increasingly become clear that alterations of chromatin architecture orchestrated by histone modifications and ATP-dependent chromatin remodeling complexes play a key role in controlling of inflammatory response genes (Medzhitov and Horng, 2009;Smale, 2010).
3.1. LPS-induced chromatin modification and target gene expression
LPS, a large molecule consisting of a lipid and a polysaccharide joined by a covalent bond, is the major component of the outer membrane of gram-negative bacteria and is one of the best-characterized agonist of host inflammatory response. LPS is recognized by Toll-like receptor 4 (TLR4) and activates the downstream signaling pathways, including the NF-κB signaling cascades, MAPK cascades and interferon regulatory factor (IRF) signaling cascades and induce the transcription of proinflammatory cytokine genes such as interleukin-6 (IL-6), IL-12 and tumor necrosis factor (TNF) (Akira and Takeda, 2004;Takeda et al., 2003). The first evidence of the involvement of chromatin remodeling in LPS-induced gene expression dates back to 1999, when it was observed that nucleosome remodeling appears to contribute to the rapid induction of p40 subunit of IL-12 (IL-12p40). Upon activation by LPS, a positioned nucleosome, which spans the IL-12p40 gene promoter, is rapidly and selectively repositioned prior to initiation of transcription process (Weinmann et al., 1999). Further studies demonstrated that the nucleosome remodeling by LPS requires TLR4 signaling but is independent of c-Rel, one of the NF- κB subunits required for transcription of integrated Il-12p40 promoter (Weinmann et al., 2001). In the year 2000, Saccani and colleagues (Saccani et al., 2002) revealed that upon LPS stimulation, H3 phosphorylation at serine 10 (H3S10) occurs selectively on the IL-12p40 promoter as well as promoters of a subset of other NF-κB-responsive proinflammatory genes such as IL-6, IL-8, and CC-chemokine ligand 2 (CCL2) but not TNF-α, MIP-1α and CCL3. This phosphorylation event was shown to be dependent on the activation of p38 MAPK signaling pathway by LPS, and specific inhibition of p38 activation blocks H3S10 phosphorylation, recruitment of NF-κB to the selective promoters and gene expression (Saccani et al., 2002). Therefore, it is postulated that phosphorylation of H3S10 via the p38 MAPK signaling pathway promotes the loosening of chromatin at certain selective promoters, thereby permitting accessibility to NF-κB and allowing transcription to occur. There are some evidence that link H3S10 mark with transcriptional activation. Serine to alanine substitution at position 10 of H3 or deletion of Snf1, a histone H3 kinase which phosphorylates the serine 10, abrogates transcriptional activation of LPS- inducible genes (Lo et al., 2001;Lo et al., 2000).
LPS activates TLR-dependent signaling to produce inflammatory cytokines and chemokines, which contribute to the efficient control and clearance of invading pathogens. However, production of these inflammatory mediators is tightly regulated because excessive production results in amplified inflammatory response and fatal illness characteristic of severe septic shock. Therefore, the host has readily available mechanisms in place which allow to dampen the response to LPS or even confer unresponsiveness to successive stimuli with LPS, a phenomenon named LPS or endotoxin tolerance (Cavaillon and Adib-Conquy, 2006;Cavaillon et al., 2003). The mechanisms underlying endotoxin tolerance are not completely understood, but are characterized by impaired TLR-mediated activation of both NF-κB- and MAPK-dependent genes (Adib-Conquy et al., 2006;Adib-Conquy et al., 2000). Endotoxin tolerance has been shown to be associated with chromatin remodeling in the promoter regions of several tolerizable genes (Chan et al., 2005;El et al., 2007). Chang and colleagues have demonstrated that chromatin remodeling and NF-κB p65 recruitment at the IL-1β gene promoter are altered in LPS-tolerant THP-1 cells, when compared to normal THP-1 cells (Chan et al., 2005). Upon LPS treatment, increased phosphorylation of H3S10 and demethylation of H3K9 are observed in normal THP-1 cells, which represent an “open” chromatin state; however, these modifications are impaired in LPS-tolerant cells. Concomitantly, recruitment of NF- κB p65 but not NF- κB p50 to the IL-1 gene promoter is impaired in LPS-tolerant cells despite that the activation and nuclear accumulation of NF- κB is not changed. Similar histone modifications and NF- κB binding were also observed at the TNF-α promoter during endotoxin tolerance (El et al., 2007). Interestingly, LPS tolerance negatively regulates expression of proinflammatory mediators without affecting antimicrobial effectors. Using microarrays and real-time PCR, Foster and colleagues (Foster et al., 2007) identified two classes of genes based on their responsiveness to re-stimulation with LPS: so called tolerizable genes, which include proinflammatory mediators, and non-tolerizable genes, which include antimicrobial effectors. Induction of tolerance to LPS inhibits expression of the proinflammatory genes, while the other group of genes remain inducible. Both classes of gene promoters show H4 acetylation and H3K4 tri-methylation, which mark an “open” chromatin state, upon initial stimulation with LPS; however, this kind of “open” chromatin state and recruitment of Brg1 are lost in tolerizable genes upon LPS re-stimulation. In contrast, these epigenetic marks are maintained in the genes that remain inducible. Aung and colleagues reported that HDACs are transiently repressed then induced to express in murine bone marrow-derived macrophages when treated with LPS. HDACs are recruited to different gene promoters to regulate the expression of the latter.
3.2. Manipulation of host chromatin remodelling process by bacteria to facilitate infection
Interestingly, intracellular pathogens, such as Listeria monocytogenes, Shigella flexneri, and Helicobacter pylori, affecting the expression of host defense gene via modulation of chromatin structure has also been reported in recent years. Listeria monocytogenes is a gram positive bacterium that causes listeriosis. Two different mechanisms have been reported to be used by L. monocytogenes to modify histones during the course of infection. In endothelial cells, L. monocytogenes has been shown to selectively induce serine 10 phosphorylation and lysine 14 acetylation of H3 and lysine 8 acetylation of H4 at the IL-8 but not the Interferon-γ (IFN-γ) gene promoter through the activation of p38 and ERK MAPK pathway. A subsequent study showed that activation of p38 MAPK signaling pathway and NF-κB by L. monocytogenes depends on nucleotide-binding oligomerization domain-containing protein 1 (NOD1 ). NOD1 is critical for L. monocytogenes induced secretion of IL-8. Interestingly, only invasive bacteria which can enter into the host cell cytoplasm induce IL-8 production in endothelial cells (Opitz et al., 2006). In another study, L. monocytogenes has been found to induce a dramatic H3 dephosphorylation at serine 10 (H3S10) as well as a deacetylation of H4 during early phase of infection (Hamon et al., 2007). In contrast to the report described as above, entry of bacteria into the host cells is not required for these histone modifications. The LLO released by L. monocytogenes is a member of CDC (cholesterol-dependent cytolysin) toxin family, which is identified as a major effector sufficient for induction of H3S10 dephosphorylation and H4 deacetylation. LLO –induced H3S10 dephosphorylation specifically occurs in the case of genes whose expression is regulated by LLO, a number of which are involved in immunity. Interestingly, other members of the large family of CDC toxins, such as PFO and PLY secreted by Clostridium perfringens and Streptococcus pneumonia, respectively, dephosphorylate H3S10 through a mechanism analogous to that of LLO (Hamon et al., 2007), suggesting that different bacteria may subvert immune response through a similar mechanism.
Shigella flexneri is a human intestinal pathogen, causing dysentery by invading the epithelium of the colon and is responsible, worldwide, for more than one million deaths per year. Arbibe and colleagues have shown that S. flexneri infection abrogates phosphorylation of H3S10 at the promoters of a specific subset of genes, such as IL-8 and CCL-20. The underlying mechanism is that the type III effector protein, OspF, secreted by S. flexneri enters into the nucleus and specifically dephosphorylates ERK and p38 MAPKs and then blocks MAPK-dependent phosphorylation of H3S10. This occurs in a gene-selective way, and renders selected gene promoter sites inaccessible to NF-κB, thereby reducing the expression of a subset of NF-κB-responsive genes, including IL8 (Arbibe et al., 2007). This specificity might be a consequence of OspF’s ability to inactivate MAPKs, thereby preventing them from entering into nucleus. Once activated, MAPKs translocate into nucleus and are recruited to the chromatin covering their target genes, where they regulate the phosphorylation of transcription factors, histones and chromatin-remodeling enzymes (Chow and Davis, 2006). It has been shown that OspF–induced down-regulation of inflammatory response is accomplished through the interaction of OspF with host retinoblastoma (Rb) protein, which has been linked to histone modification (Zurawski et al., 2009). OspF also has the phosphothreonine lyase activity, a unique activity that has been found in a family of conserved effectors secreted by type III secretion system including OspF, SpvC from nontyphoid Salmonella species, and HopAI1 from the plant pathogen Pseudomonas syringae (Kramer et al., 2007;Li et al., 2007b;Zhang et al., 2007). These effectors specifically inactivate their host MAPK pathway by carrying out a β elimination reaction to irreversibly remove the phosphate moiety from the phosphothreonine in phosphorylated MAPKs. Inhibition of MAPK signaling by OspF attenuates the recruitment of polymorphonuclear leukocytes to Shigella infection sites by suppressing the activation of a portion of NF-κB-responsive genes in mice (Arbibe et al., 2007), thereby contributing to the survival and persistent infection of the pathogens.
Helicobacter pylori is a Gram-negative bacterium that colonizes the human gastric mucosa. The chronic infection generates a state of inflammation which may develop toward chronic gastritis, peptic ulcers and gastric malignancies (Peek, Jr. and Crabtree, 2006). The virulence factors of Helicobacter pylori have been suggested to play a crucial role in the development of inflammation and in affecting the host immune system (Gebert et al., 2003;Lu et al., 2005). For example, in mouse macrophage, H. pylori peptidyl prolyl cis-, trans-isomerase (HP0175) has been shown to induce H3S10 phosphorylation at the IL-6 promoter resulting in increased IL-6 gene transcription and protein expression (Pathak et al., 2006). HP0175-induced IL-6 gene transcription is dependent on the TLR4 –dependent activation of ERK and p38 MAPKs, which subsequently activate mitogen- and stress-activated protein kinase 1 (MSK1), a serine kinase responsible for H3S10 phosphorylation. This modification allows for recruitment of NF-κB to the IL-6 promoter and activation of gene transactivation. Interestingly, H. pylori infection has also been shown to dephosphorylate H3S10 and deacetylate H3K23 in a time- and dose- dependent manner in gastric epithelial cells (Ding et al., 2010). Therefore, the effect of a specific histone modification in host cells appears to be cell type specific and gene promoter specific. Further studies demonstrate that cag pathogenicity island (PAI) is responsible for the dephosphorylation of H3S10 and this modification is independent of ERK and p38 signaling pathways as well as IFN signaling. In addition, H3S10 dephosphorylation is associated with changes in the host gene expression, which contributes to bacterial infection and pathogenesis (Ding et al., 2010). Treatment of gastric epithelial cells with TSA, a general inhibitor of HDACs which non-specifically increases histone H3 and H4 acetylation at multiple sites results in altered gene transcription pattern in both IL-8 and c-fos genes upon H. pylori infection. TSA reduces IL-8 but increases c-fos gene transcription in the presence of H. pylori infection (Ding et al., 2010). H. pylori has also been shown to regulate the cell cycle controlled protein p21(WAF), which is associated with the release of HDAC-1from the promoter and histone H4 acetylation (Xia et al., 2008).
4. Chromatin remodeling and IFN-γ-induced transcriptional response
IFN-γ is a cytokine secreted by activated T cells and natural killer cells. IFN-γ can induce expression of the major histocompatibility complex class II (MHC-II) on the cell surface (Boehm et al., 1997), which presents antigens to CD4+ T cells and plays a crucial role in normal immune response. IFN-γ activates gene expression mainly via the activation of JAK (Janus tyrosine kinase)/STATI (signal transducer and activator of transcription) signaling pathway, leading to the translocation of active STAT1 homodimers into the nucleus. The STAT1 homodimers then bind to the IFN-γ -activated sites (GAS) present in the promoters of IFN-γ -responsive genes thereby mediating the transcription of these genes, including class II transactivator (CIITA), which is necessary for both constitutive and inducible expression of MHC-II (Schroder et al., 2004).
Chromatin remodeling, mediated by ATP-dependent chromatin remodeling complex and or histone-modifying enzymes, has also been shown to be involved in the activation of IFN-γ -responsive genes, such as CIITA and HLA-DR (Ni et al., 2005;Pattenden et al., 2002;Zika et al., 2003). SWI/SNF complex often cooperates with histone-modifying enzymes to regulate transcription of genes, including those which are induced by IFN-γ (Chi, 2004;Wright and Ting, 2006). Studies have demonstrated that the SWI/SNF complex and CREB-binding protein (CBP), a transcriptional co-activator with histone acetyltransferase activity, are recruited to CIITA promoter in an IFN-γ-inducible fashion, leading to transcriptional activation of CIITA (Kretsovali et al., 1998;Pattenden et al., 2002). HLA-DR is a MHC–II surface molecule whose transcriptional activation is tightly associated with CIITA. However, forced expression of CIITA in BRG1- and BRM-deficient SW13 cells cannot activate expression of the MHC-II genes (Mudhasani and Fontes, 2002). BRG1 or BRM represent the catalytic subunit of mammalian SWI/SNF chromatin remodeling complex, suggesting that the SWI/SNF complex, which contains BRG1 might play additional roles in MHC-II expression. Further studies have indicated that BRG1 is recruited by CIITA to the MHC-II gene promoters and this recruitment is essential for activation of MHC-II gene expression (Mudhasani and Fontes, 2002). Interestingly, CIITA itself has intrinsic HAT activity, which can bind not onlyBRG1 but also HATs, such as CBP and/or p300 (Ting and Trowsdale, 2002). Furthermore, CIITA is associated with increased acetylation modifications of H3 and H4 at MHC-II promoter mediated directly through its intrinsic HAT activity or by the recruitment of HATs, such as CBP (Beresford and Boss, 2001;Kretsovali et al., 1998). IFN-γ induced transactivation of CIITA and expression of MHC-II is inhibited by HDACs/mSin3A corepressor complex whereas enhanced by TSA, a general inhibitor of HDAC. Co-immunoprecipitation assay revealed that CIITA interacts strongly with HDAC1 and weakly with HDAC2 (Zika et al., 2003). All these data suggest that CIITA may act as a modulator to coordinate functions of chromatin remodeling complex, HATs and HDACs.
In the context of host-pathogen interaction, intracellular pathogens have been shown to subvert the host immune response by affecting the macrophage responsiveness to IFN-γ but the underlying mechanism remains unclear. Intracellular pathogens may affect IFN-γ response via different ways. For example, Leishamania donovani inhibited IFN-γ response through down-regulation of IFN-γ receptor expression or interfering with the JAK/STAT1 signaling pathway (Nandan and Reiner, 1995;Ray et al., 2000). By contrast, mycobacteria such as Mycobacterium avium and Mycobacterium tuberculosis impair IFN-γ response through inhibition of IFN-γ -responsive gene expression without interfering with the JAK/STAT1 signaling pathway (Kincaid EZ, J Immunol, 2003, 171:2042-2049). Interestingly, only a subset of IFN-γ responsive genes get affected, including CIITA, HLA-DR and CD64, while others remained unaffected (Pennini et al., 2006;Wang et al., 2005). Further studies showed that infection with M. tuberculosis affects the chromatin remodeling on CIITA gene since IFN-γ -induced histone acetylation and recruitment of BRG1 were both impaired (Pennini et al., 2006). Additionally, LpqH, a mycobacterial cell wall protein, induces binding of the C/EBP transcriptional repressor to the CIITA promoter and inhibits IFN-γ -induced CIITA transcription (Pennini et al., 2007). It has been shown that C/EBP can recruit HDAC-1-containing transcriptional repressor complex to the promoter of peroxisome proliferator-activated receptor beta thereby inhibiting its transcription (Di-Poi et al., 2005). Therefore, M. tuberculosis might induce the recruitment of C/EBP resulting in transcriptional repression. The exact molecular mechanism by which M. tuberculosis inhibits IFN-γ -induced CIITA transcription remains to be elucidated. Similarly to CIITA, IFN-γ -induced histone acetylation gets impaired at the HLA-DR promoter and HLA-DR transcription becomes inhibited when the cells get infected with M. tuberculosis. Furthermore, inhibition of HDAC activities rescues histone acetylation, suggesting a role of HDACs in the transcriptional repression induced by M. tuberculosis (Wang et al., 2005). Indeed, Mycobacterial infection increases the expression of mSin3A (a co-repressor associated HDACs), enabling competition with CBP for binding to the HLA-DR promoter.
A recent study has demonstrated that infection with Toxoplasma gondii renders murine macrophages globally unresponsive to IFN-γ stimulation without affecting the nuclear translocation of STAT1 triggered by IFN-γ in infected macrophages. However, the binding of STAT1 to the STAT1-responsive promoters is aberrant. A number of genes, which were induced by IFN-γ in uninfected macrophages, were not induced in the T. gondii-infected cells. Among them, there are several genes previously shown to be repressed by T. gondii, such as CIITA, MHC class II molecule H2-Eα, and interferon- regulatory factor 1(IRF-1) (Lang et al., 2012). By analyzing the underlying mechanism, the authors revealed that assembly of chromatin remodeling complex and histone acetylation at the IFN-γ -responsive promoters are impaired upon infection with T. gondii. Treatment with HADC inhibitor restores the responsiveness of T. gondii-infected macrophages to IFN-γ, leading to an increase in the expression of IFN-γ-inducible genes, such as CIITA and H2-A/E.
5. The potential role of HDAC inhibitors in treatment of infection
HDAC inhibitors have been developed clinically for cancer therapy due to their abilities to induce cell-cycle arrest and apoptosis (Adcock, 2007). Studies have demonstrated that HDAC inhibitors can exert anti-inflammatory effects via the suppression of cytokine and nitric oxide production (Blanchard and Chipoy, 2005;Dinarello et al., 2011), suggesting their therapeutic potential in inflammatory diseases including infectious diseases. For example, HDAC inhibitors have been examined for the treatment of HIV infection and the current results are exciting and encouraging (Wightman et al., 2012). Couple of other studies have demonstrated that HDAC inhibitors, TSA and apicidin, can inhibit the growth of Plasmodium falciparum, the main parasite causing malaria in humans (Colletti et al., 2001a;Colletti et al., 2001b). Similarly, azelaic bishydroxamic acid and suberohydroxamic acid, two other HDAC inhibitors, also show anti-malarial activity against P. falciparum (Andrews et al., 2000). The potential of HDAC inhibitors as anti-bacterial agents has also been investigated; however, the results are contradictory.
5.1. Inhibition of infection by targeting histone modifying enzymes in the pathogen
Candida albicans is an opportunistic pathogen that is normally found in the gut microflora of healthy individuals; however, C. albicans can cause severe and life-threatening diseases in immuosuppressed patients such as HIV infected, organ transplant and cancer chemotherapy patients (Tzung et al., 2001). There is a very high rate of mortality from systemic candidiasis, ranging between 14 and 90% and averaging between 30 to 40%, depending on the disease group studied (Blot et al., 2003). For patients with Candida infections, antifungal drug resistance is a major clinical problem. H3K56 acetylation is mediated by HAT Rtt109 and seems to be much more abundant in yeasts than in mammals (Garcia et al., 2007a;Xie et al., 2009), and close homologues of Rtt109 have not yet been detected in mammals (Bazan, 2008). Therefore, it is expected that Rtt109 might be a unique target for antifungal therapeutics. Indeed, Wurtele and colleagues demonstrated that modulation of the acetylation of H3K56 exhibits potential as an anti-fungal therapy (Wurtele et al., 2010). Interestingly, similar results have been found in a study by Lopes da Rosa et al (Lopes da et al., 2010). Wurtele and colleagues showed that deleting Rtt109, an acetyltransferase of H3K56, leads to increased sensitivity to some anti-fungal drugs. Both teams also demonstrated that Rtt109 mutants are considerably less virulent in a mouse model infected with C.albicans. Wurtele and colleagues further investigated how the growth of C. albicans is affected by chemical modification of H3 in vitro and in vivo. They have observed that the growth of C. albicans is greatly inhibited when HST3, the H3 deacetylase acting on lysine 56, is inhibited by nicotinamide (a form of Vitamin B3 and product of the NAD+-dependent deacetylation reaction). Furthermore, modulation of H3K56 acetylation reduces the virulence of wild-type C. albicans in mice when nicotinamide was given in the drinking water of mice to repress HST3 (Wurtele et al., 2010). These results, together with the study by Lopes da Rosa and colleagues, provide basis for targeting H3 modifying enzymes to fight fungal infections. Although important catalytic residues in Rtt109 are much different from those in mammalian homologues, it is still a challenge to find suitable fungal-specific inhibitors of H3 modifying enzymes in the future.
5.2. Effects of HDAC inhibitors on host defense against bacterial infection
In a mouse model of septic shock induced by LPS, administration of of suberoylanilide hydroxamic acid (SAHA) (50mg/kg intraperitoneally), improves long-term survival rates of mice whether given before or post a lethal dose of LPS, which may be due to the down-regulation of MyD88-dependent pathway and decreased expression of proinflammatory mediators such as TNF-alpha, IL-1β, and IL-6 (Li et al., 2010;Li et al., 2009). Further studies demonstrated that treatment with SAHA increases anti-inflammatory IL-10 levels while decreasing proinflammatory IL-6 and MAP kinase production in the liver of septic shock mice (Finkelstein et al., 2010). In contrast, it has also been shown that treatment with HDAC inhibitors lead to impaired host defense against bacterial infections. Studies have shown that HDAC inhibitors, TSA, SAHA, and VPA, can impair innate immune responses to TLR agonists by down-regulating the expression of genes involved in microbial sensing, such as C-type lectins and adhesion molecules, as well as genes involved in host defense, such as cytokines and chemokines, thereby increasing susceptibility to infection (Roger et al., 2011). Interestingly, while LPS-induced IFN-β production is enhanced by HDAC inhibitors, the expression of a number of IFN-β /STAT1-dependent genes is strongly inhibited by TSA and VPA, suggesting that increased IFN-β production cannot overcome the potent inhibitory effects of HDAC inhibitors. Surprisingly, VPA was shown to increase the mortality of mice infected with C. albicans or K. pneumonia, but protect mice from toxic shock and severe sepsis in mouse models (Roger et al., 2011). When murine macrophages were treated with TSA and VPA, their ability to kill Escherichia coli and Staphyloccocus aureus was attenuated, with impaired phagocytosis and production of reactive oxygen and nitrogen species (Mombelli et al., 2011). Together, these data reveal the complex effector mechanisms of HDAC inhibitors and suggest that more studies are required to fully understand this complex process.
6. Concluding remarks
The activation and suppression of innate immunity are central principles of host-pathogen interaction and need to be very well controlled. To establish persistent infection, intracellular pathogens must acquire efficient mechanisms to evade the host immune response. Interference with host posttranscriptional modifications by bacterial pathogens is a strategy widely used by the pathogens to promote survival and replication during the course of infection. MAPK, IFN-γ and transcription factor NF-κB signaling pathways are common targets for bacteria-induced posttranscriptional modifications (Ribet and Cossart, 2010). Interestingly, in the past few years, evidence has accumulated that targeting of histone modifications and chromatin remodeling, and subsequently subverting the host immune response, is a new and exciting field in the study of host-pathogen interaction. Phosphorylation of H3 and acetylation of H3 and/or H4 at lysine residues are frequently associated with transactivation. Conversely, dephosphorylation and methylation of histones are more often associated with gene suppression (Berger, 2002;Kouzarides, 2007;Verdone et al., 2006). Several strains of bacteria, including L. monocytogenes, C. perfringens, S. pneumonia and H. pylori, induce the same dephosphorylation of H3S10, while S. flexneri blocks phosphorylation of H3S10; all of which lead to decreased phosphorylation of H3S10 and are associated with altered host immune response.
The molecular mechanisms by which bacterial infection induces histone modification and chromatin remodeling remain to be understood. For many pathogens, it is very difficult to hypothesize about the extent or the mechanics of epigenetic change they might induce. Currently available data largely provide snapshots of what is happening to the usual host genes studied in an infection model. More comprehensive global studies, such as ChIP-on–chip (chromatin immunoprecipitation coupled with expression microarray technology) for mapping global chromatin modifications, are now necessary and possible. This might provide fundamental clues to better understand the role and mechanism of chromatin regulation in the control of immune gene expression in inflammatory and infectious diseases.
\n',keywords:null,chapterPDFUrl:"https://cdn.intechopen.com/pdfs/44218.pdf",chapterXML:"https://mts.intechopen.com/source/xml/44218.xml",downloadPdfUrl:"/chapter/pdf-download/44218",previewPdfUrl:"/chapter/pdf-preview/44218",totalDownloads:3081,totalViews:494,totalCrossrefCites:1,totalDimensionsCites:4,totalAltmetricsMentions:1,introChapter:null,impactScore:1,impactScorePercentile:54,impactScoreQuartile:3,hasAltmetrics:1,dateSubmitted:"June 27th 2012",dateReviewed:"January 25th 2013",datePrePublished:null,datePublished:"April 17th 2013",dateFinished:"April 15th 2013",readingETA:"0",abstract:null,reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/44218",risUrl:"/chapter/ris/44218",book:{id:"3536",slug:"chromatin-remodelling"},signatures:"Yong Zhong Xu, Cynthia Kanagaratham and Danuta Radzioch",authors:[{id:"105594",title:"Prof.",name:"Danuta",middleName:null,surname:"Radzioch",fullName:"Danuta Radzioch",slug:"danuta-radzioch",email:"danuta.radzioch@mcgill.ca",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"McGill University",institutionURL:null,country:{name:"Canada"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Chromatin structure in transcription regulation",level:"1"},{id:"sec_2_2",title:"2.1. Histone modifications and transcription",level:"2"},{id:"sec_3_2",title:"2.2. Chromatin remodelling complex and transcription",level:"2"},{id:"sec_5",title:"3. The role of chromatin remodelling in the regulation of inflammatory gene expression",level:"1"},{id:"sec_5_2",title:"3.1. LPS-induced chromatin modification and target gene expression",level:"2"},{id:"sec_6_2",title:"3.2. Manipulation of host chromatin remodelling process by bacteria to facilitate infection",level:"2"},{id:"sec_8",title:"4. Chromatin remodeling and IFN-γ-induced transcriptional response ",level:"1"},{id:"sec_9",title:"5. The potential role of HDAC inhibitors in treatment of infection",level:"1"},{id:"sec_9_2",title:"5.1. Inhibition of infection by targeting histone modifying enzymes in the pathogen",level:"2"},{id:"sec_10_2",title:"5.2. Effects of HDAC inhibitors on host defense against bacterial infection ",level:"2"},{id:"sec_12",title:"6. Concluding remarks",level:"1"}],chapterReferences:[{id:"B1",body:'AaslandRStewartA. Fand GibsonT1996The SANT domain: a putative DNA-binding domain in the SWI-SNF and ADA complexes, the transcriptional co-repressor N-CoR and TFIIIB. Trends Biochem. Sci. 218788'},{id:"B2",body:'AdcockI. M2007HDAC inhibitors as anti-inflammatory agents. Br. J. Pharmacol. 150829831'},{id:"B3",body:'Adib-conquyMAdrieCFittingCGattolliatOBeyaertRand CavaillonJ. M2006Up-regulation of MyD88s and SIGIRR, molecules inhibiting Toll-like receptor signaling, in monocytes from septic patients. Crit Care Med. 3423772385'},{id:"B4",body:'Adib-conquyMAdrieCMoinePAsehnouneKFittingCPinskyM. RDhainautJ. Fand CavaillonJ. M2000NF-kappaB expression in mononuclear cells of patients with sepsis resembles that observed in lipopolysaccharide tolerance. Am. J. Respir. 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Department of Medicine, McGill University, Montreal, Canada
Department of Medicine, McGill University, Montreal, Canada
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1. Introduction
The first account of giant cell arteritis (GCA) can be traced back to tenth-century Baghdad by Arab ophthalmologist of medieval Islam Ali ibn Isa al-Kahhal. It was then more precisely described by Sir Jonathan Hutchinson in 1890, who noted the peculiar thrombotic appearance of the temporal artery (TA), a defining feature of the course of GCA. With the progression of the discovery of this disease and various case studies exploring its nature, ophthalmologists have additionally attempted to view how GCA could affect certain populations. During the second half of the twentieth century and the course of the twenty-first century, facilities across continents have published their findings on the tendencies of GCA to affect certain individuals more than others. In this chapter, we describe the epidemiology of GCA across continents and countries from individual reports and studies presenting the incidence rate of this vasculitis in their respective locations or populations.
2. Europe
Europe remains the continent with the most abundant publications pertaining to the epidemiology of GCA. One of the longest studies on the epidemiology of GCA was conducted in Western Norway, a retrospective study encompassing cases from 1972 to 2012 [1]. This study was one among many that noted how changing the criteria for the identification of GCA could greatly alter its incidence, especially due to the rarity of this vasculitis. For instance, the incidence rate of patients potentially affected by GCA satisfying the ACR 1990 criteria was 16.7 per 100,000 persons over 50 years of age. The incidence of patients clinically diagnosed as having GCA was 18.4 per 100,000 persons aged 50 years or more. Meanwhile, the incidence of biopsy-proven GCA was 11.2 per 100,000 persons over 50 years of age. The extended period of this study additionally contributed to the lowering of the mean annual incidence. When solely evaluating cases during a certain 5-year period (from 1992 to 1996), the incidence rate was found to be 26.7 per 100,000 persons over 50 years of age. Regardless of this, the prevalence remained among the highest recorded globally. This study also describes the increasing GCA incidence with age, where an older individual has a greater susceptibility to acquiring this vasculitis, as well as a greater ratio of women having this disease. Similarly, in the southern region of Norway, comparisons with past records from the same set of population were provided [24]. In a study spanning a period of 14 years (2000–2013), the Hospital of Southern Norway presented a GCA occurrence rate of 16.8 per 100,000 persons over the age of 50 years, one of the highest recorded globally and in line with other epidemiological findings from the Scandinavian region. As previously noted, one must consider that a small study sample and a short study period both have the potential of overestimating the incidence of a disease, as demonstrated by this study. In the same vicinity, the rate of giant cell arteritis in Western Nyland, Finland was examined [2]. From 1984 and 1988, 54 patients were diagnosed with GCA, among which 16 patients had a positive biopsy. The retrospective annual incidence of GCA was 69.8 for every 100,000 individuals older than 50 years. From 1984 to 1990, 133 patients in Iceland fulfilling the ACR criteria for GCA were identified, rendering an incidence rate of 27 in 100,000 people older than 50 years [3]. This study also suggests that the clinicians’ greater tendency to suspect GCA and perform TA biopsies (TABs) may have contributed to a higher statistical incidence. The results of these studies and their reported high mean annual incidence rates go on to highlight the possibility of a greater susceptibility to GCA among Scandinavian population. These are among the highest globally, supporting the claim that the Scandinavian population is most considerably afflicted by this inflammatory disease.
When gauging the incidence of GCA cases in other parts of Europe, we witness a lowering in the number of cases. For instance, in Italy, 285 cases of biopsy-proven GCA were observed in the Reggio Emilia area from 1986 to 2012 [4]. The adjusted incidence rate was 5.8 per 100,000 people older than 50 years of age and was significantly greater in women. In Lugo, Spain, a retrospective study was conducted from 1986 to 1995 to identify the occurrence rate of biopsy-proven GCA [5]. The mean annual incidence was computed for each 5-year period, rendering a rate of 8.26 and 10.49 per 100,000 people older than 50 years, respectively. Nearby countries and regions in the southern part of Europe presented similar incidence rates, demonstrating the moderate tendency of individuals from this area of the continent of being acquiring GCA. Namely, the incidence rate in France was concluded to be between 7 and 10 individuals out of 100,000 older than 50 years [6]. Likewise, in Slovenia, the estimated annual incidence rates of GCA were overall 8.7 per 100,000 aged greater than 50 years. This lowered rate suggests a different ethnical make up in the region that is perhaps less susceptible to acquiring this vasculitis, suggesting a genetic factor, while the geographical location in a lower latitude than the Scandinavian region may imply an environmental etiology. The exact etiology remains unknown.
Epidemiological studies from 2002 to 2008 in Southern Europe and Northwestern Turkey aimed to assess the epidemiology of GCA by following patients at Trakya University Medical Faculty [7]. During this period, the incidence of GCA was found to be 1.13 patients per 100,000 persons 50 years of age or older. The incidence of GCA for females was slightly greater than that for males. The fact that this study relied on a single center presents the possibility of missing individuals who sought care in a different location or simply neglected their condition. Regardless of this, the contribution of this report is crucial due to the paucity of epidemiological outlook on GCA in this space.
3. Asia
A retrospective study of patients with giant cell arteritis in China was performed from August 1992 to May 2014 at the Peking Union Medical College Hospital [8]. A total of 70 patients were diagnosed with GCA. The demographic data of these patients differed from that in the previously discussed epidemiological studies in Europe. First, the average age of Chinese GCA patients was 65.2 years. This age at onset is lower than the mean reported age in other populations, which hovered between 70 and 80 years. In addition, male patients with GCA predominated the study, which differed from most reports globally. Chinese male may be more susceptible to GCA than female or they may present greater health-seeking behavior. It is important to note that patients in this study were identified from a single healthcare center, which may substantially underestimate the occurrence of this vasculitis despite its current rare occurrence. On a similar note, statistical records, pathology records, and case records from university hospitals were gathered to estimate an annual incidence of one out of 100,000 people aged older than 50 years in Hong Kong [9]. These findings suggest the particularly lower frequency of GCA among the Chinese population. In 1998, a nationwide survey was performed in Japan, revealing 690 patients treated for GCA in the previous year [10]. An incidence rate of the population was calculated to be 1.47 per 100,000 people older than 50 years of age. In conclusion, the epidemiological reports of GCA from East Asian countries reveal extremely low prevalence of GCA among this population.
From 2008 to 2014, a total of 17 patients fulfilling the classification criteria for GCA in India were identified [11]. Comparably to a previously discussed study in China, the mean age of GCA patients in the Indian population was 67 years, lower than the mean age from European reports. In addition, individuals with GCA in India were predominately male. The reasoning behind a lower mean age and a male predominant patient status is unknown and was hypothesized to be due to the greater likelihood of individuals with these characteristics to seek healthcare.
The rarity of GCA among the Indian population was demonstrated at Moorfields Eye Hospital, a center in London, UK [12]. From 2006 to 2014, patients of Indian descendance were significantly less likely to have a biopsy-positive GCA. Perhaps, some ethnicities are less likely to present a positive result to the TA biopsy or clinicians may simply be more likely to diagnose these individuals with GCA. A study of this nature, in which ethnicities are compared in a population, could provide important findings on the vulnerability of certain individuals to present with this vasculitis Figures 1 and 2.
Figure 1.
A temporal artery biopsy involves acquiring a small section of the artery, which can potentially appear thrombotic. The length of the segment can vary across studies and may influence the results of the biopsy [13].
Figure 2.
Graphical representation of incidence rates of GCA among some of the populations described in the literature. The highest incidence rates appear to be among the Scandinavian countries, regardless of the criteria utilized to diagnosis the incidence of GCA.
4. Middle east
The true incidence of GCA in the Arab population is difficult to assess due to the absence of a more nationwide perspective as well as a lack of population-based study in Arab countries. In a 22-year study, the epidemiology of GCA in Saudi Arabia was investigated [13]. From 1983 to 2004, 102 patients at King Khaled Eye Specialist Hospital underwent TAB, as seen in Figure 1, and seven patients were identified with biopsy-proven GCA. They noted that the incidence of GCA increases with age. Regardless of this, many aspects of the healthcare system in Saudi Arabia closely resemble that of the United States, with a similar life expectancy and a ratio of ophthalmologists relative to the size of the population.
In 1980, the incidence of giant cell arteritis in Jerusalem over a 25-year period was evaluated in a study involving four general hospitals in Jerusalem [14]. Among them, 170 patients with GCA had a positive TA biopsy. Furthermore, 36 biopsy-negative cases were also considered as they fulfilled the 1990 ACR criteria for GCA classification and responded adequately to steroid therapy. The age-adjusted incidence rate was computed to be 11.3 per 100,000 people ≥50 years of age for all incorporated GCA cases, but lower at 9.5 for the biopsy-proven cases. Moreover, this study observed seasonal patterns with a statistically insignificant rise in GCA diagnosis during the summer. The incidence rate of GCA in this study is comparable with those in other Mediterranean countries, with a less prominent frequency of female patients.
The results of a cohort of 114 patients who met the 2016 rACR criteria for the diagnosis of GCA and underwent TAB over a 10-year period in a tertiary center, Rassoul Akram Hospital, in Tehran, Iran were described [15]. This finding reflects the increase in GCA incidence with age. Although this study did not sufficiently provided a macroscopic account of the incidence and manifestation of GCA in a population, it was the first study performed in Iran assessing the intricacies of characterizing GCA and the discrepancies that may arise as a result of heterogeneous studies, especially due to the absence of definite criteria for the diagnosis of GCA.
5. Africa
Africa stands out for its scarcity of information on GCA and its epidemiology. Perhaps, this could be due to an underdeveloped healthcare system, which hinders the proper equipment and tools for an adequate diagnosis, which could ultimately serve as data to be studied on a larger scale. It may also be that the African population has a lower susceptibility to GCA. In addition, the life expectancy in Africa is lower, which could influence statistics related to a disease with an increased likelihood of manifesting at a later stage in life. Therefore, it can be hypothesized that this region presents with lower rates of this vasculitis. The two studies discussing the epidemiology of GCA in the African population both pertain to French-colonized islands. From 1991 to 2016, data from two pathology units in Martinique, West Indies were reviewed to discuss the features of cases of biopsy-proven giant cell arteritis [16]. The findings fortified the assumption that GCA is less prevalent in an African descent population. Nevertheless, the retrospective nature of the study and the exclusion of a biopsy-negative GCA may have led to an underestimation of cases of GCA.
In a retrospective study from La Reunion near the Southwest region of the Indian Ocean from 2005 to 2017, an incidence rate roughly 4–12 times lower than in most European countries was calculated [17]. An exact count was difficult to provide due to the presence of a diverse group of ethnicities in La Reunion, especially from regions of the world with a lower prevalence of GCA. A shorter life expectancy may contribute to a lower frequency of cases observed as GCA increases with age. Other characteristics were found to be analogous observations made in previous epidemiological studies.
6. North America
Studies conducted in the United States have the potential of presenting important findings due to the possibility of comparing and contrasting features of a disease between ethnicities. A retrospective study spanning 11 years was conducted in the Texas Gulf Coast. Twenty-seven out of 101,239 patients aged 40 years or older had GCA. Intriguingly, 13 of these patients were black females, rendering it a noteworthy aspect of this study in which a significantly greater proportion of patients with GCA were black individuals [18].
A report from a study spanning from 1971 to 1980 in Shelby County, Tennessee identified 26 cases of GCA [19]. The average annual incidence was computed to be 1.58 per 100,000 individuals older than 50 years of age. The predominant patient from this study was white and female. This study presents one of the lowest frequencies of GCA cases across the globe. This could partially be due to the racial makeup of this population, which has a high percentage of black residents. African descent population is assumed to present a lower incidence rate of GCA. Among other contributions to a low incidence rate such as a retrospective design as well as inconsistencies in the diagnosis criteria, this study urged the need to consider environmental factors as potential causes for the onset of the vasculitis, such as the climate, exposure to the sun, frequency of rainfall, elevation, etc.
In another region of the United States, Olmsted County, Minnesota holds a population with northern European ancestry, which appears to be the group of people most severely afflicted by GCA. Therefore, the observation of a greater incidence rate may indicate a genetic factor in the onset of GCA. Between 1950 and 1991, 125 Olmsted County inhabitants were diagnosed with giant cell arteritis. The incidence per 100,000 persons 50 years of age or older was 17.8, which was significantly higher in women than in men. The incidence of GCA had increased to 19.8 from 2000 to 2009. The annual incidence rates substantially increased over the study period and with congregated cases of GCA, suggesting a regular cyclic pattern over time, which suggested the possibility of an infectious root for giant cell arteritis.
Previous studies suggested a low incidence of GCA in black patients, although conclusions were drawn from relatively small sample sizes. Nevertheless, the impression that GCA rarely impacts black individuals is generally assumed. Some reports have sought to compare GCA more directly between two races. A multicenter study involving 10 healthcare institutions was conducted to evaluate the presentation of GCA in African Americans [20]. An African American group of patients was compared with a cohort of Caucasian patients with a positive biopsy for ophthalmic GCA. Both the groups appeared to have a similar sex distribution, as around 70% of patients in both the cohorts were females. At Johns Hopkins Wilmer Eye Institute, findings notably challenging the commonly held belief that GCA is uncommon in African Americans were presented [21]. However, annual rates may not be directly calculated due to racial distributions in patients not reflecting that of the census population of the city of Baltimore, a detail that needs to be approached diligently prior to establishing conclusions. Furthermore, the screening and diagnosis process may differ among races and ethnicities due to physicians and clinicians holding preconceived perception of a greater prevalence in certain populations.
When comparing the rate of GCA between Caucasians and Asians, a significant lower occurrence rate of GCA in Asians was identified, which they computed to be 0.26–3.8 per 100,000 individuals older than 50 years of age, in parallel with studies from Asia [22]. The data for this study were collected from the University of California San Francisco computer database for patients from July 1989 to July 2006.
Similarly, giant cell arteritis has been reported to be very rare in Hispanics. From 1996 to 2002, patients with GCA at the Bascom Palmer Eye Institute were assessed [23]. Rates of a positive temporal artery biopsy were similar among Hispanic and non-Hispanic patients. Thirty-two patients with biopsy-proven GCA revealed similar mean age, symptoms, and final visual acuity between Hispanic and non-Hispanic cohorts. Hispanic and non-Hispanic cases are similarly impacted by the onset of giant cell arteritis.
A retrospective review was performed of all the biopsy-positive cases of giant cell arteritis presenting to a neuro-ophthalmology practice in Saskatoon, Saskatchewan [24]. Records of 141 consecutive patients who underwent temporal artery biopsy at the Saskatoon Eye Centre from July 1998 to June 2003 were reviewed. The average age of the biopsy-positive patients was 76.5 years, and the patients were 2.4 times more likely to be women. A total of 35 patients had a European ancestry, while two patients were of Aboriginal descent. The estimated incidence of GCA for Saskatoon was 9.4 per 100,000 for people over the age of 50 years. This study reveals the prospect of GCA to affect the people of Aboriginal descent despite a probable low incidence rate.
7. South America
Very few studies pertaining to the epidemiology of GCA have come from South American countries. One that most closely attempted to depict the status of GCA nationwide collected findings from three university hospitals in Brazil for patients with GCA between 2009 and 2010 [25]. This was, in fact, the first study addressing the features of GCA in Brazilian patients having the disease. Most GCA patients were Caucasians, while a few were of a combined European and Indigenous lineage. The Caucasian cohort was mostly of Portuguese, Italian, or Spanish ancestry. These suggested the possibility of asymptomatic manifestations, which may skew the epidemiological perspective of this disease.
8. Oceania
The last geographic region to be discussed is Oceania, which can be hypothesized to most closely resemble findings from Europe. From 1992 to July 2011, 314 cases of biopsy-proven GCA in South Australia were studied, in which the incidence for people over the age of 50 was 3.2 per 100,000 individuals [26]. Most characteristics of the disease were in line with observations described in studies from Europe, including a similar mean age and female predominance. Seasonal variations were additionally perceived, with a greater amount of diagnosis occurring during the summer season.
Cyclical variations were similarly noted in a study conducted in Otago, New Zealand. Records of 363 consecutive patients who underwent temporal artery biopsy at Dunedin Hospital between 1996 and 2005 were reviewed, with biopsy-proven GCA diagnosed in 70 patients. The mean annual incidence of GCA in Otago for people older than 50 years was 12.73 per 100,000 persons ≥50 years of age [26].
9. Conclusion
Nordic countries present the highest annual incidence rates of GCA. This vasculitis moderately affects southern European countries (Italy, Spain, France, etc.). The lowest incidence rates have been reported in East Asia. The diverse ethnical populations in countries such as United States lead to variations across regions, such as a higher incidence rate in the Northern states due to Scandinavian ancestry. Different ethnicities may present varying susceptibility because clinicians may exhibit different degree of suspicion with certain races, leading to influence on the number of biopsies performed and diagnosis made. In some regions, race and ethnicity is self-identified, which may reveal limited information on genetic background. Figure 2 reveals the varied incidence rate observed in different populations across the globe.
The incidence rate increases substantially with age and a greater ratio of patients are women in most regions, except for Asian countries. Whether female susceptibility is genuinely lower in that region or whether this discrepancy is due to different health-seeking behavior is unknown. Although seasonal and cyclic patterns were observed in a few studied and environmental factors were suggested, such influence remains inconclusive.
The definition of giant cell arteritis is inconsistent across literature, resulting in the inclusion of heterogeneous data during extensive review. Hence, there may be an over- or underestimation of statistical values. The criteria for the diagnosis of this disease substantially varied, with incidence rates presented based on biopsy-proven cases, ACR-criteria-fulfilling cases, or unspecified clinical diagnosis. Therefore, data may vary depending on which inclusion criteria were used.
Moreover, the technicality for biopsy-proven cases (length of the segment or threshold for diagnosis) may also alter the rate of incidence. In many reviews, the length of the arterial specimen remains unmentioned.
In 2016, an alteration to the list of criteria for a more comprehensive diagnosis of GCA was submitted. Furthermore, additional diagnostic tools have recently emerged, including the color Doppler ultrasound (CDUS), despite requiring extensive experience for utilization and a proper diagnosis. Other high-resolution magnetic resonance imaging technologies include magnetic resonance angiography (MRA), positron emission tomography (PET), computed tomography (CT), CT with angiography, and conventional MRA, which alternatively permit the visualization of the temporal artery. Although most reports attempted to thoroughly describe the equipment and tools for diagnosis, the heterogeneous approach across studies hinders appropriate comparisons, which may limit a precise epidemiological outlook of the disease in question.
Although this study repeatedly describes the rarity of GCA, it remains the most common vasculitis with severe consequences if remained untreated, ultimately resulting in permanent visual loss. Therefore, clinicians should remain diligent when coming across individuals presenting symptoms of the disease because an immediate course of action may greatly influence a person’s course of life and impact their well-being physiologically and psychologically.
\n',keywords:"giant cell arteritis, epidemiology, visual loss, temporal artery biopsy, incidence rate",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/82750.pdf",chapterXML:"https://mts.intechopen.com/source/xml/82750.xml",downloadPdfUrl:"/chapter/pdf-download/82750",previewPdfUrl:"/chapter/pdf-preview/82750",totalDownloads:8,totalViews:0,totalCrossrefCites:0,dateSubmitted:"September 5th 2021",dateReviewed:"May 11th 2022",datePrePublished:"July 19th 2022",datePublished:null,dateFinished:"July 19th 2022",readingETA:"0",abstract:"Giant cell arteritis (GCA) is a systemic vasculitis that affects medium-to-large-sized arteries, in which the inflammatory reaction destroys the artery wall with the fragmentation of the elastic lamina. Such phenomena can result in vision loss if not treated promptly. Other nonocular symptoms noted include GCA, headache, tenderness in the temporal area of the scalp, myalgias and arthralgias, fever, weight loss, and jaw claudication. Clinical suspicion is an essential pathway to the diagnosis of this disease. Thus, immediate Westergren sedimentation rate and C-reactive protein should be obtained. A temporal artery biopsy, however, remains the most definitive diagnostic tool. The incidence of GCA remarkably increases with each decade of age among those aged 50 years or over. Additionally, there have been notable differences among patients of different ethnicities. The epidemiological characteristics of GCA have been primarily researched in populations from the United States as well as several European countries with emphasis on the Caucasian population. In more recent years, a handful of studies have emerged from non-European countries regarding the epidemiology of GCA. The results of these findings are in parallel with previous observations, which presumed GCA to be more common in European and North American populations.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/82750",risUrl:"/chapter/ris/82750",signatures:"Arshia Riaz, Bushra I Goraya and Imtiaz A Chaudhry",book:{id:"10304",type:"book",title:"Giant-Cell Arteritis",subtitle:null,fullTitle:"Giant-Cell Arteritis",slug:null,publishedDate:null,bookSignature:"Dr. Imtiaz A. Chaudhry",coverURL:"https://cdn.intechopen.com/books/images_new/10304.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-83969-209-3",printIsbn:"978-1-83969-208-6",pdfIsbn:"978-1-83969-210-9",isAvailableForWebshopOrdering:!0,editors:[{id:"66603",title:"Dr.",name:"Imtiaz",middleName:"A.",surname:"Chaudhry",slug:"imtiaz-chaudhry",fullName:"Imtiaz Chaudhry"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Europe",level:"1"},{id:"sec_3",title:"3. Asia",level:"1"},{id:"sec_4",title:"4. Middle east",level:"1"},{id:"sec_5",title:"5. Africa",level:"1"},{id:"sec_6",title:"6. North America",level:"1"},{id:"sec_7",title:"7. South America",level:"1"},{id:"sec_8",title:"8. Oceania",level:"1"},{id:"sec_9",title:"9. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'Brekke LK, Diamantopoulos AP, Fevang BT, Aβmus J, Esperø E, Gjesdal CG. Incidence of giant cell arteritis in Western Norway 1972-2012: A retrospective cohort study [published correction appears in Arthritis Res Ther. 2018 Dec 7;20(1):271]. Arthritis Research & Therapy. 2017;19(1):278'},{id:"B2",body:'Franzén P, Sutinen S, von Knorring J. Giant cell arteritis and polymyalgia rheumatica in a region of Finland: An epidemiologic, clinical and pathologic study, 1984-1988. The Journal of Rheumatology. 1992;19(2):273-276'},{id:"B3",body:'Baldursson O, Steinsson K, Bjornsson J, Lie JT. Giant cell arteritis in Iceland. An epidemiologic and histopathologic analysis. Arthritis and Rheumatism. 1994;37(7):1007-1012'},{id:"B4",body:'Catanoso M, Macchioni P, Boiardi L, et al. Incidence, prevalence, and survival of biopsy-proven giant cell arteritis in northern italy during a 26-year period. Arthritis Care & Research (Hoboken). 2017;69(3):430-438'},{id:"B5",body:'Gonzalez-Gay MA, Miranda-Filloy JA, Lopez-Diaz MJ, Perez-Alvarez R, Gonzalez-Juanatey C, Sanchez-Andrade A, et al. Giant cell arteritis in northwestern Spain: A 25-year epidemiologic study. Medicine. 2007;86(2):61-68'},{id:"B6",body:'Mahr A, Belhassen M, Paccalin M, et al. Characteristics and management of giant cell arteritis in France: A study based on national health insurance claims data. Rheumatology (Oxford, England). 2020;59(1):120-128'},{id:"B7",body:'Pamuk ON, Dönmez S, Karahan B, Pamuk GE, Cakir N. Giant cell arteritis and polymyalgia rheumatica in northwestern Turkey: Clinical features and epidemiological data. Clinical and Experimental Rheumatology. 2009;27(5):830-833'},{id:"B8",body:'Sun F, Ma S, Zheng W, Tian X, Zeng X. A retrospective study of chinese patients with giant cell arteritis (GCA): Clinical features and factors associated with severe ischemic manifestations. Medicine (Baltimore). 2016;95(13):e3213'},{id:"B9",body:'Tam S, Wong TC. Temporal arteritis in Hong Kong. International Journal of Rheumatic Diseases. 2008;11:163-169'},{id:"B10",body:'Kobayashi S, Yano T, Matsumoto Y, et al. Clinical and epidemiologic analysis of giant cell (temporal) arteritis from a nationwide survey in 1998 in Japan: The first government-supported nationwide survey. Arthritis and Rheumatism. 2003;49(4):594-598'},{id:"B11",body:'Sharma A, Sagar V, Prakash M, et al. Giant cell arteritis in India: Report from a tertiary care center along with total published experience from India. Neurology India. 2015;63(5):681-686'},{id:"B12",body:'Tan N, Acheson J, Ali N. Giant cell arteritis in patients of Indian Subcontinental descent in the UK. Eye (London, England). 2019;33(3):459-463'},{id:"B13",body:'Chaudhry IA, Shamsi FA, Elzaridi E, Arat YO, Bosley TM, Riley FC. Epidemiology of giant-cell arteritis in an Arab population: A 22-year study. The British Journal of Ophthalmology. 2007;91(6):715-718'},{id:"B14",body:'Bas-Lando M, Breuer GS, Berkun Y, Mates M, Sonnenblick M, Nesher G. The incidence of giant cell arteritis in Jerusalem over a 25-year period: Annual and seasonal fluctuations. Clinical and Experimental Rheumatology. 2007;25(1 Suppl 44):S15-S17'},{id:"B15",body:'Aghdam KA, Sanjari MS, Manafi N, Khorramdel S, Alemzadeh SA, Navahi RAA. Temporal artery biopsy for diagnosing giant cell arteritis: A ten-year review. Journal of Ophthalmic and Vision Research. 2020;15(2):201-209'},{id:"B16",body:'Moinet F, Molinie V, Polomat K, Merle H, Blettery M, Brunier-Agot L, et al. Biopsy proven giant cell arteritis in african descent populations: Incidence and characteristics in martinique, French West Indies. Arthritis & Rhematology. 2017;69: 275-276 (suppl. 10)'},{id:"B17",body:'Richier Q , Deltombe T, Foucher A, et al. AB0694 Giant cell arteritis epidemiology in la reunion: A retrospective cases series. Annals of the Rheumatic Diseases. 2018;77:1489'},{id:"B18",body:'Gonzalez EB, Varner WT, Lisse JR, Daniels JC, Hokanson JA. Giant-cell arteritis in the southern United States. An 11-year retrospective study from the Texas Gulf Coast. Archives of Internal Medicine. 1989;149(7):1561-1565'},{id:"B19",body:'Smith CA, Fidler WJ, Pinals RS. The epidemiology of giant cell arteritis. Report of a ten-year study in Shelby County, Tennessee. Arthritis and Rheumatism. 1983;26(10):1214-1219'},{id:"B20",body:'Garrity ST, Pistilli M, Vaphiades MS, et al. Ophthalmic presentation of giant cell arteritis in African-Americans. Eye (London, England). 2017;31(1):113-118'},{id:"B21",body:'Gruener AM, Poostchi A, Carey AR, et al. Association of giant cell arteritis with race. JAMA Ophthalmology. 2019;137(10):1175-1179'},{id:"B22",body:'Pereira LS, Yoon MK, Hwang TN, Hong JE, Ray K, Porco T, et al. Giant cell arteritis in Asians: A comparative study. The British Journal of Ophthalmology. 2011;95(2):214-216'},{id:"B23",body:'Lam BL, Wirthlin RS, Gonzalez A, Dubovy SR, Feuer WJ. Giant cell arteritis among Hispanic Americans. American Journal of Ophthalmology. 2007;143(1):161-163'},{id:"B24",body:'Ramstead CL, Patel AD. Giant cell arteritis in a neuro-ophthalmology clinic in Saskatoon, 1998-2003. Canadian Journal of Ophthalmology. 2007;42(2):295-298'},{id:"B25",body:'Souza AW, Okamoto KY, Abrantes F, Schau B, Bacchiega AB, Shinjo SK. Giant cell arteritis: A multicenter observational study in Brazil. Clinics (São Paulo, Brazil). 2013;68(3):317-322'},{id:"B26",body:'Dunstan E, Lester SL, Rischmueller M, et al. Epidemiology of biopsy-proven giant cell arteritis in South Australia. Internal Medicine Journal. 2014;44(1):32-39'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Arshia Riaz",address:null,affiliation:'
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Indexing and listing across major repositories, see details ...
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Dissemination and Promotion
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The study of biological complexity is a new frontier that requires high-throughput molecular technology, high speed computer memory, new approaches to data analysis, and the integration of interdisciplinary skills.",book:{id:"7728",slug:"synthetic-biology-new-interdisciplinary-science",title:"Synthetic Biology",fullTitle:"Synthetic Biology - New Interdisciplinary Science"},signatures:"Karim Kadri",authors:[{id:"290766",title:"Dr.",name:"Kadri",middleName:null,surname:"Karim",slug:"kadri-karim",fullName:"Kadri Karim"}]},{id:"62059",title:"Types of HVAC Systems",slug:"types-of-hvac-systems",totalDownloads:12466,totalCrossrefCites:9,totalDimensionsCites:15,abstract:"HVAC systems are milestones of building mechanical systems that provide thermal comfort for occupants accompanied with indoor air quality. HVAC systems can be classified into central and local systems according to multiple zones, location, and distribution. 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Local systems include local heating, local air-conditioning, local ventilation, and split systems.",book:{id:"6807",slug:"hvac-system",title:"HVAC System",fullTitle:"HVAC System"},signatures:"Shaimaa Seyam",authors:[{id:"247650",title:"M.Sc.",name:"Shaimaa",middleName:null,surname:"Seyam",slug:"shaimaa-seyam",fullName:"Shaimaa Seyam"},{id:"257733",title:"MSc.",name:"Shaimaa",middleName:null,surname:"Seyam",slug:"shaimaa-seyam",fullName:"Shaimaa Seyam"},{id:"395618",title:"Dr.",name:"Shaimaa",middleName:null,surname:"Seyam",slug:"shaimaa-seyam",fullName:"Shaimaa Seyam"}]},{id:"70315",title:"Some Basic and Key Issues of Switched-Reluctance Machine Systems",slug:"some-basic-and-key-issues-of-switched-reluctance-machine-systems",totalDownloads:1268,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Although switched-reluctance machine (SRM) possesses many structural advantages and application potential, it is rather difficult to successfully control with high performance being comparable to other machines. Many critical affairs must be properly treated to obtain the improved operating characteristics. This chapter presents the basic and key technologies of switched-reluctance machine in motor and generator operations. The contents in this chapter include: (1) structures and governing equations of SRM; (2) some commonly used SRM converters; (3) estimation of key parameters and performance evaluation of SRM drive; (4) commutation scheme, current control scheme, and speed control scheme of SRM drive; (5) some commonly used front-end converters and their operation controls for SRM drive; (6) reversible and regenerative braking operation controls for SRM drive; (7) some tuning issues for SRM drive; (8) operation control and some tuning issues of switched-reluctance generators; and (9) experimental application exploration for SRM systems—(a) wind generator and microgrid and (b) EV SRM drive.",book:{id:"8899",slug:"modelling-and-control-of-switched-reluctance-machines",title:"Modelling and Control of Switched Reluctance Machines",fullTitle:"Modelling and Control of Switched Reluctance Machines"},signatures:"Chang-Ming Liaw, Min-Ze Lu, Ping-Hong Jhou and Kuan-Yu Chou",authors:[{id:"37616",title:"Prof.",name:"Chang-Ming",middleName:null,surname:"Liaw",slug:"chang-ming-liaw",fullName:"Chang-Ming Liaw"},{id:"306461",title:"Mr.",name:"Min-Ze",middleName:null,surname:"Lu",slug:"min-ze-lu",fullName:"Min-Ze Lu"},{id:"306463",title:"Mr.",name:"Ping-Hong",middleName:null,surname:"Jhou",slug:"ping-hong-jhou",fullName:"Ping-Hong Jhou"},{id:"306464",title:"Mr.",name:"Kuan-Yu",middleName:null,surname:"Chou",slug:"kuan-yu-chou",fullName:"Kuan-Yu Chou"}]}],onlineFirstChaptersFilter:{topicId:"1",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"83153",title:"Perspective Chapter: Cryptocurrencies Effectiveness for Nature",slug:"perspective-chapter-cryptocurrencies-effectiveness-for-nature",totalDownloads:0,totalDimensionsCites:null,doi:"10.5772/intechopen.106493",abstract:"The rise of cryptocurrencies based on Blockchain platforms have provided multiple solutions for social and nature projects supported by concerned investors with sustainable development initiatives. Speculation and unclear uses of a cryptocurrency plays a negative role for the projects they claim to support. A positive relationship between coin investors and supported projects must position the coin value on the scale of the community involvement among the coin and project issues, thus placing the project results above speculative moves. Coin nature and social based projects may include a decentralized autonomous organization (DAO), combined with a digital currency to contribute to social and nature improvements. This organization provides a framework for the engagement of investors, beneficiaries, and implementation partners, with results measured by reliable third parties. The potential funding from non fiduciary sources for sustainable development targets may be framed under the fundraising and financial solutions models, addressing the cryptocurrency volatility risks with responsible tokenomics in attention to transaction and regulatory issues. Overall, the more clear are the object and transaction issues of a nature conservation project supported by a currency, the more successful it will be in terms of nature and social improvements and the currency valuation for all parties involved.",book:{id:"11551",title:"Blockchain",coverURL:"https://cdn.intechopen.com/books/images_new/11551.jpg"},signatures:"Luiz Cruz Villares"},{id:"83163",title:"Robust Control Algorithm for Drones",slug:"robust-control-algorithm-for-drones",totalDownloads:0,totalDimensionsCites:0,doi:"10.5772/intechopen.105966",abstract:"Drones, also known as Crewless Aircrafts (CAs), are by far the most multi - level and multi developing technologies of the modern period. This technology has recently found various uses in the transportation area, spanning from traffic monitoring applicability to traffic engineering for overall traffic flow and efficiency improvements. Because of its non-linear characteristics and under-actuated design, the CA seems to be an excellent platform to control systems study. Following a brief overview of the system, the various evolutionary and robust control algorithms were examined, along with their benefits and drawbacks. In this chapter, a mathematical and theoretical model of a CA’s dynamics is derived, using Euler’s and Newton’s laws. The result is a linearized version of the model, from which a linear controller, the Linear Quadratic Regulator (LQR), is generated. Furthermore, the performance of these nonlinear control techniques is compared to that of the LQR. Feedback-linearization controller when implemented in the simulation for the chapter, the results for the same was better than any other algorithm when compared with. The suggested regulatory paradigm of the CA-based monitoring system and analysis study will be the subject of future research, with a particular emphasis on practical applications.",book:{id:"11522",title:"Aeronautics - New Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11522.jpg"},signatures:"Parul Priya and Sushma S. Kamlu"},{id:"83171",title:"Some Results on the Non-Homogeneous Hofmann Process",slug:"some-results-on-the-non-homogeneous-hofmann-process",totalDownloads:0,totalDimensionsCites:null,doi:"10.5772/intechopen.106422",abstract:"The classical counting processes (Poisson and negative binomial) are the most traditional discrete counting processes (DCPs); however, these are based on a set of rigid assumptions. We consider a non-homogeneous counting process (which we name non-homogeneous Hofmann process – NHP) that can generate the classical counting processes (CCPs) as special cases, and also allows modeling counting processes for event history data, which usually exhibit under- or over-dispersion. We present some results of this process that will allow us to use it in other areas and establish both the probability mass function (pmf) and the cumulative distribution function (cdf) using transition intensities. This counting process (CP) will allow other researchers to work on modelling the CP, where data dispersion exists in an efficient and more flexible way.",book:{id:"12021",title:"Applied Probability Theory - New Perspectives, Recent Advances and Trends",coverURL:"https://cdn.intechopen.com/books/images_new/12021.jpg"},signatures:"Gerson Yahir Palomino Velandia and José Alfredo Jiménez Moscoso"},{id:"83152",title:"Recycled Synthetic Polymer-Based Electrospun Membranes for Filtering Applications",slug:"recycled-synthetic-polymer-based-electrospun-membranes-for-filtering-applications",totalDownloads:0,totalDimensionsCites:null,doi:"10.5772/intechopen.106683",abstract:"Synthetic polymers have been widely applied in various commercial and household applications owing to their fascinating properties of low-cost, lightweight, and processability. However, increasing population and living standards and rising demand for non-biodegradable polymers have led to the accumulation of plastic pollution resulting in the current environmental crisis. Current waste management methods such as landfilling or incineration do not solve these environmental issues. On the other hand, recycling plastic waste is the most valuable strategy for dealing with waste as raw material for high-value products. One of such products is filter membranes. Polymer fiber membranes as masks in pandemics have been one of the most sought-after products in recent years. Some types of plastic waste became a material source for the development of filter materials, which could contribute to the protection of human health. Utilizing the simple, cheap, and industrially available technological solution is also needed. Given the number of advantages, electrospinning is such a beneficial solution. The electrospun polymer waste-based membranes show excellent filtration performance and can carry many other functionalities. Therefore, this review article presents a brief overview of electrospun nanofibrous membranes based on synthetic plastic waste and summarizes the filtration performance of such membranes. This review will discuss the future perspectives of electrospun membranes as well.",book:{id:"11462",title:"Recent Developments in Nanofibers Research",coverURL:"https://cdn.intechopen.com/books/images_new/11462.jpg"},signatures:"Alena Opálková Šišková, Heba M. Abdallah, Smaher Mosad Elbayomi and Anita Eckstein Andicsová"},{id:"83166",title:"General Drag Correlations for Particle-Fluid System",slug:"general-drag-correlations-for-particle-fluid-system",totalDownloads:0,totalDimensionsCites:null,doi:"10.5772/intechopen.106427",abstract:"Particle-fluid flows are commonly encountered in industrial applications. It is of great importance to understand the fundamentals governing the behavior of such a flow system for better process design, control, and optimization. Generally, the particle-fluid flow behavior is strongly influenced by the interaction forces between fluid and particles. Among the various kinds of particle-fluid interaction forces, the drag force is the most essential. This chapter reviews the modeling of drag force for particle-fluid systems: from single particle to multiple particles, monosize to multisize, spherical to nonspherical, and Newtonian fluid to non-Newtonian fluid. Typical drag correlations in the literature are compared and assessed in terms of physical meaning, consistency, and generality.",book:{id:"11498",title:"Boundary Layer Flows - Modelling, Computation, and Applications of Laminar, Turbulent Incompressible and Compressible Flows",coverURL:"https://cdn.intechopen.com/books/images_new/11498.jpg"},signatures:"Zheng Qi, Shibo Kuang, Liangwan Rong, Kejun Dong and Aibing Yu"},{id:"82272",title:"Landslide Movement Monitoring with InSAR Technologies",slug:"landslide-movement-monitoring-with-insar-technologies",totalDownloads:2,totalDimensionsCites:0,doi:"10.5772/intechopen.105058",abstract:"Synthetic aperture radar interferometry (InSAR) is a technology that has been widely used in many areas, such as topographic mapping, land and resource survey, geological exploration, disaster prevention and mitigation, volcanic and seismic monitor and so on. Landslide, as a representative geohazard, include a wide range of phenomena involving downhill ground movement. InSAR, a technology which can measure surface deformation at the millimeter level over serveral days or years, is suitable to detect landslides with chronical and widespread movements. In this chapter, we introduce main process methods of InSAR data, including Persistent Scatter Interferometry (PSInSAR) and Distributed Scatter Interferometry (DSInSAR). A study area, Daguan County Town, one of the most landslide-prone areas in China is induced to demonstrate the practicability of InSAR in detecting landslides. Combined InSAR results with geological, geotechnical and meterological data, the distribution of landslide in Daguan County in spatial and temporal dimensions would be displayed. We also coupling numerical modeling and InSAR for characterizing landslide movements under multiple loads. The numerical results revealed that body loads dominated the cumulative downhill movements by squeezing water and air from voids, and precipitation caused seasonal movements with the direction perpendicular to the slope surface.",book:{id:"10950",title:"Landslides",coverURL:"https://cdn.intechopen.com/books/images_new/10950.jpg"},signatures:"Peifeng Ma, Yifei Cui, Weixi Wang, Hui Lin, Yuanzhi Zhang and Yi Zheng"}],onlineFirstChaptersTotal:764},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:11,numberOfPublishedChapters:91,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:333,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:11,numberOfPublishedChapters:144,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:126,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:113,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:23,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:13,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:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{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"}}}}]},series:{item:{id:"6",title:"Infectious Diseases",doi:"10.5772/intechopen.71852",issn:"2631-6188",scope:"This series will provide a comprehensive overview of recent research trends in various Infectious Diseases (as per the most recent Baltimore classification). Topics will include general overviews of infections, immunopathology, diagnosis, treatment, epidemiology, etiology, and current clinical recommendations for managing infectious diseases. Ongoing issues, recent advances, and future diagnostic approaches and therapeutic strategies will also be discussed. This book series will focus on various aspects and properties of infectious diseases whose deep understanding is essential for safeguarding the human race from losing resources and economies due to pathogens.",coverUrl:"https://cdn.intechopen.com/series/covers/6.jpg",latestPublicationDate:"August 18th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:13,editor:{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"3",title:"Bacterial Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/3.jpg",isOpenForSubmission:!0,annualVolume:11399,editor:{id:"205604",title:"Dr.",name:"Tomas",middleName:null,surname:"Jarzembowski",slug:"tomas-jarzembowski",fullName:"Tomas Jarzembowski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKriQAG/Profile_Picture_2022-06-16T11:01:31.jpg",biography:"Tomasz Jarzembowski was born in 1968 in Gdansk, Poland. He obtained his Ph.D. degree in 2000 from the Medical University of Gdańsk (UG). After specialization in clinical microbiology in 2003, he started studying biofilm formation and antibiotic resistance at the single-cell level. In 2015, he obtained his D.Sc. degree. His later study in cooperation with experts in nephrology and immunology resulted in the designation of the new diagnostic method of UTI, patented in 2017. He is currently working at the Department of Microbiology, Medical University of Gdańsk (GUMed), Poland. Since many years, he is a member of steering committee of Gdańsk branch of Polish Society of Microbiologists, a member of ESCMID. He is also a reviewer and a member of editorial boards of a number of international journals.",institutionString:"Medical University of Gdańsk, Poland",institution:null},editorTwo:{id:"484980",title:"Dr.",name:"Katarzyna",middleName:null,surname:"Garbacz",slug:"katarzyna-garbacz",fullName:"Katarzyna Garbacz",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003St8TAQAZ/Profile_Picture_2022-07-07T09:45:16.jpg",biography:"Katarzyna Maria Garbacz, MD, is an Associate Professor at the Medical University of Gdańsk, Poland and she is head of the Department of Oral Microbiology of the Medical University of Gdańsk. She has published more than 50 scientific publications in peer-reviewed journals. She has been a project leader funded by the National Science Centre of Poland. Prof. Garbacz is a microbiologist working on applied and fundamental questions in microbial epidemiology and pathogenesis. Her research interest is in antibiotic resistance, host-pathogen interaction, and therapeutics development for staphylococcal pathogens, mainly Staphylococcus aureus, which causes hospital-acquired infections. Currently, her research is mostly focused on the study of oral pathogens, particularly Staphylococcus spp.",institutionString:"Medical University of Gdańsk, Poland",institution:null},editorThree:null},{id:"4",title:"Fungal Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/4.jpg",isOpenForSubmission:!0,annualVolume:11400,editor:{id:"174134",title:"Dr.",name:"Yuping",middleName:null,surname:"Ran",slug:"yuping-ran",fullName:"Yuping Ran",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9d6QAC/Profile_Picture_1630330675373",biography:"Dr. Yuping Ran, Professor, Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China. Completed the Course Medical Mycology, the Centraalbureau voor Schimmelcultures (CBS), Fungal Biodiversity Centre, Netherlands (2006). International Union of Microbiological Societies (IUMS) Fellow, and International Emerging Infectious Diseases (IEID) Fellow, Centers for Diseases Control and Prevention (CDC), Atlanta, USA. Diploma of Dermatological Scientist, Japanese Society for Investigative Dermatology. Ph.D. of Juntendo University, Japan. Bachelor’s and Master’s degree, Medicine, West China University of Medical Sciences. Chair of Sichuan Medical Association Dermatology Committee. General Secretary of The 19th Annual Meeting of Chinese Society of Dermatology and the Asia Pacific Society for Medical Mycology (2013). In charge of the Annual Medical Mycology Course over 20-years authorized by National Continue Medical Education Committee of China. Member of the board of directors of the Asia-Pacific Society for Medical Mycology (APSMM). Associate editor of Mycopathologia. Vice-chief of the editorial board of Chinses Journal of Mycology, China. Board Member and Chair of Mycology Group of Chinese Society of Dermatology.",institutionString:null,institution:{name:"Sichuan University",institutionURL:null,country:{name:"China"}}},editorTwo:null,editorThree:null},{id:"5",title:"Parasitic Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",isOpenForSubmission:!0,annualVolume:11401,editor:{id:"67907",title:"Dr.",name:"Amidou",middleName:null,surname:"Samie",slug:"amidou-samie",fullName:"Amidou Samie",profilePictureURL:"https://mts.intechopen.com/storage/users/67907/images/system/67907.jpg",biography:"Dr. Amidou Samie is an Associate Professor of Microbiology at the University of Venda, in South Africa, where he graduated for his PhD in May 2008. He joined the Department of Microbiology the same year and has been giving lectures on topics covering parasitology, immunology, molecular biology and industrial microbiology. He is currently a rated researcher by the National Research Foundation of South Africa at category C2. He has published widely in the field of infectious diseases and has overseen several MSc’s and PhDs. His research activities mostly cover topics on infectious diseases from epidemiology to control. His particular interest lies in the study of intestinal protozoan parasites and opportunistic infections among HIV patients as well as the potential impact of childhood diarrhoea on growth and child development. He also conducts research on water-borne diseases and water quality and is involved in the evaluation of point-of-use water treatment technologies using silver and copper nanoparticles in collaboration with the University of Virginia, USA. He also studies the use of medicinal plants for the control of infectious diseases as well as antimicrobial drug resistance.",institutionString:null,institution:{name:"University of Venda",institutionURL:null,country:{name:"South Africa"}}},editorTwo:null,editorThree:null},{id:"6",title:"Viral Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/6.jpg",isOpenForSubmission:!0,annualVolume:11402,editor:{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. 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He previously worked as a post-doctoral fellow at the Ben-Gurion University of Negev, Israel; University of the Free State, South Africa; and Central University of Technology Bloemfontein, South Africa. He obtained his Ph.D. in Organic Chemistry from Nagaoka University of Technology, Japan. He has published more than seventy-four journal articles and attended several national and international conferences as speaker and chair. Dr. Kendrekar has received many international awards. He has several funded projects, namely, anti-malaria drug development, MRSA, and SARS-CoV-2 activity of curcumin and its formulations. He has filed four patents in collaboration with the University of Central Lancashire and Mayo Clinic Infectious Diseases. His present research includes organic synthesis, drug discovery and development, biochemistry, nanoscience, and nanotechnology.",institutionString:"Visiting Scientist at Lipid Nanostructures Laboratory, Centre for Smart Materials, School of Natural Sciences, University of Central Lancashire",institution:null},{id:"428125",title:"Dr.",name:"Vinayak",middleName:null,surname:"Adimule",slug:"vinayak-adimule",fullName:"Vinayak Adimule",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/428125/images/system/428125.jpg",biography:"Dr. Vinayak Adimule, MSc, Ph.D., is a professor and dean of R&D, Angadi Institute of Technology and Management, India. He has 15 years of research experience as a senior research scientist and associate research scientist in R&D organizations. He has published more than fifty research articles as well as several book chapters. He has two Indian patents and two international patents to his credit. Dr. Adimule has attended, chaired, and presented papers at national and international conferences. He is a guest editor for Topics in Catalysis and other journals. He is also an editorial board member, life member, and associate member for many international societies and research institutions. His research interests include nanoelectronics, material chemistry, artificial intelligence, sensors and actuators, bio-nanomaterials, and medicinal chemistry.",institutionString:"Angadi Institute of Technology and Management",institution:null},{id:"284317",title:"Prof.",name:"Kantharaju",middleName:null,surname:"Kamanna",slug:"kantharaju-kamanna",fullName:"Kantharaju Kamanna",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284317/images/21050_n.jpg",biography:"Prof. K. Kantharaju has received Bachelor of science (PCM), master of science (Organic Chemistry) and Doctor of Philosophy in Chemistry from Bangalore University. He worked as a Executive Research & Development @ Cadila Pharmaceuticals Ltd, Ahmedabad. He received DBT-postdoc fellow @ Molecular Biophysics Unit, Indian Institute of Science, Bangalore under the supervision of Prof. P. Balaram, later he moved to NIH-postdoc researcher at Drexel University College of Medicine, Philadelphia, USA, after his return from postdoc joined NITK-Surthakal as a Adhoc faculty at department of chemistry. Since from August 2013 working as a Associate Professor, and in 2016 promoted to Profeesor in the School of Basic Sciences: Department of Chemistry and having 20 years of teaching and research experiences.",institutionString:null,institution:{name:"Rani Channamma University, Belagavi",country:{name:"India"}}},{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/158492/images/system/158492.jpeg",biography:"Prof. Dr. Yusuf Tutar conducts his research at the Hamidiye Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Division of Biochemistry, University of Health Sciences, Turkey. He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"94311",title:"Prof.",name:"Martins",middleName:"Ochubiojo",surname:"Ochubiojo Emeje",slug:"martins-ochubiojo-emeje",fullName:"Martins Ochubiojo Emeje",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94311/images/system/94311.jpeg",biography:"Martins Emeje obtained a BPharm with distinction from Ahmadu Bello University, Nigeria, and an MPharm and Ph.D. from the University of Nigeria (UNN), where he received the best Ph.D. award and was enlisted as UNN’s “Face of Research.” He established the first nanomedicine center in Nigeria and was the pioneer head of the intellectual property and technology transfer as well as the technology innovation and support center. Prof. Emeje’s several international fellowships include the prestigious Raman fellowship. He has published more than 150 articles and patents. He is also the head of R&D at NIPRD and holds a visiting professor position at Nnamdi Azikiwe University, Nigeria. He has a postgraduate certificate in Project Management from Walden University, Minnesota, as well as a professional teaching certificate and a World Bank certification in Public Procurement. Prof. Emeje was a national chairman of academic pharmacists in Nigeria and the 2021 winner of the May & Baker Nigeria Plc–sponsored prize for professional service in research and innovation.",institutionString:"National Institute for Pharmaceutical Research and Development",institution:{name:"National Institute for Pharmaceutical Research and Development",country:{name:"Nigeria"}}},{id:"436430",title:"Associate Prof.",name:"Mesut",middleName:null,surname:"Işık",slug:"mesut-isik",fullName:"Mesut Işık",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/436430/images/19686_n.jpg",biography:null,institutionString:null,institution:{name:"Bilecik University",country:{name:"Turkey"}}},{id:"268659",title:"Ms.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/268659/images/8143_n.jpg",biography:"Dr. Zhan received his undergraduate and graduate training in the fields of preventive medicine and epidemiology and statistics at the West China University of Medical Sciences in China during 1989 to 1999. He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a scientist and Principal Investigator at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering the lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via artificial intelligence-based analyses of exosomal Raman signatures. Dr. Paul also works on spatial multiplex immunofluorescence-based tissue mapping to understand the immune repertoire in lung cancer. Dr. Paul has published in more than sixty-five peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award and the 2022 AAISCR-R Vijayalaxmi Award for Innovative Cancer Research. He is a senior member of the Institute of Electrical and Electronics Engineers (IEEE) and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. He is currently working on the protective activity of phenolic compounds in disorders associated with oxidative stress and inflammation.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. 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