Some EMT inhibitors.
\\n\\n
These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\\n\\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\\n\\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
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IntechOpen and Knowledge Unlatched formed a partnership to support researchers working in engineering sciences by enabling an easier approach to publishing Open Access content. Using the Knowledge Unlatched crowdfunding model to raise the publishing costs through libraries around the world, Open Access Publishing Fee (OAPF) was not required from the authors.
\n\nInitially, the partnership supported engineering research, but it soon grew to include physical and life sciences, attracting more researchers to the advantages of Open Access publishing.
\n\n\n\nThese books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\n\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\n\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
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\r\n\tNanotechnology is a multidisciplinary field including principles of engineering, biology, physics, and chemistry. The increasing number of nanomedicines approved clinically highlights the relevant role of nanotechnology in the field of cancer research. The successful application of nanotechnology to cancer includes two main areas; i) development of nanovectors, such as nanoparticles, which can be loaded with different bioactive compounds or imaging agents and then targeted to tumours, and ii) high throughput devices to detect the biological signatures of cancer. This cutting-edge technology provides a unique approach and technology against cancer across early diagnosis, prediction, prevention, personalised therapy, and medicine. This book focuses on nanotechnology-based approaches in the advancements of cancer therapy. It covers aspect related to diagnostic, in particular by molecular imaging, therapeutical and theranostic systems based on nanoparticles with the latest examples in clinical application.
",isbn:null,printIsbn:"979-953-307-X-X",pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,hash:"57c06a50cbefebfd7eafd8e5509f37c6",bookSignature:"Dr. Antonio Di Martino",publishedDate:null,coverURL:"//cdnintech.com/web/frontend/www/assets/cover.jpg",keywords:"Nano-oncology, Targeted therapy, Radiation Therapy, Photodynamic Therapy, Thermal Therapy, Gene Therapy, Chemotherapy, Molecular Imaging, Nanoparticles, Translational Medicine",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 13th 2019",dateEndSecondStepPublish:"March 6th 2019",dateEndThirdStepPublish:"May 5th 2019",dateEndFourthStepPublish:"July 24th 2019",dateEndFifthStepPublish:"September 22nd 2019",remainingDaysToSecondStep:"3 years",secondStepPassed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"225395",title:"Dr.",name:"Antonio",middleName:null,surname:"Di Martino",slug:"antonio-di-martino",fullName:"Antonio Di Martino",profilePictureURL:"https://mts.intechopen.com/storage/users/225395/images/system/225395.jpeg",biography:"Antonio Di Martino received his Bachelor (Industrial Chemistry) and Master Degree (Industrial Organic Chemistry and Biochemistry) in 2011 from the University of Rome La Sapienza, Italy. In 2013 he joined the Centre of Polymer Systems, Tomas Bata University in Zlin, the Czech Republic where was awarded PhD in Chemistry and Material Technology in 2016 defending a research work based on the encapsulation of bioactive compound in biopolymeric matrices. At the moment he is a senior researcher at the Centre of Polymer Systems in Zlin, Czech Republic, in the Bioactive Polymer group and his main attention is focused on developing innovative formulations based on polysaccharides for drug delivery applications.\nIn 2016 he joined the National Research Tomsk Polytechnic University as a Postdoctoral Research in the Department of Technology of Organic Substances and Polymer Materials and his research work mainly focused on the development of hybrid nanocarrier for drug delivery and diagnostic. In 2019 he became associate professor and member of the Research School in Chemistry & Applied Biomedical Sciences at Tomsk Polytechnic University, Russia. He is supervisor and consultant of Master and PhD students and his work is focused on the development of hydrogels for controlled delivery of bioactive compounds for application in pharmaceutical and biomedical area.\nHis primary research interest is the development of nano- and microcarrier based on biopolymer for multiple encapsulations and controlled delivery of bioactive compounds.\nHe has to his credit to 23 publications indexed in Web of Science (h-index 9) and active participation in projects financed by Czech Ministry of education, Russian Ministry of Education and European Union and author of one patent.",institutionString:"Tomas Bata University in Zlin",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Tomsk Polytechnic University",institutionURL:null,country:{name:"Russia"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1090",title:"Radiation Oncology",slug:"radiation-oncology"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"288104",firstName:"Ivana",lastName:"Spajic",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/288104/images/8497_n.jpg",email:"ivana.s@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:"1553",title:"Modern Practices in Radiation Therapy",subtitle:null,isOpenForSubmission:!1,hash:"f7bffcd98f458c5b6cd80615834f2b34",slug:"modern-practices-in-radiation-therapy",bookSignature:"Gopishankar Natanasabapathi",coverURL:"https://cdn.intechopen.com/books/images_new/1553.jpg",editedByType:"Edited by",editors:[{id:"97379",title:"Dr.",name:"Gopishankar",surname:"Natanasabapathi",slug:"gopishankar-natanasabapathi",fullName:"Gopishankar Natanasabapathi"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1561",title:"Brachytherapy",subtitle:null,isOpenForSubmission:!1,hash:"8c7f5404e634a5e233e051cdace59aa5",slug:"brachytherapy",bookSignature:"Kazushi Kishi",coverURL:"https://cdn.intechopen.com/books/images_new/1561.jpg",editedByType:"Edited by",editors:[{id:"100002",title:"Dr.",name:"Kazushi",surname:"Kishi",slug:"kazushi-kishi",fullName:"Kazushi Kishi"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2693",title:"Frontiers in Radiation Oncology",subtitle:null,isOpenForSubmission:!1,hash:"5761829d7f0e5eb06b7337751b38b23c",slug:"frontiers-in-radiation-oncology",bookSignature:"Tejinder Kataria",coverURL:"https://cdn.intechopen.com/books/images_new/2693.jpg",editedByType:"Edited by",editors:[{id:"141684",title:"Dr.",name:"Tejinder",surname:"Kataria",slug:"tejinder-kataria",fullName:"Tejinder Kataria"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10231",title:"Proton Therapy",subtitle:"Current Status and Future Directions",isOpenForSubmission:!1,hash:"51790b2eab420c0c09da3bf9d923e79c",slug:"proton-therapy-current-status-and-future-directions",bookSignature:"Thomas J. 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This process accounts for approximately 90% of cancer deaths. Epithelial-mesenchymal transition (EMT) is a characteristic of the majority of metastatic cells. EMT is a natural transdifferentiation mechanism that governs changes in cell states along the epithelial versus mesenchymal axes and confers epithelial-mesenchymal plasticity upon epithelial cells. In particular, epithelial cells are transformed from highly differentiated, polarized, and organized cells into undifferentiated, isolated, and mesenchymal-like cells with migratory and invasive properties. In this chapter, we summarize evidence supporting the widespread involvement of EMT in tumor pathogenesis and the regulation of cancer metastasis.
\nNormal adult tissues in terminally differentiated cells have been reprogrammed into pluripotent stem cells in the past 10 years [1, 2]. This process has resulted in the wide acceptance of the initial hypothesis that nearly any type of dedifferentiation or transdifferentiation is possible if the ectopic expression of a transcription factor is properly combined into adult cells. The successful experiments on reprogramming have led to the exploration of the factors that change the state of cells in nature rather than forced to ectopic gene expression.
\nEMT is the most important cell biology program among naturally occurring transdifferentiation programs. This process converts epithelial cells into mesenchymal derivatives, which is the reverse process of mesenchymal-epithelial transformation (MET) [3]. Accumulated evidence for the past two decades has suggested that EMT occurs during development to ensure the interconversions of cells utilized in the formation of different types of cells, thereby forming the organs of organization and complex multicellular organisms [3, 4]. This cell biological program is orchestrated by a group of transcription factors (EMT-TFs), such as the Snail, Twist, and Zeb families [4, 5].
\nTwo other aspects of EMT are worthy to be discussed in detail. The EMT program in some epithelial tissues is apparently correlated with the residence of cells in stem cell-like states. Moreover, versions of the EMT program are adopted by cancer cells to obtain a series of processes associated with higher levels of malignancy. EMT exhibits the presence of mechanical connections between an individual and the pathogenesis of cancer. These processes prior to EMT are insignificant.
\nEMT governs changes in cell states along the epithelial versus mesenchymal axes and converts epithelial cells to mesenchymal cells when this program is fully executed. Weinberg described the extreme poles of the epithelial versus mesenchymal axes. Epithelial cells, frequently with polygonal shapes in monolayer culture, are polarized along their apical-basal axis and are tightly connected with one another laterally via adherens and tight junctions in vivo. These lateral ties can ensure the structural integrity of epithelial cell sheets. By contrast, full mesenchymal cells exhibit spindle-like morphology with no sign of apical-basal polarity. These cells are loosely attached to the surrounding extracellular matrix (ECM) through focal adhesions. These features can help improve motility and explain the invasion of mesenchymal cells relative to their epithelial counterparts.
\nThe deep layer of biological contact between epithelial and mesenchymal cells is determined by the differences in their respective transcription programs. These programs also control the expression of other gene products and key structural proteins, including those involved in the maintenance of the cytoskeleton and the strengthening of cell-cell adhesion [3–5]. Thus, epithelial cells express different types of keratin to form intermediate filaments, whereas vimentin constitutes the intermediate filament protein of mesenchymal cells. The expression of cell adhesion molecules and polarized complexes in mesenchymal cells is generally inhibited. EMT is marked by the replacement of E-cadherin by N-cadherin, which leads to the formation of weak cell adhesion between adjacent cells.
\nEMT can be significantly and rapidly activated in epithelial cells in response to physiological signals in a cell autonomous or non-cell autonomous manner. When gastrulation is used as an example, EMT responds to the induction signal as follows. The program is activated in ectodermal epithelial cells and completely converts epithelial cells into mesoderm mesenchymal cells, such as fibroblast growth factor and Wnt signaling pathway [6]. Similarly, EMT can be rapidly activated in adult tissues; it reacts to wounding and promotes rapid wound healing. This process is necessary to reconstruct the epithelial barrier that is essential for protecting internal organs from external injury [7]. Such rapid conversion between epithelial and mesenchymal states suggests the plasticity of epithelial cells, which facilitates their response to EMT-inducing signals. In addition, this plasticity demonstrates that residence in one of these two states is maintained in a metastable manner, with complex molecular and cellular mechanisms to ensure that a cell is in one or another state for a long period.
\nThe description of EMT as a binary that shifts cells from a fully epithelial state into a fully mesenchymal state misreads the normal actions of this program. EMT is typically only from a fully epithelial state to a partially mesenchymal state, with certain key epithelial markers retained [8, 9]. Nevertheless, obtaining even a subset of mesenchymal traits to endow cells that previously resided in a fully epithelial state with a suite of mesenchymal traits will produce far-reaching effect on their biology.
\nNearly 80% of malignant tumors are derived from epithelial tissues, which produce common cancers, such as tumors of the lung, colon, breast, pancreas, prostate, bladder, ovary, kidney, and liver. The epithelial states of the corresponding normal cells of origin in each determined case sustain the expression of cytokeratin and E-cadherin, which are signs of the epithelial states of early tumor tissues. In addition, tumor cells in early tumors remain the key biological phenotypes of epithelial cells, such as a lack of motility and capability to form a continuous cell sheet. These qualities exhibit a sharp contrast with those of advanced cancer cells, which are products of a complex succession process that is frequently referred to as “tumor progression.” Highly invasive tumor cells present mesenchymal features, such as motility and invasion, and the latter is associated with metastasis [10–12]. The acquisition of these malignant features at the mechanism level can be explained by activating EMT, which is previously dormant in tumor cells during tumor progression.
\nThe acquisition of mesenchymal features in breast cancer is positively correlated with tumor progression and an aggressive subtype of the disease [13, 14]. Investigating a large body of loss-of-function and gain-of-function in xenograft tumor models is a direct means to describe the link between the activation of EMT and the degree of malignancy of a tumor. The consumption of EMT-TFS, such as Twist, Snail, and Zinc finger E-box binding homeobox 1 (ZEB1), in both human and mouse breast cancer cell lines significantly inhibits the metastatic dissemination, whether the site is the primary site of tumor formation (e.g., mammary fat pad mass) or after experimental introduction of cancer cells into venous circulation (i.e., tail-vein injection). By contrast, the ectopic activation of EMT can enhance metastatic dissemination of orthotopically implanted human breast cancer cells by forcing the expression of EMT-TFS [15–17].
\nEMT in patients with breast cancer does not only promote systemic dissemination but also function as a major factor of drug resistance and disease recurrence [18, 19]. A similar phenomenon has been observed in a mouse model of Her2-induced tumors in which Snail EMT-TF can be autoactivated in recurrent malignancy in vivo and make the tumors highly mesenchymal phenotype [20]. The results evidently show an association between EMT activation and tumor relapse. Moreover, the link between EMT activation and enhanced tumorigenicity has been verified in various human cancer cell lines [21]. The inhibition of epithelial-mesenchymal plasticity suppresses the valid transition of carcinoma cells from a weakly tumorigenic into a highly tumorigenic state by blocking the activation of Zeb1 EMT-TF; that is, a state where tumor-initiating cells demonstrate their improved capabilities [22].
\nRecent studies have associated EMT with the acquisition of immunosuppressive capabilities in various types of cancers. The expression of Snail EMT-TF in melanoma can simultaneously inhibit the differentiation of cytotoxic T cells and induce the immune inhibition of the formation of regulatory T cells; the latter effect is mediated through the production of platelets [23]. Meanwhile, EMT in breast cancer cells enhances the resistance of tumor cells to cytotoxic T cell-mediated lysis, which at least partially induces autophagy [24, 25]. The activation of EMT-TF ZEB1 in lung cancer cells has been linked to the upregulation of programmed death ligand 1 (PD-L1), which is an immunosuppressive molecule that can block tumor-infiltrating lymphocyte attack [26].
\nEMT activation has a pleiotropic function in driving cancer progression, and an increasing number of reports confirm that invasive cancer is related to various types of aggressive carcinoma cells. Thus, we believe that all carcinomas essentially develop traits that are related with malignancy through the activation of an EMT program in their constituent neoplastic cells. However, the EMT program associated with common cancers has not yet been determined because many clinical pathologists doubt the existence of this program and its role in the production of high-grade cancer [27]. Such reluctance primarily originates from the fact that all markers of clinical biopsy are difficult to score. Although scoring will be possible, cancer cells that underwent EMT are also difficult to distinguish from normal host tissues and adjacent tumor stromal cells. Many fibroblasts and myofibroblasts self-express EMT-related markers. Clear evidence of this program during tumor development can be obtained from cell detection that co-express both mesenchymal and epithelial traits with certain retained epithelial markers inherited from their fully epithelial precursors because cancer cells frequently experience the only part of the EMT program. Recent analysis suggests that all subtypes of invasive breast cancer tumor cells exhibit both epithelial and mesenchymal characteristics as shown by the in situ hybridization in human breast cancer specimens of pooled epithelial and mesenchymal markers [28]. In addition, a part of the circulating tumor cells is isolated from the peripheral blood of patients with advanced prostate and breast cancers, and they also co-express both epithelial and mesenchymal markers [28–30].
\nThrough the blood or lymphatic system, tumor cells can migrate far from the primary site and then settle and grow in a remote site to complete tumor metastasis. This process plays a key role in tumor disease, malignance level, and death of over 90% of tumor patients. Several questionnaires have shown the low efficiency of tumor metastasis. The majority of tumor cells can fall off into the blood or lymphatic system, such that only a small portion can form micro metastases, and even fewer can achieve actual metastases and present specific organ affinity. Moreover, the metastatic times of different tumors are not the same [31]. Thus, understanding this process is significant, and the importance of EMT should be discussed from different aspects.
\nEMT is a characteristic of most metastatic cells [32]. In particular, highly differentiated epithelial cells are converted into undifferentiated and isolated ectomesenchymal cells with migration and invasive properties. Migration is one of the four basic steps in tumor cell metastasis. Various substances, such as secretion factors, growth factors, and ECM components, can stimulate the migration of tumor cells. Cell migration stimulated by these substances can be divided into random and directed migrations. Thus, tumor cells can migrate and metastasize. The migration capability of tumor cells is related to their potential to metastasize. The density of the negative charges that separate from the surface of the tumor cells increases, which enhances electrostatic repulsion between cells. This process facilitates the removal of tumor cells into a free state from the tumor tissue. The adhesion of molecules on the surface of tumor cells is mediated by cell adhesion molecules, namely selectins, integrins, Ig superfamily, and cadherin [33]. Intercellular adhesion capability decreases in the same type, which leads to the detachment of tumor cells from the primary tumor and the abnormal intercellular adhesion contact with the implantation of tumor cells in the vascular wall. Invasion is the important biological characteristic of malignant tumors. Every organization or organ has its own structure. Tumor cells that invade an organ should respond to environmental stress, such as the lack of oxygen and nutrients, low pH, active oxygen free radicals, and inflammation regulatory factor. When the invasive capability is strong, the degree of tumor malignancy will be high. Epithelial cells lose the characteristics of the epithelial cells of ectomesenchymal cells, and the phenotype EMT process is the molecular basis of cancer stem cell invasion and metastasis. In addition, during tumor development, many tumor cells exhibit changes in good plasticity through morphology and phenotype transformation, such as collective amoeboid transition (CAT) and mesenchymal-to-amoeboid transition (MAT) [34]. EMT is a transient dynamic process that is influenced by the microenvironment. Furthermore, in vitro studies are necessary to build an improved genetic mouse model and reliable marker for EMT to realize real-time monitoring of the body, understand the mechanism of tumor evolution and EMT, establish new EMT signs, and to explore the role of transcription factors in the induction of EMT [35]. The loss of epithelial cell polarity during EMT reduces contact between the environment and stromal cells. This process enhances cell migration and mobility, which results in mesenchymal phenotypes. Moreover, changes in cell phenotype, coupled with an alteration in the expression levels of E-cadherin, vimentin, N-cadherin, and α-SMA, among others, in particular, a drop in E-cadherin level, can reduce the adhesion of cells, which facilitates the invasion and metastasis of cells. The loss of E-cadherin expression has been considered the most notable feature of EMT [36]. EMT presents increased opportunities for cell metastasis during tumorigenesis, probably because of its loose cell characteristics. EMT can promote the transfer of various tumor cells. Tumor metastasis includes several steps, such as attacks that are the precondition for cell transfer. EMT plays an important role during tumor invasion. Non-invasive tumors are turned into highly invasive tumors when the E-cadherin protein of tumor cells is cut. Experiments have established EMT marks in some tumor cells in metastases.
\nSnail, Twist, and ZEBl transcription factors closely linked with EMT can enhance invasion and promote the degradation of E-cadherin. EMT is the interaction between tumor cells and adjacent tumor-associated stromal cells caused by the induction of the transcription factor in the tumor cells. The activation of tumor EMT typically occurs during signal swaps between tumor cells and adjacent stromal cells. The progression of primary tumor cells can raise each model into the surrounding stroma. The recruitment of cells form a “reactive” matrix, induce the release of EMT signals, and start tumor cells by activating the EMT transcription factors [37]. Figure 1 shows the tumor metastasis and EMT.
\nIn EMT processes, tumor cells change from epithelial-like cells to mesenchymal-like cells and get the ability to metastasis.
Many transcription factors can induce EMT. Molecular reprogramming during an EMT is caused by three groups of transcription factors, namely the Snail, Twist, and ZEB families [38].
\nThe Snail family includes Snail1, Snail2 (Slug), and Snail3 (Smuc). These factors regulate epithelial and mesenchymal markers [39, 40]. Snail1 induces signal to initiate EMT [41, 42]. These factors inhibit other epithelial markers that affect E-cadherin and bind to the E-cadherin promoter to inhibit its transcription. The Snail factors activate the expression of mesenchymal-like and pro-invasive genes that promote cell migration [43].
\nSnail factors are absent in normal epithelial cells. Snail1 is expressed higher than Snail2 and Snail3. An upregulated nuclear Snail1 expression is associated with tumor progression and can be found in the cytoplasm of several carcinomas. Snail1 staining is found among fibroblast-like cells, endothelial cells at the peritumoral stroma, and inflammation of colorectal carcinomas [44]. Snail1 promotes the recurrence of Her2/neu-induced breast tumors in mice, and its mesenchymal-like characteristics are exhibited in recurrent human carcinomas [45]. Therefore, recurrent breast carcinomas are induced by Snail1 spontaneously. High level of Snail1 is an independent predictor for reduced relapse-free survival in breast cancer patients. This factor is considered an independent prognostic factor for worst evolution and poor survival in many carcinomas [43].
\nTwist factor induces EMT by influencing other EMT-ATFs. Twist1 represses E-cadherin by inducing Snail1 or Snail2 and then binding to its promoter [46–48]. The knockdown of Twist1 in breast cancer cells represses the metastasis in xenograft models, but does not influence the formation of primary tumors [49]. Twist1 induces N-cadherin by driving its transcription and the mechanisms of post-transcription [50, 51]. Twist1 promotes the expression of mesenchymal markers without eliciting an N-cadherin/E-cadherin switch in glioblastoma cells [52]. In cell motility, the excessive expression of Twist1 upregulates the expression of cytoskeletal and ECM genes.
\nTwist1 and Twist2 are upregulated at the invasive front of carcinomas in cancer and stromal cells [53–55]. These factors are absent in normal epithelium but are induced in many human carcinomas, such as those of the digestive tract, liver, breast, ovary endometrium, and prostate [43]. Twist factors are upregulated in the cytoplasm and nuclei of cancer cells. Twist factors are independent prognostic factors for increased tumor recurrence, tumor aggressiveness, and the low survival rate of patients [49, 53, 56]. Twist and Snail factors play distinct but collaborative roles among EMT-ATFs.
\nThe ZEB family includes zinc finger/homeodomain proteins, namely ZEB1 and ZEB2. The expression of ZEB factors drives an EMT by activating mesenchymal properties and repressing epithelial markers [43].
\nZEB1 and ZEB2 bind to E-box sequences in the E-cadherin promoter but recruit different sets of co-repressors, namely SWI/SNF and CtBP for ZEB1 and NuRD and CtBP for ZEB2. ZEB proteins bind and repress the promoters of epithelial markers, such as R- and P-cadherins, gap junctions (connexins 26 and 31), cell polarity markers (Crumbs3, Pals1-associated tight junction protein, and lethal giant larvae homologue 2), desmosomes (plakophilin 3, desmoplakin), and components of tight junctions (claudin 7, occludin, junctional adhesion molecule 1, and zonula occludens protein 3). ZEB proteins activate mesenchymal markers, such as N-cadherin and vimentin [43]. ZEB1 and ZEB2 repress epithelial splicing regulatory proteins-1 and 2, the overexpression of which inhibits EMT [57].
\nZEB1 inhibits epithelial phenotype, although this factor is found in isolated fibroblasts and immune cells in the interstitial matrix. This factor is not expressed in normal epithelium and well-differentiated carcinomas that express E-cadherin [58, 59]. ZEB1 is highly expressed in invading dedifferentiated cancer cells of many tumors, such as colorectal, breast, liver, endometrial, lung, prostate, and pancreatic carcinomas. ZEB1 and ZEB2 are expressed by stromal cells in epithelial tissues and organs of normal E-cadherin-positive epithelial cells [60]. ZEB-dependent paracrine signaling from the stroma can cooperate in E-cadherin repression in other parts of the tumor [61].
\nThe main signaling pathways involved in EMT.
Other transcription factors also induce EMT and tumor invasiveness. The homeobox factor goosecoid induces EMT by activating mesenchymal genes and repressing epithelial markers [62]. TGF-β induces goosecoid in breast epithelial cells, and goosecoid is overexpressed in ductal breast carcinomas and atypical ductal hyperplasia [62]. Figure 2 shows the main signaling pathways involved in EMT.
\nEMT significantly affects metastasis in cancers [63]. This process has attracted increasing attention because metastasis is vital in cancer recurrence and in death caused by cancer [64, 65]. In addition, understanding this process is important to determine medical diagnosis and treatment approach. Notably, sufficient information on biomarkers can lead to accurate forecast and precise therapeutic methods for metastases. Hence, proper diagnostic and therapeutic treatment for patients with early-stage cancer can promote good prognosis and prolong survival time to further improve the quality of life of patients [66, 67]. Furthermore, TBLR1, Sam68, SNAI1, Twist 2, etc. have been diagnosed markers or prognostic factors. This information is clinically important to predict survival and provide promising therapeutic targets for patients with early stage cancer [68, 69].
\nSulforaphane or salinomycin treatment changes the stemness properties of cancer stem cells (CSCs), which may have been caused by the regulation of the expression of a special gene or protein. Sulforaphane downregulates Twist-1 and vimentin. By contrast, salinomycin treatment does not only significantly reduce vimentin level but also induce and upregulate E-cadherin expression in special cancer cell lines. Various reports have indicated a key role of E-cadherin in EMT. Thus, studying these cadherins can be a promising strategy [70, 71].
\nEpithelial cancer cells tend to differentiate to acquire invasive and stem cell-like properties. Thus, EMT regulators may function as therapeutic targets of cancer progression and recurrence. EMT-TFs, such as Twist, Snail, and ZEB, will be regarded as potent therapeutic targets for pharmacologic inhibition. Traditionally, EMT regulators are nearly impossible to target; however, evidence suggests that molecular links can offer the possibility for targeting regulation as a therapeutic intervention of EMT among metabolic adaptation, epigenetic alteration, and EMT [4, 72–74].
\nEMT significantly affects epigenome restructuring. Thus, epigenetic therapies can be used to realize the pharmacologic inhibition of EMT, which makes EMT sensitive to chemotherapy. In recent years, potential EMT inhibitors function as an effective chemotherapeutic sensitive agent, such as HDAC enzymes LBH589 [75]. In addition, histone demethylase LSD1 epigenetic modifiers offer important information on the survival of EMT by reducing invasiveness or inhibiting the transfer function. Thus, inhibiting LSD1 [76] may lead to improved survival because of the inhibition of invasiveness and metastasis [76].
\nAlthough epigenetic therapies exhibit considerable potential for clinical applications, the clinical application of epigenetic drugs remains ambiguous because of its unclear mechanism. The mechanism of epigenetic drugs should be investigated further. Therefore, the enhancement of specificity may solve the potential problem on the treatment of particular epigenetic targets in the future [74].
\nDrugs are likely to become anti-cancer drugs in clinical applications. Further study on the clinical trials of cancer has shown that metformin arouses attention as a promising anti-cancer agent [77, 78]. Metformin involves systemic effects, such as reducing insulin levels and acting on one-carbon metabolism. This metabolism will be explored with epigenetic alterations based on the connection between metabolism and the epigenetic state of cells [79].
\nDecitabine, which is a DNA methyltransferase (DNMT) inhibitor, suppresses the migration capacities of SDH-mutant cells. This inhibition is evidently displayed by succinate abnormal accumulation in epigenetic dysregulation and the resultant EMT. Mutant enzymes to directly explore the inhibition approach for SDH- and FH-associated cancers are worthy to be explored [80].
\nEMT is a comprehensive reprogramming during tumor development. This process involves metabolism, epigenetics, and differentiation. In a specific tumor microenvironment, EMT-dedifferentiated cells escape the primary tumor after they acquire migration and invasion capabilities, invade the surrounding tissues, enter into the blood or lymphatic vessels, and settle in distant organs. EMT converts differentiated epithelial cancer cells to an undifferentiated state, thereby expressing stem cell markers and acquiring stem cell-like functions. This process is reversible, and mesenchymal cells can differentiate into epithelial phenotypes. Thus, an important process is developed in the macroscopic metastases in different organs.
\nDNA methylation, histone modification, and microRNA are the three types of epigenetic modification. Many studies have shown that epigenetic modifications play a key role in tumor metastasis [81]. The downregulation of E-cadherin (a cell adhesion molecule) expression during EMT is an important feature. Therefore, the precise regulation of E-cadherin expression via epigenetic modifications is extremely important to the occurrence of EMT. Several EMT-related transcription factors are recruited as E-cadherin gene promoter, which inhibits transcription [4]. Studies have shown that E-cadherin can be inhibited by the synergy of various histone modification enzymes. The E-cadherin gene promoter is inhibited to different extents to silence E-cadherin expression [82].
\nThe characteristics of EMT are reversible in the type of stem cells and malignant features. Tumor stem cells are unique undifferentiated cells, rather than increasing diffusion, compared with most differentiated epithelial cells. The diffusion of anabolic needs is related to the maintenance of an undifferentiated state, which may be metabolic alterations of the links between EMT and tumor [83]. A change in cell metabolism is an important sign of cancer. The best metabolic phenotype in tumor cell is characterized by the Warburg effect, which proves that ATP is not the only metabolite of tumor cells [84]. Further studies have shown that aerobic glycolysis can better satisfy the basic needs of cell division, known as the post-Warburg model. This process is not only associated with cancer and normal cell proliferation, but also inhibits mitotic cell differentiation. In the same inducers, bunah and inactivated tumor suppressor genes, even oxygen glycolysis capability increased in the EMT, can be attributed to cell undifferentiated state. The appropriate energy level is sufficient for biosynthesis precursor, balancing normal state, and maintaining an undifferentiated state.
\nEpigenetic modifications are complex, dynamic, and connected with the extracellular environment and nuclear transcription. Energy availability is extremely important. Energy-rich substances, such as carbohydrates and fats, in the human body translate into ATP, along with a large number of metabolites, such as glycolysis and fatty acid oxidation. These metabolites can also drive epigenetic modifications in gene expression. A change in the intermediate metabolites of EMT may not be simple. Metabolic reprogramming plays a role in the energy crisis causation of cancer cells. This process determines the epigenetic sand by modifying the undifferentiated state of the chromatin structure. Reprogrammed genes and the change in gene expression influence EMT markers and metabolic enzymes to overcome the local restriction to obtain energy in the distant tissues and organs. The microenvironment is significant for the EMT metastasis potential of cancer cells in reprogramming metabolism, epigenetics, and differentiation. Hepatic, epidermal, and fibroblast growth factors activate and maintain the EMT process. The cancer microenvironment growth factor activity generally regulates the interaction between metabolism and EMT to coordinate cell differentiation and metabolism.
\nThe transfer process is the key to the reversibility of EMT based on our previous study, in which EMT regulation is mainly at the transcription level [4]. However, numerous molecular mechanisms cooperate to change the behavior of tumor cells. In particular, the role of the transcription regulation of EMT in the regulation and control of gene expression of the transcription of alternative splicing is extremely important. Spliceosome assembly has experienced gradual, composition, and structure changes required for normal maintenance. The correlation of alternative splicing tumor progression becomes apparent. In fact, all major cell biology deregulations of cancer are related to the changes in the alternative splicing of a specific gene profile. Modifying the splicing expression and activities supervised by SR and hnRNP provides the main source of changes in the stitching program observed in cancer cells [85].
\nMalignant EMT plays a key role during transfer, and the alternative splicing program affects the cell phenotype, including protein, cell adhesion, and cytoskeleton dynamics, influences tumor microenvironment, and controls tumor metastasis formation. Cancer gene mutations initiate processes, and epigenetic changes will be necessary to promote cancer. The change in the epigenome improves the transfer of cells.
\nIn general, cells, which are affected by external environment signals, satisfy the internal requirements of nutrient and energy metabolism, as well as cooperate actively to promote the occurrence of EMT. Thus, tumor metabolic adaptations and EMT are different mechanisms for the same target cells to survive and grow. A close link and high correlation exist between metabolic reprogramming EMT and the similarity rule and fly mechanism.
\nMicroRNAs (miRNAs) are expressed endogenously as small, non-coding RNAs that regulate various biological processes by modulating gene expression at the post-transcriptional level [86]. MiRNAs play an important role in controlling tumor growth and progression. Some miRNAs function as oncogenes and tumor suppressors. Moreover, miRNAs are also master regulators of EMT and dynamically regulate balance between EMT and MET.
\nThe miR-200 family consists of five miRNA sequences, namely miR-200a, miR-200b, miR-200c, miR-141, and miR-429. Aggregated miRNAs that are expressed as two independent polycistronic pri-miRNA transcripts are as follows: miR-200a, miR-200b, and miR-429 (chromosome 1); and miR-200c and miR-141 (chromosome 12) [87].
\nThe autocrine TGF-β/ZEB/miR-200 signaling regulatory networks that control epithelial and mesenchymal states change in the cells. ZEB1/2 and TGF-β exhibit strong correlation, and negative correlations are detected between TGF-β and miR-200, as well as between ZEB1/2 and miR-200, in invasive ductal carcinomas [88]. ZEB1/2 can induce EMT by inhibiting various epithelial genes [89].
\nOther miRNAs can directly target EMT transcription factors. MiR-205 in mammary cells maintains epithelial differentiation [90–92]. MiR-29b in prostate cancer inhibits metastasis by regulating the EMT signal. MiR-148a in hepatocellular carcinoma (HCC) cells can negatively regulate Met/Snail signaling and prevent EMT and metastasis [93]. Snail and miR-34 form another double feedback loop. EMT is induced by TGF-β, and an increase in Snail expression can be inhibited by miR-34. A novel miR-203/SNAI1 feedback loop has also been reported in breast cancer. These double feedback loops can enhance the balance between EMT activation and control of the two states of the cell (epithelial and mesenchymal). A novel EMT network that integrates the negative feedback loops, miR-203/Snai1, and miR-200/ZEB has been proposed recently as a control epithelial cell plasticity switches during differentiation and cancer [94]. The expression of miR-10b in metastatic breast cancer cells is shown to be induced by the transcription factor Twist, which binds directly to the putative promoter of miR-10b. Twist-induced miR-10b inhibits the translation of mRNA encoding homeobox D10, which results in an increased expression of RHOC, which is a well-characterized prometastatic gene [95].
\nMany miRNAs interfere with EMT by targeting the structures of cell components [96–98]. MiR-155 is the direct transcriptional target of TGF-β/Smad 4 signaling [99]. MiR-155 ectopic expression can reduce the RhoA (Ras homolog gene families, member A) protein, a small GTPase protein, to modulate the formation of tight junctions in the formation of stress fibers of the actin cytoskeleton during expression and destruction [100]. The activation of miR-31 in establishing metastases results in the regression of metastasis and the enhancement of the survival of patients. In addition, the induction of miR-31 can reduce the metastatic potential of cancer cells by targeting the RhoA [101]. The upregulation of miR-9 and direct repression of E-cadherin-1 (CDH1) in human breast cancer cells are involved in the regulation of cell-cell adhesion, migration, and the epithelial cell proliferation mechanism of calcium-dependent protein. CDH1 repression results in increased cell motility and invasion [102].
\nNumerous tumor EMT inhibitors have been found in this study, and many of which are difficult to apply clinically because of stability and targeting isssues. TGF-β is an important factor in regulating EMT.
\nVarious EMT inhibitors have been found in the TGF-β signaling pathway. Thyroid transcription factor-1 is a protein encoded by the NKX2-1 gene in normal tissues that can inhibit the secretion of TGF-β, which increases the expression of E-cadherin in lung cancer cells.
\nMMPs are other key factors in the induction of EMT. The inhibitors of MMPs play an important role in blocking EMT development in tumor cells. Several MMP inhibitors, which have been tested in clinical trials, can prevent EMT in cell experiments in vitro and inhibit tumor progression in in vivo animal experiments. Orlistat Plymouth, one of the MMP inhibitors, has a relatively significant effect on non-small cell lung cancer, colorectal cancer, and glioma, both in in vitro cell experiments and in vivo animal experiments. Conducting combination chemotherapy with marimastat, captopril, and Fragmin exerts a certain effect on the treatment of advanced kidney cancer. The human body itself can also synthesize a special kind of MMP inhibitor, a tissue inhibitor of metalloproteinase (tissue inhibitors of metalloproteinases, TIMPs). TIMPs, which are produced using genetic engineering technology, can also be used as targeted drugs to treat tumors caused by the imbalance among MMPs and inhibit the progression of EMT in tumor cells.
\nCertain phytochemicals or food substances exhibit anti-cancer [103, 104] and anti-EMT properties [105]. For example, AIMs (anthocyanidins) and Morusin (a prenylated flavonoid), which are isolated from the fruits of
AIMs can inhibit NF-κB in a dose-dependent manner, and MMP-9 (EMT marker) can be regulated by NF-κB preferentially [109]. IκBα phosphorylation and GSK-3 activity can also be suppressed by increasing the levels of AIMs [110]. Moreover, AIM downregulates mesenchymal markers, such as Vim1, N-cadherin, and SNAI, as well as upregulates epithelial markers, such as E-cadherin [110]. The morphological changes induced by TNF-α [110] are also inhibited by AIM. The suppression of the migratory and invasive properties of cervical cells by AIM has also been reported. Cervical cancer contains a heterogeneous population of cells called CSCs. CSCs are cells with chemotherapy- and radiotherapy-resistant properties and are involved in tumor recurrence, metastasis, and high mortality [111, 112]. Morusin, however, are reported to be cytotoxic to several cancer cell lines, including cervical cells. Morusin can inhibit migration and proliferation by inhibiting tumor sphere formation through the inhibition of the NF-kB pathway.
\nRecent studies in our laboratory have found several EMT inhibitors, including tetracycline and some natural products. The gelatinase inhibitor doxycycline is the prototypical anti-tumor antibiotic. We have investigated the effects of doxycycline on the migration, invasion, and metastasis of human lung cancer cell lines and in a mouse model. We have also measured the effect of doxycycline on the transcription of EMT markers and used immunohistochemistry to determine whether EMT reversal is associated with doxycycline inhibition. Doxycycline dose-dependently inhibits the proliferation, migration, and invasion of NCI-H446 human small cell lung cancer cells. It also suppresses tumor growth from NCI-H446 and A549 lung cancer cell xenografts without altering body weight, inhibits Lewis lung carcinoma cell migration, and prolongs survival. The activities of the transcription factors Twist1/2, SNAI1/2, AP1, NF-κB, and Stat3 are suppressed by doxycycline, which reverses EMT and inhibits signal transduction, thereby suppressing tumor growth and metastasis. Our data demonstrate functional targeting of transcription factors by doxycycline to reverse EMT and suppress tumor proliferation and metastasis. Thus, doxycycline selectively targets malignant tumors and reduces their metastatic potential with less cytotoxicity in lung cancer patients.
\nApigenin is a naturally occurring compound with anti-inflammatory, antioxidant, and anticancer properties. We have investigated the effects of apigenin on migration and metastasis in experimental HCC cell lines in vitro and in vivo. Apigenin dose-dependently inhibits the proliferation, migration, and invasion of PLC and Bel-7402 human HCC cells. It also suppresses tumor growth in PLC cell xenografts without altering body weight, thereby prolonging survival. Apigenin reduces Snai1 and NF-κB expression, reversed increases in EMT marker levels, increases cellular adhesion, regulates actin polymerization and cell migration, and inhibits invasion and migration of HCC cells. Therefore, apigenin may inhibit EMT by inhibiting the NF-κB/Snail pathway in human HCC. Table 1 shows some EMT inhibitors found in the last 3 years.
\nMolecules | \nTumor types | \nPathway | \nReferences | \n
---|---|---|---|
Cyclin G2 | \nOvarian cancer | \nWnt/β-catenin | \nBernaudo et al. [113] | \n
FOXO3a | \nProstate cancer | \nWnt/β-catenin | \nLiu et al. [114] | \n
sFRP4 | \nHead and neck squamous cell carcinoma | \nWnt/β-catenin | \nWarrier et al. [115] | \n
sophocarpine | \nHepatocellular carcinoma | \nAKT/GSK-3β/β-catenin | \nZhang et al. [116] | \n
Bisdemethoxycurcumin | \nLung cancer | \nTGF-β | \nXu et al. [117] | \n
Ski | \nLung cancer | \nTGF-β | \nYang et al. [118] | \n
GRP78 | \nColon cancer | \nTGF-β | \nZhang et al. [119] | \n
Thymoquinone | \nBreast cancer | \nTGF-β | \nRajput et al. [120] | \n
BMP-7 | \nCholangiocarcinoma | \nTGF-β | \nDuangkumpha et al. [121] | \n
NDRG2 | \nColon cancer | \nTGF-β | \nShen et al. [122] | \n
Myrtucommulone-A and thymoquinone | \nBladder cancer and breast cancer | \nPI3K | \nIskender et al. [123] | \n
ING5 | \nBreast cancer | \nPI3K | \nZhao et al. [124] | \n
α-Mangostin | \nPancreatic cancer | \nPI3K | \nXu et al. [125] | \n
NVP-BEZ235 | \nOvarian cancer | \nPI3K | \nLin et al. [126] | \n
IL-32θ | \nColon cancer | \nSTAT3 | \nBak et al. [127] | \n
Luteolin | \nPancreatic cancer | \nSTAT3 | \nHuang et al. [128] | \n
FTY720 | \nCholangiocarcinoma | \nSTAT3 | \nLu et al. [129] | \n
NDRG2 | \nBreast cancer | \nSTAT3 | \nKim et al. [130] | \n
Some EMT inhibitors.
Contraception is the act of preventing pregnancy by interrupting the chains of events that lead to conception. It is very paramount in reducing the risk of unintended pregnancies and their attendant complications. It has been estimated that of the 210 million pregnancies that occur annually worldwide, about 80 million (38%) are unplanned, and 46 million (22%) end in abortion. Unintended unprotected intercourse is the primary cause of unwanted pregnancies, and many women with unwanted pregnancies decide to end them by abortion, which is most unsafe. Wider uptake of long-acting reversible contraceptive (LARC) methods is predicted to scale back the high rate of unintended pregnancy [1].
LARCs are defined within the UK National Institute for Health and Care Excellence guideline as contraceptive methods that need administration but once per cycle or month. Included within the category of LARCs are progestin-only contraceptive implants and other methods. Contraceptive implants are progesterone-only contraception that is inserted subdermally or within the skin. They are readily reversible with a return to fertility within days of removal. Moreover, these contraceptive devices are often safely placed within the immediate postpartum period, ensuring good contraceptive coverage [2].
In the same vein, contraceptive implants are subdermal contraception involving the delivering of a steroid progestin from polymer capsules or rods which are inserted under the skin. The hormone diffuses gradually and slowly at a stable rate, providing effective contraception within five (5) years. The safe period depends upon the precise progestin and therefore, the sort of polymer. The advantages of these implants includes the long term contraceptive action, low dose of highly effective contraception, and quick reversal to fertility after the removal of implants [3].
Furthermore, it is recorded that contraceptive implants are safe, highly effective, and long-term methods of contraception that are widely applicable to any reproductive-aged woman. Implanon is currently approved for three (3) years of use, provides excellent efficacy throughout its use, and is straightforward to insert and remove. Implants require minimal user compliance and are cost-effective. Implanon has been shown to be safe to use during lactation, may improve dysmenorrhoea (painful menstruation), and does not significantly affect bone mineral density, lipid profile, or liver enzymes. The progestin-only implants are safe options for various women including adolescents, postpartum (after birth), breastfeeding, those that are medically complicated, or those that have contraindications to or intolerance of oestrogen-containing contraceptives.
In addition, contraceptive prevalence rate is the percentage of women (15–49 years) who are in union using any type of contraception either traditional or modern. The unmet need for family planning is the ratio of women (15–49 years) not using any contraceptive methods but are either married or in a union, and who are sexually active and able to give birth to children, but do not want children again, or would really prefer to space the birth of another baby for at least two years [4, 5].
This chapter focuses on types of contraceptive implants and its mechanism of action; the side effects of contraceptive implants; health benefits and positive characteristics of contraceptive implants; those who can and cannot use contraceptive implants; reasons women are not interested in implants and factors influencing its usage.
The historical background of the contraceptive implants shows that Norplant was the earliest implant and it had been first produced in Finland in 1983 with a 5-year lifespan. It contained six rods, each containing levonorgestrel (LNG). Continuing research centered on reducing the amount of units to facilitate easier insertion and removal led to its successor, Norplant-2 or Jadelle (two-rod implant), which was approved within the U.S. in 1996 but its production was discontinued globally in 2008. Implanon was launched in 1999 as one rod of etonorgestrel, with contraceptive efficacy of three (3) years. Its successor, Implanon NXT (Nexplanon), with a redesigned applicator to ease its insertion, was introduced in 2010. It is replacing Implanon in many countries. Other implants like NesteroneTM and CapronorTM, consisting of various progestins, biodegradable rods, pellets, and microcapsules remain in development. Advancement during this area has also produced male contraceptive implants MENT acetate that contains 7α-methyl-19-nortestosterone, although still undergoing approval processes [1].
In view of the above records, the following are the identified kinds of implantable contraceptives [1, 6]:
This contraceptive is acceptable for women (14–49 years) who desire long-acting reversible contraception (LARC). It must be removed and replaced every three (3) or five (5) years. Ovulation returns within three (3) to six (6) weeks after the removal of Implanon. Implantable contraceptives provides no protection against Sexually Transmitted Infections (STIs) or Human Immunodeficiency Virus (HIV) [7].
The progestin-containing implantable contraceptives inhibit ovulation and restrict sperm penetration through sticky cervical mucus. This is done as a result of the antiestrogenic actions of the progestins, which affect the cervical mucus by making it sticky or glutinous, scanty, and impassable to sperm therefore preventing or hindering fertilisation of the ovum. High doses of progestins also prevent gonadotropin secretion, thereby halting the maturation of the follicles and ovulation. This double effect allows the efficacy and effectiveness of implantable contraceptives to be maintained though ovulation is not consistently altered in etonorgestrel implantable contraceptive users towards the end of the 3-year period of use. Oocytes are not fertilised even if the follicles grow while using progestin implantable contraceptives. Even if the follicle ruptures, the abnormalities of the ovulatory cycle or phases prevent the release of a viable ovum or egg. Although progestin suppresses endometrial activity, this is often not a contraceptively significant effect since the most mechanisms of action prevent fertilisation. There has never been any signs of embryonic development found among contraceptive implant users, showing that progestin implants are not medication or substances that cause pregnancy to terminate prematurely. Implants are simpler, easier and safer to use than other contraceptive methods because they do not require regular action by the user [8].
The following advantages of contraceptive implants had been identified [9, 10]:
High effectiveness of up to 99 percent within seven days of implant insertion;
Very inexpensive method of longterm contraception, like intrauterine devices;
It is convenient to use or adopt by all women of childbearing age (i.e. from age 14–49 years);
It is very safe for women of childbearing age;
It is very efficacious for three years;
It could be easily removed when pregnancy is expected by women;
It provides continous contraception;
The anonymity of use is provided;
It is safe during breastfeeding period for women;
It relieves excessive and difficulty menstruation in some women;
Amenorrhoea which is experienced in some women using contraceptive is often perceived to be a benefit;
It reduces the risk of pelvic inflammatory disease in women;
It is good for conditions which prevent the use of combined hormonal contraceptive;
There is quick return of fertility after the removal of contraceptive implant;
Some women experience improvement in acne following the use of the implant; and
Some protection against endometrial cancers.
The following are the disadvantages of contraceptive implants [9, 10]:
There is no protection against sexually transmitted infections (STIs) when using contraceptive implant;
There is a contra-indication with anticonvulsants, some antibiotics, or St. John’s wort;
It does not proffer immediate protection when inserted, hence, another type of effective contraceptive must be used for at least seven days following the insertion;
It has some nauseating side effects;
It diminishes sexual pleasure in some frigid women; and
It encourages promiscuity in some sexually active women.
The side effects of implants include the following: changes in bleeding patterns, including (a) lighter bleeding and fewer days of bleeding; prolonged bleeding; irregular bleeding; infrequent bleeding; and no monthly bleeding (within a year period); (b) lighter bleeding and fewer days of bleeding; irregular bleeding; infrequent bleeding; and no monthly bleeding (after a year period); (c) users of Implanon and Implanon NXT are more likely to experience infrequent bleeding, prolonged bleeding, and/or no monthly bleeding than irregular bleeding; (d) other side effects are: headaches; abdominal pain; acne (can improve or worsen); weight change; breast tenderness; dizziness; mood changes; nausea; and enlarged ovarian follicles. The bleeding changes are normal and are not harmful. It also included skin atrophy at the site of insertion; impalpable implants; neurovascular injury; fractured implants; and abnormal uterine bleeding, as the risks or side effects of contraceptive implants [1, 6].
The benefits of implantable contraceptives are: it helps protect against risks of pregnancy, including ectopic pregnancy; it protects against symptomatic pelvic inflammatory disease; it is going to help protect against iron-deficiency anaemia; and it reduces the risk of ectopic pregnancy. Contraceptive prevents pregnancy; reduces unintended pregnancy and abortion; reduces pregnancy-related morbidity and mortality; improves birth outcomes; helps women and couples time and space their pregnancies; improves maternal health behaviours; reduces cancer risk; improves mental health-related outcomes; and treats menstrual-related symptoms and disorders [6, 11].
Furthermore, it was discovered that the use of contraceptive implants brings harmony between the couples, which invariably promotes their mental health; and contraceptive implants are the most cost-effective method of family planning because it prevents unintended pregnancies and abortion among women of childbearing age [10].
It had been postulated in some studies that contraceptive implants is safe; highly effective; it is convenient; it facilitates harmony between the couples. In the same vein, implants have many positive characteristics that contribute to their rapidly rising popularity [10, 12]:
Implants can be quickly, safely, and easily inserted by medical and community health workers.
Whichever contraceptive implant a client chooses, women can be assured with highly effective contraception for up to five (5) years.
Implants have the highest effectiveness of all methods.
Implants do not entail pelvic examination or abdominal surgery (like intrauterine devices (IUDs) and feminine sterilisation).
Removal is typically a fast and uncomplicated procedure.
There is prompt return to fertility.
Implants are appropriate for limiting further births.
Implants generally have high client satisfaction, as implied in their high continuation rates.
Implants provision requires less health system infrastructure and less-highly trained staff than other provider-dependent clinical methods.
It has been stated that almost all women of childbearing age can use implantable contraceptives safely and effectively, including women who: (a) have or have not had children; (b) are married or unmarried; (c) are of any age (e.g. adolescents and women over 40 years old); (d) have just undergone an abortion, miscarriage, or ectopic pregnancy; (e) smoke cigarettes; (f) are breastfeeding; (g) have anaemia; (h) have varicositis; (i) and are living with HIV [6].
In furtherance to the above reports, implantable contraceptive should be considered for women who: (a) desire a long-acting and highly effective contraception; (b) experience serious or minor side effects of eostrogen and/or eostrogen-progestin contraception; (c) are interested in a contraceptive method that does not require continous adherence; (d) love a non-coitus-related type of contraceptive; (e) have completed childbearing but not ready for permanent sterilisation; (f) have a history of anaemia with abnormally heavy bleeding at menstruation; and (g) have chronic illnesses which threaten pregnancy [8].
However, contraceptive implants should not be considered for women: known or suspected of pregnancy; having current or past history of thrombosis or thromboembolic disorders; having hepatic tumour or active liver disease; having undiagnosed abnormal genital bleeding; having known or suspected breast cancer or history of breast cancer; and having hypersensitivity to any component of the method [8].
Some studies identified the demographic factors influencing the use of contraceptive as age; parity; marital status and marriage type e.g. polygamy has been associated with lower levels of contraceptive use. A study from Northeast Nigeria reported that women in polygamous unions are less likely to use contraceptives compared with women in monogamous unions. Polygamy, when coupled with youthful age at marriage and with a wide differences in age between spouses, may inhibit husband-wife interactions and perpetuate male dominance within the marriage. This was in line with the study carried out in Ethiopia that showed that woman’s age, number of children alive, couple’s intention for more children and discussions about contraceptive use among the couple were significantly associated with demand for modern contraceptives among women. Also, it was agreed that religion, education status and age at marriage were significantly associated with contraceptive usage. Furthermore, in a study, it was discovered that age does not affect contraceptive implants use; educational status is significant to the usage of contraceptive implants; there is an association between the age at first birth and the use of contraceptive implants, which indicates that age at first birth influences the use of contraceptive implants; and the number of liveborn children has a significant impact or influence on the use of implants. A study also indicates that any categories of women of childbearing age could use or utilise contraceptive implants [10, 13, 14, 15].
It has been stressed that age of women, the level of education of women, the religion of women, marital status of women, health care visits during antenatal care and childbirth were significantly associated with the use of any contraceptive method [16].
It had been discovered that socio-demographic factors may be alleviated by biological and behavioural factors, such as sexual activity, fecundity and desire for children. African societies as pro-natalist, believe that children are a gift from God and as such are social and economic investments; this has undesirable influence on the use of contraceptives. Studies have found that an inverse relationship exists between the number of living children and use of modern contraceptives. Evidence from variety of nations has pointed towards the partner’s disapproval and his desire for more children as key factors for non-use of contraception [13].
Furthermore, it has been stressed that there has been found a strong relationship between women’s education, especially completed primary education and entry into secondary level, and fertility reduction. Several studies have reported that women’s education has a strong positive impact on contraceptive use). In Nigeria, education has been found to increase contraceptive use. Nigerian women with tertiary level education are one-and-a-half times more likely to have ever used contraception than women with secondary education. Partner’s level of education is equally important, because it may operate through many of an equivalent pathways (childbearing preferences) because the woman’s own education, as long as education levels of husbands and wives are positively correlated. Results from some studies conducted showed that older female adolescents were quite three (3) times likely to practice contraceptive use than younger female adolescents. The findings also revealed that the level of education, working status, knowledge of ovulatory cycle, visit of the health facility and marital status were the determinants for contraceptive use among female adolescents [13, 17].
The extent of education may be a predictor of socio-economic status, which correlates with contraceptive use. It showed that women of lower socio-economic status have lower uptake rates of contraceptives. Also, exposure to mass media has strong effects on attitudes towards family planning through ideation. However, a study identified the following as reasons for rejecting contraceptive implants among women of childbearing age: fear of side effects; lack of interest; husband’s refusal; lack of information; religion influence; contraceptive failure; lack of regular sex; and it diminishes sexual pleasure [10, 13].
It has been discovered in some studies that some women were afraid of the side effects of contraceptives; some want to conceive; familial pressure; lack of knowledge, are the reasons some women of childbearing age do not accept contraceptives. Also, a research showed that the fear of side effects is the main reason for low contraceptive prevalence among young female students. However, the results of a study carried out indicated that the main reasons for switching to implant contraceptive among women of childbearing age were: convenience, contraceptive failure and experienced side effects with other contraceptive methods.
Furthermore, some studies found out in their studies that women of childbearing age who were not using any form of contraceptive was as a result of lack of knowledge; negative perception of contraceptive side effects; lack of interest; lack of regular sex; husband’s refusal; expectant of becoming pregnant; and some could not afford it. A study also showed that any categories of women of childbearing age could use or utilise contraceptive implants, they identified the following reasons women of childbearing age are not interested in contraceptive implants: fear of side effects; it diminishes sexual pleasure; it encourages promiscuity; lack of information about the contraceptive implants; expectant of becoming pregnant; contraceptive failure; husband’s refusal; lack of regular sex; lack of interest in the use of contraceptive implants; religion influence; and cultural background [10, 15, 16, 18, 19].
The following recommendations for the acceptance of contraceptive implants among women of childbearing age [10]:
All health workers should intensify efforts by properly informing women of childbearing age concerning contraceptive implants;
During antenatal and postnatal visits, women should be health educated on the benefits, the cost-effectiveness and minimal side effects of contraceptive implants;
There is the need for couples to understand each other and decide on the use of contraceptive implants, which is safe, convenient and highly effective for the family circuit.
There should be more public enlightenment campaigns on the use of contraceptive implants most especially the sexually active teenagers, so as to prevent teenage pregnancies and teenage motherhood.
Regular jingles should be on radio and television, so as to improve the knowledge of women of childbearing age towards the acceptance of contraceptive implants.
Husbands should be carried along during counselling before choosing any contraceptive implants for their spouses.
All myths, rumours and misconceptions against contraceptive implants should be dispelled by the government either through regular jingles or through the use of mass media and billboards.
Contraceptive implants and its attendant services should be rendered free to all women of childbearing age.
Any woman with the side effects of contraceptive implants should be treated or managed freely in the health institutions.
This chapter has shown that contraceptive implants or implantable contraceptive are five subdermal implants, rods the size of pencil lead that are embedded just under the skin on the inside of the upper arm. The chapter further indicated the types of contraceptive implants which included Norplant, Norplant-2 (Jadelle/Sinoplant-II), Nexplanon (Implanon NXT), Implanon, Capronor, Nestrone, and MENT (subdermal implants for men).
Furthermore, the mechanism of action of contraceptive implants, the advantages and disadvantages of contraceptive implants had been discussed including its side effects. The health benefits of the implantable contraceptive including the positive method characteristics of contraceptive implants have been well stated in the chapter.
This chapter also discussed those who can and cannot use implantable contraceptives as well as the factors influencing the acceptance of contraceptive implants. The attitude and practice of women of childbearing age to contraceptive usage had been discussed, likewise, some recommendations which would promote the use of contraceptive implants among women of childbearing age had been extensively stated in this chapter.
My appreciation goes to all researchers and/or authors whose materials were used for this work.
Furthermore, worthy of gratitude is the International Journal of Pharmaceutical Sciences and Medicine (IJPSM), for allowing me to reproduce some of our research data in their Journal.
There is no conflict of interest as far as this work is concerned.
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\n\n3. In those rare instances where IntechOpen declines to publish a book that had been previously accepted, full refunds will be made to the same account or credit card from which the Author made the original payment.
\n\nPlease note that refunded amounts will not always be exactly the same as original payment amounts due to bank transaction fees and expenses. Any such costs will be split evenly between IntechOpen and the Author.
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These cells remain in a quiescent state until they are activated by different factors, usually those generated by an alteration in the parenchymal tissue. These cells have characteristic membrane markers such as CD73, CD90, and CD105. Those are a receptor, which in response to their ligand induces strong changes in different metabolic pathways that lead to these cells, both to generate molecules with different activities and to leave their stationary phase to reproduce and even differentiate. This review describes the metabolic pathways dependent on these membrane markers and how they influence on parenchymal tissue and other stromal cells.",book:{id:"6658",slug:"stromal-cells-structure-function-and-therapeutic-implications",title:"Stromal Cells",fullTitle:"Stromal Cells - Structure, Function, and Therapeutic Implications"},signatures:"Maria Teresa Gonzalez Garza",authors:[{id:"181389",title:"Ph.D.",name:"Maria Teresa",middleName:null,surname:"Gonzalez Garza",slug:"maria-teresa-gonzalez-garza",fullName:"Maria Teresa Gonzalez Garza"}]},{id:"63044",title:"Stromal-Epithelial Interactions during Mammary Gland Development",slug:"stromal-epithelial-interactions-during-mammary-gland-development",totalDownloads:1372,totalCrossrefCites:2,totalDimensionsCites:6,abstract:"Mammary gland is an organ, which undergoes the majority of its development in the postnatal life of mammals. The complex structure of the mammary gland comprises epithelial and myoepithelial cells forming the parenchymal tissue and adipocytes, fibroblasts, vascular endothelial cells, and infiltrating immune cell composing the stromal compartment. During puberty and in adulthood, circulating hormones released from the pituitary and ovaries regulate the rate of development and functional differentiation of the mammary epithelium. In addition, growing body of evidence shows that interactions between the stromal and parenchymal compartments of the mammary gland play a crucial role in mammogenesis. This regulation takes place on a paracrine level, by locally synthesized growth factors, adipokines, and cytokines, as well as via direct cell-cell interactions. This chapter summarizes the current knowledge about the complex nature of interactions between the mammary epithelium and stroma during mammary gland development in different mammalian species.",book:{id:"6658",slug:"stromal-cells-structure-function-and-therapeutic-implications",title:"Stromal Cells",fullTitle:"Stromal Cells - Structure, Function, and Therapeutic Implications"},signatures:"Żaneta Dzięgelewska and Małgorzata Gajewska",authors:[{id:"165068",title:"Dr.",name:"Malgorzata",middleName:null,surname:"Gajewska",slug:"malgorzata-gajewska",fullName:"Malgorzata Gajewska"},{id:"249847",title:"Ms.",name:"Żaneta",middleName:null,surname:"Dzięgelewska",slug:"zaneta-dziegelewska",fullName:"Żaneta Dzięgelewska"}]},{id:"69757",title:"Flow Cytometry Applied to the Diagnosis of Primary Immunodeficiencies",slug:"flow-cytometry-applied-to-the-diagnosis-of-primary-immunodeficiencies",totalDownloads:1041,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Primary immunodeficiencies are the result of biological defects associated with functional immune abnormalities. It consists of a group of disorders showing a higher incidence and severity of infections, expression of immunological dysregulation such as inflammation and lymphoproliferation. The immunophenotyping and in vitro functional characterization of immunodeficient patients contribute, together with the clinical aspects, to define the underlying immune defect particularities. Flow cytometry applications in primary immunodeficiency assessment are multiple and include the study of a wide range of specific cell lymphocyte subpopulations. This chapter describes the main techniques used in the diagnosis of a wide variety of primary immunodeficiencies, in which intracellular proteins or activation markers involved in immunity are evaluated, as well as functional proliferation, cytokine production, phosphorylation of transcription factors, cytotoxic and degranulation capacity. Flow cytometry is a tool that allows rapid and accurate evaluation of multiple lymphocyte populations and immunological function, and this information is essential for the diagnosis and evaluation of patients with primary immunodeficiencies.",book:{id:"6913",slug:"innovations-in-cell-research-and-therapy",title:"Innovations in Cell Research and Therapy",fullTitle:"Innovations in Cell Research and Therapy"},signatures:"Mónica Martínez-Gallo and Marina García-Prat",authors:[{id:"286242",title:"Ph.D.",name:"Mónica",middleName:null,surname:"Martínez Gallo",slug:"monica-martinez-gallo",fullName:"Mónica Martínez Gallo"},{id:"286704",title:"BSc.",name:"Marina",middleName:null,surname:"García-Prat",slug:"marina-garcia-prat",fullName:"Marina García-Prat"}]},{id:"50685",title:"States of Pluripotency: Naïve and Primed Pluripotent Stem Cells",slug:"states-of-pluripotency-na-ve-and-primed-pluripotent-stem-cells",totalDownloads:4009,totalCrossrefCites:4,totalDimensionsCites:12,abstract:"Pluripotent stem cells are classified into naïve and primed based on their growth characteristics in vitro and their potential to give rise to all somatic lineages and the germ line in chimeras. In this chapter, I describe the similarities and differences between the naïve and primed pluripotent states as exemplified by mouse embryonic stem cells (mESCs), mouse epiblast stem cells (mEpiSCs), human embryonic stem cells (hESCs), and human induced pluripotent stem cells (hiPSCs). I also review the efforts for derivation of naïve human pluripotent stem cells by manipulating culture conditions during reprogramming of somatic cells and attempts to revert primed hESCs to the naïve state. Understanding the requirements for induction and maintenance of the naïve pluripotent state will facilitate studies on early human embryonic development and understanding the mechanisms involved in X inactivation in vitro. In addition, the development of naïve hiPSCs will improve the efficiency of gene targeting for the purpose of modeling human diseases as well as for generating gene‐corrected autologous pluripotent stem cells for regenerative medicine.",book:{id:"5207",slug:"pluripotent-stem-cells-from-the-bench-to-the-clinic",title:"Pluripotent Stem Cells",fullTitle:"Pluripotent Stem Cells - From the Bench to the Clinic"},signatures:"Daman Kumari",authors:[{id:"180527",title:"Dr.",name:"Daman",middleName:null,surname:"Kumari",slug:"daman-kumari",fullName:"Daman Kumari"}]}],onlineFirstChaptersFilter:{topicId:"990",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:8,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:286,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:105,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:9,numberOfPublishedChapters:101,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:11,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"May 15th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:27,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. Dr. Ekinci serves as the Editor in Chief of four international books and is involved in the Editorial Board of several international journals.",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null},{id:"17",title:"Metabolism",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",isOpenForSubmission:!0,editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. His teaching areas are energy metabolism and regulation, integration and organ specialization and metabolic adaptation.",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null},{id:"18",title:"Proteomics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",isOpenForSubmission:!0,editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. 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She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. 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Fungal infectious illness prevalence and prognosis are determined by the exposure between fungi and host, host immunological state, fungal virulence, and early and accurate diagnosis and treatment. \r\nPatients with both congenital and acquired immunodeficiency are more likely to be infected with opportunistic mycosis. Fungal infectious disease outbreaks are common during the post- disaster rebuilding era, which is characterised by high population density, migration, and poor health and medical conditions.\r\nSystemic or local fungal infection is mainly associated with the fungi directly inhaled or inoculated in the environment during the disaster. The most common fungal infection pathways are human to human (anthropophilic), animal to human (zoophilic), and environment to human (soilophile). Diseases are common as a result of widespread exposure to pathogenic fungus dispersed into the environment. \r\nFungi that are both common and emerging are intertwined. In Southeast Asia, for example, Talaromyces marneffei is an important pathogenic thermally dimorphic fungus that causes systemic mycosis. Widespread fungal infections with complicated and variable clinical manifestations, such as Candida auris infection resistant to several antifungal medicines, Covid-19 associated with Trichoderma, and terbinafine resistant dermatophytosis in India, are among the most serious disorders. \r\nInappropriate local or systemic use of glucocorticoids, as well as their immunosuppressive effects, may lead to changes in fungal infection spectrum and clinical characteristics. Hematogenous candidiasis is a worrisome issue that affects people all over the world, particularly ICU patients. CARD9 deficiency and fungal infection have been major issues in recent years. Invasive aspergillosis is associated with a significant death rate. Special attention should be given to endemic fungal infections, identification of important clinical fungal infections advanced in yeasts, filamentous fungal infections, skin mycobiome and fungal genomes, and immunity to fungal infections.\r\nIn addition, endemic fungal diseases or uncommon fungal infections caused by Mucor irregularis, dermatophytosis, Malassezia, cryptococcosis, chromoblastomycosis, coccidiosis, blastomycosis, histoplasmosis, sporotrichosis, and other fungi, should be monitored. \r\nThis topic includes the research progress on the etiology and pathogenesis of fungal infections, new methods of isolation and identification, rapid detection, drug sensitivity testing, new antifungal drugs, schemes and case series reports. It will provide significant opportunities and support for scientists, clinical doctors, mycologists, antifungal drug researchers, public health practitioners, and epidemiologists from all over the world to share new research, ideas and solutions to promote the development and progress of medical mycology.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/4.jpg",keywords:"Emerging Fungal Pathogens, Invasive Infections, Epidemiology, Cell Membrane, Fungal Virulence, Diagnosis, Treatment"},{id:"5",title:"Parasitic Infectious Diseases",scope:"Parasitic diseases have evolved alongside their human hosts. In many cases, these diseases have adapted so well that they have developed efficient resilience methods in the human host and can live in the host for years. Others, particularly some blood parasites, can cause very acute diseases and are responsible for millions of deaths yearly. Many parasitic diseases are classified as neglected tropical diseases because they have received minimal funding over recent years and, in many cases, are under-reported despite the critical role they play in morbidity and mortality among human and animal hosts. The current topic, Parasitic Infectious Diseases, in the Infectious Diseases Series aims to publish studies on the systematics, epidemiology, molecular biology, genomics, pathogenesis, genetics, and clinical significance of parasitic diseases from blood borne to intestinal parasites as well as zoonotic parasites. We hope to cover all aspects of parasitic diseases to provide current and relevant research data on these very important diseases. In the current atmosphere of the Coronavirus pandemic, communities around the world, particularly those in different underdeveloped areas, are faced with the growing challenges of the high burden of parasitic diseases. At the same time, they are faced with the Covid-19 pandemic leading to what some authors have called potential syndemics that might worsen the outcome of such infections. Therefore, it is important to conduct studies that examine parasitic infections in the context of the coronavirus pandemic for the benefit of all communities to help foster more informed decisions for the betterment of human and animal health.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",keywords:"Blood Borne Parasites, Intestinal Parasites, Protozoa, Helminths, Arthropods, Water Born Parasites, Epidemiology, Molecular Biology, Systematics, Genomics, Proteomics, Ecology"},{id:"6",title:"Viral Infectious Diseases",scope:"The Viral Infectious Diseases Book Series aims to provide a comprehensive overview of recent research trends and discoveries in various viral infectious diseases emerging around the globe. The emergence of any viral disease is hard to anticipate, which often contributes to death. A viral disease can be defined as an infectious disease that has recently appeared within a population or exists in nature with the rapid expansion of incident or geographic range. This series will focus on various crucial factors related to emerging viral infectious diseases, including epidemiology, pathogenesis, host immune response, clinical manifestations, diagnosis, treatment, and clinical recommendations for managing viral infectious diseases, highlighting the recent issues with future directions for effective therapeutic strategies.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/6.jpg",keywords:"Novel Viruses, Virus Transmission, Virus Evolution, Molecular Virology, Control and Prevention, Virus-host Interaction"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:{id:"7",title:"Biomedical Engineering",doi:"10.5772/intechopen.71985",issn:"2631-5343",scope:"Biomedical Engineering is one of the fastest-growing interdisciplinary branches of science and industry. The combination of electronics and computer science with biology and medicine has improved patient diagnosis, reduced rehabilitation time, and helped to facilitate a better quality of life. Nowadays, all medical imaging devices, medical instruments, or new laboratory techniques result from the cooperation of specialists in various fields. The series of Biomedical Engineering books covers such areas of knowledge as chemistry, physics, electronics, medicine, and biology. This series is intended for doctors, engineers, and scientists involved in biomedical engineering or those wanting to start working in this field.",coverUrl:"https://cdn.intechopen.com/series/covers/7.jpg",latestPublicationDate:"May 7th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:3,numberOfPublishedChapters:96,numberOfPublishedBooks:12,editor:{id:"50150",title:"Prof.",name:"Robert",middleName:null,surname:"Koprowski",fullName:"Robert Koprowski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTYNQA4/Profile_Picture_1630478535317",biography:"Robert Koprowski, MD (1997), PhD (2003), Habilitation (2015), is an employee of the University of Silesia, Poland, Institute of Computer Science, Department of Biomedical Computer Systems. For 20 years, he has studied the analysis and processing of biomedical images, emphasizing the full automation of measurement for a large inter-individual variability of patients. Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}},subseries:[{id:"7",title:"Bioinformatics and Medical Informatics",keywords:"Biomedical Data, Drug Discovery, Clinical Diagnostics, Decoding Human Genome, AI in Personalized Medicine, Disease-prevention Strategies, Big Data Analysis in Medicine",scope:"Bioinformatics aims to help understand the functioning of the mechanisms of living organisms through the construction and use of quantitative tools. The applications of this research cover many related fields, such as biotechnology and medicine, where, for example, Bioinformatics contributes to faster drug design, DNA analysis in forensics, and DNA sequence analysis in the field of personalized medicine. Personalized medicine is a type of medical care in which treatment is customized individually for each patient. Personalized medicine enables more effective therapy, reduces the costs of therapy and clinical trials, and also minimizes the risk of side effects. Nevertheless, advances in personalized medicine would not have been possible without bioinformatics, which can analyze the human genome and other vast amounts of biomedical data, especially in genetics. The rapid growth of information technology enabled the development of new tools to decode human genomes, large-scale studies of genetic variations and medical informatics. The considerable development of technology, including the computing power of computers, is also conducive to the development of bioinformatics, including personalized medicine. In an era of rapidly growing data volumes and ever lower costs of generating, storing and computing data, personalized medicine holds great promises. Modern computational methods used as bioinformatics tools can integrate multi-scale, multi-modal and longitudinal patient data to create even more effective and safer therapy and disease prevention methods. Main aspects of the topic are: Applying bioinformatics in drug discovery and development; Bioinformatics in clinical diagnostics (genetic variants that act as markers for a condition or a disease); Blockchain and Artificial Intelligence/Machine Learning in personalized medicine; Customize disease-prevention strategies in personalized medicine; Big data analysis in personalized medicine; Translating stratification algorithms into clinical practice of personalized medicine.",annualVolume:11403,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"5886",title:"Dr.",name:"Alexandros",middleName:"T.",surname:"Tzallas",fullName:"Alexandros Tzallas",profilePictureURL:"https://mts.intechopen.com/storage/users/5886/images/system/5886.png",institutionString:"University of Ioannina, Greece & Imperial College London",institution:{name:"University of Ioannina",institutionURL:null,country:{name:"Greece"}}},{id:"257388",title:"Distinguished Prof.",name:"Lulu",middleName:null,surname:"Wang",fullName:"Lulu Wang",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRX6kQAG/Profile_Picture_1630329584194",institutionString:null,institution:{name:"Shenzhen Technology University",institutionURL:null,country:{name:"China"}}},{id:"225387",title:"Prof.",name:"Reda",middleName:"R.",surname:"Gharieb",fullName:"Reda Gharieb",profilePictureURL:"https://mts.intechopen.com/storage/users/225387/images/system/225387.jpg",institutionString:"Assiut University",institution:{name:"Assiut University",institutionURL:null,country:{name:"Egypt"}}}]},{id:"8",title:"Bioinspired Technology and Biomechanics",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation",scope:'Bioinspired technologies take advantage of understanding the actual biological system to provide solutions to problems in several areas. Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',annualVolume:11404,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. Osma",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSDv7QAG/Profile_Picture_1626602531691",institutionString:null,institution:{name:"Universidad de Los Andes",institutionURL:null,country:{name:"Colombia"}}},{id:"69697",title:"Dr.",name:"Mani T.",middleName:null,surname:"Valarmathi",fullName:"Mani T. Valarmathi",profilePictureURL:"https://mts.intechopen.com/storage/users/69697/images/system/69697.jpg",institutionString:"Religen Inc. | A Life Science Company, United States of America",institution:null},{id:"205081",title:"Dr.",name:"Marco",middleName:"Vinícius",surname:"Chaud",fullName:"Marco Chaud",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSDGeQAO/Profile_Picture_1622624307737",institutionString:null,institution:{name:"Universidade de Sorocaba",institutionURL:null,country:{name:"Brazil"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/459237",hash:"",query:{},params:{id:"459237"},fullPath:"/profiles/459237",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()